Sublobar resection is equivalent to lobectomy for clinical stage 1A lung cancer in solid nodules.

PubMed

Altorki, Nasser K; Yip, Rowena; Hanaoka, Takaomi; Bauer, Thomas; Aye, Ralph; Kohman, Leslie; Sheppard, Barry; Thurer, Richard; Andaz, Shahriyour; Smith, Michael; Mayfield, William; Grannis, Fred; Korst, Robert; Pass, Harvey; Straznicka, Michaela; Flores, Raja; Henschke, Claudia I

2014-02-01

A single randomized trial established lobectomy as the standard of care for the surgical treatment of early-stage non-small cell lung cancer. Recent advances in imaging/staging modalities and detection of smaller tumors have once again rekindled interest in sublobar resection for early-stage disease. The objective of this study was to compare lung cancer survival in patients with non-small cell lung cancer with a diameter of 30 mm or less with clinical stage 1 disease who underwent lobectomy or sublobar resection. We identified 347 patients diagnosed with lung cancer who underwent lobectomy (n = 294) or sublobar resection (n = 53) for non-small cell lung cancer manifesting as a solid nodule in the International Early Lung Cancer Action Program from 1993 to 2011. Differences in the distribution of the presurgical covariates between sublobar resection and lobectomy were assessed using unadjusted P values determined by logistic regression analysis. Propensity scoring was performed using the same covariates. Differences in the distribution of the same covariates between sublobar resection and lobectomy were assessed using adjusted P values determined by logistic regression analysis with adjustment for the propensity scores. Lung cancer-specific survival was determined by the Kaplan-Meier method. Cox survival regression analysis was used to compare sublobar resection with lobectomy, adjusted for the propensity scores, surgical, and pathology findings, when adjusted and stratified by propensity quintiles. Among 347 patients, 10-year Kaplan-Meier for 53 patients treated by sublobar resection compared with 294 patients treated by lobectomy was 85% (95% confidence interval, 80-91) versus 86% (confidence interval, 75-96) (P = .86). Cox survival analysis showed no significant difference between sublobar resection and lobectomy when adjusted for propensity scores or when using propensity quintiles (P = .62 and P = .79, respectively). For those with cancers 20 mm or less in diameter, the 10-year rates were 88% (95% confidence interval, 82-93) versus 84% (95% confidence interval, 73-96) (P = .45), and Cox survival analysis showed no significant difference between sublobar resection and lobectomy using either approach (P = .42 and P = .52, respectively). Sublobar resection and lobectomy have equivalent survival for patients with clinical stage IA non-small cell lung cancer in the context of computed tomography screening for lung cancer. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

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.

A comparison of Cox and logistic regression for use in genome-wide association studies of cohort and case-cohort design.

PubMed

Staley, James R; Jones, Edmund; Kaptoge, Stephen; Butterworth, Adam S; Sweeting, Michael J; Wood, Angela M; Howson, Joanna M M

2017-06-01

Logistic regression is often used instead of Cox regression to analyse genome-wide association studies (GWAS) of single-nucleotide polymorphisms (SNPs) and disease outcomes with cohort and case-cohort designs, as it is less computationally expensive. Although Cox and logistic regression models have been compared previously in cohort studies, this work does not completely cover the GWAS setting nor extend to the case-cohort study design. Here, we evaluated Cox and logistic regression applied to cohort and case-cohort genetic association studies using simulated data and genetic data from the EPIC-CVD study. In the cohort setting, there was a modest improvement in power to detect SNP-disease associations using Cox regression compared with logistic regression, which increased as the disease incidence increased. In contrast, logistic regression had more power than (Prentice weighted) Cox regression in the case-cohort setting. Logistic regression yielded inflated effect estimates (assuming the hazard ratio is the underlying measure of association) for both study designs, especially for SNPs with greater effect on disease. Given logistic regression is substantially more computationally efficient than Cox regression in both settings, we propose a two-step approach to GWAS in cohort and case-cohort studies. First to analyse all SNPs with logistic regression to identify associated variants below a pre-defined P-value threshold, and second to fit Cox regression (appropriately weighted in case-cohort studies) to those identified SNPs to ensure accurate estimation of association with disease.

Fetal exposure to nonsteroidal anti-inflammatory drugs and spontaneous abortions

PubMed Central

Daniel, Sharon; Koren, Gideon; Lunenfeld, Eitan; Bilenko, Natalya; Ratzon, Ronit; Levy, Amalia

2014-01-01

Background: Spontaneous abortion is the most common complication of pregnancy. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used during pregnancy. Published data are inconsistent regarding the risk of spontaneous abortion following exposure to NSAIDs. Methods: We performed a historical cohort study involving all women who conceived between January 2003 and December 2009 and who were admitted for delivery or spontaneous abortion at Soroka Medical Center, Clalit Health Services, Israel. A computerized database of medication dispensation was linked with 2 computerized databases containing information on births and spontaneous abortions. We constructed time-varying Cox regression models and adjusted for maternal age, diabetes mellitus, hypothyroidism, obesity, hypercoagulation or inflammatory conditions, recurrent miscarriage, in vitro fertilization of the current pregnancy, intrauterine contraceptive device, ethnic background, tobacco use and year of admission. Results: The cohort included 65 457 women who conceived during the study period; of these, 58 949 (90.1%) were admitted for a birth and 6508 (9.9%) for spontaneous abortion. A total of 4495 (6.9%) pregnant women were exposed to NSAIDs during the study period. Exposure to NSAIDs was not an independent risk factor for spontaneous abortion (nonselective cyclooxygenase [COX] inhibitors: adjusted hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.99–1.22; selective COX-2 inhibitors: adjusted HR 1.43, 95% CI 0.79–2.59). There was no increased risk for specific NSAID drugs, except for a significantly increased risk with exposure to indomethacin (adjusted HR 2.8, 95% CI 1.70–4.69). We found no dose–response effect. Interpretation: We found no increased risk of spontaneous abortion following exposure to NSAIDs. Further research is needed to assess the risk following exposure to selective COX-2 inhibitors. PMID:24491470

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.

Introduction to the use of regression models in epidemiology.

PubMed

Bender, Ralf

2009-01-01

Regression modeling is one of the most important statistical techniques used in analytical epidemiology. By means of regression models the effect of one or several explanatory variables (e.g., exposures, subject characteristics, risk factors) on a response variable such as mortality or cancer can be investigated. From multiple regression models, adjusted effect estimates can be obtained that take the effect of potential confounders into account. Regression methods can be applied in all epidemiologic study designs so that they represent a universal tool for data analysis in epidemiology. Different kinds of regression models have been developed in dependence on the measurement scale of the response variable and the study design. The most important methods are linear regression for continuous outcomes, logistic regression for binary outcomes, Cox regression for time-to-event data, and Poisson regression for frequencies and rates. This chapter provides a nontechnical introduction to these regression models with illustrating examples from cancer research.

Self-Regulation and Executive Functioning as Related to Survival in Motor Neuron Disease: Preliminary Findings.

PubMed

Garcia-Willingham, Natasha E; Roach, Abbey R; Kasarskis, Edward J; Segerstrom, Suzanne C

2018-05-16

Disease progression varies widely among patients with motor neuron disease (MND). Patients with MND and coexisting dementia have shorter survival. However, implications of mild cognitive and behavioral difficulties are unclear. The present study examined the relative contribution of executive functioning and self-regulation difficulties on survival over a 6-year period among patients with MND, who scored largely within normal limits on cognitive and behavioral indices. Patients with MND (N=37, age=59.97±11.57, 46% female) completed the Wisconsin Card Sorting Task (WCST) as an executive functioning perseveration index. The Behavior Rating Inventory of Executive Functions (BRIEF-A) was used as a behavioral measure of self-regulation in two subdomains self-regulatory behavior (Behavioral Regulation) and self-regulatory problem-solving (Metacognition). Cox proportional hazard regression analyses were used. In total, 23 patients died during follow-up. In Cox proportional hazard regressions adjusted for a priori covariates, each 10-point T-score increment in patient-reported BRIEF-A self-regulatory behavior and problem-solving difficulties increased mortality risk by 94% and103%, respectively (adjusted HR=1.94, 95% CI [1.07, 3.52]; adjusted HR=2.03, 95% CI [1.19, 3.48]). In sensitivity analyses, patient-reported self-regulatory problem-solving remained significant independent of disease severity and a priori covariates (adjusted HR=1.68, 95% CI [1.01, 2.78], though the predictive value of self-regulatory behavior was attenuated in adjusted models (HR=1.67, 95% CI [0.85, 3.27). Caregiver-reported BRIEF-A ratings of patients and WCST perseverative errors did not significantly predict survival. Preliminary evidence suggests patient-reported self-regulatory problem-solving difficulties indicate poorer prognosis in MND. Further research is needed to uncover mechanisms that negatively affect patient survival.

Reduction of Racial Disparities in Prostate Cancer

DTIC Science & Technology

2007-12-01

anti-inflammatory medication, COX-2 inhibitors, aspirin, anti-TNF medications), and other medications of interest (testosterone, finasteride , alpha...compared to control-patients (mean 123) P=0.01. There were 14 (7%) control-patients who had Finasteride use, with an average of 398.6 doses per...individual. None of the prosate cancer patients had prior finasteride use. In a multiple logistic regression model (Table 2), after adjustment for the

Using instrumental variables to estimate a Cox's proportional hazards regression subject to additive confounding

PubMed Central

Tosteson, Tor D.; Morden, Nancy E.; Stukel, Therese A.; O'Malley, A. James

2014-01-01

The estimation of treatment effects is one of the primary goals of statistics in medicine. Estimation based on observational studies is subject to confounding. Statistical methods for controlling bias due to confounding include regression adjustment, propensity scores and inverse probability weighted estimators. These methods require that all confounders are recorded in the data. The method of instrumental variables (IVs) can eliminate bias in observational studies even in the absence of information on confounders. We propose a method for integrating IVs within the framework of Cox's proportional hazards model and demonstrate the conditions under which it recovers the causal effect of treatment. The methodology is based on the approximate orthogonality of an instrument with unobserved confounders among those at risk. We derive an estimator as the solution to an estimating equation that resembles the score equation of the partial likelihood in much the same way as the traditional IV estimator resembles the normal equations. To justify this IV estimator for a Cox model we perform simulations to evaluate its operating characteristics. Finally, we apply the estimator to an observational study of the effect of coronary catheterization on survival. PMID:25506259

Using instrumental variables to estimate a Cox's proportional hazards regression subject to additive confounding.

PubMed

MacKenzie, Todd A; Tosteson, Tor D; Morden, Nancy E; Stukel, Therese A; O'Malley, A James

2014-06-01

The estimation of treatment effects is one of the primary goals of statistics in medicine. Estimation based on observational studies is subject to confounding. Statistical methods for controlling bias due to confounding include regression adjustment, propensity scores and inverse probability weighted estimators. These methods require that all confounders are recorded in the data. The method of instrumental variables (IVs) can eliminate bias in observational studies even in the absence of information on confounders. We propose a method for integrating IVs within the framework of Cox's proportional hazards model and demonstrate the conditions under which it recovers the causal effect of treatment. The methodology is based on the approximate orthogonality of an instrument with unobserved confounders among those at risk. We derive an estimator as the solution to an estimating equation that resembles the score equation of the partial likelihood in much the same way as the traditional IV estimator resembles the normal equations. To justify this IV estimator for a Cox model we perform simulations to evaluate its operating characteristics. Finally, we apply the estimator to an observational study of the effect of coronary catheterization on survival.

The effect of delayed graft function on graft and patient survival in kidney transplantation: an approach using competing events analysis.

PubMed

Fonseca, Isabel; Teixeira, Laetitia; Malheiro, Jorge; Martins, La Salete; Dias, Leonídio; Castro Henriques, António; Mendonça, Denisa

2015-06-01

In kidney transplantation, the impact of delayed graft function (DGF) on long-term graft and patient survival is controversial. We examined the impact of DGF on graft and recipient survival by accounting for the possibility that death with graft function may act as a competing risk for allograft failure. We used data from 1281 adult primary deceased-donor kidney recipients whose allografts functioned at least 1 year. The probability of graft loss occurrence is overestimated using the complement of Kaplan-Meier estimates (1-KM). Both the cause-specific Cox proportional hazard regression model (standard Cox) and the subdistribution hazard regression model proposed by Fine and Gray showed that DGF was associated with shorter time to graft failure (csHR = 2.0, P = 0.002; sHR = 1.57, P = 0.009), independent of acute rejection (AR) and after adjusting for traditional factors associated with graft failure. Regarding patient survival, DGF was a predictor of patient death using the cause-specific Cox model (csHR = 1.57, P = 0.029) but not using the subdistribution model. The probability of graft loss from competing end points should not be reported with the 1-KM. Application of a regression model for subdistribution hazard showed that, independent of AR, DGF has a detrimental effect on long-term graft survival, but not on patient survival. © 2015 Steunstichting ESOT.

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.

All-cause mortality of elderly Australian veterans using COX-2 selective or non-selective NSAIDs: a longitudinal study

PubMed Central

Kerr, Stephen J; Rowett, Debra S; Sayer, Geoffrey P; Whicker, Susan D; Saltman, Deborah C; Mant, Andrea

2011-01-01

AIM To determine hazard ratios for all-cause mortality in elderly Australian veterans taking COX-2 selective and non-selective NSAIDs. METHODS Patient cohorts were constructed from claims databases (1997 to 2007) for veterans and dependants with full treatment entitlement irrespective of military service. Patients were grouped by initial exposure: celecoxib, rofecoxib, meloxicam, diclofenac, non-selective NSAID. A reference group was constructed of patients receiving glaucoma/hypothyroid medications and none of the study medications. Univariate and multivariate analyses were performed using Cox proportional hazards regression models. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for each exposure group against each of the reference group. The final model was adjusted for age, gender and co-prescription as a surrogate for cardiovascular risk. Patients were censored if the gap in supply of study prescription exceeded 30 days or if another study medication was initiated. The outcome measure in all analyses was death. RESULTS Hazard ratios and 95% CIs, adjusted for age, gender and cardiovascular risk, for each group relative to the reference group were: celecoxib 1.39 (1.25, 1.55), diclofenac 1.44 (1.28, 1.62), meloxicam 1.49 (1.25, 1.78), rofecoxib 1.58 (1.39, 1.79), non-selective NSAIDs 1.76 (1.59, 1.94). CONCLUSIONS In this large cohort of Australian veterans exposed to COX-2 selective and non-selective NSAIDs, there was a significant increased mortality risk for those exposed to either COX-2-selective or non-selective NSAIDs relative to those exposed to unrelated (glaucoma/hypothyroid) medications. PMID:21276041

Changes in survival patterns in urban Chinese patients with liver cancer

PubMed Central

Hao, Xi-Shan; Chen, Ke-Xin; Wang, Peizhong Peter; Rohan, Tom

2003-01-01

AIM: To examine the survival patterns and determinants of primary liver cancer in a geographically defined Chinese population. METHODS: Primary liver cancer cases (n = 13685) diagnosed between 1981 and 2000 were identified by the Tianjin Cancer Registry. Age-adjusted and age-specific incidence rates were examined in both males and females. Proportional hazards (Cox) regression was utilized to explore the effects of time of diagnosis, sex, age, occupation, residence, and hospital of diagnosis on survival. RESULTS: Crude and age-adjusted incidence rates in the study period were: 27.4/100000 and 26.3/100000 in males; and 11.5/100000 and 10.4/100000 in females, respectively. Cox regression analyses indicated that there was a significant improvement in survival rates over time. Industrial workers and older people had relatively poor survival rates. The hospital in which the liver cancer was diagnosed was a statistically significant predictor of survival; patients diagnosed in city hospitals were more likely to have better survival than those diagnosed in community/district hospitals. CONCLUSION: Patients diagnosed in recent years appeared to have a better outcome than those diagnosed in early times. There were also significant survival disparities with respect to occupation and hospital of diagnosis, which suggest that socioeconomic status may play an important role in determining prognosis. PMID:12800226

Analyzing Student Learning Outcomes: Usefulness of Logistic and Cox Regression Models. IR Applications, Volume 5

ERIC Educational Resources Information Center

Chen, Chau-Kuang

2005-01-01

Logistic and Cox regression methods are practical tools used to model the relationships between certain student learning outcomes and their relevant explanatory variables. The logistic regression model fits an S-shaped curve into a binary outcome with data points of zero and one. The Cox regression model allows investigators to study the duration…

Effect of a community intervention programme promoting social interactions on functional disability prevention for older adults: propensity score matching and instrumental variable analyses, JAGES Taketoyo study.

PubMed

Hikichi, Hiroyuki; Kondo, Naoki; Kondo, Katsunori; Aida, Jun; Takeda, Tokunori; Kawachi, Ichiro

2015-09-01

The efficacy of promoting social interactions to improve the health of older adults is not fully established due to residual confounding and selection bias. The government of Taketoyo town, Aichi Prefecture, Japan, developed a resident-centred community intervention programme called 'community salons', providing opportunities for social interactions among local older residents. To evaluate the impact of the programme, we conducted questionnaire surveys for all older residents of Taketoyo. We carried out a baseline survey in July 2006 (prior to the introduction of the programme) and assessed the onset of functional disability during March 2012. We analysed the data of 2421 older people. In addition to the standard Cox proportional hazard regression, we conducted Cox regression with propensity score matching (PSM) and an instrumental variable (IV) analysis, using the number of community salons within a radius of 350 m from the participant's home as an instrument. In the 5 years after the first salon was launched, the salon participants showed a 6.3% lower incidence of functional disability compared with non-participants. Even adjusting for sex, age, equivalent income, educational attainment, higher level activities of daily living and depression, the Cox adjusted HR for becoming disabled was 0.49 (95% CI 0.33 to 0.72). Similar results were observed using PSM (HR 0.52, 95% CI 0.33 to 0.83) and IV-Cox analysis (HR 0.50, 95% CI 0.34 to 0.74). A community health promotion programme focused on increasing social interactions among older adults may be effective in preventing the onset of disability. 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.

Stress Hyperglycemia and Prognosis of Minor Ischemic Stroke and Transient Ischemic Attack: The CHANCE Study (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events).

PubMed

Pan, Yuesong; Cai, Xueli; Jing, Jing; Meng, Xia; Li, Hao; Wang, Yongjun; Zhao, Xingquan; Liu, Liping; Wang, David; Johnston, S Claiborne; Wei, Tiemin; Wang, Yilong

2017-11-01

We aimed to determine the association between stress hyperglycemia and risk of new stroke in patients with a minor ischemic stroke or transient ischemic attack. A subgroup of 3026 consecutive patients from 73 prespecified sites of the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) were analyzed. Stress hyperglycemia was measured by glucose/glycated albumin (GA) ratio. Glucose/GA ratio was calculated by fasting plasma glucose divided by GA and categorized into 4 even groups according to the quartiles. The primary outcome was a new stroke (ischemic or hemorrhagic) at 90 days. We assessed the association between glucose/GA ratio and risk of stroke by multivariable Cox regression models adjusted for potential covariates. Among 3026 patients included, a total of 299 (9.9%) new stroke occurred at 3 months. Compared with patients with the lowest quartile, patients with the highest quartile of glucose/GA ratio was associated with an increased risk of stroke at 3 months after adjusted for potential covariates (12.0% versus 9.2%; adjusted hazard ratio, 1.46; 95% confidence interval, 1.06-2.01). Similar results were observed after further adjusted for fasting plasma glucose. We also observed that higher level of glucose/GA ratio was associated with an increased risk of stroke with a threshold of 0.29 using a Cox regression model with restricted cubic spline. Stress hyperglycemia, measured by glucose/GA ratio, was associated with an increased risk of stroke in patients with a minor ischemic stroke or transient ischemic attack. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. © 2017 American Heart Association, Inc.

[A SAS marco program for batch processing of univariate Cox regression analysis for great database].

PubMed

Yang, Rendong; Xiong, Jie; Peng, Yangqin; Peng, Xiaoning; Zeng, Xiaomin

2015-02-01

To realize batch processing of univariate Cox regression analysis for great database by SAS marco program. We wrote a SAS macro program, which can filter, integrate, and export P values to Excel by SAS9.2. The program was used for screening survival correlated RNA molecules of ovarian cancer. A SAS marco program could finish the batch processing of univariate Cox regression analysis, the selection and export of the results. The SAS macro program has potential applications in reducing the workload of statistical analysis and providing a basis for batch processing of univariate Cox regression analysis.

Population-based cohort study investigating the correlation of diabetes mellitus with pleural empyema in adults in Taiwan.

PubMed

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

2017-09-01

We assessed the association between diabetes mellitus and the risk of pleural empyema in Taiwan.A population-based retrospective cohort study was conducted using the database of the Taiwan National Health Insurance Program. There were 28,802 subjects aged 20 to 84 years who were newly diagnosed with diabetes mellitus from 2000 to 2010 as the diabetes group and 114,916 randomly selected subjects without diabetes mellitus as the non-diabetes group. The diabetes group and the non-diabetes group were matched by sex, age, comorbidities, and the year of index date. The incidence of pleural empyema at the end of 2011 was estimated. A multivariable Cox proportional hazards regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for pleural empyema associated with diabetes mellitus.The overall incidence of pleural empyema was 1.65-fold higher in the diabetes group than that in the non-diabetes group (1.58 vs 0.96 per 10,000 person-years, 95% CI 1.57-1.72). After adjusting for confounders, a multivariable Cox proportional hazards regression model revealed that the adjusted HR of pleural empyema was 1.71 in subjects with diabetes mellitus (95% CI 1.16-2.51), compared with those without diabetes mellitus. In further analysis, even in the absence of any comorbidity, the adjusted HR was 1.99 for subjects with diabetes mellitus alone (95% CI 1.18-3.38).Diabetic patients confer a 1.71-fold increased hazard of developing pleural empyema. Even in the absence of any comorbidity, the risk remains existent.

Intake of different types of dairy and its prospective association with risk of type 2 diabetes: The Rotterdam Study.

PubMed

Brouwer-Brolsma, E M; van Woudenbergh, G J; Oude Elferink, S J W H; Singh-Povel, C M; Hofman, A; Dehghan, A; Franco, O H; Feskens, E J M

2016-11-01

The prevalence of type 2 diabetes (T2DM) is increasing. Several studies have suggested a beneficial effect of several major dairy nutrients on insulin production and sensitivity. Conversely, harmful effects have been suggested as well. This study aimed to investigate the impact of the full-range of dairy products and its association with incidence T2DM in Dutch adults aged ≥55 years participating in the Rotterdam Study. Dairy intake was assessed with a validated FFQ, including total, skimmed, semi-skimmed, full-fat, fermented, and non-fermented dairy, and subclasses of these product groups. Verified prevalent and incident diabetes were documented. Cox proportional hazards regression and spline regression were used to analyse data, adjusting for age, sex, alcohol, smoking, education, physical activity, body mass index, intake of total energy, energy-adjusted meat, and energy-adjusted fish intake. Median total dairy intake was 398 g/day (IQR 259-559 g/day). Through 9.5 ± 4.1 years of follow-up, 393 cases of incident T2DM were reported. Cox and spline regression did not point towards associations of total dairy consumption, dairy consumption based on fat content, non-fermented or fermented dairy consumption, or individual dairy product consumption with incident T2DM. The HR for total dairy intake and T2DM was 0.93 (95% CI: 0.70-1.23) in the upper quartile (P-for trend 0.76). This prospective cohort study did not point towards an association between dairy consumption and T2DM. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Association Between Obstetric Mode of Delivery and Autism Spectrum Disorder: A Population-Based Sibling Design Study.

PubMed

Curran, Eileen A; Dalman, Christina; Kearney, Patricia M; Kenny, Louise C; Cryan, John F; Dinan, Timothy G; Khashan, Ali S

2015-09-01

Because the rates of cesarean section (CS) are increasing worldwide, it is becoming increasingly important to understand the long-term effects that mode of delivery may have on child development. To investigate the association between obstetric mode of delivery and autism spectrum disorder (ASD). Perinatal factors and ASD diagnoses based on the International Classification of Diseases, Ninth Revision (ICD-9),and the International Statistical Classification of Diseases, 10th Revision (ICD-10),were identified from the Swedish Medical Birth Register and the Swedish National Patient Register. We conducted stratified Cox proportional hazards regression analysis to examine the effect of mode of delivery on ASD. We then used conditional logistic regression to perform a sibling design study, which consisted of sibling pairs discordant on ASD status. Analyses were adjusted for year of birth (ie, partially adjusted) and then fully adjusted for various perinatal and sociodemographic factors. The population-based cohort study consisted of all singleton live births in Sweden from January 1, 1982, through December 31, 2010. Children were followed up until first diagnosis of ASD, death, migration, or December 31, 2011 (end of study period), whichever came first. The full cohort consisted of 2,697,315 children and 28,290 cases of ASD. Sibling control analysis consisted of 13,411 sibling pairs. Obstetric mode of delivery defined as unassisted vaginal delivery (VD), assisted VD, elective CS, and emergency CS (defined by before or after onset of labor). The ASD status as defined using codes from the ICD-9 (code 299) and ICD-10 (code F84). In adjusted Cox proportional hazards regression analysis, elective CS (hazard ratio, 1.21; 95% CI, 1.15-1.27) and emergency CS (hazard ratio, 1.15; 95% CI, 1.10-1.20) were associated with ASD when compared with unassisted VD. In the sibling control analysis, elective CS was not associated with ASD in partially (odds ratio [OR], 0.97; 95% CI, 0.85-1.11) or fully adjusted (OR, 0.89; 95% CI, 0.76-1.04) models. Emergency CS was significantly associated with ASD in partially adjusted analysis (OR, 1.20; 95% CI, 1.06-1.36), but this effect disappeared in the fully adjusted model (OR, 0.97; 95% CI, 0.85-1.11). This study confirms previous findings that children born by CS are approximately 20% more likely to be diagnosed as having ASD. However, the association did not persist when using sibling controls, implying that this association is due to familial confounding by genetic and/or environmental factors.

The reproductive outcome of female patients with myotonic dystrophy type 1 (DM1) undergoing PGD is not affected by the size of the expanded CTG repeat tract

PubMed Central

Seneca, Sara; De Rademaeker, Marjan; Sermon, Karen; De Rycke, Martine; De Vos, Michel; Haentjens, Patrick; Devroey, Paul; Liebaers, Ingeborg

2010-01-01

Purpose This study aims to analyze the relationship between trinucleotide repeat length and reproductive outcome in a large cohort of DM1 patients undergoing ICSI and PGD. Methods Prospective cohort study. The effect of trinucleotide repeat length on reproductive outcome per patient was analyzed using bivariate analysis (T-test) and multivariate analysis using Kaplan-Meier and Cox regression analysis. Results Between 1995 and 2005, 205 cycles of ICSI and PGD were carried out for DM1 in 78 couples. The number of trinucleotide repeats does not have an influence on reproductive outcome when adjusted for age, BMI, basal FSH values, parity, infertility status and male or female affected. Cox regression analysis indicates that cumulative live birth rate is not influenced by the number of trinucleotide repeats. The only factor with a significant effect is age (p < 0.05). Conclusion There is no evidence of an effect of trinucleotide repeat length on reproductive outcome in patients undergoing ICSI and PGD. PMID:20221684

Ethnicity matching and outcomes after kidney transplantation in the United Kingdom.

PubMed

Pisavadia, Bhavini; Arshad, Adam; Chappelow, Imogen; Nightingale, Peter; Anderson, Benjamin; Nath, Jay; Sharif, Adnan

2018-01-01

Kidneys from non-white donors have inferior outcomes, but it is unclear if ethnicity matching between donors and recipients achieves better post kidney transplant outcomes. We undertook a retrospective, population cohort study utilising UK Transplant Registry data. The cohort comprised adult, kidney-alone, transplant recipients receiving their first kidney transplant between 2003-2015, with data censored at 1st October 2016. We included 27,970 recipients stratified into white (n = 23,215), black (n = 1,679) and south Asian (n = 3,076) ethnicity, with median post-transplant follow-up of 1,676 days (IQR 716-2,869 days). Unadjusted and adjusted Cox regression survival analyses were performed to investigate ethnicity effect on risk for graft loss and mortality. In unadjusted analyses, matched ethnicity between donors-recipients resulted in better outcomes for delayed graft function, one-year creatinine, graft and patient survival but these differed by ethnicity matches. Compared to white-to-white transplants, risk for death-censored graft loss was higher in black-to-black and similar among Asian-to-Asian transplants, but mortality risk was lower for both black-to-black and Asian-to-Asian transplants. In Cox regression models, compared to white donors, we observed higher risk for graft loss with both south Asian (HR 1.38, 95%CI 1.12-1.70, p = 0.003) and black (HR 1.66, 95%CI 1.30-2.11, p<0.001) donated kidneys independent of recipient ethnicity. We observed no mortality difference with south Asian donated kidneys but increased mortality with black donated kidneys (HR 1.68, 95%CI 1.21-2.35, p = 0.002). Matching ethnicities made no significant difference in any Cox regression model. Similar results were observed after stratifying our analysis by living and deceased-donor kidney transplantation. Our data confirm inferior outcomes associated with non-white kidney donors for kidney transplant recipients of any ethnicity in a risk-adjusted model for the United Kingdom population. However, contrary to non-renal transplant literature, we did not identify any survival benefits associated with donor-recipient ethnicity matching.

Drugs to Treat Systemic Lupus Erythematosus: Relationship between Current Use and Cardiovascular Risk Factors

PubMed Central

Rho, Young Hee; Oeser, Annette; Chung, Cecilia P; Morrow, Jason D; Stein, C Michael

2008-01-01

Objectives Cardiovascular risk is increased in patients with systemic lupus erythematosus (SLE). Drugs used to treat SLE can modify traditional cardiovascular risk factors. We examined the effect of selected drugs used in the treatment of SLE on cardiovascular risk factors. Methods We compared systolic and diastolic blood pressure, serum lipid concentrations, glucose, homocysteine, and urinary F2-isoprostane concentrations in 99 patients with lupus who were either current users or non-users of systemic corticosteroids, antimalarials, non-steroidal anti-inflammatory drugs (NSAIDs), COX-2 selective NSAIDs, azathioprine, and methotrexate. Multivariable adjustment was done with linear regression modeling using sex, age and disease activity (SLEDAI) as controlling variables. Results Serum triglyceride concentrations were higher (135.1 ± 61.4 vs. 95.3 ± 47.5 mg/dL, adjusted P = 0.003) in patients receiving corticosteroids. Homocysteine concentrations were marginally higher in patients receiving methotrexate (adjusted P = 0.08). Current use of either NSAIDs or COX-2 inhibitors was not associated with increased cardiovascular risk factors. Current hydroxychloroquine use was not associated with significant alterations in lipid profiles. Conclusions In a non-random sample of patients with SLE, current corticosteroid use was associated with increased triglyceride concentrations, but other drugs had little effect on traditional cardiovascular risk factors. PMID:20157365

Box–Cox Transformation and Random Regression Models for Fecal egg Count Data

PubMed Central

da Silva, Marcos Vinícius Gualberto Barbosa; Van Tassell, Curtis P.; Sonstegard, Tad S.; Cobuci, Jaime Araujo; Gasbarre, Louis C.

2012-01-01

Accurate genetic evaluation of livestock is based on appropriate modeling of phenotypic measurements. In ruminants, fecal egg count (FEC) is commonly used to measure resistance to nematodes. FEC values are not normally distributed and logarithmic transformations have been used in an effort to achieve normality before analysis. However, the transformed data are often still not normally distributed, especially when data are extremely skewed. A series of repeated FEC measurements may provide information about the population dynamics of a group or individual. A total of 6375 FEC measures were obtained for 410 animals between 1992 and 2003 from the Beltsville Agricultural Research Center Angus herd. Original data were transformed using an extension of the Box–Cox transformation to approach normality and to estimate (co)variance components. We also proposed using random regression models (RRM) for genetic and non-genetic studies of FEC. Phenotypes were analyzed using RRM and restricted maximum likelihood. Within the different orders of Legendre polynomials used, those with more parameters (order 4) adjusted FEC data best. Results indicated that the transformation of FEC data utilizing the Box–Cox transformation family was effective in reducing the skewness and kurtosis, and dramatically increased estimates of heritability, and measurements of FEC obtained in the period between 12 and 26 weeks in a 26-week experimental challenge period are genetically correlated. PMID:22303406

Box-Cox Transformation and Random Regression Models for Fecal egg Count Data.

PubMed

da Silva, Marcos Vinícius Gualberto Barbosa; Van Tassell, Curtis P; Sonstegard, Tad S; Cobuci, Jaime Araujo; Gasbarre, Louis C

2011-01-01

Accurate genetic evaluation of livestock is based on appropriate modeling of phenotypic measurements. In ruminants, fecal egg count (FEC) is commonly used to measure resistance to nematodes. FEC values are not normally distributed and logarithmic transformations have been used in an effort to achieve normality before analysis. However, the transformed data are often still not normally distributed, especially when data are extremely skewed. A series of repeated FEC measurements may provide information about the population dynamics of a group or individual. A total of 6375 FEC measures were obtained for 410 animals between 1992 and 2003 from the Beltsville Agricultural Research Center Angus herd. Original data were transformed using an extension of the Box-Cox transformation to approach normality and to estimate (co)variance components. We also proposed using random regression models (RRM) for genetic and non-genetic studies of FEC. Phenotypes were analyzed using RRM and restricted maximum likelihood. Within the different orders of Legendre polynomials used, those with more parameters (order 4) adjusted FEC data best. Results indicated that the transformation of FEC data utilizing the Box-Cox transformation family was effective in reducing the skewness and kurtosis, and dramatically increased estimates of heritability, and measurements of FEC obtained in the period between 12 and 26 weeks in a 26-week experimental challenge period are genetically correlated.

Selecting risk factors: a comparison of discriminant analysis, logistic regression and Cox's regression model using data from the Tromsø Heart Study.

PubMed

Brenn, T; Arnesen, E

1985-01-01

For comparative evaluation, discriminant analysis, logistic regression and Cox's model were used to select risk factors for total and coronary deaths among 6595 men aged 20-49 followed for 9 years. Groups with mortality between 5 and 93 per 1000 were considered. Discriminant analysis selected variable sets only marginally different from the logistic and Cox methods which always selected the same sets. A time-saving option, offered for both the logistic and Cox selection, showed no advantage compared with discriminant analysis. Analysing more than 3800 subjects, the logistic and Cox methods consumed, respectively, 80 and 10 times more computer time than discriminant analysis. When including the same set of variables in non-stepwise analyses, all methods estimated coefficients that in most cases were almost identical. In conclusion, discriminant analysis is advocated for preliminary or stepwise analysis, otherwise Cox's method should be used.

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.

Adiponectin and Mortality in Smokers and Non-Smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study.

PubMed

Delgado, Graciela E; Siekmeier, Rüdiger; März, Winfried; Kleber, Marcus E

2016-01-01

Cardiovascular diseases (CVD) are an important cause of morbidity and mortality worldwide. A decreased concentration of adiponectin has been reported in smokers. The aim of this study was to analyze the effect of cigarette smoking on the concentration of adiponectin and potassium in active smokers (AS) and life-time non-smokers (NS) of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study, and the use of these two markers for risk prediction. Smoking status was assessed by a questionnaire and measurement of plasma cotinine concentration. The serum concentration of adiponectin was measured by ELISA. Adiponectin was binned into tertiles separately for AS and NS and the Cox regression was used to assess the effect on mortality. There were 777 AS and 1178 NS among the LURIC patients. Within 10 years (median) of follow-up 221 AS and 302 NS died. In unadjusted analyses, AS had lower concentrations of adiponectin. However, after adjustment for age and gender there was no significant difference in adiponectin concentration between AS and NS. In the Cox regression model adjusted for age and gender, adiponectin was significantly associated with mortality in AS, but not in NS, with hazard ratio (95 % CI) of 1.60 (1.14-2.24) comparing the third with first tertile. In a model further adjusted for the risk factors, such as diabetes mellitus, hypertension, coronary artery disease, body mass index, LDL-cholesterol and HDL-cholesterol, adiponectin was significantly associated with mortality with hazard ratio of 1.83 (1.28-2.62) and 1.56 (1.15-2.11) for AS and NS, respectively. We conclude that increased adiponectin is a strong and independent predictor of mortality in both AS and NS. The determination of adiponectin concentration could be used to identify individuals at increased mortality risk.

SURVIVAL DISPARITIES BY MEDICAID STATUS: AN ANALYSIS OF EIGHT CANCERS

PubMed Central

Koroukian, Siran M.; Bakaki, Paul M.; Raghavan, Derek

2011-01-01

Study Objective To compare survival and 5-year mortality, by Medicaid status, in adults diagnosed with 8 select cancers. Methods Linking records from the Ohio Cancer Incidence Surveillance System (OCISS) with Ohio Medicaid enrollment data, we identified Medicaid and non-Medicaid patients aged 15–54 years and diagnosed with the following incident cancers in the years 1996–2002: cancer of the testis; Hodgkin’s and non-Hodgkin’s lymphoma; early-stage melanoma, colon, lung, and bladder cancer; or pediatric malignancies (n=12,703). Medicaid beneficiaries were identified in the pre-diagnosis group if they were enrolled in Medicaid at least 3 months before cancer diagnosis, and in the peri/post-diagnosis group if they enrolled in Medicaid upon or after being diagnosed with cancer. We also linked the OCISS with death certificates and data from the U.S. Census. Using Cox and logistic regression analysis, we examined the association between Medicaid status and each of survival and 5-year mortality, respectively, after adjusting for patient covariates. Results Nearly 11% of the study population were Medicaid beneficiaries. Of those, 45% were identified in the peri/post-diagnosis group. Consistent with higher mortality, findings from the Cox regression model indicated that compared to non-Medicaid, patients in the Medicaid pre-diagnosis and peri/post-diagnosis groups experienced unfavorable survival outcomes (adjusted hazard ratio (AHR): 1.52, 95% confidence interval (1.27, 1.82), and 2.01 (1.70, 2.38), respectively). Conclusions Medicaid status was associated with unfavorable survival, even after adjusting for confounders. Impact The findings reflect the vulnerability of Medicaid beneficiaries and possible inadequacies in the process of care. PMID:22213271

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

Resting Heart Rate as Predictor for Left Ventricular Dysfunction and Heart Failure: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

Opdahl, Anders; Venkatesh, Bharath Ambale; Fernandes, Veronica R. S.; Wu, Colin O.; Nasir, Khurram; Choi, Eui-Young; Almeida, Andre L. C.; Rosen, Boaz; Carvalho, Benilton; Edvardsen, Thor; Bluemke, David A.; Lima, Joao A. C.

2014-01-01

OBJECTIVE To investigate the relationship between baseline resting heart rate and incidence of heart failure (HF) and global and regional left ventricular (LV) dysfunction. BACKGROUND The association of resting heart rate to HF and LV function is not well described in an asymptomatic multi-ethnic population. METHODS Participants in the Multi-Ethnic Study of Atherosclerosis had resting heart rate measured at inclusion. Incident HF was registered (n=176) during follow-up (median 7 years) in those who underwent cardiac MRI (n=5000). Changes in ejection fraction (ΔEF) and peak circumferential strain (Δεcc) were measured as markers of developing global and regional LV dysfunction in 1056 participants imaged at baseline and 5 years later. Time to HF (Cox model) and Δεcc and ΔEF (multiple linear regression models) were adjusted for demographics, traditional cardiovascular risk factors, calcium score, LV end-diastolic volume and mass in addition to resting heart rate. RESULTS Cox analysis demonstrated that for 1 bpm increase in resting heart rate there was a 4% greater adjusted relative risk for incident HF (Hazard Ratio: 1.04 (1.02, 1.06 (95% CI); P<0.001). Adjusted multiple regression models demonstrated that resting heart rate was positively associated with deteriorating εcc and decrease in EF, even in analyses when all coronary heart disease events were excluded from the model. CONCLUSION Elevated resting heart rate is associated with increased risk for incident HF in asymptomatic participants in MESA. Higher heart rate is related to development of regional and global LV dysfunction independent of subclinical atherosclerosis and coronary heart disease. PMID:24412444

Racial differences in tumor stage and survival for colorectal cancer in an insured population.

PubMed

Doubeni, Chyke A; Field, Terry S; Buist, Diana S M; Korner, Eli J; Bigelow, Carol; Lamerato, Lois; Herrinton, Lisa; Quinn, Virginia P; Hart, Gene; Hornbrook, Mark C; Gurwitz, Jerry H; Wagner, Edward H

2007-02-01

Despite declining death rates from colorectal cancer (CRC), racial disparities have continued to increase. In this study, the authors examined disparities in a racially diverse group of insured patients. This study was conducted among patients who were diagnosed with CRC from 1993 to 1998, when they were enrolled in integrated healthcare systems. Patients were identified from tumor registries and were linked to information in administrative databases. The sample was restricted to non-Hispanic whites (n = 10,585), non-Hispanic blacks (n = 1479), Hispanics (n = 985), and Asians/Pacific Islanders (n = 909). Differences in tumor stage and survival were analyzed by using polytomous and Cox regression models, respectively. In multivariable regression analyses, blacks were more likely than whites to have distant or unstaged tumors. In Cox models that were adjusted for nonmutable factors, blacks had a higher risk of death from CRC (hazard ratio [HR], 1.17; 95% confidence interval [95% CI], 1.06-1.30). Hispanics had a risk of death similar to whites (HR, 1.04; 95% CI, 0.92-1.18), whereas Asians/Pacific Islanders had a lower risk of death from CRC (HR, 0.89; 95% CI, 0.78-1.02). Adjustment for tumor stage decreased the HR to 1.11 for blacks, and the addition of receipt of surgical therapy to the model decreased the HR further to 1.06. The HR among Hispanics and Asians/Pacific Islanders was stable to adjustment for tumor stage and surgical therapy. The relation between race and survival from CRC was complex and appeared to be related to differences in tumor stage and therapy received, even in insured populations. Targeted interventions to improve the use of effective screening and treatment among vulnerable populations may be needed to eliminate disparities in CRC. (c) 2007 American Cancer Society.

Association of dipeptidyl peptidase 4 inhibitors with risk of metastases in patients with type 2 diabetes and breast, prostate or digestive system cancer.

PubMed

Rathmann, Wolfgang; Kostev, Karel

2017-04-01

Experimental and animal studies have supported the hypothesis that dipeptidyl peptidase-4 inhibitors (DPP-4i) may accelerate tumor metastasis. The aim was to analyze the relationships between DPP-4i therapy with risk of metastases in type 2 diabetes patients with breast, prostate and digestive organ cancers. Type 2 diabetes patients with first diagnoses of breast, prostate or digestive organ cancer were selected in general and internal medicine practices (Disease Analyzer Germany: 01/2008-12/2014). Propensity score matching between DPP-4i users and non-users was carried out for age, sex, diabetes duration, and metformin use. Time-dependent Cox regression models were used to estimate hazard ratios (HR) for metastases further adjusting for HbA1c, body mass index, comorbidity and co-therapy with glucose-lowering drugs (3-4years follow-up). 668 patients with newly diagnosed breast cancer, 906 with prostate cancer and 908 with digestive organ cancer were analyzed. In Cox regression, use of DPP-4i was not associated with an increased risk of metastases in patients with breast (adjusted HR, 95%CI: 1.00, 0.49-2.02), prostate (0.98, 0.54-1.77) or digestive organ cancers (0.97, 0.57-1.66). This first observational study in patients with type 2 diabetes and breast, prostate or digestive organ cancer found no increased risk of metastases in DPP-4i users. Copyright © 2017 Elsevier Inc. All rights reserved.

Intra-individual reaction time variability and all-cause mortality over 17 years: a community-based cohort study.

PubMed

Batterham, Philip J; Bunce, David; Mackinnon, Andrew J; Christensen, Helen

2014-01-01

very few studies have examined the association between intra-individual reaction time variability and subsequent mortality. Furthermore, the ability of simple measures of variability to predict mortality has not been compared with more complex measures. a prospective cohort study of 896 community-based Australian adults aged 70+ were interviewed up to four times from 1990 to 2002, with vital status assessed until June 2007. From this cohort, 770-790 participants were included in Cox proportional hazards regression models of survival. Vital status and time in study were used to conduct survival analyses. The mean reaction time and three measures of intra-individual reaction time variability were calculated separately across 20 trials of simple and choice reaction time tasks. Models were adjusted for a range of demographic, physical health and mental health measures. greater intra-individual simple reaction time variability, as assessed by the raw standard deviation (raw SD), coefficient of variation (CV) or the intra-individual standard deviation (ISD), was strongly associated with an increased hazard of all-cause mortality in adjusted Cox regression models. The mean reaction time had no significant association with mortality. intra-individual variability in simple reaction time appears to have a robust association with mortality over 17 years. Health professionals such as neuropsychologists may benefit in their detection of neuropathology by supplementing neuropsychiatric testing with the straightforward process of testing simple reaction time and calculating raw SD or CV.

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.

Association between participation in outdoor play and sport at 10 years old with physical activity in adulthood.

PubMed

Smith, Lee; Gardner, Benjamin; Aggio, Daniel; Hamer, Mark

2015-05-01

This study aimed to investigate whether active outdoor play and/or sports at age 10 is associated with sport/physical activity at 32 year follow-up using a birth cohort study. Data were from the 1970 British Cohort Study, a longitudinal observational study. The present paper included data from the age 10 years and age 42 years surveys. At age 10 the participant's mother provided information regarding how often their child played sports, and played outside on streets, parks or playgrounds. At age 42 participants reported frequency of participation in physical activities and sports. Associations between participation in sport/active outdoor play at age 10 years and adult sport/physical activity were investigated using adjusted (gender, fathers socio-occupational class, child's BMI, father's BMI, self-rated health at age 42, assessment of own weight at age 42, participant's education) Cox regression. Final adjusted Cox regression models showed that participants (n=6458) who often participated in sports at age 10 were significantly more likely to participate in sport/physical activity at age 42 (RR 1.10; 95% CI 1.01 to 1.19). Active outdoor play at age 10 was not associated with participation in sport/physical activity at age 42 (RR 0.99; 95% CI 0.91 to 1.07). Childhood activity interventions might best achieve lasting change by promoting engagement in sport rather than active outdoor play. Copyright © 2015. Published by Elsevier Inc.

Does vagotomy protect against multiple sclerosis?

PubMed

Sundbøll, Jens; Horváth-Puhó, Erzsébet; Adelborg, Kasper; Svensson, Elisabeth

2017-07-01

To examine the association between vagotomy and multiple sclerosis. We conducted a matched cohort study of all patients who underwent truncal or super-selective vagotomy and a comparison cohort, by linking Danish population-based medical registries (1977-1995). Hazard ratios (HRs) for multiple sclerosis, adjusting for potential confounders were computed by means of Cox regression analysis. Median age of multiple sclerosis onset corresponded to late onset multiple sclerosis. No association with multiple sclerosis was observed for truncal vagotomy (0-37 year adjusted HR=0.91, 95% confidence interval [CI]: 0.48-1.74) or super-selective vagotomy (0-37 year adjusted HR=1.28, 95% CI: 0.79-2.09) compared with the general population. We found no association between vagotomy and later risk of late onset multiple sclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

A simple approach to power and sample size calculations in logistic regression and Cox regression models.

PubMed

Vaeth, Michael; Skovlund, Eva

2004-06-15

For a given regression problem it is possible to identify a suitably defined equivalent two-sample problem such that the power or sample size obtained for the two-sample problem also applies to the regression problem. For a standard linear regression model the equivalent two-sample problem is easily identified, but for generalized linear models and for Cox regression models the situation is more complicated. An approximately equivalent two-sample problem may, however, also be identified here. In particular, we show that for logistic regression and Cox regression models the equivalent two-sample problem is obtained by selecting two equally sized samples for which the parameters differ by a value equal to the slope times twice the standard deviation of the independent variable and further requiring that the overall expected number of events is unchanged. In a simulation study we examine the validity of this approach to power calculations in logistic regression and Cox regression models. Several different covariate distributions are considered for selected values of the overall response probability and a range of alternatives. For the Cox regression model we consider both constant and non-constant hazard rates. The results show that in general the approach is remarkably accurate even in relatively small samples. Some discrepancies are, however, found in small samples with few events and a highly skewed covariate distribution. Comparison with results based on alternative methods for logistic regression models with a single continuous covariate indicates that the proposed method is at least as good as its competitors. The method is easy to implement and therefore provides a simple way to extend the range of problems that can be covered by the usual formulas for power and sample size determination. Copyright 2004 John Wiley & Sons, Ltd.

Urinary proteomics for prediction of mortality in patients with type 2 diabetes and microalbuminuria.

PubMed

Currie, Gemma E; von Scholten, Bernt Johan; Mary, Sheon; Flores Guerrero, Jose-Luis; Lindhardt, Morten; Reinhard, Henrik; Jacobsen, Peter K; Mullen, William; Parving, Hans-Henrik; Mischak, Harald; Rossing, Peter; Delles, Christian

2018-04-06

The urinary proteomic classifier CKD273 has shown promise for prediction of progressive diabetic nephropathy (DN). Whether it is also a determinant of mortality and cardiovascular disease in patients with microalbuminuria (MA) is unknown. Urine samples were obtained from 155 patients with type 2 diabetes and confirmed microalbuminuria. Proteomic analysis was undertaken using capillary electrophoresis coupled to mass spectrometry to determine the CKD273 classifier score. A previously defined CKD273 threshold of 0.343 for identification of DN was used to categorise the cohort in Kaplan-Meier and Cox regression models with all-cause mortality as the primary endpoint. Outcomes were traced through national health registers after 6 years. CKD273 correlated with urine albumin excretion rate (UAER) (r = 0.481, p = <0.001), age (r = 0.238, p = 0.003), coronary artery calcium (CAC) score (r = 0.236, p = 0.003), N-terminal pro-brain natriuretic peptide (NT-proBNP) (r = 0.190, p = 0.018) and estimated glomerular filtration rate (eGFR) (r = 0.265, p = 0.001). On multivariate analysis only UAER (β = 0.402, p < 0.001) and eGFR (β = - 0.184, p = 0.039) were statistically significant determinants of CKD273. Twenty participants died during follow-up. CKD273 was a determinant of mortality (log rank [Mantel-Cox] p = 0.004), and retained significance (p = 0.048) after adjustment for age, sex, blood pressure, NT-proBNP and CAC score in a Cox regression model. A multidimensional biomarker can provide information on outcomes associated with its primary diagnostic purpose. Here we demonstrate that the urinary proteomic classifier CKD273 is associated with mortality in individuals with type 2 diabetes and MA even when adjusted for other established cardiovascular and renal biomarkers.

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.

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

Increased incidence of peptic ulcer disease in central serous chorioretinopathy patients: a population-based retrospective cohort study.

PubMed

Chen, San-Ni; Lian, Iebin; Chen, Yi-Chiao; Ho, Jau-Der

2015-02-01

To investigate peptic ulcer disease and other possible risk factors in patients with central serous chorioretinopathy (CSR) using a population-based database. In this population-based retrospective cohort study, longitudinal data from the Taiwan National Health Insurance Research Database were analyzed. The study cohort comprised 835 patients with CSR and the control cohort comprised 4175 patients without CSR from January 2000 to December 2009. Conditional logistic regression was applied to examine the association of peptic ulcer disease and other possible risk factors for CSR, and stratified Cox regression models were applied to examine whether patients with CSR have an increased chance of peptic ulcer disease and hypertension development. The identifiable risk factors for CSR included peptic ulcer disease (adjusted odd ratio: 1.39, P = 0.001) and higher monthly income (adjusted odd ratio: 1.30, P = 0.006). Patients with CSR also had a significantly higher chance of developing peptic ulcer disease after the diagnosis of CSR (adjusted odd ratio: 1.43, P = 0.009). Peptic ulcer disease and higher monthly income are independent risk factors for CSR. Whereas, patients with CSR also had increased risk for peptic ulcer development.

Low-dose aspirin, non-steroidal anti-inflammatory drugs, selective COX-2 inhibitors and breast cancer recurrence

PubMed Central

Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P; Lash, Timothy L; Christiansen, Peer; Ejlertsen, Bent; Sørensen, Henrik T

2017-01-01

Background Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors may improve outcomes in breast cancer patients. We investigated the association of aspirin, NSAIDs, and use of selective COX-2 inhibitors with breast cancer recurrence. Methods We identified incident stage I–III Danish breast cancer patients in the Danish Breast Cancer Cooperative Group registry, who were diagnosed during 1996–2008. Prescriptions for aspirin (>99% low-dose aspirin), NSAIDs, and selective COX-2 inhibitors were ascertained from the National Prescription Registry (NPR). Follow-up began on the date of breast cancer primary surgery and continued until the first of recurrence, death, emigration, or 01/01/2013. We used Cox regression models to compute hazard ratios (HR) and corresponding 95% confidence intervals (95%CI) associating prescriptions with recurrence, adjusting for confounders. Results We identified 34,188 breast cancer patients with 233,130 person-years of follow-up. Median follow-up was 7.1 years; 5,325 patients developed recurrent disease. Use of aspirin, NSAIDs, or selective COX-2 inhibitors was not associated with the rate of recurrence (HRadjusted aspirin=1.0, 95% CI=0.90, 1.1; NSAIDs=0.99, 95% CI=0.92, 1.1; selective COX-2 inhibitors=1.1, 95% CI=0.98, 1.2), relative to non-use. Pre-diagnostic use of the exposure drugs was associated with reduced recurrence rates (HRaspirin=0.92, 95%CI=0.82, 1.0; HRNSAIDs=0.86, 95%CI=0.81, 0.91; HRsCOX-2inhibitors=0.88, 95%CI=0.83, 0.95). Conclusions This prospective cohort study suggests that post-diagnostic prescriptions for aspirin, NSAIDs, and selective COX-2 inhibitors have little or no association with the rate of breast cancer recurrence. Pre-diagnostic use of the drugs was, however, associated with a reduced rate of breast cancer recurrence. PMID:27007644

Depression and incident dementia. An 8-year population-based prospective study.

PubMed

Luppa, Melanie; Luck, Tobias; Ritschel, Franziska; Angermeyer, Matthias C; Villringer, Arno; Riedel-Heller, Steffi G

2013-01-01

The aim of the study was to investigate the impact of depression (categorical diagnosis; major depression, MD) and depressive symptoms (dimensional diagnosis and symptom patterns) on incident dementia in the German general population. Within the Leipzig Longitudinal Study of the Aged (LEILA 75+), a representative sample of 1,265 individuals aged 75 years and older were interviewed every 1.5 years over 8 years (mean observation time 4.3 years; mean number of visits 4.2). Cox proportional hazards and binary logistic regressions were used to estimate the effect of baseline depression and depressive symptoms on incident dementia. The incidence of dementia was 48 per 1,000 person-years (95% confidence interval (CI) 45-51). Depressive symptoms (Hazard ratio HR 1.03, 95% CI 1.01-1.05), and in particular mood-related symptoms (HR 1.08, 95% CI 1.03-1.14), showed a significant impact on the incidence of dementia only in univariate analysis, but not after adjustment for cognitive and functional impairment. MD showed only a significant impact on incidence of dementia in Cox proportional hazards regression, but not in binary logistic regression models. The present study using different diagnostic measures of depression on future dementia found no clear significant associations of depression and incident dementia. Further in-depth investigation would help to understand the nature of depression in the context of incident dementia.

Serum Uric Acid Is Associated with Poor Outcome in Black Africans in the Acute Phase of Stroke

PubMed Central

Ayeah, Chia Mark; Ba, H.; Mbahe, Salomon

2017-01-01

Background Prognostic significance of serum uric acid (SUA) in acute stroke still remains controversial. Objectives To determine the prevalence of hyperuricemia and its association with outcome of stroke patients in the Douala General Hospital (DGH). Methods This was a hospital based prospective cohort study which included acute stroke patients with baseline SUA levels and 3-month poststroke follow-up data. Associations between high SUA levels and stroke outcomes were analyzed using multiple logistic regression and survival analysis (Cox regression and Kaplan-Meier). Results A total of 701 acute stroke patients were included and the prevalence of hyperuricemia was 46.6% with a mean SUA level of 68.625 ± 24 mg/l. Elevated SUA after stroke was associated with death (OR = 2.067; 95% CI: 1.449–2.950; p < 0.001) but did not predict this issue. However, an independent association between increasing SUA concentration and mortality was noted in a Cox proportional hazards regression model (adjusted HR = 1.740; 95% CI: 1.305–2.320; p < 0.001). Furthermore, hyperuricemia was an independent predictor of poor functional outcome within 3 months after stroke (OR = 2.482; 95% CI: 1.399–4.404; p = 0.002). Conclusion The prevalence of hyperuricemia in black African stroke patients is quite high and still remains a predictor of poor outcome. PMID:29082062

Comparison between alcohol- and hepatitis C virus-related hepatocellular carcinoma: clinical presentation, treatment and outcome.

PubMed

Bucci, L; Garuti, F; Camelli, V; Lenzi, B; Farinati, F; Giannini, E G; Ciccarese, F; Piscaglia, F; Rapaccini, G L; Di Marco, M; Caturelli, E; Zoli, M; Borzio, F; Sacco, R; Maida, M; Felder, M; Morisco, F; Gasbarrini, A; Gemini, S; Foschi, F G; Missale, G; Masotto, A; Affronti, A; Bernardi, M; Trevisani, F

2016-02-01

Hepatitis C virus (HCV) and alcohol abuse are the main risk factors for hepatocellular carcinoma (HCC) in Western countries. To investigate the role of alcoholic aetiology on clinical presentation, treatment and outcome of HCC as well as on each Barcelona Clinic Liver Cancer (BCLC) stage, as compared to HCV-related HCCs. A total of 1642 HCV and 573 alcoholic patients from the Italian Liver Cancer (ITA.LI.CA) database, diagnosed with HCC between January 2000 and December 2012 were compared for age, gender, type of diagnosis, tumour burden, portal vein thrombosis (PVT), oesophageal varices, liver function tests, alpha-fetoprotein, BCLC, treatment and survival. Aetiology was tested as predictor of survival in multivariate Cox regression models and according to HCC stages. Cirrhosis was present in 96% of cases in both groups. Alcoholic patients were younger, more likely male, with HCC diagnosed outside surveillance, in intermediate/terminal BCLC stage and had worse liver function. After adjustment for the lead-time, median (95% CI) overall survival (OS) was 27.4 months (21.5-33.2) in alcoholic and 33.6 months (30.7-36.5) in HCV patients (P = 0.021). The prognostic role of aetiology disappeared when survival was assessed in each BCLC stage and in the Cox regression multivariate models. Alcoholic aetiology affects survival of HCC patients through its negative effects on secondary prevention and cancer presentation but not through a greater cancer aggressiveness or worse treatment result. In fact, survival adjusted for confounding factors was similar in alcoholic and HCV patients. © 2015 John Wiley & Sons Ltd.

Simultaneous confidence bands for Cox regression from semiparametric random censorship.

PubMed

Mondal, Shoubhik; Subramanian, Sundarraman

2016-01-01

Cox regression is combined with semiparametric random censorship models to construct simultaneous confidence bands (SCBs) for subject-specific survival curves. Simulation results are presented to compare the performance of the proposed SCBs with the SCBs that are based only on standard Cox. The new SCBs provide correct empirical coverage and are more informative. The proposed SCBs are illustrated with two real examples. An extension to handle missing censoring indicators is also outlined.

Scoring and staging systems using cox linear regression modeling and recursive partitioning.

PubMed

Lee, J W; Um, S H; Lee, J B; Mun, J; Cho, H

2006-01-01

Scoring and staging systems are used to determine the order and class of data according to predictors. Systems used for medical data, such as the Child-Turcotte-Pugh scoring and staging systems for ordering and classifying patients with liver disease, are often derived strictly from physicians' experience and intuition. We construct objective and data-based scoring/staging systems using statistical methods. We consider Cox linear regression modeling and recursive partitioning techniques for censored survival data. In particular, to obtain a target number of stages we propose cross-validation and amalgamation algorithms. We also propose an algorithm for constructing scoring and staging systems by integrating local Cox linear regression models into recursive partitioning, so that we can retain the merits of both methods such as superior predictive accuracy, ease of use, and detection of interactions between predictors. The staging system construction algorithms are compared by cross-validation evaluation of real data. The data-based cross-validation comparison shows that Cox linear regression modeling is somewhat better than recursive partitioning when there are only continuous predictors, while recursive partitioning is better when there are significant categorical predictors. The proposed local Cox linear recursive partitioning has better predictive accuracy than Cox linear modeling and simple recursive partitioning. This study indicates that integrating local linear modeling into recursive partitioning can significantly improve prediction accuracy in constructing scoring and staging systems.

Non-Asymptotic Oracle Inequalities for the High-Dimensional Cox Regression via Lasso.

PubMed

Kong, Shengchun; Nan, Bin

2014-01-01

We consider finite sample properties of the regularized high-dimensional Cox regression via lasso. Existing literature focuses on linear models or generalized linear models with Lipschitz loss functions, where the empirical risk functions are the summations of independent and identically distributed (iid) losses. The summands in the negative log partial likelihood function for censored survival data, however, are neither iid nor Lipschitz.We first approximate the negative log partial likelihood function by a sum of iid non-Lipschitz terms, then derive the non-asymptotic oracle inequalities for the lasso penalized Cox regression using pointwise arguments to tackle the difficulties caused by lacking iid Lipschitz losses.

Non-Asymptotic Oracle Inequalities for the High-Dimensional Cox Regression via Lasso

PubMed Central

Kong, Shengchun; Nan, Bin

2013-01-01

We consider finite sample properties of the regularized high-dimensional Cox regression via lasso. Existing literature focuses on linear models or generalized linear models with Lipschitz loss functions, where the empirical risk functions are the summations of independent and identically distributed (iid) losses. The summands in the negative log partial likelihood function for censored survival data, however, are neither iid nor Lipschitz.We first approximate the negative log partial likelihood function by a sum of iid non-Lipschitz terms, then derive the non-asymptotic oracle inequalities for the lasso penalized Cox regression using pointwise arguments to tackle the difficulties caused by lacking iid Lipschitz losses. PMID:24516328

Modeling the safety impacts of driving hours and rest breaks on truck drivers considering time-dependent covariates.

PubMed

Chen, Chen; Xie, Yuanchang

2014-12-01

Driving hours and rest breaks are closely related to driver fatigue, which is a major contributor to truck crashes. This study investigates the effects of driving hours and rest breaks on commercial truck driver safety. A discrete-time logistic regression model is used to evaluate the crash odds ratios of driving hours and rest breaks. Driving time is divided into 11 one hour intervals. These intervals and rest breaks are modeled as dummy variables. In addition, a Cox proportional hazards regression model with time-dependent covariates is used to assess the transient effects of rest breaks, which consists of a fixed effect and a variable effect. Data collected from two national truckload carriers in 2009 and 2010 are used. The discrete-time logistic regression result indicates that only the crash odds ratio of the 11th driving hour is statistically significant. Taking one, two, and three rest breaks can reduce drivers' crash odds by 68%, 83%, and 85%, respectively, compared to drivers who did not take any rest breaks. The Cox regression result shows clear transient effects for rest breaks. It also suggests that drivers may need some time to adjust themselves to normal driving tasks after a rest break. Overall, the third rest break's safety benefit is very limited based on the results of both models. The findings of this research can help policy makers better understand the impact of driving time and rest breaks and develop more effective rules to improve commercial truck safety. Copyright © 2014 National Safety Council and Elsevier Ltd. All rights reserved.

Practical application of cure mixture model for long-term censored survivor data from a withdrawal clinical trial of patients with major depressive disorder.

PubMed

Arano, Ichiro; Sugimoto, Tomoyuki; Hamasaki, Toshimitsu; Ohno, Yuko

2010-04-23

Survival analysis methods such as the Kaplan-Meier method, log-rank test, and Cox proportional hazards regression (Cox regression) are commonly used to analyze data from randomized withdrawal studies in patients with major depressive disorder. However, unfortunately, such common methods may be inappropriate when a long-term censored relapse-free time appears in data as the methods assume that if complete follow-up were possible for all individuals, each would eventually experience the event of interest. In this paper, to analyse data including such a long-term censored relapse-free time, we discuss a semi-parametric cure regression (Cox cure regression), which combines a logistic formulation for the probability of occurrence of an event with a Cox proportional hazards specification for the time of occurrence of the event. In specifying the treatment's effect on disease-free survival, we consider the fraction of long-term survivors and the risks associated with a relapse of the disease. In addition, we develop a tree-based method for the time to event data to identify groups of patients with differing prognoses (cure survival CART). Although analysis methods typically adapt the log-rank statistic for recursive partitioning procedures, the method applied here used a likelihood ratio (LR) test statistic from a fitting of cure survival regression assuming exponential and Weibull distributions for the latency time of relapse. The method is illustrated using data from a sertraline randomized withdrawal study in patients with major depressive disorder. We concluded that Cox cure regression reveals facts on who may be cured, and how the treatment and other factors effect on the cured incidence and on the relapse time of uncured patients, and that cure survival CART output provides easily understandable and interpretable information, useful both in identifying groups of patients with differing prognoses and in utilizing Cox cure regression models leading to meaningful interpretations.

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.

Effect of ionized serum calcium on outcomes in acute kidney injury needing renal replacement therapy: Secondary analysis of the Acute Renal Failure Trial Network Study

PubMed Central

Afshinnia, Farsad; Belanger, Karen; Palevsky, Paul M.; Young, Eric W.

2014-01-01

Background Hypocalcemia is very common in critically ill patients. While the effect of ionized calcium (iCa) on outcome is not well understood, manipulation of iCa in critically ill patients is a common practice. We analyzed all-cause mortality and several secondary outcomes in patients with acute kidney injury (AKI) by categories of serum iCa among participants in the Acute Renal Failure Trial Network (ATN) Study. Methods This is a post hoc secondary analysis of the ATN Study which was not preplanned in the original trial. Risk of mortality and renal recovery by categories of iCa were compared using multiple fixed and adjusted time-varying Cox regression models. Multiple linear regression models were used to explore the impact of baseline iCa on days free from ICU and hospital. Results A total of 685 patients were included in the analysis. Mean age was 60 (SD=15) years. There were 502 male patients (73.3%). Sixty-day all-cause mortality was 57.0%, 54.8%, and 54.4%, in patients with an iCa <1, 1–1.14, and ≥1.15 mmol/L, respectively (P=0.87). Mean of days free from ICU or hospital in all patients and the 28-day renal recovery in survivors to day 28 were not significantly different by categories of iCa. The hazard for death in a fully adjusted time-varying Cox regression survival model was 1.7 (95% CI: 1.3–2.4) comparing iCa <1 to iCa ≥1.15 mmol/L. No outcome was different for levels of iCa >1 mmol/L. Conclusion Severe hypocalcemia with iCa <1 mmol/L independently predicted mortality in patients with AKI needing renal replacement therapy. PMID:23992422

Prevalence and Evolution of Renal Impairment in People Living With HIV in Rural Tanzania.

PubMed

Mapesi, Herry; Kalinjuma, Aneth V; Ngerecha, Alphonce; Franzeck, Fabian; Hatz, Christoph; Tanner, Marcel; Mayr, Michael; Furrer, Hansjakob; Battegay, Manuel; Letang, Emilio; Weisser, Maja; Glass, Tracy R

2018-04-01

We assessed the prevalence, incidence, and predictors of renal impairment among people living with HIV (PLWHIV) in rural Tanzania. In a cohort of PLWHIV aged ≥15 years enrolled from January 2013 to June 2016, we assessed the association between renal impairment (estimated glomerural filtration rate < 90 mL/min/1.73 m 2 ) at enrollment and during follow-up with demographic and clinical characteristcis using logistic regression and Cox proportional hazards models. Of 1093 PLWHIV, 172 (15.7%) had renal impairment at enrollment. Of 921 patients with normal renal function at baseline, 117 (12.7%) developed renal impairment during a median follow-up (interquartile range) of 6.2 (0.4-14.7) months. The incidence of renal impairment was 110 cases per 1000 person-years (95% confidence interval [CI], 92-132). At enrollment, logistic regression identified older age (adjusted odds ratio [aOR], 1.79; 95% CI, 1.52-2.11), hypertension (aOR, 1.84; 95% CI, 1.08-3.15), CD4 count <200 cells/mm 3 (aOR, 1.80; 95% CI, 1.23-2.65), and World Health Organization (WHO) stage III/IV (aOR, 3.00; 95% CI, 1.96-4.58) as risk factors for renal impairment. Cox regression model confirmed older age (adjusted hazard ratio [aHR], 1.85; 95% CI, 1.56-2.20) and CD4 count <200 cells/mm 3 (aHR, 2.05; 95% CI, 1.36-3.09) to be associated with the development of renal impairment. Our study found a low prevalence of renal impairment among PLWHIV despite high usage of tenofovir and its association with age, hypertension, low CD4 count, and advanced WHO stage. These important and reassuring safety data stress the significance of noncommunicable disease surveillance in aging HIV populations in sub-Saharan Africa.

Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome.

PubMed

Morgan, Thomas M; House, John A; Cresci, Sharon; Jones, Philip; Allayee, Hooman; Hazen, Stanley L; Patel, Yesha; Patel, Riyaz S; Eapen, Danny J; Waddy, Salina P; Quyyumi, Arshed A; Kleber, Marcus E; März, Winfried; Winkelmann, Bernhard R; Boehm, Bernhard O; Krumholz, Harlan M; Spertus, John A

2011-09-29

Genome-wide association studies (GWAS) have identified new candidate genes for the occurrence of acute coronary syndrome (ACS), but possible effects of such genes on survival following ACS have yet to be investigated. We examined 95 polymorphisms in 69 distinct gene regions identified in a GWAS for premature myocardial infarction for their association with post-ACS mortality among 811 whites recruited from university-affiliated hospitals in Kansas City, Missouri. We then sought replication of a positive genetic association in a large, racially diverse cohort of myocardial infarction patients (N = 2284) using Kaplan-Meier survival analyses and Cox regression to adjust for relevant covariates. Finally, we investigated the apparent association further in 6086 additional coronary artery disease patients. After Cox adjustment for other ACS risk factors, of 95 SNPs tested in 811 whites only the association with the rs6922269 in MTHFD1L was statistically significant, with a 2.6-fold mortality hazard (P = 0.007). The recessive A/A genotype was of borderline significance in an age- and race-adjusted analysis of the entire combined cohort (N = 3095; P = 0.052), but this finding was not confirmed in independent cohorts (N = 6086). We found no support for the hypothesis that the GWAS-identified variants in this study substantially alter the probability of post-ACS survival. Large-scale, collaborative, genome-wide studies may be required in order to detect genetic variants that are robustly associated with survival in patients with coronary artery disease.

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.

A comparison between the use of Cox regression and the use of partial least squares-Cox regression to predict the survival of kidney-transplant patients

NASA Astrophysics Data System (ADS)

Solimun

2017-05-01

The aim of this research is to model survival data from kidney-transplant patients using the partial least squares (PLS)-Cox regression, which can both meet and not meet the no-multicollinearity assumption. The secondary data were obtained from research entitled "Factors affecting the survival of kidney-transplant patients". The research subjects comprised 250 patients. The predictor variables consisted of: age (X1), sex (X2); two categories, prior hemodialysis duration (X3), diabetes (X4); two categories, prior transplantation number (X5), number of blood transfusions (X6), discrepancy score (X7), use of antilymphocyte globulin(ALG) (X8); two categories, while the response variable was patient survival time (in months). Partial least squares regression is a model that connects the predictor variables X and the response variable y and it initially aims to determine the relationship between them. Results of the above analyses suggest that the survival of kidney transplant recipients ranged from 0 to 55 months, with 62% of the patients surviving until they received treatment that lasted for 55 months. The PLS-Cox regression analysis results revealed that patients' age and the use of ALG significantly affected the survival time of patients. The factor of patients' age (X1) in the PLS-Cox regression model merely affected the failure probability by 1.201. This indicates that the probability of dying for elderly patients with a kidney transplant is 1.152 times higher than that for younger patients.

Sequential cohort design applying propensity score matching to analyze the comparative effectiveness of atorvastatin and simvastatin in preventing cardiovascular events.

PubMed

Helin-Salmivaara, Arja; Lavikainen, Piia; Aarnio, Emma; Huupponen, Risto; Korhonen, Maarit Jaana

2014-01-01

Sequential cohort design (SCD) applying matching for propensity scores (PS) in accrual periods has been proposed to mitigate bias caused by channeling when calendar time is a proxy for strong confounders. We studied the channeling of patients according to atorvastatin and simvastatin initiation in Finland, starting from the market introduction of atorvastatin in 1998, and explored the SCD PS approach to analyzing the comparative effectiveness of atorvastatin versus simvastatin in the prevention of cardiovascular events (CVE). Initiators of atorvastatin or simvastatin use in the 45-75-year age range in 1998-2006 were characterized by their propensity of receiving atorvastatin over simvastatin, as estimated for 17 six-month periods. Atorvastatin (10 mg) and simvastatin (20 mg) initiators were matched 1∶1 on the PS, as estimated for the whole cohort and within each period. Cox regression models were fitted conventionally, and also for the PS matched cohort and the periodically PS matched cohort, to estimate the hazard ratios (HR) for CVEs. Atorvastatin (10 mg) was associated with a 11%-12% lower incidence of CVE in comparison with simvastatin (20 mg). The HR estimates were the same for a conventional Cox model (0.88, 95% confidence interval 0.85-0.91), for the analysis in which the PS was used to match across all periods and the Cox model was adjusted for strong confounders (0.89, 0.85-0.92), and for the analysis in which PS matching was applied within sequential periods (0.88, 0.84-0.92). The HR from a traditional PS matched analysis was 0.80 (0.77-0.83). The SCD PS approach produced effect estimates similar to those obtained in matching for PS within the whole cohort and adjusting the outcome model for strong confounders, but at the cost of efficiency. A traditional PS matched analysis without further adjustment in the outcome model produced estimates further away from unity.

Association Between Metabolic Syndrome and the Serum Uric Acid: a Cohort Study.

PubMed

Ren, Ping; Gao, Mengna

2018-05-01

Metabolic syndrome (MS) consists of a cluster of metabolic diseases, and the association between serum uric acid (SUA) and MS has recently been reported in several studies; however, whether SUA is a susceptibility or risk biomarker for the development of MS among Chinese adults is unclear. This study was designed to investigate the relationship between SUA and MS. This study involved 4,988 subjects who were followed up for 9 years. Cox regression model was used to analyze the risk factors of MS. Of the 4,988 subjects, 1,192 subjects developed MS over 9 years of follow-up. The overall 9-year cumulative incidence of MS was 23.9%, ranging from 16.6% in quartile 1 to 35.1% in quartile 4 (p for trend < 0.001). Cox regression analyses indicated that SUA was significantly associated with incident MS (HR comparing quartile 2, 3, and 4 vs. quartile 1, 1.11, 1.33, and 1.78, respectively; p < 0.001) after adjusting for multiple associated parameters. In receiver operating characteristic curve analysis, the cutoff levels for SUA to predict incident MS were 350 μmol/L and 268 μmol/L in males and females, respectively. The results of this study demonstrated that high SUA concentrations may increase the risk of MS among Chinese adults.

Erectile Dysfunction in Male Adults With Atopic Dermatitis and Psoriasis.

PubMed

Egeberg, Alexander; Hansen, Peter R; Gislason, Gunnar H; Skov, Lone; Thyssen, Jacob P

2017-03-01

Patients with psoriasis have increased risk of cardiovascular disease, but data on atopic dermatitis (AD) are less clear-cut. However, it is well-established that erectile dysfunction (ED) can serve as a risk marker for coronary disease. To investigate the incidence, prevalence, and risk of ED in men with psoriasis and AD. The sample included all Danish men at least 30 years old. In patients with AD and psoriasis, we determined disease severity based on use of systemic therapy. We performed a cross-sectional study (January 1, 2008) using logistic regression to estimate the prevalence and odds ratio of ED. Moreover, in a cohort study design, patients were followed from January 1, 2008 through December 31, 2012, and Cox regression models were used to estimate adjusted hazard ratios of new-onset ED. Models were adjusted for potential confounding factors, including age, socioeconomic status, health care consumption, smoking, alcohol abuse, diabetes, and cholesterol-lowering drug use. The outcome was initiation of pharmacotherapy used for treatment of ED. The sample consisted of 1,756,679 Danish men (age range = 30-100 years), of which 2,373 and 26,536 had adult AD (mild = 1,072; severe = 1,301) and psoriasis (mild = 21,775; severe = 4,761), respectively. Mean ages (SDs) were 53.0 (14.6), 46.7 (12.0), and 56.3 (13.8) years for the general population, patients with AD, and patients with psoriasis, respectively. Prevalences of ED were 8.7%, 6.7%, and 12.8% for the general population, patients with AD, and patients with psoriasis, respectively. Adjusted odds ratios (logistic regression) of ED were decreased in patients with AD (0.68; 0.57-0.80) but increased in those with psoriasis (1.15; 1.11-1.20). Adjusted odds ratios for mild and severe AD were 0.63 (0.48-0.82) and 0.72 (0.58-0.88), respectively, and those for psoriasis these were 1.16 (1.11-1.21) and 1.13 (1.03-1.23). Adjusted hazard ratios (Cox regression) were 0.92 (0.76-1.11) for AD and 1.14 (1.08-1.20) for psoriasis. The ED risk was not increased in men with mild AD (0.85; 0.63-1.14) or severe AD (0.97; 0.76-1.24) but was significantly increased in men with mild psoriasis (1.13; 1.09-1.20) and severe psoriasis (1.17; 1.04-1.32). We found an increased prevalence and risk of ED in men with psoriasis, whereas the risk was comparable to (and even slightly lower than) the general population for men with AD. Egeberg A, Hansen PR, Gislason GH, et al. Erectile Dysfunction in Male Adults With Atopic Dermatitis and Psoriasis. J Sex Med 2017;14:380-386. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Behavioural disorders in 6-year-old children and pyrethroid insecticide exposure: the PELAGIE mother-child cohort.

PubMed

Viel, Jean-François; Rouget, Florence; Warembourg, Charline; Monfort, Christine; Limon, Gwendolina; Cordier, Sylvaine; Chevrier, Cécile

2017-03-01

The potential impact of environmental exposure to pyrethroid insecticides on child neurodevelopment has only just started to receive attention despite their widespread use. We investigated the associations between prenatal and childhood exposure to pyrethroid insecticides and behavioural skills in 6-year-olds. The PELAGIE cohort enrolled 3421 pregnant women from Brittany, France between 2002 and 2006. 428 mothers were randomly selected for the study when their children turned 6, and 287 (67%) agreed to participate. Children's behaviour was assessed using the Strengths and Difficulties Questionnaire (SDQ). Three subscales (prosocial behaviour, internalising disorders and externalising disorders) were considered. Five pyrethroid metabolites were measured in maternal and child urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Logistic regression and reverse-scale Cox regression models were used to estimate the associations between SDQ scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders. Increased prenatal cis -3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (DCCA) concentrations were associated with internalising difficulties (Cox p value=0.05). For childhood 3-phenoxybenzoic acid (PBA) concentrations, a positive association was observed with externalising difficulties (Cox p value=0.04) and high ORs were found for abnormal or borderline social behaviour (OR 2.93, 95% CI 1.27 to 6.78, and OR 1.91, 95% CI 0.80 to 4.57, for the intermediate and highest metabolite categories, respectively). High childhood trans -DCCA concentrations were associated with reduced externalising disorders (Cox p value=0.03). The present study suggests that exposure to certain pyrethroids, at environmental levels, may negatively affect neurobehavioral development by 6 years of age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The Relationship Between the Dietary Inflammatory Index and Incident Frailty: A Longitudinal Cohort Study.

PubMed

Shivappa, Nitin; Stubbs, Brendon; Hébert, James R; Cesari, Matteo; Schofield, Patricia; Soysal, Pinar; Maggi, Stefania; Veronese, Nicola

2018-01-01

Inflammation is key risk factor for several conditions in the elderly. However, the relationship between inflammation and frailty is still unclear. We investigated whether higher dietary inflammatory index (DII) scores were associated with higher incidence of frailty in a cohort of North Americans. Longitudinal, with a follow-up of 8 years. Osteoarthritis Initiative. A total of 4421 participants with, or at high risk of, knee osteoarthritis. DII scores were calculated using the validated Block Brief 2000 Food-Frequency Questionnaire and categorized into sex-specific quartiles. Frailty was defined as 2 out of 3 of the criteria of the Study of Osteoporotic Fracture study (ie, weight loss, inability to rise from a chair 5 times, and poor energy). The strength of the association between baseline DII score and incident frailty was assessed through a Cox's regression analysis, adjusted for potential baseline confounders, and reported as hazard ratios. A total of 4421 community-dwelling participants (2564 female participants; mean age: 61.3 years) without frailty at baseline were identified from the Osteoarthritis Initiative. During 8 years of follow-up, 356 individuals developed frailty (8.2%). Using Cox's regression analysis, adjusting for 11 potential confounders, participants with the highest DII score (quartile 4) had a significantly higher risk of experiencing frailty (hazard ratio 1.37; 95% confidence interval 1.01-1.89; P = .04) compared with participants with the lowest DII score (quartile 1). The association between DII score and frailty was significant only in men. Higher DII scores, indicating a more proinflammatory diet, are associated with higher incidence of frailty, particularly in men. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Drug-Eluting Stents versus Bare-Metal Stents in Taiwanese Patients with Acute Coronary Syndrome: An Outcome Report of a Multicenter Registry

PubMed Central

Lai, Chi-Cheng; Yip, Hon-Kan; Lin, Tsung-Hsien; Wu, Chiung-Jen; Lai, Wen-Ter; Liu, Chun-Peng; Chang, Shu-Chen; Mar, Guang-Yuan

2014-01-01

Background The study aims to compare cardiovascular outcomes of using bare-metal stents (BMS) and drug-eluting stents (DES) in patients with acute coronary syndrome (ACS) through analysis of the database from the Taiwan ACS registry. Large domestic studies comparing outcomes of interventional strategies using DES and BMS in a Taiwanese population with ACS are limited. Methods and Results Collected data regarding characteristics and cardiovascular outcomes from the registry database were compared between the BMS and DES groups. A Cox regression model was used in an unadjusted or adjusted manner for analysis. Baseline characteristics apparently varied between DES group (n = 650) and BMS group (n = 1672) such as ACS types, Killip’s classifications, or coronary blood flows. Compared with the BMS group, the DES group was associated with significantly lower cumulative incidence of all-cause mortality (3.4% vs. 5.8%, p = 0.008), target vessel revascularization (TVR) (5.2% vs. 7.4%, p = 0.035), or major adverse cardiac events (MACE) (10.2% vs. 15.6%, p < 0.001) at 1 year in a real-world setting. Cox regression analysis showed the BMS group referenced as the DES group had significantly higher risk-adjusted total mortality [hazard ratio (HR) = 1.85, p = 0.026], target vessel revascularization (TVR) (HR = 1.59, p = 0.035), and MACE (HR = 1.68, p = 0.001). Conclusions The data show use of DES over BMS provided advantages to patients with ACS in terms of lower 1-year mortality, TVR, and MACE. The study suggests implantation of DES compared with BMS in Taiwanese patients with ACS is safe and beneficial in the real-world setting. PMID:27122834

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.

Effect of Cytomegalovirus Infection on Survival of Older Kidney Transplant Patients (D+/R+): Impact of Valganciclovir Prophylaxis Versus Preemptive Therapy.

PubMed

Luna, E; Caravaca, F; Ferreira, F; Fernandez, N; Martín, P; Vargas, M L; Saenz de Santamaría, J; Garcia Pino, G; Azevedo, L; Muñoz Sanz, A

2016-11-01

Kidney transplant patients with D+/R+ serology can be treated with either prophylaxis or preemptive valganciclovir. The older transplant population suffers severe immunosenescence, especially patients with latent cytomegalovirus (CMV) infection (R+). They are more likely to develop indirect CMV effects. Likewise, many patients have significant cardiovascular comorbidity, which makes them more sensitive to these indirect effects. The aim of this study was to evaluate the incidence of CMV viremia and indirect effects on survival, comparing prophylaxis (V) against preemptive (P) valganciclovir in an older kidney transplant population. We analyzed the data of 233 recipients from 2002 (age, >55 years; D+/R+) with ≥6 months of follow-up. The patients were divided into 2 groups: 167 (71.7%) in the V group and 66 (28.3%) in the P group. The incidence of CMV infection in the P group was 32% versus 6% in V group. Patients with CMV viremia showed worse survival values than patients without viremia (log rank P = .031). Five-year survivals were 74% vs 88%, respectively. Cox regression showed that the adjusted effect of CMV infection on overall survival was a significant risk (hazard ratio [HR], 2.07; 95% CI, 1.003-4.29). Patients with CMV viremia showed worse cardiovascular survival than patients without viremia, with 5-year survivals of 79% vs 94%. Cox regression showed that the adjusted effect of CMV infection was a significant risk (HR, 2.62). CMV infection has a detrimental effect on the survival of older patients. Valganciclovir prophylaxis induces a protective effect against CMV infection and could improve survival of older patients with cardiovascular comorbidities. Copyright © 2016 Elsevier Inc. All rights reserved.

