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.

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.

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 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

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

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.

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

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.

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.

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

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.

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.

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 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.

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.

A comparison of time dependent Cox regression, pooled logistic regression and cross sectional pooling with simulations and an application to the Framingham Heart Study.

PubMed

Ngwa, Julius S; Cabral, Howard J; Cheng, Debbie M; Pencina, Michael J; Gagnon, David R; LaValley, Michael P; Cupples, L Adrienne

2016-11-03

Typical survival studies follow individuals to an event and measure explanatory variables for that event, sometimes repeatedly over the course of follow up. The Cox regression model has been used widely in the analyses of time to diagnosis or death from disease. The associations between the survival outcome and time dependent measures may be biased unless they are modeled appropriately. In this paper we explore the Time Dependent Cox Regression Model (TDCM), which quantifies the effect of repeated measures of covariates in the analysis of time to event data. This model is commonly used in biomedical research but sometimes does not explicitly adjust for the times at which time dependent explanatory variables are measured. This approach can yield different estimates of association compared to a model that adjusts for these times. In order to address the question of how different these estimates are from a statistical perspective, we compare the TDCM to Pooled Logistic Regression (PLR) and Cross Sectional Pooling (CSP), considering models that adjust and do not adjust for time in PLR and CSP. In a series of simulations we found that time adjusted CSP provided identical results to the TDCM while the PLR showed larger parameter estimates compared to the time adjusted CSP and the TDCM in scenarios with high event rates. We also observed upwardly biased estimates in the unadjusted CSP and unadjusted PLR methods. The time adjusted PLR had a positive bias in the time dependent Age effect with reduced bias when the event rate is low. The PLR methods showed a negative bias in the Sex effect, a subject level covariate, when compared to the other methods. The Cox models yielded reliable estimates for the Sex effect in all scenarios considered. We conclude that survival analyses that explicitly account in the statistical model for the times at which time dependent covariates are measured provide more reliable estimates compared to unadjusted analyses. We present results from the Framingham Heart Study in which lipid measurements and myocardial infarction data events were collected over a period of 26 years.

Comparison of Survival Models for Analyzing Prognostic Factors in Gastric Cancer Patients

PubMed

Habibi, Danial; Rafiei, Mohammad; Chehrei, Ali; Shayan, Zahra; Tafaqodi, Soheil

2018-03-27

Objective: There are a number of models for determining risk factors for survival of patients with gastric cancer. This study was conducted to select the model showing the best fit with available data. Methods: Cox regression and parametric models (Exponential, Weibull, Gompertz, Log normal, Log logistic and Generalized Gamma) were utilized in unadjusted and adjusted forms to detect factors influencing mortality of patients. Comparisons were made with Akaike Information Criterion (AIC) by using STATA 13 and R 3.1.3 softwares. Results: The results of this study indicated that all parametric models outperform the Cox regression model. The Log normal, Log logistic and Generalized Gamma provided the best performance in terms of AIC values (179.2, 179.4 and 181.1, respectively). On unadjusted analysis, the results of the Cox regression and parametric models indicated stage, grade, largest diameter of metastatic nest, largest diameter of LM, number of involved lymph nodes and the largest ratio of metastatic nests to lymph nodes, to be variables influencing the survival of patients with gastric cancer. On adjusted analysis, according to the best model (log normal), grade was found as the significant variable. Conclusion: The results suggested that all parametric models outperform the Cox model. The log normal model provides the best fit and is a good substitute for Cox regression. Creative Commons Attribution License

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.

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.

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.

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.

Transition from a multiport technique to a single-port technique for lung cancer surgery: is lymph node dissection inferior using the single-port technique?†.