Chronic Stenotrophomonas maltophilia infection and mortality or lung transplantation in cystic fibrosis patients.

PubMed

Waters, Valerie; Atenafu, Eshetu G; Lu, Annie; Yau, Yvonne; Tullis, Elizabeth; Ratjen, Felix

2013-09-01

Chronic Stenotrophomonas maltophilia infection is an independent risk factor for severe pulmonary exacerbations in cystic fibrosis (CF) patients. The goal of this study was to determine the effect of chronic S. maltophilia infection on mortality and the need for lung transplantation in a longitudinal study of children and adults with CF. This was a cohort study of CF patients from the Hospital for Sick Children and St Michael's Hospital (Toronto, Canada) from 1997 to 2008. A Cox Regression model was used to estimate the hazard ratio (HR) to time of death or lung transplantation adjusting for age, gender, genotype, pancreatic status, CF related diabetes (CFRD), forced expiratory volume in 1 s (FEV1), body mass index, number of pulmonary exacerbations, Pseudomonas aeruginosa, Burkholderia cepacia complex, Aspergillus and chronic S. maltophilia infection. A total of 687 patients were followed over the 12 year study period; 95 patients underwent a lung transplantation (of which 26 died) and an additional 49 patients died (total 144 events). In a Cox Regression model adjusting for baseline FEV1, baseline infection with B. cepacia complex (HR 1.72, 95% CI 1.09-2.71) and baseline chronic S. maltophilia infection (HR 2.80, 95% CI 1.65-4.76) were significantly associated with death or lung transplant. However, in a time-varying model, infection with B. cepacia complex and chronic S. maltophilia infection were no longer significant. Baseline chronic S. maltophilia infection is associated with an almost three-fold increased risk of death or lung transplant in CF patients. It is still unclear, however, whether chronic S. maltophilia infection is simply a marker of severity of disease and ultimate mortality or whether it is causally related to disease progression. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Smoking, body weight, physical exercise, and risk of lower limb total joint replacement in a population-based cohort of men.

PubMed

Mnatzaganian, George; Ryan, Philip; Norman, Paul E; Davidson, David C; Hiller, Janet E

2011-08-01

To assess the associations of smoking, body weight, and physical activity with risk of undergoing total joint replacement (TJR) in a population-based cohort of men. A cohort study of 11,388 men that integrated clinical data with hospital morbidity data and mortality records was undertaken. The risk of undergoing TJR was modeled on baseline weight, height, comorbidity, socioeconomic status, years of smoking, and exercise in 3 separate age groups, using Cox proportional hazards regressions and competing risk regressions (CRRs). Dose-response relationships between weight and risk of TJR and between smoking and risk of TJR were observed. Being overweight independently increased the risk of TJR, while smoking lowered the risk. The decreased risk among smokers was demonstrated in both Cox and CRR models and became apparent after 23 years of exposure. Men who were in the highest quartile (≥48 years of smoking) were 42-51% less likely to undergo TJR than men who had never smoked. Tests for trend in the log hazard ratios (HRs) across both smoking and weight quantiles yielded significant P values. Vigorous exercise increased the hazard of TJR; however, the association reached statistical significance only in the 70-74-year-old age group (adjusted HR 1.64 [95% confidence interval 1.19-2.24]). Adjusting for Deyo-Charlson Index or Elixhauser's comorbidity measures did not eliminate these associations. Our findings indicate that being overweight and reporting vigorous physical activity increase the risk of TJR. This study is the first to demonstrate a strong inverse dose-response relationship between duration of smoking and risk of TJR. More research is needed to better understand the role of smoking in the pathogenesis of osteoarthritis. Copyright © 2011 by the American College of Rheumatology.

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.

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

The risk of revision in total knee arthroplasty is not affected by previous high tibial osteotomy

PubMed Central

Badawy, Mona; Fenstad, Anne M; Indrekvam, Kari; Havelin, Leif I; Furnes, Ove

2015-01-01

Background and purpose — Previous studies have found different outcomes after revision of knee arthroplasties performed after high tibial osteotomy (HTO). We evaluated the risk of revision of total knee arthroplasty with or without previous HTO in a large registry material. Patients and methods — 31,077 primary TKAs were compared with 1,399 TKAs after HTO, using Kaplan-Meier 10-year survival percentages and adjusted Cox regression analysis. Results — The adjusted survival analyses showed similar survival in the 2 groups. The Kaplan-Meier 10-year survival was 93.8% in the primary TKA group and 92.6% in the TKA-post-HTO group. Adjusted RR was 0.97 (95% CI: 0.77–1.21; p = 0.8). Interpretation — In this registry-based study, previous high tibial osteotomy did not appear to compromise the results regarding risk of revision after total knee arthroplasty compared to primary knee arthroplasty. PMID:26058747

Immortal time bias in observational studies of time-to-event outcomes.

PubMed

Jones, Mark; Fowler, Robert

2016-12-01

The purpose of the study is to show, through simulation and example, the magnitude and direction of immortal time bias when an inappropriate analysis is used. We compare 4 methods of analysis for observational studies of time-to-event outcomes: logistic regression, standard Cox model, landmark analysis, and time-dependent Cox model using an example data set of patients critically ill with influenza and a simulation study. For the example data set, logistic regression, standard Cox model, and landmark analysis all showed some evidence that treatment with oseltamivir provides protection from mortality in patients critically ill with influenza. However, when the time-dependent nature of treatment exposure is taken account of using a time-dependent Cox model, there is no longer evidence of a protective effect of treatment. The simulation study showed that, under various scenarios, the time-dependent Cox model consistently provides unbiased treatment effect estimates, whereas standard Cox model leads to bias in favor of treatment. Logistic regression and landmark analysis may also lead to bias. To minimize the risk of immortal time bias in observational studies of survival outcomes, we strongly suggest time-dependent exposures be included as time-dependent variables in hazard-based analyses. Copyright © 2016 Elsevier Inc. All rights reserved.

Duration of Mechanical Ventilation in the Emergency Department.

PubMed

Angotti, Lauren B; Richards, Jeremy B; Fisher, Daniel F; Sankoff, Jeffrey D; Seigel, Todd A; Al Ashry, Haitham S; Wilcox, Susan R

2017-08-01

Due to hospital crowding, mechanically ventilated patients are increasingly spending hours boarding in emergency departments (ED) before intensive care unit (ICU) admission. This study aims to evaluate the association between time ventilated in the ED and in-hospital mortality, duration of mechanical ventilation, ICU and hospital length of stay (LOS). This was a multi-center, prospective, observational study of patients ventilated in the ED, conducted at three academic Level I Trauma Centers from July 2011 to March 2013. All consecutive adult patients on invasive mechanical ventilation were eligible for enrollment. We performed a Cox regression to assess for a mortality effect for mechanically ventilated patients with each hour of increasing LOS in the ED and multivariable regression analyses to assess for independently significant contributors to in-hospital mortality. Our primary outcome was in-hospital mortality, with secondary outcomes of ventilator days, ICU LOS and hospital LOS. We further commented on use of lung protective ventilation and frequency of ventilator changes made in this cohort. We enrolled 535 patients, of whom 525 met all inclusion criteria. Altered mental status without respiratory pathology was the most common reason for intubation, followed by trauma and respiratory failure. Using iterated Cox regression, a mortality effect occurred at ED time of mechanical ventilation > 7 hours, and the longer ED stay was also associated with a longer total duration of intubation. However, adjusted multivariable regression analysis demonstrated only older age and admission to the neurosciences ICU as independently associated with increased mortality. Of interest, only 23.8% of patients ventilated in the ED for over seven hours had changes made to their ventilator. In a prospective observational study of patients mechanically ventilated in the ED, there was a significant mortality benefit to expedited transfer of patients into an appropriate ICU setting.

A difference in systolic blood pressure between arms is a novel predictor of the development and progression of diabetic nephropathy in patients with type 2 diabetes.

PubMed

Okada, Hiroshi; Fukui, Michiaki; Tanaka, Muhei; Matsumoto, Shinobu; Iwase, Hiroya; Kobayashi, Kanae; Asano, Mai; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto

2013-10-01

Recent studies have suggested that a difference in systolic blood pressure (SBP) between arms is associated with both vascular disease and mortality. The aim of this study was to investigate the relationship between a difference in SBP between arms and change in urinary albumin excretion or development of albuminuria in patients with type 2 diabetes. We measured SBP in 408 consecutive patients with type 2 diabetes, and calculated a difference in SBP between arms. We performed follow-up study to assess change in urinary albumin excretion or development of albuminuria, mean interval of which was 4.6 ± 1.7 years. We then evaluated the relationship of a difference in SBP between arms to diabetic nephropathy using multiple regression analysis and multiple Cox regression model. Multiple regression analyses demonstrated that a difference in SBP between arms was independently associated with change in urinary albumin excretion (β = 0.1869, P = 0.0010). Adjusted Cox regression analyses demonstrated that a difference in SBP between arms was associated with an increased hazard of development of albuminuria; hazard ratio was 1.215 (95% confidence interval 1.077-1.376). Moreover, the risk of development of albuminuria was increased in patients with a difference in SBP of equal to or more than 10 mmHg between arms; hazard ratio was 4.168 (95% confidence interval 1.478-11.70). A difference in SBP between arms could be a novel predictor of the development and progression of diabetic nephropathy in patients with type 2 diabetes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Lung Cancer Prognosis in Elderly Solid Organ Transplant Recipients

PubMed Central

Sigel, Keith; Veluswamy, Rajwanth; Krauskopf, Katherine; Mehrotra, Anita; Mhango, Grace; Sigel, Carlie; Wisnivesky, Juan

2015-01-01

Background Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC). Methods Using the Surveillance, Epidemiology and End Results registry linked to Medicare claims we identified 597 patients age ≥65 with NSCLC who had received organ transplants (kidney, liver, heart or lung) prior to cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders. Results Transplant recipients presented with earlier stage lung cancer (p=0.002) and were more likely to have squamous cell carcinoma (p=0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (p<0.05) while lung transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and non-transplant patients. Conclusions Non-lung solid organ transplant recipients who developed NSCLC had worse OS than non-transplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these two groups. PMID:25839704

[Application of SAS macro to evaluated multiplicative and additive interaction in logistic and Cox regression in clinical practices].

PubMed

Nie, Z Q; Ou, Y Q; Zhuang, J; Qu, Y J; Mai, J Z; Chen, J M; Liu, X Q

2016-05-01

Conditional logistic regression analysis and unconditional logistic regression analysis are commonly used in case control study, but Cox proportional hazard model is often used in survival data analysis. Most literature only refer to main effect model, however, generalized linear model differs from general linear model, and the interaction was composed of multiplicative interaction and additive interaction. The former is only statistical significant, but the latter has biological significance. In this paper, macros was written by using SAS 9.4 and the contrast ratio, attributable proportion due to interaction and synergy index were calculated while calculating the items of logistic and Cox regression interactions, and the confidence intervals of Wald, delta and profile likelihood were used to evaluate additive interaction for the reference in big data analysis in clinical epidemiology and in analysis of genetic multiplicative and additive interactions.

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.

COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human lung cancer cells.

PubMed

Ramer, Robert; Heinemann, Katharina; Merkord, Jutta; Rohde, Helga; Salamon, Achim; Linnebacher, Michael; Hinz, Burkhard

2013-01-01

The antitumorigenic mechanism of cannabidiol is still controversial. This study investigates the role of COX-2 and PPAR-γ in cannabidiol's proapoptotic and tumor-regressive action. In lung cancer cell lines (A549, H460) and primary cells from a patient with lung cancer, cannabidiol elicited decreased viability associated with apoptosis. Apoptotic cell death by cannabidiol was suppressed by NS-398 (COX-2 inhibitor), GW9662 (PPAR-γ antagonist), and siRNA targeting COX-2 and PPAR-γ. Cannabidiol-induced apoptosis was paralleled by upregulation of COX-2 and PPAR-γ mRNA and protein expression with a maximum induction of COX-2 mRNA after 8 hours and continuous increases of PPAR-γ mRNA when compared with vehicle. In response to cannabidiol, tumor cell lines exhibited increased levels of COX-2-dependent prostaglandins (PG) among which PGD(2) and 15-deoxy-Δ(12,14)-PGJ(2) (15d-PGJ(2)) caused a translocation of PPAR-γ to the nucleus and induced a PPAR-γ-dependent apoptotic cell death. Moreover, in A549-xenografted nude mice, cannabidiol caused upregulation of COX-2 and PPAR-γ in tumor tissue and tumor regression that was reversible by GW9662. Together, our data show a novel proapoptotic mechanism of cannabidiol involving initial upregulation of COX-2 and PPAR-γ and a subsequent nuclear translocation of PPAR-γ by COX-2-dependent PGs.

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.

Impact of COX2 genotype, ER status and body constitution on risk of early events in different treatment groups of breast cancer patients.

PubMed

Markkula, Andrea; Simonsson, Maria; Rosendahl, Ann H; Gaber, Alexander; Ingvar, Christian; Rose, Carsten; Jernström, Helena

2014-10-15

The COX2 rs5277 (306G>C) polymorphism has been associated with inflammation-associated cancers. In breast cancer, tumor COX-2 expression has been associated with increased estrogen levels in estrogen receptor (ER)-positive and activated Akt-pathway in ER-negative tumors. Our study investigated the impact of COX2 genotypes on early breast cancer events and treatment response in relation to tumor ER status and body constitution. In Sweden, between 2002 and 2008, 634 primary breast cancer patients, aged 25-99 years, were included. Disease-free survival was assessed for 570 rs5277-genotyped patients. Body measurements and questionnaires were obtained preoperatively. Clinical data, patient- and tumor-characteristics were obtained from questionnaires, patients' charts, population registries and pathology reports. Minor allele(C) frequency was 16.1%. Genotype was not linked to COX-2 tumor expression. Median follow-up was 5.1 years. G/G genotype was not associated with early events in patients with ER-positive tumors, adjusted HR 0.77 (0.46-1.29), but conferred an over 4-fold increased risk in patients with ER-negative tumors, adjusted HR 4.41 (1.21-16.02)(p(interaction) = 0.015). Chemotherapy-treated G/G-carriers with a breast volume ≥ 850 ml had an increased risk of early events irrespective of ER status, adjusted HR 8.99 (1.14-70.89). Endocrine-treated C-allele carriers with ER-positive tumors and a breast volume ≥ 850 ml had increased risk of early events, adjusted HR 2.30 (1.12-4.75). COX2 genotype, body constitution and ER status had a combined effect on the risk of early events and treatment response. The high risk for early events in certain subgroups of patients suggests that COX2 genotype in combination with body measurements may identify patients in need of more personalized treatment. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

Properties of added variable plots in Cox's regression model.

PubMed

Lindkvist, M

2000-03-01

The added variable plot is useful for examining the effect of a covariate in regression models. The plot provides information regarding the inclusion of a covariate, and is useful in identifying influential observations on the parameter estimates. Hall et al. (1996) proposed a plot for Cox's proportional hazards model derived by regarding the Cox model as a generalized linear model. This paper proves and discusses properties of this plot. These properties make the plot a valuable tool in model evaluation. Quantities considered include parameter estimates, residuals, leverage, case influence measures and correspondence to previously proposed residuals and diagnostics.

Accounting for individual differences and timing of events: estimating the effect of treatment on criminal convictions in heroin users.

PubMed

Røislien, Jo; Clausen, Thomas; Gran, Jon Michael; Bukten, Anne

2014-05-17

The reduction of crime is an important outcome of opioid maintenance treatment (OMT). Criminal intensity and treatment regimes vary among OMT patients, but this is rarely adjusted for in statistical analyses, which tend to focus on cohort incidence rates and rate ratios. The purpose of this work was to estimate the relationship between treatment and criminal convictions among OMT patients, adjusting for individual covariate information and timing of events, fitting time-to-event regression models of increasing complexity. National criminal records were cross linked with treatment data on 3221 patients starting OMT in Norway 1997-2003. In addition to calculating cohort incidence rates, criminal convictions was modelled as a recurrent event dependent variable, and treatment a time-dependent covariate, in Cox proportional hazards, Aalen's additive hazards, and semi-parametric additive hazards regression models. Both fixed and dynamic covariates were included. During OMT, the number of days with criminal convictions for the cohort as a whole was 61% lower than when not in treatment. OMT was associated with reduced number of days with criminal convictions in all time-to-event regression models, but the hazard ratio (95% CI) was strongly attenuated when adjusting for covariates; from 0.40 (0.35, 0.45) in a univariate model to 0.79 (0.72, 0.87) in a fully adjusted model. The hazard was lower for females and decreasing with older age, while increasing with high numbers of criminal convictions prior to application to OMT (all p < 0.001). The strongest predictors were level of criminal activity prior to entering into OMT, and having a recent criminal conviction (both p < 0.001). The effect of several predictors was significantly time-varying with their effects diminishing over time. Analyzing complex observational data regarding to fixed factors only overlooks important temporal information, and naïve cohort level incidence rates might result in biased estimates of the effect of interventions. Applying time-to-event regression models, properly adjusting for individual covariate information and timing of various events, allows for more precise and reliable effect estimates, as well as painting a more nuanced picture that can aid health care professionals and policy makers.

Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome

PubMed Central

2011-01-01

Background Genome-wide association studies (GWAS) have identified new candidate genes for the occurrence of acute coronary syndrome (ACS), but possible effects of such genes on survival following ACS have yet to be investigated. Methods We examined 95 polymorphisms in 69 distinct gene regions identified in a GWAS for premature myocardial infarction for their association with post-ACS mortality among 811 whites recruited from university-affiliated hospitals in Kansas City, Missouri. We then sought replication of a positive genetic association in a large, racially diverse cohort of myocardial infarction patients (N = 2284) using Kaplan-Meier survival analyses and Cox regression to adjust for relevant covariates. Finally, we investigated the apparent association further in 6086 additional coronary artery disease patients. Results After Cox adjustment for other ACS risk factors, of 95 SNPs tested in 811 whites only the association with the rs6922269 in MTHFD1L was statistically significant, with a 2.6-fold mortality hazard (P = 0.007). The recessive A/A genotype was of borderline significance in an age- and race-adjusted analysis of the entire combined cohort (N = 3095; P = 0.052), but this finding was not confirmed in independent cohorts (N = 6086). Conclusions We found no support for the hypothesis that the GWAS-identified variants in this study substantially alter the probability of post-ACS survival. Large-scale, collaborative, genome-wide studies may be required in order to detect genetic variants that are robustly associated with survival in patients with coronary artery disease. PMID:21957892

Cox regression analysis with missing covariates via nonparametric multiple imputation.

PubMed

Hsu, Chiu-Hsieh; Yu, Mandi

2018-01-01

We consider the situation of estimating Cox regression in which some covariates are subject to missing, and there exists additional information (including observed event time, censoring indicator and fully observed covariates) which may be predictive of the missing covariates. We propose to use two working regression models: one for predicting the missing covariates and the other for predicting the missing probabilities. For each missing covariate observation, these two working models are used to define a nearest neighbor imputing set. This set is then used to non-parametrically impute covariate values for the missing observation. Upon the completion of imputation, Cox regression is performed on the multiply imputed datasets to estimate the regression coefficients. In a simulation study, we compare the nonparametric multiple imputation approach with the augmented inverse probability weighted (AIPW) method, which directly incorporates the two working models into estimation of Cox regression, and the predictive mean matching imputation (PMM) method. We show that all approaches can reduce bias due to non-ignorable missing mechanism. The proposed nonparametric imputation method is robust to mis-specification of either one of the two working models and robust to mis-specification of the link function of the two working models. In contrast, the PMM method is sensitive to misspecification of the covariates included in imputation. The AIPW method is sensitive to the selection probability. We apply the approaches to a breast cancer dataset from Surveillance, Epidemiology and End Results (SEER) Program.

Collagen Triple Helix Repeat Containing-1 (CTHRC1) Expression in Oral Squamous Cell Carcinoma (OSCC): Prognostic Value and Clinico-Pathological Implications

PubMed Central

Lee, Chia Ee; Vincent-Chong, Vui King; Ramanathan, Anand; Kallarakkal, Thomas George; Karen-Ng, Lee Peng; Ghani, Wan Maria Nabillah; Rahman, Zainal Ariff Abdul; Ismail, Siti Mazlipah; Abraham, Mannil Thomas; Tay, Keng Kiong; Mustafa, Wan Mahadzir Wan; Cheong, Sok Ching; Zain, Rosnah Binti

2015-01-01

BACKGROUND: Collagen Triple Helix Repeat Containing 1 (CTHRC1) is a protein often found to be over-expressed in various types of human cancers. However, correlation between CTHRC1 expression level with clinico-pathological characteristics and prognosis in oral cancer remains unclear. Therefore, this study aimed to determine mRNA and protein expression of CTHRC1 in oral squamous cell carcinoma (OSCC) and to evaluate the clinical and prognostic impact of CTHRC1 in OSCC. METHODS: In this study, mRNA and protein expression of CTHRC1 in OSCCs were determined by quantitative PCR and immunohistochemistry, respectively. The association between CTHRC1 and clinico-pathological parameters were evaluated by univariate and multivariate binary logistic regression analyses. Correlation between CTHRC1 protein expressions with survival were analysed using Kaplan-Meier and Cox regression models. RESULTS: Current study demonstrated CTHRC1 was significantly overexpressed at the mRNA level in OSCC. Univariate analyses indicated a high-expression of CTHRC1 that was significantly associated with advanced stage pTNM staging, tumour size ≥ 4 cm and positive lymph node metastasis (LNM). However, only positive LNM remained significant after adjusting with other confounder factors in multivariate logistic regression analyses. Kaplan-Meier survival analyses and Cox model demonstrated that patients with high-expression of CTHRC1 protein were associated with poor prognosis and is an independent prognostic factor in OSCC. CONCLUSION: This study indicated that over-expression of CTHRC1 potentially as an independent predictor for positive LNM and poor prognosis in OSCC. PMID:26664254

Association of Periodontitis and Subsequent Depression: A Nationwide Population-Based Study.

PubMed

Hsu, Chih-Chao; Hsu, Yi-Chao; Chen, Hsuan-Ju; Lin, Che-Chen; Chang, Kuang-Hsi; Lee, Chang-Yin; Chong, Lee-Won; Kao, Chia-Hung

2015-12-01

Periodontitis is a systemic and chronic inflammatory disease associated with multiple physical conditions. Distress and depression are other problems affecting the progression of periodontitis. However, the causal relationship between depression and periodontitis has not been adequately investigated. This aim of this study was to determine the association between periodontitis and the subsequent development of depression.We identified 12,708 patients with newly diagnosed periodontitis from 2000 to 2005 and 50,832 frequency-matched individuals without periodontitis. Both groups were followed until diagnosed with depression, withdrawal from the National Health Insurance program, or the end of 2011. The association between periodontitis and depressio was analyzed using Cox proportional hazard regression models.The incidence density rate of depression was higher in the periodontitis group than in the nonperiodontitis group, with an adjusted hazard ratio of 1.73 (95% confidence interval 1.58-1.89) when adjusting for sex, age, and comorbidity. Cox models revealed that periodontitis was an independent risk factor for depression in patients, except for comorbidities of diabetes mellitus (DM), alcohol abuse, and cancer.Periodontitis may increase the risk of subsequent depression and was suggested an independent risk factor regardless of sex, age, and most comorbidities. However, DM, alcohol abuse, and cancer may prevent the development of subsequent depression because of DM treatment, the paradoxical effect of alcohol, and emotional distress to cancer, respectively. Prospective studies on the relationship between periodontitis and depression are warranted.

Association of Periodontitis and Subsequent Depression

PubMed Central

Hsu, Chih-Chao; Hsu, Yi-Chao; Chen, Hsuan-Ju; Lin, Che-Chen; Chang, Kuang-Hsi; Lee, Chang-Yin; Chong, Lee-Won; Kao, Chia-Hung

2015-01-01

Abstract Periodontitis is a systemic and chronic inflammatory disease associated with multiple physical conditions. Distress and depression are other problems affecting the progression of periodontitis. However, the causal relationship between depression and periodontitis has not been adequately investigated. This aim of this study was to determine the association between periodontitis and the subsequent development of depression. We identified 12,708 patients with newly diagnosed periodontitis from 2000 to 2005 and 50,832 frequency-matched individuals without periodontitis. Both groups were followed until diagnosed with depression, withdrawal from the National Health Insurance program, or the end of 2011. The association between periodontitis and depressio was analyzed using Cox proportional hazard regression models. The incidence density rate of depression was higher in the periodontitis group than in the nonperiodontitis group, with an adjusted hazard ratio of 1.73 (95% confidence interval 1.58–1.89) when adjusting for sex, age, and comorbidity. Cox models revealed that periodontitis was an independent risk factor for depression in patients, except for comorbidities of diabetes mellitus (DM), alcohol abuse, and cancer. Periodontitis may increase the risk of subsequent depression and was suggested an independent risk factor regardless of sex, age, and most comorbidities. However, DM, alcohol abuse, and cancer may prevent the development of subsequent depression because of DM treatment, the paradoxical effect of alcohol, and emotional distress to cancer, respectively. Prospective studies on the relationship between periodontitis and depression are warranted. PMID:26705230

The occurrence of Simpson's paradox if site-level effect was ignored in the TREAT Asia HIV Observational Database.

PubMed

Jiamsakul, Awachana; Kerr, Stephen J; Chandrasekaran, Ezhilarasi; Huelgas, Aizobelle; Taecharoenkul, Sineenart; Teeraananchai, Sirinya; Wan, Gang; Ly, Penh Sun; Kiertiburanakul, Sasisopin; Law, Matthew

2016-08-01

In multisite human immunodeficiency virus (HIV) observational cohorts, clustering of observations often occurs within sites. Ignoring clustering may lead to "Simpson's paradox" (SP) where the trend observed in the aggregated data is reversed when the groups are separated. This study aimed to investigate the SP in an Asian HIV cohort and the effects of site-level adjustment through various Cox regression models. Survival time from combination antiretroviral therapy (cART) initiation was analyzed using four Cox models: (1) no site adjustment; (2) site as a fixed effect; (3) stratification through site; and (4) shared frailty on site. A total of 6,454 patients were included from 23 sites in Asia. SP was evident in the year of cART initiation variable. Model (1) shows the hazard ratio (HR) for years 2010-2014 was higher than the HR for 2006-2009, compared to 2003-2005 (HR = 0.68 vs. 0.61). Models (2)-(4) consistently implied greater improvement in survival for those who initiated in 2010-2014 than 2006-2009 contrasting findings from model (1). The effects of other significant covariates on survival were similar across four models. Ignoring site can lead to SP causing reversal of treatment effects. Greater emphasis should be made to include site in survival models when possible. Copyright © 2016 Elsevier Inc. All rights reserved.

Lung Quality and Utilization in Controlled Donation after Circulatory Determination of Death Donors within the United States

PubMed Central

Mooney, Joshua J; Hedlin, Haley; Mohabir, Paul K; Vazquez, Rodrigo; Nguyen, John; Ha, Richard; Chiu, Peter; Patel, Kapilkumar; Zamora, Martin R.; Weill, David; Nicolls, Mark R; Dhillon, Gundeep S

2016-01-01

While controlled donation after circulatory determination of death (cDCDD) donors could increase the supply of donor lungs within the United States, the yield of lungs from cDCDD donors remain low compared to donation after neurologic determination of death (DNDD) donors. To explore the reason for low lung yield from cDCDD donors, Scientific Registry of Transplant Recipient data were used to assess the impact of donor lung quality on cDCDD lung utilization by fitting a logistic regression model. The relationship between center volume and cDCDD use was assessed and distance between center and donor hospital was calculated by cDCDD status. Recipient survival was compared using a multivariable Cox regression model. Lung utilization was 2.1% for cDCDD donors and 21.4% for DNDD donors. Being a cDCDD donor decreased lung donation (adjusted OR 0.101, CI 0.085–0.120). A minority of centers have performed cDCDD transplant with higher volume centers generally performing more cDCDD transplants. There was no difference in center to donor distance or recipient survival (adjusted HR 1.03, CI 0.78–1.37) between cDCDD and DNDD transplants. cDCDD lungs are underutilized compared to DNDD lungs after adjusting for lung quality. Increasing transplant center expertise and commitment to cDCDD lung procurement is needed to improve utilization. PMID:26844673

Glucose-6-Phosphate Dehydrogenase Deficiency and Physical and Mental Health until Adolescence.

PubMed

Kwok, Man Ki; Leung, Gabriel M; Schooling, C Mary

2016-01-01

To examine the association of glucose-6-phosphate dehydrogenase (G6PD) deficiency with adolescent physical and mental health, as effects of G6PD deficiency on health are rarely reported. In a population-representative Chinese birth cohort: "Children of 1997" (n = 8,327), we estimated the adjusted associations of G6PD deficiency with growth using generalized estimating equations, with pubertal onset using interval censored regression, with hospitalization using Cox proportional hazards regression and with size, blood pressure, pubertal maturation and mental health using linear regression with multiple imputation and inverse probability weighting. Among 5,520 screened adolescents (66% follow-up), 4.8% boys and 0.5% girls had G6PD deficiency. G6PD-deficiency was not associated with birth weight-for-gestational age or length/height gain into adolescence, but was associated with lower childhood body mass index (BMI) gain (-0.38 z-score, 95% confidence interval (CI) -0.57, -0.20), adjusted for sex and parental education, and later onset of pubic hair development (time ratio = 1.029, 95% CI 1.007, 1.050). G6PD deficiency was not associated with blood pressure, height, BMI or mental health in adolescence, nor with serious infectious morbidity until adolescence. G6PD deficient adolescents had broadly similar physical and mental health indicators, but transiently lower BMI gain and later pubic hair development, whose long-term implications warrant investigation.

Prognostic significance of hemoglobin level in patients with congestive heart failure and normal ejection fraction.

PubMed

Varadarajan, Padmini; Gandhi, Siddharth; Sharma, Sanjay; Umakanthan, Branavan; Pai, Ramdas G

2006-10-01

Previous studies have shown low hemoglobin (Hb) to have an adverse effect on survival in patients with congestive heart failure (CHF) and reduced left ventricular (LV) ejection fraction (EF); but its effect on survival in patients with CHF and normal EF is not known. This study sought to determine whether low Hb has an effect on survival in patients with both CHF and normal EF. Detailed chart reviews were performed by medical residents on 2,246 patients (48% with normal EF) with a discharge diagnosis of CHF in a large tertiary care hospital from 1990 to 1999. The CHF diagnosis was validated using the Framingham criteria. Mortality data were obtained from the National Death Index. Survival analysis was performed using Kaplan-Meier and Cox regression models. By Kaplan-Meier analysis, low Hb (< 12 gm/dl) compared with normal hemoglobin was associated with a lower 5-year survival in patients with CHF and both normal (38 vs. 50%, p = 0.0008) and reduced (35 vs. 48%, p = 0.0009) EF. Using the Cox regression model, low Hb was an independent predictor of mortality after adjusting for age, gender, renal dysfunction, diabetes mellitus, hypertension, and EF in both groups of patients. Low Hb has an independent adverse effect on survival in patients with CHF and both normal and reduced EF in both groups of patients.

Differing manifestations of hepatitis C and tacrolimus on hospitalized diabetes mellitus occurring after kidney transplantation.

PubMed

Abbott, Kevin C; Bernet, Victor J; Agodoa, Lawrence Y; Yuan, Christina M

2005-09-01

Previous studies suggest the association of recipient hepatitis C seropositivity (HCV+) and use of tacrolimus (TAC) with post-transplant diabetes mellitus (PTDM) may differ by manifestations of type I or type II diabetes, but this has not been assessed in the era of current immunosuppression. We performed a retrospective cohort study of 10,342 Medicare primary renal transplantation recipients without evidence of diabetes at the time of listing in the United States Renal Data System between January 1, 1998 and July 31, 2000, followed until December 31, 2000. Outcomes were hospitalizations for a primary diagnosis of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS). Cox regression analysis was used to calculate adjusted hazard ratios (AHR) for time to DKA or HHS, stratified by diabetes status at the time of transplant. In Cox regression analysis, use of TAC at discharge was independently associated with shorter time to DKA (AHR, 1.88; 95% CI, 1.05-3.37, p=0.034) but not HHS. In contrast, recipient HCV+ was independently associated with shorter time to HHS (AHR, 3.90; 1.59-9.60, p=.003), but not DKA. There was no interaction between TAC and HCV+ for either outcome. These results confirm earlier findings that TAC and HCV+ may mediate the risk of PTDM through different mechanisms, even in the modern era.

Factors Affecting Discharge to Home of Geriatric Intermediate Care Facility Residents in Japan.

PubMed

Morita, Kojiro; Ono, Sachiko; Ishimaru, Miho; Matsui, Hiroki; Naruse, Takashi; Yasunaga, Hideo

2018-04-01

To investigate factors associated with lower likelihood of discharge to home from geriatric intermediate care facilities in Japan. Retrospective cohort study. We used data from the nationwide long-term care (LTC) insurance claims database (April 2012-March 2014). Study participants were 342,758 individuals newly admitted to 3,459 geriatric intermediate care facilities during the study period. The primary outcome was discharge to home. We performed a multivariable competing-risk Cox regression with adjustment for resident-, facility-, and region-level characteristics. Resident level of care needs and several medical conditions were included as time-varying covariates. Death, admission to a hospital, and admission to another LTC facility were treated as competing risks. During the 2-year follow-up period, 19% of participants were discharged to home. In the multivariable competing-risk Cox regression, the following factors were significantly associated with lower likelihood of discharge to home: older age, higher level of care need, having several medical conditions, private ownership of the facility, more beds in the facility, and more LTC facility beds per 1,000 adults aged 65 and older in the region. Only 19% of residents were discharged to home. Our results are useful for policy-makers to promote discharge to home of older adults in geriatric intermediate care facilities. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

Malnutrition risk predicts recovery of full oral intake among older adult stroke patients undergoing enteral nutrition: Secondary analysis of a multicentre survey (the APPLE study).

PubMed

Nishioka, Shinta; Okamoto, Takatsugu; Takayama, Masako; Urushihara, Maki; Watanabe, Misuzu; Kiriya, Yumiko; Shintani, Keiko; Nakagomi, Hiromi; Kageyama, Noriko

2017-08-01

Whether malnutrition risk correlates with recovery of swallowing function of convalescent stroke patients is unknown. This study was conducted to clarify whether malnutrition risks predict achievement of full oral intake in convalescent stroke patients undergoing enteral nutrition. We conducted a secondary analysis of 466 convalescent stroke patients, aged 65 years or over, who were undergoing enteral nutrition. Patients were extracted from the "Algorithm for Post-stroke Patients to improve oral intake Level; APPLE" study database compiled at the Kaifukuki (convalescent) rehabilitation wards. Malnutrition risk was determined by the Geriatric Nutritional Risk Index as follows: severe (<82), moderate (82 to <92), mild (92 to <98), and no malnutrition risks (≥98). Swallowing function was assessed by Fujishima's swallowing grade (FSG) on admission and discharge. The primary outcome was achievement of full oral intake, indicated by FSG ≥ 7. Binary logistic regression analysis was performed to identify predictive factors, including malnutrition risk, for achieving full oral intake. Estimated hazard risk was computed by Cox's hazard model. Of the 466 individuals, 264 were ultimately included in this study. Participants with severe malnutrition risk showed a significantly lower proportion of achievement of full oral intake than lower severity groups (P = 0.001). After adjusting for potential confounders, binary logistic regression analysis showed that patients with severe malnutrition risk were less likely to achieve full oral intake (adjusted odds ratio: 0.232, 95% confidence interval [95% CI]: 0.047-1.141). Cox's proportional hazard model revealed that severe malnutrition risk was an independent predictor of full oral intake (adjusted hazard ratio: 0.374, 95% CI: 0.166-0.842). Compared to patients who did not achieve full oral intake, patients who achieved full oral intake had significantly higher energy intake, but there was no difference in protein intake and weight change. Severe malnutrition risk independently predicts the achievement of full oral intake in convalescent stroke patients undergoing enteral nutrition. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Physical frailty in older adults is associated with metabolic and atherosclerotic risk factors and cognitive impairment independent of muscle mass.

PubMed

Lee, J S W; Auyeung, T-W; Leung, J; Kwok, T; Leung, P-C; Woo, J

2011-12-01

Metabolic and atherosclerotic diseases are known risk factors for disability in old age, and can result in sarcopenia as well as cognitive impairment, which are both components of frailty syndrome. As muscle loss increases with ageing, it is unclear whether muscle loss per se, or the diseases themselves, are the underlying cause of physical frailty in those suffering from these diseases. We tested the hypothesis that metabolic and atherosclerotic diseases and cognitive impairment are associated with physical frailty independent of muscle loss in old age, and further examined their impact on the relationship between physical frailty and mortality. Prospective. Community. 4000 community dwelling Chinese elderly ≥65 years. Diabetes, hypertension, stroke, heart disease, cognitive impairment, smoking, physical activity, waist hip ratio (WHR) and ankle-brachial index (ABI)) were recorded. Physical frailty measurements (grip-strength, chair-stands, stride length and 6-metre walks) were summarized into a composite frailty score (0-20), 0 being the most frail) according to quartiles of performance. Appendicular muscle mass (ASM) was measured using dual X-ray absorptiometry. Relationships between the score and covariates were analyzed. Cox regression was used to study the impact of metabolic and atnerosclerotic risk factors on the relationship between physical frailty and 6-year mortality. After adjustment for ASM, all metabolic diseases and indexes, and cognitive impairment were significantly associated with the composite physical frailty score in univariate analysis. In multivariate analysis, cognitive impairment, high WHR, diabetes, stroke and heart disease were all independently associated with higher physical frailty with adjustment for age, physical activity level and ASM. Hypertension was associated with physical frailty in men but not in women. In Cox regression, increased physical frailty was associated with higher 6-year mortality. The impact of metabolic and atherosclerotic risk factors was however only modest after adjustment for age and cognitive function. Metabolic and atherosclerotic diseases and high WHR, was associated with physical frailty, independent of their adverse effect on cognitive function and muscle mass.

Bootstrap investigation of the stability of a Cox regression model.

PubMed

Altman, D G; Andersen, P K

1989-07-01

We describe a bootstrap investigation of the stability of a Cox proportional hazards regression model resulting from the analysis of a clinical trial of azathioprine versus placebo in patients with primary biliary cirrhosis. We have considered stability to refer both to the choice of variables included in the model and, more importantly, to the predictive ability of the model. In stepwise Cox regression analyses of 100 bootstrap samples using 17 candidate variables, the most frequently selected variables were those selected in the original analysis, and no other important variable was identified. Thus there was no reason to doubt the model obtained in the original analysis. For each patient in the trial, bootstrap confidence intervals were constructed for the estimated probability of surviving two years. It is shown graphically that these intervals are markedly wider than those obtained from the original model.

A fast identification algorithm for Box-Cox transformation based radial basis function neural network.

PubMed

Hong, Xia

2006-07-01

In this letter, a Box-Cox transformation-based radial basis function (RBF) neural network is introduced using the RBF neural network to represent the transformed system output. Initially a fixed and moderate sized RBF model base is derived based on a rank revealing orthogonal matrix triangularization (QR decomposition). Then a new fast identification algorithm is introduced using Gauss-Newton algorithm to derive the required Box-Cox transformation, based on a maximum likelihood estimator. The main contribution of this letter is to explore the special structure of the proposed RBF neural network for computational efficiency by utilizing the inverse of matrix block decomposition lemma. Finally, the Box-Cox transformation-based RBF neural network, with good generalization and sparsity, is identified based on the derived optimal Box-Cox transformation and a D-optimality-based orthogonal forward regression algorithm. The proposed algorithm and its efficacy are demonstrated with an illustrative example in comparison with support vector machine regression.

Serum calcium changes and risk of type 2 diabetes mellitus in Asian population.

PubMed

Suh, Sunghwan; Bae, Ji Cheol; Jin, Sang-Man; Jee, Jae Hwan; Park, Mi Kyoung; Kim, Duk Kyu; Kim, Jae Hyeon

2017-11-01

We examined the association between changes in serum calcium levels with the incidence of type 2 diabetes mellitus (T2DM) in apparently healthy South Korean subjects. A retrospective longitudinal analysis was conducted with subjects who had participated in comprehensive health check-ups at least four times over a 7-year period (between 2006 and 2012). In total, 23,121 subjects were categorized into tertiles based on changes in their albumin-adjusted serum calcium levels. Multivariate Cox regression models were fitted to assess the association between changes in serum calcium levels during follow-up and the relative risk of diabetes incidence. After a median follow-up of 57.4months, 1,929 (8.3%) new cases of T2DM occurred. Simple linear regression analysis showed serum calcium level changes correlated positively with changes in HbA1c and fasting plasma glucose (FPG) levels (B=5.72, p<0.001 for FPG; B=0.13, p<0.001 for HbA1c). An increase in albumin-adjusted serum calcium levels during follow-up was related to an increased risk of T2DM. After adjustment for potential confounders, the risk of T2DM was 1.6 times greater for subjects whose albumin-adjusted serum calcium levels were in the highest change tertile during follow-up than for subjects whose levels were in the lowest tertile (HR 1.65, 95% CI 1.44-1.88, P<0.001). The elevation of albumin-adjusted serum calcium levels was associated with an increased risk of T2DM, independent of baseline glycemic status. Copyright © 2017 Elsevier B.V. All rights reserved.

A method for analyzing clustered interval-censored data based on Cox's model.

PubMed

Kor, Chew-Teng; Cheng, Kuang-Fu; Chen, Yi-Hau

2013-02-28

Methods for analyzing interval-censored data are well established. Unfortunately, these methods are inappropriate for the studies with correlated data. In this paper, we focus on developing a method for analyzing clustered interval-censored data. Our method is based on Cox's proportional hazard model with piecewise-constant baseline hazard function. The correlation structure of the data can be modeled by using Clayton's copula or independence model with proper adjustment in the covariance estimation. We establish estimating equations for the regression parameters and baseline hazards (and a parameter in copula) simultaneously. Simulation results confirm that the point estimators follow a multivariate normal distribution, and our proposed variance estimations are reliable. In particular, we found that the approach with independence model worked well even when the true correlation model was derived from Clayton's copula. We applied our method to a family-based cohort study of pandemic H1N1 influenza in Taiwan during 2009-2010. Using the proposed method, we investigate the impact of vaccination and family contacts on the incidence of pH1N1 influenza. Copyright © 2012 John Wiley & Sons, Ltd.

Long QT syndrome in African-Americans.

PubMed

Fugate, Thomas; Moss, Arthur J; Jons, Christian; McNitt, Scott; Mullally, Jamie; Ouellet, Gregory; Goldenberg, Ilan; Zareba, Wojciech; Robinson, Jennifer L

2010-01-01

We evaluated the risk factors and clinical course of Long QT syndrome (LQTS) in African-American patients. The study involved 41 African-Americans and 3456 Caucasians with a QTc > or = 450 ms from the U.S. portion of the International LQTS Registry. Data included information about the medical history and clinical course of the LQTS patients with end points relating to the occurrence of syncope, aborted cardiac arrest, or LQTS-related sudden cardiac death from birth through age 40 years. The statistical analyses involved Kaplan-Meier time to event graphs and Cox regression models for multivariable risk factor evaluation. The QTc was 29 ms longer in African-Americans than Caucasians. Multivarite Cox analyses with adjustment for decade of birth revealed that the cardiac event rate was similar in African-Americans and Caucasians with LQTS and that beta-blockers were equally effective in reducing cardiac events in the two racial groups. The clinical course of LQTS in African-Americans is similar to that of Caucasians with comparable risk factors and benefit from beta-blocker therapy in the two racial groups.

Subjective Global Assessment-Dialysis Malnutrition Score and cardiovascular risk in hemodialysis patients: an observational cohort study.

PubMed

Spatola, Leonardo; Finazzi, Silvia; Calvetta, Albania; Reggiani, Francesco; Morenghi, Emanuela; Santostasi, Silvia; Angelini, Claudio; Badalamenti, Salvatore; Mugnai, Giacomo

2018-06-23

Malnutrition is an important risk factor for cardiovascular mortality in hemodialysis (HD) patients. However, current malnutrition biomarkers seem unable to accurately estimate the role of malnutrition in predicting cardiovascular risk. Our aim was to investigate the role of the Subjective Global Assessment-Dialysis Malnutrition Score (SGA-DMS) compared to two well-recognized comorbidity scores-Charlson Comorbidity Index (CCI) and modified CCI (excluding age-factor) (mCCI)-in predicting cardiovascular events in HD patients. In 86 maintenance HD patients followed from June 2015 to June 2017, we analyzed biohumoral data and clinical scores as risk factors for cardiovascular events (acute heart failure, acute coronary syndrome and stroke). Their impact on outcome was investigated by linear regression, Cox regression models and ROC analysis. Cardiovascular events occurred in 26/86 (30%) patients during the 2-year follow-up. Linear regression showed only age and dialysis vintage to be positively related to SGA-DMS: B 0.21 (95% CI 0.01; 0.30) p 0.05, and B 0.24 (0.09; 0.34) p 0.02, respectively, while serum albumin, normalized protein catabolic rate (nPCR) and dialysis dose (Kt/V) were negatively related to SGA-DMS: B - 1.29 (- 3.29; - 0.81) p 0.02; B - 0.08 (- 1.52; - 0.35) p 0.04 and B - 2.63 (- 5.25; - 0.22) p 0.03, respectively. At Cox regression analysis, SGA-DMS was not a risk predictor for cardiovascular events: HR 1.09 (0.9; 1.22), while both CCI and mCCI were significant predictors: HR 1.43 (1.13; 1.87) and HR 1.57 (1.20; 2.06) also in Cox adjusted models. ROC analysis reported similar AUCs for CCI and mCCI: 0.72 (0.60; 0.89) p 0.00 and 0.70 (0.58; 0.82) p 0.00, respectively, compared to SGA-DMS 0.56 (0.49; 0.72) p 0.14. SGA-DMS is not a superior and significant prognostic tool compared to CCI and mCCI in assessing cardiovascular risk in HD patients, even it allows to appraise both malnutrition and comorbidity status.

Lipid Adjustment for Chemical Exposures: Accounting for Concomitant Variables

PubMed Central

Li, Daniel; Longnecker, Matthew P.; Dunson, David B.

2013-01-01

Background Some environmental chemical exposures are lipophilic and need to be adjusted by serum lipid levels before data analyses. There are currently various strategies that attempt to account for this problem, but all have their drawbacks. To address such concerns, we propose a new method that uses Box-Cox transformations and a simple Bayesian hierarchical model to adjust for lipophilic chemical exposures. Methods We compared our Box-Cox method to existing methods. We ran simulation studies in which increasing levels of lipid-adjusted chemical exposure did and did not increase the odds of having a disease, and we looked at both single-exposure and multiple-exposures cases. We also analyzed an epidemiology dataset that examined the effects of various chemical exposures on the risk of birth defects. Results Compared with existing methods, our Box-Cox method produced unbiased estimates, good coverage, similar power, and lower type-I error rates. This was the case in both single- and multiple-exposure simulation studies. Results from analysis of the birth-defect data differed from results using existing methods. Conclusion Our Box-Cox method is a novel and intuitive way to account for the lipophilic nature of certain chemical exposures. It addresses some of the problems with existing methods, is easily extendable to multiple exposures, and can be used in any analyses that involve concomitant variables. PMID:24051893

Potential confounding in the association between short birth intervals and increased neonatal, infant, and child mortality

PubMed Central

Perin, Jamie; Walker, Neff

2015-01-01

Background Recent steep declines in child mortality have been attributed in part to increased use of contraceptives and the resulting change in fertility behaviour, including an increase in the time between births. Previous observational studies have documented strong associations between short birth spacing and an increase in the risk of neonatal, infant, and under-five mortality, compared to births with longer preceding birth intervals. In this analysis, we compare two methods to estimate the association between short birth intervals and mortality risk to better inform modelling efforts linking family planning and mortality in children. Objectives Our goal was to estimate the mortality risk for neonates, infants, and young children by preceding birth space using household survey data, controlling for mother-level factors and to compare the results to those from previous analyses with survey data. Design We assessed the potential for confounding when estimating the relative mortality risk by preceding birth interval and estimated mortality risk by birth interval in four categories: less than 18 months, 18–23 months, 24–35 months, and 36 months or longer. We estimated the relative risks among women who were 35 and older at the time of the survey with two methods: in a Cox proportional hazards regression adjusting for potential confounders and also by stratifying Cox regression by mother, to control for all factors that remain constant over a woman's childbearing years. We estimated the overall effects for birth spacing in a meta-analysis with random survey effects. Results We identified several factors known for their associations with neonatal, infant, and child mortality that are also associated with preceding birth interval. When estimating the effect of birth spacing on mortality, we found that regression adjustment for these factors does not substantially change the risk ratio for short birth intervals compared to an unadjusted mortality ratio. For birth intervals less than 18 months, standard regression adjustment for confounding factors estimated a risk ratio for neonatal mortality of 2.28 (95% confidence interval: 2.18–2.37). This same effect estimated within mother is 1.57 (95% confidence interval: 1.52–1.63), a decline of almost one-third in the effect on neonatal mortality. Conclusions Neonatal, infant, and child mortality are strongly and significantly related to preceding birth interval, where births within a short interval of time after the previous birth have increased mortality. Previous analyses have demonstrated this relationship on average across all births; however, women who have short spaces between births are different from women with long spaces. Among women 35 years and older where a comparison of birth spaces within mother is possible, we find a much reduced although still significant effect of short birth spaces on child mortality. PMID:26562139

Potential confounding in the association between short birth intervals and increased neonatal, infant, and child mortality.

PubMed

Perin, Jamie; Walker, Neff

2015-01-01

Recent steep declines in child mortality have been attributed in part to increased use of contraceptives and the resulting change in fertility behaviour, including an increase in the time between births. Previous observational studies have documented strong associations between short birth spacing and an increase in the risk of neonatal, infant, and under-five mortality, compared to births with longer preceding birth intervals. In this analysis, we compare two methods to estimate the association between short birth intervals and mortality risk to better inform modelling efforts linking family planning and mortality in children. Our goal was to estimate the mortality risk for neonates, infants, and young children by preceding birth space using household survey data, controlling for mother-level factors and to compare the results to those from previous analyses with survey data. We assessed the potential for confounding when estimating the relative mortality risk by preceding birth interval and estimated mortality risk by birth interval in four categories: less than 18 months, 18-23 months, 24-35 months, and 36 months or longer. We estimated the relative risks among women who were 35 and older at the time of the survey with two methods: in a Cox proportional hazards regression adjusting for potential confounders and also by stratifying Cox regression by mother, to control for all factors that remain constant over a woman's childbearing years. We estimated the overall effects for birth spacing in a meta-analysis with random survey effects. We identified several factors known for their associations with neonatal, infant, and child mortality that are also associated with preceding birth interval. When estimating the effect of birth spacing on mortality, we found that regression adjustment for these factors does not substantially change the risk ratio for short birth intervals compared to an unadjusted mortality ratio. For birth intervals less than 18 months, standard regression adjustment for confounding factors estimated a risk ratio for neonatal mortality of 2.28 (95% confidence interval: 2.18-2.37). This same effect estimated within mother is 1.57 (95% confidence interval: 1.52-1.63), a decline of almost one-third in the effect on neonatal mortality. Neonatal, infant, and child mortality are strongly and significantly related to preceding birth interval, where births within a short interval of time after the previous birth have increased mortality. Previous analyses have demonstrated this relationship on average across all births; however, women who have short spaces between births are different from women with long spaces. Among women 35 years and older where a comparison of birth spaces within mother is possible, we find a much reduced although still significant effect of short birth spaces on child mortality.

Adherence to oral anticoagulants in patients with atrial fibrillation-a population-based retrospective cohort study linking health information systems in the Valencia region, Spain: a study protocol.

PubMed

Sanfélix-Gimeno, G; Rodríguez-Bernal, C L; Hurtado, I; Baixáuli-Pérez, C; Librero, J; Peiró, S

2015-10-19

Adherence to oral anticoagulation (OAC) treatment, vitamin K antagonists or new oral anticoagulants, is an essential element for effectiveness. Information on adherence to OAC in atrial fibrillation (AF) and the impact of adherence on clinical outcomes using real-world data barely exists. We aim to describe the patterns of adherence to OAC over time in patients with AF, estimate the associated factors and their impact on clinical events, and assess the same issues with conventional measures of primary and secondary adherence-proportion of days covered (PDC) and persistence-in routine clinical practice. This is a population-based retrospective cohort study including all patients with AF treated with OAC from 2010 to date in Valencia, Spain; data will be obtained from diverse electronic records of the Valencia Health Agency. adherence trajectories. (1) primary non-adherence; (2) secondary adherence: (a) PDC, (b) persistence. Clinical outcomes: hospitalisation for haemorrhagic or thromboembolic events and death during follow-up. (1) description of baseline characteristics, adherence patterns (trajectory models or latent class growth analysis models) and conventional adherence measures; (2) logistic or Cox multivariate regression models, to assess the associations between adherence measures and the covariates, and logistic multinomial regression models, to identify characteristics associated with each trajectory; (3) Cox proportional hazard models, to assess the relationship between adherence and clinical outcomes, with propensity score adjustment applied to further control for potential confounders; (4) to estimate the importance of different healthcare levels in the variations of adherence, logistic or Cox multilevel regression models. This study has been approved by the corresponding Clinical Research Ethics Committee. We plan to disseminate the project's findings through peer-reviewed publications and presentations at relevant health conferences. Policy reports will also be prepared in order to promote the translation of our findings into policy and clinical practice. 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.

BFLCRM: A BAYESIAN FUNCTIONAL LINEAR COX REGRESSION MODEL FOR PREDICTING TIME TO CONVERSION TO ALZHEIMER’S DISEASE*

PubMed Central

Lee, Eunjee; Zhu, Hongtu; Kong, Dehan; Wang, Yalin; Giovanello, Kelly Sullivan; Ibrahim, Joseph G

2015-01-01

The aim of this paper is to develop a Bayesian functional linear Cox regression model (BFLCRM) with both functional and scalar covariates. This new development is motivated by establishing the likelihood of conversion to Alzheimer’s disease (AD) in 346 patients with mild cognitive impairment (MCI) enrolled in the Alzheimer’s Disease Neuroimaging Initiative 1 (ADNI-1) and the early markers of conversion. These 346 MCI patients were followed over 48 months, with 161 MCI participants progressing to AD at 48 months. The functional linear Cox regression model was used to establish that functional covariates including hippocampus surface morphology and scalar covariates including brain MRI volumes, cognitive performance (ADAS-Cog), and APOE status can accurately predict time to onset of AD. Posterior computation proceeds via an efficient Markov chain Monte Carlo algorithm. A simulation study is performed to evaluate the finite sample performance of BFLCRM. PMID:26900412

Predictors of cardiovascular fitness in sedentary men.

PubMed

Riou, Marie-Eve; Pigeon, Etienne; St-Onge, Josée; Tremblay, Angelo; Marette, André; Weisnagel, S John; Joanisse, Denis R

2009-04-01

The relative contribution of anthropometric and skeletal muscle characteristics to cardiorespiratory fitness was studied in sedentary men. Cardiorespiratory fitness (maximal oxygen consumption) was assessed using an incremental bicycle ergometer protocol in 37 men aged 34-53 years. Vastus lateralis muscle biopsy samples were used to assess fiber type composition (I, IIA, IIX) and areas, capillary density, and activities of glycolytic and oxidative energy metabolic pathway enzymes. Correlations (all p < 0.05) were observed between maximal oxygen consumption (L.min-1) and body mass (r = 0.53), body mass index (r = 0.39), waist circumference (r = 0.34), fat free mass (FFM; r = 0.68), fat mass (r = 0.33), the enzyme activity of cytochrome c oxidase (COX; r = 0.39), muscle type IIA (r = 0.40) and IIX (r = 0.50) fiber area, and the number of capillaries per type IIA (r = 0.39) and IIX (r = 0.37) fiber. When adjusted for FFM in partial correlations, all correlations were lost, with the exception of COX (r = 0.48). Stepwise multiple regression revealed that maximal oxygen consumption was independently predicted by FFM, COX activity, mean capillary number per fiber, waist circumference, and, to a lesser extent, muscle capillary supply. In the absence of regular physical activity, cardiorespiratory fitness is strongly predicted by the potential for aerobic metabolism of skeletal muscle and negatively correlated with abdominal fat deposition.

Premature Cardiac Aging in South Asian Compared to Afro-Caribbean Subjects in a Community-Based Screening Study.

PubMed

Shantsila, Eduard; Shantsila, Alena; Gill, Paramjit S; Lip, Gregory Y H

2016-11-10

People of South Asian (SAs) and African Caribbean (AC) origin have increased cardiovascular morbidity, but underlying mechanisms are poorly understood. Aging is the key predictor of deterioration in diastolic function, which can be assessed by echocardiography using E/e' ratio as a surrogate of left ventricular (LV) filling pressure. The study aimed to assess a possibility of premature cardiac aging in SA and AC subjects. We studied 4540 subjects: 2880 SA and 1660 AC subjects. All participants underwent detailed echocardiography, including LV ejection fraction, average septal-lateral E/e', and LV mass index (LVMI). When compared to ACs, SAs were younger, with lower mean LVMI, systolic blood pressure (BP), diastolic BP, and body mass index (BMI), as well as a lower prevalence of hypertension and smoking (P≤0.001 for all). In a multivariate linear regression model including age, sex, ethnicity, BP, heart rate, BMI, waist circumference, LVMI, history of smoking, hypertension, coronary artery disease, diabetes mellitus, medications, SA origin was independently associated with higher E/e' (regression coefficient±standard error, -0.66±0.10; P<0.001, adjusted R 2 for the model 0.21; P<0.001). Furthermore, SAs had significantly accelerated age-dependent increase in E/e' compared to ACs. On multivariable Cox regression analysis without adjustment for E/e', SA ethnicity was independently predictive of mortality (P=0.04). After additional adjustment for E/e', the ethnicity lost its significance value, whereas E/e' was independently predictive of higher risk of death (P=0.008). Premature cardiac aging is evident in SAs and may contribute to high cardiovascular morbidity in this ethnic group, compared to ACs. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Leigh syndrome associated with a novel mutation in the COX15 gene.

PubMed

Miryounesi, Mohammad; Fardaei, Majid; Tabei, Seyed Mohammadbagher; Ghafouri-Fard, Soudeh

2016-06-01

Leigh syndrome (LS) is a subacute necrotizing encephalomyelopathy with a diverse range of symptoms, such as psychomotor delay or regression, weakness, hypotonia, truncal ataxia, intention tremor as well as lactic acidosis in the blood, cerebrospinal fluid or urine. Both nuclear gene defects and mutations of the mitochondrial genome have been detected in these patients. Here we report a 7-year-old girl with hypotonia, tremor, developmental delay and psychomotor regression. However, serum lactate level as well as brain magnetic resonance imaging were normal. Mutational analysis has revealed a novel mutation in exon 4 of COX15 gene (c.415C>G) which results in p.Leu139Val. Previous studies have demonstrated that COX15 mutations are associated with typical LS as well as fatal infantile hypertrophic cardiomyopathy. Consequently, clinical manifestations of COX15 mutations may be significantly different in patients. Such information is of practical importance in genetic counseling.

Predictors of pharmacological treatment outcomes with atomoxetine or methylphenidate in patients with attention-deficit/hyperactivity disorder from China, Egypt, Lebanon, Russian Federation, Taiwan, and United Arab Emirates.

PubMed

Treuer, T; Feng, Q; Desaiah, D; Altin, M; Wu, S; El-Shafei, A; Serebryakova, E; Gado, M; Faries, D

2014-09-01

The reduced availability of data from non-Western countries limits our ability to understand attention-deficit/hyperactivity disorder (ADHD) treatment outcomes, specifically, adherence and persistence of ADHD in children and adolescents. This analysis assessed predictors of treatment outcomes in a non-Western cohort of patients with ADHD treated with atomoxetine or methylphenidate. Data from a 12-month, prospective, observational study in outpatients aged 6-17 years treated with atomoxetine (N = 234) or methylphenidate (N = 221) were analysed post hoc to determine potential predictors of treatment outcomes. Participating countries included the Russian Federation, China, Taiwan, Egypt, United Arab Emirates and Lebanon. Factors associated with remission were analysed with stepwise multiple logistic regression and classification and regression trees (CART). Cox proportional hazards models with propensity score adjustment assessed differences in atomoxetine persistence among initial-dose cohorts. In patients treated with atomoxetine who had available dosing information (N = 134), Cox proportional hazards revealed lower (< 0.5 mg/kg) initial dose was significantly associated with shorter medication persistence (p < 0.01). multiple logistic regression analysis revealed greater rates of remission for atomoxetine-treated patients were associated with age (older), country (United Arab Emirates) and gender (female) (all p < 0.05). CART analysis confirmed older age and lack of specific phobias were associated with greater remission rates. For methylphenidate, greater baseline weight (highly correlated with the age factor found for atomoxetine) and prior atomoxetine use were associated with greater remission rates. These findings may help clinicians assess factors upon initiation of ADHD treatment to improve course prediction, proper dosing and treatment adherence and persistence. Observational study, therefore no registration. © 2014 John Wiley & Sons Ltd.

Predictors of unsuccessful outcome in cemented femoral revisions using bone impaction grafting; Cox regression analysis of 208 cases.

PubMed

Te Stroet, Martijn A J; Rijnen, Wim H C; Gardeniers, Jean W M; Schreurs, B Willem; Hannink, Gerjon

2016-09-29

Despite improvements in the technique of femoral impaction bone grafting, reconstruction failures still can occur. Therefore, the aim of our study was to determine risk factors for the endpoint re-revision for any reason. We used prospectively collected demographic, clinical and surgical data of all 202 patients who underwent 208 femoral revisions using the X-change Femoral Revision System (Stryker-Howmedica), fresh-frozen morcellised allograft and a cemented polished Exeter stem in our department from 1991 to 2007. Univariable and multivariable Cox regression analyses were performed to identify potential factors associated with re-revision. The mean follow-up was 10.6 (5-21) years. The cumulative re-revision rate was 6.3% (13/208). After univariable selection, sex, age, body mass index (BMI), American Association of Anesthesiologists (ASA) classification, type of removed femoral component, and mesh used for reconstruction were included in multivariable regression analysis.In the multivariable analysis, BMI was the only factor that was significantly associated with the risk of re-revision after bone impaction grafting (BMI ≥30 vs. BMI <30, HR = 6.54 [95% CI 1.89-22.65]; p = 0.003). BMI was the only factor associated with the risk of re-revision for any reason. Besides BMI also other factors, such as Endoklinik score and the type of removed femoral component, can provide guidance in the process of preclinical decision making. With the knowledge obtained from this study, preoperative patient selection, informed consent, and treatment protocols can be better adjusted to the individual patient who needs to undergo a femoral revision with impaction bone grafting.

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.

Gastric Bypass Surgery Produces a Durable Reduction in Cardiovascular Disease Risk Factors and Reduces the Long-Term Risks of Congestive Heart Failure.

PubMed

Benotti, Peter N; Wood, G Craig; Carey, David J; Mehra, Vishal C; Mirshahi, Tooraj; Lent, Michelle R; Petrick, Anthony T; Still, Christopher; Gerhard, Glenn S; Hirsch, Annemarie G

2017-05-23

Obesity and its association with reduced life expectancy are well established, with cardiovascular disease as one of the major causes of fatality. Metabolic surgery is a powerful intervention for severe obesity, resulting in improvement in comorbid diseases and in cardiovascular risk factors. This study investigates the relationship between metabolic surgery and long-term cardiovascular events. A cohort of Roux-en-Y gastric bypass surgery (RYGB) patients was tightly matched by age, body mass index, sex, Framingham Risk Score, smoking history, use of antihypertension medication, diabetes mellitus status, and calendar year with a concurrent cohort of nonoperated control patients. The primary study end points of major cardiovascular events (myocardial infarction, stroke, and congestive heart failure) were evaluated using Cox regression. Secondary end points of longitudinal cardiovascular risk factors were evaluated using repeated-measures regression. The RYGB and matched controls (N=1724 in each cohort) were followed for up to 12 years after surgery (overall median of 6.3 years). Kaplan-Meier analysis revealed a statistically significant reduction in incident major composite cardiovascular events ( P =0.017) and congestive heart failure (0.0077) for the RYGB cohort. Adjusted Cox regression models confirmed the reductions in severe composite cardiovascular events in the RYGB cohort (hazard ratio=0.58, 95% CI=0.42-0.82). Improvements of cardiovascular risk factors (eg, 10-year cardiovascular risk score, total cholesterol, high-density lipoprotein, systolic blood pressure, and diabetes mellitus) were observed within the RYGB cohort after surgery. Gastric bypass is associated with a reduced risk of major cardiovascular events and the development of congestive heart failure. © 2017 The Authors and Geisinger Clinic. Published on behalf of the American Heart Association, Inc., by Wiley.

Short-term outcome of 1,465 computer-navigated primary total knee replacements 2005-2008.

PubMed

Gøthesen, Oystein; Espehaug, Birgitte; Havelin, Leif; Petursson, Gunnar; Furnes, Ove

2011-06-01

and purpose Improvement of positioning and alignment by the use of computer-assisted surgery (CAS) might improve longevity and function in total knee replacements, but there is little evidence. In this study, we evaluated the short-term results of computer-navigated knee replacements based on data from the Norwegian Arthroplasty Register. Primary total knee replacements without patella resurfacing, reported to the Norwegian Arthroplasty Register during the years 2005-2008, were evaluated. The 5 most common implants and the 3 most common navigation systems were selected. Cemented, uncemented, and hybrid knees were included. With the risk of revision for any cause as the primary endpoint and intraoperative complications and operating time as secondary outcomes, 1,465 computer-navigated knee replacements (CAS) and 8,214 conventionally operated knee replacements (CON) were compared. Kaplan-Meier survival analysis and Cox regression analysis with adjustment for age, sex, prosthesis brand, fixation method, previous knee surgery, preoperative diagnosis, and ASA category were used. Kaplan-Meier estimated survival at 2 years was 98% (95% CI: 97.5-98.3) in the CON group and 96% (95% CI: 95.0-97.8) in the CAS group. The adjusted Cox regression analysis showed a higher risk of revision in the CAS group (RR = 1.7, 95% CI: 1.1-2.5; p = 0.02). The LCS Complete knee had a higher risk of revision with CAS than with CON (RR = 2.1, 95% CI: 1.3-3.4; p = 0.004)). The differences were not statistically significant for the other prosthesis brands. Mean operating time was 15 min longer in the CAS group. With the introduction of computer-navigated knee replacement surgery in Norway, the short-term risk of revision has increased for computer-navigated replacement with the LCS Complete. The mechanisms of failure of these implantations should be explored in greater depth, and in this study we have not been able to draw conclusions regarding causation.

Comparative risk of cerebrovascular adverse events in community-dwelling older adults using risperidone, olanzapine and quetiapine: a multiple propensity score-adjusted retrospective cohort study.

PubMed

Chatterjee, Satabdi; Chen, Hua; Johnson, Michael L; Aparasu, Rajender R

2012-10-01

Atypical antipsychotic agents have been associated with cerebrovascular adverse events, particularly in elderly dementia patients. However, limited evidence exists regarding comparative cerebrovascular profiles of individual atypical agents, particularly in community settings. The objective of this study was to evaluate the risk of cerebrovascular events associated with use of risperidone, olanzapine and quetiapine in community-dwelling older adults in the US. A propensity score-adjusted retrospective cohort design involving the IMS LifeLink™ Health Plan Claims Database was used for the study. The study population included all older adults (aged ≥50 years) who initiated risperidone, olanzapine or quetiapine anytime during 1 July 2000 to 30 June 2008. Patients were followed until hospitalization or an emergency room visit for a cerebrovascular event, or the end of the study period, whichever occurred earlier. The Cox proportional hazard regression model with time-varying covariates was used to evaluate the risk of cerebrovascular events during the follow-up period, using olanzapine as the reference. The covariates adjusted for in the final model included multiple propensity scores and exposure to other medications that could be associated with the risk of cerebrovascular events. A total of 2,458 cerebrovascular events were identified in the study cohort: 1,081 (21.38%) for risperidone users, 816 (18.75%) for olanzapine users and 561 (21.05%) for quetiapine users. After adjusting for propensity scores and other covariates, the Cox proportional hazard model revealed that use of quetiapine [hazard ratio (HR) 0.88; 95% CI 0.78, 0.99] but not risperidone (HR 1.05; 95% CI 0.95, 1.16) was associated with a decrease in the risk of cerebrovascular adverse events compared with olanzapine. The study suggested that quetiapine use may be associated with a moderately lower risk of cerebrovascular events than olanzapine in older adults. Prescribers should closely monitor the patients treated with atypical agents for the incidence of cerebrovascular adverse events.

Lung Quality and Utilization in Controlled Donation After Circulatory Determination of Death Within the United States.

PubMed

Mooney, J J; Hedlin, H; Mohabir, P K; Vazquez, R; Nguyen, J; Ha, R; Chiu, P; Patel, K; Zamora, M R; Weill, D; Nicolls, M R; Dhillon, G S

2016-04-01

Although controlled donation after circulatory determination of death (cDCDD) could increase the supply of donor lungs within the United States, the yield of lungs from cDCDD donors remains low compared with donation after neurologic determination of death (DNDD). To explore the reason for low lung yield from cDCDD donors, Scientific Registry of Transplant Recipient data were used to assess the impact of donor lung quality on cDCDD lung utilization by fitting a logistic regression model. The relationship between center volume and cDCDD use was assessed, and the distance between center and donor hospital was calculated by cDCDD status. Recipient survival was compared using a multivariable Cox regression model. Lung utilization was 2.1% for cDCDD donors and 21.4% for DNDD donors. Being a cDCDD donor decreased lung donation (adjusted odds ratio 0.101, 95% confidence interval [CI] 0.085-0.120). A minority of centers have performed cDCDD transplant, with higher volume centers generally performing more cDCDD transplants. There was no difference in center-to-donor distance or recipient survival (adjusted hazard ratio 1.03, 95% CI 0.78-1.37) between cDCDD and DNDD transplants. cDCDD lungs are underutilized compared with DNDD lungs after adjusting for lung quality. Increasing transplant center expertise and commitment to cDCDD lung procurement is needed to improve utilization. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

The Health Hazards of Marriage. A cohort study of work related disability within 12,500 Norwegian couples - the HUNT Study.

PubMed

Vie, Gunnhild Åberge; Krokstad, Steinar; Johnsen, Roar; Bjørngaard, Johan Håkon

2013-07-01

Work disability and sickness absence increase following partner's retirement, which similarities in spouses' health could explain. We therefore studied the risk of work disability within couples, taking account of baseline health, lifestyle and socioeconomic factors. A cohort of 12,511 couples from the HUNT Study (aged 20-67 years in HUNT2, 1995-1997) was linked to national registries, identifying all new cases of disability pension up until December 2007. Data were analysed with discrete time multilevel logistic regression and Cox regression models. Partners' disability pension was included as a time-varying covariate. Follow-up time was split to examine the association dependent of time. Analyses were adjusted for age only, adjusted for health, and for lifestyle and education along with health. About 15% of an individual's propensity to receive a disability pension could be attributed couple similarity. There was an increased risk of work disability following the spouse's disability retirement [HR (hazard ratio) 1.43 (95% confidence interval 1.20-1.71) for men, HR 1.49 (95% confidence interval 1.28-1.74) for women]. The association was somewhat attenuated after adjustments for health, lifestyle and education. There was a substantial clustering of disability pensions within couples, which cannot be explained by similarities in health, lifestyle and education. This suggests partners influence each other's work ability. From a clinical perspective, the family situation needs to be taken into account when addressing health promotion and work participation.

A stratification approach using logit-based models for confounder adjustment in the study of continuous outcomes.

PubMed

Tan, Chuen Seng; Støer, Nathalie C; Chen, Ying; Andersson, Marielle; Ning, Yilin; Wee, Hwee-Lin; Khoo, Eric Yin Hao; Tai, E-Shyong; Kao, Shih Ling; Reilly, Marie

2017-01-01

The control of confounding is an area of extensive epidemiological research, especially in the field of causal inference for observational studies. Matched cohort and case-control study designs are commonly implemented to control for confounding effects without specifying the functional form of the relationship between the outcome and confounders. This paper extends the commonly used regression models in matched designs for binary and survival outcomes (i.e. conditional logistic and stratified Cox proportional hazards) to studies of continuous outcomes through a novel interpretation and application of logit-based regression models from the econometrics and marketing research literature. We compare the performance of the maximum likelihood estimators using simulated data and propose a heuristic argument for obtaining the residuals for model diagnostics. We illustrate our proposed approach with two real data applications. Our simulation studies demonstrate that our stratification approach is robust to model misspecification and that the distribution of the estimated residuals provides a useful diagnostic when the strata are of moderate size. In our applications to real data, we demonstrate that parity and menopausal status are associated with percent mammographic density, and that the mean level and variability of inpatient blood glucose readings vary between medical and surgical wards within a national tertiary hospital. Our work highlights how the same class of regression models, available in most statistical software, can be used to adjust for confounding in the study of binary, time-to-event and continuous outcomes.

Glucose-6-Phosphate Dehydrogenase Deficiency and Physical and Mental Health until Adolescence

PubMed Central

Kwok, Man Ki; Leung, Gabriel M.; Schooling, C. Mary

2016-01-01

Background To examine the association of glucose-6-phosphate dehydrogenase (G6PD) deficiency with adolescent physical and mental health, as effects of G6PD deficiency on health are rarely reported. Methods In a population-representative Chinese birth cohort: “Children of 1997” (n = 8,327), we estimated the adjusted associations of G6PD deficiency with growth using generalized estimating equations, with pubertal onset using interval censored regression, with hospitalization using Cox proportional hazards regression and with size, blood pressure, pubertal maturation and mental health using linear regression with multiple imputation and inverse probability weighting. Results Among 5,520 screened adolescents (66% follow-up), 4.8% boys and 0.5% girls had G6PD deficiency. G6PD-deficiency was not associated with birth weight-for-gestational age or length/height gain into adolescence, but was associated with lower childhood body mass index (BMI) gain (-0.38 z-score, 95% confidence interval (CI) -0.57, -0.20), adjusted for sex and parental education, and later onset of pubic hair development (time ratio = 1.029, 95% CI 1.007, 1.050). G6PD deficiency was not associated with blood pressure, height, BMI or mental health in adolescence, nor with serious infectious morbidity until adolescence. Conclusions G6PD deficient adolescents had broadly similar physical and mental health indicators, but transiently lower BMI gain and later pubic hair development, whose long-term implications warrant investigation. PMID:27824927

Excessive weight loss in exclusively breastfed full-term newborns in a Baby-Friendly Hospital.

PubMed

Mezzacappa, Maria Aparecida; Ferreira, Bruna Gil

2016-09-01

To determine the risk factors for weight loss over 8% in full-term newborns at postpartum discharge from a Baby Friendly Hospital. The cases were selected from a cohort of infants belonging to a previous study. Healthy full-term newborns with birth weight ≥2.000g, who were exclusively breastfed, and excluding twins and those undergoing phototherapy as well as those discharged after 96 hours of life, were included. The analyzed maternal variables were maternal age, parity, ethnicity, type of delivery, maternal diabetes, gender, gestational age and appropriate weight for age. Adjusted multiple and univariate Cox regression analyses were used, considering as significant p<0.05. We studied 414 newborns, of whom 107 (25.8%) had excessive weight loss. Through the univariate regression, risk factors associated with weight loss >8% were caesarean delivery and older maternal age. At the adjusted multiple regression analysis, the model to explain the weight loss was cesarean delivery (relative risk: 2.27 and 95% of confidence interval: 1.54 to 3.35). The independent predictor for weight loss >8% in exclusively breastfed full-term newborns in a Baby-Friendly Hospital was the cesarean delivery. It is possible to reduce the number of cesarean sections to minimize neonatal excessive weight loss and the resulting use of infant formula during the first week of life. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

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

Premature Atrial Contractions on the Screening Electrocardiogram and Risk of Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study.

PubMed

O'Neal, Wesley T; Kamel, Hooman; Kleindorfer, Dawn; Judd, Suzanne E; Howard, George; Howard, Virginia J; Soliman, Elsayed Z

2016-01-01

It is currently unknown if premature atrial contractions (PACs) detected on the routine screening electrocardiogram are associated with an increased risk of ischemic stroke. We examined the association between PACs and ischemic stroke in 22,975 (mean age 64 ± 9.2; 56% women; 40% black) participants from the Reasons for Geographic and Racial Differences in Stroke study. Participants who were free of stroke at baseline were included. PACs were detected from centrally read electrocardiograms at baseline. Cox regression was used to examine the association between PACs and ischemic stroke events through March 31, 2014. PACs were present in 1,687 (7.3%) participants at baseline. In a Cox regression model adjusted for stroke risk factors and potential confounders, PACs were associated with an increased risk of ischemic stroke (hazards ratio (HR) 1.34, 95% CI 1.04-1.74). The relationship was limited to non-lacunar infarcts (HR 1.42, 95% CI 1.08-1.87), and not lacunar strokes (HR 1.01, 95% CI 0.51-2.03). An interaction by sex was detected, with the association between PACs and ischemic stroke being stronger among women (HR 1.82, 95% CI 1.29-2.56) than men (HR 1.03, 95% CI 0.69-1.52; p-interaction = 0.0095). PACs detected on the routine electrocardiogram are associated with an increased risk for non-lacunar ischemic strokes, especially in women. © 2016 S. Karger AG, Basel.

Accounting for individual differences and timing of events: estimating the effect of treatment on criminal convictions in heroin users

PubMed Central

2014-01-01

Background The reduction of crime is an important outcome of opioid maintenance treatment (OMT). Criminal intensity and treatment regimes vary among OMT patients, but this is rarely adjusted for in statistical analyses, which tend to focus on cohort incidence rates and rate ratios. The purpose of this work was to estimate the relationship between treatment and criminal convictions among OMT patients, adjusting for individual covariate information and timing of events, fitting time-to-event regression models of increasing complexity. Methods National criminal records were cross linked with treatment data on 3221 patients starting OMT in Norway 1997–2003. In addition to calculating cohort incidence rates, criminal convictions was modelled as a recurrent event dependent variable, and treatment a time-dependent covariate, in Cox proportional hazards, Aalen’s additive hazards, and semi-parametric additive hazards regression models. Both fixed and dynamic covariates were included. Results During OMT, the number of days with criminal convictions for the cohort as a whole was 61% lower than when not in treatment. OMT was associated with reduced number of days with criminal convictions in all time-to-event regression models, but the hazard ratio (95% CI) was strongly attenuated when adjusting for covariates; from 0.40 (0.35, 0.45) in a univariate model to 0.79 (0.72, 0.87) in a fully adjusted model. The hazard was lower for females and decreasing with older age, while increasing with high numbers of criminal convictions prior to application to OMT (all p < 0.001). The strongest predictors were level of criminal activity prior to entering into OMT, and having a recent criminal conviction (both p < 0.001). The effect of several predictors was significantly time-varying with their effects diminishing over time. Conclusions Analyzing complex observational data regarding to fixed factors only overlooks important temporal information, and naïve cohort level incidence rates might result in biased estimates of the effect of interventions. Applying time-to-event regression models, properly adjusting for individual covariate information and timing of various events, allows for more precise and reliable effect estimates, as well as painting a more nuanced picture that can aid health care professionals and policy makers. PMID:24886472

Soccer and sexual health education: a promising approach for reducing adolescent births in Haiti.

PubMed

Kaplan, Kathryn C; Lewis, Judy; Gebrian, Bette; Theall, Katherine

2015-05-01

To explore the effect of an innovative, integrative program in female sexual reproductive health (SRH) and soccer (or fútbol, in Haitian Creole) in rural Haiti by measuring the rate of births among program participants 15-19 years old and their nonparticipant peers. A retrospective cohort study using 2006-2009 data from the computerized data-tracking system of the Haitian Health Foundation (HHF), a U.S.-based nongovernmental organization serving urban and rural populations in Haiti, was used to assess births among girls 15-19 years old who participated in HHF's GenNext program, a combination education-soccer program for youth, based on SRH classes HHF nurses and community workers had been conducting in Haiti for mothers, fathers, and youth; girl-centered health screenings; and an all-female summer soccer league, during 2006-2009 (n = 4 251). Bivariate and multiple logistic regression analyses were carried out to assess differences in the rate of births among program participants according to their level of participation (SRH component only ("EDU") versus both the SRH and soccer components ("SO") compared to their village peers who did not participate. Hazard ratios (HRs) of birth rates were estimated using Cox regression analysis of childbearing data for the three different groups. In the multiple logistic regression analysis, only the girls in the "EDU" group had significantly fewer births than the nonparticipants after adjusting for confounders (odds ratio = 0.535; 95% confidence interval (CI) = 0.304, 0.940). The Cox regression analysis demonstrated that those in the EDU group (HR = 0.893; 95% CI = 0.802, 0.994) and to a greater degree those in the SO group (HR = 0.631; 95% CI = 0.558, 0.714) were significantly protected against childbearing between the ages of 15 and 19 years. HHF's GenNext program demonstrates the effectiveness of utilizing nurse educators, community mobilization, and youth participation in sports, education, and structured youth groups to promote and sustain health for adolescent girls and young women.

[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.

Multi-omics facilitated variable selection in Cox-regression model for cancer prognosis prediction.

PubMed

Liu, Cong; Wang, Xujun; Genchev, Georgi Z; Lu, Hui

2017-07-15

New developments in high-throughput genomic technologies have enabled the measurement of diverse types of omics biomarkers in a cost-efficient and clinically-feasible manner. Developing computational methods and tools for analysis and translation of such genomic data into clinically-relevant information is an ongoing and active area of investigation. For example, several studies have utilized an unsupervised learning framework to cluster patients by integrating omics data. Despite such recent advances, predicting cancer prognosis using integrated omics biomarkers remains a challenge. There is also a shortage of computational tools for predicting cancer prognosis by using supervised learning methods. The current standard approach is to fit a Cox regression model by concatenating the different types of omics data in a linear manner, while penalty could be added for feature selection. A more powerful approach, however, would be to incorporate data by considering relationships among omics datatypes. Here we developed two methods: a SKI-Cox method and a wLASSO-Cox method to incorporate the association among different types of omics data. Both methods fit the Cox proportional hazards model and predict a risk score based on mRNA expression profiles. SKI-Cox borrows the information generated by these additional types of omics data to guide variable selection, while wLASSO-Cox incorporates this information as a penalty factor during model fitting. We show that SKI-Cox and wLASSO-Cox models select more true variables than a LASSO-Cox model in simulation studies. We assess the performance of SKI-Cox and wLASSO-Cox using TCGA glioblastoma multiforme and lung adenocarcinoma data. In each case, mRNA expression, methylation, and copy number variation data are integrated to predict the overall survival time of cancer patients. Our methods achieve better performance in predicting patients' survival in glioblastoma and lung adenocarcinoma. Copyright © 2017. Published by Elsevier Inc.

[Smoking and student survival at Universidad Santiago de Cali, 2004-2007].

PubMed

Tafur-Calderón, Luis A; Millán-Estupiñan, Juan C; Zapata-Ossa, Helmer; Ordoñez-Arana, Gustavo A; Varela, Jesús M

2010-04-01

This article presents the results of monitoring students who enrolled at Universidad Santiago de Cali (USC) during the second half of 2004. Its purpose was to determine the influence of smoking, the academic programme and the cost of enrollment on student survival over a three-year period (2004-2007). The study involved a prospective cohort of 970 students who entered the university in 2004. Cox regression was used for survival analysis to determine the relationship between independent variables and university stay. The results of this model established associations between smoking and department with survival in the university, but discarded association with the cost of enrollment. The risk of university desertion was higher amongst students from the Health faculty adjusted for smoking (RR = 1.277 (1.121-1.455)). Similarly, the risk of desertion was higher in smokers adjusted by faculty (RR = 1.194 (1.026-1.390). It was found that habitual smokers had shorter university stay than nonsmokers. University stay was longer in students enrolled in academic programmes other than health.

Risk of Stroke Among Survivors of the September 11, 2001 World Trade Center Disaster.

PubMed

Yu, Shengchao; Alper, Howard E; Nguyen, Angela-Maithy; Brackbill, Robert M

2018-05-30

The aim of this study was to investigate the association between 9/11-related posttraumatic stress disorder (PTSD), dust cloud exposure, and subsequent development of stroke among 42,527 enrollees in the World Trade Center (WTC) Health Registry. Using four waves of longitudinal data from the WTC Health Registry surveys, we employed Cox proportional hazards regression models to assess the associations. Incidence of stroke was higher among those with PTSD or intense dust cloud exposure than those without, and it was even higher for those who had experienced both. In fully adjusted models, participants with PTSD had an increased risk of developing stroke [adjusted hazards ratio (AHR) 1.69, 95% confidence interval (95% CI) 1.42 to 2.02], as did those with intense dust exposure (AHR 1.29, 95% CI 1.09 to 1.53). We found that individuals with 9/11-related PTSD and/or intense dust exposure may have an increased risk of developing stroke.

Localized Scleroderma, Systemic Sclerosis and Cardiovascular Risk: A Danish Nationwide Cohort Study.

PubMed

Hesselvig, Jeanette Halskou; Kofoed, Kristian; Wu, Jashin J; Dreyer, Lene; Gislason, Gunnar; Ahlehoff, Ole

2018-03-13

Recent findings indicate that patients with systemic sclerosis have an increased risk of cardiovascular disease. To determine whether patients with systemic sclerosis or localized scleroderma are at increased risk of cardiovascular disease, a cohort study of the entire Danish population aged ≥ 18 and ≤ 100 years was conducted, followed from 1997 to 2011 by individual-level linkage of nationwide registries. Multivariable adjusted Cox regression models were used to estimate the hazard ratios (HRs) for a composite cardiovascular disease endpoint. A total of 697 patients with localized scleroderma and 1,962 patients with systemic sclerosis were identified and compared with 5,428,380 people in the reference population. In systemic sclerosis, the adjusted HR was 2.22 (95% confidence interval 1.99-2.48). No association was seen between patients with localized scleroderma and cardiovascular disease. In conclusion, systemic sclerosis is a significant cardiovascular disease risk factor, while patients with localized scleroderma are not at increased risk of cardiovascular disease.

The Breslow estimator of the nonparametric baseline survivor function in Cox's regression model: some heuristics.

PubMed

Hanley, James A

2008-01-01

Most survival analysis textbooks explain how the hazard ratio parameters in Cox's life table regression model are estimated. Fewer explain how the components of the nonparametric baseline survivor function are derived. Those that do often relegate the explanation to an "advanced" section and merely present the components as algebraic or iterative solutions to estimating equations. None comment on the structure of these estimators. This note brings out a heuristic representation that may help to de-mystify the structure.

Hospital evaluation of health literacy and associated outcomes in patients after acute myocardial infarction.

PubMed

Rymer, Jennifer A; Kaltenbach, Lisa A; Anstrom, Kevin J; Fonarow, Gregg C; Erskine, Nathaniel; Peterson, Eric D; Wang, Tracy Y

2018-04-01

Low health literacy is common in the United States and may affect outcomes after myocardial infarction (MI). How often hospitals screen for low health literacy is unknown. We surveyed 122 hospitals in the TRANSLATE-ACS study and divided them into those that reported routinely (>75% of patients), selectively (1%-75%), or never (0%) screening MI patients for low health literacy prior to discharge. We performed logistic regression with random intercepts to compare 6-week and 6-month patient-reported medication adherence and multivariable Cox regression to compare 1-year major adverse cardiovascular events and all-cause readmission risks between hospital groups. Overall, 25 (20.5%), 47 (38.5%), and 50 (41.0%) hospitals reported routinely, selectively, or never screening patients for low health literacy, respectively. Patients discharged from hospitals that routinely screened were more likely to report 6-week medication adherence [routinely: adjusted odds ratio (OR) 1.26, 95% CI 1.01-1.57; selectively: adjusted OR 1.19, 95% CI 1.00-1.43, both referenced to those discharged from hospitals that never screened]. Compared with hospitals that never screened health literacy, 1-year major adverse cardiovascular events were similar for hospitals that reported routinely screening (adjusted HR 0.92, 95% CI 0.75-1.14) or selectively screening (adjusted HR 1.01, 95% CI 0.84-1.21). Hospitals that reported selectively screening health literacy were associated with a lower adjusted risk of 1-year all-cause readmission (adjusted HR 0.89, 95% CI 0.79-1.00, P=.041). Only a minority of US hospitals routinely screen MI patients for low health literacy. Hospital screening was associated with higher medication adherence and lower readmission risk. Further investigation is needed to understand how inpatient screening can be implemented to improve longitudinal post-MI care. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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.

Disparities in the treatment and outcomes of lung cancer among HIV-infected individuals

PubMed Central

Suneja, Gita; Shiels, Meredith S.; Melville, Sharon K.; Williams, Melanie A.; Rengan, Ramesh; Engels, Eric A.

2013-01-01

Objectives HIV-infected people have elevated risk for lung cancer and higher mortality following cancer diagnosis than HIV-uninfected individuals. It is unclear whether HIV-infected individuals with lung cancer receive similar cancer treatment as HIV-uninfected individuals. Design/methods We studied adults more than 18 years of age with lung cancer reported to the Texas Cancer Registry (N = 156 930) from 1995 to 2009. HIV status was determined by linkage with the Texas enhanced HIV/AIDS Reporting System. For nonsmall cell lung cancer (NSCLC) cases, we identified predictors of cancer treatment using logistic regression. We used Cox regression to evaluate effects of HIV and cancer treatment on mortality. Results Compared with HIV-uninfected lung cancer patients (N = 156 593), HIV-infected lung cancer patients (N = 337) were more frequently young, black, men, and with non-Hispanic distant stage disease. HIV-infected NSCLC patients less frequently received cancer treatment than HIV-uninfected patients [60.3 vs. 77.5%; odds ratio 0.39, 95% confidence interval (CI) 0.30–0.52, after adjustment for diagnosis year, age, sex, race, stage, and histologic subtype]. HIV infection was associated with higher lung cancer-specific mortality (hazard ratio 1.34, 95% CI 1.15–1.56, adjusted for demographics and tumor characteristics). Inclusion of cancer treatment in adjusted models slightly attenuated the effect of HIV on lung cancer-specific mortality (hazard ratio 1.25; 95% CI 1.06–1.47). Also, there was a suggestion that HIV was more strongly associated with mortality among untreated than among treated patients (adjusted hazard ratio 1.32 vs. 1.16, P-interaction = 0.34). Conclusion HIV-infected NSCLC patients were less frequently treated for lung cancer than HIV-uninfected patients, which may have affected survival. PMID:23079809

Differences in treatment and survival among African-American and Caucasian women with early stage operable breast cancer.

PubMed

Sail, Kavita; Franzini, Luisa; Lairson, David; Du, Xianglin

2012-01-01

To examine racial disparities associated with breast cancer treatment and survival in elderly patients with early stage operable breast cancer. We studied 23,110 women with node-positive and 31,572 women with node-negative tumor who were aged ≥65 with stages I, II, or IIIA breast cancer in 1991-2002 using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked data. Logistic regression analyses were performed to assess the odds of receiving adjuvant chemotherapy and radiation after breast conserving surgery (BCS) for blacks compared to whites. Cox proportional hazard regression models were used to determine the risk of mortality in blacks compared to whites, stratified by types of treatment. Black women with node-positive and node-negative tumors were 25% (odds ratio = 0.75, 95% CI = 0.65-0.87) and 17% (0.83, 0.70-0.99) less likely to receive chemotherapy than white women, after adjusting for patient and tumor characteristics. This relation was not attenuated and remained statistically significant even after adjustment for socioeconomic status. In women with node-negative tumor who did not receive chemotherapy, black women were significantly more likely to die than white women (hazard ratio (HR) = 1.14, 95% CI = 1.04-1.24) after adjusting for patient and tumor characteristics, and comorbidity; and (1.11, 1.01-1.22) after additionally adjusting for socioeconomic status. There were racial disparities between black and white women in receiving adjuvant chemotherapy and radiotherapy following BCS. Higher risk of mortality in black compared to white women was found only in those receiving no chemotherapy. Future studies should explore the root causes of racial disparities beyond treatment factors.

Multivariable confounding adjustment in distributed data networks without sharing of patient-level data.

PubMed

Toh, Sengwee; Reichman, Marsha E; Houstoun, Monika; Ding, Xiao; Fireman, Bruce H; Gravel, Eric; Levenson, Mark; Li, Lingling; Moyneur, Erick; Shoaibi, Azadeh; Zornberg, Gwen; Hennessy, Sean

2013-11-01

It is increasingly necessary to analyze data from multiple sources when conducting public health safety surveillance or comparative effectiveness research. However, security, privacy, proprietary, and legal concerns often reduce data holders' willingness to share highly granular information. We describe and compare two approaches that do not require sharing of patient-level information to adjust for confounding in multi-site studies. We estimated the risks of angioedema associated with angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and aliskiren in comparison with beta-blockers within Mini-Sentinel, which has created a distributed data system of 18 health plans. To obtain the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs), we performed (i) a propensity score-stratified case-centered logistic regression analysis, a method identical to a stratified Cox regression analysis but needing only aggregated risk set data, and (ii) an inverse variance-weighted meta-analysis, which requires only the site-specific HR and variance. We also performed simulations to further compare the two methods. Compared with beta-blockers, the adjusted HR was 3.04 (95% CI: 2.81, 3.27) for ACEIs, 1.16 (1.00, 1.34) for ARBs, and 2.85 (1.34, 6.04) for aliskiren in the case-centered analysis. The corresponding HRs were 2.98 (2.76, 3.21), 1.15 (1.00, 1.33), and 2.86 (1.35, 6.04) in the meta-analysis. Simulations suggested that the two methods may produce different results under certain analytic scenarios. The case-centered analysis and the meta-analysis produced similar results without the need to share patient-level data across sites in our empirical study, but may provide different results in other study settings. Copyright © 2013 John Wiley & Sons, Ltd.

Proton pump inhibitor and histamine-2 receptor antagonist use and risk of liver cancer in two population-based studies.

PubMed

Tran, K T; McMenamin, Ú C; Hicks, B; Murchie, P; Thrift, A P; Coleman, H G; Iversen, L; Johnston, B T; Lee, A J; Cardwell, C R

2018-05-09

Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly used. PPIs have been shown to promote liver cancer in rats; however, only one study has examined the association in humans. To investigate PPIs and H2RAs and risk of primary liver cancer in two large independent study populations. We conducted a nested case-control study within the Primary Care Clinical Informatics Unit (PCCIU) database in which up to five controls were matched to cases with primary liver cancer, recorded by General Practitioners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations with prescribed PPIs and H2RAs were calculated using conditional logistic regression. We also conducted a prospective cohort study within the UK Biobank using self-reported medication use and cancer-registry recorded primary liver cancer. Hazard ratios (HRs) and 95% CIs were calculated using Cox regression. In the PCCIU case-control analysis, 434 liver cancer cases were matched to 2103 controls. In the UK Biobank cohort, 182 of 475 768 participants developed liver cancer. In both, ever use of PPIs was associated with increased liver cancer risk (adjusted OR 1.80, 95% CI 1.34, 2.41 and adjusted HR 1.99, 95% CI 1.34, 2.94 respectively). There was little evidence of association with H2RA use (adjusted OR 1.21, 95% CI 0.84, 1.76 and adjusted HR 1.70, 95% CI 0.82, 3.53 respectively). We found some evidence that PPI use was associated with liver cancer. Whether this association is causal or reflects residual confounding or reverse causation requires additional research. © 2018 John Wiley & Sons Ltd.

Modeling time-to-event (survival) data using classification tree analysis.

PubMed

Linden, Ariel; Yarnold, Paul R

2017-12-01

Time to the occurrence of an event is often studied in health research. Survival analysis differs from other designs in that follow-up times for individuals who do not experience the event by the end of the study (called censored) are accounted for in the analysis. Cox regression is the standard method for analysing censored data, but the assumptions required of these models are easily violated. In this paper, we introduce classification tree analysis (CTA) as a flexible alternative for modelling censored data. Classification tree analysis is a "decision-tree"-like classification model that provides parsimonious, transparent (ie, easy to visually display and interpret) decision rules that maximize predictive accuracy, derives exact P values via permutation tests, and evaluates model cross-generalizability. Using empirical data, we identify all statistically valid, reproducible, longitudinally consistent, and cross-generalizable CTA survival models and then compare their predictive accuracy to estimates derived via Cox regression and an unadjusted naïve model. Model performance is assessed using integrated Brier scores and a comparison between estimated survival curves. The Cox regression model best predicts average incidence of the outcome over time, whereas CTA survival models best predict either relatively high, or low, incidence of the outcome over time. Classification tree analysis survival models offer many advantages over Cox regression, such as explicit maximization of predictive accuracy, parsimony, statistical robustness, and transparency. Therefore, researchers interested in accurate prognoses and clear decision rules should consider developing models using the CTA-survival framework. © 2017 John Wiley & Sons, Ltd.

A global goodness-of-fit statistic for Cox regression models.

PubMed

Parzen, M; Lipsitz, S R

1999-06-01

In this paper, a global goodness-of-fit test statistic for a Cox regression model, which has an approximate chi-squared distribution when the model has been correctly specified, is proposed. Our goodness-of-fit statistic is global and has power to detect if interactions or higher order powers of covariates in the model are needed. The proposed statistic is similar to the Hosmer and Lemeshow (1980, Communications in Statistics A10, 1043-1069) goodness-of-fit statistic for binary data as well as Schoenfeld's (1980, Biometrika 67, 145-153) statistic for the Cox model. The methods are illustrated using data from a Mayo Clinic trial in primary billiary cirrhosis of the liver (Fleming and Harrington, 1991, Counting Processes and Survival Analysis), in which the outcome is the time until liver transplantation or death. The are 17 possible covariates. Two Cox proportional hazards models are fit to the data, and the proposed goodness-of-fit statistic is applied to the fitted models.

Survival Disparity of African American Versus Non-African American Patients With ESRD Due to SLE.

PubMed

Nee, Robert; Martinez-Osorio, Jorge; Yuan, Christina M; Little, Dustin J; Watson, Maura A; Agodoa, Lawrence; Abbott, Kevin C

2015-10-01

A recent study showed an increased risk of death in African Americans compared with whites with end-stage renal disease (ESRD) due to lupus nephritis (LN). We assessed the impact of age stratification, socioeconomic factors, and kidney transplantation on the disparity in patient survival among African American versus non-African American patients with LN-caused ESRD, compared with other causes. Retrospective cohort study. Using the US Renal Data System database, we identified 12,352 patients with LN-caused ESRD among 1,132,202 patients who initiated maintenance dialysis therapy from January 1, 1995, through December 31, 2006, and were followed up until December 31, 2010. Baseline demographics and comorbid conditions, Hispanic ethnicity, socioeconomic factors (employment status, Medicare/Medicaid insurance, and area-level median household income based on zip code as obtained from the 2000 US census), and kidney transplantation as a time-dependent variable. All-cause mortality. Multivariable Cox and competing-risk regressions. Mean duration of follow-up in the LN-caused ESRD and other-cause ESRD cohorts were 6.24±4.20 (SD) and 4.06±3.61 years, respectively. 6,106 patients with LN-caused ESRD (49.43%) and 853,762 patients with other-cause ESRD (76.24%) died during the study period (P<0.001). Patients with LN-caused ESRD were significantly younger (mean age, 39.92 years) and more likely women (81.65%) and African American (48.13%) than those with other-cause ESRD. In the fully adjusted multivariable Cox regression model, African American (vs non-African American) patients with LN-caused ESRD had significantly increased risk of death at age 18 to 30 years (adjusted HR, 1.43; 95% CI, 1.24-1.65) and at age 31 to 40 years (adjusted HR, 1.17; 95% CI, 1.02-1.34). Among patients with other-cause ESRD, African Americans were at significantly increased risk at age 18 to 30 years (adjusted HR, 1.17; 95% CI, 1.11-1.22). We used zip code-based median household income as a surrogate for patient income. Residual socioeconomic confounders may exist. African Americans are at significantly increased risk of death compared with non-African Americans with LN-caused ESRD at age 18 to 40 years, a racial disparity risk that is 10 years longer than that in the general ESRD population. Accounting for area-level median household income and transplantation significantly attenuated the disparity in mortality of African American versus non-African American patients with LN-caused ESRD. Published by Elsevier Inc.

Cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction and cerebrovascular accident.

PubMed

Abraham, N S; El-Serag, H B; Hartman, C; Richardson, P; Deswal, A

2007-04-15

To assess degree of cyclooxygenase-2 (COX-2) selectivity of a non-steroidal anti-inflammatory drug (NSAID) and risk of myocardial infarction (MI) or cerebrovascular accident (CVA). Prescription fill data were linked to medical records of a merged VA-Medicare dataset. NSAIDs were categorized by Cox-2 selectivity. Incidence of CVA and MI within 180 days of index prescription was assessed using Cox-proportional hazards models adjusted for gender, race, cardiovascular and pharmacological risk factors and propensity for prescription of highly COX-2 selective NSAIDs. Of 384,322 patients (97.5% men and 85.4% white), 79.4% were prescribed a poorly selective, 16.4% a moderately selective and 4.2% a highly selective NSAID. There were 985 incident cases of MI and 586 cases of CVA in >145 870 person-years. Highly selective agents had the highest rate of MI (12.3 per 1000 person-years; [95% CI: 12.2-12.3]) and CVA (8.1 per 1000 person-years; [95% CI: 8.0-8.2]). Periods without NSAID exposure were associated with lowest risk. In adjusted models, highly selective COX-2 selective NSAIDs were associated with a 61% increase in CVA and a 47% increase in MI, when compared with poorly selective NSAIDs. The risk of MI and CVA increases with any NSAID. Highly COX-2 selective NSAIDs confer the greatest risk.

ORACLE INEQUALITIES FOR THE LASSO IN THE COX MODEL

PubMed Central

Huang, Jian; Sun, Tingni; Ying, Zhiliang; Yu, Yi; Zhang, Cun-Hui

2013-01-01

We study the absolute penalized maximum partial likelihood estimator in sparse, high-dimensional Cox proportional hazards regression models where the number of time-dependent covariates can be larger than the sample size. We establish oracle inequalities based on natural extensions of the compatibility and cone invertibility factors of the Hessian matrix at the true regression coefficients. Similar results based on an extension of the restricted eigenvalue can be also proved by our method. However, the presented oracle inequalities are sharper since the compatibility and cone invertibility factors are always greater than the corresponding restricted eigenvalue. In the Cox regression model, the Hessian matrix is based on time-dependent covariates in censored risk sets, so that the compatibility and cone invertibility factors, and the restricted eigenvalue as well, are random variables even when they are evaluated for the Hessian at the true regression coefficients. Under mild conditions, we prove that these quantities are bounded from below by positive constants for time-dependent covariates, including cases where the number of covariates is of greater order than the sample size. Consequently, the compatibility and cone invertibility factors can be treated as positive constants in our oracle inequalities. PMID:24086091

ORACLE INEQUALITIES FOR THE LASSO IN THE COX MODEL.

PubMed

Huang, Jian; Sun, Tingni; Ying, Zhiliang; Yu, Yi; Zhang, Cun-Hui

2013-06-01

We study the absolute penalized maximum partial likelihood estimator in sparse, high-dimensional Cox proportional hazards regression models where the number of time-dependent covariates can be larger than the sample size. We establish oracle inequalities based on natural extensions of the compatibility and cone invertibility factors of the Hessian matrix at the true regression coefficients. Similar results based on an extension of the restricted eigenvalue can be also proved by our method. However, the presented oracle inequalities are sharper since the compatibility and cone invertibility factors are always greater than the corresponding restricted eigenvalue. In the Cox regression model, the Hessian matrix is based on time-dependent covariates in censored risk sets, so that the compatibility and cone invertibility factors, and the restricted eigenvalue as well, are random variables even when they are evaluated for the Hessian at the true regression coefficients. Under mild conditions, we prove that these quantities are bounded from below by positive constants for time-dependent covariates, including cases where the number of covariates is of greater order than the sample size. Consequently, the compatibility and cone invertibility factors can be treated as positive constants in our oracle inequalities.

Genetic Variation in the Human SORBS1 Gene is Associated With Blood Pressure Regulation and Age at Onset of Hypertension: A SAPPHIRe Cohort Study.

PubMed

Chang, Tien-Jyun; Wang, Wen-Chang; Hsiung, Chao A; He, Chih-Tsueng; Lin, Ming-Wei; Sheu, Wayne Huey-Herng; Chang, Yi-Cheng; Quertermous, Tom; Chen, Ida; Rotter, Jerome; Chuang, Lee-Ming

2016-03-01

Essential hypertension is a complex disease involving multiple genetic and environmental factors. A human gene containing a sorbin homology domain and 3 SH3 domains in the C-terminal region, termed SORBS1, plays a significant role in insulin signaling. We previously found a significant association between the T228A polymorphism and insulin resistance, obesity, and type 2 diabetes. It has been hypothesized that a set of genes responsible for insulin resistance may be closely linked with genes susceptible to the development of hypertension. Identification of insulin resistance-related genetic factors may, therefore, enhance our understanding of essential hypertension. This study aimed to examine whether common SORBS1 genetic variations are associated with blood pressure and age at onset of hypertension in an ethnic Chinese cohort.We genotyped 9 common tagged single nucleotide polymorphisms of the SORBS1 gene in 1136 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study. Blood pressure was measured upon enrolment. The associations of the SORBS1 single nucleotide polymorphisms with blood pressure and the presence of hypertension were analyzed with a generalized estimating equation model. We used the false-discovery rate measure Q value with a cutoff <0.1 to adjust for multiple comparisons. In the Cox regression analysis for hypertension-free survival, a robust sandwich variance estimator was used to deal with the within-family correlations with age at onset of hypertension. Gender, body mass index, and antihypertension medication were adjustment covariates in the Cox regression analysis.In this study, genetic variants of rs2281939 and rs2274490 were significantly associated with both systolic and diastolic blood pressure. A genetic variant of rs2274490 was also significantly associated with the presence of hypertension. Furthermore, genetic variants of rs2281939 and rs2274490 were associated with age at onset of hypertension after adjustment for gender, body mass index, and antihypertension medication.In conclusion, we provide evidence for an association between common SORBS1 genetic variations and blood pressure, presence of hypertension, and age at onset of hypertension. The biological mechanism of genetic variation associated with blood pressure regulation needs further investigation.

Prevalent digoxin use and subsequent risk of death or hospitalization in ambulatory heart failure patients with a reduced ejection fraction-Findings from the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) randomized controlled trial.

PubMed

Ambrosy, Andrew P; Bhatt, Ankeet S; Stebbins, Amanda L; Wruck, Lisa M; Fudim, Marat; Greene, Stephen J; Kraus, William E; O'Connor, Christopher M; Piña, Ileana L; Whellan, David J; Mentz, Robert J

2018-05-01

Despite more than 200 years of clinical experience and a pivotal trial, recently published research has called into question the safety and efficacy of digoxin therapy in heart failure (HF). HF-ACTION (ClinicalTrials.gov Number: NCT00047437) enrolled 2331 outpatients with HF and an EF ≤35% between April 2003 and February 2007 and randomized them to aerobic exercise training versus usual care. Patients were grouped according to prevalent digoxin status at baseline. The association between digoxin therapy and outcomes was assessed using Cox proportional hazard and inverse-probability weighted (IPW) regression models adjusted for demographics, medical history, medications, laboratory values, quality of life, and exercise parameters. The prevalence of digoxin therapy decreased from 52% during the first 6 months of enrollment to 35% at the end of the HF-ACTION trial (P <0.0001). Study participants were 59± 13 years of age, 72% were male, and approximately half had an ischemic etiology of HF. Patients receiving digoxin at baseline tended to be younger and were more likely to report New York Heart Association functional class III/IV symptoms (rather than class II) compared to those not receiving digoxin. Patients taking digoxin had worse baseline exercise capacity as measured by peak VO 2 and 6-min walk test and greater impairments in health status as reflected by the Kansas City Cardiomyopathy Questionnaire. The association between digoxin and the risk of death or hospitalization differed depending on whether Cox proportional hazard (Hazard Ratio 1.03, 95% Confidence Interval 0.92-1.16; P = .62) or IPW regression models (HR 1.08, 95% CI 1.00-1.17; P = .057) were used to adjust for potential confounders. Although digoxin use was associated with high-risk clinical features, the association between digoxin therapy and outcomes was dependent on the statistical methods used for multivariable adjustment. Clinical equipoise exists and additional prospective research is required to clarify the role of digoxin in contemporary clinical practice including its effects on functional capacity, quality of life, and long-term outcomes. Copyright © 2018. Published by Elsevier Inc.

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.

Box-Cox transformation of left-censored data with application to the analysis of coronary artery calcification and pharmacokinetic data.

PubMed

Han, Cong; Kronmal, Richard

2004-12-15

Box-Cox transformation is investigated for regression models for left-censored data. Examples are provided using coronary calcification data from the Multi-Ethnic Study of Atherosclerosis and pharmacokinetic data of a nicotine nasal spray. Copyright 2004 John Wiley & Sons, Ltd.

Predictors of course in obsessive-compulsive disorder: logistic regression versus Cox regression for recurrent events.

PubMed

Kempe, P T; van Oppen, P; de Haan, E; Twisk, J W R; Sluis, A; Smit, J H; van Dyck, R; van Balkom, A J L M

2007-09-01

Two methods for predicting remissions in obsessive-compulsive disorder (OCD) treatment are evaluated. Y-BOCS measurements of 88 patients with a primary OCD (DSM-III-R) diagnosis were performed over a 16-week treatment period, and during three follow-ups. Remission at any measurement was defined as a Y-BOCS score lower than thirteen combined with a reduction of seven points when compared with baseline. Logistic regression models were compared with a Cox regression for recurrent events model. Logistic regression yielded different models at different evaluation times. The recurrent events model remained stable when fewer measurements were used. Higher baseline levels of neuroticism and more severe OCD symptoms were associated with a lower chance of remission, early age of onset and more depressive symptoms with a higher chance. Choice of outcome time affects logistic regression prediction models. Recurrent events analysis uses all information on remissions and relapses. Short- and long-term predictors for OCD remission show overlap.

Influence of the timing of cardiac surgery on the outcome of patients with infective endocarditis and stroke.

PubMed

Barsic, Bruno; Dickerman, Stuart; Krajinovic, Vladimir; Pappas, Paul; Altclas, Javier; Carosi, Giampiero; Casabé, José H; Chu, Vivian H; Delahaye, Francois; Edathodu, Jameela; Fortes, Claudio Querido; Olaison, Lars; Pangercic, Ana; Patel, Mukesh; Rudez, Igor; Tamin, Syahidah Syed; Vincelj, Josip; Bayer, Arnold S; Wang, Andrew

2013-01-01

The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.

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.

Anthropometric factors and cutaneous melanoma: Prospective data from the population-based Janus Cohort.

PubMed

Stenehjem, Jo S; Veierød, Marit B; Nilsen, Lill Tove; Ghiasvand, Reza; Johnsen, Bjørn; Grimsrud, Tom K; Babigumira, Ronnie; Rees, Judith R; Robsahm, Trude E

2018-02-15

The aim of the present study was to prospectively examine risk of cutaneous melanoma (CM) according to measured anthropometric factors, adjusted for exposure to ultraviolet radiation (UVR), in a large population-based cohort in Norway. The Janus Cohort, including 292,851 Norwegians recruited 1972-2003, was linked to the Cancer Registry of Norway and followed for CM through 2014. Cox regression was used to estimate hazard ratios (HRs) of CM with 95% confidence intervals (CIs). Restricted cubic splines were incorporated into the Cox models to assess possible non-linear relationships. All analyses were adjusted for attained age, indicators of UVR exposure, education, and smoking status. During a mean follow-up of 27 years, 3,000 incident CM cases were identified. In men, CM risk was positively associated with body mass index, body surface area (BSA), height and weight (all p trends  < 0.001), and the exposure-response curves indicated an exponential increase in risk for all anthropometric factors. Weight loss of more than 2 kg in men was associated with a 53% lower risk (HR 0.47, 95% CI: 0.39, 0.57). In women, CM risk increased with increasing BSA (p trend  = 0.002) and height (p trend  < 0.001). The shape of the height-CM risk curve indicated an exponential increase. Our study suggests that large body size, in general, is a CM risk factor in men, and is the first to report that weight loss may reduce the risk of CM among men. © 2017 UICC.

Periodontal Disease Associated with Higher Risk of Dementia: Population-Based Cohort Study in Taiwan.

PubMed

Lee, Ya-Ling; Hu, Hsiao-Yun; Huang, Li-Ying; Chou, Pesus; Chu, Dachen

2017-09-01

To determine the magnitude and temporal aspect of the effect of poor dental health and periodontal disease (PD) on dementia. Retrospective cohort study SETTING: Taiwan National Health Insurance Research Database. Individuals with newly diagnosed PD (N = 182,747) MEASUREMENTS: Participants were followed from January 1, 2000, to December 31, 2010. Participants were assigned to dental prophylaxis, intensive periodontal treatment, tooth extraction, or no treatment, according to International Classification of Diseases codes and PD treatment codes. The incidence rate of dementia of the groups was compared. The association between PD and dementia was analyzed using Cox regression, with adjustments for age, sex, monthly income, residential urbanicity, and comorbidities. The incidence of dementia was significantly higher in the group with PD that did not receive treatment (0.76% per year) and in the group that had teeth extracted (0.57% per year) than in the group that underwent intensive PD treatment (0.35% per year) and the group that received dental prophylaxis (0.39% per year) (P < .001). After adjusting for confounders, the Cox proportional hazards model revealed a higher risk of dementia in the group with PD who did not undergo treatment (hazard ratio (HR) = 1.14, 95% confidence interval (CI) = 1.04-1.24) and the group that had teeth extracted (HR = 1.10, 95% CI = 1.04-1.16) than in the group that received dental prophylaxis. Subjects who had more severe PD or did not receive periodontal treatment were at greater risk of developing dementia. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Preemptive Deceased Donor Kidney Transplantation: Considerations of Equity and Utility

PubMed Central

Chen, B. Po-Han; Coresh, Josef; Segev, Dorry L.

2013-01-01

Summary Background and objectives There exists gross disparity in national deceased donor kidney transplant availability and practice: waiting times exceed 6 years in some regions, but some patients receive kidneys before they require dialysis. This study aimed to quantify and characterize preemptive deceased donor kidney transplant recipients and compare their outcomes with patients transplanted shortly after dialysis initiation. Design, setting, participants, & measurements Using the Scientific Registry of Transplant Recipients database, first-time adult deceased donor kidney transplant recipients between 1995 and 2011 were classified as preemptive, early (on dialysis≤1 year), or late recipients. Random effects logistic regression and multivariate Cox proportional hazards regression were used to identify characteristics of preemptive deceased donor kidney transplant and evaluate survival in preemptive and early recipients, respectively. Results Preemptive recipients were 9.0% of the total recipient population. Patients with private insurance (adjusted odds ratio=3.15, 95% confidence interval=3.01–3.29, P<0.001), previous (nonkidney) transplant (adjusted odds ratio=1.94, 95% confidence interval=1.67–2.26, P<0.001), and zero-antigen mismatch (adjusted odds ratio=1.45, 95% confidence interval=1.37–1.54, P<0.001; Caucasians only) were more likely to receive preemptive deceased donor kidney transplant, even after accounting for center-level clustering. African Americans were less likely to receive preemptive deceased donor kidney transplant (adjusted odds ratio=0.44, 95% confidence interval=0.41–0.47, P<0.001). Overall, patients transplanted preemptively had similar survival compared with patients transplanted within 1 year after initiating dialysis (adjusted hazard ratio=1.06, 95% confidence interval=0.99–1.12, P=0.07). Conclusions Preemptive deceased donor kidney transplant occurs most often among Caucasians with private insurance, and survival is fairly similar to survival of recipients on dialysis for <1 year. PMID:23371953

Effects of Education and Income on Treatment and Outcome in Patients With Acute Myeloid Leukemia in a Tax-Supported Health Care System: A National Population-Based Cohort Study.

PubMed

Østgård, Lene Sofie Granfeldt; Nørgaard, Mette; Medeiros, Bruno C; Friis, Lone Smidstrup; Schoellkopf, Claudia; Severinsen, Marianne Tang; Marcher, Claus Werenberg; Nørgaard, Jan Maxwell

2017-11-10

Purpose Previous US studies have shown that socioeconomic status (SES) affects survival in acute myeloid leukemia (AML). However, no large study has investigated the association between education or income and clinical characteristics, treatment, and outcome in AML. Methods To investigate the effects of education and income in a tax-supported health care system, we conducted a population-based study using individual-level SES and clinical data on all Danish patients with AML (2000 to 2014). We compared treatment intensity, allogeneic transplantation, and response rates by education and income level using logistic regression (odds ratios). We used Cox regression (hazard ratios [HRs]) to compare survival, adjusting for age, sex, SES, and clinical prognostic markers. Results Of 2,992 patients, 1,588 (53.1%) received intensive chemotherapy. Compared with low-education patients, highly educated patients more often received allogeneic transplantation (16.3% v 8.7%). In intensively treated patients younger than 60 years of age, increased mortality was observed in those with lower and medium education (1-year survival, 66.7%; adjusted HR, 1.47; 95% CI, 1.11 to 1.93; and 1-year survival, 67.6%; adjusted HR, 1.55; CI, 1.21 to 1.98, respectively) compared with higher education (1-year survival, 76.9%). Over the study period, 5-year survival improvements were limited to high-education patients (from 39% to 58%), increasing the survival gap between groups. In older patients, low-education patients received less intensive therapy (30% v 48%; adjusted odds ratio, 0.65; CI, 0.44 to 0.98) compared with high-education patients; however, remission rates and survival were not affected in those intensively treated. Income was not associated with therapy intensity, likelihood of complete remission, or survival (high income: adjusted HR, 1.0; medium income: adjusted HR, 0.96; 95% CI, 0.82 to 1.12; low income: adjusted HR, 1.06; CI, .88 to 1.27). Conclusion In a universal health care system, education level, but not income, affects transplantation rates and survival in younger patients with AML. Importantly, recent survival improvement has exclusively benefitted highly educated patients.

Association Between Physical Therapy and Risk of Coronary Artery Disease and Dyslipidemia Among Osteoarthritis Patients: A Nationwide Database Study.

PubMed

Yeh, Huan-Jui; Chou, Yiing-Jenq; Yang, Nan-Ping; Cheng, Chi-Chia; Huang, Nicole

2016-01-01

To provide empirical evidence on the effect of early physical therapy (PT) within the first year of osteoarthritis (OA) diagnosis on reduction in OA-related comorbidities in patients with OA. Retrospective cohort study. The study was conducted using a nationally representative sample of 1 million National Health Insurance enrollees. Newly diagnosed patients with OA (N=13,545). One-to-one propensity score matching was used to match patients who received PT within the first year of OA diagnosis (PT group; n=3403) with an equal number of patients with OA who did not receive PT (non-PT group). Not applicable. The 4-year cumulative risk of comorbidities including coronary artery disease (CAD), diabetes mellitus, dyslipidemia, osteoporosis, gastrointestinal tract ulcer, and renal failure was estimated. A Cox proportional hazards regression analysis was performed to identify the dose-response relation between the PT dosage and the risk of OA-related comorbidities. A total of 3403 patients (25.1%) received PT within the first year of OA diagnosis. The PT group had a significantly lower 4-year cumulative risk of dyslipidemia (P=.05) and a potentially lower 4-year cumulative risk of CAD (P=.09). After adjusting for other potential confounders, the Cox proportional hazards regression analysis showed that patients with OA who received a high PT dosage had a low risk of CAD and dyslipidemia. Patients with OA who received PT had a lower risk of OA-related comorbidities such as dyslipidemia or CAD. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Decreased levels of serum complement C3 and natural killer cells add to the predictive value of total immunoglobulin G for severe infection in heart transplant recipients.

PubMed

Sarmiento, E; del Pozo, N; Gallego, A; Fernández-Yañez, J; Palomo, J; Villa, A; Ruiz, M; Muñoz, P; Rodríguez, C; Rodríguez-Molina, J; Navarro, J; Kotsch, K; Fernandez-Cruz, E; Carbone, J

2012-10-01

Infection remains a source of mortality in heart recipients. We previously reported that post-transplant immunoglobulin G (IgG) quantification can help identify the risk for infection. We assessed whether other standardized parameters of humoral and cellular immunity could prove useful when identifying patients at risk of infection. We prospectively studied 133 heart recipients over a 12-month period. Forty-eight patients had at least one episode of severe infection. An event was defined as an infection requiring intravenous antimicrobial therapy. Cox regression analysis revealed an association between the risk of developing infection and the following: lower IgG2 subclass levels (day 7: relative hazard [RH] 1.71; day 30: RH 1.76), lower IgA levels (day 7: RH 1.61; day 30: RH 1.91), lower complement C3 values (day 7: RH 1.25), lower CD3 absolute counts (day 30: RH 1.10), lower absolute natural killer [NK] cell count (day 7: RH 1.24), and lower IgG concentrations (day 7: RH 1.31; day 30: RH 1.36). Cox regression bivariate analysis revealed that lower day 7 C3 levels, IgG2 concentration, and absolute NK cell count remained significant after adjustment for total IgG levels. Data suggest that early immune monitoring including C3, IgG2, and NK cell testing in addition to IgG concentrations is useful when attempting to identify the risk of infection in heart transplant recipients. © 2012 John Wiley & Sons A/S.

Soluble form of receptor for advanced glycation end products and incidence of new cardiovascular events among patients with cardiovascular disease.

PubMed

Reichert, Stefan; Triebert, Ulrike; Santos, Alexander Navarrete; Hofmann, Britt; Schaller, Hans-Günter; Schlitt, Axel; Schulz, Susanne

2017-11-01

Soluble RAGE (sRAGE) serum level could be a biomarker for atherosclerosis and subsequent diseases such as cardiovascular disease (CVD). Therefore, we wanted to investigate whether peripheral sRAGE level is associated with new cardiovascular events among patients with CVD using the Cox's regression analysis. In this three-year longitudinal cohort study, 1002 in-patients with angiographically proven CVD were included. In 933 patients, sRAGE levels were determined by a commercial available ELISA kit at the time of baseline examination. The combined endpoint was defined as myocardial infarction, stroke/TIA (non-fatal, fatal), and cardiovascular death. For risk analysis, sRAGE values were distributed in quartiles. For generation of adjusted hazard ratios (HR), other risk factors for CVD, such as age, gender, current smoking, body mass index, diabetes, hypertension, dyslipoproteinemia, family history of CVD, severe periodontitis, serum levels for C-reactive protein and interleukin-6, were recorded. 886 patients completed the 3-year follow-up. The overall incidence of the combined endpoint was 16%. Patients with sRAGE levels >838.19 pg/ml (fourth quartile) had the highest incidence of recurrent CVD events (24.9% versus 13.1%, p < 0.0001). In multivariate Cox regression with respect to further confounders for CVD, the association between sRAGE and new CVD events was confirmed (HR = 1.616, 95% CI 1.027-2.544, p = 0.038). Elevated sRAGE serum level is associated with further adverse events in patients with CVD. Copyright © 2017 Elsevier B.V. All rights reserved.

Dietary sodium to potassium ratio and the incidence of hypertension and cardiovascular disease: A population-based longitudinal study.

PubMed

Mirmiran, Parvin; Bahadoran, Zahra; Nazeri, Pantea; Azizi, Fereidoun

2018-01-30

There is an interaction between dietary sodium/potassium intake in the pathogenesis of hypertension (HTN) and cardiovascular disease (CVD). The aim of this study was to investigate the association of dietary sodium to potassium (Na/K) ratio and the risk of HTN and CVD in a general population of Iranian adults. In this prospective cohort study, adults men and women with complete baseline data were selected from among participants of the Tehran Lipid and Glucose Study and were followed up for 6.3 years for incidence of HTN and CVD outcomes. Dietary sodium and potassium were assessed using a valid and reliable 168-item food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between dietary sodium, potassium and their ratio and risk of outcomes. During the study follow-up, 291 (15.1%) and 79 (5.0%) new cases of HTN and CVD were identified, respectively. No significant association was observed between usual intakes of sodium, potassium and dietary Na/K ratio with the incidence of HTN. There was no significant association between dietary intakes of sodium and potassium per se and the risk of CVD, whereas when dietary sodium to potassium ratio was considered as exposure in the fully-adjusted Cox regression model, and participants in the highest compared to lowest tertile had a significantly increased risk of CVD (HR = 2.19, 95% CI = 1.16-4.14). Our findings suggest that high dietary Na/K ratio could contribute to increased risk of CVD events.

Marijuana use and risk of lung cancer: a 40-year cohort study.

PubMed

Callaghan, Russell C; Allebeck, Peter; Sidorchuk, Anna

2013-10-01

Cannabis (marijuana) smoke and tobacco smoke contain many of the same potent carcinogens, but a critical-yet unresolved-medical and public-health issue is whether cannabis smoking might facilitate the development of lung cancer. The current study aimed to assess the risk of lung cancer among young marijuana users. A population-based cohort study examined men (n = 49,321) aged 18-20 years old assessed for cannabis use and other relevant variables during military conscription in Sweden in 1969-1970. Participants were tracked until 2009 for incident lung cancer outcomes in nationwide linked medical registries. Cox regression modeling assessed relationships between cannabis smoking, measured at conscription, and the hazard of subsequently receiving a lung cancer diagnosis. At the baseline conscription assessment, 10.5 % (n = 5,156) reported lifetime use of marijuana and 1.7 % (n = 831) indicated lifetime use of more than 50 times, designated as "heavy" use. Cox regression analyses (n = 44,284) found that such "heavy" cannabis smoking was significantly associated with more than a twofold risk (hazard ratio 2.12, 95 % CI 1.08-4.14) of developing lung cancer over the 40-year follow-up period, even after statistical adjustment for baseline tobacco use, alcohol use, respiratory conditions, and socioeconomic status. Our primary finding provides initial longitudinal evidence that cannabis use might elevate the risk of lung cancer. In light of the widespread use of marijuana, especially among adolescents and young adults, our study provides important data for informing the risk-benefit calculus of marijuana smoking in medical, public-health, and drug-policy settings.

No evidence of a causal relationship between hypothyroidism and glaucoma: A Danish nationwide register-based cohort study.

PubMed

Thvilum, Marianne; Brandt, Frans; Brix, Thomas Heiberg; Hegedüs, Laszlo

2018-01-01

An interrelationship between hypothyroidism and glaucoma, due to a shared autoimmune background or based on deposition of mucopolysaccharides in the trabecular meshwork in the eye, has been suggested but is at present unsubstantiated. Therefore, our objective was to investigate, at a nationwide and population-based level, whether there is such an association. Observational cohort study using record-linkage data from nationwide Danish health registers. 121,799 individuals diagnosed with a first episode of hypothyroidism were identified and were matched with 4 non-hypothyroid controls according to age and sex. Prevalence of glaucoma was recorded and cases and controls were followed over a mean of 7.1 years (range 0-17). Logistic and Cox regression models were used to assess the risk of glaucoma before and after the diagnosis of hypothyroidism, respectively. Overall, we found a higher prevalence of glaucoma in subjects with hypothyroidism as compared to controls (4.6% vs. 4.3%, p < 0.001). Prior to the diagnosis of hypothyroidism, the odds ratio (OR) was significantly increased for glaucoma [1.09; 95% confidence interval (CI): 1.04-1.13]. Based on the Cox regression model, there was no increased risk of glaucoma after the diagnosis of hypothyroidism [hazard ratio (HR) 1.00; 95% CI: 0.96-1.06], and the HR decreased further after adjusting for pre-existing co-morbidity (0.88; 95% CI: 0.84-0.93). There was an increased risk of glaucoma before but not after the diagnosis of hypothyroidism, suggesting that screening for glaucoma in hypothyroid individuals is unwarranted.

ESC guidelines adherence is associated with improved survival in patients from the Norwegian Heart Failure Registry.

PubMed

De Blois, Jonathan; Fagerland, Morten Wang; Grundtvig, Morten; Semb, Anne Grete; Gullestad, Lars; Westheim, Arne; Hole, Torstein; Atar, Dan; Agewall, Stefan

2015-01-01

To assess the adherence to heart failure (HF) guidelines for angiotensin-converting enzyme-I (ACE-I), angiotensin II receptor blockers (ARB), and β-blockers and the possible association of ACE-I or ARB, β-blockers, and statins with survival in the large contemporary Norwegian Heart Failure Registry. The study included 5761 outpatients who were diagnosed with HF of any aetiology (mean left ventricular ejection fraction 32% ± 11%) from January 2000 to January 2010 and followed up until death or February 2010. Adherence to treatment according to the guidelines was high. Cox regression analysis to identify risk factors for all-cause mortality, after adjustment for many factors, showed that ACE-I ≥ 50% of target dose, use of beta-blockers, and statins were significantly related to improved survival (P = 0.003, P < 0.001, and P < 0.001, respectively). Propensity scoring showed the same benefit for these variables. Both multivariable and propensity scoring analyses showed survival benefits with β-blockers, statins, and adequate doses of ACE-I in this contemporary HF cohort. This study stresses the importance of guidelines adherence, even in the context of high levels of adherence to guidelines. Moreover, respecting the recommended target doses of ACE-I appears to have a crucial role in survival improvement and, in the multivariate Cox regression analysis, ARB treatment was not significantly associated with a lower all-cause mortality. Published on behalf of the European Society of Cardiology. All rights reserved. ©The Author 2015. For permissions please email: journals.permissions@oup.com.

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.

The association of emergency department administration of sodium bicarbonate after out of hospital cardiac arrest with outcomes.

PubMed

Chen, Yi-Chuan; Hung, Ming-Szu; Liu, Chia-Yen; Hsiao, Cheng-Ting; Yang, Yao-Hsu

2018-03-05

Sodium bicarbonate administration is mostly restricted to in-hospital use in Taiwan. This study was conducted to investigate the effect of sodium bicarbonate on outcomes among patients with out-of-hospital cardiac arrest (OHCA). This population-based study used a 16-year database to analyze the association between sodium bicarbonate administration for resuscitation in the emergency department (ED) and outcomes. All adult patients with OHCA were identified through diagnostic and procedure codes. The primary outcome was survival to hospital admission and secondary outcome was the rate of death within the first 30days of incidence of cardiac arrest. Cox proportional-hazards regression, logistic regression, and propensity analyses were conducted. Among 5589 total OHCA patients, 15.1% (844) had survival to hospital admission. For all patients, a positive association was noted between sodium bicarbonate administration during resuscitation in the ED and survival to hospital admission (adjusted odds ratio [OR]: 4.47; 95% confidence interval [CI]: 3.82-5.22, p<0.001). In propensity-matched patients, a positive association was also noted (adjusted OR, 4.61; 95% CI: 3.90-5.46, p<0.001). Among patients with OHCA in Taiwan, administration of sodium bicarbonate during ED resuscitation was significantly associated with an increased rate of survival to hospital admission. Copyright © 2018. Published by Elsevier Inc.

Outcome of heart-lung and bilateral sequential lung transplantation for cystic fibrosis: a UK national study.

PubMed

Ganesh, J S; Rogers, C A; Bonser, R S; Banner, N R

2005-06-01

Cystic fibrosis (CF) patients requiring transplantation for respiratory failure may undergo either heart-lung (HLT) or bilateral sequential lung (BSLT) transplantation. The choice of operation varies between surgeons, centres and countries. The current authors investigated whether operation type influenced outcome in adult CF patients transplanted in the UK between July 1995 and June 2002. Propensity scores for receipt of BSLT versus HLT were derived using logistic regression. Cox regression was used to compare survival. In total, 88 BSLTs and 93 HLTs were identified. Patient characteristics were similar overall, but HLT recipients were more likely to be on long-term oxygen therapy and to have had prior resuscitation. There were 72 deaths (29 BSLT and 43 HLT) within 4 yrs. There was a trend towards higher unadjusted survival following BSLT, but, after adjustment, no difference was found (hazard ratio = 0.77; 95% confidence interval 0.29-2.06). Time to the first rejection episode and infection rates were also similar. A total of 82% of hearts from HLT recipients were used as domino heart transplants. In conclusion, after adjusting for comorbidity, donor factors and ischaemia time, it was found that heart-lung and bilateral sequential lung transplantation achieved a similar outcome. The use of domino heart transplantation ameliorated the impact of heart-lung transplantation on total organ availability.

Coffee intake, cardiovascular disease and all-cause mortality: observational and Mendelian randomization analyses in 95 000-223 000 individuals.

PubMed

Nordestgaard, Ask Tybjærg; Nordestgaard, Børge Grønne

2016-12-01

Coffee has been associated with modestly lower risk of cardiovascular disease and all-cause mortality in meta-analyses; however, it is unclear whether these are causal associations. We tested first whether coffee intake is associated with cardiovascular disease and all-cause mortality observationally; second, whether genetic variations previously associated with caffeine intake are associated with coffee intake; and third, whether the genetic variations are associated with cardiovascular disease and all-cause mortality. First, we used multivariable adjusted Cox proportional hazard regression models evaluated with restricted cubic splines to examine observational associations in 95 366 White Danes. Second, we estimated mean coffee intake according to five genetic variations near the AHR (rs4410790; rs6968865) and CYP1A1/2 genes (rs2470893; rs2472297; rs2472299). Third, we used sex- and age adjusted Cox proportional hazard regression models to examine genetic associations with cardiovascular disease and all-cause mortality in 112 509 Danes. Finally, we used sex and age-adjusted logistic regression models to examine genetic associations with ischaemic heart disease including the Cardiogram and C4D consortia in a total of up to 223 414 individuals. We applied similar analyses to ApoE genotypes associated with plasma cholesterol levels, as a positive control. In observational analyses, we observed U-shaped associations between coffee intake and cardiovascular disease and all-cause mortality; lowest risks were observed in individuals with medium coffee intake. Caffeine intake allele score (rs4410790 + rs2470893) was associated with a 42% higher coffee intake. Hazard ratios per caffeine intake allele were 1.02 (95% confidence interval: 1.00-1.03) for ischaemic heart disease, 1.02 (0.99-1.02) for ischaemic stroke, 1.02 (1.00-1.03) for ischaemic vascular disease, 1.02 (0.99-1.06) for cardiovascular mortality and 1.01 (0.99-1.03) for all-cause mortality. Including international consortia, odds ratios per caffeine intake allele for ischaemic heart disease were 1.00 (0.98-1.02) for rs4410790, 1.01 (0.99-1.03) for rs6968865, 1.02 (1.00-1.04) for rs2470893, 1.02 (1.00-1.04) for rs2472297 and 1.03 (0.99-1.06) for rs2472299. Conversely, 5% lower cholesterol level caused by ApoE genotype had a corresponding odds ratio for ischaemic heart disease of 0.93 (0.89-0.97). Observationally, coffee intake was associated with U-shaped lower risk of cardiovascular disease and all-cause mortality; however, genetically caffeine intake was not associated with risk of cardiovascular disease or all-cause mortality. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Comparison of exact, efron and breslow parameter approach method on hazard ratio and stratified cox regression model

NASA Astrophysics Data System (ADS)

Fatekurohman, Mohamat; Nurmala, Nita; Anggraeni, Dian

2018-04-01

Lungs are the most important organ, in the case of respiratory system. Problems related to disorder of the lungs are various, i.e. pneumonia, emphysema, tuberculosis and lung cancer. Comparing all those problems, lung cancer is the most harmful. Considering about that, the aim of this research applies survival analysis and factors affecting the endurance of the lung cancer patient using comparison of exact, Efron and Breslow parameter approach method on hazard ratio and stratified cox regression model. The data applied are based on the medical records of lung cancer patients in Jember Paru-paru hospital on 2016, east java, Indonesia. The factors affecting the endurance of the lung cancer patients can be classified into several criteria, i.e. sex, age, hemoglobin, leukocytes, erythrocytes, sedimentation rate of blood, therapy status, general condition, body weight. The result shows that exact method of stratified cox regression model is better than other. On the other hand, the endurance of the patients is affected by their age and the general conditions.

A simple linear regression method for quantitative trait loci linkage analysis with censored observations.

PubMed

Anderson, Carl A; McRae, Allan F; Visscher, Peter M

2006-07-01

Standard quantitative trait loci (QTL) mapping techniques commonly assume that the trait is both fully observed and normally distributed. When considering survival or age-at-onset traits these assumptions are often incorrect. Methods have been developed to map QTL for survival traits; however, they are both computationally intensive and not available in standard genome analysis software packages. We propose a grouped linear regression method for the analysis of continuous survival data. Using simulation we compare this method to both the Cox and Weibull proportional hazards models and a standard linear regression method that ignores censoring. The grouped linear regression method is of equivalent power to both the Cox and Weibull proportional hazards methods and is significantly better than the standard linear regression method when censored observations are present. The method is also robust to the proportion of censored individuals and the underlying distribution of the trait. On the basis of linear regression methodology, the grouped linear regression model is computationally simple and fast and can be implemented readily in freely available statistical software.

Severely Elevated Blood Pressure and Early Mortality in Children with Traumatic Brain Injuries: The Neglected End of the Spectrum

PubMed Central

Borgman, Matthew A.; Cannon, Jeremy W.; Kuppermann, Nathan; Neff, Lucas P.

2018-01-01

Introduction In adults with traumatic brain injuries (TBI), hypotension and hypertension at presentation are associated with mortality. The effect of age-adjusted blood pressure in children with TBI has been insufficiently studied. We sought to determine if age-adjusted hypertension in children with severe TBI is associated with mortality. Methods This was a retrospective analysis of the Department of Defense Trauma Registry (DoDTR) between 2001 and 2013. We included for analysis patients <18 years with severe TBI defined as Abbreviated Injury Severity (AIS) scores of the head ≥3. We defined hypertension as moderate for systolic blood pressures (SBP) between the 95th and 99th percentile for age and gender and severe if greater than the 99th percentile. Hypotension was defined as SBP <90 mmHg for children >10 years or < 70mmHg + (2 × age) for children ≤10 years. We performed multivariable logistic regression and Cox regression to determine if BP categories were associated with mortality. Results Of 4,990 children included in the DoDTR, 740 met criteria for analysis. Fifty patients (6.8%) were hypotensive upon arrival to the ED, 385 (52.0%) were normotensive, 115 (15.5%) had moderate hypertension, and 190 (25.7%) had severe hypertension. When compared to normotensive patients, moderate and severe hypertension patients had similar Injury Severity Scores, similar AIS head scores, and similar frequencies of neurosurgical procedures. Multivariable logistic regression demonstrated that hypotension (odd ratio [OR] 2.85, 95 confidence interval [CI] 1.26–6.47) and severe hypertension (OR 2.58, 95 CI 1.32–5.03) were associated with increased 24-hour mortality. Neither hypotension (Hazard ratio (HR) 1.52, 95 CI 0.74–3.11) nor severe hypertension (HR 1.65, 95 CI 0.65–2.30) was associated with time to mortality. Conclusion Pediatric age-adjusted hypertension is frequent after severe TBI. Severe hypertension is strongly associated with 24-hour mortality. Pediatric age-adjusted blood pressure needs to be further evaluated as a critical marker of early mortality. PMID:29760839

Severely Elevated Blood Pressure and Early Mortality in Children with Traumatic Brain Injuries: The Neglected End of the Spectrum.

PubMed

Johnson, M Austin; Borgman, Matthew A; Cannon, Jeremy W; Kuppermann, Nathan; Neff, Lucas P

2018-05-01

In adults with traumatic brain injuries (TBI), hypotension and hypertension at presentation are associated with mortality. The effect of age-adjusted blood pressure in children with TBI has been insufficiently studied. We sought to determine if age-adjusted hypertension in children with severe TBI is associated with mortality. This was a retrospective analysis of the Department of Defense Trauma Registry (DoDTR) between 2001 and 2013. We included for analysis patients <18 years with severe TBI defined as Abbreviated Injury Severity (AIS) scores of the head ≥3. We defined hypertension as moderate for systolic blood pressures (SBP) between the 95 th and 99 th percentile for age and gender and severe if greater than the 99th percentile. Hypotension was defined as SBP <90 mmHg for children >10 years or < 70mmHg + (2 × age) for children ≤10 years. We performed multivariable logistic regression and Cox regression to determine if BP categories were associated with mortality. Of 4,990 children included in the DoDTR, 740 met criteria for analysis. Fifty patients (6.8%) were hypotensive upon arrival to the ED, 385 (52.0%) were normotensive, 115 (15.5%) had moderate hypertension, and 190 (25.7%) had severe hypertension. When compared to normotensive patients, moderate and severe hypertension patients had similar Injury Severity Scores, similar AIS head scores, and similar frequencies of neurosurgical procedures. Multivariable logistic regression demonstrated that hypotension (odd ratio [OR] 2.85, 95 confidence interval [CI] 1.26-6.47) and severe hypertension (OR 2.58, 95 CI 1.32-5.03) were associated with increased 24-hour mortality. Neither hypotension (Hazard ratio (HR) 1.52, 95 CI 0.74-3.11) nor severe hypertension (HR 1.65, 95 CI 0.65-2.30) was associated with time to mortality. Pediatric age-adjusted hypertension is frequent after severe TBI. Severe hypertension is strongly associated with 24-hour mortality. Pediatric age-adjusted blood pressure needs to be further evaluated as a critical marker of early mortality.

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.

Long term mortality in critically ill burn survivors.

PubMed

Nitzschke, Stephanie; Offodile, Anaeze C; Cauley, Ryan P; Frankel, Jason E; Beam, Andrew; Elias, Kevin M; Gibbons, Fiona K; Salim, Ali; Christopher, Kenneth B

2017-09-01

Little is known about long term survival risk factors in critically ill burn patients who survive hospitalization. We hypothesized that patients with major burns who survive hospitalization would have favorable long term outcomes. We performed a two center observational cohort study in 365 critically ill adult burn patients who survived to hospital discharge. The exposure of interest was major burn defined a priori as >20% total body surface area burned [TBSA]. The modified Baux score was determined by age + %TBSA+ 17(inhalational injury). The primary outcome was all-cause 5year mortality based on the US Social Security Administration Death Master File. Adjusted associations were estimated through fitting of multivariable logistic regression models. Our final model included adjustment for inhalational injury, presence of 3rd degree burn, gender and the acute organ failure score, a validated ICU risk-prediction score derived from age, ethnicity, surgery vs. medical patient type, comorbidity, sepsis and acute organ failure covariates. Time-to-event analysis was performed using Cox proportional hazard regression. Of the cohort patients studied, 76% were male, 29% were non white, 14% were over 65, 32% had TBSA >20%, and 45% had inhalational injury. The mean age was 45, 92% had 2nd degree burns, 60% had 3rd degree burns, 21% received vasopressors, and 26% had sepsis. The mean TBSA was 20.1%. The mean modified Baux score was 72.8. Post hospital discharge 5year mortality rate was 9.0%. The 30day hospital readmission rate was 4%. Patients with major burns were significantly younger (41 vs. 47 years) had a significantly higher modified Baux score (89 vs. 62), and had significantly higher comorbidity, acute organ failure, inhalational injury and sepsis (all P<0.05). There were no differences in gender and the acute organ failure score between major and non-major burns. In the multivariable logistic regression model, major burn was associated with a 3 fold decreased odds of 5year post-discharge mortality compared to patients with TBSA<20% [OR=0.29 (95%CI 0.11-0.78; P=0.014)]. The adjusted model showed good discrimination [AUC 0.81 (95%CI 0.74-0.89)] and calibration (Hosmer-Lemeshow χ 2 P=0.67). Cox proportional hazard multivariable regression modeling, adjusting for inhalational injury, presence of 3rd degree burn, gender and the acute organ failure score, showed that major burn was predictive of lower mortality following hospital admission [HR=0.34 (95% CI 0.15-0.76; P=0.009)]. The modified Baux score was not predictive for mortality following hospital discharge [OR 5year post-discharge mortality=1.00 (95%CI 0.99-1.02; P=0.74); HR for post-discharge mortality=1.00 (95% CI 0.99-1.02; P=0.55)]. Critically ill patients with major burns who survive to hospital discharge have decreased 5year mortality compared to those with less severe burns. ICU Burn unit patients who survive to hospital discharge are younger with less comorbidities. The observed relationship is likely due to the relatively higher physiological reserve present in those who survive a Burn ICU course which may provide for a survival advantage during recovery after major burn. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

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.

Personality predicts time to remission and clinical status in hypochondriasis during a 6-year follow-up.

PubMed

Greeven, Anja; van Balkom, Anton J L M; Spinhoven, Philip

2014-05-01

We aimed to investigate whether personality characteristics predict time to remission and psychiatric status. The follow-up was at most 6 years and was performed within the scope of a randomized controlled trial that investigated the efficacy of cognitive behavioral therapy, paroxetine, and placebo in hypochondriasis. The Life Chart Interview was administered to investigate for each year if remission had occurred. Personality was assessed at pretest by the Abbreviated Dutch Temperament and Character Inventory. Cox's regression models for recurrent events were compared with logistic regression models. Sixteen (36.4%) of 44 patients achieved remission during the follow-up period. Cox's regression yielded approximately the same results as the logistic regression. Being less harm avoidant and more cooperative were associated with a shorter time to remission and a remitted state after the follow-up period. Personality variables seem to be relevant for describing patients with a more chronic course of hypochondriacal complaints.

Prescriptions for cyclooxygenase-2 inhibitors and other nonsteroidal anti-inflammatory agents in a medicaid managed care population: African Americans versus Caucasians.

PubMed

Shaya, Fadia T; Blume, Steven

2005-01-01

To determine whether race is a predictor of a patient's likelihood of being prescribed selective cyclooxygenase-2 inhibitors (COX-2s) versus other nonsteroidal anti-inflammatory agents (NSAIDs) in Medicaid managed care plans (MCO). All medical and prescription claims for Medicaid MCO enrollees receiving at least one prescription for a COX-2 or NSAID between January 2000 and June 2002 were retrieved. Selected for study were adults claiming at least one COX-2 prescription or NSAID prescription with a minimum 30 days of supply after June 2000; having 60 total days of supply or more over the study period was also required for study inclusion. The probability of being prescribed a COX-2 was estimated as a logistic function of patient age, gender, race, city/suburban/rural residence, and history of rheumatoid arthritis, osteoarthritis, chronic back pain, acute pains, gastrointestinal problems, use of anticoagulants or corticosteroids, and comorbidities. Of the 16,868 enrollees meeting the selection criteria, 4,005 (24%) were prescribed a COX-2 and 12,863 another NSAID. Half of those studied were African American, three-quarters were female, and a third were 50-64 years old. After adjusting for confounders, odds of a COX-2 prescription were a third less for African Americans and other races compared to Caucasians (OR, 0.67; 95% confidence intervals, 0.62-0.73). Patient race is a significant predictor of COX-2 prescriptions in the Medicaid population, even after adjusting for other demographic and clinical variables. Cost to the patient was not a factor, as the patient copayment was 1 US dollar for any prescription.

Maintenance therapy of childhood acute lymphoblastic leukemia revisited-Should drug doses be adjusted by white blood cell, neutrophil, or lymphocyte counts?

PubMed

Schmiegelow, Kjeld; Nersting, Jacob; Nielsen, Stine Nygaard; Heyman, Mats; Wesenberg, Finn; Kristinsson, Jon; Vettenranta, Kim; Schrøeder, Henrik; Weinshilboum, Richard; Jensen, Katrine Lykke; Grell, Kathrine; Rosthoej, Susanne

2016-12-01

6-Mercaptopurine (6MP) and methotrexate (MTX) based maintenance therapy is a critical phase of childhood acute lymphoblastic leukemia treatment. Wide interindividual variations in drug disposition warrant frequent doses adjustments, but there is a lack of international consensus on dose adjustment guidelines. To identify relapse predictors, we collected 28,255 data sets on drug doses and blood counts (median: 47/patient) and analyzed erythrocyte (Ery) levels of cytotoxic 6MP/MTX metabolites in 9,182 blood samples (median: 14 samples/patient) from 532 children on MTX/6MP maintenance therapy targeted to a white blood cell count (WBC) of 1.5-3.5 × 10 9 /l. After a median follow-up of 13.8 years for patients in remission, stepwise Cox regression analysis did not find age, average doses of 6MP and MTX, hemoglobin, absolute lymphocyte counts, thrombocyte counts, or Ery levels of 6-thioguanine nucleotides or MTX (including its polyglutamates) to be significant relapse predictors. The parameters significantly associated with risk of relapse (N = 83) were male sex (hazard ratio [HR] 2.0 [1.3-3.1], P = 0.003), WBC at diagnosis (HR = 1.04 per 10 × 10 9 /l rise [1.00-1.09], P = 0.048), the absolute neutrophil count (ANC; HR = 1.7 per 10 9 /l rise [1.3-2.4], P = 0.0007), and Ery thiopurine methyltransferase activity (HR = 2.7 per IU/ml rise [1.1-6.7], P = 0.03). WBC was significantly related to ANC (Spearman correlation coefficient, r s  = 0.77; P < 0.001), and only a borderline significant risk factor for relapse (HR = 1.28 [95% CI: 1.00-1.64], P = 0.046) when ANC was excluded from the Cox model. This study indicates that a low neutrophil count is likely to be the best hematological target for dose adjustments of maintenance therapy. © 2016 Wiley Periodicals, Inc.

Famine Exposure in the Young and the Risk of Type 2 Diabetes in Adulthood

PubMed Central

van Abeelen, Annet F.M.; Elias, Sjoerd G.; Bossuyt, Patrick M.M.; Grobbee, Diederick E.; van der Schouw, Yvonne T.; Roseboom, Tessa J.; Uiterwaal, Cuno S.P.M.

2012-01-01

The developmental origins hypothesis proposes that undernutrition during early development is associated with an increased type 2 diabetes risk in adulthood. We investigated the association between undernutrition during childhood and young adulthood and type 2 diabetes in adulthood. We studied 7,837 women from Prospect-EPIC (European Prospective Investigation Into Cancer and Nutrition) who were exposed to the 1944–1945 Dutch famine when they were between age 0 and 21 years. We used Cox proportional hazards regression models to explore the effect of famine on the risk of subsequent type 2 diabetes in adulthood. We adjusted for potential confounders, including age at famine exposure, smoking, and level of education. Self-reported famine exposure during childhood and young adulthood was associated with an increased type 2 diabetes risk in a dose-dependent manner. In those who reported moderate famine exposure, the age-adjusted type 2 diabetes hazard ratio (HR) was 1.36 (95% CI [1.09–1.70]); in those who reported severe famine exposure, the age-adjusted HR was 1.64 (1.26–2.14) relative to unexposed women. These effects did not change after adjustment for confounders. This study provides the first direct evidence, using individual famine exposure data, that a short period of moderate or severe undernutrition during postnatal development increases type 2 diabetes risk in adulthood. PMID:22648386

Occupational sedentariness and breast cancer risk.

PubMed

Johnsson, Anna; Broberg, Per; Johnsson, Anders; Tornberg, Åsa B; Olsson, Håkan

2017-01-01

Epidemiological studies have indicated that physical activity reduces the risk of developing breast cancer. More recently, sedentary behavior has been suggested as a risk factor independent of physical activity level. The purpose of the present study was to investigate occupational sedentariness and breast cancer risk in pre- and postmenopausal women. In a population-based prospective cohort study (n = 29 524), working history was assessed by a questionnaire between 1990 and 1992. Participants were classified as having: (1) sedentary occupations only; (2) mixed occupations or (3) non-sedentary occupations only. The association between occupational sedentariness and breast cancer incidence was analyzed by Cox regression, adjusted for known risk factors and participation in competitive sports. Women with a working history of occupational sedentariness had a significantly increased risk of breast cancer (adjusted HR 1.20; 95% CI 1.05, 1.37) compared with those with mixed or non-sedentary occupations. The association was stronger among women younger than 55 years (adjusted HR 1.54; 95% CI 1.20, 1.96), whereas no association was seen in women 55 years or older. Adjustment for participation in competitive sports did not change the association. We found that occupational sedentariness was associated with increased breast cancer risk, especially in women younger than 55 years. This may be a modifiable risk factor by planning breaks during the working day. Whether this reduces the risk of breast cancer needs to be further studied.

Modeled Urea Distribution Volume and Mortality in the HEMO Study

PubMed Central

Greene, Tom; Depner, Thomas A.; Levin, Nathan W.; Chertow, Glenn M.

2011-01-01

Summary Background and objectives In the Hemodialysis (HEMO) Study, observed small decreases in achieved equilibrated Kt/Vurea were noncausally associated with markedly increased mortality. Here we examine the association of mortality with modeled volume (Vm), the denominator of equilibrated Kt/Vurea. Design, setting, participants, & measurements Parameters derived from modeled urea kinetics (including Vm) and blood pressure (BP) were obtained monthly in 1846 patients. Case mix–adjusted time-dependent Cox regressions were used to relate the relative mortality hazard at each time point to Vm and to the change in Vm over the preceding 6 months. Mixed effects models were used to relate Vm to changes in intradialytic systolic BP and to other factors at each follow-up visit. Results Mortality was associated with Vm and change in Vm over the preceding 6 months. The association between change in Vm and mortality was independent of vascular access complications. In contrast, mortality was inversely associated with V calculated from anthropometric measurements (Vant). In case mix–adjusted analysis using Vm as a time-dependent covariate, the association of mortality with Vm strengthened after statistical adjustment for Vant. After adjustment for Vant, higher Vm was associated with slightly smaller reductions in intradialytic systolic BP and with risk factors for mortality including recent hospitalization and reductions in serum albumin concentration and body weight. Conclusions An increase in Vm is a marker for illness and mortality risk in hemodialysis patients. PMID:21511841

Effects of Transferring to the Rehabilitation Ward on Long-Term Mortality Rate of First-Time Stroke Survivors: A Population-Based Study.

PubMed

Chen, Chien-Min; Yang, Yao-Hsu; Chang, Chia-Hao; Chen, Pau-Chung

2017-12-01

To assess the long-term health outcomes of acute stroke survivors transferred to the rehabilitation ward. Long-term mortality rates of first-time stroke survivors during hospitalization were compared among the following sets of patients: patients transferred to the rehabilitation ward, patients receiving rehabilitation without being transferred to the rehabilitation ward, and patients receiving no rehabilitation. Retrospective cohort study. Patients (N = 11,419) with stroke from 2005 to 2008 were initially assessed for eligibility. After propensity score matching, 390 first-time stroke survivors were included. None. Cox proportional hazards regression model was used to assess differences in 5-year poststroke mortality rates. Based on adjusted hazard ratios (HRs), the patients receiving rehabilitation without being transferred to the rehabilitation ward (adjusted HR, 2.20; 95% confidence interval [CI], 1.36-3.57) and patients receiving no rehabilitation (adjusted HR, 4.00; 95% CI, 2.55-6.27) had significantly higher mortality risk than the patients transferred to the rehabilitation ward. Mortality rate of the stroke survivors was affected by age ≥65 years (compared with age <45y; adjusted HR, 3.62), being a man (adjusted HR, 1.49), having ischemic stroke (adjusted HR, 1.55), stroke severity (Stroke Severity Index [SSI] score≥20, compared with SSI score<10; adjusted HR, 2.68), and comorbidity (Charlson-Deyo Comorbidity Index [CCI] score≥3, compared with CCI score=0; adjusted HR, 4.23). First-time stroke survivors transferred to the rehabilitation ward had a 5-year mortality rate 2.2 times lower than those who received rehabilitation without transfer to the rehabilitation ward and 4 times lower than those who received no rehabilitation. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Outcomes in African-Americans vs. Caucasians using thymoglobulin or interleukin-2 receptor inhibitor induction: analysis of USRDS database.

PubMed

Jindal, Rahul M; Das, Neal P; Neff, Robert T; Hurst, Frank P; Falta, Edward M; Elster, Eric A; Abbott, Kevin C

2009-01-01

We used the USRDS database to test the hypothesis that graft survival was similar using either rabbit antithymocyte globulin (rATG) vs. interleukin-2 receptor inhibitor (IL2i) in the Prograf era. We further explored the variable of race in the two groups of patients. We conducted a retrospective cohort study of kidney transplant patients in the USRDS from 2000 through 2005 to compare graft survival (including death) using rATG vs. IL2i with particular reference to outcomes between African-Americans vs. Caucasians. Kaplan-Meier analysis was performed to assess patient and graft survival after transplantation, stratified by recipient induction with rATG versus IL2i. Cox regression analysis was performed to assess adjusted survival after transplantation, assessing whether induction rATG (vs. IL2i) was significant as an interaction term (i.e. an effect modifier) with black race for graft survival. Propensity score analysis was used to address potential confounding by indication. In stratified Cox Regression analysis limited to IL2i, black race was significantly associated with graft loss (adjusted hazard ratio (AHR) 1.17, 95% CI, 1.09-1.26). In analysis limited to rATG induction, black race was not significant (AHR 1.00, 95% CI, 0.92-1.10). We detected a significant interaction between rATG and black race (in comparison with non-black race) for the development of graft loss (AHR, 0.86, 95% CI, 0.76-0.97). Analysis limited to black recipients showed that while use of rATG was not significantly different from IL2i (AHR 0.95, 95% CI 0.87-1.04), the direction of this association was in the opposite direction of non-blacks. Patient and graft survival were similar in African-American and Caucasian recipients of kidney transplantation using either rATG or IL2i. Limitations of the study are the retrospective nature of USRDS data, center-bias in using rATG vs. IL2i and lack of data on steroid dosage. Results of the present study call for a critical review of induction practices. (c) 2008 S. Karger AG, Basel.

Short-term outcome of 1,465 computer-navigated primary total knee replacements 2005–2008

PubMed Central

2011-01-01

Background and purpose Improvement of positioning and alignment by the use of computer-assisted surgery (CAS) might improve longevity and function in total knee replacements, but there is little evidence. In this study, we evaluated the short-term results of computer-navigated knee replacements based on data from the Norwegian Arthroplasty Register. Patients and methods Primary total knee replacements without patella resurfacing, reported to the Norwegian Arthroplasty Register during the years 2005–2008, were evaluated. The 5 most common implants and the 3 most common navigation systems were selected. Cemented, uncemented, and hybrid knees were included. With the risk of revision for any cause as the primary endpoint and intraoperative complications and operating time as secondary outcomes, 1,465 computer-navigated knee replacements (CAS) and 8,214 conventionally operated knee replacements (CON) were compared. Kaplan-Meier survival analysis and Cox regression analysis with adjustment for age, sex, prosthesis brand, fixation method, previous knee surgery, preoperative diagnosis, and ASA category were used. Results Kaplan-Meier estimated survival at 2 years was 98% (95% CI: 97.5–98.3) in the CON group and 96% (95% CI: 95.0–97.8) in the CAS group. The adjusted Cox regression analysis showed a higher risk of revision in the CAS group (RR = 1.7, 95% CI: 1.1–2.5; p = 0.02). The LCS Complete knee had a higher risk of revision with CAS than with CON (RR = 2.1, 95% CI: 1.3–3.4; p = 0.004)). The differences were not statistically significant for the other prosthesis brands. Mean operating time was 15 min longer in the CAS group. Interpretation With the introduction of computer-navigated knee replacement surgery in Norway, the short-term risk of revision has increased for computer-navigated replacement with the LCS Complete. The mechanisms of failure of these implantations should be explored in greater depth, and in this study we have not been able to draw conclusions regarding causation. PMID:21504309

Prostate Cancer Radiation Therapy and Risk of Thromboembolic Events

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

Bosco, Cecilia, E-mail: Cecilia.t.bosco@kcl.ac.uk; Garmo, Hans; Regional Cancer Centre, Uppsala, Akademiska Sjukhuset, Uppsala

Purpose: To investigate the risk of thromboembolic disease (TED) after radiation therapy (RT) with curative intent for prostate cancer (PCa). Patients and Methods: We identified all men who received RT as curative treatment (n=9410) and grouped according to external beam RT (EBRT) or brachytherapy (BT). By comparing with an age- and county-matched comparison cohort of PCa-free men (n=46,826), we investigated risk of TED after RT using Cox proportional hazard regression models. The model was adjusted for tumor characteristics, demographics, comorbidities, PCa treatments, and known risk factors of TED, such as recent surgery and disease progression. Results: Between 2006 and 2013, 6232more » men with PCa received EBRT, and 3178 underwent BT. A statistically significant association was found between EBRT and BT and risk of pulmonary embolism in the crude analysis. However, upon adjusting for known TED risk factors these associations disappeared. No significant associations were found between BT or EBRT and deep venous thrombosis. Conclusion: Curative RT for prostate cancer using contemporary methodologies was not associated with an increased risk of TED.« less

Aortic Valve Calcification and Risk of Stroke: The Rotterdam Study.

PubMed

Bos, Daniel; Bozorgpourniazi, Atefeh; Mutlu, Unal; Kavousi, Maryam; Vernooij, Meike W; Moelker, Adriaan; Franco, Oscar H; Koudstaal, Peter J; Ikram, M Arfan; van der Lugt, Aad

2016-11-01

It remains uncertain whether aortic valve calcification (AVC) is a risk factor for stroke. From the population-based Rotterdam Study, 2471 participants (mean age: 69.6 years; 51.8% women) underwent computed tomography to quantify AVC. We assessed prevalent stroke and continuously monitored the remaining participants for the incidence of stroke. Logistic and Cox regression models were used to investigate associations of AVC with prevalent stroke and risk of incident stroke. AVC was present in 33.1% of people. At baseline, 97 participants had ever suffered a stroke. During 18 665 person-years of follow-up (mean: 7.9 years), 135 people experienced a first-ever stroke. The presence of AVC was not associated with prevalent stroke (fully adjusted odds ratio: 0.97 (95% confidence interval, 0.61-1.53]) or with an increased risk of stroke (fully adjusted hazard ratio: 0.99 (95% confidence interval, 0.69-1.44]). Although AVC is a common finding in middle-aged and elderly community-dwelling people, our results suggest that AVC is not associated with an increased risk of stroke. © 2016 American Heart Association, Inc.

Diabetes increases the risk of an appendectomy in patients with antibiotic treatment of noncomplicated appendicitis.

PubMed

Tsai, Ming-Chieh; Lin, Herng-Ching; Lee, Cha-Ze

2017-07-01

This retrospective cohort study examined whether diabetic patients have a higher risk for recurrent appendicitis during a 1-year follow-up period after successful antibiotic treatment for patients with acute uncomplicated appendicitis than nondiabetic patients using a population-based database. We included 541 appendicitis patients who received antibiotic treatment for acute appendicitis. We individually tracked each patient for a 1-year period to identify those who subsequently underwent an appendectomy during the follow-up period. Cox proportional hazard regressions suggested that the adjusted hazard ratio of an appendectomy during the 1-year follow-up period was 1.75 for appendicitis patients with diabetes than appendicitis patients without diabetes. We found that among females, the adjusted hazard ratio of an appendectomy was 2.18 for acute appendicitis patients with diabetes than their counterparts without diabetes. However, we failed to observe this relationship in males. We demonstrated a relationship between diabetes and a subsequent appendectomy in females who underwent antibiotic treatment for noncomplicated appendicitis. Copyright © 2016 Elsevier Inc. All rights reserved.

Urate levels predict survival in amyotrophic lateral sclerosis: Analysis of the expanded Pooled Resource Open-Access ALS clinical trials database.

PubMed

Paganoni, Sabrina; Nicholson, Katharine; Chan, James; Shui, Amy; Schoenfeld, David; Sherman, Alexander; Berry, James; Cudkowicz, Merit; Atassi, Nazem

2018-03-01

Urate has been identified as a predictor of amyotrophic lateral sclerosis (ALS) survival in some but not all studies. Here we leverage the recent expansion of the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database to study the association between urate levels and ALS survival. Pooled data of 1,736 ALS participants from the PRO-ACT database were analyzed. Cox proportional hazards regression models were used to evaluate associations between urate levels at trial entry and survival. After adjustment for potential confounders (i.e., creatinine and body mass index), there was an 11% reduction in risk of reaching a survival endpoint during the study with each 1-mg/dL increase in uric acid levels (adjusted hazard ratio 0.89, 95% confidence interval 0.82-0.97, P < 0.01). Our pooled analysis provides further support for urate as a prognostic factor for survival in ALS and confirms the utility of the PRO-ACT database as a powerful resource for ALS epidemiological research. Muscle Nerve 57: 430-434, 2018. © 2017 Wiley Periodicals, Inc.

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.

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

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.

Cox-nnet: An artificial neural network method for prognosis prediction of high-throughput omics data

PubMed Central

Ching, Travers; Zhu, Xun

2018-01-01

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. PMID:29634719

Functional form and risk adjustment of hospital costs: Bayesian analysis of a Box-Cox random coefficients model.

PubMed

Hollenbeak, Christopher S

2005-10-15

While risk-adjusted outcomes are often used to compare the performance of hospitals and physicians, the most appropriate functional form for the risk adjustment process is not always obvious for continuous outcomes such as costs. Semi-log models are used most often to correct skewness in cost data, but there has been limited research to determine whether the log transformation is sufficient or whether another transformation is more appropriate. This study explores the most appropriate functional form for risk-adjusting the cost of coronary artery bypass graft (CABG) surgery. Data included patients undergoing CABG surgery at four hospitals in the midwest and were fit to a Box-Cox model with random coefficients (BCRC) using Markov chain Monte Carlo methods. Marginal likelihoods and Bayes factors were computed to perform model comparison of alternative model specifications. Rankings of hospital performance were created from the simulation output and the rankings produced by Bayesian estimates were compared to rankings produced by standard models fit using classical methods. Results suggest that, for these data, the most appropriate functional form is not logarithmic, but corresponds to a Box-Cox transformation of -1. Furthermore, Bayes factors overwhelmingly rejected the natural log transformation. However, the hospital ranking induced by the BCRC model was not different from the ranking produced by maximum likelihood estimates of either the linear or semi-log model. Copyright (c) 2005 John Wiley & Sons, Ltd.

Effects of electroacupuncture on luteal regression and steroidogenesis in ovarian hyperstimulation syndrome model rat.

PubMed

Huang, Xuan; Chen, Li; Xia, You-Bing; Xie, Min; Sun, Qin; Yao, Bing

2018-03-15

Electroacupuncture (EA) is an effective and safe therapeutic method widely used for treating clinical diseases. Previously, we found that EA could decrease serum hormones and reduce ovarian size in ovarian hyperstimulation syndrome (OHSS) rat model. Nevertheless, the mechanisms that contribute to these improvements remain unclear. HE staining was used to count the number of corpora lutea (CL) and follicles. Immunohistochemical and ELISA were applied to examine luteal functional and structural regression. Immunoprecipitation was used for analyzing the interaction between NPY (neuropeptide Y) and COX-2; western blotting and qRT-PCR were used to evaluate the expressions of steroidogenic enzymes and PKA/CREB pathway. EA treatment significantly reduced the ovarian weight and the number of CL, also decreased ovarian and serum levels of PGE2 and COX-2 expression; increased ovarian PGF2α levels and PGF2α/PGE2 ratio; decreased PCNA expression and distribution; and increased cyclin regulatory inhibitor p27 expression to have further effect on the luteal formation, and promote luteal functional and structural regression. Moreover, expression of COX-2 in ovaries was possessed interactivity increased expression of NPY. Furthermore, EA treatment lowered the serum hormone levels, inhibited PKA/CREB pathway and decreased the expressions of steroidogenic enzymes. Hence, interaction with COX-2, NPY may affect the levels of PGF2α and PGE2 as well as impact the proliferation of granulosa cells in ovaries, thus further reducing the luteal formation, and promoting luteal structural and functional regression, as well as the ovarian steroidogenesis following EA treatment. EA treatment could be an option for preventing OHSS in ART. Copyright © 2018 Elsevier Inc. All rights reserved.

Molecular Classification Substitutes for the Prognostic Variables Stage, Age, and MYCN Status in Neuroblastoma Risk Assessment.

PubMed

Rosswog, Carolina; Schmidt, Rene; Oberthuer, André; Juraeva, Dilafruz; Brors, Benedikt; Engesser, Anne; Kahlert, Yvonne; Volland, Ruth; Bartenhagen, Christoph; Simon, Thorsten; Berthold, Frank; Hero, Barbara; Faldum, Andreas; Fischer, Matthias

2017-12-01

Current risk stratification systems for neuroblastoma patients consider clinical, histopathological, and genetic variables, and additional prognostic markers have been proposed in recent years. We here sought to select highly informative covariates in a multistep strategy based on consecutive Cox regression models, resulting in a risk score that integrates hazard ratios of prognostic variables. A cohort of 695 neuroblastoma patients was divided into a discovery set (n=75) for multigene predictor generation, a training set (n=411) for risk score development, and a validation set (n=209). Relevant prognostic variables were identified by stepwise multivariable L1-penalized least absolute shrinkage and selection operator (LASSO) Cox regression, followed by backward selection in multivariable Cox regression, and then integrated into a novel risk score. The variables stage, age, MYCN status, and two multigene predictors, NB-th24 and NB-th44, were selected as independent prognostic markers by LASSO Cox regression analysis. Following backward selection, only the multigene predictors were retained in the final model. Integration of these classifiers in a risk scoring system distinguished three patient subgroups that differed substantially in their outcome. The scoring system discriminated patients with diverging outcome in the validation cohort (5-year event-free survival, 84.9±3.4 vs 63.6±14.5 vs 31.0±5.4; P<.001), and its prognostic value was validated by multivariable analysis. We here propose a translational strategy for developing risk assessment systems based on hazard ratios of relevant prognostic variables. Our final neuroblastoma risk score comprised two multigene predictors only, supporting the notion that molecular properties of the tumor cells strongly impact clinical courses of neuroblastoma patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Random Survival Forest in practice: a method for modelling complex metabolomics data in time to event analysis.