PubMed

Liu, Chia-Chuan; Shih, Chih-Shiun; Pennarun, Nicolas; Cheng, Chih-Tao

2016-01-01

The feasibility and radicalism of lymph node dissection for lung cancer surgery by a single-port technique has frequently been challenged. We performed a retrospective cohort study to investigate this issue. Two chest surgeons initiated multiple-port thoracoscopic surgery in a 180-bed cancer centre in 2005 and shifted to a single-port technique gradually after 2010. Data, including demographic and clinical information, from 389 patients receiving multiport thoracoscopic lobectomy or segmentectomy and 149 consecutive patients undergoing either single-port lobectomy or segmentectomy for primary non-small-cell lung cancer were retrieved and entered for statistical analysis by multivariable linear regression models and Box-Cox transformed multivariable analysis. The mean number of total dissected lymph nodes in the lobectomy group was 28.5 ± 11.7 for the single-port group versus 25.2 ± 11.3 for the multiport group; the mean number of total dissected lymph nodes in the segmentectomy group was 19.5 ± 10.8 for the single-port group versus 17.9 ± 10.3 for the multiport group. In linear multivariable and after Box-Cox transformed multivariable analyses, the single-port approach was still associated with a higher total number of dissected lymph nodes. The total number of dissected lymph nodes for primary lung cancer surgery by single-port video-assisted thoracoscopic surgery (VATS) was higher than by multiport VATS in univariable, multivariable linear regression and Box-Cox transformed multivariable analyses. This study confirmed that highly effective lymph node dissection could be achieved through single-port VATS in our setting. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

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.

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

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.

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.

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

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.

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.

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.

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.

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.

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.

[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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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.

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.

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.

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.

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.

A comparison between standard methods and structural nested modelling when bias from a healthy worker survivor effect is suspected: an iron-ore mining cohort study.

PubMed

Björ, Ove; Damber, Lena; Jonsson, Håkan; Nilsson, Tohr

2015-07-01

Iron-ore miners are exposed to extremely dusty and physically arduous work environments. The demanding activities of mining select healthier workers with longer work histories (ie, the Healthy Worker Survivor Effect (HWSE)), and could have a reversing effect on the exposure-response association. The objective of this study was to evaluate an iron-ore mining cohort to determine whether the effect of respirable dust was confounded by the presence of an HWSE. When an HWSE exists, standard modelling methods, such as Cox regression analysis, produce biased results. We compared results from g-estimation of accelerated failure-time modelling adjusted for HWSE with corresponding unadjusted Cox regression modelling results. For all-cause mortality when adjusting for the HWSE, cumulative exposure from respirable dust was associated with a 6% decrease of life expectancy if exposed ≥15 years, compared with never being exposed. Respirable dust continued to be associated with mortality after censoring outcomes known to be associated with dust when adjusting for the HWSE. In contrast, results based on Cox regression analysis did not support that an association was present. The adjustment for the HWSE made a difference when estimating the risk of mortality from respirable dust. The results of this study, therefore, support the recommendation that standard methods of analysis should be complemented with structural modelling analysis techniques, such as g-estimation of accelerated failure-time modelling, to adjust for the HWSE. 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.

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

Disease Characteristics, Patterns of Care, and Survival in Very Elderly Patients with Diffuse Large B-Cell Lymphoma

PubMed Central

Williams, Jessica N.; Rai, Ashish; Lipscomb, Joseph; Koff, Jean L.; Nastoupil, Loretta J.; Flowers, Christopher R.

2015-01-01

Background Although rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered standard therapy for diffuse large B-cell lymphoma (DLBCL), patterns of use and the impact of R-CHOP on survival in patients >80 years are less clear. Methods We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to characterize presentation, treatment, and survival patterns in DLBCL patients diagnosed from 2002–2009. Chi-squared tests compared characteristics and initial treatments of DLBCL patients >80 years and ≤80 years. Multivariable logistic regression models examined factors associated with treatment selection in patients >80 years; standard and propensity score-adjusted multivariable Cox proportional hazards models examined relationships between treatment regimen, treatment duration, and survival. Results Among 4,635 patients with DLBCL, 1,156 (25%) were >80 years. Patients >80 were less likely to receive R-CHOP and more likely to be observed or receive rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP); both p<0.0001. Marital status, stage, disease site, performance status, radiation therapy, and growth factor support were associated with initial R-CHOP in patients >80. In propensity score-matched multivariable Cox proportional hazards models examining relationships between treatment regimen and survival, R-CHOP was the only regimen associated with improved OS (hazard ratio (HR) = 0.45, 95% confidence interval (CI) = 0.33–0.62) and LRS (HR=0.58, 95% CI 0.38–0.88). Conclusions Although DLBCL patients >80 years were less likely to receive R-CHOP, this regimen conferred the longest survival and should be considered for this population. Further studies are needed to characterize the impact of DLBCL treatment on quality of life in this age group. PMID:25675909

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

PubMed

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

2015-08-01

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

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

PubMed

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

2015-10-01

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

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

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

Low Bone Density and Bisphosphonate Use and the Risk of Kidney Stones.