PubMed

Dietrich, Stefan; Floegel, Anna; Troll, Martina; Kühn, Tilman; Rathmann, Wolfgang; Peters, Anette; Sookthai, Disorn; von Bergen, Martin; Kaaks, Rudolf; Adamski, Jerzy; Prehn, Cornelia; Boeing, Heiner; Schulze, Matthias B; Illig, Thomas; Pischon, Tobias; Knüppel, Sven; Wang-Sattler, Rui; Drogan, Dagmar

2016-10-01

The application of metabolomics in prospective cohort studies is statistically challenging. Given the importance of appropriate statistical methods for selection of disease-associated metabolites in highly correlated complex data, we combined random survival forest (RSF) with an automated backward elimination procedure that addresses such issues. Our RSF approach was illustrated with data from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, with concentrations of 127 serum metabolites as exposure variables and time to development of type 2 diabetes mellitus (T2D) as outcome variable. Out of this data set, Cox regression with a stepwise selection method was recently published. Replication of methodical comparison (RSF and Cox regression) was conducted in two independent cohorts. Finally, the R-code for implementing the metabolite selection procedure into the RSF-syntax is provided. The application of the RSF approach in EPIC-Potsdam resulted in the identification of 16 incident T2D-associated metabolites which slightly improved prediction of T2D when used in addition to traditional T2D risk factors and also when used together with classical biomarkers. The identified metabolites partly agreed with previous findings using Cox regression, though RSF selected a higher number of highly correlated metabolites. The RSF method appeared to be a promising approach for identification of disease-associated variables in complex data with time to event as outcome. The demonstrated RSF approach provides comparable findings as the generally used Cox regression, but also addresses the problem of multicollinearity and is suitable for high-dimensional data. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Evaluation of methodology for the analysis of 'time-to-event' data in pharmacogenomic genome-wide association studies.

PubMed

Syed, Hamzah; Jorgensen, Andrea L; Morris, Andrew P

2016-06-01

To evaluate the power to detect associations between SNPs and time-to-event outcomes across a range of pharmacogenomic study designs while comparing alternative regression approaches. Simulations were conducted to compare Cox proportional hazards modeling accounting for censoring and logistic regression modeling of a dichotomized outcome at the end of the study. The Cox proportional hazards model was demonstrated to be more powerful than the logistic regression analysis. The difference in power between the approaches was highly dependent on the rate of censoring. Initial evaluation of single-nucleotide polymorphism association signals using computationally efficient software with dichotomized outcomes provides an effective screening tool for some design scenarios, and thus has important implications for the development of analytical protocols in pharmacogenomic studies.

Estimating restricted mean treatment effects with stacked survival models

PubMed Central

Wey, Andrew; Vock, David M.; Connett, John; Rudser, Kyle

2016-01-01

The difference in restricted mean survival times between two groups is a clinically relevant summary measure. With observational data, there may be imbalances in confounding variables between the two groups. One approach to account for such imbalances is estimating a covariate-adjusted restricted mean difference by modeling the covariate-adjusted survival distribution, and then marginalizing over the covariate distribution. Since the estimator for the restricted mean difference is defined by the estimator for the covariate-adjusted survival distribution, it is natural to expect that a better estimator of the covariate-adjusted survival distribution is associated with a better estimator of the restricted mean difference. We therefore propose estimating restricted mean differences with stacked survival models. Stacked survival models estimate a weighted average of several survival models by minimizing predicted error. By including a range of parametric, semi-parametric, and non-parametric models, stacked survival models can robustly estimate a covariate-adjusted survival distribution and, therefore, the restricted mean treatment effect in a wide range of scenarios. We demonstrate through a simulation study that better performance of the covariate-adjusted survival distribution often leads to better mean-squared error of the restricted mean difference although there are notable exceptions. In addition, we demonstrate that the proposed estimator can perform nearly as well as Cox regression when the proportional hazards assumption is satisfied and significantly better when proportional hazards is violated. Finally, the proposed estimator is illustrated with data from the United Network for Organ Sharing to evaluate post-lung transplant survival between large and small-volume centers. PMID:26934835

Childhood Epilepsy, Febrile Seizures, and Subsequent Risk of ADHD.

PubMed

Bertelsen, Elin Næs; Larsen, Janne Tidselbak; Petersen, Liselotte; Christensen, Jakob; Dalsgaard, Søren

2016-08-01

Epilepsy, febrile seizures, and attention-deficit/hyperactivity disorder (ADHD) are disorders of the central nervous system and share common risk factors. Our goal was to examine the association in a nationwide cohort study with prospective follow-up and adjustment for selected confounders. We hypothesized that epilepsy and febrile seizures were associated with subsequent ADHD. A population-based cohort of all children born in Denmark from 1990 through 2007 was followed up until 2012. Incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) for ADHD were estimated by using Cox regression analysis, comparing children with epilepsy and febrile seizure with those without these disorders, adjusted for socioeconomic and perinatal risk factors, as well as family history of neurologic and psychiatric disorders. A total of 906 379 individuals were followed up for 22 years (∼10 million person-years of observation); 21 079 individuals developed ADHD. Children with epilepsy had a fully adjusted IRR of ADHD of 2.72 (95% CI, 2.53-2.91) compared with children without epilepsy. Similarly, in children with febrile seizure, the fully adjusted IRR of ADHD was 1.28 (95% CI, 1.20-1.35). In individuals with both epilepsy and febrile seizure, the fully adjusted IRR of ADHD was 3.22 (95% CI, 2.72-3.83). Our findings indicate a strong association between epilepsy in childhood and, to a lesser extent, febrile seizure and subsequent development of ADHD, even after adjusting for socioeconomic and perinatal risk factors, and family history of epilepsy, febrile seizures, or psychiatric disorders. Copyright © 2016 by the American Academy of Pediatrics.

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.

Locoregional Control of Non-Small Cell Lung Cancer in Relation to Automated Early Assessment of Tumor Regression on Cone Beam Computed Tomography

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

Brink, Carsten, E-mail: carsten.brink@rsyd.dk; Laboratory of Radiation Physics, Odense University Hospital; Bernchou, Uffe

2014-07-15

Purpose: Large interindividual variations in volume regression of non-small cell lung cancer (NSCLC) are observable on standard cone beam computed tomography (CBCT) during fractionated radiation therapy. Here, a method for automated assessment of tumor volume regression is presented and its potential use in response adapted personalized radiation therapy is evaluated empirically. Methods and Materials: Automated deformable registration with calculation of the Jacobian determinant was applied to serial CBCT scans in a series of 99 patients with NSCLC. Tumor volume at the end of treatment was estimated on the basis of the first one third and two thirds of the scans.more » The concordance between estimated and actual relative volume at the end of radiation therapy was quantified by Pearson's correlation coefficient. On the basis of the estimated relative volume, the patients were stratified into 2 groups having volume regressions below or above the population median value. Kaplan-Meier plots of locoregional disease-free rate and overall survival in the 2 groups were used to evaluate the predictive value of tumor regression during treatment. Cox proportional hazards model was used to adjust for other clinical characteristics. Results: Automatic measurement of the tumor regression from standard CBCT images was feasible. Pearson's correlation coefficient between manual and automatic measurement was 0.86 in a sample of 9 patients. Most patients experienced tumor volume regression, and this could be quantified early into the treatment course. Interestingly, patients with pronounced volume regression had worse locoregional tumor control and overall survival. This was significant on patient with non-adenocarcinoma histology. Conclusions: Evaluation of routinely acquired CBCT images during radiation therapy provides biological information on the specific tumor. This could potentially form the basis for personalized response adaptive therapy.« less

Preoperative atrial fibrillation and long-term survival after open heart surgery in a rural tertiary heart institute.

PubMed

O'Neal, Wesley T; Efird, Jimmy T; Davies, Stephen W; Choi, Yuk Ming; Anderson, Curtis A; Kindell, Linda C; O'Neal, Jason B; Ferguson, T Bruce; Chitwood, W Randolph; Kypson, Alan P

2013-01-01

Preoperative atrial fibrillation (AF) is associated with increased morbidity and mortality after open heart surgery. However, the impact of preoperative AF on long-term survival after open heart surgery has not been widely examined in rural populations. Patients from rural regions are less likely to receive treatment for cardiac conditions and to have adequate medical insurance coverage. To examine the influence of preoperative AF on long-term survival following open heart surgery in rural eastern North Carolina. Long-term survival was compared in patients with and without preoperative AF after coronary artery bypass grafting (CABG) and CABG plus valve (CABG + V) surgery between 2002 and 2011. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. The study population consisted of 5438 patients. A total of 263 (5%) patients had preoperative AF. Preoperative AF was an independent predictor of long-term survival (open heart surgery: adjusted HR = 1.6, 95% CI = 1.3-2.0; CABG: adjusted HR = 1.6, 95% CI = 1.3-2.1; CABG + V: adjusted HR = 1.6, 95% CI = 1.1-2.3). Preoperative AF is an important predictor of long-term survival after open heart surgery in this rural population. Copyright © 2013 Elsevier Inc. All rights reserved.

Association of Fitness With Incident Dyslipidemias Over 25 Years in the Coronary Artery Risk Development in Young Adults Study.

PubMed

Sarzynski, Mark A; Schuna, John M; Carnethon, Mercedes R; Jacobs, David R; Lewis, Cora E; Quesenberry, Charles P; Sidney, Stephen; Schreiner, Pamela J; Sternfeld, Barbara

2015-11-01

Few studies have examined the longitudinal associations of fitness or changes in fitness on the risk of developing dyslipidemias. This study examined the associations of (1) baseline fitness with 25-year dyslipidemia incidence and (2) 20-year fitness change on dyslipidemia development in middle age in the Coronary Artery Risk Development in Young Adults Study (CARDIA). Multivariable Cox proportional hazards regression models were used to test the association of baseline fitness (1985-1986) with dyslipidemia incidence over 25 years (2010-2011) in CARDIA (N=4,898). Modified Poisson regression models were used to examine the association of 20-year change in fitness with dyslipidemia incidence between Years 20 and 25 (n=2,487). Data were analyzed in June 2014 and February 2015. In adjusted models, the risk of incident low high-density lipoprotein cholesterol (HDL-C); high triglycerides; and high low-density lipoprotein cholesterol (LDL-C) was significantly lower, by 9%, 16%, and 14%, respectively, for each 2.0-minute increase in baseline treadmill endurance. After additional adjustment for baseline trait level, the associations remained significant for incident high triglycerides and high LDL-C in the total population and for incident high triglycerides in both men and women. In race-stratified models, these associations appeared to be limited to whites. In adjusted models, change in fitness did not predict 5-year incidence of dyslipidemias, whereas baseline fitness significantly predicted 5-year incidence of high triglycerides. Our findings demonstrate the importance of cardiorespiratory fitness in young adulthood as a risk factor for developing dyslipidemias, particularly high triglycerides, during the transition to middle age. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Association of Fitness With Incident Dyslipidemias Over 25 Years in the Coronary Artery Risk Development in Young Adults Study

PubMed Central

Sarzynski, Mark A.; Schuna, John M.; Carnethon, Mercedes R.; Jacobs, David R.; Lewis, Cora E.; Quesenberry, Charles P.; Sidney, Stephen; Schreiner, Pamela J.; Sternfeld, Barbara

2015-01-01

Introduction Few studies have examined the longitudinal associations of fitness or changes in fitness on the risk of developing dyslipidemias. This study examined the associations of: (1) baseline fitness with 25-year dyslipidemia incidence; and (2) 20-year fitness change on dyslipidemia development in middle age in the Coronary Artery Risk Development in young Adults (CARDIA) study. Methods Multivariable Cox proportional hazards regression models were used to test the association of baseline fitness (1985–1986) with dyslipidemia incidence over 25 years (2010–2011) in CARDIA (N=4,898). Modified Poisson regression models were used to examine the association of 20-year change in fitness with dyslipidemia incidence between Years 20 and 25 (n=2,487). Data were analyzed in June 2014 and February 2015. Results In adjusted models, the risk of incident low high-density lipoprotein cholesterol (HDL-C), high triglycerides, and high low-density lipoprotein cholesterol (LDL-C) was significantly lower, by 9%, 16%, and 14%, respectively, for each 2.0-minute increase in baseline treadmill endurance. After additional adjustment for baseline trait level, the associations remained significant for incident high triglycerides and high LDL-C in the total population and for incident high triglycerides in both men and women. In race-stratified models, these associations appeared to be limited to whites. In adjusted models, change in fitness did not predict 5-year incidence of dyslipidemias, whereas baseline fitness significantly predicted 5-year incidence of high triglycerides. Conclusions Our findings demonstrate the importance of cardiorespiratory fitness in young adulthood as a risk factor for developing dyslipidemias, particularly high triglycerides, during the transition to middle age. PMID:26165197

Prognostic Value of the Nutritional Risk Index in Heart Transplant Recipients.

PubMed

Barge-Caballero, Eduardo; García-López, Fernando; Marzoa-Rivas, Raquel; Barge-Caballero, Gonzalo; Couto-Mallón, David; Paniagua-Martín, María J; Solla-Buceta, Miguel; Velasco-Sierra, Carlos; Pita-Gutiérrez, Francisco; Herrera-Noreña, José M; Cuenca-Castillo, José J; Vázquez-Rodríguez, José Manuel; Crespo-Leiro, María G

2017-08-01

To study the prognostic impact of preoperative nutritional status, as assessed through the nutritional risk index (NRI), on postoperative outcomes after heart transplantation (HT). We conducted a retrospective, single-center study of 574 patients who underwent HT from 1991 to 2014. Preoperative NRI was calculated as 1.519 × serum albumin (g/L) + 41.7 × (body weight [kg] / ideal body weight [kg]). The association between preoperative NRI and postoperative outcomes was analyzed by means of multivariable logistic regression and multivariable Cox regression. Mean NRI before HT was 100.9 ± 9.9. According to this parameter, the prevalence of severe nutritional risk (NRI < 83.5), moderate nutritional risk (83.5 ≤ NRI < 97.5), and mild nutritional risk (97.5 ≤ NRI < 100) was 5%, 22%, and 10%, respectively. One year post-transplant mortality rates in these 4 categories were 18.2%, 25.3%, 7.9% and 10.2% (P < .001), respectively. The NRI was independently associated with a lower risk of postoperative infection (adjusted OR, 0.97; 95%CI, 0.95-1.00; P = .027) and prolonged postoperative ventilator support (adjusted OR, 0.96; 95%CI, 0.94-0.98; P = .001). Patients at moderate or severe nutritional risk had significantly higher 1-year post-HT mortality (adjusted HR, 1.55; 95%CI, 1.22-1.97; P < .001). Malnourished patients have a higher risk of postoperative complications and mortality after HT. Preoperative NRI determination may help to identify HT candidates who might benefit from nutritional intervention. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

The Association of Albuminuria With Tubular Reabsorption of Uric Acid: Results From a General Population Cohort

PubMed Central

Scheven, Lieneke; Joosten, Michel M.; de Jong, Paul E.; Bakker, Stephan J. L.; Gansevoort, Ron T.

2014-01-01

Background Elevated albuminuria as well as an increased serum uric acid concentration is associated with poor cardiovascular outcome. We questioned whether these 2 variables (albuminuria and serum uric concentration) may be interrelated via tubular uric acid reabsorption. Methods and Results Included were 7688 participants of the PREVEND Study, an observational, general population‐based cohort study. Linear regression analyses were used to test associations of baseline albuminuria with baseline serum uric acid concentration and tubular uric acid reabsorption (calculated as [100−fractional uric acid excretion]%). Cox regression analyses were used to study the association of baseline serum uric acid and albuminuria with incident cardiovascular morbidity and mortality. In cross‐sectional analyses, albuminuria was associated positively with serum uric acid concentration, both crude and after adjustment for potential confounders (both P<0.001). Albuminuria was found to be associated positively with tubular uric acid reabsorption, again both crude and after adjustment for potential confounders (both P<0.001). In longitudinal analyses during a median follow‐up of 10.5 years, 702 cardiovascular events occurred. After adjusting for cardiovascular risk factors, both albuminuria and serum uric acid were associated with incident cardiovascular events (Hazard Ratios 1.09 [1.03 to 1.17], P=0.01 and 1.19 [1.09 to 1.30], P<0.001, respectively). A significant interaction between these variables was present (P<0.001), consistent with high serum uric acid being less predictive for cardiovascular morbidity and mortality in the presence of high albuminuria and vice versa. Conclusions Albuminuria is strongly associated with tubular uric acid reabsorption, and consequently with serum uric acid concentration. This phenomenon may explain in part why albuminuria is associated with cardiovascular outcome. PMID:24772520

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.

Colorectal cancer outcomes and treatment patterns in patients too young for average-risk screening.

PubMed

Abdelsattar, Zaid M; Wong, Sandra L; Regenbogen, Scott E; Jomaa, Diana M; Hardiman, Karin M; Hendren, Samantha

2016-03-15

Although colorectal cancer (CRC) screening guidelines recommend initiating screening at age 50 years, the percentage of cancer cases in younger patients is increasing. To the authors' knowledge, the national treatment patterns and outcomes of these patients are largely unknown. The current study was a population-based, retrospective cohort study of the nationally representative Surveillance, Epidemiology, and End Results registry for patients diagnosed with CRC from 1998 through 2011. Patients were categorized as being younger or older than the recommended screening age. Differences with regard to stage of disease at diagnosis, patterns of therapy, and disease-specific survival were compared between age groups using multinomial regression, multiple regression, Cox proportional hazards regression, and Weibull survival analysis. Of 258,024 patients with CRC, 37,847 (15%) were aged <50 years. Young patients were more likely to present with regional (relative risk ratio, 1.3; P<.001) or distant (relative risk ratio, 1.5; P<.001) disease. Patients with CRC with distant metastasis in the younger age group were more likely to receive surgical therapy for their primary tumor (adjusted probability: 72% vs 63%; P<.001), and radiotherapy also was more likely in younger patients with CRC (adjusted probability: 53% vs 48%; P<.001). Patients younger than the recommended screening age had better overall disease-specific survival (hazards ratio, 0.77; P<.001), despite a larger percentage of these individuals presenting with advanced disease. Patients with CRC diagnosed at age <50 years are more likely to present with advanced-stage disease. However, they receive more aggressive therapy and achieve longer disease-specific survival, despite the greater percentage of patients with advanced-stage disease. These findings suggest the need for improved risk assessment and screening decisions for younger adults. © 2016 American Cancer Society.

Survival analysis of postoperative nausea and vomiting in patients receiving patient-controlled epidural analgesia.

PubMed

Lee, Shang-Yi; Hung, Chih-Jen; Chen, Chih-Chieh; Wu, Chih-Cheng

2014-11-01

Postoperative nausea and vomiting as well as postoperative pain are two major concerns when patients undergo surgery and receive anesthetics. Various models and predictive methods have been developed to investigate the risk factors of postoperative nausea and vomiting, and different types of preventive managements have subsequently been developed. However, there continues to be a wide variation in the previously reported incidence rates of postoperative nausea and vomiting. This may have occurred because patients were assessed at different time points, coupled with the overall limitation of the statistical methods used. However, using survival analysis with Cox regression, and thus factoring in these time effects, may solve this statistical limitation and reveal risk factors related to the occurrence of postoperative nausea and vomiting in the following period. In this retrospective, observational, uni-institutional study, we analyzed the results of 229 patients who received patient-controlled epidural analgesia following surgery from June 2007 to December 2007. We investigated the risk factors for the occurrence of postoperative nausea and vomiting, and also assessed the effect of evaluating patients at different time points using the Cox proportional hazards model. Furthermore, the results of this inquiry were compared with those results using logistic regression. The overall incidence of postoperative nausea and vomiting in our study was 35.4%. Using logistic regression, we found that only sex, but not the total doses and the average dose of opioids, had significant effects on the occurrence of postoperative nausea and vomiting at some time points. Cox regression showed that, when patients consumed a higher average dose of opioids, this correlated with a higher incidence of postoperative nausea and vomiting with a hazard ratio of 1.286. Survival analysis using Cox regression showed that the average consumption of opioids played an important role in postoperative nausea and vomiting, a result not found by logistic regression. Therefore, the incidence of postoperative nausea and vomiting in patients cannot be reliably determined on the basis of a single visit at one point in time. Copyright © 2014. Published by Elsevier Taiwan.

Factors determining disease duration in Alzheimer's disease: a postmortem study of 103 cases using the Kaplan-Meier estimator and Cox regression.

PubMed

Armstrong, R A

2014-01-01

Factors associated with duration of dementia in a consecutive series of 103 Alzheimer's disease (AD) cases were studied using the Kaplan-Meier estimator and Cox regression analysis (proportional hazard model). Mean disease duration was 7.1 years (range: 6 weeks-30 years, standard deviation = 5.18); 25% of cases died within four years, 50% within 6.9 years, and 75% within 10 years. Familial AD cases (FAD) had a longer duration than sporadic cases (SAD), especially cases linked to presenilin (PSEN) genes. No significant differences in duration were associated with age, sex, or apolipoprotein E (Apo E) genotype. Duration was reduced in cases with arterial hypertension. Cox regression analysis suggested longer duration was associated with an earlier disease onset and increased senile plaque (SP) and neurofibrillary tangle (NFT) pathology in the orbital gyrus (OrG), CA1 sector of the hippocampus, and nucleus basalis of Meynert (NBM). The data suggest shorter disease duration in SAD and in cases with hypertensive comorbidity. In addition, degree of neuropathology did not influence survival, but spread of SP/NFT pathology into the frontal lobe, hippocampus, and basal forebrain was associated with longer disease duration.

Is schizophrenia associated with an increased risk of chronic kidney disease? A nationwide matched-cohort study.

PubMed

Tzeng, Nian-Sheng; Hsu, Yung-Ho; Ho, Shinn-Ying; Kuo, Yu-Ching; Lee, Hua-Chin; Yin, Yun-Ju; Chen, Hong-An; Chen, Wen-Liang; Chu, William Cheng-Chung; Huang, Hui-Ling

2015-01-27

The impact of schizophrenia on vital diseases, such as chronic kidney disease (CKD), has not as yet been verified. This study aims to establish whether there is an association between schizophrenia and CKD. A nationwide matched cohort study. Taiwan's National Health Insurance Research Database. A total of 2338 patients with schizophrenia, and 7014 controls without schizophrenia (1:3), matched cohort for sex, age group, geography, urbanisation and monthly income, between 1 January 2003 and 31 December 2007, based on the International Classifications of Disease Ninth Edition (ICD-9), Clinical Modification codes. After making adjustments for confounding risk factors, a Cox proportional hazards model was used to compare the risk of developing CKD during a 3-year follow-up period from the index date. Of the 2338-subject case cohort, 163 (6.97%) developed a CKD, as did 365 (5.20%) of the 7014 control participants. Cox proportional hazards regression analysis revealed that patients with schizophrenia were more likely to develop CKD (HR=1.36, 95% CI 1.13 to 1.63; p<0.001). After adjusting for gender, age group, hypertension, diabetes mellitus, hyperlipidaemia, heart disease and non-steroid anti-inflammatory drugs (NSAIDs) usage, the HR for patients with schizophrenia was 1.25 (95% CI 1.04 to 1.50; p<0.05). Neither typical nor atypical antipsychotics was associated an increased risk of CKD in patients with schizophrenia. The findings from this population-based retrospective cohort study suggest that schizophrenia is associated with a 25% increase in the risk of developing CKD within only a 3-year follow-up period. 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.

Inability to access addiction treatment predicts injection initiation among street-involved youth in a Canadian setting.

PubMed

DeBeck, Kora; Kerr, Thomas; Nolan, Seonaid; Dong, Huiru; Montaner, Julio; Wood, Evan

2016-01-06

Preventing injection drug use among vulnerable youth is critical for reducing serious drug-related harms. Addiction treatment is one evidence-based intervention to decrease problematic substance use; however, youth frequently report being unable to access treatment services and the impact of this on drug use trajectories remains largely unexplored. This study examines the relationship between being unable to access addiction treatment and injection initiation among street-involved youth. Data were derived from the At-Risk Youth Study (ARYS), a prospective cohort of street-involved youth aged 14-26 who use illicit drugs, from September 2005 to May 2014. An extended Cox model with time-dependent variables was used to identify factors independently associated with injection initiation. Among 462 participants who were injection naïve at baseline, 97 (21 %) initiated injection drug use over study follow-up and 129 (28 %) reported trying but being unable to access addiction treatment in the previous 6 months at some point during the study period. The most frequently reported reason for being unable to access treatment was being put on a wait list. In a multivariable Cox regression analysis, being unable to access addiction treatment remained independently associated with a more rapid rate of injection initiation (Adjusted Hazard Ratio =2.02; 95 % Confidence Interval: 1.12-3.62), after adjusting for potential confounders. Inability to access addiction treatment was common among our sample and associated with injection initiation. Findings highlight the need for easily accessible, evidence-based addiction treatment for high-risk youth as a means to prevent injection initiation and subsequent serious drug-related harms.

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.

Cortical superficial siderosis and first-ever cerebral hemorrhage in cerebral amyloid angiopathy

PubMed Central

Boulouis, Gregoire; Xiong, Li; Jessel, Michel J.; Roongpiboonsopit, Duangnapa; Ayres, Alison; Schwab, Kristin M.; Rosand, Jonathan; Gurol, M. Edip; Greenberg, Steven M.; Viswanathan, Anand

2017-01-01

Objective: To investigate whether cortical superficial siderosis (cSS) is associated with increased risk of future first-ever symptomatic lobar intracerebral hemorrhage (ICH) in patients with cerebral amyloid angiopathy (CAA) presenting with neurologic symptoms and without ICH. Methods: Consecutive patients meeting modified Boston criteria for probable CAA in the absence of ICH from a single-center cohort were analyzed. cSS and other small vessel disease MRI markers were assessed according to recent consensus recommendations. Patients were followed prospectively for future incident symptomatic lobar ICH. Prespecified Cox proportional hazard models were used to investigate cSS and first-ever lobar ICH risk adjusting for potential confounders. Results: The cohort included 236 patients with probable CAA without lobar ICH at baseline. cSS prevalence was 34%. During a median follow-up of 3.26 years (interquartile range 1.42–5.50 years), 27 of 236 patients (11.4%) experienced a first-ever symptomatic lobar ICH. cSS was a predictor of time until first ICH (p = 0.0007, log-rank test). The risk of symptomatic ICH at 5 years of follow-up was 19% (95% confidence interval [CI] 11%–32%) for patients with cSS at baseline vs 6% (95% CI 3%–12%) for patients without cSS. In multivariable Cox regression models, cSS presence was the only independent predictor of increased symptomatic ICH risk during follow-up (HR 4.04; 95% CI 1.73–9.44, p = 0.001), after adjusting for age, lobar cerebral microbleeds burden, and white matter hyperintensities. Conclusions: cSS is consistently associated with an increased risk of future lobar ICH in CAA with potentially important clinical implications for patient care decisions such as antithrombotic use. PMID:28356458

Angiographic evidence of proliferative retinopathy predicts neuropsychiatric morbidity in diabetic patients.

PubMed

Serlin, Yonatan; Shafat, Tali; Levy, Jaime; Winter, Aaron; Shneck, Marina; Knyazer, Boris; Parmet, Yisrael; Shalev, Hadar; Ur, Ehud; Friedman, Alon

2016-05-01

Diabetic retinopathy (DR) is a common vasculopathy categorized as either non-proliferative (NPDR) or proliferative (PDR),characterized by dysfunctional blood-retinal barrier (BRB) and diagnosed using fluorescein angiography (FA). Since the BRB is similar in structure and function to the blood-brain barrier (BBB) and BBB dysfunction plays a key role in the pathogenesis of brain disorders, we hypothesized that PDR, the severe form of DR, is likely to mirror BBB damage and to predict a worse neuropsychiatric outcome. A retrospective cohort study was conducted among subjects with diabetes (N=2982) with FA-confirmed NPDR (N=2606) or PDR (N=376). Incidence and probability to develop brain pathologies and mortality were investigated in a 10-year follow-up study. We used Kaplan-Meier, Cox and logistic regression analyses to examine association between DR severity and neuropsychiatric morbidity adjusting for confounders. Patients with PDR had significantly higher rates of all-cause brain pathologies (P<0.001), specifically stroke (P=0.005), epilepsy (P=0.006) and psychosis (P=0.024), and a shorter time to develop any neuropsychiatric event (P<0.001) or death (P=0.014) compared to NPDR. Cox adjusted hazard ratio for developing all-cause brain impairments was higher for PDR (HR=1.37, 95% CI 1.16-1.61, P<0.001) which was an independent predictor for all-cause brain impairments (OR 1.30, 95% CI 1.04-1.64, P=0.022), epilepsy (OR 2.16, 95% CI 1.05-4.41, P=0.035) and mortality (HR=1.35, 95% CI 1.06-1.70, P=0.014). This is the first study to confirm that angiography-proven microvasculopathy identifies patients at high risk for neuropsychiatric morbidity and mortality. Copyright © 2016. Published by Elsevier Ltd.

The effect of anti-rheumatic medications for coronary artery diseases risk in patients with rheumatoid arthritis might be changed over time: A nationwide population-based cohort study

PubMed Central

Lin, Lichi; Chen, Chyong-Mei; Chiou, Jeng-Yuan; Wang, Yu-Hsun; Wang, Paul Yung-Pou; Wei, James Cheng-Chung

2017-01-01

Objectives To determine whether anti-rheumatic drug usage is associated with risk of coronary artery diseases (CAD) in incident Rheumatoid Arthritis (RA) patients. Methods Data were obtained from the Taiwan National Health Insurance Research Database. The study cohort comprised 6260 patients who were newly diagnosed with RA between 2001–2010. The study endpoint was occurrence of CAD according to the ICD-9-CM codes. We used the WHO Defined Daily Dose (DDD) as a tool to assess the drugs exposure. The Cox proportional hazards regression model was used to estimate the hazard ratio (HR) of disease after controlling for demographic and other co-morbidities. When the proportionality assumption is violated, a spline curve of the Scaled Schoenfeld residuals is fitted to demonstrate the estimated effect on CAD over time for drug usage. Results Among RA patients, use of celecoxib, and etoricoxib was associated with significantly decreased incidence of CAD. The adjusted HR(95% CI) of CAD for low-dose celecoxib (DDD≦1) and high-dose user were 0.47(0.34, 0.65) and 0.37(0.24, 0.58) during the 4 year follow-up time; however, it became 0.98(0.70, 1.37) and1.29(0.85, 1.95). Adjusted HR(95% CI) of CAD for etoricoxib users remained 0.47(0.26, 0.84). Conclusions This study revealed association of decreased CAD risk in RA patients taking 2 different kinds of COX-2i in comparison with nonusers. The effect might be changed over time, after about 4 years. PMID:28658301

Intradermal and virosomal influenza vaccines for preventing influenza hospitalization in the elderly during the 2011-2012 influenza season: a comparative effectiveness study using the Valencia health care information system.

PubMed

Puig-Barberà, J; Natividad-Sancho, A; Calabuig-Pérez, J; Lluch-Rodrigo, J A; Pastor-Villalba, E; Martínez-Úbeda, S; Díez-Domingo, J

2014-09-22

The use of intradermal vaccination or virosomal vaccines could increase protection against influenza among the vulnerable population of older adults. Studies assessing the comparative effectiveness of these two influenza vaccine types in this age group are lacking. We conducted a retrospective cohort study to estimate the comparative effectiveness of intradermal seasonal trivalent-influenza vaccine (TIV) delivered by a microneedle injection system and a virosomal-TIV intramuscularly delivered for prevention of influenza hospitalization in non-institutionalized adults aged ≥65 years. We obtained administrative data on immunization status and influenza hospitalization for the 2011-2012 influenza season, and used Cox regression models to assess comparative effectiveness. We estimated crude and adjusted (age, sex, comorbidity, pharmaceutical claims, recent pneumococcal vaccination and number of hospitalizations for all causes other than influenza between the previous and current influenza seasons) hazard ratios (HR). Overall, 164,021 vaccinated subjects were evaluated. There were 127 hospitalizations for influenza among 62,058 subjects, contributing 914,740 person-weeks at risk in the virosomal-TIV group, and 133 hospitalizations for influenza among 101,963 subjects, contributing 1,504,570 person-weeks at risk in the intradermal-TIV group. The crude HR of intradermal-TIV relative to virosomal-TIV was 0.64 (95% confidence interval (CI): 0.50-0.81), and the adjusted Cox estimated HR was 0.67 (95% CI: 0.52-0.85). During the 2011-2012 influenza season the risk of hospitalization for influenza was reduced by 33% in non-institutionalized elderly adults who were vaccinated with intradermal-TIV compared with virosomal-TIV. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Renin-angiotensin II-aldosterone system blockers and time to renal replacement therapy in children with CKD.

PubMed

Abraham, Alison G; Betoko, Aisha; Fadrowski, Jeffrey J; Pierce, Christopher; Furth, Susan L; Warady, Bradley A; Muñoz, Alvaro

2017-04-01

Clinical care decisions to treat chronic kidney disease (CKD) in a growing child must often be made without the benefit of evidence from clinical trials. We used observational data from the Chronic Kidney Disease in Children cohort to estimate the effectiveness of renin-angiotensin II-aldosterone system blockade (RAAS) to delay renal replacement therapy (RRT) in children with CKD. A total of 851 participants (median age: 11 years, median glomerular filtration rate [GFR]: 52 ml/min/1.73 m 2 , median urine protein to creatinine ratio: 0.35 mg/mg) were included. RAAS use was reported at annual study visits. Both Cox proportional hazards models with time-varying RAAS exposure and Cox marginal structural models (MSM) were used to evaluate the effect of RAAS use on time to RRT. Analyses were adjusted or weighted to control for age, male sex, glomerular diagnosis, GFR, nephrotic range proteinuria, anemia, elevated blood pressure, acidosis, elevated phosphate and elevated potassium. There were 217 RRT events over a 4.1-year median follow-up. At baseline, 472 children (55 %) were prevalent RAAS users, who were more likely to be older, have a glomerular etiology, have higher urine protein, be anemic, have elevated serum phosphate and potassium, take more medications, but less likely to have elevated blood pressure, compared with non-users. RAAS use was found to reduce the risk of RRT by 21 % (hazard ratio: 0.79) to 37 % (hazard ratio: 0.63) from standard regression adjustment and MSM models, respectively. These results support inferences from adult studies of a substantial benefit of RAAS use in pediatric CKD patients.

Risk of Retinal Vein Occlusion in Patients With End-Stage Renal Disease: A 12-Year, Retrospective, Nationwide Cohort Study in South Korea.

PubMed

Lee, Kyung Sik; Nam, Ki Heon; Kim, Dong Wook; Kang, Eui Chun; Koh, Hyoung Jun

2018-01-01

The present study aimed to evaluate the risk of retinal vein occlusion (RVO) in Korean patients with end-stage renal disease (ESRD). In this retrospective, nationwide, propensity score-matched cohort study, subjects were randomly enrolled from the 12-year longitudinal Korean National Health Insurance Service-National Sample Cohort 2002-2013 database comprising 1 million subjects. The ESRD group comprised 988 patients newly diagnosed with ESRD from 2003 onward by washing out data from 2002. The comparison group comprised 4940 (5 for each patient with ESRD) randomly selected propensity score-matched individuals not diagnosed with ESRD. Each sampled patient was tracked until 2013 for RVO development. Multiple conditional Cox regression analysis was performed to compare the risk of RVO between the two groups. The mean follow-up period was 7.37 years. The incidence of RVO was 3.95% in the ESRD group and 2.17% in the comparison group (P = 0.001). ESRD was associated with greater risk of RVO development after adjustment for possible confounders (adjusted hazard ratio [HR], 2.122; 95% confidence interval [CI], 1.396-3.226; P = 0.0004). The 50- to 60-year (adjusted HR, 2.635; 95% CI, 1.100-6.313; P = 0.0297) and 60- to 70-year (adjusted HR, 2.544; 95% CI, 1.059-6.110; P = 0.0368) age groups exhibited higher risk of RVO compared with the <40-year age group. Hyperlipidemia (adjusted HR, 1.670; 95% CI, 1.176-2.371; P = 0.0042) and hypertension (adjusted HR, 1.896; 95% CI, 1.165-3.086; P = 0.01) were also associated with RVO. An association between ESRD and subsequent RVO development was found after adjustment for possible confounding factors.

Comparison of Cox's Regression Model and Parametric Models in Evaluating the Prognostic Factors for Survival after Liver Transplantation in Shiraz during 2000-2012.

PubMed

Adelian, R; Jamali, J; Zare, N; Ayatollahi, S M T; Pooladfar, G R; Roustaei, N

2015-01-01

Identification of the prognostic factors for survival in patients with liver transplantation is challengeable. Various methods of survival analysis have provided different, sometimes contradictory, results from the same data. To compare Cox's regression model with parametric models for determining the independent factors for predicting adults' and pediatrics' survival after liver transplantation. This study was conducted on 183 pediatric patients and 346 adults underwent liver transplantation in Namazi Hospital, Shiraz, southern Iran. The study population included all patients undergoing liver transplantation from 2000 to 2012. The prognostic factors sex, age, Child class, initial diagnosis of the liver disease, PELD/MELD score, and pre-operative laboratory markers were selected for survival analysis. Among 529 patients, 346 (64.5%) were adult and 183 (34.6%) were pediatric cases. Overall, the lognormal distribution was the best-fitting model for adult and pediatric patients. Age in adults (HR=1.16, p<0.05) and weight (HR=2.68, p<0.01) and Child class B (HR=2.12, p<0.05) in pediatric patients were the most important factors for prediction of survival after liver transplantation. Adult patients younger than the mean age and pediatric patients weighing above the mean and Child class A (compared to those with classes B or C) had better survival. Parametric regression model is a good alternative for the Cox's regression model.

The long-term outcomes of cirrhotic patients with pleural effusion.

PubMed

Hung, Tsung-Hsing; Tseng, Chih-Wei; Tsai, Chih-Chun; Tsai, Chen-Chi; Tseng, Kuo-Chih; Hsieh, Yu-Hsi

2018-01-01

A pleural effusion is an abnormal collection of fluid in the pleural space and may cause related morbidity or mortality in cirrhotic patients. Currently, there are insufficient data to support the long-term prognosis for cirrhotic patients with pleural effusion. In this study, we investigated the short- and long-term effects of pleural effusion on mortality in cirrhotic patients and evaluated the benefit of liver transplantation in these patients. The National Health Insurance Database, derived from the Taiwan National Health Insurance Program, was used to identify 3,487 cirrhotic patients with pleural effusion requiring drainage between January 1, 2007 and December 31, 2010. The proportional hazards Cox regression model was used to control for possible confounding factors. The 30-day, 90-day, 1-year, and 3-year mortalities were 20.1%, 40.2%, 59.1%, and 75.9%, respectively, in the cirrhotic patients with pleural effusion. After Cox proportional hazard regression analysis adjusted by patient gender, age, complications of cirrhosis and comorbid disorders, old age, esophageal variceal bleeding, hepatocellular carcinoma, hepatic encephalopathy, pneumonia, renal function impairment, and without liver transplantation conferred higher risks for 3-year mortality in the cirrhotic patients with pleura effusion. Liver transplantation is the most important factor to determine the 3-year mortalities (HR: 0.17, 95% CI 0.11- 0.26, P < 0.001). The 30-day, 30 to 90-day, 90-day to 1-year, and 1 to 3-year mortalities were 5.7%, 13.4%, 20.4%, and 21.7% respectively, in the liver transplantation group, and 20.5%, 41.0%, 61.2%, and 77.5%, respectively, in the non-liver transplantation group. In cirrhotic patients, the presence of pleural effusion predicts poor long-term outcomes. Liver transplantation could dramatically improve the survival and should be suggested as soon as possible.

Physiological growth hormone replacement and rate of recurrence of craniopharyngioma: the Genentech National Cooperative Growth Study.

PubMed

Smith, Timothy R; Cote, David J; Jane, John A; Laws, Edward R

2016-10-01

OBJECTIVE The object of this study was to establish recurrence rates in patients with craniopharyngioma postoperatively treated with recombinant human growth hormone (rhGH) as a basis for determining the risk of rhGH therapy in the development of recurrent tumor. METHODS The study included 739 pediatric patients with craniopharyngioma who were naïve to GH upon entering the Genentech National Cooperative Growth Study (NCGS) for treatment. Reoperation for tumor recurrence was documented as an adverse event. Cox proportional-hazards regression models were developed for time to recurrence, using age as the outcome and enrollment date as the predictor. Patients without recurrence were treated as censored. Multivariate logistic regression was used to examine the incidence of recurrence with adjustment for the amount of time at risk. RESULTS Fifty recurrences in these 739 surgically treated patients were recorded. The overall craniopharyngioma recurrence rate in the NCGS was 6.8%, with a median follow-up time of 4.3 years (range 0.7-6.4 years.). Age at the time of study enrollment was statistically significant according to both Cox (p = 0.0032) and logistic (p < 0.001) models, with patients under 9 years of age more likely to suffer recurrence (30 patients [11.8%], 0.025 recurrences/yr of observation, p = 0.0097) than those ages 9-13 years (17 patients [6.0%], 0.17 recurrences/yr of observation) and children older than 13 years (3 patients [1.5%], 0.005 recurrences/yr of observation). CONCLUSIONS Physiological doses of GH do not appear to increase the recurrence rate of craniopharyngioma after surgery in children, but long-term follow-up of GH-treated patients is required to establish a true natural history in the GH treatment era.

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.

The relationship between different settings of medical service and incident frailty.

PubMed

Bolzetta, Francesco; Wetle, Terrie; Besdine, Richard; Noale, Marianna; Cester, Alberto; Crepaldi, Gaetano; Maggi, Stefania; Veronese, Nicola

2018-07-15

Some studies have reported a potential association between usual source of health care and disability, but no one has explored the association with frailty, a state of early and potential reversible disability. We therefore aimed to explore the association between older persons' self-reported usual source of health care at baseline and the onset of frailty. Information regarding usual source of health care was captured through self-report and categorized as 1) private doctor's office, 2) public clinic, 3) Health Maintenance Organization (HMO), or 4) hospital clinic/emergency department (ED). Frailty was defined using the Study of Osteoporotic Fracture (SOF) index as the presence of at least two of the following criteria: (i) weight loss ≥5% between baseline and any subsequent follow-up visit; (ii) inability to do five chair stands; and (iii) low energy level according to the SOF definition. Multivariable Cox's regression analyses, calculating hazard ratios (HRs) with 95% confidence intervals (CIs), were undertaken. Of the 4292 participants (mean age: 61.3), 58.7% were female. During the 8-year follow-up, 348 subjects (8.1% of the baseline population) developed frailty. Cox's regression analysis, adjusting for 14 potential confounders showed that, compared to those using a private doctor's office, people using a public clinic for their care had a significantly higher risk of developing frailty (HR = 1.56; 95%CI: 1.07-2.70), similar to those using HMO (HR = 1.48; 95%CI: 1.03-2.24) and those using a hospital/ED (HR = 1.76; 95%CI: 1.03-3.02). Participants receiving health care from sources other than private doctors are at increased risk of frailty, highlighting the need for screening for frailty in these health settings. Copyright © 2018 Elsevier Inc. All rights reserved.

No evidence of a causal relationship between hypothyroidism and glaucoma: A Danish nationwide register-based cohort study

PubMed Central

2018-01-01

Background An interrelationship between hypothyroidism and glaucoma, due to a shared autoimmune background or based on deposition of mucopolysaccharides in the trabecular meshwork in the eye, has been suggested but is at present unsubstantiated. Therefore, our objective was to investigate, at a nationwide and population-based level, whether there is such an association. Subjects and methods Observational cohort study using record-linkage data from nationwide Danish health registers. 121,799 individuals diagnosed with a first episode of hypothyroidism were identified and were matched with 4 non-hypothyroid controls according to age and sex. Prevalence of glaucoma was recorded and cases and controls were followed over a mean of 7.1 years (range 0–17). Logistic and Cox regression models were used to assess the risk of glaucoma before and after the diagnosis of hypothyroidism, respectively. Results Overall, we found a higher prevalence of glaucoma in subjects with hypothyroidism as compared to controls (4.6% vs. 4.3%, p < 0.001). Prior to the diagnosis of hypothyroidism, the odds ratio (OR) was significantly increased for glaucoma [1.09; 95% confidence interval (CI): 1.04–1.13]. Based on the Cox regression model, there was no increased risk of glaucoma after the diagnosis of hypothyroidism [hazard ratio (HR) 1.00; 95% CI: 0.96–1.06], and the HR decreased further after adjusting for pre-existing co-morbidity (0.88; 95% CI: 0.84–0.93). Conclusions There was an increased risk of glaucoma before but not after the diagnosis of hypothyroidism, suggesting that screening for glaucoma in hypothyroid individuals is unwarranted. PMID:29444121

The effect of preexisting respiratory co-morbidities on burn outcomes☆

PubMed Central

Knowlin, Laquanda T.; Stanford, Lindsay B.; Cairns, Bruce A.; Charles, Anthony G.

2018-01-01

Introduction Burns cause physiologic changes in multiple organ systems in the body. Burn mortality is usually attributable to pulmonary complications, which can occur in up to 41% of patients admitted to the hospital after burn. Patients with preexisting comorbidities such as chronic lung diseases may be more susceptible. We therefore sought to examine the impact of preexisting respiratory disease on burn outcomes. Methods A retrospective analysis of patients admitted to a regional burn center from 2002–2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA, pre-existing comorbidities, smoker status, length of hospital stay, and days of mechanical ventilation. Bivariate analysis was performed and Cox regression modeling using significant variables was utilized to estimate hazard of progression to mechanical ventilation and mortality. Results There were a total of 7640 patients over the study period. Overall survival rate was 96%. 8% (n=672) had a preexisting respiratory disease. Chronic lung disease patients had a higher mortality rate (7%) compared to those without lung disease (4%, p<0.01). The adjusted Cox regression model to estimate the hazard of progression to mechanical ventilation in patients with respiratory disease was 21% higher compared to those without respiratory disease (HR=1.21, 95% CI=1.01–1.44). The hazard of progression to mortality is 56% higher (HR=1.56, 95% CI=1.10–2.19) for patients with pre-existing respiratory disease compared to those without respiratory disease after controlling for patient demographics and injury characteristics. Conclusion Preexisting chronic respiratory disease significantly increases the hazard of progression to mechanical ventilation and mortality in patients following burn. Given the increasing number of Americans with chronic respiratory diseases, there will likely be a greater number of individuals at risk for worse outcomes following burn. PMID:28341260

The effect of preexisting respiratory co-morbidities on burn outcomes.

PubMed

Knowlin, Laquanda T; Stanford, Lindsay B; Cairns, Bruce A; Charles, Anthony G

2017-03-01

Burns cause physiologic changes in multiple organ systems in the body. Burn mortality is usually attributable to pulmonary complications, which can occur in up to 41% of patients admitted to the hospital after burn. Patients with preexisting comorbidities such as chronic lung diseases may be more susceptible. We therefore sought to examine the impact of preexisting respiratory disease on burn outcomes. A retrospective analysis of patients admitted to a regional burn center from 2002-2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA, pre-existing comorbidities, smoker status, length of hospital stay, and days of mechanical ventilation. Bivariate analysis was performed and Cox regression modeling using significant variables was utilized to estimate hazard of progression to mechanical ventilation and mortality. There were a total of 7640 patients over the study period. Overall survival rate was 96%. 8% (n=672) had a preexisting respiratory disease. Chronic lung disease patients had a higher mortality rate (7%) compared to those without lung disease (4%, p<0.01). The adjusted Cox regression model to estimate the hazard of progression to mechanical ventilation in patients with respiratory disease was 21% higher compared to those without respiratory disease (HR=1.21, 95% CI=1.01-1.44). The hazard of progression to mortality is 56% higher (HR=1.56, 95% CI=1.10-2.19) for patients with pre-existing respiratory disease compared to those without respiratory disease after controlling for patient demographics and injury characteristics. Preexisting chronic respiratory disease significantly increases the hazard of progression to mechanical ventilation and mortality in patients following burn. Given the increasing number of Americans with chronic respiratory diseases, there will likely be a greater number of individuals at risk for worse outcomes following burn. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Adolescent meat intake and breast cancer risk.

PubMed

Farvid, Maryam S; Cho, Eunyoung; Chen, Wendy Y; Eliassen, A Heather; Willett, Walter C

2015-04-15

The breast is particularly vulnerable to carcinogenic influences during adolescence due to rapid proliferation of mammary cells and lack of terminal differentiation. We investigated consumption of adolescent red meat and other protein sources in relation to breast cancer risk in the Nurses' Health Study II cohort. We followed prospectively 44,231 women aged 33-52 years who, in 1998, completed a detailed questionnaire about diet during adolescence. Relative risks (RR) and 95% confidence intervals (95%CI) were estimated using Cox proportional hazard regression. We documented 1132 breast cancer cases during 13-year follow-up. In multivariable Cox regression models with major breast cancer risk factors adjustment, greater consumption of total red meat in adolescence was significantly associated with higher premenopausal breast cancer risk (highest vs. lowest quintiles, RR, 1.43; 95%CI, 1.05-1.94; Ptrend  = 0.007), but not postmenopausal breast cancer. Adolescent intake of poultry was associated with lower risk of breast cancer overall (RR, 0.76; 95%CI, 0.60-0.97; for each serving/day). Adolescent intakes of iron, heme iron, fish, eggs, legumes and nuts were not associated with breast cancer. Replacement of one serving/day of total red meat with one serving of combination of poultry, fish, legumes, and nuts was associated with a 15% lower risk of breast cancer overall (RR, 0.85; 95%CI, 0.74-0.96) and a 23% lower risk of premenopausal breast cancer (RR, 0.77; 95%CI, 0.64-0.92). In conclusion, higher consumption of red meat during adolescence was associated with premenopausal breast cancer. Substituting other dietary protein sources for red meat in adolescent diet may decrease premenopausal breast cancer risk. © 2014 UICC.

Adolescent meat intake and breast cancer risk

PubMed Central

Farvid, Maryam S; Cho, Eunyoung; Chen, Wendy Y; Eliassen, A. Heather; Willett, Walter C

2015-01-01

The breast is particularly vulnerable to carcinogenic influences during adolescence due to rapid proliferation of mammary cells and lack of terminal differentiation. We investigated consumption of adolescent red meat and other protein sources in relation to breast cancer risk in the Nurses' Health Study II cohort. We followed prospectively 44,231 women aged 33-52 years who, in 1998, completed a detailed questionnaire about diet during adolescence. Relative risks (RR) and 95% confidence intervals (95%CI) were estimated using Cox proportional hazard regression. We documented 1132 breast cancer cases during 13-year follow-up. In multivariable Cox regression models with major breast cancer risk factors adjustment, greater consumption of adolescent total red meat was significantly associated with higher premenopausal breast cancer risk (highest vs lowest quintiles, RR, 1.42; 95%CI, 1.05-1.94; Ptrend=0.007), but not postmenopausal breast cancer. Adolescent poultry intake was associated with lower risk of breast cancer overall (RR, 0.75; 95%CI, 0.59-0.96; for each serving/day). Adolescent intakes of iron, heme iron, fish, eggs, legumes and nuts were not associated with breast cancer. Replacement of one serving/day of total red meat with one serving of combination of poultry, fish, legumes, and nuts was associated with a 16% lower risk of breast cancer overall (RR, 0.84; 95%CI, 0.74-0.96) and a 24% lower risk of premenopausal breast cancer (RR, 0.76; 95%CI, 0.64-0.92). Higher consumption of red meat during adolescence was associated with premenopausal breast cancer. Substituting other dietary protein sources for red meat in adolescent diet may decrease premenopausal breast cancer risk. PMID:25220168

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

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.

Long-term pediatric skin eruption-related hospitalizations in offspring conceived via fertility treatment.

PubMed

Krieger, Yuval; Wainstock, Tamar; Sheiner, Eyal; Harlev, Avi; Landau, Daniella; Horev, Amir; Bogdanov-Berezovsky, Alexander; Walfisch, Asnat

2018-03-01

Although concerns have been raised regarding the long-term health risks of offspring conceived following fertility treatments, limited information is available regarding their health status beyond the neonatal period. We aimed to evaluate the risk of long-term eruptive dermatological morbidity among children born following fertility treatments as compared to those conceived spontaneously. A population-based cohort study was conducted, including all singleton deliveries occurring between the years 1991 and 2014 at a single tertiary medical center. Fetuses with congenital malformations and multiple gestations were excluded. Children delivered following fertility treatment pregnancies and spontaneous pregnancies were compared. Hospitalizations of the offspring up to the age of 18 years involving cutaneous eruptions were evaluated. A Kaplan-Meier survival curve was used to compare cumulative morbidity incidence and a Cox regression model to control for confounders. During the study period, 242,187 singleton deliveries met the inclusion criteria, 1.8% of which were following fertility treatments (n = 4324). Eruptive dermatological morbidity of the offspring up to the age of 18 years was significantly more common in the fertility treatment group (1.5%) as compared to spontaneous pregnancies (1.1%; P = 0.023). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of eruptive dermatological morbidity following fertility treatments (log-rank P = 0.007). Using the Cox regression model, while controlling for multiple confounders, fertility treatment was noted as an independent risk factor for long-term pediatric eruptive dermatological morbidity (adjusted HR = 1.43, CI 1.12-1.83, P = 0.004). Singletons conceived via fertility treatments appear to be at an increased risk for long-term eruptive dermatological morbidity. © 2018 The International Society of Dermatology.

[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.

DRUG USE PATTERNS PREDICT RISK OF NON-FATAL OVERDOSE AMONG STREET-INVOLVED YOUTH IN A CANADIAN SETTING

PubMed Central

Mitra, Goldis; Wood, Evan; Nguyen, Paul; Kerr, Thomas; DeBeck, Kora

2015-01-01

Background Non-fatal drug overdose is a major cause of morbidity among people who use drugs, although few studies have examined this risk among street-involved youth. We sought to determine the risk factors associated with non-fatal overdose among Canadian street-involved youth who reported illicit drug use. Methods Using data from a prospective cohort of street-involved youth in Vancouver, Canada, we identified youth without a history of overdose and employed Cox regression analyses to determine factors associated with time to non-fatal overdose between September 2005 and May 2012. Results Among 615 participants, 98 (15.9%) reported a non-fatal overdose event during follow-up, resulting in an incidence density of 7.67 cases per 100 person-years. In multivariate Cox regression analyses, binge drug use (adjusted hazard ratio [AHR] = 1.85; 95% confidence interval [CI] = 1.20 – 2.84), non-injection crystal methamphetamine use (AHR = 1.70; 95% CI = 1.12 – 2.58), non-injection prescription opiate use (AHR = 2.56; 95% CI = 1.36 – 4.82), injection prescription opiate use (AHR = 2.49; 95% CI = 1.40 – 4.45) and injection heroin use (AHR = 1.85; 95% CI = 1.14 – 3.00) were positively associated with time to non-fatal overdose. Social, behavioural and demographic factors were not significantly associated with time to non-fatal overdose event. Conclusions Rates of non-fatal overdose were high among street-involved youth. Drug use patterns, in particular prescription opiate use, were associated with overdose. These findings underscore the importance of addiction treatment and prevention efforts aimed at reducing the risk of overdose among youth. PMID:26096535

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.

Hemoglobin Concentration and Risk of Incident Stroke in Community-Living Adults.

PubMed

Panwar, Bhupesh; Judd, Suzanne E; Warnock, David G; McClellan, William M; Booth, John N; Muntner, Paul; Gutiérrez, Orlando M

2016-08-01

In previous observational studies, hemoglobin concentrations have been associated with an increased risk of stroke. However, these studies were limited by a relatively low number of stroke events, making it difficult to determine whether the association of hemoglobin and stroke differed by demographic or clinical factors. Using Cox proportional hazards analysis and Kaplan-Meier plots, we examined the association of baseline hemoglobin concentrations with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort of black and white adults aged ≥45 years. A total of 518 participants developed stroke over a mean 7±2 years of follow-up. There was a statistically significant interaction between hemoglobin and sex (P=0.05) on the risk of incident stroke. In Cox regression models adjusted for demographic and clinical variables, there was no association of baseline hemoglobin concentration with incident stroke in men, whereas in women, the lowest (<12.4 g/dL) and highest (>14.0 g/dL) quartiles of hemoglobin were associated with higher risk of stroke when compared with the second quartile (12.4-13.2 g/dL; quartile 1: hazard ratio, 1.59; 95% confidence interval, 1.09-2.31; quartile 2: referent; quartile 3: hazard ratio, 0.91; 95% confidence interval, 0.59-1.38; quartile 4: hazard ratio, 1.59; 95% confidence interval, 1.08-2.35). Similar results were observed in models stratified by hemoglobin and sex and when hemoglobin was modeled as a continuous variable using restricted quadratic spline regression. Lower and higher hemoglobin concentrations were associated with a higher risk of incident stroke in women. No such associations were found in men. © 2016 American Heart Association, Inc.

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.

Lower body mass index predicts worse cancer-specific prognosis in octogenarians with colorectal cancer.

PubMed

Adachi, Tomohiro; Hinoi, Takao; Kinugawa, Yusuke; Enomoto, Toshiyuki; Maruyama, Satoshi; Hirose, Hajime; Naito, Masanori; Tanaka, Keitaro; Miyake, Yasuhiro; Watanabe, Masahiko

2016-08-01

High body mass index (BMI) is a risk factor for colorectal cancer. However, the prognostic impact of BMI and other factors may differ between elderly and younger colorectal cancer patients. We analyze here prognostic factors in the surgical management of octogenarians with colorectal cancer and clarify the prognostic impact of BMI. Cox regression analysis and propensity score methods were used to retrospectively examine the association of BMI with mortality in 1613 octogenarian patients who underwent curative surgery for stage 0-III colorectal cancer. In the Cox regression analysis, lower BMI (<18.5 kg/m(2); p = 0.001), age ≥83 years (p = 0.008), American Society of Anesthesiology class ≥3: (p = 0.001), performance status ≥2 (p = 0.003), Union for International Cancer Control (UICC) stage ≥III (p = 0.001), and postoperative adverse events (p = 0.001) were independently associated with decreased overall survival. Lower BMI (p = 0.001) and UICC stage ≥III (p = 0.001) were independently associated with decreased cancer-specific survival. After covariate adjustment, lower BMI was a risk factor for overall [hazard ratio (HR) 1.62; 95 % confidence interval (CI) 1.26-2.05; p = 0.0004] and cancer-specific survival (HR 2.00; 95 % CI 1.39-2.87; p = 0.0038) compared with normal BMI (18.5-24.9 kg/m(2)). Lower BMI is significantly and independently associated with increased mortality risk in octogenarians who undergo curative surgery for colorectal cancer. Lower BMI should be used for prognosis assessment in octogenarians with colorectal cancer.

Association of nutritional status as measured by the Mini-Nutritional Assessment Short Form with changes in mobility, institutionalization and death after hip fracture.

PubMed

Nuotio, M; Tuominen, P; Luukkaala, T

2016-03-01

We examined the association of nutritional status as measured by the Mini-Nutritional Assessment Short Form (MNA-SF) with changes in mobility, institutionalization and death after hip fracture. Population-based prospective data were collected on 472 out of 693 consecutive hip fracture patients aged 65 years and over between January 2010 and December 2012. Declined vs same or improved mobility level, institutionalization and death during the 4-month follow-up were the outcomes. Age, gender, American Society of Anesthesiologists scores, pre-fracture diagnosis of a memory disorder, mobility level, living arrangements and MNA-SF scores at baseline were the independent variables. Age-adjusted and multivariate logistic regression and Cox proportional hazards models were conducted. At baseline, 41 (9%) patients were malnourished and 200 (42%) patients at risk of malnutrition according to the MNA-SF. During the follow-up, 90 (19%) had died. In the multivariate Cox proportional hazards model, malnutrition (hazard ratio 2.16; 95% confidence interval (CI) 1.07-4.34) was associated with mortality. In the multivariate binary logistic regression analyses, risk of malnutrition (odds ratios (OR) 2.42; 95% CI 1.25-4.66) and malnutrition (OR 6.10;95% CI 2.01-18.5) predicted institutionalization. Risk of malnutrition (OR 2.03; 95% CI 1.24-3.31) was associated with decline in the mobility level. Malnutrition or risk of malnutrition as measured by the MNA-SF were independent predictors of negative outcomes after hip fracture. Patients classified as being at risk of malnutrition by the MNA-SF may constitute a patient population with mild-to-moderate malnutrition and may require specific attention when nutritional interventions are designed after hip fracture.

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.

Management of immunosuppressive therapy in liver transplant recipients who develop bloodstream infection.

PubMed

Bartoletti, Michele; Vandi, Giacomo; Furii, Francesca; Bertuzzo, Valentina; Ambretti, Simone; Tedeschi, Sara; Pascale, Renato; Cristini, Francesco; Campoli, Caterina; Morelli, Maria Cristina; Cescon, Matteo; Pinna, Antonio Daniele; Viale, Pierluigi; Giannella, Maddalena

2018-05-29

Data about the optimal management of immunosuppressive therapy in liver transplant (LT) recipients with bloodstream infection (BSI) are missing. We aimed to describe the management of immunosuppressive therapy at diagnosis of BSI in LT recipients and to assess its impact on 28-day mortality. We performed a single-centre retrospective study of all LT recipients diagnosed with BSI, over 10-year period. Multivariate Cox regression analysis of risk factors for all-cause 28-day mortality was adjusted for the propensity score of being managed with "any reduction" in immunosuppressive therapy at the diagnosis of BSI. We identified 209 episodes of BSI in 157 LT recipients: 107 (68%) male, median age 54 (IQR 48-63) years. "Any reduction" was made in 90 (43%) cases including: dosage reduction of ≥1 immunosuppressive drug in 31 (15%), discontinuation of ≥1 immunosuppressive drug in 28 (13%), both dosage reduction and discontinuation in 13 (6%), complete withdrawal of immunosuppressive therapy in 18 (9%) cases. All-cause 28-day mortality rate was 13.4%, varying from 22% to 7% (p=0.002) in cases with and without "any reduction". Cox regression showed septic shock (aHR 3.15, p=0.007) and "any reduction" (aHR 2.50, p=0.02) as independent risk factors for all-cause 28-day mortality, while Escherichia coli (aHR 0.38, p=0.03) and source control (aHR 0.43, p=0.04) were protective factors. The final model did not change after the introduction of the propensity score for "any reduction". Any reduction in the immunosuppressive therapy was common and was associated with worse outcome in LT recipients developing BSI. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Insulin Resistance and Prognosis of Nondiabetic Patients With Ischemic Stroke: The ACROSS-China Study (Abnormal Glucose Regulation in Patients With Acute Stroke Across China).

PubMed

Jing, Jing; Pan, Yuesong; Zhao, Xingquan; Zheng, Huaguang; Jia, Qian; Mi, Donghua; Chen, Weiqi; Li, Hao; Liu, Liping; Wang, Chunxue; He, Yan; Wang, David; Wang, Yilong; Wang, Yongjun

2017-04-01

Insulin resistance was common in patients with stroke. This study investigated the association between insulin resistance and outcomes in nondiabetic patients with first-ever acute ischemic stroke. Patients with ischemic stroke without history of diabetes mellitus in the ACROSS-China registry (Abnormal Glucose Regulation in Patients With Acute Stroke Across China) were included. Insulin resistance was defined as a homeostatis model assessment-insulin resistance (HOMA-IR) index in the top quartile (Q4). HOMA-IR was calculated as fasting insulin (μU/mL)×fasting glucose (mmol/L)/22.5. Multivariable logistic regression or Cox regression was performed to estimate the association between HOMA-IR and 1-year prognosis (mortality, stroke recurrence, poor functional outcome [modified Rankin scale score 3-6], and dependence [modified Rankin scale score 3-5]). Among the 1245 patients with acute ischemic stroke enrolled in this study, the median HOMA-IR was 1.9 (interquartile range, 1.1-3.1). Patients with insulin resistance were associated with a higher mortality risk than those without (adjusted hazard ratio, 1.68; 95% confidence interval, 1.12-2.53; P =0.01), stroke recurrence (adjusted hazard ratio, 1.57, 95% confidence interval, 1.12-2.19; P =0.008), and poor outcome (adjusted odds ratio, 1.42; 95% confidence interval, 1.03-1.95; P =0.03) but not dependence after adjustment for potential confounders. Higher HOMA-IR quartile categories were associated with a higher risk of 1-year death, stroke recurrence, and poor outcome ( P for trend =0.005, 0.005, and 0.001, respectively). Insulin resistance was associated with an increased risk of death, stroke recurrence, and poor outcome but not dependence in nondiabetic patients with acute ischemic stroke. © 2017 American Heart Association, Inc.

Association between enterovirus infection and speech and language impairments: A nationwide population-based study.

PubMed

Hung, Tai-Hsin; Chen, Vincent Chin-Hung; Yang, Yao-Hsu; Tsai, Ching-Shu; Lu, Mong-Liang; McIntyre, Roger S; Lee, Yena; Huang, Kuo-You

2018-06-01

Delay and impairment in Speech and language are common developmental problems in younger populations. Hitherto, there has been minimal study of the association between common childhood infections (e.g. enterovirus [EV]) and speech and language. The impetus for evaluating this association is provided by evidence linking inflammation to neurodevelopmental disorders. Herein we sought to determine whether an association exists between EV infection and subsequent diagnoses of speech and language impairments in a nationwide population-based sample in Taiwan. Our study acquired data from the Taiwan National Health Insurance Research Database. The sample was comprised of individuals under 18 years of age with newly diagnosed EV infection during the period from January 1998 to December 2011. 39669 eligible cases were compared to matched controls and assessed during the study period for incident cases of speech and language impairments. Cox regression analyses were applied, adjusting for sex, age and other physical and mental problems. In the fully adjusted Cox regression model for hazard ratios, EV infection as positively associated with speech and language impairments (HR = 1.14, 95% CI: 1.06-1.22) after adjusting for age, sex and other confounds. Compared to the control group, the hazard ratio for speech and language impairments was 1.12 (95% CI: 1.03-1.21) amongst the group of EV infection without hospitalization, and 1.26 (95% CI: 1.10-1.45) amongst the group of EV infection with hospitalization. EV infection is temporally associated with incident speech and language impairments. Our findings herein provide rationale for educating families that EV infection may be associated with subsequent speech and language problems in susceptible individuals and that monitoring for such a presentation would be warranted. WHAT THIS PAPER ADDS?: Speech and language impairments associated with central nervous system infections have been reported in the literature. EV are medically important human pathogens and associated with select neuropsychiatric diseases. Notwithstanding, relatively few reports have mentioned the effects of EV infection on speech and language problems. Our study used a nationwide longitudinal dataset and identified that children with EV infection have a greater risk for speech and language impairments as compared with control group. Infected children combined other comorbidities or risk factors might have greater possibility to develop speech problems. Clinicians should be vigilant for the onset of language developmental abnormalities of preschool children with EV infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mid-Life Proteinuria and Late-Life Cognitive Function and Dementia in Elderly Men: The Honolulu-Asia Aging Study

PubMed Central

Higuchi, Masaya; Chen, Randi; Abbott, Robert D.; Bell, Christina; Launer, Lenore; Ross, G. Webster; Petrovitch, Helen; Masaki, Kamal

2015-01-01

Background Impaired renal function has been linked to cognitive impairment. We assessed mid-life proteinuria and late-life cognitive function in elderly Asian males. Methods The Honolulu Heart Program is a prospective study that began in 1965 with 8,006 Japanese-American men ages 45–68 years. Mid-life proteinuria was detected by urine dipstick in 1971–74. The Honolulu-Asia Aging Study began 20 years later, with cognitive assessment by the Cognitive Abilities Screening Instrument (CASI) in 3,734 men. Standard criteria were used to classify 8-year incident dementia and subtypes. RESULTS The age-adjusted incidence of dementia increased significantly from 13.8, to 22.8, to 39.7 per 1,000 person years follow-up, among those with no, trace and positive mid-life proteinuria, p=0.004. Using linear regression adjusting for age, education, APOEε4, stroke, hypertension, systolic blood pressure, diabetes, fasting blood glucose, physical activity and baseline CASI, those with positive proteinuria had significantly higher annual change in CASI over 8 years follow-up (−1.24, p=0.02), reference=no proteinuria. Multivariate Cox regression found positive proteinuria had a significant association with incident all-cause dementia (RR=2.66, 95%CI=1.09–6.53, p=0.03), but no significant associations with incident Alzheimer’s disease or vascular dementia. CONCLUSION Mid-life proteinuria was an independent predictor for late-life incident all-cause dementia and cognitive decline over 8 years. PMID:25626635

Improved survival after stroke: is admission to hospital the major explanation? Trend analyses of the Auckland Regional Community Stroke Studies.

PubMed

Carter, Kristie N; Anderson, Craig S; Hackett, Maree L; Barber, P Alan; Bonita, Ruth

2007-01-01

There is uncertainty regarding the impact of changes in stroke care and natural history of stroke in the community. We examined factors responsible for trends in survival after stroke in a series of population-based studies. We used statistical models to assess temporal trends in 28-day and 1-year case fatality after first-ever stroke cases registered in 3 stroke incidence studies undertaken in Auckland, New Zealand, over uniform 12-month calendar periods in 1981-1982 (n = 1,030), 1991-1992 (1,305) and 2001-2002 (1,423). Cox proportional hazards regression was used to evaluate the significance of pre-defined 'patient', 'disease' and 'service/care' factors on these trends. Overall, there was a 40% decline in 28-day case fatality after stroke over the study periods, from 32% (95% confidence interval, 29-35%) in 1981-1982 to 23% (21-25%) in 1991-1992 and then 19% (17-21%) in 2002-2003. Similar relative declines were seen in 1-year case fatality. In regression models, the trends were still significant after adjusting for patient and disease factors. However, further adjustment for care factors (higher hospital admission and neuroimaging) explained most of the improvement in survival. These data show significant downwards trends in case fatality after stroke in Auckland over 20 years, which can largely be attributed to improved stroke care associated with increases in hospital admission and brain imaging during the acute phase of the illness.

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.

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

Nguyen, Paul L., E-mail: E-pnguyen@LROC.harvard.ed; Harvard Medical School, Boston, MA; Chen, Ming H.

Background: Brachytherapy for prostate cancer can be technically challenging in men with small prostates ({<=}20 cc), but it is unknown whether their outcomes are different than those of men with larger prostates. Methods and Materials: We studied 6,416 men treated with brachytherapy in one of 21 community-based practices. Cox regression and Fine and Gray's regression were used to determine whether volume {<=}20 cc was associated with a higher risk of all-cause mortality (ACM) or prostate cancer-specific mortality (PCSM), respectively, after adjustment for other known prognostic factors. Results: 443 patients (6.9%) had a prostate volume {<=}20 cc. After a median follow-upmore » of 2.91 years (interquartile range, 1.06-4.79), volume {<=}20 cc was associated with a significantly higher risk of ACM (adjusted hazard ratio = 1.33 [95% CI 1.08-1.65], p = 0.0085) with 3-year estimates of ACM for {<=}20 cc vs. >20 cc of 13.0% vs. 6.9% (p = 0.028). Only 23 men (0.36%) have died of prostate cancer, and no difference was seen in PCSM by volume (p = 0.4). Conclusion: Men with small prostates at the time of implant had a 33% higher risk of ACM, and the underlying cause of this remains uncertain. No increase in PCSM was observed in men with volume {<=}20cc, suggesting that a small prostate should not in itself be a contraindication for brachytherapy, but inasmuch as absolute rates of PCSM were small, further follow-up will be needed to confirm this finding.« less

COX-2 overexpression in resected pancreatic head adenocarcinomas correlates with favourable prognosis

PubMed Central

2014-01-01

Background Overexpression of cyclooxygenase-2 (COX-2) has been implicated in oncogenesis and progression of adenocarcinomas of the pancreatic head. The data on the prognostic importance of COX expression in these tumours is inconsistent and conflicting. We evaluated how COX-2 overexpression affected overall postoperative survival in pancreatic head adenocarcinomas. Methods The study included 230 consecutive pancreatoduodenectomies for pancreatic cancer (PC, n = 92), ampullary cancer (AC, n = 62) and distal bile duct cancer (DBC, n = 76). COX-2 expression was assessed by immunohistochemistry. Associations between COX-2 expression and histopathologic variables including degree of differentiation, histopathologic type of differentiation (pancreatobiliary vs. intestinal) and lymph node ratio (LNR) were evaluated. Unadjusted and adjusted survival analysis was performed. Results COX-2 staining was positive in 71% of PC, 77% in AC and 72% in DBC. Irrespective of tumour origin, overall patient survival was more favourable in patients with COX-2 positive tumours than COX-2 negative (p = 0.043 in PC, p = 0.011 in AC, p = 0.06 in DBC). In tumours of pancreatobiliary type of histopathological differentiation, COX-2 expression did not significantly affect overall patient survival. In AC with intestinal differentiation COX-2 expression significantly predicted favourable survival (p = 0.003). In PC, COX-2 expression was significantly associated with high degree of differentiation (p = 0.002). COX-2 and LNR independently predicted good prognosis in a multivariate model. Conclusions COX-2 is overexpressed in pancreatic cancer, ampullary cancer and distal bile duct cancer and confers a survival benefit in all three cancer types. In pancreatic cancer, COX-2 overexpression is significantly associated with the degree of differentiation and independently predicts a favourable prognosis. PMID:24950702

Box-Cox transformation of firm size data in statistical analysis

NASA Astrophysics Data System (ADS)

Chen, Ting Ting; Takaishi, Tetsuya

2014-03-01

Firm size data usually do not show the normality that is often assumed in statistical analysis such as regression analysis. In this study we focus on two firm size data: the number of employees and sale. Those data deviate considerably from a normal distribution. To improve the normality of those data we transform them by the Box-Cox transformation with appropriate parameters. The Box-Cox transformation parameters are determined so that the transformed data best show the kurtosis of a normal distribution. It is found that the two firm size data transformed by the Box-Cox transformation show strong linearity. This indicates that the number of employees and sale have the similar property as a firm size indicator. The Box-Cox parameters obtained for the firm size data are found to be very close to zero. In this case the Box-Cox transformations are approximately a log-transformation. This suggests that the firm size data we used are approximately log-normal distributions.

Censored quantile regression with recursive partitioning-based weights

PubMed Central

Wey, Andrew; Wang, Lan; Rudser, Kyle

2014-01-01

Censored quantile regression provides a useful alternative to the Cox proportional hazards model for analyzing survival data. It directly models the conditional quantile of the survival time and hence is easy to interpret. Moreover, it relaxes the proportionality constraint on the hazard function associated with the popular Cox model and is natural for modeling heterogeneity of the data. Recently, Wang and Wang (2009. Locally weighted censored quantile regression. Journal of the American Statistical Association 103, 1117–1128) proposed a locally weighted censored quantile regression approach that allows for covariate-dependent censoring and is less restrictive than other censored quantile regression methods. However, their kernel smoothing-based weighting scheme requires all covariates to be continuous and encounters practical difficulty with even a moderate number of covariates. We propose a new weighting approach that uses recursive partitioning, e.g. survival trees, that offers greater flexibility in handling covariate-dependent censoring in moderately high dimensions and can incorporate both continuous and discrete covariates. We prove that this new weighting scheme leads to consistent estimation of the quantile regression coefficients and demonstrate its effectiveness via Monte Carlo simulations. We also illustrate the new method using a widely recognized data set from a clinical trial on primary biliary cirrhosis. PMID:23975800

Big Data Toolsets to Pharmacometrics: Application of Machine Learning for Time‐to‐Event Analysis

PubMed Central

Gong, Xiajing; Hu, Meng

2018-01-01

Abstract Additional value can be potentially created by applying big data tools to address pharmacometric problems. The performances of machine learning (ML) methods and the Cox regression model were evaluated based on simulated time‐to‐event data synthesized under various preset scenarios, i.e., with linear vs. nonlinear and dependent vs. independent predictors in the proportional hazard function, or with high‐dimensional data featured by a large number of predictor variables. Our results showed that ML‐based methods outperformed the Cox model in prediction performance as assessed by concordance index and in identifying the preset influential variables for high‐dimensional data. The prediction performances of ML‐based methods are also less sensitive to data size and censoring rates than the Cox regression model. In conclusion, ML‐based methods provide a powerful tool for time‐to‐event analysis, with a built‐in capacity for high‐dimensional data and better performance when the predictor variables assume nonlinear relationships in the hazard function. PMID:29536640

Older Patients With Early-stage Breast Cancer: Adjuvant Radiation Therapy and Predictive Factors for Cancer-related Death.

PubMed

Nagar, Himanshu; Yan, Weisi; Christos, Paul; Chao, K S Clifford; Nori, Dattatreyudu; Ravi, Akkamma

2017-06-01

Studies have shown that older women are undertreated for breast cancer. Few data are available on cancer-related death in elderly women aged 70 years and older with pathologic stage T1a-b N0 breast cancer and the impact of prognostic factors on cancer-related death. The Surveillance, Epidemiology, and End Results (SEER) database was queried for women aged 70 years or above diagnosed with pT1a or pT1b, N0 breast cancer who underwent breast conservation surgery from 1999 to 2003. The Kaplan-Meier survival analysis was performed to evaluate breast cause-specific survival (CSS) and overall survival (OS), and the log-rank test was employed to compare CSS/OS between different groups of interest. Multivariable analysis (MVA), using Cox proportional hazards regression analysis, was performed to evaluate the independent effect of age, race, stage, grade, ER status, and radiation treatment on CSS. Adjusted hazard ratios were calculated from the MVA and reflect the increased risk of breast cancer death. Competing-risks survival regression was also performed to adjust the univariate and multivariable CSS hazard ratios for the competing event of death due to causes other than breast cancer. Patients aged 85 and above had a greater risk of breast cancer death compared with patients aged 70 to 74 years (referent category) (adjusted hazard ratio [HRs]=1.98). Race had no effect on CSS. Patients with stage T1bN0 breast cancer had a greater risk of breast cancer death compared with stage T1aN0 patients (adjusted HR=1.35; P=0.09). ER negative patients had a greater risk of breast cancer death compared with ER positive patients (adjusted HR=1.59; P<0.017). Patients with higher grade tumors had a greater risk of breast cancer death compared with patients with grade 1 tumors (referent category) (adjusted HRs=1.69 and 2.96 for grade 2 and 3, respectively). Patients who underwent radiation therapy had a lower risk of breast cancer death compared with patients who did not (adjusted HR=0.55; P<0.0001). Older patients with higher grade, pT1b, ER-negative breast cancer had increased risk of breast cancer-related death. Adjuvant radiation therapy may provide a CSS benefit in this elderly patient population.

Is platelet transfusion associated with hospital-acquired infections in critically ill patients?

PubMed

Aubron, Cécile; Flint, Andrew W; Bailey, Michael; Pilcher, David; Cheng, Allen C; Hegarty, Colin; Martinelli, Antony; Reade, Michael C; Bellomo, Rinaldo; McQuilten, Zoe

2017-01-06

Platelets are commonly transfused to critically ill patients. Reports suggest an association between platelet transfusion and infection. However, there is no large study to have determined whether platelet transfusion in critically ill patients is associated with hospital-acquired infection. We conducted a multi-centre study using prospectively maintained databases of two large academic intensive care units (ICUs) in Australia. Characteristics of patients who received platelets in ICUs between 2008 and 2014 were compared to those of patients who did not receive platelets. Association between platelet administration and infection (bacteraemia and/or bacteriuria) was modelled using multiple logistic regression and Cox regression, with blood components as time-varying covariates. A propensity covariate adjustment was also performed to verify results. Of the 18,965 patients included, 2250 (11.9%) received platelets in ICU with a median number of 1 platelet unit (IQR 1-3) administered. Patients who received platelets were more severely ill at ICU admission (mean Acute Physiology and Chronic Health Evaluation III score 65 (SD 29) vs 52 (SD 25), p < 0.01) and had more comorbidities (31% vs 19%, p < 0.01) than patients without platelet transfusion. Invasive mechanical ventilation (87% vs 57%, p < 0.01) and renal replacement therapy (20% vs 4%, p < 0.01) were more frequently administered in patients receiving platelets than in patients without platelets. On univariate analysis, platelet transfusion was associated with hospital-acquired infection in the ICU (7.7% vs 1.4%, p < 0.01). After adjusting for confounders, including other blood components administered, patient severity, centre, year, and diagnosis category, platelet transfusions were independently associated with infection (adjusted OR 2.56 95% CI 1.98-3.31, p < 0.001). This association was also found in survival analysis with blood components as time-varying covariates (adjusted HR 1.85, 95% CI 1.41-2.41, p < 0.001) and when only bacteraemia was considered (adjusted OR 3.30, 95% CI 2.30-4.74, p <0.001). Platelet transfusions remained associated with infection after propensity covariate adjustment. After adjustment for confounders, including patient severity and other blood components, platelet transfusion was independently associated with ICU-acquired infection. Further research aiming to better understand this association and to prevent this complication is warranted.

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.

Antidepressant use and mortality in very old people.

PubMed

Boström, Gustaf; Hörnsten, Carl; Brännström, Jon; Conradsson, Mia; Nordström, Peter; Allard, Per; Gustafson, Yngve; Littbrand, Håkan

2016-07-01

Antidepressant treatment may increase the risk of death. The association between antidepressants and mortality has been evaluated in community-dwelling older people, but not in representative samples of very old people, among whom dementia, multimorbidity, and disability are common. Umeå 85+/GERDA study participants (n = 992) aged 85, 90, and ≥95 years were followed for up to five years. Cox proportional hazard regression models were used to analyze mortality risk associated with baseline antidepressant treatment, adjusted for potential confounders. Mean age was 89 years; 27% of participants had dementia, 20% had stroke histories, 29% had heart failure, and 16% used antidepressants. In age- and sex-adjusted analyses, antidepressant use was associated with a 76% increased mortality risk (hazard ratio [HR] = 1.76; 95% confidence interval [CI], 1.41-2.19). Adding adjustment for Geriatric Depression Scale score, HR was 1.62 (95% CI, 1.29-2.03). The association was not significant when adjusting for additional confounding factors (HR = 1.08; 95% CI, 0.85-1.38). Interaction analyses in the fully adjusted model revealed a significant interaction between sex and antidepressant use (HR: 1.76; 95% CI, 1.05-2.94). Among male and female antidepressant users, the HRs for death were 0.76 (95% CI, 0.47-1.24) and 1.28 (95% CI, 0.97-1.70), respectively. Among very old people, baseline antidepressant treatment does not seem to be independently associated with increased mortality risk. However, the risk may be different in men and women. This difference and the potential risk of initial treatment require further investigation in future cohort studies of very old people.

Mortality and prostate cancer risk in 19,598 men after surgery for benign prostatic hyperplasia.

PubMed

Holman, C D; Wisniewski, Z S; Semmens, J B; Rouse, I L; Bass, A J

1999-07-01

To examine postoperative mortality and prostate cancer risk after the first prostatectomy for benign prostatic hypertrophy over a 17-year period in a population-based cohort of men in Western Australia, using improved methods to adjust for comorbidity. The relative survival from death and prostate cancer incidence was calculated against the background population rates. The outcomes of transurethral resection of the prostate (TURP) and open prostatectomy (OP) were compared adjusting for calendar year, age, admission type and comorbidity using Cox regression. Fractional polynomials were used to take account of nonlinearity in confounder effects. At 10 years, the relative survival was 116.5% in TURP patients and 123.5% after OP. Adjusting only for confounding by age, calendar year and admission type, TURP had a higher mortality rate than OP (rate ratio, RR, 1. 20; 95% confidence interval 1.08-1.34). The RR fell to 1.10 (0.99-1. 23) after adjustment for comorbidity and to 1.07 (0.95-1.19) when accounting for nonlinearity. The relative survival from the incidence of prostate cancer at 10 years was 103.7% after TURP and 104.5% after OP. The RR adjusted for age and calendar year was 1.44 (0.94-2.21) for incidence and 1.37 (0.81-2.29) for prostate cancer mortality. There is at most a small and clinically unimportant excess mortality risk from TURP; any difference could be due to a protective effect of OP on the long-term risk of prostate cancer and a lower rate of repeat prostatectomy.