PubMed

Prochaska, Megan; Taylor, Eric; Vaidya, Anand; Curhan, Gary

2017-08-07

Previous studies have demonstrated lower bone density in patients with kidney stones, but no longitudinal studies have evaluated kidney stone risk in individuals with low bone density. Small studies with short follow-up reported reduced 24-hour urine calcium excretion with bisphosphonate use. We examined history of low bone density and bisphosphonate use and the risk of incident kidney stone as well as the association with 24-hour calcium excretion. We conducted a prospective analysis of 96,092 women in the Nurses' Health Study II. We used Cox proportional hazards models to adjust for age, body mass index, thiazide use, fluid intake, supplemental calcium use, and dietary factors. We also conducted a cross-sectional analysis of 2294 participants using multivariable linear regression to compare 24-hour urinary calcium excretion between participants with and without a history of low bone density, and among 458 participants with low bone density, with and without bisphosphonate use. We identified 2564 incident stones during 1,179,860 person-years of follow-up. The multivariable adjusted relative risk for an incident kidney stone for participants with history of low bone density compared with participants without was 1.39 (95% confidence interval [95% CI], 1.20 to 1.62). Among participants with low bone density, the multivariable adjusted relative risk for an incident kidney stone for bisphosphonate users was 0.68 (95% CI, 0.48 to 0.98). In the cross-sectional analysis of 24-hour urine calcium excretion, the multivariable adjusted mean difference in 24-hour calcium was 10 mg/d (95% CI, 1 to 19) higher for participants with history of low bone density. However, among participants with history of low bone density, there was no association between bisphosphonate use and 24-hour calcium with multivariable adjusted mean difference in 24-hour calcium of -2 mg/d (95% CI, -25 to 20). Low bone density is an independent risk factor for incident kidney stone and is associated with higher 24-hour urine calcium excretion. Among participants with low bone density, bisphosphonate use was associated with lower risk of incident kidney stone but was not independently associated with 24-hour urine calcium excretion. Copyright © 2017 by the American Society of Nephrology.

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

PubMed

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

2015-08-01

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

Impact of heart rate in atrial fibrillation versus sinus rhythm on mortality in octogenarian patients with acute coronary syndrome

PubMed Central

Li, Shijun; Barywani, Salim; Fu, Michael

2017-01-01

Introduction 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. Methods 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. Results 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. Conclusion 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. PMID:29255559

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

PubMed Central

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

2011-01-01

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

Are classic predictors of voltage valid in cardiac amyloidosis? A contemporary analysis of electrocardiographic findings.

PubMed

Sperry, Brett W; Vranian, Michael N; Hachamovitch, Rory; Joshi, Hariom; McCarthy, Meghann; Ikram, Asad; Hanna, Mazen

2016-07-01

Low voltage electrocardiography (ECG) coupled with increased ventricular wall thickness is the hallmark of cardiac amyloidosis. However, patient characteristics influencing voltage in the general population, including bundle branch block, have not been evaluated in amyloid heart disease. A retrospective analysis was performed of patients with newly diagnosed cardiac amyloidosis from 2002 to 2014. ECG voltage was calculated using limb (sum of QRS complex in leads I, II and III) and precordial (Sokolow: S in V1 plus R in V5-V6) criteria. The associations between voltage and clinical variables were tested using multivariable linear regression. A Cox model assessed the association of voltage with mortality. In 389 subjects (transthyretin ATTR 186, light chain AL 203), 30% had conduction delay (QRS >120ms). In those with narrow QRS, 68% met low limb, 72% low Sokolow and 57% both criteria, with lower voltages found in AL vs ATTR. LV mass index as well as other typical factors that impact voltage (age, sex, race, hypertension, BSA, and smoking) in the general population were not associated with voltage in this cardiac amyloidosis cohort. Patients with LBBB and IVCD had similar voltages when compared to those with narrow QRS. Voltage was significantly associated with mortality (p<0.001 for both criteria) after multivariable adjustment. Classic predictors of ECG voltage in the general population are not valid in cardiac amyloidosis. In this cohort, the prevalence estimates of ventricular conduction delay and low voltage are higher than previously reported. Voltage predicts mortality after multivariable adjustment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

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.

Bootstrapping Cox’s Regression Model.

DTIC Science & Technology

1985-11-01

crucial points a multivariate martingale central limit theorem. Involved in this is a p x p covariance matrix Z with elements T j2= f {2(s8 ) - s(l)( s ,8o...1980). The statistical analaysis of failure time data. Wiley, New York. Meyer, P.-A. (1971). Square integrable martingales, a survey. Lecture Notes

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.

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

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.

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

PubMed

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

2010-05-01

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

Gene-Based Association Analysis for Censored Traits Via Fixed Effect Functional Regressions.

PubMed

Fan, Ruzong; Wang, Yifan; Yan, Qi; Ding, Ying; Weeks, Daniel E; Lu, Zhaohui; Ren, Haobo; Cook, Richard J; Xiong, Momiao; Swaroop, Anand; Chew, Emily Y; Chen, Wei

2016-02-01

Genetic studies of survival outcomes have been proposed and conducted recently, but statistical methods for identifying genetic variants that affect disease progression are rarely developed. Motivated by our ongoing real studies, here we develop Cox proportional hazard models using functional regression (FR) to perform gene-based association analysis of survival traits while adjusting for covariates. The proposed Cox models are fixed effect models where the genetic effects of multiple genetic variants are assumed to be fixed. We introduce likelihood ratio test (LRT) statistics to test for associations between the survival traits and multiple genetic variants in a genetic region. Extensive simulation studies demonstrate that the proposed Cox RF LRT statistics have well-controlled type I error rates. To evaluate power, we compare the Cox FR LRT with the previously developed burden test (BT) in a Cox model and sequence kernel association test (SKAT), which is based on mixed effect Cox models. The Cox FR LRT statistics have higher power than or similar power as Cox SKAT LRT except when 50%/50% causal variants had negative/positive effects and all causal variants are rare. In addition, the Cox FR LRT statistics have higher power than Cox BT LRT. The models and related test statistics can be useful in the whole genome and whole exome association studies. An age-related macular degeneration dataset was analyzed as an example. © 2016 WILEY PERIODICALS, INC.

Gene-based Association Analysis for Censored Traits Via Fixed Effect Functional Regressions

PubMed Central

Fan, Ruzong; Wang, Yifan; Yan, Qi; Ding, Ying; Weeks, Daniel E.; Lu, Zhaohui; Ren, Haobo; Cook, Richard J; Xiong, Momiao; Swaroop, Anand; Chew, Emily Y.; Chen, Wei

2015-01-01

Summary Genetic studies of survival outcomes have been proposed and conducted recently, but statistical methods for identifying genetic variants that affect disease progression are rarely developed. Motivated by our ongoing real studies, we develop here Cox proportional hazard models using functional regression (FR) to perform gene-based association analysis of survival traits while adjusting for covariates. The proposed Cox models are fixed effect models where the genetic effects of multiple genetic variants are assumed to be fixed. We introduce likelihood ratio test (LRT) statistics to test for associations between the survival traits and multiple genetic variants in a genetic region. Extensive simulation studies demonstrate that the proposed Cox RF LRT statistics have well-controlled type I error rates. To evaluate power, we compare the Cox FR LRT with the previously developed burden test (BT) in a Cox model and sequence kernel association test (SKAT) which is based on mixed effect Cox models. The Cox FR LRT statistics have higher power than or similar power as Cox SKAT LRT except when 50%/50% causal variants had negative/positive effects and all causal variants are rare. In addition, the Cox FR LRT statistics have higher power than Cox BT LRT. The models and related test statistics can be useful in the whole genome and whole exome association studies. An age-related macular degeneration dataset was analyzed as an example. PMID:26782979

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

PubMed Central

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

2007-01-01

Objective To examine the effects of non-alcoholic beverage and caffeine consumption on all-cause mortality in older adults. Methods 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. Results 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: 0.90, 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 a 8% increased risk (95% CI: 1.01–1.16). Neither milk nor tea had a significant effect on mortality after multivariable adjustment. Conclusions Moderate caffeine consumption appeared beneficial in risking 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. PMID:17275898

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.

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

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

PubMed

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

2014-06-01

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

The antagonistic effect between STAT1 and Survivin and its clinical significance in gastric cancer.