Immunohistochemical and morphometric evaluation of COX-1 and COX-2 in the remodeled lung in idiopathic pulmonary fibrosis and systemic sclerosis* ,**

PubMed Central

Parra, Edwin Roger; Lin, Flavia; Martins, Vanessa; Rangel, Maristela Peres; Capelozzi, Vera Luiza

2013-01-01

OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients, correlating that expression with patient survival. METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP) in SSc patients and usual interstitial pneumonia (UIP) in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival. RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP), and low COX-1 expression in alveolar septa. CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that. PMID:24473763

Alternatives for using multivariate regression to adjust prospective payment rates

PubMed Central

Sheingold, Steven H.

1990-01-01

Multivariate regression analysis has been used in structuring three of the adjustments to Medicare's prospective payment rates. Because the indirect-teaching adjustment, the disproportionate-share adjustment, and the adjustment for large cities are responsible for distributing approximately $3 billion in payments each year, the specification of regression models for these adjustments is of critical importance. In this article, the application of regression for adjusting Medicare's prospective rates is discussed, and the implications that differing specifications could have for these adjustments are demonstrated. PMID:10113271

Pioglitazone does not affect the risk of ovarian cancer: analysis of a nationwide reimbursement database in Taiwan.

PubMed

Tseng, Chin-Hsiao

2013-10-01

The association between pioglitazone and ovarian cancer has not been studied. The reimbursement databases of all Taiwanese patients with a diagnosis of diabetes and under oral anti-diabetic agents or insulin from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006 and a total of 546,632 female patients with type 2 diabetes were followed up for ovarian cancer incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of pioglitazone exposure [using cutoffs of the Kaiser Permanente Northern California study and tertile cutoffs derived from the databases] were calculated and the hazard ratios were estimated by Cox regression in unadjusted, age-adjusted and fully adjusted models. There were 30,783 ever-users and 515,849 never-users, with respective numbers of incident ovarian cancer of 49 (0.16%) and 946 (0.18%), and respective incidence of 43.08 and 51.47 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) in unadjusted, age-adjusted and fully adjusted models were 0.822 (0.616-1.095), 0.823 (0.617-1.097) and 0.968 (0.718-1.305), respectively. In the dose-response analyses, none of the categories showed a significant hazard ratio, and all P-trends were >0.05 without statistical significance. This study does not support a positive or negative association between pioglitazone use and ovarian cancer in female patients with type 2 diabetes. © 2013.

Density of calcium in the ascending thoracic aorta and risk of incident cardiovascular disease events.

PubMed

Thomas, Isac C; McClelland, Robyn L; Michos, Erin D; Allison, Matthew A; Forbang, Nketi I; Longstreth, W T; Post, Wendy S; Wong, Nathan D; Budoff, Matthew J; Criqui, Michael H

2017-10-01

The volume and density of coronary artery calcium (CAC) both independently predict cardiovascular disease (CVD) beyond standard risk factors, with CAC density inversely associated with incident CVD after accounting for CAC volume. We tested the hypothesis that ascending thoracic aorta calcium (ATAC) volume and density predict incident CVD events independently of CAC. The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study of participants without clinical CVD at baseline. ATAC and CAC were measured from baseline cardiac computed tomography (CT). Cox regression models were used to estimate the associations of ATAC volume and density with incident coronary heart disease (CHD) events and CVD events, after adjustment for standard CVD risk factors and CAC volume and density. Among 6811 participants, 234 (3.4%) had prevalent ATAC and 3395 (49.8%) had prevalent CAC. Over 10.3 years, 355 CHD and 562 CVD events occurred. One-standard deviation higher ATAC density was associated with a lower risk of CHD (HR 0.48 [95% CI 0.29-0.79], p<0.01) and CVD (HR 0.56 [0.37-0.84], p<0.01) after full adjustment. ATAC volume was not associated with outcomes after full adjustment. ATAC was uncommon in a cohort free of clinical CVD at baseline. However, ATAC density was inversely associated with incident CHD and CVD after adjustment for CVD risk factors and CAC volume and density. Copyright © 2017 Elsevier B.V. All rights reserved.

Magnesium intake, plasma C-peptide, and colorectal cancer incidence in US women: a 28-year follow-up study

PubMed Central

Zhang, X; Giovannucci, E L; Wu, K; Smith-Warner, S A; Fuchs, C S; Pollak, M; Willett, W C; Ma, J

2012-01-01

Background: Laboratory studies suggest a possible role of magnesium intake in colorectal carcinogenesis but epidemiological evidence is inconclusive. Method: We tested magnesium–colorectal cancer hypothesis in the Nurses' Health Study, in which 85 924 women free of cancer in 1980 were followed until June 2008. Cox proportional hazards regression models were used to estimate multivariable relative risks (MV RRs, 95% confidence intervals). Results: In the age-adjusted model, magnesium intake was significantly inversely associated with colorectal cancer risk; the RRs from lowest to highest decile of total magnesium intake were 1.0 (ref), 0.93, 0.81, 0.72, 0.74, 0.77, 0.72, 0.75, 0.80, and 0.67 (Ptrend<0.001). However, in the MV model adjusted for known dietary and non-dietary risk factors for colorectal cancer, the association was significantly attenuated; the MV RRs were 1.0 (ref), 0.96, 0.85, 0.78, 0.82, 0.86, 0.84, 0.91, 1.02, and 0.93 (Ptrend=0.77). Similarly, magnesium intakes were significantly inversely associated with concentrations of plasma C-peptide in age-adjusted model (Ptrend=0.002) but not in multivariate-adjusted model (Ptrend=0.61). Results did not differ by subsite or modified by calcium intakes or body mass index. Conclusion: These prospective results do not support an independent association of magnesium intake with either colorectal cancer risk or plasma C-peptide levels in women. PMID:22415230

An appraisal of statistical procedures used in derivation of reference intervals.

PubMed

Ichihara, Kiyoshi; Boyd, James C

2010-11-01

When conducting studies to derive reference intervals (RIs), various statistical procedures are commonly applied at each step, from the planning stages to final computation of RIs. Determination of the necessary sample size is an important consideration, and evaluation of at least 400 individuals in each subgroup has been recommended to establish reliable common RIs in multicenter studies. Multiple regression analysis allows identification of the most important factors contributing to variation in test results, while accounting for possible confounding relationships among these factors. Of the various approaches proposed for judging the necessity of partitioning reference values, nested analysis of variance (ANOVA) is the likely method of choice owing to its ability to handle multiple groups and being able to adjust for multiple factors. Box-Cox power transformation often has been used to transform data to a Gaussian distribution for parametric computation of RIs. However, this transformation occasionally fails. Therefore, the non-parametric method based on determination of the 2.5 and 97.5 percentiles following sorting of the data, has been recommended for general use. The performance of the Box-Cox transformation can be improved by introducing an additional parameter representing the origin of transformation. In simulations, the confidence intervals (CIs) of reference limits (RLs) calculated by the parametric method were narrower than those calculated by the non-parametric approach. However, the margin of difference was rather small owing to additional variability in parametrically-determined RLs introduced by estimation of parameters for the Box-Cox transformation. The parametric calculation method may have an advantage over the non-parametric method in allowing identification and exclusion of extreme values during RI computation.

Quantile Regression with Censored Data

ERIC Educational Resources Information Center

Lin, Guixian

2009-01-01

The Cox proportional hazards model and the accelerated failure time model are frequently used in survival data analysis. They are powerful, yet have limitation due to their model assumptions. Quantile regression offers a semiparametric approach to model data with possible heterogeneity. It is particularly powerful for censored responses, where the…

Educational achievement among long-term survivors of congenital heart defects: a Danish population-based follow-up study.

PubMed

Olsen, Morten; Hjortdal, Vibeke E; Mortensen, Laust H; Christensen, Thomas D; Sørensen, Henrik T; Pedersen, Lars

2011-04-01

Congenital heart defect patients may experience neurodevelopmental impairment. We investigated their educational attainments from basic schooling to higher education. Using administrative databases, we identified all Danish patients with a cardiac defect diagnosis born from 1 January, 1977 to 1 January, 1991 and alive at age 13 years. As a comparison cohort, we randomly sampled 10 persons per patient. We obtained information on educational attainment from Denmark's Database for Labour Market Research. The study population was followed until achievement of educational levels, death, emigration, or 1 January, 2006. We estimated the hazard ratio of attaining given educational levels, conditional on completing preceding levels, using discrete-time Cox regression and adjusting for socio-economic factors. Analyses were repeated for a sub-cohort of patients and controls born at term and without extracardiac defects or chromosomal anomalies. We identified 2986 patients. Their probability of completing compulsory basic schooling was approximately 10% lower than that of control individuals (adjusted hazard ratio = 0.79, ranged from 0.75 to 0.82 0.79; 95% confidence interval: 0.75-0.82). Their subsequent probability of completing secondary school was lower than that of the controls, both for all patients (adjusted hazard ratio = 0.74; 95% confidence interval: 0.69-0.80) and for the sub-cohort (adjusted hazard ratio = 0.80; 95% confidence interval: 0.73-0.86). The probability of attaining a higher degree, conditional on completion of youth education, was affected both for all patients (adjusted hazard ratio = 0.88; 95% confidence interval: 0.76-1.01) and for the sub-cohort (adjusted hazard ratio = 0.92; 95% confidence interval: 0.79-1.07). The probability of educational attainment was reduced among long-term congenital heart defect survivors.

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.

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

Comparison of statistical approaches dealing with time-dependent confounding in drug effectiveness studies.

PubMed

Karim, Mohammad Ehsanul; Petkau, John; Gustafson, Paul; Platt, Robert W; Tremlett, Helen

2018-06-01

In longitudinal studies, if the time-dependent covariates are affected by the past treatment, time-dependent confounding may be present. For a time-to-event response, marginal structural Cox models are frequently used to deal with such confounding. To avoid some of the problems of fitting marginal structural Cox model, the sequential Cox approach has been suggested as an alternative. Although the estimation mechanisms are different, both approaches claim to estimate the causal effect of treatment by appropriately adjusting for time-dependent confounding. We carry out simulation studies to assess the suitability of the sequential Cox approach for analyzing time-to-event data in the presence of a time-dependent covariate that may or may not be a time-dependent confounder. Results from these simulations revealed that the sequential Cox approach is not as effective as marginal structural Cox model in addressing the time-dependent confounding. The sequential Cox approach was also found to be inadequate in the presence of a time-dependent covariate. We propose a modified version of the sequential Cox approach that correctly estimates the treatment effect in both of the above scenarios. All approaches are applied to investigate the impact of beta-interferon treatment in delaying disability progression in the British Columbia Multiple Sclerosis cohort (1995-2008).

Is Ki67 prognostic for aggressive prostate cancer? A multicenter real-world study.

PubMed

Fantony, Joseph J; Howard, Lauren E; Csizmadi, Ilona; Armstrong, Andrew J; Lark, Amy L; Galet, Colette; Aronson, William J; Freedland, Stephen J

2018-06-15

To test if Ki67 expression is prognostic for biochemical recurrence (BCR) after radical prostatectomy (RP). Ki67 immunohistochemistry was performed on tissue microarrays constructed from specimens obtained from 464 men undergoing RP at the Durham and West LA Veterans Affairs Hospitals. Hazard ratios (HR) for Ki67 expression and time to BCR were estimated using Cox regression. Ki67 was associated with more recent surgery year (p < 0.001), positive margins (p = 0.001) and extracapsular extension (p < 0.001). In center-stratified analyses, the adjusted HR for Ki67 expression and BCR approached statistical significance for west LA (HR: 1.54; p = 0.06), but not Durham (HR: 1.10; p = 0.74). This multi-institutional 'real-world' study provides limited evidence for the prognostic role of Ki67 in predicting outcome after RP.

Physical capacity and risk for long-term sickness absence: a prospective cohort study among 8664 female health care workers.

PubMed

Rasmussen, Charlotte Diana Nørregaard; Andersen, Lars Louis; Clausen, Thomas; Strøyer, Jesper; Jørgensen, Marie Birk; Holtermann, Andreas

2015-05-01

To assess the prospective associations between self-reported physical capacity and risk of long-term sickness absence among female health care workers. Female health care workers answered a questionnaire about physical capacity and were followed in a national register of sickness absence lasting for two or more consecutive weeks during 1-year follow-up. Using Cox regression hazard ratio analyses adjusted for age, smoking, body mass index, physical workload, job seniority, psychosocial work conditions, and previous sickness absence, we modeled risk estimates for sickness absence from low and medium physical capacity. Low and medium aerobic fitness, low muscle strength, low flexibility, and low overall physical capacity significantly increased the risk for sickness absence with 20% to 34% compared with health care workers with high capacity. Low physical capacity increases the risk of long-term sickness absence among female health care workers.

Predictors of Dropout From Inpatient Substance Use Treatment: A Prospective Cohort Study.

PubMed

Andersson, Helle Wessel; Steinsbekk, Aslak; Walderhaug, Espen; Otterholt, Eli; Nordfjærn, Trond

2018-01-01

Dropout from inpatient treatment for substance use disorder (SUD) is an ongoing challenge. The aim of this study was to identify demographic, substance use, and psychological factors that predict dropout from postdetoxification inpatient SUD treatment. A total of 454 patients from 5 inpatient SUD centers in Central Norway were consecutively included in this naturalistic, prospective cohort study. A total of 132 patients (28%) did not complete the planned treatment stay (dropped out). Cox regression analysis showed that higher levels of intrinsic motivation for changing personal substance use reduced the dropout risk (adjusted hazard ratio [adjHR]: 0.62, 95% confidence interval [CI]: 0.48-0.79). Higher levels of mental distress were associated with an increased risk for dropout (adjHR: 1.48, 95% CI: 1.11-1.97). The role of mental health and motivation in reducing dropout risk from inpatient SUD treatment should be targeted in future prospective intervention studies.

Lesions of endodontic origin and risk of coronary heart disease.

PubMed

Caplan, D J; Chasen, J B; Krall, E A; Cai, J; Kang, S; Garcia, R I; Offenbacher, S; Beck, J D

2006-11-01

A paucity of epidemiologic research exists regarding systemic health consequences of endodontic disease. This study evaluated whether incident radiographically evident lesions of endodontic origin were related to development of coronary heart disease (CHD) among 708 male participants in the VA Dental Longitudinal Study. At baseline and every three years for up to 32 years, participants (who were not VA patients) received complete medical and dental examinations, including full-mouth radiographs. Cox regression models estimated the relationship between incident lesions of endodontic origin and time to CHD diagnosis. Among those < or = 40 years old, incident lesions of endodontic origin were significantly associated with time to CHD diagnosis (p < 0.05), after adjustment for covariates of interest, with hazard ratios decreasing as age increased. Among those > 40 years old, no statistically significant association was observed. These findings are consistent with research that suggests relationships between chronic periodontal inflammation and the development of CHD, especially among younger men.

Toward the understanding of the molecular basis for the inhibition of COX-1 and COX-2 by phenolic compounds present in Uruguayan propolis and grape pomace.

PubMed

Paulino, Margot; Alvareda, Elena; Iribarne, Federico; Miranda, Pablo; Espinosa, Victoria; Aguilera, Sara; Pardo, Helena

2016-12-01

Propolis and grape pomace have significant amounts of phenols which can take part in anti-inflammatory mechanisms. As the cyclooxygenases 1 and 2 (COX-1 and COX-2) are involved in said mechanisms, the possibility for a selective inhibition of COX-2 was analyzed in vitro and in silico. Propolis and grape pomace from Uruguayan species were collected, extracted in hydroalcoholic mixture and analyzed. Based on phenols previously identified, and taking as reference the crystallographic structures of COX-1 and COX-2 in complex with the commercial drug Celecoxib, a molecular docking procedure was devised to adjust 123 phenolic molecular models at the enzyme-binding sites. The most important results of this work are that the extracts have an overall inhibition activity very similar in COX-1 and COX-2, i.e. they do not possess selective inhibition activity for COX-2. Nevertheless, 10 compounds of the phenolic database turned out to be more selective and 94 phenols resulted with similar selectivity than Celecoxib, an outcome that accounts for the overall experimental inhibition measures. Binding site environment observations showed increased polarity in COX-2 as compared with COX-1, suggesting that polarity is the key for selectivity. Accordingly, the screening of molecular contacts pointed to the residues: Arg106, Gln178, Leu338, Ser339, Tyr341, Tyr371, Arg499, Ala502, Val509, and Ser516, which would explain, at the atomic level, the anti-inflammatory effect of the phenolic compounds. Among them, Gln178 and Arg499 appear to be essential for the selective inhibition of COX-2.

Evaluation of Cox's model and logistic regression for matched case-control data with time-dependent covariates: a simulation study.

PubMed

Leffondré, Karen; Abrahamowicz, Michal; Siemiatycki, Jack

2003-12-30

Case-control studies are typically analysed using the conventional logistic model, which does not directly account for changes in the covariate values over time. Yet, many exposures may vary over time. The most natural alternative to handle such exposures would be to use the Cox model with time-dependent covariates. However, its application to case-control data opens the question of how to manipulate the risk sets. Through a simulation study, we investigate how the accuracy of the estimates of Cox's model depends on the operational definition of risk sets and/or on some aspects of the time-varying exposure. We also assess the estimates obtained from conventional logistic regression. The lifetime experience of a hypothetical population is first generated, and a matched case-control study is then simulated from this population. We control the frequency, the age at initiation, and the total duration of exposure, as well as the strengths of their effects. All models considered include a fixed-in-time covariate and one or two time-dependent covariate(s): the indicator of current exposure and/or the exposure duration. Simulation results show that none of the models always performs well. The discrepancies between the odds ratios yielded by logistic regression and the 'true' hazard ratio depend on both the type of the covariate and the strength of its effect. In addition, it seems that logistic regression has difficulty separating the effects of inter-correlated time-dependent covariates. By contrast, each of the two versions of Cox's model systematically induces either a serious under-estimation or a moderate over-estimation bias. The magnitude of the latter bias is proportional to the true effect, suggesting that an improved manipulation of the risk sets may eliminate, or at least reduce, the bias. Copyright 2003 JohnWiley & Sons, Ltd.

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.

Chronic Rhinosinusitis Associated with Erectile Dysfunction: A Population-Based Study.

PubMed

Tai, Shu-Yu; Wang, Ling-Feng; Tai, Chih-Feng; Huang, Yu-Ting; Chien, Chen-Yu

2016-08-31

Few studies have investigated the relationship between chronic rhinosinusitis (CRS) and erectile dysfunction (ED). This case-control study aimed to investigate the association between CRS and the risk of ED in a large national sample. Tapping Taiwan's National Health Insurance Research Database, we identified people 30 years or older with a new primary diagnosis of CRS between 1996 and 2007. The cases were compared with sex- and age-matched controls. We identified 14 039 cases and recruited 140 387 matched controls. Both groups were followed up in the same database until the end of 2007 for instances of ED. Of those with CRS, 294 (2.1%) developed ED during a mean (SD) follow-up of 3.20 (2.33) years, while 1 661 (1.2%) of the matched controls developed ED, mean follow up 2.97 (2.39) years. Cox regression analyses were performed adjusting for sex, age, insurance premium, residence, hypertension, hyperlipidemia, diabetes, obesity, coronary heart disease, chronic kidney disease, chronic obstructive pulmonary disease, asthma, allergic rhinitis, arrhythmia, ischemic stroke, intracerebral hemorrhage, and medications. CRS was revealed to be an independent predictor of ED in the fully adjusted model (HR = 1.51; 95% CI = 1.33-1.73; P < 0.0001).

Association between Periodontal disease and Prostate cancer: Results of a 12-year Longitudinal Cohort Study in South Korea

PubMed Central

Lee, Jae-Hong; Kweon, Helen Hye-In; Choi, Jung-Kyu; Kim, Young-Taek; Choi, Seong-Ho

2017-01-01

The incidence of prostate cancer (PC) accompanying periodontal disease (PD) is anticipated to increase due to population aging. The aim of this study was to determine the association between PD and PC using data in the National Health Insurance Service-Health Examinee Cohort (NHIS-HEC). A random stratified sample of 187,934 South Koreans was collected from the NHIS database from 2002 to 2013. We assessed the relationship between PD and PC while adjusting for potential confounding factors (sex, age, household income, insurance status, residence area, hypertension, diabetes mellitus, cerebral infarction, angina pectoris, myocardial infarction, smoking status, alcohol intake, and regular exercise). The overall incidence of PC with PD among those aged 40 years and older was 0.28% (n = 531). In the multivariate Cox proportional-hazard regression analysis with adjustment for confounding factors, PD was associated with a 14% higher risk of PC (HR = 1.14, 95% CI = 1.01-1.31, P = 0.042). The findings of this study suggest that PD is significantly and positively associated with PC. Further studies are required to identify the mechanisms underlying the links between PD and PC. PMID:28928887

Adiposity and risks of colorectal and small intestine cancer in Chinese adults: a prospective study of 0.5 million people.

PubMed

Pang, Yuanjie; Kartsonaki, Christiana; Guo, Yu; Chen, Yiping; Yang, Ling; Bian, Zheng; Bragg, Fiona; Millwood, Iona Y; Mao, Enke; Li, Yilei; Shi, Liya; Chen, Junshi; Li, Liming; Holmes, Michael V; Chen, Zhengming

2018-06-06

Uncertainty remains about the associations of adiposity with intestinal cancer in China and by its anatomical subtype. The prospective China Kadoorie Biobank recorded 3024 incident cases of colorectal (CRC) and 143 cases of small intestine (SIC) cancer during a 10-year follow-up among 509 568 participants without prior cancer at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for specific cancers associated with adiposity. Overall mean body mass index (BMI) was 23.7  kg/m 2 . BMI was positively associated with CRC (HR per SD 1.10 [95% CI 1.06-1.14]), colon (1.13 [1.07-1.18]), and rectal (1.07 [1.02-1.13]) cancer. For waist circumference, the corresponding HRs per SD were 1.14 (1.10-1.18), 1.18 (1.13-1.24), and 1.11 (1.05-1.16), respectively. The adjusted HRs were somewhat greater in men than women. Adiposity was positively, but non-significantly, associated with SIC risk. Among relatively lean Chinese adults, adiposity was associated with risks of colon and rectal cancer, with the associations somewhat stronger in men than women.

Body mass index and outcomes in patients receiving chemotherapy for intermediate-grade B-cell non-Hodgkin lymphoma.

PubMed

Jones, Jeffrey A; Fayad, Luis E; Elting, Linda S; Rodriguez, Maria A

2010-09-01

We conducted a retrospective cohort study examining the influence of obesity on treatment outcome and survival among 712 patients with intermediate-grade B-cell NHL receiving frontline therapy between 1988 and 2001. Baseline adiposity was approximated by body mass index categorized according to the World Health Organization schema. Logistic and Cox proportional hazards regression modeling was used to adjust for baseline patient demographic, disease, and treatment variables. Approximately 37% of cohort patients were overweight (BMI 25 to <30 kg/m(2)) and more than 23% were obese (BMI >or= 30 kg/m(2)). Risk factors were similar across groups and treatment intensity did not vary by BMI. Median follow-up was 45.7 and 62.8 months for PFS and OS, respectively. After adjustment for other significant prognostic factors, BMI in the overweight range was associated with significantly reduced hazard for both PFS (OR 0.72, p = 0.011) and OS (OR 0.74, p = 0.030). Increased BMI is associated with significantly improved survival among patients with treatment-naive, intermediate-grade B-cell NHL. Prospective confirmation of these results is warranted given the increasing prevalence of both NHL and obesity.

Impact of breastfeeding duration on age at menarche.

PubMed

Al-Sahab, Ban; Adair, Linda; Hamadeh, Mazen J; Ardern, Chris I; Tamim, Hala

2011-05-01

The study aims to assess the relation between breastfeeding duration and age at menarche. Analysis was based on a cohort of 994 Filipino girls born in 1983-1984 and followed up from infancy to adulthood by the Cebu Longitudinal Health and Nutrition Survey. The main outcome was self-reported age at menarche. Cox regression was used to investigate the relation between duration of exclusive and any breastfeeding with age at menarche with adjustment sequentially for specific sets of known socioeconomic, maternal, genetic, and prenatal confounders. The estimated median of age at menarche was 13.08 years. After adjustment for potential confounders of the association of breastfeeding with age at menarche, exclusive breastfeeding duration retained an independent and significant association with age at menarche. An increase in 1 month of exclusive breastfeeding decreases the hazard of attaining earlier menarche by 6% (hazard ratio = 0.94, 95% confidence interval: 0.90, 0.98). Any breastfeeding duration was not associated with age at menarche. Although this is the first longitudinal study that reveals a negative association between exclusive breastfeeding and early menarche, the relation is still elusive. Further longitudinal studies within different contexts are warranted to assess the generalizability of these findings.

C-reactive protein levels and treatment resistance in schizophrenia-A Danish population-based cohort study.

PubMed

Horsdal, Henriette Thisted; Wimberley, Theresa; Benros, Michael Eriksen; Gasse, Christiane

2017-11-01

Schizophrenia is associated with increased levels of inflammatory markers. However, it remains unclear whether inflammatory markers are associated with treatment-resistant schizophrenia. We conducted a population-based follow-up study among individuals with a first-time schizophrenia diagnosis and a baseline C-reactive protein measurement (a commonly available marker of systemic inflammation) from 2000 to 2012. We defined treatment resistance as the earliest observed instance of either clozapine initiation or hospital admission due to schizophrenia after having received at least 2 prior antipsychotic monotherapy trials of adequate duration. We used adjusted Cox regression analysis to calculate hazard ratios. We identified 390 individuals with a C-reactive protein measurement at first-time schizophrenia diagnosis. A nonsignificant higher median C-reactive protein (4.0 vs. 3.1 mg/L, p = .13) was observed among the 52 (13.3%) treatment-resistant individuals. Increased levels of C-reactive protein (above 3 mg/L) at baseline were not associated with treatment resistance (adjusted hazard ratio = 0.99, 95% confidence interval [0.56, 1.73]). C-reactive protein, as a single inflammatory marker, appears insufficient to detect treatment-resistant schizophrenia. Copyright © 2017 John Wiley & Sons, Ltd.

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.

Effect of childhood socioeconomic conditions on cancer onset in later life: an ambidirectional cohort study.

PubMed

van der Linden, Bernadette W A; Courvoisier, Delphine S; Cheval, Boris; Sieber, Stefan; Bracke, Piet; Guessous, Idris; Burton-Jeangros, Claudine; Kliegel, Matthias; Cullati, Stéphane

2018-05-17

Living in low socioeconomic conditions during childhood is associated with poor health outcomes in later life. Whether this link also applies to cancer is unclear. We examined whether childhood socioeconomic conditions (CSCs) are associated with cancer risk in later life and whether this effect remained after adjusting for adulthood socioeconomic conditions (ASCs). Data for 26,431 individuals ≥ 50 years old included in SHARE were analysed. CSCs were constructed by using indicators of living conditions at age 10. ASC indicators were education, main occupation, and household income. Gender-stratified associations of CSCs with cancer onset (overall and by site) were assessed by Cox regression. In total, 2852 individuals were diagnosed with cancer. For both men and women, risk of overall cancer was increased for advantaged CSCs and remained so after adjusting for ASCs (hazard ratio = 1.36, 95% CI 1.10, 1.63, and 1.70, 95% CI 1.41, 2.07). Advantaged CSCs are associated with an increased risk of overall cancer at older age, but results vary by cancer sites and sex. Participation in cancer screening or exposure to risk factors may differ by social conditions.

Impact of total radiotherapy dose on survival for head and neck Merkel cell carcinoma after resection.

PubMed

Patel, Sagar A; Qureshi, Muhammad M; Mak, Kimberley S; Sahni, Debjani; Giacalone, Nicholas J; Ezzat, Waleed; Jalisi, Scharukh; Truong, Minh Tam

2017-07-01

Head and neck Merkel cell carcinoma (MCC) is commonly treated with surgery and adjuvant radiotherapy (RT) for high-risk features. The optimal radiation dose is unknown. One thousand six hundred twenty-five eligible patients with head and neck MCC were identified in the National Cancer Data Base (NCDB). Radiation dose was divided into 3 groups: 30 to <50 Gray (Gy), 50-55 Gy, and >55-70 Gy. Cox regression was used to compare overall survival (OS) between groups, accounting for age, sex, stage, surgery type, margin status, comorbidities, and use of chemotherapy. With a median follow-up of 33.5 months, 3-year OS was 48.9%, 70.3%, and 58.7% for 30 to <50 Gy, 50-55 Gy, and >55-70 Gy, respectively (P < .001). Compared to 50-55 Gy, doses between 30 to <50 Gy (adjusted hazard ratio [HR] 1.53; 95% confidence interval [CI] 1.17-1.99; P = .002) and >55-70 Gy (adjusted HR 1.21; 95% CI 1.0-1.46; P = .06) were associated with worse survival. Adjuvant radiation doses within 50-55 Gy may be optimal for head and neck MCC. © 2017 Wiley Periodicals, Inc.

Differences in Colorectal Cancer Outcomes by Race and Insurance.

PubMed

Tawk, Rima; Abner, Adrian; Ashford, Alicestine; Brown, Clyde Perry

2015-12-22

Colorectal cancer (CRC) is the second most common cancer among African American women and the third most common cancer for African American men. The mortality rate from CRC is highest among African Americans compared to any other racial or ethnic group. Much of the disparity in mortality is likely due to diagnosis at later stages of the disease, which could result from unequal access to screening. The purpose of this study is to determine the impact of race and insurance status on CRC outcomes among CRC patients. Data were drawn from the Surveillance, Epidemiology, and End Results database. Logistic regressions models were used to examine the odds of receiving treatment after adjusting for insurance, race, and other variables. Cox proportional hazard models were used to measure the risk of CRC death after adjusting for sociodemographic and tumor characteristics when associating race and insurance with CRC-related death. Blacks were diagnosed at more advanced stages of disease than whites and had an increased risk of death from both colon and rectal cancers. Lacking insurance was associated with an increase in CRC related-deaths. Findings from this study could help profile and target patients with the greatest disparities in CRC health outcomes.

No Trend in the Intergenerational Transmission of Divorce

PubMed Central

LI, JUI-CHUNG ALLEN; WU, LAWRENCE L.

2008-01-01

Previous studies on trends in the intergenerational transmission of divorce have produced mixed findings, with two studies (McLanahan and Bumpass 1988; Teachman 2002) reporting no trend in divorce transmission and one study (Wolfinger 1999) finding that divorce transmission has weakened substantially. Using a stratified Cox proportional hazard model, we analyze data from the National Survey of Families and Households and find no evidence for any trend in divorce transmission. To reconcile apparent differences in results, we note that the General Social Survey data used by Wolfinger lack information on marital duration, permitting analysis only for whether respondents have divorced by interview. As a result, an apparent decline in divorce transmission could be due to inadequate adjustments for the longer exposures to risk by earlier marriage cohorts, yielding a higher probability of divorce by interview for earlier cohorts relative to more recent cohorts even if divorce risks are identical across all marriage cohorts. We confirm this possibility by using a series of discrete-time hazard logistic regressions to investigate the sensitivity of estimates of trends in divorce transmission to different adjustments for exposure to risk. We conclude that there has been no trend in the intergenerational transmission of divorce. PMID:19110902

Drugs Used in the Treatment of Rheumatoid Arthritis: Relationship between Current Use and Cardiovascular Risk Factors

PubMed Central

Rho, Young Hee; Oeser, Annette; Chung, Cecilia P; Milne, Ginger L; Stein, C Michael

2009-01-01

Objectives Drugs used for the treatment of rheumatoid arthritis (RA) have the potential to affect cardiovascular risk factors. There is concern that corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors could affect cardiovascular risk adversely, while drugs such as the antimalarial, hydroxychloroquine, may have beneficial effects. However, there is limited information about cardiovascular risk factors in patients with RA receiving different drugs. Methods We measured cardiovascular risk factors including systolic and diastolic blood pressure, serum HDL and LDL cholesterol, glucose and homocysteine concentrations and urinary F2-isoprostane excretion in 169 patients with RA. Risk factors were compared according to current use of corticosteroids, methotrexate, antimalarials, NSAIDs, COX-2 inhibitors, leflunomide and TNF-α blockers. Comparisons were adjusted for age, sex, race, disease activity (DAS28 score), current hypertension, diabetes, smoking status and statin use. Results No cardiovascular risk factor differed significantly among current users and non-users of NSAIDs, COX-2 inhibitors, methotrexate and TNF-α blockers. Serum HDL cholesterol concentrations were significantly higher in patients currently receiving corticosteroids (42.2 ± 10.5 vs. 50.2 ± 15.3 mg/dL, adjusted P < 0.001). Diastolic blood pressure (75.9 ± 11.2 vs. 72.0 ± 9.1 mm Hg, adjusted P = 0.02), serum LDL cholesterol (115.6 ± 34.7 vs. 103.7 ± 27.8 mg/dL, adjusted P = 0.03) and triglyceride concentrations (157.7 ± 202.6 vs. 105.5 ± 50.5 mg/dL, adjusted P = 0.03) were significantly lower in patients taking antimalarial drugs. Plasma glucose was significantly lower in current lefunomide users (93.0 ± 19.2 vs. 83.6 ± 13.4 mg/dL, adjusted P = 0.006). Conclusions In a cross-sectional setting drugs used to treat RA did not have major adverse effects on cardiovascular risk factors and use of antimalarials was associated with beneficial lipid profiles. PMID:19684849

COX-2 verexpression in pretreatment biopsies predicts response of rectal cancers to neoadjuvant radiochemotherapy

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

Smith, Fraser M.; Reynolds, John V.; Kay, Elaine W.

2006-02-01

Purpose: To determine the utility of COX-2 expression as a response predictor for patients with rectal cancer who are undergoing neoadjuvant radiochemotherapy (RCT). Methods and Materials: Pretreatment biopsies (PTB) from 49 patients who underwent RCT were included. COX-2 and proliferation in PTB were assessed by immunohistochemistry (IHC) and apoptosis was detected by TUNEL stain. Response to treatment was assessed by a 5-point tumor-regression grade (TRG) based on the ratio of residual tumor to fibrosis. Results: Good response (TRG 1 + 2), moderate response (TRG 3), and poor response (TRG 4 + 5) were seen in 21 patients (42%), 11 patientsmore » (22%), and 17 patients (34%), respectively. Patients with COX-2 overexpression in PTB were more likely to demonstrate moderate or poor response (TRG 3 + 4) to treatment than were those with normal COX-2 expression (p = 0.026, chi-square test). Similarly, poor response was more likely if patients had low levels of spontaneous apoptosis in PTBs (p = 0.0007, chi-square test). Conclusions: COX-2 overexpression and reduced apoptosis in PTB can predict poor response of rectal cancer to RCT. As COX-2 inhibitors are commercially available, their administration to patients who overexpress COX-2 warrants assessment in clinical trials in an attempt to increase overall response rates.« less

Socioeconomic status inconsistency and risk of stroke among Japanese middle-aged women.

PubMed

Honjo, Kaori; Iso, Hiroyasu; Inoue, Manami; Sawada, Norie; Tsugane, Shoichiro

2014-09-01

Little research has been conducted to examine the effect of inconsistencies in socioeconomic status on cardiovascular health. In particular, no studies have been reported in Asian countries, including Japan, which is thought to have high socioeconomic status inconsistency among women. We examined the effect of status inconsistency between education level and occupation on stroke risk in a prospective 20-year study of 14 742 middle-aged Japanese women included in the prospective Japan Public Health Center-based (JPHC) Study Cohort I in 1990. Status inconsistency between education level and occupation was determined (qualified, overqualified, and underqualified), and the association with risk of stroke was examined. Cox proportional regression analysis was used to determine hazard ratios, which were adjusted for age, marital status, and geographical area. Adjusted hazard ratio for stroke in overqualified compared with qualified women was 2.06 (95% confidence interval, 1.13-3.78). Adjusted hazard ratios for stroke among highly educated manual workers and workers in service industry were 3.47 (95% confidence interval, 1.54-7.84) and 3.21 (95% confidence interval, 1.49-6.90), respectively, when compared with highly educated professionals/managers. High academic qualifications without an appropriate job could be a risk factor for stroke among Japanese women. Our result suggests that status inconsistency could be a potential explanation for the increased stroke risk among highly educated women. © 2014 American Heart Association, Inc.

Lung cancer survival in England: trends in non-small-cell lung cancer survival over the duration of the National Lung Cancer Audit

PubMed Central

Khakwani, A; Rich, A L; Powell, H A; Tata, L J; Stanley, R A; Baldwin, D R; Duffy, J P; Hubbard, R B

2013-01-01

Background: In comparison with other European and North American countries, England has poor survival figures for lung cancer. Our aim was to evaluate the changes in survival since the introduction of the National Lung Cancer Audit (NLCA). Methods: We used data from the NLCA to identify people with non-small-cell lung cancer (NSCLC) and stratified people according to their performance status (PS) and clinical stage. Using Cox regression, we calculated hazard ratios (HRs) for death according to the year of diagnosis from 2004/2005 to 2010; adjusted for patient features including age, sex and co-morbidity. We also assessed whether any changes in survival were explained by the changes in surgical resection rates or histological subtype. Results: In this cohort of 120 745 patients, the overall median survival did not change; but there was a 1% annual improvement in survival over the study period (adjusted HR 0.99, 95% confidence interval (CI) 0.98–0.99). Survival improvement was only seen in patients with good PS and early stage (adjusted HR 0.97, 95% CI 0.95–0.99) and this was partly accounted for by changes in resection rates. Conclusion: Survival has only improved for a limited group of people with NSCLC and increasing surgical resection rates appeared to explain some of this improvement. PMID:24052044

Risk of hypersensitivity pneumonitis and interstitial lung diseases among pigeon breeders.

PubMed

Cramer, Christine; Schlünssen, Vivi; Bendstrup, Elisabeth; Stokholm, Zara Ann; Vestergaard, Jesper Medom; Frydenberg, Morten; Kolstad, Henrik Albert

2016-09-01

We studied the risk of hypersensitivity pneumonitis and other interstitial lung diseases (ILDs) among pigeon breeders.This is a retrospective follow-up study from 1980 to 2013 of 6920 pigeon breeders identified in the records of the Danish Racing Pigeon Association. They were compared with 276 800 individually matched referents randomly drawn from the Danish population. Hospital based diagnoses of hypersensitivity pneumonitis and other ILDs were identified in the National Patient Registry 1977-2013. Stratified Cox regression analyses estimated the hazard ratios (HR) of hypersensitivity pneumonitis and other ILDs adjusted for occupation, residence and redeemed prescription of medication with ILDs as a possible side-effect. Subjects were censored at death, emigration or a diagnosis of connective tissue disease.The overall incidence rate of ILD was 77.4 per 100 000 person-years among the pigeon breeders and 50.0 among the referents. This difference corresponded to an adjusted HR of 1.56 (95% CI 1.26-1.94). The adjusted HRs of hypersensitivity pneumonitis and other ILDs for pigeon breeders were 14.36 (95% CI 8.10-25.44) and 1.33 (95% CI 1.05-1.69), respectively.This study shows an increased risk of ILD among pigeon breeders compared with the referent population. Protective measures are recommended even though ILD leading to hospital contact remains rare among pigeon breeders. Copyright ©ERS 2016.

Heart Rate Response to a Timed Walk & Cardiovascular Outcomes in Older Adults: The Cardiovascular Health Study

PubMed Central

Girotra, Saket; Kitzman, Dalane W.; Kop, Willem J.; Stein, Phyllis K.; Gottdiener, John S.; Mukamal, Kenneth J.

2012-01-01

OBJECTIVES To determine the relationship between heart rate response during low-grade physical exertion (six-minute walk) with mortality and adverse cardiovascular outcomes in the elderly. METHODS Participants in the Cardiovascular Health Study, who completed a six-minute walk test, were included. We used delta heart rate (difference between post-walk heart rate and resting heart rate) as a measure of chronotropic response and examined its association with 1) all-cause mortality and 2) incident coronary heart disease (CHD) event, using multivariable Cox regression models. RESULTS We included 2224 participants (mean age 77±4 years; 60% women, 85% white). The average delta heart rate was 26 beats/min. Participants in the lowest tertile of delta heart rate (<20 beats/min) had higher risk-adjusted mortality (hazard ratio [HR] 1.18; 95% confidence interval [CI][1.00, 1.40]) and incident CHD (HR 1.37; 95% CI[1.05, 1.78]) compared to subjects in the highest tertile (≥30 beats/min), with a significant linear trend across tertiles (P for trend <0.05 for both outcomes). This relationship was not significant after adjustment for distance walked. CONCLUSION Impaired chronotropic response during six-minute walk test was associated with an increased risk of mortality and incident CHD among the elderly. This association was attenuated after adjusting for distance walked. PMID:22722364

Traffic air pollution and mortality from cardiovascular disease and all causes: a Danish cohort study.

PubMed

Raaschou-Nielsen, Ole; Andersen, Zorana Jovanovic; Jensen, Steen Solvang; Ketzel, Matthias; Sørensen, Mette; Hansen, Johnni; Loft, Steffen; Tjønneland, Anne; Overvad, Kim

2012-09-05

Traffic air pollution has been linked to cardiovascular mortality, which might be due to co-exposure to road traffic noise. Further, personal and lifestyle characteristics might modify any association. We followed up 52 061 participants in a Danish cohort for mortality in the nationwide Register of Causes of Death, from enrollment in 1993-1997 through 2009, and traced their residential addresses from 1971 onwards in the Central Population Registry. We used dispersion-modelled concentration of nitrogen dioxide (NO₂) since 1971 as indicator of traffic air pollution and used Cox regression models to estimate mortality rate ratios (MRRs) with adjustment for potential confounders. Mean levels of NO₂ at the residence since 1971 were significantly associated with mortality from cardiovascular disease (MRR, 1.26; 95% confidence interval [CI], 1.06-1.51, per doubling of NO₂ concentration) and all causes (MRR, 1.13; 95% CI, 1.04-1.23, per doubling of NO₂ concentration) after adjustment for potential confounders. For participants who ate < 200 g of fruit and vegetables per day, the MRR was 1.45 (95% CI, 1.13-1.87) for mortality from cardiovascular disease and 1.25 (95% CI, 1.11-1.42) for mortality from all causes. Traffic air pollution is associated with mortality from cardiovascular diseases and all causes, after adjustment for traffic noise. The association was strongest for people with a low fruit and vegetable intake.

Cancer mortality in women and men who survived the siege of Leningrad (1941-1944).

PubMed

Koupil, Ilona; Plavinskaja, Svetlana; Parfenova, Nina; Shestov, Dmitri B; Danziger, Phoebe Day; Vågerö, Denny

2009-03-15

The population of Leningrad suffered from severe starvation, cold and psychological stress during the siege in World War II in 1941-1944. We investigated the long-term effects of the siege on cancer mortality in 3,901 men and 1,429 women, born between 1910 and 1940. All study subjects were residents of St. Petersburg, formerly Leningrad, between 1975 and 1982. One third of them had experienced the siege as children, adolescents or young adults (age range, 1-31 years at the peak of starvation in 1941-1942). Associations of siege exposure with risk of death from cancer were studied using a multivariable Cox regression, stratified by gender and period of birth, adjusted for age, smoking, alcohol and social characteristics, from 1975 to 1977 (men) and 1980 to 1982, respectively (women), until the end of 2005. Women who were 10-18 years old at the peak of starvation were taller as adults (age-adjusted difference, 1.7 cm; 95% CI, 0.5-3.0) and had a higher risk of dying from breast cancer compared with unexposed women born during the same period (age-adjusted HR, 9.9; 95% CI, 1.1-86.5). Mortality from prostate cancer was nonsignificantly higher in exposed men. The experience of severe starvation and stress during childhood and adolescence may have long-term effects on cancer in surviving men and women.

Gastroduodenal Ulcers and ABO Blood Group: the Japan Nurses' Health Study (JNHS).

PubMed

Alkebsi, Lobna; Ideno, Yuki; Lee, Jung-Su; Suzuki, Shosuke; Nakajima-Shimada, Junko; Ohnishi, Hiroshi; Sato, Yasunori; Hayashi, Kunihiko

2018-01-05

Although several studies have shown that blood type O is associated with increased risk of peptic ulcer, few studies have investigated these associations in Japan. We sought to investigate the association between the ABO blood group and risk of gastroduodenal ulcers (GDU) using combined analysis of both retrospective and prospective data from a large cohort study of Japanese women, the Japan Nurses' Health Study (JNHS; n = 15,019). The impact of the ABO blood group on GDU risk was examined using Cox regression analysis to estimate hazard ratios (HRs) and 95% confidence intervals (CI), with adjustment for potential confounders. Compared with women with non-O blood types (A, B, and AB), women with blood type O had a significantly increased risk of GDU from birth (multivariable-adjusted HR 1.18; 95% CI, 1.04-1.34). Moreover, the highest cumulative incidence of GDU was observed in women born pre-1956 with blood type O. In a subgroup analysis stratified by birth year (pre-1956 or post-1955), the multivariable-adjusted HR of women with blood type O was 1.22 (95% CI, 1.00-1.49) and 1.15 (95% CI, 0.98-1.35) in the pre-1956 and post-1955 groups, respectively. In this large, combined, ambispective cohort study of Japanese women, older women with blood type O had a higher risk of developing GDU than those with other blood types.

Statin use after esophageal cancer diagnosis and survival: A population based cohort study.

PubMed

Cardwell, Chris R; Spence, Andrew D; Hughes, Carmel M; Murray, Liam J

2017-06-01

A recent epidemiological study of esophageal cancer patients concluded statin use post-diagnosis was associated with large (38%) and significant reductions in cancer-specific mortality. We investigated statin use and cancer-specific mortality in a large population-based cohort of esophageal cancer patients. Newly diagnosed [2009-2012] esophageal cancer patients were identified from the Scottish Cancer Registry and linked with the Prescribing Information System and Scotland Death Records (to January 2015). Time-dependent Cox regression models were used to calculate hazard ratios (HR) for cancer-specific mortality and 95% confidence intervals (CIs) by post-diagnostic statin use (using a 6 month lag to reduce reverse causation) and to adjust these HRs for potential confounders. 1921 esophageal cancer patients were included in the main analysis, of whom 651 (34%) used statins after diagnosis. There was little evidence of a reduction in esophageal cancer-specific mortality in statin users compared with non-users after diagnosis (adjusted HR=0.93, 95% CI, 0.81, 1.07) and no dose response associations were seen. However, statin users compared with non-users in the year before diagnosis had a weak reduction in esophageal cancer-specific mortality (adjusted HR=0.88, 95% CI, 0.79, 0.99). In this large population-based esophageal cancer cohort, there was little evidence of a reduction in esophageal cancer-specific mortality with statin use after diagnosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Smoking and hemorrhagic stroke mortality in a prospective cohort study of older Chinese.

PubMed

Xu, Lin; Schooling, Catherine Mary; Chan, Wai Man; Lee, Siu Yin; Leung, Gabriel M; Lam, Tai Hing

2013-08-01

Hemorrhagic stroke is more common in non-Western settings and does not always share risk factors with other cardiovascular diseases. The association of smoking with hemorrhagic stroke subtypes has not been established. We examined the association of cigarette smoking with hemorrhagic stroke, by subtype (intracerebral hemorrhage and subarachnoid hemorrhage), in a large cohort of older Chinese from Hong Kong. Multivariable Cox regression analysis was used to assess the adjusted associations of smoking at baseline with death from hemorrhagic stroke and its subtypes, using a population-based prospective cohort of 66 820 Chinese aged>65 years enrolled from July 1998 to December 2001 at all the 18 Elderly Health Centers of the Hong Kong Government Department of Health and followed until May 31, 2012. After follow-up for an average of 10.9 years (SD=3.1), 648 deaths from hemorrhagic stroke had occurred, of which 530 (82%) were intracerebral hemorrhage. Current smoking was associated with a higher risk of hemorrhagic stroke (hazard ratio, 2.19; 95% confidence interval, 1.49-3.22), intracerebral hemorrhage (1.94; 1.25-3.01), and subarachnoid hemorrhage (3.58; 1.62-7.94), adjusted for age, sex, education, public assistance, housing type, monthly expenditure, alcohol use, and exercise. Further adjustment for hypertension and body mass index slightly changed the estimates. Smoking is strongly associated with hemorrhagic stroke mortality, particularly for subarachnoid hemorrhage.

Association of higher parental and grandparental education and higher school grades with risk of hospitalization for eating disorders in females: the Uppsala birth cohort multigenerational study.

PubMed

Ahrén-Moonga, Jennie; Silverwood, Richard; Klinteberg, Britt Af; Koupil, Ilona

2009-09-01

Eating disorders are a leading cause of disease burden among young women. This study investigated associations of social characteristics of parents and grandparents, sibling position, and school performance with incidence of eating disorders. The authors studied Swedish females born in 1952-1989 (n = 13,376), third-generation descendants of a cohort born in Uppsala in 1915-1929. Data on grandparental and parental social characteristics, sibling position, school grades, hospitalizations, emigrations, and deaths were obtained by register linkages. Associations with incidence of hospitalization for eating disorders were studied with multivariable Cox regression, adjusted for age and study period. Overall incidence of hospitalization for eating disorders was 32.0/100,000 person-years. Women with more highly educated parents and maternal grandparents were at higher risk (hazard ratio for maternal grandmother with higher education relative to elementary education = 6.5, 95% confidence interval: 2.2, 19.3, adjusted for parental education). Independent of family social characteristics, women with the highest school grades had a higher risk of eating disorders (hazard ratio = 7.7, 95% confidence interval: 2.5, 24.1 for high compared with low grades in Swedish, adjusted for parental education). Thus, higher parental and grandparental education and higher school grades may increase risk of hospitalization for eating disorders in female offspring, possibly because of high internal and external demands.

Obesity Paradox: Comparison of Heart Failure Patients With and Without Comorbid Diabetes.

PubMed

Lee, Kyoung Suk; Moser, Debra K; Lennie, Terry A; Pelter, Michele M; Nesbitt, Thomas; Southard, Jeffrey A; Dracup, Kathleen

2017-03-01

Diabetes is a common comorbid condition in patients with heart failure and is strongly associated with poor outcomes. Patients with heart failure who have diabetes are more likely to be obese than are those without diabetes. Obesity is positively associated with survival in patients with heart failure, but how comorbid diabetes influences the relationship between obesity and favorable prognosis is unclear. To explore whether the relationship between body mass index and survival differs between patients with heart failure who do or do not have diabetes. The sample consisted of 560 ambulatory patients with heart failure (mean age, 66 years; mean body mass index, 32; diabetes, 41%). The association between body mass index and all-cause mortality was examined by using multivariate Cox proportional hazards regression after adjustments for covariates. In patients without diabetes, higher body mass index was associated with a lower risk for all-cause mortality after adjustments for covariates (hazard ratio, 0.952; 95% CI, 0.909-0.998). In patients with diabetes, body mass index was not predictive of all-cause death after adjustments for covariates. Obesity was a survival benefit in heart failure patients without comorbid diabetes but not in those with comorbid diabetes. The mechanisms underlying the difference in the relationship between obesity and survival due to the presence of diabetes in patients with heart failure need to be elucidated. ©2017 American Association of Critical-Care Nurses.

Surgery for left ventricular aneurysm: early and late survival after simple linear repair and endoventricular patch plasty.

PubMed

Lundblad, Runar; Abdelnoor, Michel; Svennevig, Jan Ludvig

2004-09-01

Simple linear resection and endoventricular patch plasty are alternative techniques to repair postinfarction left ventricular aneurysm. The aim of the study was to compare these 2 methods with regard to early mortality and long-term survival. We retrospectively reviewed 159 patients undergoing operations between 1989 and 2003. The epidemiologic design was of an exposed (simple linear repair, n = 74) versus nonexposed (endoventricular patch plasty, n = 85) cohort with 2 endpoints: early mortality and long-term survival. The crude effect of aneurysm repair technique versus endpoint was estimated by odds ratio, rate ratio, or relative risk and their 95% confidence intervals. Stratification analysis by using the Mantel-Haenszel method was done to quantify confounders and pinpoint effect modifiers. Adjustment for multiconfounders was performed by using logistic regression and Cox regression analysis. Survival curves were analyzed with the Breslow test and the log-rank test. Early mortality was 8.2% for all patients, 13.5% after linear repair and 3.5% after endoventricular patch plasty. When adjusted for multiconfounders, the risk of early mortality was significantly higher after simple linear repair than after endoventricular patch plasty (odds ratio, 4.4; 95% confidence interval, 1.1-17.8). Mean follow-up was 5.8 +/- 3.8 years (range, 0-14.0 years). Overall 5-year cumulative survival was 78%, 70.1% after linear repair and 91.4% after endoventricular patch plasty. The risk of total mortality was significantly higher after linear repair than after endoventricular patch plasty when controlled for multiconfounders (relative risk, 4.5; 95% confidence interval, 2.0-9.7). Linear repair dominated early in the series and patch plasty dominated later, giving a possible learning-curve bias in favor of patch plasty that could not be adjusted for in the regression analysis. Postinfarction left ventricular aneurysm can be repaired with satisfactory early and late results. Surgical risk was lower and long-term survival was higher after endoventricular patch plasty than simple linear repair. Differences in outcome should be interpreted with care because of the retrospective study design and the chronology of the 2 repair methods.

Keeping data continuous when analyzing the prognostic impact of a tumor marker: an example with cathepsin D in breast cancer.

PubMed

Bossard, N; Descotes, F; Bremond, A G; Bobin, Y; De Saint Hilaire, P; Golfier, F; Awada, A; Mathevet, P M; Berrerd, L; Barbier, Y; Estève, J

2003-11-01

The prognostic value of cathepsin D has been recently recognized, but as many quantitative tumor markers, its clinical use remains unclear partly because of methodological issues in defining cut-off values. Guidelines have been proposed for analyzing quantitative prognostic factors, underlining the need for keeping data continuous, instead of categorizing them. Flexible approaches, parametric and non-parametric, have been proposed in order to improve the knowledge of the functional form relating a continuous factor to the risk. We studied the prognostic value of cathepsin D in a retrospective hospital cohort of 771 patients with breast cancer, and focused our overall survival analysis, based on the Cox regression, on two flexible approaches: smoothing splines and fractional polynomials. We also determined a cut-off value from the maximum likelihood estimate of a threshold model. These different approaches complemented each other for (1) identifying the functional form relating cathepsin D to the risk, and obtaining a cut-off value and (2) optimizing the adjustment for complex covariate like age at diagnosis in the final multivariate Cox model. We found a significant increase in the death rate, reaching 70% with a doubling of the level of cathepsin D, after the threshold of 37.5 pmol mg(-1). The proper prognostic impact of this marker could be confirmed and a methodology providing appropriate ways to use markers in clinical practice was proposed.

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.

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.

Cox Regression Models with Functional Covariates for Survival Data.

PubMed

Gellar, Jonathan E; Colantuoni, Elizabeth; Needham, Dale M; Crainiceanu, Ciprian M

2015-06-01

We extend the Cox proportional hazards model to cases when the exposure is a densely sampled functional process, measured at baseline. The fundamental idea is to combine penalized signal regression with methods developed for mixed effects proportional hazards models. The model is fit by maximizing the penalized partial likelihood, with smoothing parameters estimated by a likelihood-based criterion such as AIC or EPIC. The model may be extended to allow for multiple functional predictors, time varying coefficients, and missing or unequally-spaced data. Methods were inspired by and applied to a study of the association between time to death after hospital discharge and daily measures of disease severity collected in the intensive care unit, among survivors of acute respiratory distress syndrome.

Phobic anxiety symptom scores and incidence of type 2 diabetes in US men and women

PubMed Central

Farvid, Maryam S; Qi, Lu; Hu, Frank B; Kawachi, Ichiro; Okereke, Olivia I; Kubzansky, Laura; Willett, Walter C

2013-01-01

Context Emotional stress may be a risk factor for type 2 diabetes (T2D), but the relation between phobic anxiety symptom scores and risk of T2D is uncertain. Objective To evaluate prospectively the association between phobic anxiety symptom scores and incident T2D in three cohorts of US men and women. Design, Setting and Patients We followed 30,830 men in the Health Professional’s Follow-Up Study (HPFS) (1988–2008), 69,336 women in the Nurses’ Health Study (NHS) (1988–2008), and 80,120 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, was 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. Results During 3,110,248 person-years of follow-up, we documented 12,876 incident T2D cases. In multivariable Cox regression models with adjustment for major lifestyle and dietary risk factors, the HRs of T2D across categories of increasing levels of CCI (scores= 2-<3, 3-<4, 4-<6, 6), compared with a score of <2, were increased significantly by 6%, 10%, 11% and 13% (Ptrend =0.0005) for NHS; and by 19%, 11%, 22%, and 29% (Ptrend <0.0001) for NHS II. Each score increment in CCI was associated with 3% higher risk of T2D in NHS (HRs, 1.03, 95%CI:1.02-1.04) and 4% higher risk of T2D in NHS II (HRs, 1.04, 95%CI:1.03-1.05). Further adjustment for self-reported depression and antidepressant use did not change the results. In HPFS, the association between CCI and T2D was not significant after adjusting for lifestyle variables. Conclusion Our results suggest that higher phobic anxiety symptom scores are associated with an increased risk of T2D in women. PMID:24184473

Comparative economic evaluation of home-based and hospital-based palliative care for terminal cancer patients.

PubMed

Kato, Koki; Fukuda, Haruhisa

2017-11-01

To quantify the difference between adjusted costs for home-based palliative care and hospital-based palliative care in terminally ill cancer patients. We carried out a case-control study of home-care patients (cases) who had died at home between January 2009 and December 2013, and hospital-care patients (controls) who had died at a hospital between April 2008 and December 2013. Data on patient characteristics were obtained from insurance claims data and medical records. We identified the determinants of home care using a multivariate logistic regression analysis. Cox proportional hazards analysis was used to examine treatment duration in both types of care, and a generalized linear model was used to estimate the reduction in treatment costs associated with home care. The case and control groups comprised 48 and 99 patients, respectively. Home care was associated with one or more person(s) living with the patient (adjusted OR 6.54, 95% CI 1.18-36.05), required assistance for activities of daily living (adjusted OR 3.61, 95% CI 1.12-10.51), non-use of oxygen inhalation therapy (adjusted OR 12.75, 95% CI 3.53-46.02), oral or suppository opioid use (adjusted OR 5.74, 95% CI 1.11-29.54) and transdermal patch opioid use (adjusted OR 8.30, 95% CI 1.97-34.93). The adjusted hazard ratio of home care for treatment duration was not significant (adjusted OR 0.95, 95% CI 0.59-1.53). However, home care was significantly associated with a reduction of $7523 (95% CI $7093-7991, P = 0.015) in treatment costs. Despite similar treatment durations between the groups, treatment costs were substantially lower in the home-care group. These findings might inform the policymaking process for improving the home-care support system. Geriatr Gerontol Int 2017; 17: 2247-2254. © 2017 Japan Geriatrics Society.

Serum Bicarbonate and Kidney Disease Progression and Cardiovascular Outcome in Patients With Diabetic Nephropathy: A Post Hoc Analysis of the RENAAL (Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan) Study and IDNT (Irbesartan Diabetic Nephropathy Trial).

PubMed

Schutte, Elise; Lambers Heerspink, Hiddo J; Lutgers, Helen L; Bakker, Stephan J L; Vart, Priya; Wolffenbuttel, Bruce H R; Umanath, Kausik; Lewis, Julia B; de Zeeuw, Dick; Gansevoort, Ron T

2015-09-01

Low serum bicarbonate level has been reported to be an independent predictor of kidney function decline and mortality in patients with chronic kidney disease. Mechanisms underlying low serum bicarbonate levels may differ in patients with and without diabetes. We aimed to specifically investigate the association of serum bicarbonate level with kidney disease progression and cardiovascular outcome in a cohort of patients with type 2 diabetes and nephropathy. Post hoc analysis of 2 multicenter randomized controlled trials. 2,628 adults with type 2 diabetes and nephropathy. Serum bicarbonate level. Incidence of: (1) end-stage renal disease (ESRD), (2) ESRD or doubling of serum creatinine level, (3) all-cause mortality, (4) cardiovascular events (fatal/nonfatal stroke/myocardial infarction), and (5) heart failure. Serum bicarbonate was measured at baseline as total carbon dioxide. Associations of baseline serum bicarbonate level with end points were investigated using Cox regression models. Serum bicarbonate levels were studied as a continuous variable and stratified in quartiles. Follow-up was 2.8±1.0 (SD) years. Cox regression analyses showed that serum bicarbonate level had inverse associations with incident ESRD (HR, 0.91; 95% CI, 0.89-0.93; P<0.001) and incidence of the combined end point of ESRD or serum creatinine doubling (HR, 0.94; 95% CI, 0.92-0.96; P<0.001). These associations were independent of age, sex, and cardiovascular risk factors, but disappeared after adjustment for baseline estimated glomerular filtration rate (all P>0.05). Analysis of bicarbonate quartiles showed similar results for the quartile with the lowest bicarbonate (≤21 mEq/L) versus the quartile with normal bicarbonate levels (24-26 mEq/L). There was no association of bicarbonate level with cardiovascular events and heart failure. Post hoc analysis and single measurement of serum bicarbonate. In this cohort of patients with type 2 diabetes with nephropathy, serum bicarbonate level associations with kidney disease end points were not retained after adjustment for estimated glomerular filtration rate, which is in contrast to results of earlier studies in nondiabetic populations. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Mortality associated with bevacizumab intravitreal injections in age-related macular degeneration patients after acute myocardial infarct: a retrospective population-based survival analysis.

PubMed

Hanhart, Joel; Comaneshter, Doron S; Freier-Dror, Yossi; Vinker, Shlomo

2018-04-01

Intraocular injections of antivascular endothelial growth factor (VEGF) agents are currently the main therapy in age-related macular degeneration (AMD). The safety of bevacizumab, an anti-VEGF compound frequently delivered off label, is debated, particularly for high-group risks. We aim to analyze the mortality associated with intravitreal injections of bevacizumab for AMD in patients previously diagnosed with acute myocardial infarct (MI). In a national database, we identified bevacizumab-treated AMD patients with a diagnosis of MI prior to their first bevacizumab injection, delivered between September 2008 and October 2014 (n = 2100). We then generated sub-groups of patients treated within 3 months (n = 11), 6 months (n = 24), 12 months (n = 52), and 24 months (n = 124) after MI. Those patients were compared to age- and gender-matched members that had a MI at the same time and had never been exposed to anti-VEGF. Survival analysis was performed using propensity score-adjusted Cox regression. Bevacizumab-treated patients were slightly and insignificantly older than controls (mean age 83.25 vs 83.19 year, P = .75). Gender distribution was similar. In a Cox regression adjusted with propensity score, the following differences in mortality were found: within 3 months between MI and initiation of bevacizumab treatment, OR = 6.22 (95% C.I 1.08-35.97, P < .05); within 6 months, OR = 2.37 (95% C.I 0.93-6.02, P = .071); within 12 months, OR = 3.00 (95% C.I 1.44-6.28, P < .01); within 24 months after MI, OR = 2.24 (95% C.I 1.35-3.70, P < .01); and MI any time prior to first bevacizumab injection, OR = 1.71 (95% C.I 1.53-1.92, P < .001). We report increased mortality associated with the use of intravitreal bevacizumab in AMD patients after MI, compared to age- and gender-matched post-MI patients with no exposure to any anti-VEGF agent. Caution should be taken while offering bevacizumab to AMD patients after MI.

Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study.

PubMed

Heffron, Renee; Donnell, Deborah; Rees, Helen; Celum, Connie; Mugo, Nelly; Were, Edwin; de Bruyn, Guy; Nakku-Joloba, Edith; Ngure, Kenneth; Kiarie, James; Coombs, Robert W; Baeten, Jared M

2012-01-01

Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. We aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners. In this prospective study, we followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries. Among injectable and oral hormonal contraceptive users and non-users, we compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men. The primary outcome measure was HIV-1 seroconversion. We used Cox proportional hazards regression and marginal structural modelling to assess the effect of contraceptive use on HIV-1 risk. Among 1314 couples in which the HIV-1-seronegative partner was female (median follow-up 18·0 [IQR 12·6-24·2] months), rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not (adjusted hazard ratio 1·98, 95% CI 1·06-3·68, p=0·03). Among 2476 couples in which the HIV-1-seronegative partner was male (median follow-up 18·7 [IQR 12·8-24·2] months), rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception (adjusted hazard ratio 1·97, 95% CI 1·12-3·45, p=0·02). Marginal structural model analyses generated much the same results to the Cox proportional hazards regression. Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, especially injectable methods, and about the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1. US National Institutes of Health and the Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Timing of angiography with a routine invasive strategy and long-term outcomes in non-ST-segment elevation acute coronary syndrome: a collaborative analysis of individual patient data from the FRISC II (Fragmin and Fast Revascularization During Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction) Trials.

PubMed

Damman, Peter; van Geloven, Nan; Wallentin, Lars; Lagerqvist, Bo; Fox, Keith A A; Clayton, Tim; Pocock, Stuart J; Hirsch, Alexander; Windhausen, Fons; Tijssen, Jan G P; de Winter, Robbert J

2012-02-01

This study sought to investigate long-term outcomes after early or delayed angiography in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS) undergoing a routine invasive management. The optimal timing of angiography in patients with nSTE-ACS is currently a topic for debate. Long-term follow-up after early (within 2 days) angiography versus delayed (within 3 to 5 days) angiography was investigated in the FRISC-II (Fragmin and Fast Revascularization During Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction) (FIR) nSTE-ACS patient-pooled database. The main outcome was cardiovascular death or myocardial infarction up to 5-year follow-up. Hazard ratios (HR) were calculated with Cox regression models. Adjustments were made for the FIR risk score, study, and the propensity of receiving early angiography using inverse probability weighting. Of 2,721 patients originally randomized to the routine invasive arm, consisting of routine angiography and subsequent revascularization if suitable, 975 underwent early angiography and 1,141 delayed angiography. No difference was observed in 5-year cardiovascular death or myocardial infarction in unadjusted (HR: 1.06, 95% confidence interval [CI]: 0.79 to 1.42, p=0.61) and adjusted (HR: 0.93, 95% CI: 0.75 to 1.16, p=0.54) Cox regression models. In the FIR database of patients presenting with nSTE-ACS, the timing of angiography was not related to long-term cardiovascular mortality or myocardial infarction. (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes [ICTUS]; ISRCTN82153174. Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction [the Third Randomised Intervention Treatment of Angina Trials (RITA-3)]; ISRCTN07752711). Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Genetic Polymorphisms in RNA Binding Proteins Contribute to Breast Cancer Survival

PubMed Central

Upadhyay, Rohit; Sanduja, Sandhya; Kaza, Vimala; Dixon, Dan A.

2012-01-01

The RNA-binding proteins TTP and HuR control expression of numerous genes associated with breast cancer pathogenesis by regulating mRNA stability. However, the role of genetic variation in TTP (ZFP36) and HuR (ELAVL1) genes is unknown in breast cancer prognosis. A total of 251 breast cancer patients (170 Caucasians and 81 African-Americans) were enrolled and followed-up from 2001 to 2011 (or until death). Genotyping was performed for 10 SNPs in ZFP36 and 7 in ELAVL1 genes. On comparing both races with one another, significant differences were found for clinical and genetic variables. The influence of genetic polymorphisms on survival was analyzed by using Cox-regression, Kaplan-Meier analysis, and the log-rank test. Univariate (Kaplan-Meier/Cox-regression) and multivariate (Cox-regression) analysis showed that the TTP gene polymorphism ZFP36*2 A>G was significantly associated with poor prognosis of Caucasian patients (HR = 2.03; 95% CI = 1.09–3.76; P = 0.025; log-rank P = 0.022). None of the haplotypes, but presence of more than six risk genotypes in Caucasian patients, was significantly associated with poor prognosis (HR=2.42; 95% CI=1.17–4.99; P = 0.017; log-rank P = 0.007). The effect of ZFP36*2 A>G on gene expression was evaluated from patients' tissue samples. Both TTP mRNA and protein expression was significantly decreased in ZFP36*2 G allele carriers compared to A allele homozygotes. Conversely, upregulation of the TTP-target gene COX-2 was observed ZFP36*2 G allele carriers. Through its ability to attenuate TTP gene expression, the ZFP36*2 A>G gene polymorphism has appeared as a novel prognostic breast cancer marker in Caucasian patients. PMID:22907529

Assessing uncertainty in published risk estimates using ...

EPA Pesticide Factsheets

Introduction: The National Research Council recommended quantitative evaluation of uncertainty in effect estimates for risk assessment. This analysis considers uncertainty across model forms and model parameterizations with hexavalent chromium [Cr(VI)] and lung cancer mortality as an example. The objective is to characterize model uncertainty by evaluating estimates across published epidemiologic studies of the same cohort.Methods: This analysis was based on 5 studies analyzing a cohort of 2,357 workers employed from 1950-74 in a chromate production plant in Maryland. Cox and Poisson models were the only model forms considered by study authors to assess the effect of Cr(VI) on lung cancer mortality. All models adjusted for smoking and included a 5-year exposure lag, however other latency periods and model covariates such as age and race were considered. Published effect estimates were standardized to the same units and normalized by their variances to produce a standardized metric to compare variability within and between model forms. A total of 5 similarly parameterized analyses were considered across model form, and 16 analyses with alternative parameterizations were considered within model form (10 Cox; 6 Poisson). Results: Across Cox and Poisson model forms, adjusted cumulative exposure coefficients (betas) for 5 similar analyses ranged from 2.47 to 4.33 (mean=2.97, σ2=0.63). Within the 10 Cox models, coefficients ranged from 2.53 to 4.42 (mean=3.29, σ2=0.

Primary Surgery vs Radiotherapy for Early Stage Oral Cavity Cancer.

PubMed

Ellis, Mark A; Graboyes, Evan M; Wahlquist, Amy E; Neskey, David M; Kaczmar, John M; Schopper, Heather K; Sharma, Anand K; Morgan, Patrick F; Nguyen, Shaun A; Day, Terry A

2018-04-01

Objective The goal of this study is to determine the effect of primary surgery vs radiotherapy (RT) on overall survival (OS) in patients with early stage oral cavity squamous cell carcinoma (OCSCC). In addition, this study attempts to identify factors associated with receiving primary RT. Study Design Retrospective cohort study. Setting National Cancer Database (NCDB, 2004-2013). Subjects and Methods Reviewing the NCDB from 2004 to 2013, patients with early stage I to II OCSCC were identified. Kaplan-Meier estimates of survival, Cox regression analysis, and propensity score matching were used to examine differences in OS between primary surgery and primary RT. Multivariable logistic regression analysis was performed to identify factors associated with primary RT. Results Of the 20,779 patients included in the study, 95.4% (19,823 patients) underwent primary surgery and 4.6% (956 patients) underwent primary RT. After adjusting for covariates, primary RT was associated with an increased risk of mortality (adjusted hazard ratio [aHR], 1.97; 99% confidence interval [CI], 1.74-2.22). On multivariable analysis, factors associated with primary RT included age ≥70 years, black race, Medicaid or Medicare insurance, no insurance, oral cavity subsite other than tongue, clinical stage II disease, low-volume treatment facilities, and earlier treatment year. Conclusion Primary RT for early stage OCSCC is associated with increased mortality. Approximately 5% of patients receive primary RT; however, this percentage is decreasing. Patients at highest risk for receiving primary RT include those who are elderly, black, with public insurance, and treated at low-volume facilities.

The predictive value of the antioxidative function of HDL for cardiovascular disease and graft failure in renal transplant recipients.

PubMed

Leberkühne, Lynn J; Ebtehaj, Sanam; Dimova, Lidiya G; Dikkers, Arne; Dullaart, Robin P F; Bakker, Stephan J L; Tietge, Uwe J F

2016-06-01

Protection of low-density lipoproteins (LDL) against oxidative modification is a key anti-atherosclerotic property of high-density lipoproteins (HDL). This study evaluated the predictive value of the HDL antioxidative function for cardiovascular mortality, all-cause mortality and chronic graft failure in renal transplant recipients (RTR). The capacity of HDL to inhibit native LDL oxidation was determined in vitro in a prospective cohort of renal transplant recipients (RTR, n = 495, median follow-up 7.0 years). The HDL antioxidative functionality was significantly higher in patients experiencing graft failure (57.4 ± 9.7%) than in those without (54.2 ± 11.3%; P = 0.039), while there were no differences for cardiovascular and all-cause mortality. Specifically glomerular filtration rate (P = 0.001) and C-reactive protein levels (P = 0.006) associated independently with antioxidative functionality in multivariate linear regression analyses. Cox regression analysis demonstrated a significant relationship between antioxidative functionality of HDL and graft failure in age-adjusted analyses, but significance was lost following adjustment for baseline kidney function and inflammatory load. No significant association was found between HDL antioxidative functionality and cardiovascular and all-cause mortality. This study demonstrates that the antioxidative function of HDL (i) does not predict cardiovascular or all-cause mortality in RTR, but (ii) conceivably contributes to the development of graft failure, however, not independent of baseline kidney function and inflammatory load. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Subjective life expectancy and actual mortality: results of a 10-year panel study among older workers.

PubMed

van Solinge, Hanna; Henkens, Kène

2018-06-01

This research examined the judgemental process underlying subjective life expectancy (SLE) and the predictive value of SLE on actual mortality in older adults in the Netherlands. We integrated theoretical insights from life satisfaction research with existing models of SLE. Our model differentiates between bottom-up (objective data of any type) and top-down factors (psychological variables). The study used data from the first wave of the Netherlands Interdisciplinary Demographic Institute Work and Retirement Panel. This is a prospective cohort study among Dutch older workers. The analytical sample included 2278 individuals, assessed at age 50-64 in 2001, with vital statistics tracked through 2011. We used a linear regression model to estimate the impact of bottom-up and top-down factors on SLE. Cox proportional hazard regression was used to determine the impact of SLE on the timing of mortality, crude and adjusted for actuarial correlates of general life expectancy, family history, health and trait-like dispositions. Results reveal that psychological variables play a role in the formation of SLE. Further, the results indicate that SLE predicts actual mortality, crude and adjusted for socio-demographic, biomedical and psychological confounders. Education has an additional effect on mortality. Those with higher educational attainment were less likely to die within the follow-up period. This SES gradient in mortality was not captured in SLE. The findings indicate that SLE is an independent predictor of mortality in a pre-retirement cohort in the Netherlands. SLE does not fully capture educational differences in mortality. Particularly, higher-educated individuals underestimate their life expectancy.

Race, Wealth, and Solid Waste Facilities in North Carolina

PubMed Central

Norton, Jennifer M.; Wing, Steve; Lipscomb, Hester J.; Kaufman, Jay S.; Marshall, Stephen W.; Cravey, Altha J.

2007-01-01

Background Concern has been expressed in North Carolina that solid waste facilities may be disproportionately located in poor communities and in communities of color, that this represents an environmental injustice, and that solid waste facilities negatively impact the health of host communities. Objective Our goal in this study was to conduct a statewide analysis of the location of solid waste facilities in relation to community race and wealth. Methods We used census block groups to obtain racial and economic characteristics, and information on solid waste facilities was abstracted from solid waste facility permit records. We used logistic regression to compute prevalence odds ratios for 2003, and Cox regression to compute hazard ratios of facilities issued permits between 1990 and 2003. Results The adjusted prevalence odds of a solid waste facility was 2.8 times greater in block groups with ≥50% people of color compared with block groups with < 10% people of color, and 1.5 times greater in block groups with median house values < $60,000 compared with block groups with median house values ≥$100,000. Among block groups that did not have a previously permitted solid waste facility, the adjusted hazard of a new permitted facility was 2.7 times higher in block groups with ≥50% people of color compared with block groups with < 10% people of color. Conclusion Solid waste facilities present numerous public health concerns. In North Carolina solid waste facilities are disproportionately located in communities of color and low wealth. In the absence of action to promote environmental justice, the continued need for new facilities could exacerbate this environmental injustice. PMID:17805426

Prevalence, Incidence, and Clearance of Anogenital Warts in Kenyan Men Reporting High-Risk Sexual Behavior, Including Men Who Have Sex With Men

PubMed Central

Neme, Santiago; Wahome, Elizabeth; Mwashigadi, Grace; Thiong'o, Alexander N.; Stekler, Joanne D.; Wald, Anna; Sanders, Eduard J.; Graham, Susan M.

2015-01-01

Background. Human papillomavirus (HPV) causes a spectrum of disease, ranging from warts to cancer. Prevalence, incidence, and factors associated with anogenital warts in East African men are unknown. Methods. Kenyan men reporting high-risk sexual behavior were inspected for anogenital warts at enrollment and follow-up visits. Logistic regression was performed to identify associations with anogenital warts at baseline. Cox regression was performed to analyze predictors of incident anogenital warts, and Kaplan–Meier curves were used to estimate clearance. Results. Baseline anogenital wart prevalence in 1137 men was 2.9% (95% confidence interval [CI], 2.0%–4.0%) overall, 2.0% in human immunodeficiency virus (HIV)-uninfected men, and 9.4% in HIV-1-infected men (adjusted odds ratio, 5.43; 95% CI, 2.03–11.29). Over a median of 1.4 years, anogenital wart incidence among 1104 men was 5.3 (95% CI, 4.3–6.5) per 100 person-years. Having HIV-1 infection at baseline (adjusted hazard ratio [aHR], 1.66; 95% CI, 1.01–2.72) or a genital syndrome during follow-up (aHR, 4.78; 95% CI, 3.03–7.56) was associated with increased wart incidence. Wart clearance was lower in HIV-1-infected men (log-rank P<.001). Conclusions. Anogenital wart prevalence and incidence were increased in HIV-1-infected men, and anogenital warts co-occurred with other genital syndromes. Quadrivalent HPV vaccination should be recommended for young men in settings with high HIV-1 prevalence. PMID:26110169

Parity, Lactation, Bone Strength, and 16-year Fracture Risk in Adult Women: Findings From the Study of Women’s Health Across the Nation (SWAN)

PubMed Central

Mori, Takahiro; Ishii, Shinya; Greendale, Gail A.; Cauley, Jane A.; Ruppert, Kristine; Crandall, Carolyn J.; Karlamangla, Arun S.

2015-01-01

Our objective was to examine the associations of lifetime parity and accumulated length of lactation with bone strength in women prior to the menopause transition and fracture risk during and after the transition. Participants were 2239 pre- or early perimenopausal women from the Study of Women's Health Across the Nation (SWAN), ages 42–53 at baseline, who had no childbirths after age 42. Bone mineral density (BMD) was measured in the femoral neck and the lumbar spine at the baseline SWAN visit using dual-energy x-ray absorptiometry, and composite indices of femoral neck strength relative to load (in three failure modes: compression, bending, and impact) were calculated from femoral neck BMD, femoral neck size, and body size. Data on fractures after age 42 were collected for a median follow-up of 15.7 years (interquartile range, 11.4 –18.5 years). In multiple linear regression adjusted for covariates, lifetime parity was associated positively with femoral neck strength relative to load (0.024 standard deviation (SD) increment in impact strength index per childbirth, p= 0.049), but accumulated length of lactation was associated negatively with lumbar spine BMD (0.018 SD decrement per every additional 6 months of lactation p=0.040). In Cox proportional hazards regression adjusted for covariates, neither parity nor lactation was associated with fracture hazard after age 42. In conclusion, parity and lactation have little impact on peak bone strength prior to menopause, and do not affect fracture risk after age 42 over 16-year follow-up. PMID:25528102

Evaluating cardiovascular mortality in type 2 diabetes patients: an analysis based on competing risks Markov chains and additive regression models.

PubMed

Rosato, Rosalba; Ciccone, G; Bo, S; Pagano, G F; Merletti, F; Gregori, D

2007-06-01

Type 2 diabetes represents a condition significantly associated with increased cardiovascular mortality. The aims of the study are: (i) to estimate the cumulative incidence function for cause-specific mortality using Cox and Aalen model; (ii) to describe how the prediction of cardiovascular or other causes mortality changes for patients with different pattern of covariates; (iii) to show if different statistical methods may give different results. Cox and Aalen additive regression model through the Markov chain approach, are used to estimate the cause-specific hazard for cardiovascular or other causes mortality in a cohort of 2865 type 2 diabetic patients without insulin treatment. The models are compared in the estimation of the risk of death for patients of different severity. For younger patients with a better covariates profile, the Cumulative Incidence Function estimated by Cox and Aalen model was almost the same; for patients with the worst covariates profile, models gave different results: at the end of follow-up cardiovascular mortality rate estimated by Cox and Aalen model was 0.26 [95% confidence interval (CI) = 0.21-0.31] and 0.14 (95% CI = 0.09-0.18). Standard Cox and Aalen model capture the risk process for patients equally well with average profiles of co-morbidities. The Aalen model, in addition, is shown to be better at identifying cause-specific risk of death for patients with more severe clinical profiles. This result is relevant in the development of analytic tools for research and resource management within diabetes care.

Comparative analysis of COX-2, vascular endothelial growth factor and microvessel density in human renal cell carcinomas.

PubMed

Hemmerlein, B; Galuschka, L; Putzer, N; Zischkau, S; Heuser, M

2004-12-01

Cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are frequently up-regulated in malignant tumours and play a role in proliferation, apoptosis, angiogenesis and tumour invasion. In the present study, the expression of COX-2 and VEGF in renal cell carcinoma (RCC) was analysed and correlated with the microvessel density (MVD). COX-2 and VEGF were analysed by realtime reverse transcriptase-polymerase chain reaction and immunohistochemistry. The MVD was assessed by CD31 immunohistochemistry. The expression of COX-2 and VEGF was determined in the RCC cell lines A498 and Caki-1 under short-term hypoxia and in multicellular tumour cell aggregates. COX-2 was expressed in RCC by tumour epithelia, endothelia and macrophages in areas of cystic tumour regression and tumour necrosis. COX-2 protein in RCC was not altered in comparison with normal renal tissue. VEGF mRNA was up-regulated in RCC and positively correlated with MVD. RCC with high up-regulation of VEGF mRNA showed weak intracytoplasmic expression of VEGF in tumour cells. Intracytoplasmic VEGF protein expression was negatively correlated with MVD. In RCC with necrosis the MVD was reduced in comparison with RCC without necrosis. A498 RCC cells down-regulated COX-2 and up-regulated VEGF under conditions of hypoxia. In Caki-1 cells COX-2 expression remained stable, whereas VEGF was significantly up-regulated. In multicellular A498 cell aggregates COX-2 and VEGF were up-regulated centrally, whereas no gradient was found in Caki-1 cells. COX-2 and VEGF are potential therapeutic targets because COX-2 and VEGF are expressed in RCC and associated cell populations such as endothelia and monocytes/macrophages.

Big Data Toolsets to Pharmacometrics: Application of Machine Learning for Time-to-Event Analysis.

PubMed

Gong, Xiajing; Hu, Meng; Zhao, Liang

2018-05-01

Additional value can be potentially created by applying big data tools to address pharmacometric problems. The performances of machine learning (ML) methods and the Cox regression model were evaluated based on simulated time-to-event data synthesized under various preset scenarios, i.e., with linear vs. nonlinear and dependent vs. independent predictors in the proportional hazard function, or with high-dimensional data featured by a large number of predictor variables. Our results showed that ML-based methods outperformed the Cox model in prediction performance as assessed by concordance index and in identifying the preset influential variables for high-dimensional data. The prediction performances of ML-based methods are also less sensitive to data size and censoring rates than the Cox regression model. In conclusion, ML-based methods provide a powerful tool for time-to-event analysis, with a built-in capacity for high-dimensional data and better performance when the predictor variables assume nonlinear relationships in the hazard function. © 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Handling nonnormality and variance heterogeneity for quantitative sublethal toxicity tests.

PubMed

Ritz, Christian; Van der Vliet, Leana

2009-09-01

The advantages of using regression-based techniques to derive endpoints from environmental toxicity data are clear, and slowly, this superior analytical technique is gaining acceptance. As use of regression-based analysis becomes more widespread, some of the associated nuances and potential problems come into sharper focus. Looking at data sets that cover a broad spectrum of standard test species, we noticed that some model fits to data failed to meet two key assumptions-variance homogeneity and normality-that are necessary for correct statistical analysis via regression-based techniques. Failure to meet these assumptions often is caused by reduced variance at the concentrations showing severe adverse effects. Although commonly used with linear regression analysis, transformation of the response variable only is not appropriate when fitting data using nonlinear regression techniques. Through analysis of sample data sets, including Lemna minor, Eisenia andrei (terrestrial earthworm), and algae, we show that both the so-called Box-Cox transformation and use of the Poisson distribution can help to correct variance heterogeneity and nonnormality and so allow nonlinear regression analysis to be implemented. Both the Box-Cox transformation and the Poisson distribution can be readily implemented into existing protocols for statistical analysis. By correcting for nonnormality and variance heterogeneity, these two statistical tools can be used to encourage the transition to regression-based analysis and the depreciation of less-desirable and less-flexible analytical techniques, such as linear interpolation.