PubMed

Deng, Hao; Zhen, Hongyan; Fu, Zhengqi; Huang, Xuan; Zhou, Hongyan; Liu, Lijiang

2012-01-01

In previous studies, we observed that STAT1 and Survivin correlated negatively with gastric cancer tissues, and that the functions of the IFN-γ-STAT1 pathway and Survivin in gastric cancer are the same as those reported for other types of cancer. In this study, the SGC7901 gastric cancer cell line and 83 gastric cancer specimens were used to confirm the relationship between STAT1 and Survivin, as well as the clinical significance of this relationship in gastric cancer. IFN-γ and STAT1 and Survivin antisense oligonucleotides (ASONs) were used to knock down the expression in SGC7901 cells. The protein expression of STAT1 and Survivin was tested by immunocytochemical and image analysis methods. A gastric cancer tissue microarray was prepared and tested by immunohistochemical methods. Data were analyzed by the Spearman's rank correlation analysis, the χ(2) test and Cox's multivariate regression analysis. Upon knockdown of IFN-γ, STAT1 and Survivin expression by ASON in the SGC7901 cell line, an antagonistic effect was observed between STAT1 and Survivin. In gastric cancer tissues, STAT1 showed a negative correlation with depth of invasion (p<0.05) in gastric cancer tissues exhibiting a negative Survivin protein expression. Furthermore, in tissues exhibiting a negative STAT1 protein expression, Survivin correlated negatively with N stage (p<0.05). Pathological and molecular markers were used to conduct Cox's multivariate regression analysis, and depth of invasion and N stage were found to be prognostic factors (p<0.05). On the other hand, in tissues exhibiting a negative Survivin protein expression, Cox's multivariate regression analysis revealed that the differentiation type and STAT1 protein expression were prognostic factors (p<0.05). There is an antagonistic effect between STAT1 and Survivin in gastric cancer, and this antagonistic effect is of clinical significance in gastric cancer.

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.

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.

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

Survival outcomes of pediatric osteosarcoma and Ewing's sarcoma: a comparison of surgery type within the SEER database, 1988-2007.

PubMed

Schrager, Justin; Patzer, Rachel E; Mink, Pamela J; Ward, Kevin C; Goodman, Michael

2011-01-01

Survival following diagnosis of pediatric Ewing's sarcoma or osteosarcoma is increasing in the United States, but whether survival differs between patients who receive limb salvage surgery compared to amputation has not been evaluated in nationally representative, population-based data. Multivariable-adjusted survival was calculated using Cox regression models among surgically treated pediatric (age <20) osteosarcoma and Ewing's sarcoma patients with bone cancer of the limbs or joints reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program during 1988-2007. Over half (66.3%) of the 890 osteosarcoma patients underwent limb salvage surgery. Five-year overall survival among patients who received limb salvage was 72.7% for osteosarcoma patients and 71.8% for Ewing's sarcoma patients. Among patients who received amputation, 5-year survival was 60.1% for osteosarcoma and 63.1% for Ewing's sarcoma patients. After multivariable adjustment, the mortality was 35% greater for amputation vs limb salvage (HR=1.35, 95% CI: 1.05-1.75). Among 165 Ewing's sarcoma patients, 73.9% underwent limb salvage (vs amputation), and the adjusted mortality was higher for patients receiving amputation, although results were not statistically significant (HR=1.61, 95% CI: 0.80-3.21). Limb salvage surgery (vs amputation) is associated with longer survival among pediatric patients with bone cancer of the limbs or joints. Patient and physician characteristics and the effectiveness of neoadjuvant therapy may play a role in surgery choice, but we were unable to control for these factors.

Gastrointestinal toxicity among patients taking selective COX-2 inhibitors or conventional NSAIDs, alone or combined with proton pump inhibitors: a case-control study.

PubMed

Bakhriansyah, Mohammad; Souverein, Patrick C; de Boer, Anthonius; Klungel, Olaf H

2017-10-01

To assess the risk of gastrointestinal perforation, ulcers, or bleeding (PUB) associated with the use of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) with proton pump inhibitors (PPIs) and selective COX-2 inhibitors, with or without PPIs compared with conventional NSAIDs. A case-control study was performed within conventional NSAIDs and/or selective COX-2 inhibitors users identified from the Dutch PHARMO Record Linkage System in the period 1998-2012. Cases were patients aged ≥18 years with a first hospital admission for PUB. For each case, up to four controls were matched for age and sex at the date a case was hospitalized (index date). Logistic regression analysis was used to calculate odds ratios (ORs). At the index date, 2634 cases and 5074 controls were current users of conventional NSAIDs or selective COX-2 inhibitors. Compared with conventional NSAIDs, selective COX-2 inhibitors with PPIs had the lowest risk of PUB (adjusted OR 0.51, 95% confidence interval [CI]: 0.35-0.73) followed by selective COX-2 inhibitors (adjusted OR 0.66, 95%CI: 0.48-0.89) and conventional NSAIDs with PPIs (adjusted OR 0.79, 95%CI: 0.68-0.92). Compared with conventional NSAIDs, the risk of PUB was lower for those aged ≥75 years taking conventional NSAIDs with PPIs compared with younger patients (adjusted interaction OR 0.79, 95%CI: 0.64-0.99). However, those aged ≥75 years taking selective COX-2 inhibitors, the risk was higher compared with younger patients (adjusted interaction OR 1.22, 95%CI: 1.01-1.47). Selective COX-2 inhibitors with PPIs, selective COX-2 inhibitors, and conventional NSAIDs with PPIs were associated with lower risks of PUB compared with conventional NSAIDs. These effects were modified by age. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

Sickness absence due to back pain or depressive episode and the risk of all-cause and diagnosis-specific disability pension: A Swedish cohort study of 4,823,069 individuals.

PubMed

Dorner, T E; Alexanderson, K; Svedberg, P; Ropponen, A; Stein, K V; Mittendorfer-Rutz, E

2015-10-01

The aim of this study was to investigate the associations between sickness absence due to back pain or depressive episode with future all-cause and diagnosis-specific disability pension, while adjusting for comorbidity and socio-demographics, for all and stratifying for sex. In total, 4,823,069 individuals aged 16-64 years, living in Sweden at the end of 2004, not on old-age or disability pension in 2005 and without ongoing sickness absence at the turn of 2004/2005 formed the study population. Crude and adjusted hazard ratios (HRs) for all-cause and diagnosis-specific disability pension (2006-2010) in relation to diagnosis-specific sickness absence with sickness benefits paid by the Social Insurance Agency were estimated using Cox regression. The HR for all-cause disability pension was 7.52 (7.25-7.52) in individuals with an incident sick-leave spell due to back pain, compared to individuals without sickness absence in 2005 in the fully adjusted (socio-demographics and comorbidity) model. The fully adjusted (multivariate) HRs for diagnosis-specific disability pension were musculoskeletal diagnoses 23.87 (22.75-25.04), mental 2.49 (2.27-2.73) or all other diagnoses, 3.44 (3.17-3.75). In individuals with an incident sick-leave spell due to a depressive episode in 2005, the multivariate adjusted HR for all-cause disability pension was 12.87 (12.42-13.35), while the multivariate HRs for disability pension due to musculoskeletal diagnoses were 4.39 (3.89-4.96), for mental diagnoses 25.32 (24.29-26.38) and for all other somatic diagnoses 3.44 (3.09-3.82). Men who were sickness absent due to a depressive episode had a higher HR for disability pension compared to women. Results indicate that sickness absence due to a depressive episode or back pain is a strong risk factor for a future disability pension due to mental, musculoskeletal or other somatic diagnoses. © 2015 European Pain Federation - EFIC®

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

PubMed Central

2016-01-01

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

Diagnosis of pernicious anemia and the risk of pancreatic cancer.

PubMed

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

2014-04-01

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

[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.

Methodological comparison of marginal structural model, time-varying Cox regression, and propensity score methods: the example of antidepressant use and the risk of hip fracture.