Mammographic density defined by higher than conventional brightness thresholds better predicts breast cancer risk

PubMed Central

Nguyen, Tuong L; Aung, Ye K; Evans, Christopher F; Dite, Gillian S; Stone, Jennifer; MacInnis, Robert J; Dowty, James G; Bickerstaffe, Adrian; Aujard, Kelly; Rommens, Johanna M; Song, Yun-Mi; Sung, Joohon; Jenkins, Mark A; Southey, Melissa C; Giles, Graham G; Apicella, Carmel; Hopper, John L

2017-01-01

Abstract Background: Mammographic density defined by the conventional pixel brightness threshold, and adjusted for age and body mass index (BMI), is a well-established risk factor for breast cancer. We asked if higher thresholds better separate women with and without breast cancer. Methods: We studied Australian women, 354 with breast cancer over-sampled for early-onset and family history, and 944 unaffected controls frequency-matched for age at mammogram. We measured mammographic dense area and percent density using the CUMULUS software at the conventional threshold, which we call Cumulus, and at two increasingly higher thresholds, which we call Altocumulus and Cirrocumulus, respectively. All measures were Box–Cox transformed and adjusted for age and BMI. We estimated the odds per adjusted standard deviation (OPERA) using logistic regression and the area under the receiver operating characteristic curve (AUC). Results: Altocumulus and Cirrocumulus were correlated with Cumulus (r ∼ 0.8 and 0.6, respectively). For dense area, the OPERA was 1.62, 1.74 and 1.73 for Cumulus, Altocumulus and Cirrocumulus, respectively (all P < 0.001). After adjusting for Altocumulus and Cirrocumulus, Cumulus was not significant (P > 0.6). The OPERAs for percent density were less but gave similar findings. The mean of the standardized adjusted Altocumulus and Cirrocumulus dense area measures was the best predictor; OPERA = 1.87 [95% confidence interval (CI): 1.64–2.14] and AUC = 0.68 (0.65–0.71). Conclusions: The areas of higher mammographically dense regions are associated with almost 30% stronger breast cancer risk gradient, explain the risk association of the conventional measure and might be more aetiologically important. This has substantial implications for clinical translation and molecular, genetic and epidemiological research. PMID:28338721

Mammographic density defined by higher than conventional brightness thresholds better predicts breast cancer risk.

PubMed

Nguyen, Tuong L; Aung, Ye K; Evans, Christopher F; Dite, Gillian S; Stone, Jennifer; MacInnis, Robert J; Dowty, James G; Bickerstaffe, Adrian; Aujard, Kelly; Rommens, Johanna M; Song, Yun-Mi; Sung, Joohon; Jenkins, Mark A; Southey, Melissa C; Giles, Graham G; Apicella, Carmel; Hopper, John L

2017-04-01

Mammographic density defined by the conventional pixel brightness threshold, and adjusted for age and body mass index (BMI), is a well-established risk factor for breast cancer. We asked if higher thresholds better separate women with and without breast cancer. We studied Australian women, 354 with breast cancer over-sampled for early-onset and family history, and 944 unaffected controls frequency-matched for age at mammogram. We measured mammographic dense area and percent density using the CUMULUS software at the conventional threshold, which we call Cumulus , and at two increasingly higher thresholds, which we call Altocumulus and Cirrocumulus , respectively. All measures were Box-Cox transformed and adjusted for age and BMI. We estimated the odds per adjusted standard deviation (OPERA) using logistic regression and the area under the receiver operating characteristic curve (AUC). Altocumulus and Cirrocumulus were correlated with Cumulus (r ∼ 0.8 and 0.6 , respectively) . For dense area, the OPERA was 1.62, 1.74 and 1.73 for Cumulus, Altocumulus and Cirrocumulus , respectively (all P  < 0.001). After adjusting for Altocumulus and Cirrocumulus , Cumulus was not significant ( P  > 0.6). The OPERAs for percent density were less but gave similar findings. The mean of the standardized adjusted Altocumulus and Cirrocumulus dense area measures was the best predictor; OPERA = 1.87 [95% confidence interval (CI): 1.64-2.14] and AUC = 0.68 (0.65-0.71). The areas of higher mammographically dense regions are associated with almost 30% stronger breast cancer risk gradient, explain the risk association of the conventional measure and might be more aetiologically important. This has substantial implications for clinical translation and molecular, genetic and epidemiological research. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association

Social participation and coronary heart disease risk in a large prospective study of UK women

PubMed Central

Balkwill, Angela; Canoy, Dexter; Reeves, Gillian K; Green, Jane; Beral, Valerie; Cairns, Benjamin J

2015-01-01

Background Participation in social activities is thought to prevent heart disease, but evidence is inconclusive. Design We assessed whether participating in social activities reduces the risk of coronary heart disease (CHD) in a large prospective study of 735,159 middle-aged UK women. Methods Women reported their participation in eight social activities (religious group, voluntary work, adult education, art/craft/music, dancing, sports club, yoga, bingo) and were followed for first CHD event (hospital admission or death) over the next 8.6 years. Cox regression models were used to estimate relative risks for CHD incidence by participation in each and in any of the social activities. Results After adjustment for age and region only, every activity except bingo was associated with a reduced risk of CHD (n = 30,756 cases in total). However, after additional adjustment for 11 factors (deprivation, education, smoking, physical activity, body mass index, alcohol, marital status, self-rated health, happiness, hypertension, diabetes), every relative risk estimate moved close to 1.0. For example, for participation in any of the activities compared with none, the relative risk adjusted for age and region only was 0.83 (99% confidence interval 0.81–0.86), but changed to 1.06 (99% confidence interval 1.02–1.09) after additional adjustment. Adjustment for education, self-rated health, smoking and physical activity attenuated the associations most strongly. Residual confounding and other unmeasured factors may well account for any small remaining associations. Conclusions Associations between participation in various social activities and CHD risk appear to be largely or wholly due to confounding by personal characteristics of the participants. PMID:26416995

Does stage of cancer, comorbidity or lifestyle factors explain educational differences in survival after endometrial cancer? A cohort study among Danish women diagnosed 2005-2009.

PubMed

Seidelin, Ulla Holten; Ibfelt, Else; Andersen, Ingelise; Steding-Jessen, Marianne; Høgdall, Claus; Kjær, Susanne Krüger; Dalton, Susanne Oksbjerg

2016-06-01

Several studies have documented an association between socioeconomic position and survival from gynaecological cancer, but the mechanisms are unclear. The aim of this study was to examine the association between level of education and survival after endometrial cancer among Danish women; and whether differences in stage at diagnosis and comorbidity contribute to the educational differences in survival. Women with endometrial cancer diagnosed between 2005 and 2009 were identified in the Danish Gynaecological Cancer Database, with information on clinical characteristics, surgery, body mass index (BMI) and smoking status. Information on highest attained education, cohabitation and comorbidity was obtained from nationwide administrative registries. Logistic regression models were used to determine the association between level of education and cancer stage and Cox proportional hazards model for analyses of overall survival. Of the 3638 patients identified during the study period, 787 had died by the end of 2011. The group of patients with short education had a higher odds ratio (OR) for advanced stage at diagnosis, but this was not statistically significant (adjusted OR 1.20; 95% CI 0.97-1.49). The age-adjusted hazard ratio (HR) for dying of patients with short education was 1.47 (CI 95% 1.17-1.80). Adjustment for cohabitation status, BMI, smoking and comorbidity did not change HRs, but further adjustment for cancer stage yielded a HR of 1.36 (1.11-1.67). Early detection in all educational groups might reduce social inequalities in survival, however, the unexplained increased risk for death after adjustment for prognostic factors, warrants increased attention to patients with short education in all age groups throughout treatment and rehabilitation.

Use of incretin agents and risk of acute and chronic pancreatitis: A population-based cohort study.

PubMed

Knapen, Lotte M; de Jong, Roy G P J; Driessen, Johanna H M; Keulemans, Yolande C; van Erp, Nielka P; De Bruin, Marie L; Leufkens, Hubert G M; Croes, Sander; de Vries, Frank

2017-03-01

To determine the association between the use of incretin agents (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) for the treatment of type 2 diabetes mellitus (T2DM) and the risk of any, acute and chronic pancreatitis. A population-based cohort study was conducted using data from the UK Clinical Practice Research Datalink (CPRD 2007-2012). A total of 182 428 adult patients with ≥1 non-insulin antidiabetic drug (NIAD) prescription were matched to control subjects without diabetes. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of pancreatitis in incretin-users (N = 28 370) compared with controls and with other NIAD users. Adjustments were made for lifestyle, disease and drug history. In a sensitivity analysis, a new-user design was used. Current incretin users had a 1.5-fold increased risk of any pancreatitis compared with NIAD users (adjusted HR 1.47, 95% CI 1.06-2.04). In incident current incretin users the risk of any and acute pancreatitis was increased 2.1- and 2.0-fold compared with NIAD users (adjusted HR 2.12, 95% CI 1.31-3.43 and adjusted HR 1.96, 95% CI 1.13-3.41), whereas there was no increased risk found for chronic pancreatitis. Incretin use was associated with an increased risk of any pancreatitis. Moreover, risk of any and acute pancreatitis was higher when applying a new-user design. We were not able to detect an association with chronic pancreatitis, but the number in this subgroup was small. © 2016 John Wiley & Sons Ltd.

High-Performance Membrane Dialyzers and Mortality in Hemodialysis Patients: A 2-Year Cohort Study from the Annual Survey of the Japanese Renal Data Registry.

PubMed

Abe, Masanori; Hamano, Takayuki; Wada, Atsushi; Nakai, Shigeru; Masakane, Ikuto

2017-01-01

Little information is available regarding the type of dialyzer which results in good prognosis. This study is aimed at investigating the association between 7 types of dialyzers and 2-year mortality. We conducted a cohort study using data from a nationwide registry of the Japanese Society for Dialysis Therapy. Subjects were 136,676 patients on maintenance hemodialysis (HD) between 2009 and 2011 who underwent maintenance HD for at least 2 years and were treated with one of the following 7 types of high-performance membrane dialyzers: cellulose triacetate (CTA), ethylene vinyl alcohol (EVAL), polyacrylonitrile (PAN), polyester polymer alloy (PEPA), polyethersulfone (PES), polymethylmethacrylate (PMMA), and polysulfone (PS). Cox regression was used to estimate the association between baseline dialyzers and all-cause 2-year mortality, adjusting for potential confounders. Data were adjusted using basic factors, with PS as a reference group, and the hazard ratio (HR) was significantly higher in CTA, PMMA, PAN, and EVAL groups. Further data adjustment for Kt/V yielded the same results as were obtained from data adjusted for basic factors. After further adjustment for nutrition- and inflammation-related factors, HR was significantly lowered for the PES and PMMA groups compared with the PS group (HR 0.88; 95% CI 0.82-0.94 and HR 0.84 95% CI 0.76-0.93, respectively). After propensity score matching, HR for the PES and PMMA groups was significantly lowered compared with the PS group. The use of different membrane types may affect mortality. Further long-term prospective studies are needed to clarify whether the PES and PMMA membranes can improve prognosis. © 2017 S. Karger AG, Basel.

Coffee consumption and incidence of lung cancer in the NIH-AARP Diet and Health Study

PubMed Central

Guertin, Kristin A; Freedman, Neal D; Loftfield, Erikka; Graubard, Barry I; Caporaso, Neil E; Sinha, Rashmi

2016-01-01

Background: Coffee drinkers had a higher risk of lung cancer in some previous studies, but as heavy coffee drinkers tend to also be cigarette smokers, such findings could be confounded. Therefore, we examined this association in the nearly half a million participants of the US NIH-AARP Diet and Health Study. Methods: Typical coffee intake and smoking history were queried at baseline. During 4 155 256 person-years of follow-up, more than 9000 incident lung cancer cases occurred. We used Cox proportional hazards regression to estimate hazard ratios (HRs)and 95% confidence intervals for coffee intake and subsequent incidence of lung cancer. We also comprehensively adjusted for tobacco smoking and examined associations by detailed strata of tobacco use. Results: Coffee drinkers were far more likely to smoke than non-drinkers. Although coffee drinking was associated with lung cancer in age- and sex- adjusted models (HR for ≥ 6 cups/day compared with none: 4.56, 4.08-5.10), this association was substantially attenuated after adjusting for smoking (HR: 1.27, 1.14-1.42). Similar findings were observed for each different histological type of lung cancer, and for participants drinking predominantly caffeinated or decaffeinated coffee. Little evidence for an association was observed in our stratified analyses, either within never smokers or in most categories of tobacco use. Conclusions: Coffee drinking was positively associated with lung cancer in our study, although the association was substantially attenuated after adjustment for tobacco smoking. As our adjustment for lifetime tobacco use was imperfect, it is likely that the remaining association is due to residual confounding by smoking, although other explanations are possible. PMID:26082405

Social participation and coronary heart disease risk in a large prospective study of UK women.

PubMed

Floud, Sarah; Balkwill, Angela; Canoy, Dexter; Reeves, Gillian K; Green, Jane; Beral, Valerie; Cairns, Benjamin J

2016-06-01

Participation in social activities is thought to prevent heart disease, but evidence is inconclusive. We assessed whether participating in social activities reduces the risk of coronary heart disease (CHD) in a large prospective study of 735,159 middle-aged UK women. Women reported their participation in eight social activities (religious group, voluntary work, adult education, art/craft/music, dancing, sports club, yoga, bingo) and were followed for first CHD event (hospital admission or death) over the next 8.6 years. Cox regression models were used to estimate relative risks for CHD incidence by participation in each and in any of the social activities. After adjustment for age and region only, every activity except bingo was associated with a reduced risk of CHD (n = 30,756 cases in total). However, after additional adjustment for 11 factors (deprivation, education, smoking, physical activity, body mass index, alcohol, marital status, self-rated health, happiness, hypertension, diabetes), every relative risk estimate moved close to 1.0. For example, for participation in any of the activities compared with none, the relative risk adjusted for age and region only was 0.83 (99% confidence interval 0.81-0.86), but changed to 1.06 (99% confidence interval 1.02-1.09) after additional adjustment. Adjustment for education, self-rated health, smoking and physical activity attenuated the associations most strongly. Residual confounding and other unmeasured factors may well account for any small remaining associations. Associations between participation in various social activities and CHD risk appear to be largely or wholly due to confounding by personal characteristics of the participants. © The European Society of Cardiology 2015.

Triglyceride to high-density lipoprotein cholesterol ratio predicts cardiovascular outcomes in prevalent dialysis patients.

PubMed

Chen, Hung-Yuan; Tsai, Wan-Chuan; Chiu, Yen-Ling; Hsu, Shih-Ping; Pai, Mei-Fen; Yang, Ju-Yeh; Peng, Yu-Sen

2015-03-01

Triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, an indicator of atherogenic dyslipidemia, is a predictor of cardiovascular (CV) outcomes in the general population and has been correlated with atherosclerotic events. Whether the TG/HDL-C ratio can predict CV outcomes and survival in dialysis patients is unknown. We performed this prospective, observational cohort study and enrolled 602 dialysis patients (539 hemodialysis and 63 peritoneal dialysis) from a single center in Taiwan followed up for a median of 3.9 years. The outcomes were the occurrence of CV events, CV death, and all-cause mortality during follow-up. The association of baseline TG/HDL-C ratio with outcomes was explored with Cox regression models, which were adjusted for demographic parameters and inflammatory/nutritional markers. Overall, 203 of the patients experienced CV events and 169 patients died, of whom 104 died due to CV events. Two hundred fifty-four patients reached the composite CV outcome. Patients with higher TG/HDL-C levels (quintile 5) had a higher incidence of CV events (adjusted hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.19-3.47), CV mortality (adjusted HR 1.91, 95% CI 1.07-3.99), composite CV outcome (adjusted HR 2.2, 95% CI 1.37-3.55), and all-cause mortality (adjusted HR 1.94, 95% CI 1.1-3.39) compared with the patients in quintile 1. However, in diabetic dialysis patients, the TG/HDL-C ratio did not predict the outcomes. The TG/HDL-C ratio is a reliable and easily accessible predictor to evaluate CV outcomes and survival in prevalent nondiabetic dialysis patients. ClinicalTrials.gov: NCT01457625.

Triglyceride to High-Density Lipoprotein Cholesterol Ratio Predicts Cardiovascular Outcomes in Prevalent Dialysis Patients

PubMed Central

Chen, Hung-Yuan; Tsai, Wan-Chuan; Chiu, Yen-Ling; Hsu, Shih-Ping; Pai, Mei-Fen; Yang, Ju-Yeh; Peng, Yu-Sen

2015-01-01

Abstract Triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, an indicator of atherogenic dyslipidemia, is a predictor of cardiovascular (CV) outcomes in the general population and has been correlated with atherosclerotic events. Whether the TG/HDL-C ratio can predict CV outcomes and survival in dialysis patients is unknown. We performed this prospective, observational cohort study and enrolled 602 dialysis patients (539 hemodialysis and 63 peritoneal dialysis) from a single center in Taiwan followed up for a median of 3.9 years. The outcomes were the occurrence of CV events, CV death, and all-cause mortality during follow-up. The association of baseline TG/HDL-C ratio with outcomes was explored with Cox regression models, which were adjusted for demographic parameters and inflammatory/nutritional markers. Overall, 203 of the patients experienced CV events and 169 patients died, of whom 104 died due to CV events. Two hundred fifty-four patients reached the composite CV outcome. Patients with higher TG/HDL-C levels (quintile 5) had a higher incidence of CV events (adjusted hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.19–3.47), CV mortality (adjusted HR 1.91, 95% CI 1.07–3.99), composite CV outcome (adjusted HR 2.2, 95% CI 1.37–3.55), and all-cause mortality (adjusted HR 1.94, 95% CI 1.1–3.39) compared with the patients in quintile 1. However, in diabetic dialysis patients, the TG/HDL-C ratio did not predict the outcomes. The TG/HDL-C ratio is a reliable and easily accessible predictor to evaluate CV outcomes and survival in prevalent nondiabetic dialysis patients. ClinicalTrials.gov: NCT01457625 PMID:25761189

Reproductive Factors and Incidence of Heart Failure Hospitalization in the Women’s Health Initiative

PubMed Central

Hall, Philip S.; Nah, Gregory; Howard, Barbara V.; Lewis, Cora E.; Allison, Matthew A.; Sarto, Gloria E.; Waring, Molly E.; Jacobson, Lisette T.; Manson, JoAnn E.; Klein, Liviu; Parikh, Nisha I.

2017-01-01

BACKGROUND Reproductive factors reflective of endogenous sex hormone exposure might have an effect on cardiac remodeling and the development of heart failure (HF). OBJECTIVES This study examined the association between key reproductive factors and the incidence of HF. METHODS Women from a cohort of the Women’s Health Initiative were systematically evaluated for the incidence of HF hospitalization from study enrollment through 2014. Reproductive factors (number of live births, age at first pregnancy, and total reproductive duration [time from menarche to menopause]) were self-reported at study baseline in 1993 to 1998. We employed Cox proportional hazards regression analysis in age- and multivariable-adjusted models. RESULTS Among 28,516 women, with an average age of 62.7 ± 7.1 years at baseline, 1,494 (5.2%) had an adjudicated incident HF hospitalization during an average follow-up of 13.1 years. After adjusting for covariates, total reproductive duration in years was inversely associated with incident HF: hazard ratios (HRs) of 0.99 per year (95% confidence interval [CI]: 0.98 to 0.99 per year) and 0.95 per 5 years (95% CI: 0.91 to 0.99 per 5 years). Conversely, early age at first pregnancy and nulliparity were significantly associated with incident HF in age-adjusted models, but not after multivariable adjustment. Notably, nulliparity was associated with incident HF with preserved ejection fraction in the fully adjusted model (HR: 2.75; 95% CI: 1.16 to 6.52). CONCLUSIONS In postmenopausal women, shorter total reproductive duration was associated with higher risk of incident HF, and nulliparity was associated with higher risk for incident HF with preserved ejection fraction. Whether exposure to endogenous sex hormones underlies this relationship should be investigated in future studies. PMID:28521890

Psychosocial work environment and mental health-related long-term sickness absence among nurses.

PubMed

Roelen, Corné A M; van Hoffen, Marieke F A; Waage, Siri; Schaufeli, Wilmar B; Twisk, Jos W R; Bjorvatn, Bjørn; Moen, Bente E; Pallesen, Ståle

2018-02-01

We investigated which job demands and job resources were predictive of mental health-related long-term sickness absence (LTSA) in nurses. The data of 2059 nurses were obtained from the Norwegian survey of Shift work, Sleep and Health. Job demands (psychological demands, role conflict, and harassment at the workplace) and job resources (social support at work, role clarity, and fair leadership) were measured at baseline and linked to mental health-related LTSA during 2-year follow-up. Cox regression models estimated hazard ratios (HR) and related 95% confidence intervals (CI). The c-statistic was used to investigate the discriminative ability of the Cox regression models. A total of 1533 (75%) nurses were included in the analyses; 103 (7%) of them had mental health-related LTSA during 2-year follow-up. Harassment (HR = 1.07; 95% CI 1.01-1.17) and social support (HR = 0.92; 95% CI 0.87-0.98) were associated with mental health-related LTSA. However, the Cox regression model did not discriminate between nurses with and without mental health-related LTSA (c = 0.59; 95% CI 0.53-0.65). Harassment was positively and social support at the workplace was negatively related to mental health-related LTSA, but both failed to discriminate between nurses with and without mental health-related LTSA during 2-year follow-up.

Comparison of Weibull and Lognormal Cure Models with Cox in the Survival Analysis Of Breast Cancer Patients in Rafsanjan.

PubMed

Hoseini, Mina; Bahrampour, Abbas; Mirzaee, Moghaddameh

2017-02-16

Breast cancer is the most common cancer after lung cancer and the second cause of death. In this study we compared Weibull and Lognormal Cure Models with Cox regression on the survival of breast cancer. A cohort study. The current study retrospective cohort study was conducted on 140 patients referred to Ali Ibn Abitaleb Hospital, Rafsanjan southeastern Iran from 2001 to 2015 suffering from breast cancer. We determined and analyzed the effective survival causes by different models using STATA14. According to AIC, log-normal model was more consistent than Weibull. In the multivariable Lognormal model, the effective factors like smoking, second -hand smoking, drinking herbal tea and the last breast-feeding period were included. In addition, using Cox regression factors of significant were the disease grade, size of tumor and its metastasis (p-value<0.05). As Rafsanjan is surrounded by pistachio orchards and pesticides applied by farmers, people of this city are exposed to agricultural pesticides and its harmful consequences. The effect of the pesticide on breast cancer was studied and the results showed that the effect of pesticides on breast cancer was not in agreement with the models used in this study. Based on different methods for survival analysis, researchers can decide how they can reach a better conclusion. This comparison indicates the result of semi-parametric Cox method is closer to clinical experiences evidences.

Actinic cheilitis: epithelial expression of COX-2 and its association with mast cell tryptase and PAR-2.

PubMed

Rojas, I Gina; Martínez, Alejandra; Brethauer, Ursula; Grez, Patricia; Yefi, Roger; Luza, Sandra; Marchesani, Francisco J

2009-03-01

Cyclooxygenase-2 (COX-2) is overexpressed in various types of human malignancies, including oral cancers. Recent studies have shown that mast cell-derived protease tryptase can induce COX-2 expression by the cleavage of proteinase-activated receptor-2 (PAR-2). Actinic cheilitis (AC) is a premalignant form of lip cancer characterized by an increased density of tryptase-positive mast cells. To investigate the possible contribution of tryptase to COX-2 overexpression during early lip carcinogenesis, normal lip (n=24) and AC (n=45) biopsies were processed for COX-2, PAR-2 and tryptase detection, using RT-PCR and immunohistochemistry. Expression scores were obtained for each marker and tested for statistical significance using Mann-Whitney and Spearmann's correlation tests as well as multivariate logistic regression analysis. Increased epithelial co-expression of COX-2 and PAR-2, as well as, elevated subepithelial density of tryptase-positive mast cells were found in AC as compared to normal lip (P<0.001). COX-2 overexpression was found to be a significant predictor of AC (P<0.034, forward stepwise, Wald), and to be correlated with both tryptase-positive mast cells and PAR-2 expression (P<0.01). The results suggest that epithelial COX-2 overexpression is a key event in AC, which is associated with increased tryptase-positive mast cells and PAR-2. Therefore, tryptase may contribute to COX-2 up-regulation by epithelial PAR-2 activation during early lip carcinogenesis.

Age-adjusted Charlson comorbidity index score as predictor of survival of patients with digestive system cancer who have undergone surgical resection.

PubMed

Tian, Yaohua; Jian, Zhong; Xu, Beibei; Liu, Hui

2017-10-03

Comorbidities have considerable effects on survival outcomes. The primary objective of this retrospective study was to examine the association between age-adjusted Charlson comorbidity index (ACCI) score and postoperative in-hospital mortality in patients with digestive system cancer who have undergone surgical resection of their cancers. Using electronic hospitalization summary reports, we identified 315,464 patients who had undergone surgery for digestive system cancer in top-rank (Grade 3A) hospitals in China between 2013 and 2015. The Cox proportional hazard regression model was applied to evaluate the effect of ACCI score on postoperative mortality, with adjustments for sex, type of resection, anesthesia methods, and caseload of each healthcare institution. The postoperative in-hospital mortality rate in the study cohort was 1.2% (3,631/315,464). ACCI score had a positive graded association with the risk of postoperative in-hospital mortality for all cancer subtypes. The adjusted HRs for postoperative in-hospital mortality scores ≥ 6 for esophagus, stomach, colorectum, pancreas, and liver and gallbladder cancer were 2.05 (95% CI: 1.45-2.92), 2.00 (95% CI: 1.60-2.49), 2.54 (95% CI: 2.02-3.21), 2.58 (95% CI: 1.68-3.97), and 4.57 (95% CI: 3.37-6.20), respectively, compared to scores of 0-1. These findings suggested that a high ACCI score is an independent predictor of postoperative in-hospital mortality in Chinese patients with digestive system cancer who have undergone surgical resection.

Associations of Red and Processed Meat with Survival among Patients with Cancers of the Upper Aerodigestive Tract and Lung

PubMed Central

Miles, Fayth L.; Chang, Shen-Chih; Morgenstern, Hal; Tashkin, Donald; Rao, Jian-Yu; Cozen, Wendy; Mack, Thomas; Lu, Qing-Yi; Zhang, Zuo-Feng

2016-01-01

The effect of red and processed meats on cancer survival is unclear. We sought to examine the role of total and processed red meat consumption on all-cause mortality among patients with cancers of the upper aerodigestive tract (UADT) and lung, in order to test our hypothesis that red or processed meat was associated with overall mortality in these patients. Using data from a population-based case-control study conducted in Los Angeles County, we conducted a case-only analysis to examine the association of red or processed meat consumption on mortality after 12 years of follow-up, using a diet history questionnaire. Cox regression was used to estimate adjusted hazards ratios (HRs) with 95% confidence intervals (CIs), adjusting for potential confounders. Of 601 UADT cancer cases and 611 lung cancer cases, there were 248 and 406 deaths, respectively, yielding crude mortality rates of 0.07 and 0.12 deaths per year. Comparing the highest with lowest quartile of red meat consumption, the adjusted HR was 1.64 (95% CI: 1.04, 2.57) among UADT cancer cases; for red or processed meat the adjusted HR was 1.76 (95% CI: 1.10, 2.82). A dose-response trend was observed. A weaker association was observed with red meat consumption and overall mortality among lung cancer cases. In conclusion, this case-only analysis demonstrated that increased consumption of red or processed meats was associated with mortality among UADT cancer cases, and weakly associated with mortality among lung cancer cases. PMID:27188908

Associations of red and processed meat with survival among patients with cancers of the upper aerodigestive tract and lung.

PubMed

Miles, Fayth L; Chang, Shen-Chih; Morgenstern, Hal; Tashkin, Donald; Rao, Jian-Yu; Cozen, Wendy; Mack, Thomas; Lu, Qing-Yi; Zhang, Zuo-Feng

2016-06-01

The effect of red and processed meats on cancer survival is unclear. We sought to examine the role of total and processed red meat consumption on all-cause mortality among patients with cancers of the upper aerodigestive tract (UADT) and lung, in order to test our hypothesis that red or processed meat was associated with overall mortality in these patients. Using data from a population-based case-control study conducted in Los Angeles County, we conducted a case-only analysis to examine the association of red or processed meat consumption on mortality after 12 years of follow-up, using a diet history questionnaire. Cox regression was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for potential confounders. Of 601 UADT cancer cases and 611 lung cancer cases, there were 248 and 406 deaths, respectively, yielding crude mortality rates of 0.07 and 0.12 deaths per year. Comparing the highest with lowest quartile of red meat consumption, the adjusted HR was 1.64 (95% CI, 1.04-2.57) among UADT cancer cases; for red or processed meat, the adjusted HR was 1.76 (95% CI, 1.10-2.82). A dose-response trend was observed. A weaker association was observed with red meat consumption and overall mortality among lung cancer cases. In conclusion, this case-only analysis demonstrated that increased consumption of red or processed meats was associated with mortality among UADT cancer cases and WAS weakly associated with mortality among lung cancer cases. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of Neighborhood Socioeconomic Conditions on the Risk of Stroke in Japan

PubMed Central

Honjo, Kaori; Iso, Hiroyasu; Nakaya, Tomoki; Hanibuchi, Tomoya; Ikeda, Ai; Inoue, Manami; Sawada, Norie; Tsugane, Shoichiro

2015-01-01

Background Neighborhood deprivation has been shown in many studies to be an influential factor in cardiovascular disease risk. However, no previous studies have examined the effect of neighborhood socioeconomic conditions on the risk of stroke in Asian countries. Methods This study investigated whether neighborhood deprivation was associated with the risk of stroke and stroke death using data from the Japan Public Health Center-based Prospective Study. We calculated the adjusted hazard ratios of stroke mortality (mean follow-up, 16.4 years) and stroke incidence (mean follow-up, 15.4 years) according to the area deprivation index (ADI) among 90 843 Japanese men and women aged 40–69 years. A Cox proportional-hazard regression model using a shared frailty model was applied. Results The adjusted hazard ratios of stroke incidence, in order of increasing deprivation with reference to the least deprived area, were 1.16 (95% CI, 1.04–1.29), 1.12 (95% CI, 1.00–1.26), 1.18 (95% CI, 1.02–1.35), and 1.19 (95% CI, 1.01–1.41), after adjustment for individual socioeconomic conditions. Behavioral and psychosocial factors attenuated the association, but the association remained significant. The associations were explained by adjusting for biological cardiovascular risk factors. No significant association with stroke mortality was identified. Conclusions Our results indicate that the neighborhood deprivation level influences stroke incidence in Japan, suggesting that area socioeconomic conditions could be a potential target for public health intervention to reduce the risk of stroke. PMID:25757802

Race and survival following brachytherapy-based treatment for men with localized or locally advanced adenocarcinoma of the prostate.

PubMed

Winkfield, Karen M; Chen, Ming-Hui; Dosoretz, Daniel E; Salenius, Sharon A; Katin, Michael; Ross, Rudi; D'Amico, Anthony V

2011-11-15

We investigated whether race was associated with risk of death following brachytherapy-based treatment for localized prostate cancer, adjusting for age, cardiovascular comorbidity, treatment, and established prostate cancer prognostic factors. The study cohort was composed of 5,360 men with clinical stage T1-3N0M0 prostate cancer who underwent brachytherapy-based treatment at 20 centers within the 21st Century Oncology consortium. Cox regression multivariable analysis was used to evaluate the risk of death in African-American and Hispanic men compared to that in Caucasian men, adjusting for age, pretreatment prostate-specific antigen (PSA) level, Gleason score, clinical T stage, year and type of treatment, median income, and cardiovascular comorbidities. After a median follow-up of 3 years, there were 673 deaths. African-American and Hispanic races were significantly associated with an increased risk of all-cause mortality (ACM) (adjusted hazard ratio, 1.77 and 1.79; 95% confidence intervals, 1.3-2.5 and 1.2-2.7; p < 0.001 and p = 0.005, respectively). Other factors significantly associated with an increased risk of death included age (p < 0.001), Gleason score of 8 to 10 (p = 0.04), year of brachytherapy (p < 0.001), and history of myocardial infarction treated with stent or coronary artery bypass graft (p < 0.001). After adjustment for prostate cancer prognostic factors, age, income level, and revascularized cardiovascular comorbidities, African-American and Hispanic races were associated with higher ACM in men with prostate cancer. Additional causative factors need to be identified. Copyright © 2011 Elsevier Inc. All rights reserved.

Trauma, comorbidity, and mortality following diagnoses of severe stress and adjustment disorders: a nationwide cohort study.

PubMed

Gradus, Jaimie L; Antonsen, Sussie; Svensson, Elisabeth; Lash, Timothy L; Resick, Patricia A; Hansen, Jens Georg

2015-09-01

Longitudinal outcomes following stress or trauma diagnoses are receiving attention, yet population-based studies are few. The aims of the present cohort study were to examine the cumulative incidence of traumatic events and psychiatric diagnoses following diagnoses of severe stress and adjustment disorders categorized using International Classification of Diseases, Tenth Revision, codes and to examine associations of these diagnoses with all-cause mortality and suicide. Data came from a longitudinal cohort of all Danes who received a diagnosis of reaction to severe stress or adjustment disorders (International Classification of Diseases, Tenth Revision, code F43.x) between 1995 and 2011, and they were compared with data from a general-population cohort. Cumulative incidence curves were plotted to examine traumatic experiences and psychiatric diagnoses during the study period. A Cox proportional hazards regression model was used to examine the associations of the disorders with mortality and suicide. Participants with stress diagnoses had a higher incidence of traumatic events and psychiatric diagnoses than did the comparison group. Each disorder was associated with a higher rate of all-cause mortality than that seen in the comparison cohort, and strong associations with suicide were found after adjustment. This study provides a comprehensive assessment of the associations of stress disorders with a variety of outcomes, and we found that stress diagnoses may have long-lasting and potentially severe consequences. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

A higher incidence rate of acute coronary syndrome following radiation therapy in patients with breast cancer and a history of coronary artery diseases.

PubMed

Lee, Yen-Chien; Chuang, Jen-Pin; Hsieh, Pi-Ching; Chiou, Meng-Jiun; Li, Chung-Yi

2015-07-01

This study aims to investigate whether patients with breast cancer and a history of cardiovascular diseases (CADs) are at an increased incidence of acute coronary syndrome (ACS) after receiving radiation therapy (RT). In Taiwan, 5828 patients who had a history of CAD were newly diagnosed of breast cancer and received mastectomy between 1999 and 2009. Among these patients, 1851 also received RT. The study cohort was prospectively followed to the end of 2010 for estimating the incidence of ACS in association with exposure to RT. A Cox proportional hazard model that was adjusted for covariates was used to estimate the hazard ratio (HR) of ACS. Over the study period, the incident rates of ACS for RT and control patients were estimated at 1.51 and 1.77 per 100 person-years, respectively. Covariate-adjusted regression analysis indicated that the hazard of ACS significantly increased in RT patients at an adjusted HR of 1.48 [95% confidence interval (CI) 1.18-1.87]. Both hypertension and diabetes significantly increased the hazard of ACS in this patient cohort, with adjusted HRs of 3.31 (95% CI 1.94-5.66) and 1.50 (95% CI 1.19-1.89), respectively. This 12-year follow-up study suggested excess of ACS events in association with RT exposure in patients with breast cancer who had a higher cardiovascular risk. In consideration of the benefit associated with RT, intensive cardiac care should be given to patients with breast cancer and high cardiovascular risk.

Non-alcoholic beverage and caffeine consumption and mortality: the Leisure World Cohort Study.

PubMed

Paganini-Hill, Annlia; Kawas, Claudia H; Corrada, María M

2007-04-01

To examine the effects of non-alcoholic beverage and caffeine consumption on all-cause mortality in older adults. The Leisure World Cohort Study is a prospective study of residents of a California retirement community. A baseline postal health survey included details on coffee, tea, milk, soft drink, and chocolate consumption. Participants were followed for 23 years (1981-2004). Risk ratios (RRs) of death were calculated using Cox regression for 8644 women and 4980 men (median age at entry, 74 years) and adjusted for age, gender, and multiple potential confounders. Caffeine consumption exhibited a U-shaped mortality curve. Moderate caffeine consumers had a significantly reduced risk of death (multivariable-adjusted RR=0.94, 95% CI: 0.89, 0.99 for 100-199 mg/day and RR=0.90, 95% CI: 0.85, 0.94 for 200-399 mg/day compared with those consuming <50 mg/day). Individuals who drank more than 1 can/week of artificially sweetened (but not sugar-sweetened) soft drink (cola and other) had an 8% increased risk (95% CI: 1.01-1.16). Neither milk nor tea had a significant effect on mortality after multivariable adjustment. Moderate caffeine consumption appeared beneficial in reducing risk of death. Attenuation in the observed associations between mortality and intake of tea and milk with adjustment for potential confounders suggests that such consumption identifies those with other mortality-associated lifestyle and health risks. The increased death risk with consumption of artificially sweetened, but not sugar-sweetened, soft drinks suggests an effect of the sweetener rather than other components of the soft drinks, although residual confounding remains a possibility.

The Association Between Broad Antigen HLA Mismatches, Eplet HLA Mismatches and Acute Rejection After Kidney Transplantation.

PubMed

Do Nguyen, Hung Thanh; Wong, Germaine; Chapman, Jeremy R; McDonald, Stephen P; Coates, Patrick T; Watson, Narelle; Russ, Graeme R; D'Orsogna, Lloyd; Lim, Wai Hon

2016-12-01

Epitope matching, which evaluates mismatched amino acids within antigen-antibody interaction sites (eplets), may better predict acute rejection than broad antigen matching alone. We aimed to determine the association between eplet mismatches and acute rejection in kidney transplant recipients. The association between eplet mismatches, broad antigen mismatches and acute rejection was assessed using adjusted Cox proportional hazard regression. Model discrimination for acute rejection was evaluated using the area under receiver operating characteristic curves. Of the 3,499 kidney transplant recipients from 2006 to 2011, the average (SD) number of broad antigen and eplet mismatches were 3.4 (1.7) and 22.8 (12.2), respectively. Compared with 0 to 2 eplet mismatches, the adjusted hazard ratio (HR) for acute rejection among those with 20 or greater eplet mismatches was 2.16 (95% confidence interval [CI], 1.33-3.52; P = 0.001). The adjusted area under the curve for broad antigen mismatches was 0.58 (95% CI, 0.56-0.61), similar to that for eplet mismatches (HR, 0.59; 95% CI, 0.56-0.61; P = 0.365). In recipients who were considered as low immunological risk (0-2 broad antigen HLA-ABDR mismatch), those with 20 or greater eplet mismatches experienced an increased risk of rejection compared to those with less than 20 mismatches (adjusted HR, 1.85; 95% CI, 1.11-3.08; P = 0.019). Increasing number of eplet mismatches is associated with acute rejection in kidney transplant recipients. Consideration of eplet HLA mismatches may improve risk stratification for acute rejection in a selected group of kidney transplant candidates.

Occupational burnout and severe injuries: an eight-year prospective cohort study among Finnish forest industry workers.

PubMed

Ahola, Kirsi; Salminen, Simo; Toppinen-Tanner, Salla; Koskinen, Aki; Väänänen, Aki

2013-01-01

Burnout is a psychological consequence of prolonged work stress. Studies have shown that it is related to physical and mental disorders. The safety outcomes of burnout have been studied to a lesser extent and only in the work context. This study explored the effect of burnout on future severe injuries regardless of their context. A total of 10,062 forest industry employees (77% men, 63% manual workers) without previous injuries participated in 1996 or 2000 in the "Still Working" study examining the work-related antecedents of health and mortality. Burnout was assessed using the Maslach Burnout Inventory-General Survey. Injuries leading to death or hospitalization were regarded as severe. We extracted such injuries from independent national registers. The relationship between burnout and new injuries was analyzed using Cox proportional regression. The analyses were adjusted for age, sex, marital status, and occupational status. There were 788 new injuries over eight years. Injuries were more common among male and manual workers. After adjustments, each one-unit increase in the burnout score was related to a 9% increase in the risk of injury (95% confidence interval: 1.2-1.17). Experiencing symptoms at least monthly was related to a 1.18-fold adjusted injury risk (95% CI: 1.2-1.36). Of the subscales of burnout, exhaustion and cynicism but not lack of professional efficacy predicted injuries after adjustments. In addition to mental and physical disorders, burnout predicts severe injuries. Developing work conditions and optimizing workload may enhance safety and decrease health expenses related to all injuries.

Ambulatory arterial stiffness index and 24-hour ambulatory pulse pressure as predictors of mortality in Ohasama, Japan.

PubMed

Kikuya, Masahiro; Staessen, Jan A; Ohkubo, Takayoshi; Thijs, Lutgarde; Metoki, Hirohito; Asayama, Kei; Obara, Taku; Inoue, Ryusuke; Li, Yan; Dolan, Eamon; Hoshi, Haruhisa; Hashimoto, Junichiro; Totsune, Kazuhito; Satoh, Hiroshi; Wang, Ji-Guang; O'Brien, Eoin; Imai, Yutaka

2007-04-01

Ambulatory arterial stiffness index (AASI) and pulse pressure (PP) are indexes of arterial stiffness and can be computed from 24-hour blood pressure recordings. We investigated the prognostic value of AASI and PP in relation to fatal outcomes. In 1542 Ohasama residents (baseline age, 40 to 93 years; 63.4% women), we applied Cox regression to relate mortality to AASI and PP while adjusting for sex, age, BMI, 24-hour MAP, smoking and drinking habits, diabetes mellitus, and a history of cardiovascular disease. During 13.3 years (median), 126 cardiovascular and 63 stroke deaths occurred. The sex- and age-standardized incidence rates of cardiovascular and stroke mortality across quartiles were U-shaped for AASI and J-shaped for PP. Across quartiles, the multivariate-adjusted hazard ratios for cardiovascular and stroke death significantly deviated from those in the whole population in a U-shaped fashion for AASI, whereas for PP, none of the HRs departed from the overall risk. The hazard ratios for cardiovascular mortality across ascending AASI quartiles were 1.40 (P=0.04), 0.82 (P=0.25), 0.64 (P=0.01), and 1.35 (P=0.03). Additional adjustment of AASI for PP and sensitivity analyses by sex, excluding patients on antihypertensive treatment or with a history of cardiovascular disease, or censoring deaths occurring within 2 years of enrollment, produced confirmatory results. In a Japanese population, AASI predicted cardiovascular and stroke mortality over and beyond PP and other risk factors, whereas in adjusted analyses, PP did not carry any prognostic information.

EuroQol (EQ-5D) measure of quality of life predicts mortality, emergency department utilization, and hospital discharge rates in HIV-infected adults under care.

PubMed

Mathews, William C; May, Susanne

2007-01-25

Health-related quality of life (HR-QOL) is a relevant and quantifiable outcome of care. We implemented HR-QOL assessment at all primary care visits at UCSD Owen Clinic using EQ-5D. The study aim was to estimate the prognostic value of EQ-5D for survival, hospitalization, and emergency department (ED) utilization after controlling for CD4 and HIV plasma viral load (pVL). We conducted a retrospective analysis of HIV clinic based cohort (1996-2000). The EQ-5D includes single item measures of: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each item is coded using 3-levels (1 = no problems; 2 = some problems; 3 = severe problems). The instrument includes a global rating of current health using a visual analog scale (VAS) ranging from 0 (worst imaginable) to 100 (best imaginable). An additional single item measure of health change (better, much the same, worse) was included. A predicted VAS (pVAS) was estimated by regressing the 5 EQ-5D health states on VAS using reference cell coding of health states and random effects linear models. Survival models were fit using Cox modelling. Hospitalization and ED rate models were estimated using population-averaged Poisson models. 965 patients met eligibility criteria. 12% were female; 42% were non-white. Median time-at-risk was 1.2 years. Median CD4 was 233. Median log10(pVL) was 4.6. 47 deaths occurred. In two Cox models controlling for CD4 and pVL, the adjusted hazard ratios (aHR) for VAS and pVAS as time-varying covariates were 0.73 (95% CI: 0.63-0.83) and 0.66 (95% CI: 0.56-0.77) respectively, for every 10 point increase in (p)VAS rating. In Poisson regression models predicting ED visit rates and hospital discharge rates controlling for current CD4 and pVL, each of the EQ-5D health dimensions, VAS, and health change items were significantly (p < 0.05) associated with the outcomes. For ED visit rates, the adjusted incidence rate ratios (aIRR) were 0.86 (0.83-0.89) and 0.79 (0.75-0.82) for VAS and pVAS, respectively. For hospital discharge rates, the aIRR's were 0.85 (0.82-0.88) and 0.79 (0.75-0.82) for VAS and pVAS, respectively. EQ-5D is a brief and prognostically useful predictor of mortality, hospitalization, and ED utilization among adults under care for HIV infection, even after adjusting for CD4 and HIV plasma viral load.

Aspirin Does Not Increase Heart Failure Events in Heart Failure Patients: From the WARCEF Trial.

PubMed

Teerlink, John R; Qian, Min; Bello, Natalie A; Freudenberger, Ronald S; Levin, Bruce; Di Tullio, Marco R; Graham, Susan; Mann, Douglas L; Sacco, Ralph L; Mohr, J P; Lip, Gregory Y H; Labovitz, Arthur J; Lee, Seitetz C; Ponikowski, Piotr; Lok, Dirk J; Anker, Stefan D; Thompson, John L P; Homma, Shunichi

2017-08-01

The aim of this study was to determine whether aspirin increases heart failure (HF) hospitalization or death in patients with HF with reduced ejection fraction receiving an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Because of its cyclooxygenase inhibiting properties, aspirin has been postulated to increase HF events in patients treated with ACE inhibitors or ARBs. However, no large randomized trial has addressed the clinical relevance of this issue. We compared aspirin and warfarin for HF events (hospitalization, death, or both) in the 2,305 patients enrolled in the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial (98.6% on ACE inhibitor or ARB treatment), using conventional Cox models for time to first event (489 events). In addition, to examine multiple HF hospitalizations, we used 2 extended Cox models, a conditional model and a total time marginal model, in time to recurrent event analyses (1,078 events). After adjustment for baseline covariates, aspirin- and warfarin-treated patients did not differ in time to first HF event (adjusted hazard ratio: 0.87; 95% confidence interval: 0.72 to 1.04; p = 0.117) or first hospitalization alone (adjusted hazard ratio: 0.88; 95% confidence interval: 0.73 to 1.06; p = 0.168). The extended Cox models also found no significant differences in all HF events or in HF hospitalizations alone after adjustment for covariates. Among patients with HF with reduced ejection fraction in the WARCEF trial, there was no significant difference in risk of HF events between the aspirin and warfarin-treated patients. (Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction trial [WARCEF]; NCT00041938). Copyright © 2017 American College of Cardiology Foundation. All rights reserved.

QSAR analyses of conformationally restricted 1,5-diaryl pyrazoles as selective COX-2 inhibitors: application of connection table representation of ligands.

PubMed

Prasanna, S; Manivannan, E; Chaturvedi, S C

2005-04-15

As a part of our continuing efforts in discerning the structural and physicochemical requirements for selective COX-2 over COX-1 inhibition among the fused pyrazole ring systems, herein we report the QSAR analyses of the title compounds. The conformational flexibility of the title compounds was examined using a simple connection table representation. The conformational investigation was aided by calculating a connection table parameter called fraction of rotable bonds, b_rotR encompassing the number of rotable bonds and b_count, the number of bonds including implicit hydrogens of each ligand. The hydrophobic and steric correlation of the title compounds towards selective COX-2 inhibition was reported previously in one of our recent publications. In this communication, we attempt to calculate Wang-Ford charges of the non-hydrogen common atoms of AM1 optimized geometries of the title compounds. Owing to the partial conformational flexibility of title compounds, conformationally restricted and unrestricted descriptors were calculated from MOE. Correlation analysis of these 2D, 3D and Wang-Ford charges was accomplished by linear regression analysis. 2D molecular descriptor b_single, 3D molecular descriptors glob, std_dim3 showed significant contribution towards COX-2 inhibitory activity. Balaban J, a connectivity topological index showed a negative and positive contribution towards COX-1 and selective COX-2 over COX-1 inhibition, respectively. Wang-Ford charges calculated on C(7) showed a significant contribution towards COX-1 inhibitory activity whereas charges calculated on C(8) were crucial in governing the selectivity of COX-2 over COX-1 inhibition among these congeners.

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.

African Americans Are Less Likely to Receive Care by a Cardiologist During an Intensive Care Unit Admission for Heart Failure.

PubMed

Breathett, Khadijah; Liu, Wenhui G; Allen, Larry A; Daugherty, Stacie L; Blair, Irene V; Jones, Jacqueline; Grunwald, Gary K; Moss, Marc; Kiser, Tyree H; Burnham, Ellen; Vandivier, R William; Clark, Brendan J; Lewis, Eldrin F; Mazimba, Sula; Battaglia, Catherine; Ho, P Michael; Peterson, Pamela N

2018-05-01

This study sought to determine whether the likelihood of receiving primary intensive care unit (ICU) care by a cardiologist versus a noncardiologist was greater for Caucasians than for African Americans admitted to an ICU for heart failure (HF). The authors further evaluated whether primary ICU care by a cardiologist is associated with higher in-hospital survival, irrespective of race. Increasing data demonstrate an association between better HF outcomes and care by a cardiologist. It is unclear if previously noted racial differences in cardiology care persist in an ICU setting. Using the Premier database, adult patients admitted to an ICU with a primary discharge diagnosis of HF from 2010 to 2014 were included. Hierarchical logistic regression models were used to determine the association between race and primary ICU care by a cardiologist, adjusting for patient and hospital variables. Cox regression with inverse probability weighting was used to assess the association between cardiology care and in-hospital mortality. Among 104,835 patients (80.3% Caucasians, 19.7% African Americans), Caucasians had higher odds of care by a cardiologist than African Americans (adjusted odds ratio: 1.42; 95% confidence interval: 1.34 to 1.51). Compared with a noncardiologist, primary ICU care by a cardiologist was associated with higher in-hospital survival (adjusted hazard ratio: 1.20, 95% confidence interval: 1.11 to 1.28). The higher likelihood of survival did not differ by patient race (interaction p = 0.32). Among patients admitted to an ICU for HF, African Americans were less likely than Caucasians to receive primary care by a cardiologist. Primary care by a cardiologist was associated with higher survival for both Caucasians and African Americans. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Milk and yogurt consumption are linked with higher bone mineral density but not with hip fracture: the Framingham Offspring Study

PubMed Central

Sahni, Shivani; Tucker, Katherine L.; Kiel, Douglas P.; Quach, Lien; Casey, Virginia A.; Hannan, Marian T.

2013-01-01

Purpose To examine associations of milk, yogurt, cheese, cream, most dairy (total dairy without cream) and fluid dairy (milk+yogurt) with bone density (BMD) at femoral neck (FN), trochanter (TR) and spine, and with incident hip fracture over 12-y follow-up in the Framingham Offspring Study. Methods 3,212 participants completed a food frequency questionnaire (1991–1995 or 1995–1998) and were followed for hip fracture until 2007. 2,506 participants had DXA BMD (1996–2001). Linear regression was used to estimate adjusted mean BMD while Cox-proportional hazards regression was used to estimate adjusted hazard ratios (HR) for hip fracture risk. Final models simultaneously included dairy foods adjusting for each other. Results Mean baseline age was 55 (±1.6)y, range: 26–85). Most dairy intake was positively associated with hip and spine BMD. Intake of fluid dairy and milk were related with hip but not spine BMD. Yogurt intake was associated with TR-BMD alone. Cheese and cream intakes were not associated with BMD. In final models, yogurt intake remained positively associated with TR-BMD, while cream tended to be negatively associated with FN-BMD. Yogurt intake showed a weak protective trend for hip fracture [HR(95%CI): ≤4 serv/wk: 0.46 (0.21–1.03) vs. >4 serv/wk: 0.43 (0.06–3.27)]. No other dairy groups showed a significant association (HRs range: 0.53–1.47) with limited power (n, fractures=43). Conclusion Milk and yogurt intakes were associated with hip but not spine BMD, while cream may adversely influence BMD. Thus, not all dairy products are equally beneficial for the skeleton. Suggestive fracture results for milk and yogurt intakes need further confirmation. PMID:23371478

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

Long-Term Ozone Exposure and Mortality in a Large Prospective Study

PubMed Central

Jerrett, Michael; Pope, C. Arden; Krewski, Daniel; Gapstur, Susan M.; Diver, W. Ryan; Beckerman, Bernardo S.; Marshall, Julian D.; Su, Jason; Crouse, Daniel L.; Burnett, Richard T.

2016-01-01

Rationale: Tropospheric ozone (O3) is potentially associated with cardiovascular disease risk and premature death. Results from long-term epidemiological studies on O3 are scarce and inconclusive. Objectives: In this study, we examined associations between chronic ambient O3 exposure and all-cause and cause-specific mortality in a large cohort of U.S. adults. Methods: Cancer Prevention Study II participants were enrolled in 1982. A total of 669,046 participants were analyzed, among whom 237,201 deaths occurred through 2004. We obtained estimates of O3 concentrations at the participant’s residence from a hierarchical Bayesian space–time model. Estimates of fine particulate matter (particulate matter with an aerodynamic diameter of up to 2.5 μm [PM2.5]) and NO2 concentrations were obtained from land use regression. Cox proportional hazards regression models were used to examine mortality associations adjusted for individual- and ecological-level covariates. Measurements and Main Results: In single-pollutant models, we observed significant positive associations between O3, PM2.5, and NO2 concentrations and all-cause and cause-specific mortality. In two-pollutant models adjusted for PM2.5, significant positive associations remained between O3 and all-cause (hazard ratio [HR] per 10 ppb, 1.02; 95% confidence interval [CI], 1.01–1.04), circulatory (HR, 1.03; 95% CI, 1.01–1.05), and respiratory mortality (HR, 1.12; 95% CI, 1.08–1.16) that were unchanged with further adjustment for NO2. We also observed positive mortality associations with both PM2.5 (both near source and regional) and NO2 in multipollutant models. Conclusions: Findings derived from this large-scale prospective study suggest that long-term ambient O3 contributes to risk of respiratory and circulatory mortality. Substantial health and environmental benefits may be achieved by implementing further measures aimed at controlling O3 concentrations. PMID:26680605

Early presence of anti-angiogenesis-related adverse events as a potential biomarker of antitumor efficacy in metastatic gastric cancer patients treated with apatinib: a cohort study.

PubMed

Liu, Xinyang; Qin, Shukui; Wang, Zhichao; Xu, Jianming; Xiong, Jianping; Bai, Yuxian; Wang, Zhehai; Yang, Yan; Sun, Guoping; Wang, Liwei; Zheng, Leizhen; Xu, Nong; Cheng, Ying; Guo, Weijian; Yu, Hao; Liu, Tianshu; Lagiou, Pagona; Li, Jin

2017-09-05

Reliable biomarkers of apatinib response in gastric cancer (GC) are lacking. We investigated the association between early presence of common adverse events (AEs) and clinical outcomes in metastatic GC patients. We conducted a retrospective cohort study using data on 269 apatinib-treated GC patients in two clinical trials. AEs were assessed at baseline until 28 days after the last dose of apatinib. Clinical outcomes were compared between patients with and without hypertension (HTN), proteinuria, or hand and foot syndrome (HFS) in the first 4 weeks. Time-to-event variables were assessed using Kaplan-Meier methods and Cox proportional hazard regression models. Binary endpoints were assessed using logistic regression models. Landmark analyses were performed as sensitivity analyses. Predictive model was analyzed, and risk scores were calculated to predict overall survival. Presence of AEs in the first 4 weeks was associated with prolonged median overall survival (169 vs. 103 days, log-rank p = 0.0039; adjusted hazard ratio (HR) 0.64, 95% confidence interval [CI] 0.64-0.84, p = 0.001), prolonged median progression-free survival (86.5 vs. 62 days, log-rank p = 0.0309; adjusted HR 0.69, 95% CI 0.53-0.91, p = 0.007), and increased disease control rate (54.67 vs. 32.77%; adjusted odds ratio 2.67, p < 0.001). Results remained significant in landmark analyses. The onset of any single AE or any combinations of the AEs were all statistically significantly associated with prolonged OS, except for the presence of proteinuria. An AE-based prediction model and subsequently derived scoring system showed high calibration and discrimination in predicting overall survival. Presence of HTN, proteinuria, or HFS during the first cycle of apatinib treatment was a viable biomarker of antitumor efficacy in metastatic GC patients.

Eradication of hepatitis C virus and non-liver-related non-acquired immune deficiency syndrome-related events in human immunodeficiency virus/hepatitis C virus coinfection.

PubMed

Berenguer, Juan; Rodríguez-Castellano, Elena; Carrero, Ana; Von Wichmann, Miguel A; Montero, Marta; Galindo, María J; Mallolas, Josep; Crespo, Manuel; Téllez, María J; Quereda, Carmen; Sanz, José; Barros, Carlos; Tural, Cristina; Santos, Ignacio; Pulido, Federico; Guardiola, Josep M; Rubio, Rafael; Ortega, Enrique; Montes, María L; Jusdado, Juan J; Gaspar, Gabriel; Esteban, Herminia; Bellón, José M; González-García, Juan

2017-08-01

We assessed non-liver-related non-acquired immunodeficiency syndrome (AIDS)-related (NLR-NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk. The NLR-NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR-NAR cancer, bone events, and non-AIDS-related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4 + T-cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti-HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5-year follow-up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval [CI], 0.35-0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17-1.09; P = 0.075). Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver-related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344-356). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

Female breast cancer management and survival: The experience of major public hospitals in South Australia over 3 decades-trends by age and in the elderly.

PubMed

Roder, David; Farshid, Gelareh; Kollias, Jim; Koczwara, Bogda; Karapetis, Christos; Adams, Jacqui; Joshi, Rohit; Keefe, Dorothy; Miller, Caroline; Powell, Kate; Fusco, Kellie; Eckert, Marion; Buckley, Elizabeth; Beckmann, Kerri; Price, Timothy

2017-12-01

Clinical registry data from major South Australian public hospitals were used to investigate trends in invasive breast-cancer treatment and survival by age. Disease-specific survival was calculated for the 1980 to 2013 diagnostic period using Kaplan-Meier product-limit estimates, with a censoring of live cases on December 31, 2014. Cox proportional hazards regression was used to examine differences in survival by age and tumour characteristic. First-round treatments following diagnosis were analysed, using multiple logistic regression to adjust for confounding. Five-year survival increased from 75% in the 1980s to 87% in 2000 to 2013, consistent with national trends, and with increases occurring irrespective of age. There was an increased use of breast conserving surgery, radiotherapy, chemotherapy, and hormone treatments. Five-year survival was lower for women aged 80+ years, increasing from 65% in the 1980s to 74% in 2000 to 2013. Lower survival in these older women persisted after adjusting for TNM stage, other clinical variables, and diagnostic year, without evidence of a reduced disparity over time. Older women were less likely to have surgery, radiotherapy, and chemotherapy throughout 1980 to 2013. By comparison, their use of hormone therapy was elevated. The adjusted relative odds of mastectomy (as opposed to breast conserving surgery) were lower for the 80+ year age range. Breast-cancer survival increases applied to all ages, including 80+ years, but poorer outcomes persisted in this older group and the gap did not reduce. A key question is whether the best trade-off now exists between optimally therapeutic cancer treatment and accommodations for frailty and co-morbidity in the aged, or whether opportunities exist for better trade-offs and better survival. Local registry data are important for describing local service activity and outcomes by age for local service providers, health administrations and consumer groups; monitoring disparities; and indicating effects of local initiatives. © 2017 John Wiley & Sons, Ltd.

Temporal relationship of first-episode non-affective psychosis with cannabis use: a clinical verification of an epidemiological hypothesis.

PubMed

Barrigón, María L; Gurpegui, Manuel; Ruiz-Veguilla, Miguel; Diaz, Francisco J; Anguita, Manuel; Sarramea, Fernando; Cervilla, Jorge

2010-05-01

We analyzed the association of age at onset of psychosis treatment (AOPT) with having a history of cannabis use in patients with a first episode of non-affective psychosis. We also investigated the impact on the AOPT of exposure to cannabis in adolescence, compared with young adulthood, and of the additional exposure to cocaine. We recruited 112 consecutive patients (66 men and 46 women; age range, 18-57years) with a first psychotic episode. The composite international diagnostic interview (CIDI) was used to assess drug use and to define the age at onset of heaviest use (AOHU) of a drug, defined as the age when drug was used the most for each patient. The effect of cannabis and cocaine AOHU on AOPT was explored through Kruskal-Wallis and Mann-Whitney tests, and logistic regression. Sex-adjusted cumulative hazard curves and Cox regression models were used to compare the AOPT of patients with and without a history of cannabis use, or associated cocaine use. We found that the AOPT was significantly associated with the use of cannabis, independently of sex, use of cocaine, tobacco smoking or excessive alcohol consumption. There was a dose-response relationship between cannabis AOHU and AOPT: the earlier the AOHU the earlier the AOPT. Hazard curves showed that patients with a history of cannabis use had a higher hazard of having a first-episode psychosis than the rest of the patients (sex-adjusted log-rank chi(2)=23.43, df=1, p<0.001). Their respective median AOPT (25th, 75th percentiles) were 23.5 (21, 28) and 33.5years (27, 45) (for log-transformed AOPT, t=5.6, df=110, p<0.001). The sex-adjusted hazard ratio of psychosis onset comparing both groups was 2.66 (95% CI, 1.74-4.05). Our results are in favor of a catalytic role for cannabis use in the onset of psychosis. Copyright 2009 Elsevier Ltd. All rights reserved.

Association of Proton Pump Inhibitors Usage with Risk of Pneumonia in Dementia Patients.

PubMed

Ho, Sai-Wai; Teng, Ying-Hock; Yang, Shun-Fa; Yeh, Han-Wei; Wang, Yu-Hsun; Chou, Ming-Chih; Yeh, Chao-Bin

2017-07-01

To determine the association between usages of proton pump inhibitors (PPIs) and subsequent risk of pneumonia in dementia patients. Retrospective cohort study. Taiwanese National Health Insurance Research Database. The study cohort consisted of 786 dementia patients with new PPI usage and 786 matched dementia patients without PPI usage. The study endpoint was defined as the occurrence of pneumonia. The Cox proportional hazard model was used to estimate the pneumonia risk. Defined daily dose methodology was applied to evaluate the cumulative and dose-response relationships of PPI. Incidence of pneumonia was higher among patients with PPI usage (adjusted hazard ratio (HR) = 1.89; 95% CI = 1.51-2.37). Cox model analysis also demonstrated that age (adjusted HR = 1.05; 95% CI = 1.03-1.06), male gender (adjusted HR = 1.57; 95% CI = 1.25-1.98), underlying cerebrovascular disease (adjusted HR = 1.30; 95% CI = 1.04-1.62), chronic pulmonary disease (adjusted HR = 1.39; 95% CI = 1.09-1.76), congestive heart failure (adjusted HR = 1.54; 95% CI = 1.11-2.13), diabetes mellitus (adjusted HR = 1.54; 95% CI = 1.22-1.95), and usage of antipsychotics (adjusted HR = 1.29; 95% CI = 1.03-1.61) were independent risk factors for pneumonia. However, usage of cholinesterase inhibitors and histamine receptor-2 antagonists were shown to decrease pneumonia risk. PPI usage in dementia patients is associated with an 89% increased risk of pneumonia. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Mechanical dyssynchrony is additive to ECG criteria and independently associated with reverse remodelling and clinical response to cardiac resynchronisation therapy in patients with advanced heart failure

PubMed Central

Bank, Alan J; Gage, Ryan M; Marek, Josef J; Onishi, Toshinari; Burns, Kevin V; Schwartzman, David; Saba, Samir; Gorcsan, John

2015-01-01

Background QRS duration and morphology are known established predictors of cardiac resynchronisation therapy (CRT) response, whereas mechanical dyssynchrony is not. Our aim was to determine if mechanical dyssynchrony provides independent prognostic information on CRT response. Methods We studied 369 consecutive patients with heart failure (HF) with low ejection fraction (EF) and widened QRS receiving CRT. Radial dyssynchrony (septal-posterior radial peak strain delay ≥130 ms by speckle tracking) assessment was possible in 318 patients (86%). Associations with left ventricular end-systolic volume (LVESV) changes were examined using linear regression, and clinical outcomes analysed using Cox regression adjusted for multiple established outcome correlates. Results Patients with radial dyssynchrony before CRT (64%) had greater improvements in EF (8.8±9.4 vs 6.1±9.7 units, p=0.04) and LVESV (−30±41 vs −10±30 mL, p<0.01). Radial dyssynchrony was independently associated with reduction in LVESV (regression coefficient −10.5 mL, 95% CI −20.5 to −0.5, p=0.040) as was left bundle-branch block (−17.7 mL, −27.6 to −7.7, p=0.001). Patients with radial dyssynchrony had a 46% lower incidence of death, transplant or implantation of a left ventricular assist device (adjusted HR 0.54, 95% CI 0.31 to 0.92, p=0.02) and a 39% lower incidence of death or HF hospitalisation (0.61, 0.40 to 0.93, p=0.02) over 2 years. Conclusions Radial dyssynchrony was associated with significant improvements in LVESV and clinical outcomes following CRT and is independent of QRS duration or morphology, and additive to current ECG selection criteria to predict response to CRT. PMID:25973213

Comparative effectiveness of allopurinol versus febuxostat for preventing incident renal disease in older adults: an analysis of Medicare claims data.

PubMed

Singh, Jasvinder A; Cleveland, John D

2017-10-01

To assess the comparative effectiveness of allopurinol versus febuxostat for preventing incident renal disease in elderly. In a retrospective cohort study using 2006-2012 Medicare claims data, we included patients newly treated with allopurinol or febuxostat (baseline period of 183 days without either medication). We used 5:1 propensity-matched Cox regression analyses to compare the HR of incident renal disease with allopurinol use (and dose) versus febuxostat (reference). Sensitivity analyses included multivariable-adjusted regression models. There were 31 465 new allopurinol or febuxostat treatment episodes in 26 443 patients; 8570 ended in incident renal disease. Crude rates of incident renal disease per 1000 person-years were 192 with allopurinol versus 338 with febuxostat. Crude rates of incident renal disease per 1000 person-years were lower with higher daily dose: allopurinol <200, 200-299 and ≥300 mg/day with 238, 176 and 155; and febuxostat 40 and 80 mg/day with 341 and 326, respectively. In propensity-matched analyses, compared with febuxostat, allopurinol use was associated with lower HR of incident renal disease, 0.61 (95% CI 0.49 to 0.77). Compared with febuxostat 40 mg/day, allopurinol doses <200, 200-299 and ≥300 mg/day were associated with lower HR of incident renal disease, 0.75 (95% CI 0.65 to 0.86), 0.61 (95% CI 0.52 to 0.73) and 0.48 (95% CI 0.41 to 0.55), respectively. Sensitivity analyses using multivariable-adjusted regression confirmed these findings. Allopurinol was associated with a lower risk of incident renal disease in elderly patients than febuxostat. Future studies need to examine the mechanism of this potential renal benefit of allopurinol. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A Review of the Study Designs and Statistical Methods Used in the Determination of Predictors of All-Cause Mortality in HIV-Infected Cohorts: 2002–2011

PubMed Central

Otwombe, Kennedy N.; Petzold, Max; Martinson, Neil; Chirwa, Tobias

2014-01-01

Background Research in the predictors of all-cause mortality in HIV-infected people has widely been reported in literature. Making an informed decision requires understanding the methods used. Objectives We present a review on study designs, statistical methods and their appropriateness in original articles reporting on predictors of all-cause mortality in HIV-infected people between January 2002 and December 2011. Statistical methods were compared between 2002–2006 and 2007–2011. Time-to-event analysis techniques were considered appropriate. Data Sources Pubmed/Medline. Study Eligibility Criteria Original English-language articles were abstracted. Letters to the editor, editorials, reviews, systematic reviews, meta-analysis, case reports and any other ineligible articles were excluded. Results A total of 189 studies were identified (n = 91 in 2002–2006 and n = 98 in 2007–2011) out of which 130 (69%) were prospective and 56 (30%) were retrospective. One hundred and eighty-two (96%) studies described their sample using descriptive statistics while 32 (17%) made comparisons using t-tests. Kaplan-Meier methods for time-to-event analysis were commonly used in the earlier period (n = 69, 76% vs. n = 53, 54%, p = 0.002). Predictors of mortality in the two periods were commonly determined using Cox regression analysis (n = 67, 75% vs. n = 63, 64%, p = 0.12). Only 7 (4%) used advanced survival analysis methods of Cox regression analysis with frailty in which 6 (3%) were used in the later period. Thirty-two (17%) used logistic regression while 8 (4%) used other methods. There were significantly more articles from the first period using appropriate methods compared to the second (n = 80, 88% vs. n = 69, 70%, p-value = 0.003). Conclusion Descriptive statistics and survival analysis techniques remain the most common methods of analysis in publications on predictors of all-cause mortality in HIV-infected cohorts while prospective research designs are favoured. Sophisticated techniques of time-dependent Cox regression and Cox regression with frailty are scarce. This motivates for more training in the use of advanced time-to-event methods. PMID:24498313

Elevated risk of incarceration among street-involved youth who initiate drug dealing.

PubMed

Hoy, Carly; Barker, Brittany; Regan, Jackie; Dong, Huiru; Richardson, Lindsey; Kerr, Thomas; DeBeck, Kora

2016-11-22

Street-involved youth are known to be an economically vulnerable population that commonly resorts to risky activities such as drug dealing to generate income. While incarceration is common among people who use illicit drugs and associated with increased economic vulnerability, interventions among this population remain inadequate. Although previous research has documented the role of incarceration in further entrenching youth in both the criminal justice system and street life, less is known whether recent incarceration predicts initiating drug dealing among vulnerable youth. This study examines the relationship between incarceration and drug dealing initiation among street-involved youth. Between September 2005 and November 2014, data were collected through the At-Risk Youth Study, a cohort of street-involved youth who use illicit drugs, in Vancouver, Canada. An extended Cox model with time-dependent variables was used to examine the relationship between recent incarceration and initiation into drug dealing, controlling for relevant confounders. Among 1172 youth enrolled, only 194 (16.6%) were drug dealing naïve at baseline and completed at least one additional study visit to facilitate the assessment of drug dealing initiation. Among this sample, 56 (29%) subsequently initiated drug dealing. In final multivariable Cox regression analysis, recent incarceration was significantly associated with initiating drug dealing (adjusted hazard ratio = 2.31; 95% confidence interval (CI) 1.21-4.42), after adjusting for potential confounders. Measures of recent incarceration lagged to the prior study follow-up were not found to predict initiation of drug dealing (hazard ratio = 1.50; 95% CI 0.66-3.42). These findings suggest that among this study sample, incarceration does not appear to significantly propel youth to initiate drug dealing. However, the initiation of drug dealing among youth coincides with an increased risk of incarceration and their consequent vulnerability to the significant harms associated therein. Given that existing services tailored to street-involved youth are inadequate, evidence-based interventions should be invested and scaled up as a public health priority.

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.

Impact of residual kidney function on hemodialysis adequacy and patient survival.

PubMed

Wang, Mengjing; Obi, Yoshitsugu; Streja, Elani; Rhee, Connie M; Chen, Jing; Hao, Chuanming; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2018-04-23

Both dialysis dose and residual kidney function (RKF) contribute to solute clearance and are associated with outcomes in hemodialysis patients. We hypothesized that the association between dialysis dose and mortality is attenuated with greater RKF. Among 32 251 incident hemodialysis patients in a large US dialysis organization (2007-11), we examined the interaction between single-pool Kt/V (spKt/V) and renal urea clearance (rCLurea) levels in survival analyses using multivariable Cox proportional hazards regression model. The median rCLurea and mean baseline spKt/V were 3.06 [interquartile range (IQR) 1.74-4.85] mL/min/1.73 m2 and 1.32 ± 0.28, respectively. A total of 7444 (23%) patients died during the median follow-up of 1.2 years (IQR 0.5-2.2 years) with an incidence of 15.4 deaths per 100 patient-years. The Cox model with adjustment for case-mix and laboratory variables showed that rCLurea modified the association between spKt/V and mortality (Pinteraction = 0.03); lower spKt/V was associated with higher mortality among patients with low rCLurea (i.e. <3  mL/min/1.73 m2) but not among those with higher rCLurea. The adjusted mortality hazard ratios (aHRs) and 95% confidence intervals of the low (<1.2) versus high (≥1.2) spKt/V were 1.40 (1.12-1.74), 1.21 (1.10-1.33), 1.06 (0.98-1.14), and 1.00 (0.93-1.08) for patients with rCLurea of 0.0, 1.0, 3.0 and 6.0 mL/min/1.73 m2, respectively. Incident hemodialysis patients with substantial RKF do not exhibit the expected better survival at higher hemodialysis doses. RKF levels should be taken into account when deciding on the dose of dialysis treatment among incident hemodialysis patients.

Delivery of a very low birth weight infant and increased maternal risk of cancer and death: a population study with 16 years of follow-up.

PubMed

Grisaru-Granovsky, Sorina; Gordon, Ethel Sherry; Haklai, Ziona; Schimmel, Michael S; Drukker, Lior; Samueloff, Arnon; Keinan-Boker, Lital

2015-11-01

Pregnancy complications represent sentinel events for women's future health. We investigated whether delivery of a very low birth weight (VLBW) infant is associated with increased maternal risk for future incidence of maternal cancer and death. This is a population-based cohort study of linked Israeli Ministry of Health datasets between 1995 and 2011. Women delivering a live singleton <1,500 g infant (VLBW group) were compared with women delivering a live singleton, 3,000-3,500 g (control). The first pregnancy eligible for entry into the study, the "index pregnancy," reflected exposure status for each participant. Primary outcomes were maternal cancer and death. Cancer diagnoses were further classified by primary site. Cox regression models adjusted for follow-up period and maternal characteristics at index pregnancy: Age at delivery, ethnicity, years of education, marital status, and previous cancer afforded calculation of hazard ratios (HR) and 95% confidence intervals (CI). During the study period, 982,091 mothers with 2,243,736 live births were identified; of these, 13,773 births were VLBW eligible for inclusion in the study and 448,743 births were controls. Groups differed significantly by average follow-up and all maternal characteristics evaluated. Overall rate of cancers and death was significantly increased for VLBW women compared to controls: 18.4 versus 15.7% and 7.3 versus 3.2%, both p < 0.0001. The Cox model adjusted for maternal characteristics showed significantly increased risk of cancer (all sites) in the VLBW women: HR 1.18 (95% CI 1.02-1.37) and for death: HR 2.13 (95% CI 1.68-2.71), and an increased combined risk of both outcomes: HR 1.4 (95% CI 1.23-1.59). The delivery of a VLBW newborn is an independent lifetime risk factor for subsequent maternal cancers and death. These women may benefit from targeted cancer screening and counseling.

Anti-rheumatic drug use and risk of hospitalization for congestive heart failure in rheumatoid arthritis.

PubMed

Bernatsky, S; Hudson, M; Suissa, S

2005-05-01

To assess the risk of hospitalization for congestive heart failure (CHF) associated with the use of disease-modifying anti-rheumatic drugs (DMARDs) and other medications used in RA. We used a case-control design nested within an administrative database cohort of patients with rheumatoid arthritis (RA) who were dispensed a DMARD between September 1998 and December 2001. Subjects identified with a prior history of CHF were excluded. For each hospitalized case of CHF identified during follow-up, 10 controls matched on age and time were randomly selected from the cohort. Conditional logistic regression was used to estimate the rate ratio (RR) of hospitalizations for CHF associated with the current use of specific drugs, adjusted for sex and co-morbidity. The cohort included 41 885 patients; 75% were women, with an average age at cohort entry of 51 yr. During follow-up, 520 hospitalizations for CHF occurred, for a rate of 10.1 per 1000 per year. The adjusted RR of CHF for current use of any DMARD was 0.7 (95% CI 0.6-0.9) relative to no current use. By DMARD category, there was evidence of a beneficial effect for both tumour necrosis factor-alpha antagonists (RR 0.5, 95% CI 0.2-0.9) and methotrexate monotherapy (RR 0.8, 95% CI 0.6-1.0). For non-DMARD medications, the rate of CHF was not clearly increased or decreased, except for COX-2 inhibitors. The data suggested an increased risk of CHF with rofecoxib (RR 1.3, 95% CI 1.0-3.1) and a decreased risk of CHF with celecoxib (RR 0.6, 95% CI 0.4, 1.0). The use of DMARDs was associated with a reduction in the risk of hospitalizations for CHF in this RA cohort. The increased risk with rofecoxib alongside a decreased risk with celecoxib suggests the absence of a class effect with respect to COX-II inhibitors for some types of cardiovascular morbidity.

Outcome of intracerebral hemorrhage associated with different oral anticoagulants

PubMed Central

Wilson, Duncan; Seiffge, David J.; Traenka, Christopher; Basir, Ghazala; Purrucker, Jan C.; Rizos, Timolaos; Sobowale, Oluwaseun A.; Sallinen, Hanne; Yeh, Shin-Joe; Wu, Teddy Y.; Ferrigno, Marc; Houben, Rik; Schreuder, Floris H.B.M.; Perry, Luke A.; Tanaka, Jun; Boulanger, Marion; Al-Shahi Salman, Rustam; Jäger, Hans R.; Ambler, Gareth; Shakeshaft, Clare; Yakushiji, Yusuke; Choi, Philip M.C.; Staals, Julie; Cordonnier, Charlotte; Jeng, Jiann-Shing; Veltkamp, Roland; Dowlatshahi, Dar; Engelter, Stefan T.; Parry-Jones, Adrian R.; Meretoja, Atte

2017-01-01

Objective: In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non–vitamin K antagonist oral anticoagulation–related ICH (NOAC-ICH) and vitamin K antagonist–associated ICH (VKA-ICH). Methods: We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours. Results: We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6–38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0–27.9) for VKA-ICH (p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52–1.64] [p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18–1.19 [p = 0.11]). Conclusions: In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH. PMID:28381513

Outcome of intracerebral hemorrhage associated with different oral anticoagulants.

PubMed

Wilson, Duncan; Seiffge, David J; Traenka, Christopher; Basir, Ghazala; Purrucker, Jan C; Rizos, Timolaos; Sobowale, Oluwaseun A; Sallinen, Hanne; Yeh, Shin-Joe; Wu, Teddy Y; Ferrigno, Marc; Houben, Rik; Schreuder, Floris H B M; Perry, Luke A; Tanaka, Jun; Boulanger, Marion; Al-Shahi Salman, Rustam; Jäger, Hans R; Ambler, Gareth; Shakeshaft, Clare; Yakushiji, Yusuke; Choi, Philip M C; Staals, Julie; Cordonnier, Charlotte; Jeng, Jiann-Shing; Veltkamp, Roland; Dowlatshahi, Dar; Engelter, Stefan T; Parry-Jones, Adrian R; Meretoja, Atte; Werring, David J

2017-05-02

In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non-vitamin K antagonist oral anticoagulation-related ICH (NOAC-ICH) and vitamin K antagonist-associated ICH (VKA-ICH). We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours. We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6-38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0-27.9) for VKA-ICH ( p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [ p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52-1.64] [ p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [ p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18-1.19 [ p = 0.11]). In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

The influence of individual socioeconomic status on the clinical outcomes in ischemic stroke patients with different neighborhood status in Shanghai, China

PubMed Central

Yan, Han; Liu, Baoxin; Meng, Guilin; Shang, Bo; Jie, Qiqiang; Wei, Yidong; Liu, Xueyuan

2017-01-01

Objective: Socioeconomic status (SES) is being recognized as an important factor in both social and medical problems. The aim of present study is to examine the relationship between SES and ischemic stroke and investigate whether SES is a predictor of clinical outcomes among patients with different neighborhood status from Shanghai, China. Methods: A total of 471 first-ever ischemic stroke patients aged 18-80 years were enrolled in this retrospective study. The personal SES of each patient was evaluated using a summed score derived from his or her educational level, household income, occupation, and medical reimbursement rate. Clinical adverse events and all-cause mortality were analyzed to determine whether SES was a prognostic factor, its prognostic impact was then assessed based on different neighborhood status using multivariable Cox proportional hazard models after adjusting for other covariates. Results: The individual SES showed a significant positive correlation with neighborhood status (r = 0.370; P < 0.001). The incidence of clinical adverse events and mortality were significantly higher in low SES patients compared with middle and high SES patients (P = 0.001 and P = 0.037, respectively). After adjusting other risk factors and neighborhood status, Kaplan-Meier analysis showed clinical adverse events and deaths were still higher in the low SES patients (all P < 0.05). Multivariate Cox regression analysis demonstrated that both personal SES and neighborhood status are independent prognostic factors for ischemic stroke (all P < 0.05). Besides, among patients with low and middle neighborhood status, lower individual SES was significantly associated with clinical adverse events and mortality (all P < 0.05). Conclusion: Both individual SES and neighborhood status are significantly associated with the prognosis after ischemic stroke. A lower personal SES as well as poorer neighborhood status may significantly increase risk for adverse clinical outcomes among ischemic stroke patients. PMID:28138313

Cisplatin and Etoposide Versus Carboplatin and Paclitaxel With Concurrent Radiotherapy for Stage III Non–Small-Cell Lung Cancer: An Analysis of Veterans Health Administration Data

PubMed Central

Santana-Davila, Rafael; Devisetty, Kiran; Szabo, Aniko; Sparapani, Rodney; Arce-Lara, Carlos; Gore, Elizabeth M.; Moran, Amy; Williams, Christina D.; Kelley, Michael J.; Whittle, Jeffrey

2015-01-01

Purpose The optimal chemotherapy regimen to use with radiotherapy in stage III non–small-cell lung cancer is unknown. Here, we compare the outcome of patents treated within the Veterans Health Administration with either etoposide-cisplatin (EP) or carboplatin-paclitaxel (CP). Methods We identified patients treated with EP and CP with concurrent radiotherapy from 2001 to 2010. Survival rates were compared using Cox proportional hazards regression models with adjustments for confounding provided by propensity score methods and an instrumental variables analysis. Comorbidities and treatment complications were identified through administrative data. Results A total of 1,842 patients were included; EP was used in 27% (n = 499). Treatment with EP was not associated with a survival advantage in a Cox proportional hazards model (hazard ratio [HR], 0.97; 95% CI, 0.85 to 1.10), a propensity score matched cohort (HR, 1.07; 95% CI, 0.91 to 1.24), or a propensity score adjusted model (HR, 0.97; 95% CI, 0.85 to 1.10). In an instrumental variables analysis, there was no survival advantage for patients treated in centers where EP was used more than 50% of the time as compared with centers where EP was used in less than 10% of the patients (HR, 1.07; 95% CI, 0.90 to 1.26). Patients treated with EP, compared with patients treated with CP, had more hospitalizations (2.4 v 1.7 hospitalizations, respectively; P < .001), outpatient visits (17.6 v 12.6 visits, respectively; P < .001), infectious complications (47.3% v 39.4%, respectively; P = .0022), acute kidney disease/dehydration (30.5% v 21.2%, respectively; P < .001), and mucositis/esophagitis (18.6% v 14.4%, respectively; P = .0246). Conclusion After accounting for prognostic variables, patients treated with EP versus CP had similar overall survival, but EP was associated with increased morbidity. PMID:25422491

Increased COX-2 expression in epithelial and stromal cells of high mammographic density tissues and in a xenograft model of mammographic density.

PubMed

Chew, G L; Huo, C W; Huang, D; Hill, P; Cawson, J; Frazer, H; Hopper, J L; Haviv, I; Henderson, M A; Britt, K; Thompson, E W

2015-08-01

Mammographic density (MD) adjusted for age and body mass index is one of the strongest known risk factors for breast cancer. Given the high attributable risk of MD for breast cancer, chemoprevention with a safe and available agent that reduces MD and breast cancer risk would be beneficial. Cox-2 has been implicated in MD-related breast cancer risk, and was increased in stromal cells in high MD tissues in one study. Our study assessed differential Cox-2 expression in epithelial and stromal cells in paired samples of high and low MD human breast tissue, and in a validated xenograft biochamber model of MD. We also examined the effects of endocrine treatment upon Cox-2 expression in high and low MD tissues in the MD xenograft model. Paired high and low MD human breast tissue samples were immunostained for Cox-2, then assessed for differential expression and staining intensity in epithelial and stromal cells. High and low MD human breast tissues were separately maintained in biochambers in mice treated with Tamoxifen, oestrogen or placebo implants, then assessed for percentage Cox-2 staining in epithelial and stromal cells. Percentage Cox-2 staining was greater for both epithelial (p = 0.01) and stromal cells (p < 0.0001) of high compared with low MD breast tissues. In high MD biochamber tissues, percentage Cox-2 staining was greater in stromal cells of oestrogen-treated versus placebo-treated tissues (p = 0.05).