PubMed

Ali, M Sanni; Groenwold, Rolf H H; Belitser, Svetlana V; Souverein, Patrick C; Martín, Elisa; Gatto, Nicolle M; Huerta, Consuelo; Gardarsdottir, Helga; Roes, Kit C B; Hoes, Arno W; de Boer, Antonius; Klungel, Olaf H

2016-03-01

Observational studies including time-varying treatments are prone to confounding. We compared time-varying Cox regression analysis, propensity score (PS) methods, and marginal structural models (MSMs) in a study of antidepressant [selective serotonin reuptake inhibitors (SSRIs)] use and the risk of hip fracture. A cohort of patients with a first prescription for antidepressants (SSRI or tricyclic antidepressants) was extracted from the Dutch Mondriaan and Spanish Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) general practice databases for the period 2001-2009. The net (total) effect of SSRI versus no SSRI on the risk of hip fracture was estimated using time-varying Cox regression, stratification and covariate adjustment using the PS, and MSM. In MSM, censoring was accounted for by inverse probability of censoring weights. The crude hazard ratio (HR) of SSRI use versus no SSRI use on hip fracture was 1.75 (95%CI: 1.12, 2.72) in Mondriaan and 2.09 (1.89, 2.32) in BIFAP. After confounding adjustment using time-varying Cox regression, stratification, and covariate adjustment using the PS, HRs increased in Mondriaan [2.59 (1.63, 4.12), 2.64 (1.63, 4.25), and 2.82 (1.63, 4.25), respectively] and decreased in BIFAP [1.56 (1.40, 1.73), 1.54 (1.39, 1.71), and 1.61 (1.45, 1.78), respectively]. MSMs with stabilized weights yielded HR 2.15 (1.30, 3.55) in Mondriaan and 1.63 (1.28, 2.07) in BIFAP when accounting for censoring and 2.13 (1.32, 3.45) in Mondriaan and 1.66 (1.30, 2.12) in BIFAP without accounting for censoring. In this empirical study, differences between the different methods to control for time-dependent confounding were small. The observed differences in treatment effect estimates between the databases are likely attributable to different confounding information in the datasets, illustrating that adequate information on (time-varying) confounding is crucial to prevent bias. Copyright © 2016 John Wiley & Sons, Ltd.

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.

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.

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.

Papillary type 2 versus clear cell renal cell carcinoma: Survival outcomes.

PubMed

Simone, G; Tuderti, G; Ferriero, M; Papalia, R; Misuraca, L; Minisola, F; Costantini, M; Mastroianni, R; Sentinelli, S; Guaglianone, S; Gallucci, M

2016-11-01

To compare the cancer specific survival (CSS) between p2-RCC and a Propensity Score Matched (PSM) cohort of cc-RCC patients. Fifty-five (4.6%) patients with p2-RCC and 920 cc-RCC patients were identified within a prospectively maintained institutional dataset of 1205 histologically proved RCC patients treated with either RN or PN. Univariable and multivariable Cox regression analyses were used to identify predictors of CSS after surgical treatment. A 1:2 PSM analysis based on independent predictors of oncologic outcomes was employed and CSS was compared between PSM selected cc-RCC patients using Kaplan-Meier and Cox regression analysis. Overall, 55 (4.6%) p2-RCC and 920 (76.3%) cc-RCC patients were selected from the database; p2-RCC were significantly larger (p = 0.001), more frequently locally advanced (p < 0.001) and node positive (p < 0.001) and had significantly higher Fuhrman grade (p < 0.001) than cc-RCC. On multivariable Cox regression analysis age (p = 0.025), histologic subtype (p = 0.029), pN stage (p = 0.006), size, pT stage, cM stage, sarcomatoid features and Fuhrman grade (all p < 0.001) were independent predictors of CSS. After applying the PSM, 82 cc-RCC selected cases were comparable to 41 p2-RCC for age (p = 0.81), tumor size (p = 0.39), pT (p = 1.00) and pN (p = 0.62) stages, cM stage (p = 0.71) and Fuhrman grade (p = 1). In this PSM cohort, 5 yr CSS was significantly lower in the p2-RCC (63% vs 72.4%; p = 0.047). At multivariable Cox analysis p2 histology was an independent predictor of CSM (HR 2.46, 95% CI 1.04-5.83; p = 0.041). We confirmed the tendency of p2-RCC to present as locally advanced and metastatic disease more frequently than cc-RCC and demonstrated p2-RCC histology as an independent predictor of worse oncologic outcomes. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Assessment of the prognostic and predictive utility of the Breast Cancer Index (BCI): an NCIC CTG MA.14 study.