Bayesian dynamic regression models for interval censored survival data with application to children dental health.

PubMed

Wang, Xiaojing; Chen, Ming-Hui; Yan, Jun

2013-07-01

Cox models with time-varying coefficients offer great flexibility in capturing the temporal dynamics of covariate effects on event times, which could be hidden from a Cox proportional hazards model. Methodology development for varying coefficient Cox models, however, has been largely limited to right censored data; only limited work on interval censored data has been done. In most existing methods for varying coefficient models, analysts need to specify which covariate coefficients are time-varying and which are not at the time of fitting. We propose a dynamic Cox regression model for interval censored data in a Bayesian framework, where the coefficient curves are piecewise constant but the number of pieces and the jump points are covariate specific and estimated from the data. The model automatically determines the extent to which the temporal dynamics is needed for each covariate, resulting in smoother and more stable curve estimates. The posterior computation is carried out via an efficient reversible jump Markov chain Monte Carlo algorithm. Inference of each coefficient is based on an average of models with different number of pieces and jump points. A simulation study with three covariates, each with a coefficient of different degree in temporal dynamics, confirmed that the dynamic model is preferred to the existing time-varying model in terms of model comparison criteria through conditional predictive ordinate. When applied to a dental health data of children with age between 7 and 12 years, the dynamic model reveals that the relative risk of emergence of permanent tooth 24 between children with and without an infected primary predecessor is the highest at around age 7.5, and that it gradually reduces to one after age 11. These findings were not seen from the existing studies with Cox proportional hazards models.

Development of a five-year mortality model in systemic sclerosis patients by different analytical approaches.

PubMed

Beretta, Lorenzo; Santaniello, Alessandro; Cappiello, Francesca; Chawla, Nitesh V; Vonk, Madelon C; Carreira, Patricia E; Allanore, Yannick; Popa-Diaconu, D A; Cossu, Marta; Bertolotti, Francesca; Ferraccioli, Gianfranco; Mazzone, Antonino; Scorza, Raffaella

2010-01-01

Systemic sclerosis (SSc) is a multiorgan disease with high mortality rates. Several clinical features have been associated with poor survival in different populations of SSc patients, but no clear and reproducible prognostic model to assess individual survival prediction in scleroderma patients has ever been developed. We used Cox regression and three data mining-based classifiers (Naïve Bayes Classifier [NBC], Random Forests [RND-F] and logistic regression [Log-Reg]) to develop a robust and reproducible 5-year prognostic model. All the models were built and internally validated by means of 5-fold cross-validation on a population of 558 Italian SSc patients. Their predictive ability and capability of generalisation was then tested on an independent population of 356 patients recruited from 5 external centres and finally compared to the predictions made by two SSc domain experts on the same population. The NBC outperformed the Cox-based classifier and the other data mining algorithms after internal cross-validation (area under receiving operator characteristic curve, AUROC: NBC=0.759; RND-F=0.736; Log-Reg=0.754 and Cox= 0.724). The NBC had also a remarkable and better trade-off between sensitivity and specificity (e.g. Balanced accuracy, BA) than the Cox-based classifier, when tested on an independent population of SSc patients (BA: NBC=0.769, Cox=0.622). The NBC was also superior to domain experts in predicting 5-year survival in this population (AUROC=0.829 vs. AUROC=0.788 and BA=0.769 vs. BA=0.67). We provide a model to make consistent 5-year prognostic predictions in SSc patients. Its internal validity, as well as capability of generalisation and reduced uncertainty compared to human experts support its use at bedside. Available at: http://www.nd.edu/~nchawla/survival.xls.

Survival in Patients with Advanced Non-cystic Fibrosis Bronchiectasis Versus Cystic Fibrosis on the Waitlist for Lung Transplantation.

PubMed

Hayes, Don; Kopp, Benjamin T; Tobias, Joseph D; Woodley, Frederick W; Mansour, Heidi M; Tumin, Dmitry; Kirkby, Stephen E

2015-12-01

Survival in non-cystic fibrosis (CF) bronchiectasis is not well studied. The United Network for Organ Sharing database was queried from 1987 to 2013 to compare survival in adult patients with non-CF bronchiectasis to patients with CF listed for lung transplantation (LTx). Each subject was tracked from waitlist entry date until death or censoring to determine survival differences between the two groups. Of 2112 listed lung transplant candidates with bronchiectasis (180 non-CF, 1932 CF), 1617 were used for univariate Cox and Kaplan-Meier survival function analysis, 1173 for multivariate Cox models, and 182 for matched-pairs analysis based on propensity scores. Compared to CF, patients with non-CF bronchiectasis had a significantly lower mortality by univariate Cox analysis (HR 0.565; 95 % CI 0.424, 0.754; p < 0.001). Adjusting for potential confounders, multivariate Cox models identified a significant reduction in risk for death associated with non-CF bronchiectasis who were lung transplant candidates (HR 0.684; 95 % CI 0.475, 0.985; p = 0.041). Results were consistent in multivariate models adjusting for pulmonary hypertension and forced expiratory volume in one second. Non-CF bronchiectasis with advanced lung disease was associated with significantly lower mortality hazard compared to CF bronchiectasis on the waitlist for LTx. Separate referral and listing criteria for LTx in non-CF and CF populations should be considered.

[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.

[HIV/AIDS related mortality in southern Shanxi province and its risk factors].

PubMed

Ning, Shaoping; Xue, Zidong; Wei, Jun; Mu, Shengcai; Xu, Yajuan; Jia, Shaoxian; Qiu, Chao; Xu, Jianqing

2015-03-01

To explore factors influencing mortality rate of HIV/AIDS and to improve the effectiveness of antiretroviral therapy (ART). By means of retrospective cohort study and the AIDS control information system, HIV/AIDS case reports and antiviral treatment information of 4 cities in southern Shanxi province up to end of December 2012 were selected, to calculate the mortality rate and treatment coverage based on further data collected, along with analysis using the Cox proportional hazards survival regression. 4 040 cases confirmed of HIV/AIDS were included in this study. The average age was (36.0 ± 12.9) years, with 65.3% being male, 56.5% being married, 73.5% having junior high school education or lower, 58.4% being peasants, 54.3% with sexually transmitted infection (40.1% were heterosexual, 14.2% were homosexual), and 38.9% were infected via blood transmission (20.2% were former plasma donors, 16.2% blood transfusion or products recipients, 2.4% were injection drug users). Overall mortality decreased from 40.2 per 100 person/year in 2004 to 6.3 per 100 person/year in 2012, with treatment coverage concomitantly increasing from almost 14.8% to 63.4%. Cox proportional hazards survival regression was used on 4 040 qualified cases, demonstrating the top mortality risk factor was without antiretroviral therapy (RR = 14.9, 95% CI: 12.7-17.4). Cox proportional hazards survival regression was made on 1 938 cases of antiviral treatment, demonstrating that the mortality risk of underweight or obese before treatment was higher than those of normal and overweight cases (RR = 2.7, 95% CI: 1.6-4.5), and the mortality of those having a CD4(+) T-lymphocyte count ≤ 50 cells per µl before treatment was more than 50 cases (RR = 2.6, 95% CI: 1.5-4.5); Cox proportional hazards survival regression was made on 2 102 cases of untreated cases, demonstrating the mortality risk of those initially diagnosed as AIDS was higher than those initially diagnosed as HIV (RR = 3.4, 95% CI: 2.9-4.0). The ART could successfully make lower HIV/AIDS mortality rate, indicating effective ART can further decrease mortality.

DNA polymorphisms predict time to progression from uncomplicated to complicated Crohn's disease.

PubMed

Pernat Drobež, Cvetka; Repnik, Katja; Gorenjak, Mario; Ferkolj, Ivan; Weersma, Rinse K; Potočnik, Uroš

2018-04-01

Most patients with Crohn's disease (CD) are diagnosed with the uncomplicated inflammatory form of the disease (Montreal stage B1). However, the majority of them will progress to complicated stricturing (B2) and penetrating (B3) CD during their lifetimes. The aim of our study was to identify the genetic factors associated with time to progression from uncomplicated to complicated CD. Patients with an inflammatory phenotype at diagnosis were followed up for 10 years. Genotyping was carried out using Illumina ImmunoChip. After quality control, association analyses, Bonferroni's adjustments, linear and Cox's regression, and Kaplan-Meier analysis were carried out for 111 patients and Manhattan plots were constructed. Ten years after diagnosis, 39.1% of the patients still had the inflammatory form and 60.9% progressed to complicated disease, with an average time to progression of 5.91 years. Ileal and ileocolonic locations were associated with the complicated CD (P=1.08E-03). We found that patients with the AA genotype at single-nucleotide polymorphism rs16857259 near the gene CACNA1E progressed to the complicated form later (8.80 years) compared with patients with the AC (5.11 years) or CC (2.00 years) genotypes (P=3.82E-07). In addition, nine single-nucleotide polymorphisms (near the genes RASGRP1, SULF2, XPO1, ZBTB44, HLA DOA/BRD2, HLA DRB1/HLA DQA1, PPARA, PUDP, and KIAA1614) showed a suggestive association with disease progression (P<10). Multivariate Cox's regression analysis on the basis of clinical and genetic data confirmed the association of the selected model with disease progression (P=5.73E-16). Our study confirmed the association between the locus on chromosome 1 near the gene CACNA1E with time to progression from inflammatory to stricturing or penetrating CD. Predicting the time to progression is useful to the clinician in terms of individualizing patients' management.

Incidence and risk factors of postoperative pneumonia following cancer surgery in adult patients with selected solid cancer: results of "Cancer POP" study.

PubMed

Jung, Jiwon; Moon, Song Mi; Jang, Hee-Chang; Kang, Cheol-In; Jun, Jae-Bum; Cho, Yong Kyun; Kang, Seung-Ji; Seo, Bo-Jeong; Kim, Young-Joo; Park, Seong-Beom; Lee, Juneyoung; Yu, Chang Sik; Kim, Sung-Han

2018-01-01

The aim of this study was to investigate the incidence and risk factors of postoperative pneumonia (POP) within 1 year after cancer surgery in patients with the five most common cancers (gastric, colorectal, lung, breast cancer, and hepatocellular carcinoma [HCC]) in South Korea. This was a multicenter and retrospective cohort study performed at five nationwide cancer centers. The number of cancer patients in each center was allocated by the proportion of cancer surgery. Adult patients were randomly selected according to the allocated number, among those who underwent cancer surgery from January to December 2014 within 6 months after diagnosis of cancer. One-year cumulative incidence of POP was estimated using Kaplan-Meier analysis. An univariable Cox's proportional hazard regression analysis was performed to identify risk factors for POP development. As a multivariable analysis, confounders were adjusted using multiple Cox's PH regression model. Among the total 2000 patients, the numbers of patients with gastric cancer, colorectal cancer, lung cancer, breast cancer, and HCC were 497 (25%), 525 (26%), 277 (14%), 552 (28%), and 149 (7%), respectively. Overall, the 1-year cumulative incidence of POP was 2.0% (95% CI, 1.4-2.6). The 1-year cumulative incidences in each cancer were as follows: lung 8.0%, gastric 1.8%, colorectal 1.0%, HCC 0.7%, and breast 0.4%. In multivariable analysis, older age, higher Charlson comorbidity index (CCI) score, ulcer disease, history of pneumonia, and smoking were related with POP development. In conclusions, the 1-year cumulative incidence of POP in the five most common cancers was 2%. Older age, higher CCI scores, smoker, ulcer disease, and previous pneumonia history increased the risk of POP development in cancer patients. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Association between occupational stressors and type 2 diabetes among Chinese police officers: a 4-year follow-up study in Tianjin, China.

PubMed

Yu, Hao; Liu, Jin-chuan; Fan, Ya-jiao; Li, Chen; Zhang, Li-xin; Chen, Xi; Yue, Song; Lu, Wen-li; Yang, Xi-lin; Tang, Nai-jun

2016-02-01

To explore the relationship between occupational stressors and the incidence of type 2 diabetes mellitus among police officers. Baseline data were collected from policemen who completed the Occupational Stress Inventory-Revised (OSI-R) questionnaire, a self-designed questionnaire, and underwent free clinical measurements at the Medical Center of Police Hospital in Tianjin, China, in April 2007. A total of 5811 policemen participated in follow-up with the dynamic observation of new-onset diabetes (NOD) events occurring annually between 2008 and 2011. Occupational stress was measured by the OSI-R questionnaire, which contains 14 different scales. Cox proportional hazards regression was used to calculate the hazard ratios (HR) of the incidence of type 2 diabetes mellitus (T2DM) by occupational stressors. A total of 3.1% of the participants (n = 179) developed NOD in the follow-up period from 2008 to 2011, and the incidence rates of NOD were 0.58% in 2008, 0.98% in 2009, 0.52% in 2010, and 1.01% in 2011. Role overload (RO), role boundary (RB), physical environment (PE), interpersonal strain (IS), and physical strain (PHS) were associated with the incidence of T2DM (RO: HR = 1.574, 95% CI = 1.071-2.372; RB: HR = 1.645, 95% CI = 1.144-2.365; PE: HR = 2.292, 95% CI = 1.545-3.400; IS: HR = 1.537, 95% CI = 1.079-2.191; and PHS: HR = 1.680, 95% CI = 1.167-2.006) after adjustment for confounding factors. A subgroup Cox regression analysis among traffic control police officers showed the specific work stressors remained robust except RO. Several aspects of stressors were independent predictors of T2DM in a prospective cohort study in Tianjin, China. This practical information can be applied to the development of psychological interventions against T2DM.

Obstetric mode of delivery and attention-deficit/hyperactivity disorder: a sibling-matched study.

PubMed

Curran, Eileen A; Khashan, Ali S; Dalman, Christina; Kenny, Louise C; Cryan, John F; Dinan, Timothy G; Kearney, Patricia M

2016-04-01

It has been suggested that birth by caesarean section (CS) may affect psychological development through changes in microbiota or stress response. We assessed the impact of mode of delivery, specifically CS, on the development of attention-deficit/hyperactivity disorder (ADHD), using a large, population-based cohort. The study cohort consisted of all singleton live births in Sweden from 1990 to 2008 using data from Swedish national registers. Mode of delivery included: unassisted vaginal delivery(VD), assisted VD, elective CS or emergency CS. ADHD was determined using International Classification of Diseases version 10 (F90 or F98.8), or prescription for ADHD medication. We used Cox regression to assess the association between birth by CS and ADHD in the total study population, adjusting for perinatal and sociodemographic factors, then stratified Cox regression analysis on maternal identification number to assess the association among siblings. Our cohort consisted of 1 722 548 children, and among these 47 778 cases of ADHD. The hazard ratio (HR) of the association between elective CS, compared with unassisted VD, and ADHD was 1.15 [95% confidence interval (CI): 1.11-1.20] in the cohort, and 1.05 (95% CI: 0.93-1.18) in the stratified analysis. The HR of the association between emergency CS and ADHD was 1.16 (95% CI: 1.12-1.20])in the cohort and 1.13 (95% CI: 1.01-1.26) in the stratified analysis. Birth by CS is associated with a small increased risk of ADHD. However among siblings the association only remained for emergency CS. If this were a causal effect by CS, the association would be expected to persist for both types of CS, suggesting the observed association is due to confounding. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Cardiovascular Complications and Short-term Mortality Risk in Community-Acquired Pneumonia.

PubMed

Violi, Francesco; Cangemi, Roberto; Falcone, Marco; Taliani, Gloria; Pieralli, Filippo; Vannucchi, Vieri; Nozzoli, Carlo; Venditti, Mario; Chirinos, Julio A; Corrales-Medina, Vicente F

2017-06-01

Previous reports suggest that community-acquired pneumonia (CAP) is associated with an enhanced risk of cardiovascular complications. However, a contemporary and comprehensive characterization of this association is lacking. In this multicenter study, 1182 patients hospitalized for CAP were prospectively followed for up to 30 days after their hospitalization for this infection. Study endpoints included myocardial infarction, new or worsening heart failure, atrial fibrillation, stroke, deep venous thrombosis, cardiovascular death, and total mortality. Three hundred eighty (32.2%) patients experienced intrahospital cardiovascular events (CVEs) including 281 (23.8%) with heart failure, 109 (9.2%) with atrial fibrillation, 89 (8%) with myocardial infarction, 11 (0.9%) with ischemic stroke, and 1 (0.1%) with deep venous thrombosis; 28 patients (2.4%) died for cardiovascular causes. Multivariable Cox regression analysis showed that intrahospital Pneumonia Severity Index (PSI) class (hazard ratio [HR], 2.45, P = .027; HR, 4.23, P < .001; HR, 5.96, P < .001, for classes III, IV, and V vs II, respectively), age (HR, 1.02, P = .001), and preexisting heart failure (HR, 1.85, P < .001) independently predicted CVEs. One hundred three (8.7%) patients died by day 30 postadmission. Thirty-day mortality was significantly higher in patients who developed CVEs compared with those who did not (17.6% vs 4.5%, P < .001). Multivariable Cox regression analysis showed that intrahospital CVEs (HR, 5.49, P < .001) independently predicted 30-day mortality (after adjustment for age, PSI score, and preexisting comorbid conditions). CVEs, mainly those confined to the heart, complicate the course of almost one-third of patients hospitalized for CAP. More importantly, the occurrence of CVEs is associated with a 5-fold increase in CAP-associated 30-day mortality. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Predictors of Survival among Adult Ethiopian Patients in the National ART Program at Seven University Teaching Hospitals: A Prospective Cohort Study.

PubMed

Fekade, Daniel; Weldegebreal, Teklu; Teklu, Alula M; Damen, Melake; Abdella, Saro; Baraki, Nega; Belayhun, Bekele; Berhan, Eyoel; Kebede, Amha; Assefa, Yibeltal

2017-02-01

In Ethiopia, the publicly funded antiretroviral treatment (ART) program was started in 2005. Two hundred seventy-five thousand patients were enrolled in the national ART program by 2012. However, there is limited data on mortality and predictors of death among adult patients in the ART program. The study aimed to estimate mortality and risk factors for death among adult, ART-naïve patients, started in the national ART program from January 2009 to July 2013. Multi-site, prospective, observational cohort study of adult, age > 18 years, ART-naïve patients, started in the national ART program at seven university-affiliated hospitals from January 2009 - July 2013. Kaplan-Meier and Cox regression analyses were used to estimate survival and determine risk factors for death. A total of 976 patients, 594 females (60.9 %), were enrolled into the study. Median age of the cohort was 33years. The median CD4 count at start of ART was 144 cells/µl (interquartile range (IQR) 78-205), and 34.2% (330/965) had CD4 < 100. Sixty-three percent (536/851) had viral load greater than 5 log copies/ml (IQR 4.7-5.7) at base line. One hundred and one deaths were recorded during follow-up period, all-cause mortality rate 10.3%; 5.4 deaths/100 person years of observation, 95% confidence interval 4.4-6.5. Seventy percent of the deaths occurred within six months of starting ART. Cox regression analyses showed that the following measures independently predicted mortality: age >51 years, (Adjusted Hazard Ratio (AHR) 4.01, P=0.003), WHO stages III&IV, (AHR 1.76, p = 0.025), CD4 count, <100, (AHR 2.36, p =0.006), and viral load >5 log copies /ml (CHR 1.71, p = 0.037). There is high early on- ART mortality in patients presenting with advanced immunodeficiency. Detecting cases and initiating ART before onset of advanced immunodeficiency might improve survival.

A tale of two countries: all-cause mortality among people living with HIV and receiving combination antiretroviral therapy in the UK and Canada.

PubMed

Patterson, S; Jose, S; Samji, H; Cescon, A; Ding, E; Zhu, J; Anderson, J; Burchell, A N; Cooper, C; Hill, T; Hull, M; Klein, M B; Loutfy, M; Martin, F; Machouf, N; Montaner, Jsg; Nelson, M; Raboud, J; Rourke, S B; Tsoukas, C; Hogg, R S; Sabin, C

2017-10-01

We sought to compare all-cause mortality of people living with HIV and accessing care in Canada and the UK. Individuals from the Canadian Observational Cohort (CANOC) collaboration and UK Collaborative HIV Cohort (UK CHIC) study who were aged ≥ 18 years, had initiated antiretroviral therapy (ART) for the first time between 2000 and 2012 and who had acquired HIV through sexual transmission were included in the analysis. Cox regression was used to investigate the difference in mortality risk between the two cohort collaborations, accounting for loss to follow-up as a competing risk. A total of 19 960 participants were included in the analysis (CANOC, 4137; UK CHIC, 15 823). CANOC participants were more likely to be older [median age 39 years (interquartile range (IQR): 33, 46 years) vs. 36 years (IQR: 31, 43 years) for UK CHIC participants], to be male (86 vs. 73%, respectively), and to report men who have sex with men (MSM) sexual transmission risk (72 vs. 56%, respectively) (all P < 0.001). Overall, 762 deaths occurred during 98 798 person-years (PY) of follow-up, giving a crude mortality rate of 7.7 per 1000 PY [95% confidence interval (CI): 7.1, 8.3 per 1000 PY]. The crude mortality rates were 8.6 (95% CI: 7.4, 10.0) and 7.5 (95% CI: 6.9, 8.1) per 1000 PY among CANOC and UK CHIC study participants, respectively. No statistically significant difference in mortality risk was observed between the cohort collaborations in Cox regression accounting for loss to follow-up as a competing risk (adjusted hazard ratio 0.86; 95% CI: 0.72-1.03). Despite differences in national HIV care provision and treatment guidelines, mortality risk did not differ between CANOC and UK CHIC study participants who acquired HIV through sexual transmission. © 2017 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

Real-world impact of non-breast cancer-specific death on overall survival in resectable breast cancer.

PubMed

Fu, Jianfei; Wu, Lunpo; Jiang, Mengjie; Li, Dan; Jiang, Ting; Fu, Wei; Wang, Liangjing; Du, Jinlin

2017-07-01

The real-world occurrence rate of non-breast cancer-specific death (non-BCSD) and its impact on patients with breast cancer are poorly recognized. Women with resectable breast cancer from 1990 to 2007 in the Surveillance, Epidemiology, and End Results database (n = 199,963) were analyzed. The outcome events of breast cancer were classified as breast cancer-specific death (BCSD), non-BCSD, or survival. Binary logistics was used to estimate the occurrence rates of non-BCSD and BCSD with different clinicopathological factors. The Gray method was used to measure the cumulative incidence of non-BCSD and BCSD. The ratio of non-BCSDs to all causes of death and stacked cumulative incidence function plots were used to present the impact of non-BCSD on overall survival (OS). Models of Cox proportional hazards regression and competing risk regression were compared to highlight the suitable model. There were 12,879 non-BCSDs (6.44%) and 28,784 BCSDs (14.39%). The oldest age group (>62 years), black race, and a single or divorced marital status were associated with more non-BCSDs. With adjustments for age, a hormone receptor-positive (HoR+) status was no longer related to increased non-BCSDs. In patients with grade 1, stage I disease and an HoR+ status as well as the oldest subgroup, a great dilution of non-BCSD on all causes of death could be observed, and this led to incorrect interpretations. The inaccuracy, caused by the commonly used Cox proportional hazards model, could be corrected by a competing risk model. OS was largely impaired by non-BCSD during early breast cancer. For some future clinical trial planning, especially for the oldest patients and those with HoR+ breast cancer, non-BCSD should be considered a competing risk event. Cancer 2017;123:2432-43. © 2017 American Cancer Society. © 2017 American Cancer Society.

Primary Sjogren's syndrome and the risk of acute pancreatitis: a nationwide cohort study.

PubMed

Chang, Chi-Ching; Chang, Yu-Sheng; Wang, Shu-Hung; Lin, Shyr-Yi; Chen, Yi-Hsuan; Chen, Jin Hua

2017-08-11

Studies on the risk of acute pancreatitis in patients with primary Sjogren's syndrome (pSS) are limited. We evaluated the effects of pSS on the risk of acute pancreatitis in a nationwide, population-based cohort in Taiwan. Population-based retrospective cohort study. We studied the claims data of the >97% Taiwan population from 2002 to 2012. We identified 9468 patients with pSS by using the catastrophic illness registry of the National Health Insurance Database in Taiwan. We also selected 37 872 controls that were randomly frequency matched by age (in 5 year bands), sex and index year from the general population. We analysed the risk of acute pancreatitis by using Cox proportional hazards regression models including sex, age and comorbidities. From 23.74 million people in the cohort, 9468 patients with pSS (87% women, mean age=55.6 years) and 37 872 controls were followed-up for 4.64 and 4.74 years, respectively. A total of 44 cases of acute pancreatitis were identified in the pSS cohort versus 105 cases in the non-pSS cohort. Multivariate Cox regression analysis indicated that the incidence rate of acute pancreatitis was significantly higher in the pSS cohort than in the non-pSS cohort (adjusted HR (aHR) 1.48, 95% CI 1.03 to 2.12). Cyclophosphamide use increased the risk of acute pancreatitis (aHR 5.27, 95% CI 1.16 to 23.86). By contrast, hydroxychloroquine reduced the risk of acute pancreatitis (aHR 0.23, 95% CI 0.09 to 0.55). This nationwide, retrospective cohort study demonstrated that the risk of acute pancreatitis was significantly higher in patients with pSS than in the general population. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

IMPACT OF STAGE MIGRATION AND PRACTICE CHANGES ON HIGH RISK PROSTATE CANCER: RESULTS FROM PATIENTS TREATED WITH RADICAL PROSTATECTOMY OVER THE LAST TWO DECADES

PubMed Central

Fossati, N.; Passoni, N. M.; Moschini, M.; Gandaglia, G.; Larcher, A.; Freschi, M.; Guazzoni, G.; Sjoberg, D. D.; Vickers, A. J.; Montorsi, F.; Briganti, A.

2016-01-01

Background Phenotype of prostate cancer at diagnosis has changed through the years. We aim to evaluate the impact of year of surgery on clinical, pathologic and oncologic outcomes of high-risk prostate cancer patients. Patients and methods We evaluated 1,033 clinically high-risk patients, defined as the presence of at least one of the following risk factors: pre-operative prostate specific antigen (PSA) level >20 ng/ml, and/or clinical stage ≥T3, and/or biopsy Gleason score ≥8. Patients were treated between 1990 and 2013 at a single Institution. Year-per-year trends of clinical and pathologic characteristics were examined. Multivariable Cox regression analysis was used to test the relationship between year of surgery and oncologic outcomes. Results We observed a decrease over time in the proportion of high-risk patients with a pre-operative PSA level >20 ng/ml or clinical stage cT3. An opposite trend was seen for biopsy Gleason score ≥8. We observed a considerable increase in the median number of lymph nodes removed that was associated with an increased rate of LNI. At multivariable Cox regression analysis, year of surgery was associated with a reduced risk of biochemical recurrence (HR per 5-year: 0.90; 95% CI: 0.84–0.96; p=0.01) and distant metastasis (HR per 5-year: 0.91; 95% CI: 0.83–0.99; p=0.039), after adjusting for age, pre-operative PSA, pathologic stage, lymph node invasion, surgical margin status, and pathological Gleason score. Conclusions In this single center study, an increased diagnosis of localized and less extensive high-grade prostate cancer was observed over the last two decades. High-risk patients selected for radical prostatectomy showed better cancer control over time. Better definitions of what constitutes high-risk prostate cancer among contemporary patients are needed. PMID:25787671

A comparison of the effects of C2-cyclosporine and C0-tacrolimus on renal function and cardiovascular risk factors in kidney transplant recipients.

PubMed

Kim, S Joseph; Prasad, G V Ramesh; Huang, Michael; Nash, Michelle M; Famure, Olusegun; Park, Joseph; Thenganatt, Mary Ann; Chowdhury, Nizamuddin; Cole, Edward H; Fenton, Stanley S A; Cattran, Daniel C; Zaltzman, Jeffrey S; Cardella, Carl J

2006-10-15

There are few data directly comparing the effects of two-hour postingestion monitored cyclosporine (C2-CsA) vs. trough-monitored tacrolimus (C0-Tac) on renal function and cardiovascular risk factors. We studied 378 (202 C2-CsA vs. 176 C0-Tac) incident kidney transplant recipients in Toronto, Canada, from August 1, 2000 and December 31, 2003. Outcomes included changes in estimated glomerular filtration rate (eGFR at 1 and 6 months by modification of diet in renal disease four-variable equation), mean arterial pressure (MAP), total cholesterol (TC), and new-onset diabetes mellitus (NODM) at six months posttransplant. The independent effect of treatment/monitoring strategies on continuous outcomes and time-to-NODM was modeled using linear and Cox regression, respectively. Mean eGFR was 59.5 vs. 62.9 ml/min at one month and 50.6 vs. 61.2 ml/min at six months for C2-CsA vs. C0-Tac, respectively. Multiple linear regression revealed the slope of eGFR to be 0.93 ml/min/month lower in C2-CsA patients. This was equivalent to an adjusted average eGFR difference of 4.64 ml/min between months one and six posttransplant. There was no significant difference in average MAP and TC. In a stepwise multivariable Cox model and a propensity score analysis, there was no significant association between the type of treatment/monitoring strategy and time-to-NODM. There was a greater decline in eGFR for patients on C2-CsA (vs. C0-Tac) between one and six months posttransplant. However, MAP, TC, and the risk of NODM were comparable in both treatment/monitoring groups. The long-term impact of short-term reductions in eGFR as a function of the type of treatment/monitoring strategy requires further study.

Will Rogers revisited: prospective observational study of survival of 3592 patients with colorectal cancer according to number of nodes examined by pathologists

PubMed Central

George, S; Primrose, J; Talbot, R; Smith, J; Mullee, M; Bailey, D; du Boulay, C; Jordan, H

2006-01-01

To investigate the relationship between survival in colorectal cancer patients and the number of lymph nodes examined by a pathologist, previously attributed to stage migration, we used data from a cohort of 5174 colorectal cancer patients recruited between September 1991 and August 1994, and followed-up for 5 years. We selected cases with data present on all prognostic variables, and stratified them into three groups by number of nodes examined. We made a multivariate survival comparison using a Cox regression model. In all, there were 3592 cases with data present on all prognostic variables. Patients who had >10 nodes identified had a significant survival advantage over those who had 5–10 identified, who had in turn a similar advantage over those with 0–4 identified (P<0.001). This effect was present in the whole group and at all Dukes' stages, although statistically significant only in stages B (P=0.004) and C (P=0.019). The effect remained after adjustment in a Cox regression model in which the mean number of nodes taken out by each surgical firm did not predict survival. In a sub-group with data on lymphocytic infiltration into the primary tumour a survival advantage was noted in those with prominent rather than mild infiltration (P<0.001): the former also tended to have more nodes found (P=0.015). Stage migration alone cannot explain these results, as survival advantages are noted across the whole population independent of stage. Lymphocytic infiltration into the primary tumour is prognostically important, and is associated with the number of nodes found. Reactive enlargement of lymph nodes in the mesentery may make them easier to find, reflect immune response to the tumour, and thus indirectly impact upon survival. PMID:16969342

Prognostic value of cardiopulmonary exercise testing in heart failure with preserved ejection fraction. The Henry Ford HospITal CardioPulmonary EXercise Testing (FIT-CPX) project.

PubMed

Shafiq, Ali; Brawner, Clinton A; Aldred, Heather A; Lewis, Barry; Williams, Celeste T; Tita, Christina; Schairer, John R; Ehrman, Jonathan K; Velez, Mauricio; Selektor, Yelena; Lanfear, David E; Keteyian, Steven J

2016-04-01

Although cardiopulmonary exercise (CPX) testing in patients with heart failure and reduced ejection fraction is well established, there are limited data on the value of CPX variables in patients with HF and preserved ejection fraction (HFpEF). We sought to determine the prognostic value of select CPX measures in patients with HFpEF. This was a retrospective analysis of patients with HFpEF (ejection fraction ≥ 50%) who performed a CPX test between 1997 and 2010. Selected CPX variables included peak oxygen uptake (VO2), percent predicted maximum oxygen uptake (ppMVO2), minute ventilation to carbon dioxide production slope (VE/VCO2 slope) and exercise oscillatory ventilation (EOV). Separate Cox regression analyses were performed to assess the relationship between each CPX variable and a composite outcome of all-cause mortality or cardiac transplant. We identified 173 HFpEF patients (45% women, 58% non-white, age 54 ± 14 years) with complete CPX data. During a median follow-up of 5.2 years, there were 42 deaths and 5 cardiac transplants. The 1-, 3-, and 5-year cumulative event-free survival was 96%, 90%, and 82%, respectively. Based on the Wald statistic from the Cox regression analyses adjusted for age, sex, and β-blockade therapy, ppMVO2 was the strongest predictor of the end point (Wald χ(2) = 15.0, hazard ratio per 10%, P < .001), followed by peak VO2 (Wald χ(2) = 11.8, P = .001). VE/VCO2 slope (Wald χ(2)= 0.4, P = .54) and EOV (Wald χ(2) = 0.15, P = .70) had no significant association to the composite outcome. These data support the prognostic utility of peak VO2 and ppMVO2 in patients with HFpEF. Additional studies are needed to define optimal cut points to identify low- and high-risk patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk and prognostic factors for pneumonia and choking amongst Parkinson's disease patients with dysphagia.

PubMed

Goh, Kwang-Hwee; Acharyya, Sanchalika; Ng, Samuel Yong-Ern; Boo, Jasmine Pei-Ling; Kooi, Amanda Hui-Juan; Ng, Hwee-Lan; Li, Wei; Tay, Kay-Yaw; Au, Wing-Lok; Tan, Louis Chew-Seng

2016-08-01

To evaluate the time to hospitalisation and baseline factors associated with pneumonia/choking in Parkinson's Disease (PD) patients. Although dysphagia and pneumonia are common problems in PD, scarce research has been performed. A total of 194 PD patients who underwent a VFS evaluation were retrospectively selected. The mode of feeding and admissions for pneumonia/choking were analyzed. Baseline clinical and demographic variables were compared between feeding groups. Kaplan-Meier survival analysis was performed to estimate time to pneumonia/choking. Clinical variables significantly associated with pneumonia/choking free survival were identified using Cox regression. Hospitalisation for pneumonia/choking occurred in 89 out of 194 patients, with the highest admission rate in rejected enteral feeding group (66.7%), followed by enteral feeding (61.8%) and oral feeding (38.8%) groups. The estimates of median time to event were 11, 14, and 47 months for rejected enteral feeding, enteral and oral feeding groups respectively (log-rank test p < 0.001). The rejected enteral feeding group had the highest risk of pneumonia/choking (HR 4.61, 95%CI:2.33-9.08, p < 0.001), followed by enteral feeding group (HR 2.29, 95%CI:1.25-4.19, p = 0.007), when compared to oral feeding group after adjusting for possible confounders. A stepwise Cox regression showed that the rejected enteral feeding (HR 4.89, 95%CI:2.19-10.88, p < 0.001), enteral mode of feeding (HR 2.43, 95%CI:1.11-5.32, p = 0.026), and Charlson weighted index of co-morbidity (HR 1.27, 95%CI:1.03-1.58, p = 0.028) were independently associated with higher hazard of pneumonia/choking. Compliance to feeding recommendations is important to reduce the risk of hospitalisation for pneumonia/choking. The recommended mode of feeding and comorbidity index was significantly associated with pneumonia/choking risk. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hyperlipidemia and statins use for the risk of new-onset anxiety/depression in patients with head and neck cancer: A population-based study.

PubMed

Huang, Chung-I; Lin, Li-Ching; Tien, Hung-Cheng; Que, Jenny; Ting, Wei Chen; Chen, Po-Chun; Wu, Hsin-Min; Ho, Chung-Han; Wang, Jhi-Joung; Wang, Ren-Hong; Yang, Ching-Chieh

2017-01-01

Anxiety/depression is common among patients with head and neck cancer (HNC), and can negatively affect treatment compliance and outcome. The aim of this study was to assess the association between hyperlipidemia and the risk of new-onset anxiety/depression after the diagnosis of HNC and the influence of administering statins. A matched longitudinal cohort study of 1632 subjects (408 HNC patients with preexisting hyperlipidemia and 1224 age- and sex-matched HNC patients without hyperlipidemia) was included and analyzed by using data from Taiwan's National Health Insurance Research Database from January 1996 to December 2012. The incidence and hazard ratios (HRs) for the development of new-onset anxiety/depression were examined between the two groups. Cox proportional hazard regression was applied to estimate the relative risks of anxiety/depressive disorders adjusted for potential confounding factors. To estimate the risks of anxiety/depression in different sub-groups, a stratified analysis was also used. HNC patients with preexisting hyperlipidemia had a higher risk for comorbidities such as hypertension, diabetes mellitus, and cardiovascular disease (P <0.001). The incidence rate of anxiety/depression in the HNC patients with preexisting hyperlipidemia was also significantly higher than that among patients without hyperlipidemia (10.78% vs 7.27%, respectively; P = 0.03). A Cox regression model revealed that preexisting hyperlipidemia was an independent risk factor for anxiety/depression (aHR, 1.96; 95% CI, 1.30-2.94). Statins use was protective against anxiety/depression among HNC patients with hyperlipidemia (aHR, 0.85; 95% CI, 0.46-1.57), especially for individuals older than 65 years and for females. Preexisting hyperlipidemia was associated with increased risk of new-onset anxiety/depression in the HNC patients. Statins use for HNC patients with hyperlipidemia could decrease the risk of anxiety/depression, especially for those older than 65 years and for female patients.

Hyperlipidemia and statins use for the risk of new-onset anxiety/depression in patients with head and neck cancer: A population-based study

PubMed Central

Huang, Chung-I; Lin, Li-Ching; Tien, Hung-Cheng; Que, Jenny; Ting, Wei Chen; Chen, Po-Chun; Wu, Hsin-Min; Ho, Chung-Han; Wang, Jhi-Joung; Wang, Ren-Hong; Yang, Ching-Chieh

2017-01-01

Objective Anxiety/depression is common among patients with head and neck cancer (HNC), and can negatively affect treatment compliance and outcome. The aim of this study was to assess the association between hyperlipidemia and the risk of new-onset anxiety/depression after the diagnosis of HNC and the influence of administering statins. Methods A matched longitudinal cohort study of 1632 subjects (408 HNC patients with preexisting hyperlipidemia and 1224 age- and sex-matched HNC patients without hyperlipidemia) was included and analyzed by using data from Taiwan’s National Health Insurance Research Database from January 1996 to December 2012. The incidence and hazard ratios (HRs) for the development of new-onset anxiety/depression were examined between the two groups. Cox proportional hazard regression was applied to estimate the relative risks of anxiety/depressive disorders adjusted for potential confounding factors. To estimate the risks of anxiety/depression in different sub-groups, a stratified analysis was also used. Results HNC patients with preexisting hyperlipidemia had a higher risk for comorbidities such as hypertension, diabetes mellitus, and cardiovascular disease (P <0.001). The incidence rate of anxiety/depression in the HNC patients with preexisting hyperlipidemia was also significantly higher than that among patients without hyperlipidemia (10.78% vs 7.27%, respectively; P = 0.03). A Cox regression model revealed that preexisting hyperlipidemia was an independent risk factor for anxiety/depression (aHR, 1.96; 95% CI, 1.30–2.94). Statins use was protective against anxiety/depression among HNC patients with hyperlipidemia (aHR, 0.85; 95% CI, 0.46–1.57), especially for individuals older than 65 years and for females. Conclusions Preexisting hyperlipidemia was associated with increased risk of new-onset anxiety/depression in the HNC patients. Statins use for HNC patients with hyperlipidemia could decrease the risk of anxiety/depression, especially for those older than 65 years and for female patients. PMID:28362860

Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus.

PubMed

Lee, Chi Ho; Woo, Yu Cho; Chow, Wing Sun; Cheung, Chloe Yu Yan; Fong, Carol Ho Yi; Yuen, Michele Mae Ann; Xu, Aimin; Tse, Hung Fat; Lam, Karen Siu Ling

2017-06-06

Fibroblast growth factor 21 (FGF21) has demonstrated beneficial effects on lipid and carbohydrate metabolism. In cross-sectional studies, an association of raised circulating FGF21 levels with coronary heart disease (CHD) was found in some but not all studies. Here we investigated prospectively whether baseline serum FGF21 levels could predict incident CHD in subjects with type 2 diabetes mellitus and no known cardiovascular diseases. Baseline serum FGF21 levels were measured in 3528 Chinese subjects with type 2 diabetes mellitus recruited from the Hong Kong West Diabetes Registry. The role of baseline serum FGF21 levels in predicting incident CHD over a median follow-up of 3.8 years was analyzed using Cox regression analysis. Among 3528 recruited subjects without known cardiovascular diseases, 147 (4.2%) developed CHD over a mean follow-up of 4 years. Baseline serum log-transformed FGF21 levels were significantly higher in those who had incident CHD than those who did not (222.7 pg/mL [92.8-438.4] versus 151.1 pg/mL [75.6-274.6]; P <0.001). On multivariable Cox regression analysis, baseline serum FGF21 levels, using an optimal cutoff of 206.22 pg/mL derived from our study, independently predicted incident CHD (hazard ratio, 1.55; 95% CI, 1.10-2.19; P =0.013) and significantly improved net reclassification index and integrated discrimination improvement after adjustment for conventional cardiovascular risk factors. We have demonstrated, for the first time, that serum FGF21 level is an independent predictor of incident CHD and might be usefully utilized as a biomarker for identifying type 2 diabetes mellitus subjects with raised CHD risk, for primary prevention. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes.

PubMed

Nowak, Christoph; Carlsson, Axel C; Östgren, Carl Johan; Nyström, Fredrik H; Alam, Moudud; Feldreich, Tobias; Sundström, Johan; Carrero, Juan-Jesus; Leppert, Jerzy; Hedberg, Pär; Henriksen, Egil; Cordeiro, Antonio C; Giedraitis, Vilmantas; Lind, Lars; Ingelsson, Erik; Fall, Tove; Ärnlöv, Johan

2018-05-24

Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. We combined data from six prospective epidemiological studies of 30-77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularised Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample. Of 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (±SD) of 6.4 ± 2.3 years. We replicated associations (<5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)-12, IL-27 subunit α (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF)-23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis-inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample. We identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardiovascular event.

Prognosis Related to Metastatic Burden Measured by 18F-Fluorocholine PET/CT in Castrate Resistant Prostate Cancer

PubMed Central

Kwee, Sandi A.; Lim, John; Watanabe, Alex; Kromer-Baker, Kathleen; Coel, Marc N.

2015-01-01

This study investigates the prognostic significance of metabolically active tumor volume (MATV) measurements applied to fluorine-18 fluorocholine (FC) PET/CT in castrate-resistant prostate cancer (CRPC). Methods FC PET/CT imaging was performed in 30 patients with CRPC. Metastatic disease was quantified on the basis of maximum standardized uptake value (SUVmax), MATV, and total lesion activity (TLA = MATV × mean SUV). Tumor burden indices derived from whole-body summation of PET tumor volume measurements (ie. net MATV and net TLA) were evaluated as variables in Cox regression and Kaplan-Meier survival analyses. Results Net MATV ranged from 0.12 cm3 to 1543.9 cm3 (median 52.6 cm3). Net TLA ranged from 0.40g to 6688.7g (median 225.1g). PSA level at the time of PET correlated significantly with net MATV (Pearson r = 0.65, p = 0.0001) and net TLA (r = 0.60, p = 0.0005) but not highest lesional SUVmax of each scan. Survivors were followed for a median 23 months (range 6 – 38 months). On Cox regression analyses, overall survival was significantly associated with net MATV (p = 0.0068), net TLA (p = 0.0072), and highest lesion SUVmax (p = 0.0173), and borderline associated with PSA level (p = 0.0458). Only net MATV and net TLA remained significant in univariate-adjusted survival analyses. Kaplan-Meier analysis demonstrated significant differences in survival between groups stratified by median net MATV (log-rank P = 0.0371), net TLA (log-rank P = 0.0371), and highest lesion SUVmax (log-rank P = 0.0223). Conclusions Metastatic prostate cancer detected by FC PET/CT can be quantified based on volumetric measurements of tumor metabolic activity. The prognostic value of FC PET/CT may stem from this capacity to assess whole-body tumor burden. With further clinical validation, FC PET-based indices of global disease activity and mortality risk could prove useful in patient-individualized treatment of CRPC. PMID:24676753

Morbidity before and after the diagnosis of hyperthyroidism: a nationwide register-based study.

PubMed

Brandt, Frans; Thvilum, Marianne; Almind, Dorthe; Christensen, Kaare; Green, Anders; Hegedüs, Laszlo; Brix, Thomas Heiberg

2013-01-01

Hyperthyroidism has been linked with different morbidities, like atrial fibrillation, stroke and diabetes mellitus. However, our knowledge regarding the extent and temporal relation between hyperthyroidism and other diseases is fragmented. Here, we aimed at evaluating various morbidities before and after the diagnosis of hyperthyroidism. Observational cohort study. From nationwide Danish health registers 2631 hyperthyroid singletons and 375 twin pairs discordant for hyperthyroidism were identified and followed for an average of 6 years (range 0-13). Data on the occurrence of cardiovascular diseases, lung diseases, diabetes mellitus, rheumatic diseases and malignant diseases was obtained by person-to-person record linkage with the National Danish Patient Register and/or the Danish National Prescription Registry (lung diseases and diabetes mellitus). Logistic and Cox regression models were used to assess the risk of morbidity before and after the diagnosis of hyperthyroidism, respectively. All Cox regression analyses were adjusted for the degree of co-morbidity preceding the diagnosis of hyperthyroidism, using the Charlson score. Hyperthyroid individuals had a significantly higher risk of being diagnosed with cardiovascular diseases (odds ratio (OR) 1.65; 95% confidence interval (CI): 1.45-1.87), lung diseases (OR 1.53; 95% CI: 1.29-1.60), and diabetes mellitus (OR 1.43, 95% CI: 1.20-1.72), but not with malignant diseases (OR 1.16, 95% CI: 0.99-1.36) prior to the diagnosis of hyperthyroidism. After the diagnosis of hyperthyroidism, subjects had a significantly higher risk of being diagnosed with cardiovascular diseases (hazard ratio (HR) 1.34; 95% CI: 1.15-1.56), lung diseases (HR 1.28; 95% CI: 1.10-1.49), and diabetes mellitus (HR 1.46; 95% CI: 1.16-1.84), but not with rheumatic diseases (HR 1.39, 95% CI: 0.92-2.09) or malignant diseases (HR 1.18, 95% CI 0.97-1.42). We demonstrate a significantly increased burden of morbidity, both before and after the diagnosis of hyperthyroidism.

Comparative Effectiveness of 5 Treatment Strategies for Early-Stage Non-Small Cell Lung Cancer in the Elderly

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

Shirvani, Shervin M.; Jiang, Jing; Chang, Joe Y.

2012-12-01

Purpose: The incidence of early-stage non-small cell lung cancer (NSCLC) among older adults is expected to increase because of demographic trends and computed tomography-based screening; yet, optimal treatment in the elderly remains controversial. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort spanning 2001-2007, we compared survival outcomes associated with 5 strategies used in contemporary practice: lobectomy, sublobar resection, conventional radiation therapy, stereotactic ablative radiation therapy (SABR), and observation. Methods and Materials: Treatment strategy and covariates were determined in 10,923 patients aged {>=}66 years with stage IA-IB NSCLC. Cox regression, adjusted for patient and tumor factors, compared overall and disease-specificmore » survival for the 5 strategies. In a second exploratory analysis, propensity-score matching was used for comparison of SABR with other options. Results: The median age was 75 years, and 29% had moderate to severe comorbidities. Treatment distribution was lobectomy (59%), sublobar resection (11.7%), conventional radiation (14.8%), observation (12.6%), and SABR (1.1%). In Cox regression analysis with a median follow-up time of 3.2 years, SABR was associated with the lowest risk of death within 6 months of diagnosis (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.38-0.63; referent is lobectomy). After 6 months, lobectomy was associated with the best overall and disease-specific survival. In the propensity-score matched analysis, survival after SABR was similar to that after lobectomy (HR 0.71; 95% CI 0.45-1.12; referent is SABR). Conventional radiation and observation were associated with poor outcomes in all analyses. Conclusions: In this population-based experience, lobectomy was associated with the best long-term outcomes in fit elderly patients with early-stage NSCLC. Exploratory analysis of SABR early adopters suggests efficacy comparable with that of surgery in select populations. Evaluation of these therapies in randomized trials is urgently needed.« less

Outcome of acute myeloid leukemia and high-risk myelodysplastic syndrome according to health insurance status.

PubMed

Al-Ameri, Ali; Anand, Ankit; Abdelfatah, Mohamed; Kanaan, Zeyad; Hammonds, Tracy; Haller, Nairmeen; Cherry, Mohamad

2014-12-01

Age, cytogenetic status, and molecular features are the most important prognostic factors in acute myeloid leukemia (AML). This study aimed to analyze the outcomes of patients with AML or high-risk myelodysplastic syndrome (MDS) according to insurance status. A retrospective chart review was performed, covering all patients with AML and high-risk MDS evaluated and treated at Akron General Medical Center between 2002 and 2012. A Cox regression model was analyzed to account for survival over time, adjusted for insurance type, while controlling for patient age at diagnosis and patient risk of mortality. A total of 130 adult patients (age ≥ 18 years) were identified. Insurance information was available for 97 patients enrolled in the study; 3 were excluded because of self-pay status. Cox regression analysis with insurance type as the predictor found that overall survival declines over time and that the rate of decline may be influenced by insurance type (χ(2)(2) = 6.4; P = .044). The likelihood of survival in patients with Medicaid or Medicare without supplemental insurance was .552 (95% CI, .338-.903; P = .018) times the likelihood in patients who had Medicare with supplemental insurance. To explain the difference, variables of age, gender, and risk of mortality were added to the model. Age and risk of mortality were found to be significant predictors of survival. The addition of insurance type to the model did not significantly contribute (χ(2)(3) = 3.83; P = .147). No significant difference in overall survival was observed when patients with AML or high-risk MDS were analyzed according to their health insurance status. The overall survival was low in this study compared with the national average. Early referral to a specialized center or possible clinical trial enrollment may be a good alternative to improve outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

Single nucleotide polymorphisms in long noncoding RNA, ANRIL, are not associated with severe periodontitis but with adverse cardiovascular events among patients with cardiovascular disease.

PubMed

Schulz, S; Seitter, L; Werdan, K; Hofmann, B; Schaller, H-G; Schlitt, A; Reichert, S

2018-05-06

Biological plausibility of an association between severe periodontitis and cardiovascular disease (CVD) has been proven. Genetic characteristics play an important role in both complex inflammatory diseases. Polymorphisms (single nucleotide polymorphisms [SNPs]) in the long noncoding RNA, antisense noncoding RNA in the INK4 locus (ANRIL), were shown to play a leading role in both diseases. The primary objectives of the study were to assess, among cardiovascular (CV angiographically proven ≥50% stenosis of a main coronary artery) patients, the impact of ANRIL SNPs rs133049 and rs3217992 on the severity of periodontitis and the previous history of coronary events, as well as on the occurrence of further adverse CV events. The prevalence of severe periodontitis was analyzed in 1002 CV patients. ANRIL SNPs rs133049 and rs3217992 were genotyped. The prognostic value of both ANRIL SNPs for combined CV endpoint (stroke/transient ischemic attack [TIA], myocardial infarction, death from a CV-related event, death from stroke) was evaluated after a 3-year follow-up period. Hazard ratios (HRs) were adjusted for established CV risk factors applying Cox regression. ANRIL SNPs rs133049 and rs3217992 were not associated with severe periodontitis or history of CVD in CV patients. In the Kaplan-Meier survival curve including the log rank-test (P = .036) and Cox regression (hazard ratio = 1.684, P = .009) the AA genotype of rs3217992 was shown to be an independent predictor for adverse CV events after 3 years of follow-up. SNPs in ANRIL are not risk modulators for severe periodontitis and history of CVD in CV patients. The AA genotype of ANRIL SNPs rs3217992 possesses prognostic power for further CV events within 3 years of follow-up. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Covariate Imbalance and Adjustment for Logistic Regression Analysis of Clinical Trial Data

PubMed Central

Ciolino, Jody D.; Martin, Reneé H.; Zhao, Wenle; Jauch, Edward C.; Hill, Michael D.; Palesch, Yuko Y.

2014-01-01

In logistic regression analysis for binary clinical trial data, adjusted treatment effect estimates are often not equivalent to unadjusted estimates in the presence of influential covariates. This paper uses simulation to quantify the benefit of covariate adjustment in logistic regression. However, International Conference on Harmonization guidelines suggest that covariate adjustment be pre-specified. Unplanned adjusted analyses should be considered secondary. Results suggest that that if adjustment is not possible or unplanned in a logistic setting, balance in continuous covariates can alleviate some (but never all) of the shortcomings of unadjusted analyses. The case of log binomial regression is also explored. PMID:24138438

Optimizing the time-frame for the definition of bleeding-related death after acute variceal bleeding in cirrhosis.

PubMed

Merkel, C; Gatta, A; Bellumat, A; Bolognesi, M; Borsato, L; Caregaro, L; Cavallarin, G; Cielo, R; Cristina, P; Cucci, E; Donada, C; Donadon, V; Enzo, E; Martin, R; Mazzaro, C; Sacerdoti, D; Torboli, P

1996-01-01

To identify the best time-frame for defining bleeding-related death after variceal bleeding in patients with cirrhosis. Prospective long-term evaluation of a cohort of 155 patients admitted with variceal bleeding. Eight medical departments in seven hospitals in north-eastern Italy. Non-linear regression analysis of a hazard curve for death, and Cox's multiple regression analyses using different zero-time points. Cumulative hazard plots gave two slopes, the first corresponding to the risk of death from acute bleeding, the second a baseline risk of death. The first 30 days were outside the confidence limits of the regression curve for the baseline risk of death. Using Cox's regression analysis, the significant predictors of overall mortality risk were balanced between factors related to severity of bleeding and those related to severity of liver disease. If only deaths occurring after 30 days were considered, only predictors related to the severity of liver disease were found to be of importance. Thirty days after bleeding is considered to be a reasonable time-frame for the definition of bleeding-related death in patients with cirrhosis and variceal bleeding.

Increased risk of tinnitus in patients with chronic kidney disease: A nationwide, population-based cohort study.

PubMed

Shih, Cheng-Ping; Lin, Hung-Che; Chung, Chi-Hsiang; Hsiao, Po-Jen; Wang, Chih-Hung; Lee, Jih-Chin; Chien, Wu-Chien

2017-01-01

Tinnitus mostly results from central and peripheral auditory pathology. Chronic kidney disease (CKD) is a major risk factor for cerebrovascular disease. However, no studies have evaluated the association between tinnitus and CKD. The aim of this study is to investigate the risk of tinnitus in patients with CKD. This retrospective cohort study was conducted using Taiwan National Health Insurance Research Database from 2000 to 2010. We established a CKD group (n = 185,430) and a non-CKD comparison group (n = 556,290) to investigate the incidence of tinnitus. Cox proportional hazard regression analysis was used to evaluate the effects of CKD on tinnitus risk. The results showed CKD significantly increased the risk of tinnitus (adjusted hazard ratio, 3.02; 95% CI, 2.655-3.456, P<0.001). A subgroup analysis revealed the increase in risk of tinnitus is more in CKD patients with heart failure (adjusted hazard ratio, 9.975; 95% CI, 5.001-18.752) and diabetes mellitus (adjusted hazard ratio, 3.712; 95% CI, 2.856-5.007). Furthermore, compared to non-CKD patients, the risk of tinnitus was increased 4.586-fold (95% CI, 2.399-6.7) in CKD patients with dialysis and 2.461-fold (95% CI, 1.033-3.454) in CKD patients without dialysis. This study is the first to report that CKD is associated with an increased risk of tinnitus. Among CKD cohort, patients with dialysis are at a higher risk of tinnitus than those without dialysis.

A Cluster Randomized Trial of Tailored Breastfeeding Support for Women with Gestational Diabetes.

PubMed

Stuebe, Alison M; Bonuck, Karen; Adatorwovor, Reuben; Schwartz, Todd A; Berry, Diane C

2016-12-01

Women with gestational diabetes mellitus (GDM) and their infants are at increased risk of developing metabolic disease; however, longer breastfeeding is associated with a reduction in these risks. We tested an intervention to increase breastfeeding duration among women with GDM. We conducted a cluster randomized trial to determine the efficacy of a breastfeeding education and support program for women with GDM. Women were enrolled between 22 and 36 weeks of pregnancy and cluster randomized to an experimental lifestyle intervention or wait-list control group. Breastfeeding duration and intensity were prespecified secondary outcomes of the trial. Duration of exclusive and any breastfeeding was assessed at 6 weeks and at 4, 7, and 10 months postpartum. We quantified differences in breastfeeding rates using Kaplan-Meier estimates, log-rank tests, and Cox regression models. We enrolled 100 women, of whom 52% were African American, 31% non-Hispanic white, 11% Hispanic, 9% American Indian or Alaskan Native, 2% Asian, 2% other, and 4% more than one race. In models accounting for within-cluster correlation and adjusted for study site, breastfeeding intention, and African American race, women allocated to the intervention group were less likely to stop breastfeeding (adjusted hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.21-0.74) or to introduce formula (adjusted HR 0.50, 95% CI 0.34-0.72). Our results suggest that targeted breastfeeding education for women with GDM is feasible and efficacious. http://clinicaltrials.gov/ct2/show/NCT01809431.

Pulmonary infections and risk of lung cancer among persons with AIDS.

PubMed

Shebl, Fatma M; Engels, Eric A; Goedert, James J; Chaturvedi, Anil K

2010-11-01

Lung cancer risk is significantly increased among persons with AIDS (PWA), and increased smoking may not explain all of the elevated risk, suggesting a role for additional cofactors. We investigated whether AIDS-defining pulmonary infections (recurrent pneumonia, Pneumocystis jirovecii pneumonia, and pulmonary tuberculosis) affected the risk of subsequent lung cancer over 10 years after AIDS onset among 322,675 PWA, whose records were linked with cancer registries in 11 US regions. We assessed lung cancer hazard ratios (HRs) using Cox regression and indirectly adjusted HRs for confounding by smoking. Individuals with recurrent pneumonia (n = 5317) were at significantly higher lung cancer risk than those without [HR = 1.63, 95% confidence interval (CI) = 1.08 to 2.46, adjusted for age, race, sex, HIV acquisition mode, CD4 count, and AIDS diagnosis year]. This association was especially strong among young PWA (<50 years HR = 1.99 vs. ≥50 years HR = 1.10) and was significantly elevated during 5-10 years after recurrent pneumonia diagnosis (HR = 2.41; 95% CI = 1.07 to 5.47). Although attenuated, HRs for recurrent pneumonia remained nonsignificantly elevated after indirect adjustment for smoking. Lung cancer risk was unrelated to tuberculosis [(n = 13,878) HR = 1.12, 95% CI = 0.82 to 1.53] or Pneumocystis jirovecii pneumonia [(n = 69,771) HR = 0.97, 95% CI = 0.80 to 1.18]. The increased lung cancer risk associated with recurrent pneumonia supports the hypothesis that chronic pulmonary inflammation arising from infections contributes to lung carcinogenesis.

Frontal Lobe Function and Risk of Hip Fracture in Patient With Alzheimer Disease: An Analysis of Linked Data.

PubMed

Roh, Hyun Woong; Hong, Chang Hyung; Lee, SooJin; Lee, Yunhwan; Lee, Kang Soo; Chang, Ki Jung; Oh, Byoung Hoon; Choi, Seong Hye; Kim, Seong Yoon; Back, Joung Hwan; Chung, Young Ki; Lim, Ki Young; Noh, Jai Sung; Son, Sang Joon

2015-11-01

To determine the association between frontal lobe function and risk of hip fracture in patients with Alzheimer disease (AD).Retrospective cohort study using multicenter hospital-based dementia registry and national health insurance claim data was done. Participants who had available data of neuropsychological test, national health insurance claim, and other covariates were included. A total of 1660 patients with AD were included based on Stroop Test results. A total of 1563 patients with AD were included based on the Controlled Oral Word Association Test (COWAT) results. Hip fracture was measured by validated identification criteria using national health insurance claim data. Frontal lobe function was measured by Stroop Test and COWAT at baseline.After adjusting for potential covariates, including cognitive function in other domains (language, verbal and nonverbal memory, and attention), the Cox proportional hazard regression analysis revealed that risk of a hip fracture was decreased with a hazard ratio (HR) of 0.98 per one point of increase in the Stroop Test (adjusted HR = 0.98, 95% confidence interval [CI]: 0.97-1.00) and 0.93 per one point increase in COWAT (adjusted HR = 0.93, 95% CI: 0.88-0.99).The risk of hip fracture in AD patients was associated with baseline frontal lobe function. The result of this research presents evidence of association between frontal lobe function and risk of hip fracture in patients with AD.

Gastroduodenal Ulcers and ABO Blood Group: the Japan Nurses’ Health Study (JNHS)

PubMed Central

Ideno, Yuki; Lee, Jung-Su; Suzuki, Shosuke; Nakajima-Shimada, Junko; Ohnishi, Hiroshi; Sato, Yasunori; Hayashi, Kunihiko

2018-01-01

Background Although several studies have shown that blood type O is associated with increased risk of peptic ulcer, few studies have investigated these associations in Japan. We sought to investigate the association between the ABO blood group and risk of gastroduodenal ulcers (GDU) using combined analysis of both retrospective and prospective data from a large cohort study of Japanese women, the Japan Nurses’ Health Study (JNHS; n = 15,019). Methods The impact of the ABO blood group on GDU risk was examined using Cox regression analysis to estimate hazard ratios (HRs) and 95% confidence intervals (CI), with adjustment for potential confounders. Results Compared with women with non-O blood types (A, B, and AB), women with blood type O had a significantly increased risk of GDU from birth (multivariable-adjusted HR 1.18; 95% CI, 1.04–1.34). Moreover, the highest cumulative incidence of GDU was observed in women born pre-1956 with blood type O. In a subgroup analysis stratified by birth year (pre-1956 or post-1955), the multivariable-adjusted HR of women with blood type O was 1.22 (95% CI, 1.00–1.49) and 1.15 (95% CI, 0.98–1.35) in the pre-1956 and post-1955 groups, respectively. Conclusion In this large, combined, ambispective cohort study of Japanese women, older women with blood type O had a higher risk of developing GDU than those with other blood types. PMID:29093357

Frontal Lobe Function and Risk of Hip Fracture in Patient With Alzheimer Disease

PubMed Central

Roh, Hyun Woong; Hong, Chang Hyung; Lee, SooJin; Lee, Yunhwan; Lee, Kang Soo; Chang, Ki Jung; Oh, Byoung Hoon; Choi, Seong Hye; Kim, Seong Yoon; Back, Joung Hwan; Chung, Young Ki; Lim, Ki Young; Noh, Jai Sung; Son, Sang Joon

2015-01-01

Abstract To determine the association between frontal lobe function and risk of hip fracture in patients with Alzheimer disease (AD). Retrospective cohort study using multicenter hospital-based dementia registry and national health insurance claim data was done. Participants who had available data of neuropsychological test, national health insurance claim, and other covariates were included. A total of 1660 patients with AD were included based on Stroop Test results. A total of 1563 patients with AD were included based on the Controlled Oral Word Association Test (COWAT) results. Hip fracture was measured by validated identification criteria using national health insurance claim data. Frontal lobe function was measured by Stroop Test and COWAT at baseline. After adjusting for potential covariates, including cognitive function in other domains (language, verbal and nonverbal memory, and attention), the Cox proportional hazard regression analysis revealed that risk of a hip fracture was decreased with a hazard ratio (HR) of 0.98 per one point of increase in the Stroop Test (adjusted HR = 0.98, 95% confidence interval [CI]: 0.97–1.00) and 0.93 per one point increase in COWAT (adjusted HR = 0.93, 95% CI: 0.88–0.99). The risk of hip fracture in AD patients was associated with baseline frontal lobe function. The result of this research presents evidence of association between frontal lobe function and risk of hip fracture in patients with AD. PMID:26559259

Association between parity and risk of suicide among parous women.

PubMed

Yang, Chun-Yuh

2010-04-06

There are limited empirical data to support the theory of a protective effect of parenthood against suicide, as proposed by Durkheim in 1897. I conducted this study to examine whether there is an association between parity and risk of death from suicide among women. The study cohort consisted of 1,292,462 women in Taiwan who had a first live birth between Jan. 1, 1978, and Dec. 31, 1987. The women were followed up from the date of their first birth to Dec. 31, 2007. Their vital status was ascertained by means of linking records with data from a computerized mortality database. Cox proportional hazard regression models were used to estimate hazard ratios of death from suicide associated with parity. There were 2252 deaths from suicide during 32 464 187 person-years of follow-up. Suicide-related mortality was 6.94 per 100,000 person-years. After adjustment for age at first birth, marital status, years of schooling and place of delivery, the adjusted hazard ratio was 0.61 (95% confidence interval [CI] 0.54-0.68) among women with two live births and 0.40 (95% CI 0.35-0.45) among those with three or more live births, compared with women who had one live birth. I observed a significantly decreasing trend in adjusted hazard ratios of suicide with increasing parity. This study provides evidence to support Durkheim's hypothesis that parenthood confers a protective effect against suicide.

Effectiveness of penicillin, dicloxacillin and cefuroxime for penicillin-susceptible Staphylococcus aureus bacteraemia: a retrospective, propensity-score-adjusted case-control and cohort analysis.

PubMed

Nissen, Jette Lindbjerg; Skov, Robert; Knudsen, Jenny Dahl; Ostergaard, Christian; Schønheyder, Henrik Carl; Frimodt-Møller, Niels; Benfield, Thomas

2013-08-01

Penicillin-susceptible Staphylococcus aureus isolates account for a fifth of cases of S. aureus bacteraemia (SAB) in Denmark, but little is known about treatment outcomes with penicillins or other antimicrobials. Here we compare penicillin, dicloxacillin and cefuroxime as definitive treatments in relation to 30 day mortality. A retrospective chart review of 588 penicillin-susceptible S. aureus cases at five centres from January 1995 to December 2010. Data on demographics, antimicrobial treatment, clinical signs and symptoms, and mortality at day 30 were collected. Hazard ratios (HRs) with 95% CIs associated with mortality were modelled using propensity-score-adjusted Cox proportional hazards regression analysis. Propensity-score-matched case-control studies were carried out. Definitive therapy with cefuroxime was associated with an increased risk of 30 day mortality compared with penicillin (adjusted HR 2.54, 95% CI 1.49-4.32). Other variables that were statistically significantly associated with 30 day mortality included increasing age, disease severity and a primary respiratory focus. Osteomyelitis/arthritis was associated with a lower risk of death than were other secondary manifestations. Propensity-score-matched case-control studies confirmed an increased risk of 30 day mortality: cefuroxime treatment (39%) versus penicillin treatment (20%), P = 0.037; and cefuroxime treatment (38%) versus dicloxacillin treatment (10%), P = 0.004. Definitive therapy for penicillin-susceptible SAB with cefuroxime was associated with a significantly higher mortality than was seen with therapy with penicillin or dicloxacillin.

Respiratory distress syndrome in preterm infants and risk of epilepsy in a Danish cohort.

PubMed

Thygesen, Sandra Kruchov; Olsen, Morten; Pedersen, Lars; Henderson, Victor W; Østergaard, John Rosendahl; Sørensen, Henrik Toft

2018-03-01

Infant respiratory distress syndrome (IRDS) may be complicated by intracerebral hemorrhage, a known trigger of epilepsy. However, few data exist on long term epilepsy risk following IRDS. We therefore examined the association between IRDS in preterm infants and childhood epilepsy. We conducted a population-based cohort study using individual-level data linkage among nationwide registries. All infants born at 32-36 weeks of gestation in 1978-2009 were identified in the Medical Birth Registry. We identified children with IRDS and those with epilepsy using the Danish National Patient Registry. We computed the cumulative incidence of epilepsy with follow-up from birth until epilepsy, emigration, death, age 15, or December 31, 2014. We used Cox's regression analysis to compute hazard ratios comparing children with and without IRDS, adjusting for sex, birth year, gestational age, multiplicity, major malformations, and maternal age. We identified 95,026 infants, of whom 6426 (6.8%) had IRDS. The cumulative incidence of epilepsy was 3.4% by age 15 in children with IRDS and 2.1% in children without IRDS. The adjusted hazard ratio of epilepsy among children with IRDS compared to those without was 1.4 (95% CI 1.2-1.6). When we restricted the IRDS cohort to children with no simultaneous morbidities that had clinical symptoms overlapping with IRDS, the overall adjusted HR was 1.1 (95% CI 0.9-1.4). In children born preterm at 32-36 weeks' gestation, IRDS was associated with increased risk of childhood epilepsy.

Negative psychological aspects and survival in lung cancer patients.

PubMed

Nakaya, Naoki; Saito-Nakaya, Kumi; Akechi, Tatsuo; Kuriyama, Shinichi; Inagaki, Masatoshi; Kikuchi, Nobutaka; Nagai, Kanji; Tsugane, Shoichiro; Nishiwaki, Yutaka; Tsuji, Ichiro; Uchitomi, Yosuke

2008-05-01

We conducted a prospective cohort study in Japan to investigate associations between negative psychological aspects and cancer survival. Between July 1999 and July 2004, a total of 1178 lung cancer patients were enrolled. The questionnaire asked about socioeconomic variables, smoking status, clinical symptoms, and psychological aspects after diagnosis. Negative psychological aspects were assessed for the subscales of helplessness/hopelessness and depression. Clinical stage, performance status (PS), and histologic type were obtained from medical charts. The subjects were followed up until December 2004, and 686 had died. A Cox regression model was used to estimate the hazards ratio (HR) of all-cause mortality. After adjustment for socioeconomic variables and smoking status in addition to sex, age, and histologic type, both helplessness/hopelessness and depression subscales showed significant linear positive associations with the risk of mortality (p for trend<0.001 for both). However, after adjustment for clinical state variables in addition to sex, age, and histologic type, these significant linear positive associations were no longer observed (p for trend=0.41 and 0.26, respectively). Our data supported the hypothesis that the association between helplessness/hopelessness and depression and the risk of mortality among lung cancer patients was largely confounded by clinical state variables including clinical stage, PS, and clinical symptoms. (c) 2007 John Wiley & Sons, Ltd.

Isoniazid Toxicity among an Older Veteran Population: A Retrospective Cohort Study.

PubMed

Vinnard, Christopher; Gopal, Anand; Linkin, Darren R; Maslow, Joel

2013-01-01

our objective was to determine the incidence of toxicity among veterans initiating isoniazid therapy for latent tuberculosis infection (LTBI) and determine whether advancing age was a risk factor for toxicity. we performed a retrospective cohort study among all adults initiating isoniazid treatment for LTBI at a Veterans Medical Center from 1999 to 2005. We collected data on patient demographics, co-morbidities, site of initiation, and treatment outcome. 219 patients initiated isoniazid therapy for LTBI during the period of observation, and the completion of therapy was confirmed in 100 patients (46%). Among 18/219 patients (8%) that discontinued therapy due to a documented suspected toxicity, the median time to onset was 3 months (IQR 1-5 months). In an adjusted Cox regression model, there was no association between discontinuation due to suspected toxicity and advancing age (HR 1.03, 95% CI 0.99, 1.07). In contrast, hepatitis C infection was a significant predictor of cessation due to toxicity in the adjusted analysis (HR 3.03, 95% CI 1.08, 8.52). cessation of isoniazid therapy due to suspected toxicity was infrequently observed among a veteran population and was not associated with advancing age. Alternative LTBI treatment approaches should be further examined in the veteran population.

Yogurt consumption, weight change and risk of overweight/obesity: the SUN cohort study.

PubMed

Martinez-Gonzalez, M A; Sayon-Orea, C; Ruiz-Canela, M; de la Fuente, C; Gea, A; Bes-Rastrollo, M

2014-11-01

Epidemiological studies on the association between yogurt consumption and the risk of overweight/obesity are scarce. We prospectively examined the association of yogurt consumption with overweight/obesity and average annual weight gain. Prospective cohort study of 8516 men and women (mean age 37.1, SD: 10.8 y). Participants were followed-up every two years. Participants were classified in 5 categories of yogurt consumption at baseline: 0-2, >2-<5, 5-<7, 7 and ≥ 7 servings/week. Outcomes were: 1) average yearly weight change during follow-up; and 2) incidence of overweight/obesity. Linear regression models and Cox models were used to adjust for potential confounders. After a median follow-up of 6.6 years, 1860 incident cases of overweight/obesity were identified. A high (>7 servings/week) consumption of total and whole-fat yogurt was associated with lower incidence of overweight/obesity [multivariable adjusted hazard ratios = 0.80 (95% CI: 0.68-0.94); and 0.62 (0.47-0.82) respectively] in comparison with low consumption (0-2 servings/week). This inverse association was stronger among participants with higher fruit consumption. In this Mediterranean cohort, yogurt consumption was inversely associated with the incidence of overweight/obesity, especially among participants with higher fruit consumption. Copyright © 2014 Elsevier B.V. All rights reserved.

Workplace social capital and all-cause mortality: a prospective cohort study of 28,043 public-sector employees in Finland.

PubMed

Oksanen, Tuula; Kivimäki, Mika; Kawachi, Ichiro; Subramanian, S V; Takao, Soshi; Suzuki, Etsuji; Kouvonen, Anne; Pentti, Jaana; Salo, Paula; Virtanen, Marianna; Vahtera, Jussi

2011-09-01

We examined the association between workplace social capital and all-cause mortality in a large occupational cohort from Finland. We linked responses of 28 043 participants to surveys in 2000 to 2002 and in 2004 to national mortality registers through 2009. We used repeated measurements of self- and coworker-assessed social capital. We carried out Cox proportional hazard and fixed-effects logistic regressions. During the 5-year follow-up, 196 employees died. A 1-unit increase in the mean of repeat measurements of self-assessed workplace social capital (range 1-5) was associated with a 19% decrease in the risk of all-cause mortality (age- and gender-adjusted hazard ratio [HR] = 0.81; 95% confidence interval [CI] = 0.66, 0.99). The corresponding point estimate for the mean of coworker-assessed social capital was similar, although the association was less precisely estimated (age- and gender-adjusted HR = 0.77; 95% CI = 0.50, 1.20). In fixed-effects analysis, a 1-unit increase in self-assessed social capital across the 2 time points was associated with a lower mortality risk (odds ratio = 0.81; 95% CI = 0.55, 1.19). Workplace social capital appears to be associated with lowered mortality in the working-aged population.

Mitochondrial genetic haplogroups and incident obesity: a longitudinal cohort study.

PubMed

Veronese, Nicola; Stubbs, Brendon; Koyanagi, Ai; Vaona, Alberto; Demurtas, Jacopo; Schofield, Patricia; Thompson, Trevor; Maggi, Stefania

2018-04-01

A small number of case-control studies have suggested that mitochondrial haplogroups could be associated with obesity. We examined whether obesity risk was influenced by mitochondrial haplogroup in a large North American cohort across an 8-year period. We conducted a longitudinal cohort study including individuals from the Osteoarthritis Initiative. Mitochondrial haplogroups were determined by sequencing and PCR-RFLP techniques using this nomenclature: HV, JT, KU, IWX, and super HV/others. The strength of the association between mitochondrial haplogroups and incident obesity was quantified with hazard ratios (HRs), adjusted for potential confounders using a Cox's regression analysis. Overall, 2342 non-obese Caucasian participants (56.7% women) with a mean ± SD age of 62.0 ± 9.5 years at baseline were included. During a median follow-up of 8 years, 334 individuals ( = 14.3% of baseline population) became obese. After adjusting for nine potential confounders, the haplogroups IWX carried a significant 48% higher risk of obesity (HR = 1.48; 95% CI: 1.02-2.39) compared to the HV haplotype (the most frequent type). Only the presence of the IWX haplogroups appears to be linked to increased obesity risk, independent of potential baseline confounders. Future cohort studies are needed to confirm these findings and to determine potential underlying mechanisms.

Workplace Social Capital and All-Cause Mortality: A Prospective Cohort Study of 28 043 Public-Sector Employees in Finland

PubMed Central

Kivimäki, Mika; Kawachi, Ichiro; Subramanian, S. V.; Takao, Soshi; Suzuki, Etsuji; Kouvonen, Anne; Pentti, Jaana; Salo, Paula; Virtanen, Marianna; Vahtera, Jussi

2011-01-01

Objectives. We examined the association between workplace social capital and all-cause mortality in a large occupational cohort from Finland. Methods. We linked responses of 28 043 participants to surveys in 2000 to 2002 and in 2004 to national mortality registers through 2009. We used repeated measurements of self- and coworker-assessed social capital. We carried out Cox proportional hazard and fixed-effects logistic regressions. Results. During the 5-year follow-up, 196 employees died. A 1-unit increase in the mean of repeat measurements of self-assessed workplace social capital (range 1–5) was associated with a 19% decrease in the risk of all-cause mortality (age- and gender-adjusted hazard ratio [HR] = 0.81; 95% confidence interval [CI] = 0.66, 0.99). The corresponding point estimate for the mean of coworker-assessed social capital was similar, although the association was less precisely estimated (age- and gender-adjusted HR = 0.77; 95% CI = 0.50, 1.20). In fixed-effects analysis, a 1-unit increase in self-assessed social capital across the 2 time points was associated with a lower mortality risk (odds ratio = 0.81; 95% CI = 0.55, 1.19). Conclusions. Workplace social capital appears to be associated with lowered mortality in the working-aged population. PMID:21778502

Depression or anxiety and all-cause mortality in adults with atrial fibrillation--A cohort study in Swedish primary care.

PubMed

Wändell, Per; Carlsson, Axel C; Gasevic, Danijela; Wahlström, Lars; Sundquist, Jan; Sundquist, Kristina

2016-01-01

Our aim was to study depression and anxiety in atrial fibrillation (AF) patients as risk factors for all-cause mortality in a primary care setting. The study population included adults (n = 12 283) of 45 years and older diagnosed with AF in 75 primary care centres in Sweden. The association between depression or anxiety and all-cause mortality was explored using Cox regression analysis, with hazard ratios (HRs) and 95% confidence intervals (95% CIs). Analyses were conducted in men and women, adjusted for age, educational level, marital status, neighborhood socio-economic status (SES), change of neighborhood status and anxiety or depression, respectively, and cardiovascular co-morbidities. As a secondary analysis, background factors and their association with depression or anxiety were explored. The risk of all-cause mortality was higher among men with depression compared to their counterparts without depression even after full adjustment (HR = 1.28, 95% CI 1.08-1.53). For anxiety among men and anxiety or depression among women with AF, no associations were found. Cerebrovascular disease was more common among depressed AF patients. Increased awareness of the higher mortality among men with AF and subsequent depression is called for. We suggest a tight follow-up and treatment of both ailments in clinical practice.

Sleep problems and disability retirement: a register-based follow-up study.

PubMed

Lallukka, Tea; Haaramo, Peija; Lahelma, Eero; Rahkonen, Ossi

2011-04-15

Among aging employees, sleep problems are prevalent, but they may have serious consequences that are poorly understood. This study examined whether sleep problems are associated with subsequent disability retirement. Baseline questionnaire survey data collected in 2000-2002 among employees of the city of Helsinki, Finland, were linked with register data on disability retirement diagnoses by the end of 2008 (n = 457) for those with written consent for such linkages (74%; N = 5,986). Sleep problems were measured by the Jenkins Sleep Questionnaire. Cox regression analysis was used to calculate hazard ratios and 95% confidence intervals for disability retirement. Gender- and age-adjusted frequent sleep problems predicted disability retirement due to all causes (hazard ratio (HR) = 3.22, 95% confidence interval (CI): 2.26, 4.60), mental disorders (HR = 9.06, 95% CI: 3.27, 25.10), and musculoskeletal disorders (HR = 3.27, 95% CI: 1.91, 5.61). Adjustments for confounders, that is, baseline sociodemographic factors, work arrangements, psychosocial working conditions, and sleep duration, had negligible effects on these associations, whereas baseline physical working conditions and health attenuated the associations. Health behaviors and obesity did not mediate the examined associations. In conclusion, sleep problems are associated with subsequent disability retirement. To prevent early exit from work, sleep problems among aging employees need to be addressed.

Higher revision risk for unicompartmental knee arthroplasty in low-volume hospitals

PubMed Central

Espehaug, Birgitte; Indrekvam, Kari; Havelin, Leif I; Furnes, Ove

2014-01-01

Background and purpose Some studies have found high complication rates and others have found low complication rates after unicompartmental knee arthroplasty (UKA). We evaluated whether hospital procedure volume influences the risk of revision using data from the Norwegian Arthroplasty Register (NAR). Materials and methods 5,791 UKAs have been registered in the Norwegian Arthroplasty Register. We analyzed the 4,460 cemented medial Oxford III implants that were used from 1999 to 2012; this is the most commonly used UKA implant in Norway. Cox regression (adjusted for age, sex, and diagnosis) was used to estimate risk ratios (RRs) for revision. 4 different volume groups were compared: 1–10, 11–20, 21–40, and > 40 UKA procedures annually per hospital. We also analyzed the reasons for revision. Results and interpretation We found a lower risk of revision in hospitals performing more than 40 procedures a year than in those with less than 10 UKAs a year, with an unadjusted RR of 0.53 (95% CI: 0.35–0.81) and adjusted RR of 0.59 (95% CI: 0.39–0.90). Low-volume hospitals appeared to have a higher risk of revision due to dislocation, instability, malalignment, and fracture than high-volume hospitals. PMID:24847789

Relationship between characteristics of volunteer community health workers and antiretroviral treatment outcomes in a community-based treatment programme in Uganda.

PubMed

Alibhai, Arif; Kipp, Walter; Saunders, L Duncan; Rubaale, Tom; Mill, Judy; Konde-Lule, Joseph

2017-09-01

Community health workers (CHWs) can help to redress the shortages of health human resources needed to scale up antiretroviral treatment (ART). However, the selection of CHWs could influence the effectiveness of a CHW programme. The purpose of this observational study was to assess whether sociodemographic characteristics and geographic proximity to patients of volunteer CHWs were predictors of clinical outcomes in a community-based ART (CBART) programme in Kabarole, Uganda. Data from CHW surveys for 41 CHWs and clinic charts for 185 patients in the CBART programme were analysed using multivariable logistic and Cox regression models. Time to travel to patients was the only statistically significant characteristic of CHWs associated with ART outcomes. Patients whose CHWs had to travel one or more hours had a 71% lower odds of virologic suppression (adjusted OR = 0.29, 95% CI = 0.13-0.65, p = .002) and a 4.52 times higher mortality hazard rate (adjusted HR = 4.52, 95% CI = 1.20-17.09, p = .026) compared to patients whose CHWs had to travel less than one hour. The findings show that the sociodemographic characteristics of CHWs were not as important as the geographic distance they had to travel to patients.

Maternal exposure to heatwave and preterm birth in Brisbane, Australia.

PubMed

Wang, J; Williams, G; Guo, Y; Pan, X; Tong, S

2013-12-01

To quantify the short-term effects of maternal exposure to heatwave on preterm birth. An ecological study. A population-based study in Brisbane, Australia. All pregnant women who had a spontaneous singleton live birth in Brisbane between November and March in 2000-2010 were studied. Daily data on pregnancy outcomes, meteorological factors, and ambient air pollutants were obtained. The Cox proportional hazards regression model with time-dependent variables was used to examine the short-term impact of heatwave on preterm birth. A series of cut-off temperatures and durations were used to define heatwave. Multivariable analyses were also performed to adjust for socio-economic factors, demographic factors, meteorological factors, and ambient air pollutants. Spontaneous preterm births. The adjusted hazard ratios (HRs) ranged from 1.13 (95% CI 1.03-1.24) to 2.00 (95% CI 1.37-2.91) by using different heatwave definitions, after controlling for demographic, socio-economic, and meteorological factors, and air pollutants. Heatwave was significantly associated with preterm birth: the associations were robust to the definitions of heatwave. The threshold temperatures, instead of duration, could be more likely to influence the evaluation of birth-related heatwaves. The findings of this study may have significant public health implications as climate change progresses. © 2013 RCOG.

Utilization of psychiatric care and antidepressants among people with different severity of depression: a population-based cohort study in Stockholm, Sweden.

PubMed

Sun, Yuying; Möller, Jette; Lundin, Andreas; Wong, Samuel Y S; Yip, Benjamin H K; Forsell, Yvonne

2018-06-01

To identify how severity of depression predicts future utilization of psychiatric care and antidepressants. Data derived from a longitudinal population-based study in Stockholm, Sweden, include 10443 participants aged 20-64 years. Depression was assessed by Major Depression Inventory and divided into subsyndromal, mild, moderate and severe depression. Outcomes were the first time of hospitalization, specialized outpatient care and prescribed drugs obtained from national register records. The association between severity of depression and outcomes was tested by Cox regression analysis, after adjusting for gender, psychiatric treatment history and socio-environmental factors. The cumulative incidences of hospitalizations, outpatient care and antidepressants were 4.0, 11.2, and 21.9% respectively. Compared to the non-depressed group, people with different severity of depression (subsyndromal, mild, moderate and severe depression) all had significantly higher risk of all three psychiatric services (all log-rank test P < 0.001). Use of psychiatric care and antidepressants increased by rising severity of depression. Although the associations between severity of depression and psychiatric services were significant, the dose relationship was not present in people with previous psychiatric history or after adjusting for gender and other factors. People with subsyndromal to severe depression all have increased future psychiatric service utilization compared to non-depressed people.

Intakes of caffeine, coffee and tea and risk of amyotrophic lateral sclerosis: Results from five cohort studies.

PubMed

Fondell, Elinor; O'Reilly, É Ilis J; Fitzgerald, Kathryn C; Falcone, Guido J; Kolonel, Laurence N; Park, Yikyung; Gapstur, Susan M; Ascherio, Alberto

2015-01-01

Caffeine is thought to be neuroprotective by antagonizing the adenosine A2A receptors in the brain and thereby protecting motor neurons from excitotoxicity. We examined the association between consumption of caffeine, coffee and tea and risk of amyotrophic lateral sclerosis (ALS). Longitudinal analyses based on over 1,010,000 males and females in five large cohort studies (the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health-AARP Diet and Health Study). Cohort-specific multivariable-adjusted risk ratios (RR) and 95% confidence intervals (CI) estimates of ALS incidence or death were estimated by Cox proportional hazards regression and pooled using random-effects models. Results showed that a total of 1279 cases of ALS were documented during a mean of 18 years of follow-up. Caffeine intake was not associated with ALS risk; the pooled multivariable-adjusted RR comparing the highest to the lowest quintile of intake was 0.96 (95% CI 0.81-1.16). Similarly, neither coffee nor tea was associated with ALS risk. In conclusion, the results of this large study do not support associations of caffeine or caffeinated beverages with ALS risk.

Intakes of caffeine, coffee and tea and risk of Amyotrophic Lateral Sclerosis: Results from five cohort studies

PubMed Central

Fondell, Elinor; O'Reilly, Éilis J.; Fitzgerald, Kathryn C.; Falcone, Guido J.; Kolonel, Laurence N.; Park, Yikyung; Gapstur, Susan M.; Ascherio, Alberto

2015-01-01

Objective Caffeine is thought to be neuroprotective by antagonizing the adenosine A2A receptors in the brain and thereby protecting motor neurons from excitotoxicity. We examined the association between consumption of caffeine, coffee and tea and risk of Amyotrophic Lateral Sclerosis (ALS). Methods Longitudinal analyses based on over 1 010 000 men and women in 5 large cohort studies [the Nurses’ Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health – AARP Diet and Health Study]. Cohort-specific multivariable-adjusted risk ratios (RR) and 95% confidence intervals (CI) estimates of ALS incidence or death was estimated by Cox proportional hazards regression and pooled using random-effects models. Results A total of 1279 cases of ALS were documented during a mean of 18 years of follow-up. Caffeine intake was not associated with ALS risk; the pooled multivariable-adjusted RR comparing the highest to the lowest quintile of intake was 0.96 (95% CI 0.81-1.16). Similarly, neither coffee nor tea was associated with ALS risk. Conclusion The results of this large study do not support associations of caffeine or caffeinated beverages with ALS risk. PMID:25822002

Employment exit and entry among U.S. adults with and without arthritis during the Great Recession. A longitudinal study: 2007-2009, NHIS/MEPS.

PubMed

Theis, K A; Roblin, D; Helmick, C G; Luo, R

2018-05-28

Negative employment consequences of arthritis are known but not fully understood. Examining transitions in and out of work can provide valuable information. To examine associations of arthritis with employment during the Great Recession and predictors of employment transitions. Data were for 3,277 adults ages 30-62 years with and without arthritis from the 2007 National Health Interview Survey followed in the Medical Expenditure Panel Survey 2008-2009. Employment (working vs. not working) was ascertained at baseline and five follow-ups. We estimated Kaplan Meier survival curves with 95% confidence intervals (CI) separately for time to stopping work (working at baseline) and starting work (not working at baseline) using Cox proportional hazards regression models with hazard ratios (HR). Arthritis was significantly associated with greater risk of stopping work (HR = 1.7, 95% CI = 1.3-2.2; adjusted HR= 1.5, 95% CI = 1.1-2.0) and significantly associated with 40% lower chance of starting work (HR = 0.6, 95% CI = 0.4-0.8); which reversed on adjustment (HR = 1.5, 95% CI = 1.0-2.2). Employment predictors were mixed by outcome. During the Great Recession, adults with arthritis stopped work at higher rates and started work at lower rates than those without arthritis.

Percutaneous Endoscopic Gastrostomy Tube Is a Negative Prognostic Factor for Recurrent/Metastatic Head and Neck Cancer.

PubMed

Siano, Marco; Jarisch, Nadine; Joerger, Markus; Espeli, Vittoria

2018-06-01

Recurrent/metastatic head and neck squamous cell cancer (r/mHNSCC) patients often need a percutaneous endoscopic gastrostomy feeding tube (PEG). Among known prognostic factors, PEG could be prognostic as well. We retrospectively analyzed r/mHNSCC patients referred for systemic treatment. Kaplan-Meier and multivariate cox regression models were applied to assess prognostic impact of PEG. One hunderd and ten patients were identified, 42 had a PEG at treatment start. Median survival from start of 1st-line systemic treatment was 8 months (95%CI=6.5-12.0 months), 4.5 months (95%CI=2.5-7.0 months) for patients with PEG and 11.5 months (95%CI=7.5-14.5 months) without PEG (adjusted HR=1.98, p=0.011). Similarly, survival from first recurrence of distant metastases was lower in patients with PEG as compared to patients without (7.5 vs. 15.5 months, adjusted HR=2.60, p<0.001). Presence of PEG feeding tube has an unfavourable prognostic impact on survival in patients with r/mHNSCC. While any causality remains speculative, potential complications should be appreciated before PEG implantation. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Birth Weight and Subsequent Risk of Cancer

PubMed Central

Spracklen, Cassandra N; Wallace, Robert B; Sealy-Jefferson, Shawnita; Robinson, Jennifer G; Freudenheim, Jo L; Wellons, Melissa F; Saftlas, Audrey F; Snetselaar, Linda G; Manson, JoAnn E; Hou, Lifang; Qi, Lihong; Chlebowski, Rowan T; Ryckman, Kelli K

2014-01-01

Background We aimed to determine the association between self-reported birth weight and incident cancer in the Women’s Health Initiative Observational Study cohort, a large multiethnic cohort of postmenopausal women. Methods 65,850 women reported their birth weight by category (<6 lbs., 6 lbs.–7 lbs. 15 oz., 8 lbs.–9 lbs. 15 oz., and ≥10 lbs.). All self-reported, incident cancers were adjudicated by study staff. We used Cox proportional hazards regression to estimate crude and adjusted hazard ratios (aHR) for associations between birth weight and: 1) all cancer sites combined, 2) gynecologic cancers, and 3) several site-specific cancer sites. Results After adjustments, birth weight was positively associated with the risk of lung cancer (p=0.01), and colon cancer (p=0.04). An inverse trend was observed between birth weight and risk for leukemia (p=0.04). A significant trend was not observed with breast cancer risk (p=0.67); however, women born weighing ≥10 lbs. were less likely to develop breast cancer compared to women born between 6 lbs.–7 lbs. 15 oz (aHR 0.77, 95% CI 0.63, 0.94). Conclusion Birth weight category appears to be significantly associated with the risk of any postmenopausal incident cancer, though the direction of the association varies by cancer type. PMID:25096278

Recent gestational diabetes was associated with mothers stopping predominant breastfeeding earlier in a multi-ethnic population.

PubMed

Baerug, Anne; Sletner, Line; Laake, Petter; Fretheim, Atle; Løland, Beate Fossum; Waage, Christin W; Birkeland, Kåre I; Jenum, Anne Karen

2018-06-01

It has previously been shown that breastfeeding may reduce the risk of type 2 diabetes in mothers with recent gestational diabetes mellitus (GDM). This study compared the cessation of predominant breastfeeding in mothers with and without recent GDM in a multi-ethnic population. From May 2008 to May 2010, healthy pregnant women attending antenatal care provided by community health services in Eastern Oslo, Norway were recruited. We included 616 women-58% non-Western-and interviewed and examined them at a mean of 15 and 28 weeks of gestation and 14 weeks' postpartum. Cox regression models examined the association between GDM, as assessed by the 2013 World Health Organization criteria, and breastfeeding cessation. Overall, 190 of the 616 (31%) mothers had GDM and they ended predominant breastfeeding earlier than mothers without GDM, with an adjusted hazard ratio (aHR) of 1.33 and 95% confidence interval (95% CI) of 1.01-1.77. Mothers of South Asian origin ended predominant breastfeeding earlier than Western European mothers in the adjusted analysis (aHR 1.53, 95% CI: 1.04-2.25), but Middle Eastern mothers did not. Recent gestational diabetes was associated with earlier cessation of predominant breastfeeding in Western European and non-Western women. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Cardiorespiratory fitness and components of the metabolic syndrome in sedentary men.

PubMed

Riou, Marie-Eve; Pigeon, Etienne; St-Onge, Josée; Tremblay, Angelo; Marette, André; Weisnagel, John; Joanisse, Denis R

2009-01-01

To investigate the relationships between fitness and components of the metabolic syndrome in sedentary men. 39 subjects (34-53 years) were evaluated for fitness (VO(2max)) and anthropometric, metabolic, and skeletal muscle phenotypes. VO(2max) was assessed on a bicycle ergometer whereas other variables were obtained from an oral glucose tolerance test (OGTT), hydrostatic weighing, and a muscle biopsy. Pearson and partial correlations adjusted for fat mass (FM), waist circumference (WC), muscle enzyme activities (citrate synthase (CS), cytochrome c oxidase (COX)), and capillary density were used to investigate the independent relationships be tween variables. Negative correlations between VO(2max) and WC as well as blood pressure and OGTT test were observed. When adjusted for FM, correlations remained between VO(2max) and WC (r = -0.46, p < 0.01) and systolic blood pressure (r = -0.35, p < 0.05). When adjusted for WC and CS activity, all correlations were lost except for high-sensitivity C-reactive protein (hs-CRP) (r = -0.34, p < 0.05) which remained when adjusted for CS activity. Adjustment for COX activity failed to remove correlations with hs-CRP (r = -0.36, p < 0.05), age (r = 0.34, p < 0.05), WC (r = -0.35, p < 0.05), and blood pressure. Negative correlations persisted when fitness was adjusted for the mean number of capillaries. The effects of fitness on components of the metabolic syndrome in sedentary men are explained by abdominal obesity and muscle phenotypes.

Sex Differences in Functional Stress Test Versus CT Angiography in Symptomatic Patients With Suspected CAD: Insights From PROMISE

PubMed Central

Pagidipati, Neha J.; Hemal, Kshipra; Coles, Adrian; Mark, Daniel B.; Dolor, Rowena J.; Pellikka, Patricia A.; Hoffmann, Udo; Litwin, Sheldon E.; Udelson, James; Daubert, Melissa A.; Shah, Svati H.; Martinez, Beth; Lee, Kerry L.; Douglas, Pamela S.

2016-01-01

Background Risk stratification is an important goal of cardiac noninvasive tests (NITs), yet little contemporary data exist on the prognostic value of different NITs by patient sex. Objectives To compare the results and prognostic information derived from anatomic versus stress testing in stable men and women with suspected coronary artery disease. Methods In 8966 PROMISE trial patients tested as randomized (4500 computed tomographic angiography [CTA], 52% female; 4466 stress testing, 53% female), we assessed the relationship between sex and NIT results using logistic regression, and the relationship between sex and a composite of death, myocardial infarction, and unstable angina hospitalization using Cox proportional hazards models. Results In women, a positive CTA (≥70% stenosis) was less likely than a positive stress test (8% vs. 12%, adjusted OR 0.67 [95% CI 0.55-0.82]). Compared with negative tests, a positive CTA was more strongly associated with subsequent clinical events than a positive stress test (CTA adjusted HR 5.86 [95% CI 3.32-10.35]; stress adjusted HR 2.27 [95% CI 1.21-4.25]; adjusted p=0.028). Men were more likely to have a positive CTA than stress test (16% vs. 14%, adjusted OR 1.23 [95% CI 1.04-1.47]). Compared with negative tests, a positive CTA was less strongly associated with subsequent clinical events than a positive stress test in men, although this difference was not statistically significant (CTA adjusted HR 2.80 [95% CI 1.76-4.45]; stress adjusted HR 4.42 [95% CI 2.77-7.07]; adjusted p=0.168). Negative CTA and stress tests were equally likely to predict an event in both sexes (adjusted p-values=NS). A significant interaction between sex, NIT type, and test result (p=0.01) suggests that sex and NIT type jointly influence the relationship between test result and clinical events. Conclusions The prognostic value of an NIT result varies by test type and patient sex. Women appear to derive more prognostic information from a CTA, while men tend to derive similar prognostic value from both test types. PMID:27058908

Choice of time-scale in Cox's model analysis of epidemiologic cohort data: a simulation study.

PubMed

Thiébaut, Anne C M; Bénichou, Jacques

2004-12-30

Cox's regression model is widely used for assessing associations between potential risk factors and disease occurrence in epidemiologic cohort studies. Although age is often a strong determinant of disease risk, authors have frequently used time-on-study instead of age as the time-scale, as for clinical trials. Unless the baseline hazard is an exponential function of age, this approach can yield different estimates of relative hazards than using age as the time-scale, even when age is adjusted for. We performed a simulation study in order to investigate the existence and magnitude of bias for different degrees of association between age and the covariate of interest. Age to disease onset was generated from exponential, Weibull or piecewise Weibull distributions, and both fixed and time-dependent dichotomous covariates were considered. We observed no bias upon using age as the time-scale. Upon using time-on-study, we verified the absence of bias for exponentially distributed age to disease onset. For non-exponential distributions, we found that bias could occur even when the covariate of interest was independent from age. It could be severe in case of substantial association with age, especially with time-dependent covariates. These findings were illustrated on data from a cohort of 84,329 French women followed prospectively for breast cancer occurrence. In view of our results, we strongly recommend not using time-on-study as the time-scale for analysing epidemiologic cohort data. 2004 John Wiley & Sons, Ltd.

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.

Prognostic and Predictive Value of CpG Island Methylator Phenotype in Patients with Locally Advanced Nonmetastatic Sporadic Colorectal Cancer

PubMed Central

Long, Yadong; Xu, Ye; Guan, Zuqing; Lian, Peng; Peng, Junjie

2014-01-01

Purpose. In the present study, the prognostic significance of CpG island methylator phenotype (CIMP) in stage II/III sporadic colorectal cancer was evaluated using a five-gene panel. Methods. Fifty stage II/III colorectal cancer patients who received radical resection were included in this study. Promoter methylation of p14ARF, hMLH1, p16INK4a, MGMT, and MINT1 was determined by methylation specific polymerase chain reaction (MSP). CIMP positive was defined as hypermethylation of three or more of the five genes. Impact factors on disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier method (log-rank test) and adjusted Cox proportional hazards model. Results. Twenty-four percent (12/50) of patients were characterized as CIMP positive. Univariate analysis showed stage III (P = 0.049) and CIMP positive (P = 0.014) patients who had significantly inferior DFS. In Cox regression analysis, CIMP positive epigenotype was independently related with poor DFS with HR = 2.935 and 95% CI: 1.193–7.220 (P = 0.019). In patients with CIMP positive tumor, those receiving adjuvant chemotherapy had a poor DFS than those without adjuvant chemotherapy (P = 0.023). Conclusions. CIMP positive was significantly correlated with decreased DFS in stage II/III colorectal cancer. Patients with CIMP positive locally advanced sporadic colorectal cancers may not benefit from 5-fluorouracil based adjuvant chemotherapy. PMID:24822060

Diabetic foot ulcer incidence in relation to plantar pressure magnitude and measurement location.

PubMed

Ledoux, William R; Shofer, Jane B; Cowley, Matthew S; Ahroni, Jessie H; Cohen, Victoria; Boyko, Edward J

2013-01-01

We prospectively examined the relationship between site-specific peak plantar pressure (PPP) and ulcer risk. Researchers have previously reported associations between diabetic foot ulcer and elevated plantar foot pressure, but the effect of location-specific pressures has not been studied. Diabetic subjects (n=591) were enrolled from a single VA hospital. Five measurements of in-shoe plantar pressure were collected using F-Scan. Pressures were measured at 8 areas: heel, lateral midfoot, medial midfoot, first metatarsal, second through fourth metatarsal, fifth metatarsal, hallux, and other toes. The relationship between incident plantar foot ulcer and PPP or pressure-time integral (PTI) was assessed using Cox regression. During follow-up (2.4years), 47 subjects developed plantar ulcers (10 heel, 12 metatarsal, 19 hallux, 6 other). Overall mean PPP was higher for ulcer subjects (219 vs. 194kPa), but the relationship differed by site (the metatarsals with ulcers had higher pressure, while the opposite was true for the hallux and heel). A statistical analysis was not performed on the means, but hazard ratios from a Cox survival analysis were nonsignificant for PPP across all sites and when adjusted for location. However, when the metatarsals were considered separately, higher baseline PPP was significantly associated with greater ulcer risk; at other sites, this relationship was nonsignificant. Hazard ratios for all PTI data were nonsignificant. Location must be considered when assessing the relationship between PPP and plantar ulceration. © 2013.

Diabetic foot ulcer incidence in relation to plantar pressure magnitude and measurement location☆,☆☆,★

PubMed Central

Ledoux, William R.; Shofer, Jane B.; Cowley, Matthew S.; Ahroni, Jessie H.; Cohen, Victoria; Boyko, Edward J.

2014-01-01

Aims We prospectively examined the relationship between site-specific peak plantar pressure (PPP) and ulcer risk. Researchers have previously reported associations between diabetic foot ulcer and elevated plantar foot pressure, but the effect of location-specific pressures has not been studied. Methods Diabetic subjects (n = 591) were enrolled from a single VA hospital. Five measurements of in-shoe plantar pressure were collected using F-Scan. Pressures were measured at 8 areas: heel, lateral midfoot, medial midfoot, first metatarsal, second through fourth metatarsal, fifth metatarsal, hallux, and other toes. The relationship between incident plantar foot ulcer and PPP or pressure–time integral (PTI) was assessed using Cox regression. Results During follow-up (2.4 years), 47 subjects developed plantar ulcers (10 heel, 12 metatarsal, 19 hallux, 6 other). Overall mean PPP was higher for ulcer subjects (219 vs. 194 kPa), but the relationship differed by site (the metatarsals with ulcers had higher pressure, while the opposite was true for the hallux and heel). A statistical analysis was not performed on the means, but hazard ratios from a Cox survival analysis were nonsignificant for PPP across all sites and when adjusted for location. However, when the metatarsals were considered separately, higher baseline PPP was significantly associated with greater ulcer risk; at other sites, this relationship was nonsignificant. Hazard ratios for all PTI data were nonsignificant. Conclusions Location must be considered when assessing the relationship between PPP and plantar ulceration. PMID:24012295

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.

Comparison of Statistical Approaches Dealing with Time-dependent Confounding in Drug Effectiveness Studies

PubMed Central

Karim, Mohammad Ehsanul; Petkau, John; Gustafson, Paul; Platt, Robert W.; Tremlett, Helen

2017-01-01

In longitudinal studies, if the time-dependent covariates are affected by the past treatment, time-dependent confounding may be present. For a time-to-event response, marginal structural Cox models (MSCMs) are frequently used to deal with such confounding. To avoid some of the problems of fitting MSCM, the sequential Cox approach has been suggested as an alternative. Although the estimation mechanisms are different, both approaches claim to estimate the causal effect of treatment by appropriately adjusting for time-dependent confounding. We carry out simulation studies to assess the suitability of the sequential Cox approach for analyzing time-to-event data in the presence of a time-dependent covariate that may or may not be a time-dependent confounder. Results from these simulations revealed that the sequential Cox approach is not as effective as MSCM in addressing the time-dependent confounding. The sequential Cox approach was also found to be inadequate in the presence of a time-dependent covariate. We propose a modified version of the sequential Cox approach that correctly estimates the treatment effect in both of the above scenarios. All approaches are applied to investigate the impact of beta-interferon treatment in delaying disability progression in the British Columbia Multiple Sclerosis cohort (1995 – 2008). PMID:27659168

Marital status and survival in patients with renal cell carcinoma.

PubMed

Li, Yan; Zhu, Ming-Xi; Qi, Si-Hua

2018-04-01

Previous studies have shown that marital status is an independent prognostic factor for survival in several types of cancer. In this study, we investigated the effects of marital status on survival outcomes among renal cell carcinoma (RCC) patients.We identified patients diagnosed with RCC between 1973 and 2013 from the Surveillance, Epidemiology and End Results (SEER) database. Kaplan-Meier analysis and Cox regression were used to identify the effects of marital status on overall survival (OS) and cancer-specific survival (CSS).We enrolled 97,662 eligible RCC patients, including 64,884 married patients, and 32,778 unmarried (9831 divorced/separated, 9692 widowed, and 13,255 single) patients at diagnosis. The 5-year OS and CSS rates of the married, separated/divorced, widowed, and single patients were 73.7%, 69.5%, 58.3%, and 73.2% (OS), and 82.2%, 80.7%, 75.7%, and 83.3% (CSS), respectively. Multivariate Cox regression showed that, compared with married patients, widowed individuals showed poorer OS (hazard ratio, 1.419; 95% confidence interval, 1.370-1.469) and CSS (hazard ratio, 1.210; 95% confidence interval, 1.144-1.279). Stratified analyses and multivariate Cox regression showed that, in the insured and uninsured groups, married patients had better survival outcomes while widowed patients suffered worse OS outcomes; however, this trend was not significant for CSS.In RCC patients, married patients had better survival outcomes while widowed patients tended to suffer worse survival outcomes in terms of both OS and CSS.

Marital status and survival in patients with renal cell carcinoma

PubMed Central

Li, Yan; Zhu, Ming-xi; Qi, Si-hua

2018-01-01

Abstract Previous studies have shown that marital status is an independent prognostic factor for survival in several types of cancer. In this study, we investigated the effects of marital status on survival outcomes among renal cell carcinoma (RCC) patients. We identified patients diagnosed with RCC between 1973 and 2013 from the Surveillance, Epidemiology and End Results (SEER) database. Kaplan–Meier analysis and Cox regression were used to identify the effects of marital status on overall survival (OS) and cancer-specific survival (CSS). We enrolled 97,662 eligible RCC patients, including 64,884 married patients, and 32,778 unmarried (9831 divorced/separated, 9692 widowed, and 13,255 single) patients at diagnosis. The 5-year OS and CSS rates of the married, separated/divorced, widowed, and single patients were 73.7%, 69.5%, 58.3%, and 73.2% (OS), and 82.2%, 80.7%, 75.7%, and 83.3% (CSS), respectively. Multivariate Cox regression showed that, compared with married patients, widowed individuals showed poorer OS (hazard ratio, 1.419; 95% confidence interval, 1.370–1.469) and CSS (hazard ratio, 1.210; 95% confidence interval, 1.144–1.279). Stratified analyses and multivariate Cox regression showed that, in the insured and uninsured groups, married patients had better survival outcomes while widowed patients suffered worse OS outcomes; however, this trend was not significant for CSS. In RCC patients, married patients had better survival outcomes while widowed patients tended to suffer worse survival outcomes in terms of both OS and CSS. PMID:29668592

Refining adverse drug reaction signals by incorporating interaction variables identified using emergent pattern mining.

PubMed

Reps, Jenna M; Aickelin, Uwe; Hubbard, Richard B

2016-02-01

To develop a framework for identifying and incorporating candidate confounding interaction terms into a regularised cox regression analysis to refine adverse drug reaction signals obtained via longitudinal observational data. We considered six drug families that are commonly associated with myocardial infarction in observational healthcare data, but where the causal relationship ground truth is known (adverse drug reaction or not). We applied emergent pattern mining to find itemsets of drugs and medical events that are associated with the development of myocardial infarction. These are the candidate confounding interaction terms. We then implemented a cohort study design using regularised cox regression that incorporated and accounted for the candidate confounding interaction terms. The methodology was able to account for signals generated due to confounding and a cox regression with elastic net regularisation correctly ranking the drug families known to be true adverse drug reactions above those that are not. This was not the case without the inclusion of the candidate confounding interaction terms, where confounding leads to a non-adverse drug reaction being ranked highest. The methodology is efficient, can identify high-order confounding interactions and does not require expert input to specify outcome specific confounders, so it can be applied for any outcome of interest to quickly refine its signals. The proposed method shows excellent potential to overcome some forms of confounding and therefore reduce the false positive rate for signal analysis using longitudinal data. Copyright © 2015 Elsevier Ltd. All rights reserved.

Long Term Exposure to NO2 and Diabetes Incidence in the Black Women's Health Study

PubMed Central

Coogan, Patricia F.; White, Laura F.; Yu, Jeffrey; Burnett, Richard T.; Marshall, Julian D.; Seto, Edmund; Brook, Robert D.; Palmer, Julie R.; Rosenberg, Lynn; Jerrett, Michael

2016-01-01

While laboratory studies show that air pollutants can potentiate insulin resistance, the epidemiologic evidence regarding the association of air pollution with diabetes incidence is conflicting. The purpose of the present study was to assess the association of the traffic-related nitrogen dioxide (NO2) with the incidence of diabetes in a longitudinal cohort study of African American women. We used Cox proportional hazards models to calculate hazard ratios and 95% confidence intervals (CI) for diabetes associated with exposure to NO2 among 43,003 participants in the Black Women's Health Study (BWHS). Pollutant levels at participant residential locations were estimated with 1) a land use regression model for participants living in 56 metropolitan areas, and 2) a dispersion model for participants living in 27 of the cities. From 1995-2011, 4387 cases of diabetes occurred. The hazard ratios per interquartile range of NO2 (9.7 ppb), adjusted for age, metropolitan area, education, vigorous exercise, body mass index, smoking, and diet, were 0.96 (95% CI 0.88-1.06) using the land use regression model estimates and 0.94 (95% CI 0.80, 1.10) using the dispersion model estimates. The present results do not support the hypothesis that exposure to NO2 contributes to diabetes incidence in African American women. PMID:27124624

Increased dietary sodium is independently associated with greater mortality among prevalent hemodialysis patients.

PubMed

Mc Causland, Finnian R; Waikar, Sushrut S; Brunelli, Steven M

2012-07-01

Dietary sodium is thought to play a major role in the pathogenesis of hypertension, hypervolemia, and mortality in hemodialysis patients; hence, sodium restriction is almost universally recommended. Since the evidence upon which to base these assumptions is limited, we undertook a post-hoc analysis of 1770 patients in the Hemodialysis Study with available dietary, clinical, and laboratory information. Within this cohort, 772 were men, 1113 black, and 786 diabetic, with a mean age of 58 years and a median dietary sodium intake of 2080 mg/day. After case-mix adjustment, linear regression modeling found that higher dietary sodium was associated with a greater ultrafiltration requirement, caloric and protein intake; sodium to calorie intake ratio was associated with a greater ultrafiltration requirement; and sodium to potassium ratio was associated with higher serum sodium. No indices were associated with the pre-dialysis systolic blood pressure. Cox regression modeling found that higher baseline dietary sodium and the ratio of sodium to calorie or potassium were each independently associated with greater all-cause mortality. No association between a prescribed dietary sodium restriction and mortality were found. Thus, higher reported dietary sodium intake is independently associated with greater mortality among prevalent hemodialysis patients. Randomized trials will be necessary to determine whether dietary sodium restriction improves survival.

FABP4 and Cardiovascular Events in Peripheral Arterial Disease.

PubMed

Höbaus, Clemens; Herz, Carsten Thilo; Pesau, Gerfried; Wrba, Thomas; Koppensteiner, Renate; Schernthaner, Gerit-Holger

2018-05-01

Fatty acid-binding protein 4 (FABP4) is a possible biomarker of atherosclerosis. We evaluated FABP4 levels, for the first time, in patients with peripheral artery disease (PAD) and the possible association between baseline FABP4 levels and cardiovascular events over time. Patients (n = 327; mean age 69 ± 10 years) with stable PAD were enrolled in this study. Serum FABP4 was measured by bead-based multiplex assay. Cardiovascular events were analyzed by FABP4 tertiles using Kaplan-Meier and Cox regression analyses after 5 years. Serum FABP4 levels showed a significant association with the classical 3-point major adverse cardiovascular event (MACE) end point (including death, nonlethal myocardial infarction, or nonfatal stroke) in patients with PAD ( P = .038). A standard deviation increase of FABP4 resulted in a hazard ratio (HR) of 1.33 (95% confidence interval [95% CI]: 1.03-1.71) for MACE. This association increased (HR: 1.47, 95% CI: 1.03-1.71) after multivariable adjustment ( P = .020). Additionally, in multivariable linear regression analysis, FABP4 was linked to estimated glomerular filtration rate ( P < .001), gender ( P = .005), fasting triglycerides ( P = .048), and body mass index ( P < .001). Circulating FABP4 may be a useful additional biomarker to evaluate patients with stable PAD at risk of major cardiovascular complications.

Twins' risk of childhood asthma mediated by gestational age and birthweight.

PubMed

Ullemar, V; Lundholm, C; Almqvist, C

2015-08-01

Children born with low gestational age (GA) or low birthweight (BW) are at increased risk of asthma. Twins as compared to singletons are on average more likely to be born with lower GA and BW and have been hypothesized to comprise a high-risk population for asthma. Many previous studies have not accounted for potential confounders or mediators. To investigate the association between twinship and childhood asthma or early life wheeze and identify potential mediators, such as GA/BW. The study population consisted of two cohorts including all children born in Sweden from 1 January 1993 to 1 June 2001 (n = 756,363 singletons, n = 22,478 twins) and 1 July 2005 to 31 December 2009 (n = 456,239 singletons, n = 12,872 twins). Asthma was defined using validated register-based outcomes of diagnosis or medication. The data were analysed using logistic (older cohort) and Cox regression (younger cohort). Adjusted models incorporated potential confounding or mediating factors including gestational age and birthweight. In the younger cohort, the crude hazard ratio (HR) of asthma medication after 1.5 years of age was 1.12 (95% CI 1.01-1.23), and fully adjusted HR was 0.80, 95% CI 0.72-0.89. Crude HR of asthma diagnosis in the same age group was 1.14 (95% CI 0.99-1.30), fully adjusted 0.78 (0.68-0.98). Adjusted analyses in the older group yielded similar results. Twins were at significantly higher unadjusted risk of asthma or early life wheeze compared to singletons in the younger, but not in the older cohort. Associations attenuated following adjustment for GA/BW, suggesting that GA/BW mediates the effect of twinship on asthma risk. After adjustments, twins were at lower risk of asthma outcomes, possibly due to unmeasured confounding. © 2015 John Wiley & Sons Ltd.

The association of neck circumference with incident congestive heart failure and coronary heart disease mortality in a community-based population with or without sleep-disordered breathing.

PubMed

Zhang, Jingjing; Guo, Qi; Peng, Liyuan; Li, Jiamei; Gao, Ya; Yan, Bin; Fang, Bangjiang; Wang, Gang

2018-05-31

Neck circumference (NC), representing upper body subcutaneous adipose tissue, may be correlated with increased risk of overweight/obesity, obstructive sleep apnoea, and metabolic and cardiovascular disease. However, the relationship between NC and the incidence of congestive heart failure (CHF) or mortality due to coronary heart disease (CHD) in a community-based population with and without sleep-disordered breathing (SDB) has not yet been clarified. We performed a prospective study using the Sleep Heart Health Study (SHHS) cohort. Cox proportional hazards regression models were used to estimate the association of different levels of NC with CHF incidence or CHD mortality in 2234 individuals with SDB and 2199 without SDB, respectively. After adjusting for age, sex, and body mass index (BMI), NC was significantly associated with CHF when comparing the highest NC quartile group with the lowest (hazard ratio, HR, 2.265, 95% confidence interval, CI, 1.074-4.777) in the non-SDB population. This association diminished after further adjustment for other risk factors, but remained statistically significant, with an adjusted HR of 1.082 (95% CI 1.003-1.166) per unit increase in NC. Additionally, after adjustment for age, sex, and BMI, NC was also shown to be remarkably associated with CHD mortality (HR 1.141, 95% CI 1.014-1.282) per unit increase in NC in the non-SDB population but not in the SDB population. After adjustment for all the covariates, there was a significant association between NC and CHD death in those without SDB, with an adjusted HR of 1.134 (95% CI 1.001-1.284) per unit increase in NC. NC may correlate with CHF incidence and CHD mortality in population without SDB. NC measurement may help risk stratification for cardiovascular diseases. NCT00005275 , January 1994.

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.

Adjustment of regional regression equations for urban storm-runoff quality using at-site data

USGS Publications Warehouse

Barks, C.S.

1996-01-01

Regional regression equations have been developed to estimate urban storm-runoff loads and mean concentrations using a national data base. Four statistical methods using at-site data to adjust the regional equation predictions were developed to provide better local estimates. The four adjustment procedures are a single-factor adjustment, a regression of the observed data against the predicted values, a regression of the observed values against the predicted values and additional local independent variables, and a weighted combination of a local regression with the regional prediction. Data collected at five representative storm-runoff sites during 22 storms in Little Rock, Arkansas, were used to verify, and, when appropriate, adjust the regional regression equation predictions. Comparison of observed values of stormrunoff loads and mean concentrations to the predicted values from the regional regression equations for nine constituents (chemical oxygen demand, suspended solids, total nitrogen as N, total ammonia plus organic nitrogen as N, total phosphorus as P, dissolved phosphorus as P, total recoverable copper, total recoverable lead, and total recoverable zinc) showed large prediction errors ranging from 63 percent to more than several thousand percent. Prediction errors for 6 of the 18 regional regression equations were less than 100 percent and could be considered reasonable for water-quality prediction equations. The regression adjustment procedure was used to adjust five of the regional equation predictions to improve the predictive accuracy. For seven of the regional equations the observed and the predicted values are not significantly correlated. Thus neither the unadjusted regional equations nor any of the adjustments were appropriate. The mean of the observed values was used as a simple estimator when the regional equation predictions and adjusted predictions were not appropriate.

Ten‐Year Blood Pressure Trajectories, Cardiovascular Mortality, and Life Years Lost in 2 Extinction Cohorts: the Minnesota Business and Professional Men Study and the Zutphen Study

PubMed Central

Tielemans, Susanne M. A. J.; Geleijnse, Johanna M.; Menotti, Alessandro; Boshuizen, Hendriek C.; Soedamah‐Muthu, Sabita S.; Jacobs, David R.; Blackburn, Henry; Kromhout, Daan

2015-01-01

Background Blood pressure (BP) trajectories derived from measurements repeated over years have low measurement error and may improve cardiovascular disease prediction compared to single, average, and usual BP (single BP adjusted for regression dilution). We characterized 10‐year BP trajectories and examined their association with cardiovascular mortality, all‐cause mortality, and life years lost. Methods and Results Data from 2 prospective and nearly extinct cohorts of middle‐aged men—the Minnesota Business and Professional Men Study (n=261) and the Zutphen Study (n=632)—were used. BP was measured annually during 1947–1957 in Minnesota and 1960–1970 in Zutphen. BP trajectories were identified by latent mixture modeling. Cox proportional hazards and linear regression models examined BP trajectories with cardiovascular mortality, all‐cause mortality, and life years lost. Associations were adjusted for age, serum cholesterol, smoking, and diabetes mellitus. Mean initial age was about 50 years in both cohorts. After 10 years of BP measurements, men were followed until death on average 20 years later. All Minnesota men and 98% of Zutphen men died. Four BP trajectories were identified, in which mean systolic BP increased by 5 to 49 mm Hg in Minnesota and 5 to 20 mm Hg in Zutphen between age 50 and 60. The third systolic BP trajectories were associated with 2 to 4 times higher cardiovascular mortality risk, 2 times higher all‐cause mortality risk, and 4 to 8 life years lost, compared to the first trajectory. Conclusions Ten‐year BP trajectories were the strongest predictors, among different BP measures, of cardiovascular mortality, all‐cause mortality, and life years lost in Minnesota. However, average BP was the strongest predictor in Zutphen. PMID:25753924

Return to Work in Employees on Sick Leave due to Neck or Shoulder Pain: A Randomized Clinical Trial Comparing Multidisciplinary and Brief Intervention with One-Year Register-Based Follow-Up.

PubMed

Moll, Line Thorndal; Jensen, Ole Kudsk; Schiøttz-Christensen, Berit; Stapelfeldt, Christina Malmose; Christiansen, David Høyrup; Nielsen, Claus Vinther; Labriola, Merete

2018-06-01

Purpose The aim of this study was to evaluate the effect of a multidisciplinary intervention (MDI) compared to a brief intervention (BI) with respect to return to work (RTW), pain and disability in workers on sick leave because of neck or shoulder pain. Methods 168 study participants with sickness absence for 4-16 weeks due to neck or shoulder pain were enrolled in a hospital-based clinical study and randomized to either MDI or BI. The primary outcome was RTW obtained by a national registry on public transfer payments. Secondary outcomes were self-reported pain and disability levels. One-year follow-up RTW rates were estimated by Cox proportional hazard regression adjusted for gender, age, sick leave prior to inclusion, part-time sick leave and clinical diagnosis. Secondary outcomes were analysed using logistic and linear regression analysis for pain and disability, respectively. Results In the MDI group, 50 participants (59%) experienced four or more continuous weeks of RTW while 48 (58%) returned to work in the BI group during the 1 year of follow-up. Results showed a statistically non significant tendency towards a lower rate of RTW in the MDI group than in the BI group (adjusted HR = 0.84, 95% CI 0.54, 1.31). There were no statistically significant differences in secondary outcomes between the MDI and BI groups. Conclusion The brief and the multidisciplinary interventions performed equally with respect to both primary and secondary outcomes. The added focus on RTW in the multidisciplinary group did not improve RTW rates in this group.

Causes of Death in Men With Prevalent Diabetes and Newly Diagnosed High- Versus Favorable-Risk Prostate Cancer

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

D'Amico, Anthony V., E-mail: adamico@partners.or; Braccioforte, Michelle H.; Moran, Brian J.

2010-08-01

Purpose: To determine whether prevalent diabetes mellitus (pDM) affects the presentation, extent of radiotherapy, or prostate cancer (PCa)-specific mortality (PCSM) and whether PCa aggressiveness affects the risk of non-PCSM, DM-related mortality, and all-cause mortality in men with pDM. Methods: Between October 1997 and July 2907, 5,279 men treated at the Chicago Prostate Cancer Center with radiotherapy for PCa were included in the study. Logistic and competing risk regression analyses were performed to assess whether pDM was associated with high-grade PCa, less aggressive radiotherapy, and an increased risk of PCSM. Competing risks and Cox regression analyses were performed to assess whethermore » PCa aggressiveness described by risk group in men with pDM was associated with the risk of non-PCSM, DM-related mortality, and all-cause mortality. Analyses were adjusted for predictors of high-grade PCa and factors that could affect treatment extent and mortality. Results: Men with pDM were more likely (adjusted hazard ratio [AHR], 1.9; 95% confidence interval [CI], 1.3-2.7; p = .002) to present with high-grade PCa but were not treated less aggressively (p = .33) and did not have an increased risk of PCSM (p = .58) compared to men without pDM. Among the men with pDM, high-risk PCa was associated with a greater risk of non-PCSM (AHR, 2.2; 95% CI, 1.1-4.5; p = .035), DM-related mortality (AHR, 5.2; 95% CI, 2.0-14.0; p = .001), and all-cause mortality (AHR, 2.4; 95% CI, 1.2-4.7; p = .01) compared to favorable-risk PCa. Conclusion: Aggressive management of pDM is warranted in men with high-risk PCa.« less

A CD4+ cell count <200 cells per cubic millimeter at 2 years after initiation of combination antiretroviral therapy is associated with increased mortality in HIV-infected individuals with viral suppression.

PubMed

Loutfy, Mona R; Genebat, Miguel; Moore, David; Raboud, Janet; Chan, Keith; Antoniou, Tony; Milan, David; Shen, Anya; Klein, Marina B; Cooper, Curtis; Machouf, Nima; Rourke, Sean B; Rachlis, Anita; Tsoukas, Chris; Montaner, Julio S G; Walmsley, Sharon L; Smieja, Marek; Bayoumi, Ahmed; Mills, Edward; Hogg, Robert S

2010-12-01

To determine the long-term impact of immunologic discordance (viral load <50 copies/mL and CD4+ count <=200 cells/mm3) in antiretroviral-naive patients initiating combination antiretroviral therapy (cART). Our analysis included antiretroviral-naive individuals from a population-based Canadian Observational Cohort that initiated cART after January 1, 2000, and achieved virologic suppression. Multivariable Cox proportional hazards regression was used to examine the association between 1-year and 2-year immunologic discordance and time to death from all-causes. Correlates of immunologic discordance were assessed with logistic regression. Immunologic discordance was observed in 19.9% (404 of 2028) and 10.2% (176 of 1721) of individuals at 1 and 2 years after cART initiation, respectively. Two-year immunologic discordance was associated with an increased risk of death [adjusted hazard ratio = 2.69; 95% confidence interval (CI): 1.26 to 5.78]. One-year immunologic discordance was not associated with death (adjusted hazard ratio = 1.12; 95% CI: 0.54 to 2.30). Two-year immunologic discordance was associated with older age (aOR per decade = 1.23; 95% CI: 1.03 to 1.48), male gender (aOR = 1.86; 95% CI: 1.09 to 3.16), injection drug use (aOR = 2.75; 95% CI: 1.81 to 4.17), and lower baseline CD4+ count (aOR per 100 cells = 0.24; 95% CI: 0.19 to 0.31) and viral load (aOR per log10 copies/mL = 0.46; 95% CI: 0.33 to 0.65). Immunologic discordance after 2 years of cART in antiretroviral-naive individuals was significantly associated with an increased risk of mortality.

Direct vs. Expressed Breast Milk Feeding: Relation to Duration of Breastfeeding.

PubMed

Pang, Wei Wei; Bernard, Jonathan Y; Thavamani, Geetha; Chan, Yiong Huak; Fok, Doris; Soh, Shu-E; Chua, Mei Chien; Lim, Sok Bee; Shek, Lynette P; Yap, Fabian; Tan, Kok Hian; Gluckman, Peter D; Godfrey, Keith M; van Dam, Rob M; Kramer, Michael S; Chong, Yap-Seng

2017-05-27

Studies examining direct vs. expressed breast milk feeding are scarce. We explored the predictors of mode of breastfeeding and its association with breastfeeding duration in a multi-ethnic Asian population. We included 541 breastfeeding mother-infant pairs from the Growing Up in Singapore Toward healthy Outcomes cohort. Mode of breastfeeding (feeding directly at the breast, expressed breast milk (EBM) feeding only, or mixed feeding (a combination of the former 2 modes)) was ascertained at three months postpartum. Ordinal logistic regression analyses identified predictors of breast milk expression. Cox regression models examined the association between mode of breastfeeding and duration of any and of full breastfeeding. Maternal factors independently associated with a greater likelihood of breast milk expression instead of direct breastfeeding were Chinese (vs. Indian) ethnicity, (adjusted odds ratio, 95% CI; 3.41, 1.97-5.91), tertiary education (vs. secondary education or lower) (2.22, 1.22-4.04), primiparity (1.54, 1.04-2.26) and employment during pregnancy (2.53, 1.60-4.02). Relative to those who fed their infants directly at the breast, mothers who fed their infants EBM only had a higher likelihood of early weaning among all mothers who were breastfeeding (adjusted hazard ratio, 95% CI; 2.20, 1.61-3.02), and among those who were fully breastfeeding (2.39, 1.05-5.41). Mothers who practiced mixed feeding, however, were not at higher risk of earlier termination of any or of full breastfeeding. Mothers who fed their infants EBM exclusively, but not those who practiced mixed feeding, were at a higher risk of terminating breastfeeding earlier than those who fed their infants directly at the breast. More education and support are required for women who feed their infants EBM only.

Prediagnosis Sleep Duration, Napping, and Mortality Among Colorectal Cancer Survivors in a Large US Cohort

PubMed Central

Arem, Hannah; Pfeiffer, Ruth; Matthews, Charles

2017-01-01

Abstract Study Objectives: Prediagnosis lifestyle factors can influence colorectal cancer (CRC) survival. Sleep deficiency is linked to metabolic dysfunction and chronic inflammation, which may contribute to higher mortality from cardiometabolic conditions and promote tumor progression. We hypothesized that prediagnosis sleep deficiency would be associated with poor CRC survival. No previous study has examined either nighttime sleep or daytime napping in relation to survival among men and women diagnosed with CRC. Methods: We examined self-reported sleep duration and napping prior to diagnosis in relation to mortality among 4869 CRC survivors in the NIH-AARP Diet and Health Study. Vital status was ascertained by linkage to the Social Security Administration Death Master File and the National Death Index. We examined the associations of sleep and napping with mortality using traditional Cox regression (total mortality) and Compositing Risk Regression (cardiovascular disease [CVD] and CRC mortality). Models were adjusted for confounders (demographics, cancer stage, grade and treatment, smoking, physical activity, and sedentary behavior) as well as possible mediators (body mass index and health status) in separate models. Results: Compared to participants reporting 7–8 hours of sleep per day, those who reported <5 hr had a 36% higher all-cause mortality risk (Hazard Ratio (95% Confidence Interval), 1.36 (1.08–1.72)). Short sleep (<5 hr) was also associated with a 54% increase in CRC mortality (Substitution Hazard Ratio (95% Confidence Interval), 1.54 (1.11–2.14)) after adjusting for confounders and accounting for competing causes of death. Compared to no napping, napping 1 hr or more per day was associated with significantly higher total and CVD mortality but not CRC mortality. Conclusion: Prediagnosis short sleep and long napping were associated with higher mortality among CRC survivors. PMID:28329353

Physical activity increases survival after heart valve surgery.

PubMed

Lund, K; Sibilitz, K L; Berg, S K; Thygesen, L C; Taylor, R S; Zwisler, A D

2016-09-01

Increased physical activity predicts survival and reduces risk of readmission in patients with coronary heart disease. However, few data show how physical activity is associated with survival and readmission after heart valve surgery. Objective were to assess the association between physical activity levels 6-12 months after heart valve surgery and (1) survival, (2) hospital readmission 18-24 months after surgery and (3) participation in exercise-based cardiac rehabilitation. Prospective cohort study with registry data from The CopenHeart survey, The Danish National Patient Register and The Danish Civil Registration System of 742 eligible patients. Physical activity was quantified with the International Physical Activity Questionnaire and analysed using Kaplan-Meier analysis and Cox regression and logistic regression methods. Patients with a moderate to high physical activity level had a reduced risk of mortality (3 deaths in 289 patients, 1%) compared with those with a low physical activity level (13 deaths in 235 patients, 5.5%) with a fully adjusted HR of 0.19 (95% CI 0.05 to 0.70). In contrast, physical activity level was not associated with the risk of hospital readmission. Patients who participated in exercise-based cardiac rehabilitation (n=297) were more likely than the non-participants (n=200) to have a moderate or high physical activity level than a low physical activity level (fully adjusted OR: 1.52, 95% CI 1.03 to 2.24). Moderate to high levels of physical activity after heart valve surgery are positively associated with higher survival rates and participation in cardiac rehabilitation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Cancer Stage at Diagnosis and Survival among Persons with Social Security Disability Insurance on Medicare

PubMed Central

McCarthy, Ellen P; Ngo, Long H; Chirikos, Thomas N; Roetzheim, Richard G; Li, Donglin; Drews, Reed E; Iezzoni, Lisa I

2007-01-01

Objective To examine stage at diagnosis and survival for disabled Medicare beneficiaries diagnosed with cancer under age 65 and compare their experiences with those of other persons diagnosed under age 65. Data Sources Surveillance, Epidemiology, and End Results (SEER) Program data and SEER-Medicare linked data for 1988–1999. SEER-11 Program includes 11 population-based tumor registries collecting information on all incident cancers in catchment areas. Tumor registry and Medicare data are linked for persons enrolled in Medicare. Study Design 307,595 incident cases of non-small cell lung (51,963), colorectal (52,092), breast (142,281), and prostate (61,259) cancer diagnosed in persons under age 65 from 1988 to 1999. Persons who qualified for Social Security Disability Insurance and had Medicare (SSDI/Medicare) were identified from Medicare enrollment files. Ordinal polychotomous logistic regression and Cox proportional hazards regression were used to estimate adjusted associations between disability status and later-stage diagnoses and mortality (all-cause and cancer-specific). Principal Findings Persons with SSDI/Medicare had lower rates of Stages III/IV diagnoses than others for lung (63.3 versus 69.5 percent) and prostate (25.5 versus 30.8 percent) cancers, but not for breast or colorectal cancers. After adjustment, they remained less likely to be diagnosed at later stages for lung and prostate cancers. Nevertheless, persons with SSDI/Medicare experienced higher all-cause mortality for each cancer. Cancer-specific mortality was higher among persons with SSDI/Medicare for breast and colorectal cancer patients. Conclusions Disabled Medicare beneficiaries are diagnosed with cancer at similar or earlier stages than others. However, they experience higher rates of cancer-related mortality when diagnosed at the same stage of breast and colorectal cancer. PMID:17362209

A Prospective Study of Different Types of Dietary Fiber and Risk of Cardiovascular Disease: Tehran Lipid and Glucose Study.

PubMed

Mirmiran, Parvin; Bahadoran, Zahra; Khalili Moghadam, Sajad; Zadeh Vakili, Azita; Azizi, Fereidoun

2016-11-07

This study was designed to examine the hypothesis that dietary of intake different types of fiber could modify the risk of cardiovascular disease (CVD) in a large prospective cohort among Iranian adults. In 2006-2008, we used a validated food frequency questionnaire to assess dietary fiber intake among 2295 health professionals with no previous history of heart disease. Subjects were subsequently followed until 2012 for incidence of CVD events. Multivariate Cox proportional hazard regression models, adjusted for potential confounders were used to estimate the risk of CVD across tertiles of total dietary fiber and different types of fiber. Linear regression models were also used to indicate the association of dietary fiber intakes with changes of cardiovascular risk factors during the follow-up. Mean age of participants (42.8% men) was 38.2 ± 13.4, at baseline. Mean (SD) dietary intake of total fiber was 23.4 (8.9) g/day. After adjustment for cardiovascular risk score and dietary confounders, a significant inverse association was observed between intakes of total, soluble and insoluble dietary fiber and CVD risk, in the highest compared to the lowest tertiles (HR = 0.39, 95% CI = 0.18-0.83, HR = 0.19, 95% CI = 0.09-0.41, and HR = 0.31, 95% CI = 0.14-0.69, respectively). Inverse relations were observed between risk of CVD and dietary fiber from legumes, fruits and vegetables; however, dietary fiber intake from grain and nut sources was not related to risk of CVD. Our findings confirmed that higher intakes of dietary fiber from different sources is associated with CVD events and modify its major risk-related factors.

A Prospective Study of Different Types of Dietary Fiber and Risk of Cardiovascular Disease: Tehran Lipid and Glucose Study

PubMed Central

Mirmiran, Parvin; Bahadoran, Zahra; Khalili Moghadam, Sajad; Zadeh Vakili, Azita; Azizi, Fereidoun

2016-01-01

Background and aim: This study was designed to examine the hypothesis that dietary of intake different types of fiber could modify the risk of cardiovascular disease (CVD) in a large prospective cohort among Iranian adults. Methods: In 2006–2008, we used a validated food frequency questionnaire to assess dietary fiber intake among 2295 health professionals with no previous history of heart disease. Subjects were subsequently followed until 2012 for incidence of CVD events. Multivariate Cox proportional hazard regression models, adjusted for potential confounders were used to estimate the risk of CVD across tertiles of total dietary fiber and different types of fiber. Linear regression models were also used to indicate the association of dietary fiber intakes with changes of cardiovascular risk factors during the follow-up. Results: Mean age of participants (42.8% men) was 38.2 ± 13.4, at baseline. Mean (SD) dietary intake of total fiber was 23.4 (8.9) g/day. After adjustment for cardiovascular risk score and dietary confounders, a significant inverse association was observed between intakes of total, soluble and insoluble dietary fiber and CVD risk, in the highest compared to the lowest tertiles (HR = 0.39, 95% CI = 0.18–0.83, HR = 0.19, 95% CI = 0.09–0.41, and HR = 0.31, 95% CI = 0.14–0.69, respectively). Inverse relations were observed between risk of CVD and dietary fiber from legumes, fruits and vegetables; however, dietary fiber intake from grain and nut sources was not related to risk of CVD. Conclusion: Our findings confirmed that higher intakes of dietary fiber from different sources is associated with CVD events and modify its major risk-related factors. PMID:27827978

Long-term traffic-related exposures and asthma onset in schoolchildren in oslo, norway.

PubMed

Oftedal, Bente; Nystad, Wenche; Brunekreef, Bert; Nafstad, Per

2009-05-01

Whether there is a causal relation between long-term exposure to traffic and asthma development is so far not clear. This may be explained by inaccurate exposure assessment. We investigated the associations of long-term traffic-related exposures with asthma onset assessed retrospectively and respiratory symptoms in 9- to 10-year-old children. We collected information on respiratory outcomes and potential confounding variables by parental questionnaire in 2,871 children in Oslo. Nitrogen dioxide exposure was assessed by the EPISODE dispersion model and assigned at updated individual addresses during lifetime. Distance to major road was assigned at birth address and address by date of questionnaire. Cox proportional hazard regression and logistic regression were used. We did not find positive associations between any long-term traffic-related exposure and onset of doctor-diagnosed asthma. An interquartile range (IQR) increase of NO(2) exposure before asthma onset was associated with an adjusted risk ratio of 0.82 [95% confidence interval (CI), 0.67-1.02]. Handling early asthma cases (children < 4 years of age) with recovery during follow-up as noncases gave a less negative association. The associations for late asthma onset (>/= 4 years of age) were positive but not statistically significant. For current symptoms, an IQR increase of previous year's NO(2) exposure was associated with adjusted odds ratios of 1.01 (95% CI, 0.83-1.23) for wheeze, 1.10 (95% CI, 0.79-1.51) for severe wheeze, and 1.01 (95% CI, 0.84-1.21) for dry cough. We were not able to find positive associations of long-term traffic-related exposures with asthma onset or with current respiratory symptoms in 9- to 10-year-old children in Oslo.

Influence of Competing Risks on Estimating the Expected Benefit of Warfarin Among Atrial Fibrillation Patients not Currently Taking Anticoagulants: the ATRIA Study

PubMed Central

Ashburner, Jeffrey M.; Go, Alan S.; Chang, Yuchiao; Fang, Margaret C.; Fredman, Lisa; Applebaum, Katie M.; Singer, Daniel E.

2016-01-01

Background/Objectives To date, studies examining the association between warfarin therapy and incidence of ischemic stroke among patients with atrial fibrillation (AF) have not accounted for the competing risk of death. Competing risk analysis may provide greater understanding of the “real world” impact of anticoagulation on stroke risk over a multiyear time span. Design Cohort study Setting ATRIA Study community-based cohort Participants 13,559 adults with nonvalvular AF between 1996 and 2003. Measurements All events were clinician-adjudicated. We used extended Cox regression with longitudinal warfarin exposure to estimate cause-specific hazard ratios (HR) for thromboembolism (TE) and the competing risk event (all cause death). The Fine and Gray subdistribution regression approach was used to estimate this association while accounting for competing death events. As a secondary analysis, follow-up was limited to 1, 3, and 5-years. Results The rate of death was much higher in the non-warfarin group (8.1 deaths/100 person-years) compared to the warfarin group (5.5 deaths/100 person-years). The cause-specific HR indicated a large reduction in TE with warfarin use (adjusted HR: 0.57, 95% CI: 0.50–0.65). However, after accounting for competing death events, this association was substantially attenuated (adjusted HR: 0.87, 95% CI: 0.77–0.99). In analyses limited to 1-year of follow-up with fewer competing death events, the results for models that did and did not account for competing risks were similar. Conclusion Analyses accounting for competing death events may provide a more realistic estimate of the longer-term stroke prevention benefits of anticoagulants for patients with AF, particularly those who are not currently treated with anticoagulants. PMID:27861698

Acculturation and Outcomes among Patients with Heart Failure

PubMed Central

Peterson, Pamela N.; Campagna, Elizabeth J.; Maravi, Moises; Allen, Larry A.; Bull, Sheana; Steiner, John F.; Havranek, Edward P.; Dickinson, L. Miriam; Masoudi, Frederick A

2013-01-01

Background Acculturation to U.S. society among minority patients may influence health outcomes beyond race and ethnicity alone. In particular, those who are foreign-born and who do not speak English as their primary language may have greater challenges interacting with the health care system and thus be at greater risk for adverse outcomes. Methods and Results We studied patients hospitalized with a principal discharge diagnosis of HF between January 2000 and December 2007 in an integrated delivery system that cares for minority patients. Individuals were defined as having low acculturation if their primary language was not English and their country of birth was outside of the U.S. Multivariable logistic regression and Cox proportional hazards regression were used to determine the independent risk of 30-day rehospitalization and 1-year mortality, respectively. Candidate adjustment variables included demographics (age, gender, race/ethnicity), coexisting illnesses, laboratory values, left ventricular systolic function, and characteristics of the index admission. Of 1,268 patients, 30% (n=379) were Black, 39% (n=498) Hispanic, and 27% (n= 348) White. Eighteen percent (n=228) had low acculturation. After adjustment, low acculturation was associated with a higher risk of readmission at 30 days (OR 1.70; 95% CI 1.07-2.68) but not 1-year all-cause mortality (HR 0.69; 95% CI 0.42-1.14). Conclusions Patients with HF who are foreign-born and do not speak English as their primary language have a greater risk of rehospitalization, independent of clinical factors and race/ethnicity. Future studies should evaluate whether culturally concordant interventions focusing on such patients may improve outcomes for this patient population. PMID:22247483

Patient education-level affects treatment allocation and prognosis in esophageal- and gastroesophageal junctional cancer in Sweden.

PubMed

Linder, Gustav; Sandin, Fredrik; Johansson, Jan; Lindblad, Mats; Lundell, Lars; Hedberg, Jakob

2018-02-01

Low socioeconomic status and poor education elevate the risk of developing esophageal- and junctional cancer. High education level also increases survival after curative surgery. The present study aimed to investigate associations, if any, between patient education-level and treatment allocation after diagnosis of esophageal- and junctional cancer and its subsequent impact on survival. A nation-wide cohort study was undertaken. Data from a Swedish national quality register for esophageal cancer (NREV) was linked to the National Cancer Register, National Patient Register, Prescribed Drug Register, Cause of Death Register and educational data from Statistics Sweden. The effect of education level (low; ≤9 years, intermediate; 10-12 years and high >12 years) on the probability of allocation to curative treatment was analyzed with logistic regression. The Kaplan-Meier-method and Cox proportional hazard models were used to assess the effect of education on survival. A total of 4112 patients were included. In a multivariate logistic regression model, high education level was associated with greater probability of allocation to curative treatment (adjusted OR: 1.48, 95% CI: 1.08-2.03, p = 0,014) as was adherence to a multidisciplinary treatment-conference (adjusted OR: 3.13, 95% CI: 2.40-4.08, p < 0,001). High education level was associated with improved survival in the patients allocated to curative treatment (HR: 0.82, 95% CI: 0.69-0.99, p = 0,036). In this nation-wide cohort of esophageal- and junctional cancer patients, including data regarding many confounders, high education level was associated with greater probability of being offered curative treatment and improved survival. Copyright © 2017 Elsevier Ltd. All rights reserved.

Breast-feeding duration and gluten introduction among mothers with celiac disease.

PubMed

Welander, Adina; Montgomery, Scott; Ludvigsson, Johnny; Ludvigsson, Jonas F

2014-07-01

Both breast-feeding duration and age at gluten introduction have been implicated in the pathogenesis of celiac disease (CD). We hypothesized that parental CD affects the feeding pattern of the offspring, mediated by parental health awareness increasing adherence to infant feeding guidelines. Prospectively collected infant feeding data were obtained through the All Babies in Southeast Sweden study. Information regarding infant feeding was available in 9414 children. Twenty-two mothers had a history of biopsy-verified CD before delivery of a child in the study, and 9392 mothers had no diagnosis of CD before birth and thus constituted the unexposed or control population. Cox regression was used to compare the risk of early weaning and gluten introduction according to parental CD status, and logistic regression to assess whether mothers with CD were more likely to breast-feed their children at gluten introduction. Some 63% of children were breast-fed for at least 9 months. We found no association between maternal CD and early weaning (adjusted hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.6-1.7), or between paternal CD and early weaning (HR 0.5, 95% CI 0.1-1.9). Sixty percent of children were introduced to gluten in months 5 and 6. Maternal CD was not associated with age at gluten introduction (adjusted HR 0.8, 95% CI 0.6-1.3). There was no statistically significant association between maternal CD and breast-feeding at the time of gluten introduction (odds ratio 1.4, 95% CI 0.4-4.7). Feeding patterns do not seem to vary between offspring and mothers with CD and those without.

Insurance-Based Differences in Time to Diagnostic Follow-up after Positive Screening Mammography.

PubMed

Durham, Danielle D; Robinson, Whitney R; Lee, Sheila S; Wheeler, Stephanie B; Reeder-Hayes, Katherine E; Bowling, J Michael; Olshan, Andrew F; Henderson, Louise M

2016-11-01

Insurance may lengthen or inhibit time to follow-up after positive screening mammography. We assessed the association between insurance status and time to initial diagnostic follow-up after a positive screening mammogram. Using 1995-2010 data from a North Carolina population-based registry of breast imaging and cancer outcomes, we identified women with a positive screening mammogram. We compared receipt of follow-up within 60 days of screening using logistic regression and evaluated time to follow-up initiation using Cox proportional hazards regression. Among 43,026 women included in the study, 73% were <65 years and 27% were 65+ years. Median time until initial diagnostic follow-up was similar by age group and insurance status. In the adjusted model for women <65, uninsured women experienced a longer time to initiation of diagnostic follow-up [HR, 0.47; 95% confidence interval (CI), 0.25-0.89] versus women with private insurance. There were increased odds of these uninsured women not meeting the Centers for Disease Control and Prevention guideline for follow-up within 60 days (OR, 1.59; 95% CI, 1.31-1.94). Among women ages 65+, women with private insurance experienced a faster time to follow-up (adjusted HR, 2.09; 95% CI, 1.27-3.44) than women with Medicare and private insurance. Approximately 10% of women had no follow-up by 365 days. We found differences in time to initial diagnostic follow-up after a positive screening mammogram by insurance status and age group. Uninsured women younger than 65 years at a positive screening event had delayed follow-up. Replication of these findings and examination of their clinical significance warrant additional investigation. Cancer Epidemiol Biomarkers Prev; 25(11); 1474-82. ©2016 AACR. ©2016 American Association for Cancer Research.

Associations Between Medication Class and Subsequent Augmentation of Depression Treatment in Privately Insured US Adults.

PubMed

Ameli, Omid; Soria-Saucedo, Rene; Smith, Eric G; Cabral, Howard J; Soley-Bori, Marina; Kazis, Lewis E

2017-06-01

Treatment augmentation is an important clinical decision in the pharmacotherapy for depression, yet few studies have examined the rates of treatment augmentation by medication class. The aim of this study was to examine which initial pharmacotherapies for depression are more likely than others to result in subsequent treatment augmentation. This study is a retrospective cohort analysis of administrative data of 214,705 privately insured US adults between the age of 18 and 64 years who were diagnosed with a new episode of depression in 2009. Propensity score-adjusted logistic regression and Cox regression were used to model the effect of the class of initial monotherapy on treatment augmentation. Risk adjustors included depression severity, comorbidities, provider type, insurance, and demographic characteristics. The class of initial monotherapy and the health care provider type were the main independent variables of interest. The outcome was the augmentation of monotherapy. Thirty-four percent of individuals received treatment augmentation. Compared with selective serotonin reuptake inhibitor monotherapy, second-generation antipsychotics as the initial treatment were associated with significant increase in the likelihood of augmentation compared with the other classes (hazards ratio, 2.59; 95% confidence interval [CI], 2.51-2.68). This result was corroborated after propensity score adjustment (odds ratio, 2.85; 95% CI, 2.70-3.00) when comparing second-generation antipsychotics to the other classes of pharmacotherapy. The other significant predictor of treatment augmentation was the provider type. Mental health specialists were 27% more likely to augment a treatment compared with generalists (hazards ratio, 1.27; 95% CI, 1.25-1.30). The type of initial antidepressant therapy is associated with the chances of treatment augmentation. Second-generation antipsychotics progressed to augmentation more rapidly than the other classes.

Racial disparity in consultation, treatment, and the impact on survival in metastatic colorectal cancer.

PubMed

Simpson, Daniel R; Martínez, María Elena; Gupta, Samir; Hattangadi-Gluth, Jona; Mell, Loren K; Heestand, Gregory; Fanta, Paul; Ramamoorthy, Sonia; Le, Quynh-Thu; Murphy, James D

2013-12-04

Black patients with metastatic colorectal cancer have inferior survival compared to white patients. The purpose of this study was to examine disparity in specialist consultation and multimodality treatment and the impact that treatment inequality has on survival. We identified 9935 non-Hispanic white and 1281 black patients with stage IV colorectal cancer aged 66 years and older from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Logistic regression models identified race-based differences in consultation rates and subsequent treatment with surgery, chemotherapy, or radiation. Multivariable Cox regression models identified potential factors that explain race-based survival differences. All statistical tests were two-sided. Black patients had lower rates of consultation with surgery, medical oncology, and radiation oncology. Among patients seen in consultation, black patients received less surgery directed at the primary tumor, liver- or lung-directed surgery, chemotherapy, and radiotherapy. Unadjusted survival analysis found a 15% higher chance of dying for black patients compared with white patients (hazard ratio [HR] = 1.15; 95% confidence interval (CI) = 1.08 to 1.22; P < .001). Adjustment for patient, tumor, and demographic variables marginally reduced the risk of death (HR = 1.08; 95% CI = 1.01 to 1.15; P = .03). After adjustment for differences in treatment, the increased risk of death for black patients disappeared. Our study shows racial disparity in specialist consultation as well as subsequent treatment with multimodality therapy for metastatic colorectal cancer, and it suggests that inferior survival for black patients may stem from this treatment disparity. Further research into the underlying causes of this inequality will improve access to treatment and survival in metastatic colorectal cancer.

The Cumulative Burden of Mental, Substance Use, and General Medical Disorders and Rehospitalization and Mortality After an Injury.

PubMed

Zatzick, Douglas F; Rowhani-Rahbar, Ali; Wang, Jin; Russo, Joan; Darnell, Doyanne; Ingraham, Leah; Whiteside, Lauren K; Guiney, Roxanne; Hedrick, Margot Kelly; Rivara, Frederick P

2017-06-01

Each year in the United States, 1.5-2.5 million individuals require hospitalization for an injury. Multiple mental, substance use, and chronic general medical disorders are endemic among injury survivors with and without traumatic brain injury (TBI), yet few studies have assessed the association between the cumulative burden of these conditions and health care outcomes. This study of patients hospitalized for an injury assessed associations between comorbid mental, substance use, and general medical disorders, TBI, and violent events or suicide attempts and the postinjury outcomes of recurrent hospitalization and death. Recurrent hospitalization and all-cause mortality were examined in this population-based retrospective cohort study. A total of 76,942 patients hospitalized for an injury in Washington State during 2006-2007 were followed for five years. ICD-9-CM codes identified conditions prior to or at the index injury admission. Index admissions related to injuries from firearms, assaultive violence, suicide attempts, and overdoses were identified through E-codes. Adjusted regression analyses demonstrated a significant, dose-response relationship between an increasing cumulative burden of disorders and an increasing risk of recurrent hospitalization (four or more conditions, relative risk=3.89, 95% confidence interval [CI]=3.66-4.14). Adjusted Cox proportional hazard regression demonstrated a similar relationship between increasing cumulative burden of disorders and all-cause mortality (four or more conditions, hazard ratio=5.33, CI=4.71-6.04). Increasing cumulative burden of disorders was associated with greater postinjury risk of recurrent hospitalization and death. Orchestrated investigative and policy efforts could introduce screening and intervention procedures that target this spectrum of comorbidity.

Midlife use of written Japanese and protection from late life dementia

PubMed Central

Crane, Paul K.; Gibbons, Laura E.; Arani, Keerthi; Nguyen, Viet; Rhoads, Kristoffer; McCurry, Susan M.; Launer, Lenore; Masaki, Kamal; White, Lon

2011-01-01

Background The cognitive reserve hypothesis would predict that use of written Japanese should confer protection against dementia because of the complexity of its ideograms compared with written English. We sought to test this hypothesis in analyses from a longitudinal study of Japanese-American men. Methods Participants were second-generation Japanese-American men (Nisei) on the island of Oahu, Hawaii, who were seen in 1965 and in subsequent examinations to detect dementia beginning in 1991-1993. Use of spoken and written Japanese was self-reported in 1965 (Analyses 1 and 2), and mid-life use of written Japanese and written English was self-reported in 1994-1996 (Analysis 3). We analyzed prevalent dementia outcomes in 1991-1993 (Analysis 1, n=3,139) using logistic regression, and incident dementia outcomes in 1994-2002 (Analysis 2, n=2,299) and in 1997-2002 (Analysis 3, n=1,655) using Cox proportional hazards regression. Dementia outcomes included all-cause dementia, probable and possible Alzheimer disease, and probable vascular dementia. We adjusted models for probable and possible confounders. Results Participants who reported proficiency with written Japanese were older and had lower incomes. For Analysis 1, there were 154 prevalent cases of dementia, 74 of Alzheimer disease, and 43 of vascular dementia; for Analysis 2, 236 incident cases of dementia, 138 of Alzheimer disease, and 45 of vascular dementia; and for Analysis 3, 125 incident cases of dementia, 80 of Alzheimer disease, and 20 of vascular dementia. There was no relationship in adjusted models between self-reported proficiency with written Japanese and any dementia outcomes. Conclusions Proficiency with written Japanese does not appear to be protective for dementia. PMID:19593152

Relationship between heart rate variability and pulse wave velocity and their association with patient outcomes in chronic kidney disease

PubMed Central

Chandra, Preeti; Sands, Robin L.; Gillespie, Brenda W.; Levin, Nathan W.; Kotanko, Peter; Kiser, Margaret; Finkelstein, Fredric; Hinderliter, Alan; Rajagopalan, Sanjay; Sengstock, David; Saran, Rajiv

2014-01-01

Background: Arterial stiffness and low heart rate variability (HRV) have each been associated with increased cardiovascular risk in a variety of patient populations. We explored the relationship between HRV and pulse wave velocity (PWV measure of arterial stiffness) in patients with chronic kidney disease (CKD prior to ESRD) along with examining their association with the outcomes of cardiovascular disease (CVD), death, and progression to end stage renal disease (ESRD). Methods: The RRI-CKD Study is a 4-center prospective cohort study of CKD stages 3 – 5 (n = 834). A subset underwent both HRV testing by 24-hour Holter and carotid-femoral PWV (n = 240). Multiple linear regression was used to assess predictors of PWV and Cox regression to investigate the association of HRV and PWV with time to first CVD event or death and ESRD. Results: Although several HRV measures were inversely correlated with PWV, this association was attenuated after adjustment for age and/or diabetes and no longer significant after adjustment for C-reactive protein. Low HRV and high PWV were individually associated with increased risk of the composite endpoint of CVD/death in multivariable analysis. The risk of the composite of CVD/death was highest for patients with both low HRV and high PWV. Conclusion: Age, diabetes, and inflammation together explained the inverse association between HRV and PWV. Inflammation may play a role in the pathogenesis of both low HRV and high PWV. The combination of low HRV and high PWV showed the strongest association with a composite CVD outcome. Mechanisms underlying abnormalities in PWV and HRV, and the role of these measures as intermediate outcomes in future trials in CKD patients, merit further study. PMID:24356038

Incidence of Tube Feeding in 7174 Newly Admitted Nursing Home Residents With and Without Dementia.

PubMed

Schulze, Jana; Mazzola, Rosa; Hoffmann, Falk

2016-02-01

Tube feeding is a common form of long-term nutritional support, especially for nursing home residents, of whom many have dementia. Estimating the incidence of feeding tube placement in nursing home residents with and without dementia. Using claims data, we studied a cohort of newly admitted nursing home residents aged 65 years and older between 2004 and 2009. Analyses were stratified by dementia. We estimated incidence rates and performed multivariate Cox regression analyses. The study cohort included 7174 nursing home residents. Over a mean follow-up of 1.3 years, 273 people received a feeding tube. The incidence per 1000 person-years was 28.4, with higher estimates for patients with dementia. When adjusting for age, sex, and level of care as a time-dependent covariate, influence of dementia decreased to a nonsignificant hazard ratio. It seems that not dementia itself but the overall clinical condition might be a predictor of tube feeding placement. © The Author(s) 2015.

Evaluation of US Veterans Nutrition Education for Diabetes Prevention.

PubMed

Erickson, Megan; Braun, Katie; List, Riesa; Utech, Anne; Moore, Carolyn; White, Donna L; Garcia, Jose M

2016-09-01

Evaluate the effectiveness of nutrition education interventions for diabetes prevention. Retrospective cohort design. Tertiary-care US Veterans' Hospital, July 2007 to July 2012, using pre-existing database. Prediabetic, adult veterans (n = 372), mostly men (94.4%, n = 351). Visits with existing nutrition education classes were collected. diabetes status; predictors: visits/encounters, age, body mass index, weight change, and hemoglobin A1c. Cox proportional hazards method, χ(2) test, and logistic regression. In this sample, prediabetic veterans who received nutrition education were less likely to develop diabetes when compared with prediabetic veterans who did not receive nutrition education (hazard ratio, 0.71; 95% confidence interval, 0.55-0.92; P < .01). This difference remained significant after adjusting for body mass index and weight change. Nutrition education was significantly associated with preventing the progression from prediabetes to diabetes in US Veterans participating in a nutrition education intervention at the Michael E. DeBakey Veterans Affairs Medical Center. Copyright © 2016 Society for Nutrition Education and Behavior. All rights reserved.

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.

Dose-response relationships between internally-deposited uranium and select health outcomes in gaseous diffusion plant workers, 1948-2011.

PubMed

Yiin, James H; Anderson, Jeri L; Bertke, Stephen J; Tollerud, David J

2018-05-09

To examine dose-response relationships between internal uranium exposures and select outcomes among a cohort of uranium enrichment workers. Cox regression was conducted to examine associations between selected health outcomes and cumulative internal uranium with consideration for external ionizing radiation, work-related medical X-rays and contaminant radionuclides technetium ( 99 Tc) and plutonium ( 239 Pu) as potential confounders. Elevated and monotonically increasing mortality risks were observed for kidney cancer, chronic renal diseases, and multiple myeloma, and the association with internal uranium absorbed organ dose was statistically significant for multiple myeloma. Adjustment for potential confounders had minimal impact on the risk estimates. Kidney cancer, chronic renal disease, and multiple myeloma mortality risks were elevated with increasing internal uranium absorbed organ dose. The findings add to evidence of an association between internal exposure to uranium and cancer. Future investigation includes a study of cancer incidence in this cohort. © 2018 Wiley Periodicals, Inc.

Predictors of Dropout From Inpatient Substance Use Treatment: A Prospective Cohort Study

PubMed Central

Andersson, Helle Wessel; Steinsbekk, Aslak; Walderhaug, Espen; Otterholt, Eli; Nordfjærn, Trond

2018-01-01

Introduction: Dropout from inpatient treatment for substance use disorder (SUD) is an ongoing challenge. The aim of this study was to identify demographic, substance use, and psychological factors that predict dropout from postdetoxification inpatient SUD treatment. Materials and methods: A total of 454 patients from 5 inpatient SUD centers in Central Norway were consecutively included in this naturalistic, prospective cohort study. Results: A total of 132 patients (28%) did not complete the planned treatment stay (dropped out). Cox regression analysis showed that higher levels of intrinsic motivation for changing personal substance use reduced the dropout risk (adjusted hazard ratio [adjHR]: 0.62, 95% confidence interval [CI]: 0.48-0.79). Higher levels of mental distress were associated with an increased risk for dropout (adjHR: 1.48, 95% CI: 1.11-1.97). Conclusions: The role of mental health and motivation in reducing dropout risk from inpatient SUD treatment should be targeted in future prospective intervention studies. PMID:29531472

The relationship of illness management and recovery to state hospital readmission.

PubMed

Bartholomew, Tom; Zechner, Michelle

2014-09-01

The current study examined the association between number of hours attended of the Illness Management and Recovery (IMR) program and psychiatric readmission rates after discharge from a state psychiatric hospital. The study used archival data, N = 1186, from a large northeastern state psychiatric hospital in the United States. A Cox's regression survival analyses was conducted, adjusting for extreme outliers and controlling for sociodemographic covariates, to examine the association between different amounts of IMR and the risk for returning to the hospital. After controlling for the client characteristics of age, sex, marital status, psychiatric diagnosis, and Global Assessment of Functioning score at discharge, as well as controlling for mean daily dose of generic hospital programming and the number of days of hospitalization, it was found that, for each hour of IMR, there was an associated 1.1% reduction in the risk for returning to the hospital. This suggests that participation in IMR while in inpatient settings may assist individuals in reducing their risk for returning to the hospital.

Early mortality in children with acute lymphoblastic leukemia in a developing country: the role of malnutrition at diagnosis. A multicenter cohort MIGICCL study.

PubMed

Martín-Trejo, Jorge Alfonso; Núñez-Enríquez, Juan Carlos; Fajardo-Gutiérrez, Arturo; Medina-Sansón, Aurora; Flores-Lujano, Janet; Jiménez-Hernández, Elva; Amador-Sanchez, Raquel; Peñaloza-Gonzalez, José Gabriel; Alvarez-Rodriguez, Francisco Javier; Bolea-Murga, Victoria; Espinosa-Elizondo, Rosa Martha; de Diego Flores-Chapa, José; Pérez-Saldivar, Maria Luisa; Rodriguez-Zepeda, María Del Carmen; Dorantes-Acosta, Elisa María; Núñez-Villegas, Nora Nancy; Velazquez-Aviña, Martha Margarita; Torres-Nava, José Refugio; Reyes-Zepeda, Nancy Carolina; González-Bonilla, César Raúl; Flores-Villegas, Luz Victoria; Rangel-López, Angélica; Rivera-Luna, Roberto; Paredes-Aguilera, Rogelio; Cárdenas-Cardós, Rocío; Martínez-Avalos, Armando; Gil-Hernández, Ana Elena; Duarte-Rodríguez, David Aldebarán; Mejía-Aranguré, Juan Manuel

2017-04-01

The role of malnutrition at diagnosis as a predictor of early mortality in Mexican leukemia children remains controversial. The objective of present study was to investigate whether malnutrition was a predictor of early mortality during the first year of treatment in Mexican acute lymphoblastic leukemia (ALL) children through the first population-based study. A total of 794 newly diagnosed ALL pediatric patients from public hospitals of Mexico City were enrolled. A multivariate Cox proportional hazards regression model was constructed and adjusted by patient's age at diagnosis, gender, hospital of treatment, and socioeconomic status. Early mortality was high (12.1%) and malnutrition by different indicators was not associated with mortality at induction phase and at 6th month; a high risk of dying (RR = 2.08; 95% CI: 1.08-4.01) was observed in the group of malnourished children with a high-risk ALL.

Trimethoprim use in early pregnancy and the risk of miscarriage: a register-based nationwide cohort study.

PubMed

Andersen, J T; Petersen, M; Jimenez-Solem, E; Broedbaek, K; Andersen, E W; Andersen, N L; Afzal, S; Torp-Pedersen, C; Keiding, N; Poulsen, H E

2013-08-01

The antibiotic trimethoprim acts as a folate antagonist. Since trophoblasts are very sensitive to drugs that interfere with the folic acid cycle and thereby inhibit DNA synthesis, use of trimethoprim during the first trimester could be associated with miscarriage. A nationwide cohort study including all women in Denmark with a registered pregnancy between 1997 and 2005 was conducted. We used nationwide registers to identify all women giving birth, having a record of miscarriage or induced abortion. Data on exposure to trimethoprim were obtained from the National Prescription Register. Cox proportional hazard regression analysis with exposure to trimethoprim as a time-dependent variable was used to estimate the risk of miscarriage. The adjusted hazard ratio of having a miscarriage after exposure to trimethoprim in the first trimester compared to non-exposure was 2∙04 (95% confidence interval 1∙43-2∙91). Our results indicate that trimethoprim exposure in the first trimester is associated with a doubling of the hazard of miscarriage.

Predictors for return to work for those with occupational respiratory disease: clinical and structural factors.

PubMed

Zoeckler, Jeanette M; Cibula, Donald A; Morley, Christopher P; Lax, Michael B

2013-12-01

Few occupational researchers have examined "return to work" among patients with work-related respiratory diseases. In addition, prior studies have emphasized individual patient characteristics rather than a more multi-dimensional approach that includes both clinical and structural factors. A retrospective chart review identified patients with occupational respiratory diseases in the Occupational Health Clinical Center, Syracuse, NY between 1991 and 2009. We assessed predictors of work status using an exploratory, sequential mixed methods research design, multinomial (n = 188) and Cox regressions (n = 130). The findings suggest that patients with an increased number of diagnoses, non-union members, and those who took more than a year before clinical presentation had significantly poorer work status outcomes, after adjusting for age, education level, and relevant diagnoses. Efforts to prevent slow return to work after developing occupational respiratory disease should recognize the importance of timely access to occupational health services, disease severity, union membership, and smoking status. © 2013 Wiley Periodicals, Inc.

Association of Healthy Habits Beliefs and Mortality in Older Adults: A Longitudinal Analysis of the Mexican Health and Aging Study.

PubMed

Fernandez-Villa, Julio M; Marquez, David X; Sanchez-Garrido, Natalia; Perez-Zepeda, Mario U; Gonzalez-Lara, Mariana

2017-06-01

The aim of this article is to establish the association between beliefs about healthy habits and mortality in a group of Mexican older adults. This is an 11-year follow-up secondary analysis of the Mexican Health and Aging Study. There was a significant difference ( p < .001) in survival rate between those participants who believed that healthy habits have the potential to improve health compared with those who did not. After adjustment for confounders, Cox regression models showed a hazard ratio (HR) of 0.17 (95% confidence interval [CI] [0.07, 0.38], p < .001) for the group that believed in healthy habits. Although the mechanism is not completely clear, according to our results, believing that healthy habits can improve health was associated with lower rates of mortality. Further research should elucidate potential strategies for changing beliefs in older adults with the goal of improving their overall health.

Smokers' increased risk for disability pension: social confounding or health-mediated effects? Gender-specific analyses of the Hordaland Health Study cohort.

PubMed

Haukenes, Inger; Riise, Trond; Haug, Kjell; Farbu, Erlend; Maeland, John Gunnar

2013-09-01

Studies indicate that cigarette smokers have an increased risk for disability pension, presumably mediated by adverse health effects. However, smoking is also related to socioeconomic status. The current study examined the association between smoking and subsequent disability pension, and whether the association is explained by social confounding and/or health-related mediation. A subsample of 7934 men and 8488 women, aged 40-46, from the Hordaland Health Study, Norway (1997-1999), provided baseline information on smoking status, self-reported health measures and socioeconomic status. Outcome was register-based disability pension from 12 months after baseline to end of 2004. Gender stratified Cox regression analyses were used adjusted for socioeconomic status, physical activity, self-reported health and musculoskeletal pain sites. A total of 155 (2%) men and 333 (3.9%) women were granted disability pension during follow-up. The unadjusted disability risk associated with heavy smoking versus non-smoking was 1.88 (95% CI 1.23 to 2.89) among men and 3.06 (95% CI 2.23 to 4.20) among women. In multivariate analyses, adjusting for socioeconomic status, HRs were 1.33 (95% CI 0.84 to 2.11) among men and 2.22 (95% CI 1.58 to 3.13) among women. Final adjustment for physical activity, self-reported health and musculoskeletal pain further reduced the effect of heavy smoking in women (HR=1.53, 95% CI 1.09 to 2.16). Socioeconomic status confounded the smoking-related risk for disability pension; for female heavy smokers, however, a significant increased risk persisted after adjustment. Women may be particularly vulnerable to heavy smoking and to its sociomedical consequences, such as disability pension.