PubMed

Sgroi, Dennis C; Chapman, Judy-Anne W; Badovinac-Crnjevic, T; Zarella, Elizabeth; Binns, Shemeica; Zhang, Yi; Schnabel, Catherine A; Erlander, Mark G; Pritchard, Kathleen I; Han, Lei; Shepherd, Lois E; Goss, Paul E; Pollak, Michael

2016-01-04

Biomarkers that can be used to accurately assess the residual risk of disease recurrence in women with hormone receptor-positive breast cancer are clinically valuable. We evaluated the prognostic value of the Breast Cancer Index (BCI), a continuous risk index based on a combination of HOXB13:IL17BR and molecular grade index, in women with early breast cancer treated with either tamoxifen alone or tamoxifen plus octreotide in the NCIC MA.14 phase III clinical trial (ClinicalTrials.gov Identifier NCT00002864; registered 1 November 1999). Gene expression analysis of BCI by real-time polymerase chain reaction was performed blinded to outcome on RNA extracted from archived formalin-fixed, paraffin-embedded tumor samples of 299 patients with both lymph node-negative (LN-) and lymph node-positive (LN+) disease enrolled in the MA.14 trial. Our primary objective was to determine the prognostic performance of BCI based on relapse-free survival (RFS). MA.14 patients experienced similar RFS on both treatment arms. Association of gene expression data with RFS was evaluated in univariate analysis with a stratified log-rank test statistic, depicted with a Kaplan-Meier plot and an adjusted Cox survivor plot. In the multivariate assessment, we used stratified Cox regression. The prognostic performance of an emerging, optimized linear BCI model was also assessed in a post hoc analysis. Of 299 samples, 292 were assessed successfully for BCI for 146 patients accrued in each MA.14 treatment arm. BCI risk groups had a significant univariate association with RFS (stratified log-rank p = 0.005, unstratified log-rank p = 0.007). Adjusted 10-year RFS in BCI low-, intermediate-, and high-risk groups was 87.5 %, 83.9 %, and 74.7 %, respectively. BCI had a significant prognostic effect [hazard ratio (HR) 2.34, 95 % confidence interval (CI) 1.33-4.11; p = 0.004], although not a predictive effect, on RFS in stratified multivariate analysis, adjusted for pathological tumor stage (HR 2.22, 95 % CI 1.22-4.07; p = 0.01). In the post hoc multivariate analysis, higher linear BCI was associated with shorter RFS (p = 0.002). BCI had a strong prognostic effect on RFS in patients with early-stage breast cancer treated with tamoxifen alone or with tamoxifen and octreotide. BCI was prognostic in both LN- and LN+ patients. This retrospective study is an independent validation of the prognostic performance of BCI in a prospective trial.

Marital status, treatment, and survival in patients with glioblastoma multiforme: a population based study.

PubMed

Chang, Susan M; Barker, Fred G

2005-11-01

Social factors influence cancer treatment choices, potentially affecting patient survival. In the current study, the authors studied the interrelations between marital status, treatment received, and survival in patients with glioblastoma multiforme (GM), using population-based data. The data source was the Surveillance, Epidemiology, and End Results (SEER) Public Use Database, 1988-2001, 2004 release, all registries. Multivariate logistic, ordinal, and Cox regression analyses adjusted for demographic and clinical variables were used. Of 10,987 patients with GM, 67% were married, 31% were unmarried, and 2% were of unknown marital status. Tumors were slightly larger at the time of diagnosis in unmarried patients (49% of unmarried patients had tumors larger than 45 mm vs. 45% of married patients; P = 0.004, multivariate analysis). Unmarried patients were less likely to undergo surgical resection (vs. biopsy; 75% of unmarried patients vs. 78% of married patients) and were less likely to receive postoperative radiation therapy (RT) (70% of unmarried patients vs. 79% of married patients). On multivariate analysis, the odds ratio (OR) for resection (vs. biopsy) in unmarried patients was 0.88 (95% confidence interval [95% CI], 0.79-0.98; P = 0.02), and the OR for RT in unmarried patients was 0.69 (95% CI, 0.62-0.77; P < 0.001). Unmarried patients more often refused both surgical resection and RT. Unmarried patients who underwent surgical resection and RT were found to have a shorter survival than similarly treated married patients (hazard ratio for unmarried patients, 1.10; P = 0.003). Unmarried patients with GM presented with larger tumors, were less likely to undergo both surgical resection and postoperative RT, and had a shorter survival after diagnosis when compared with married patients, even after adjustment for treatment and other prognostic factors. (c) 2005 American Cancer Society.

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

PubMed

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

2016-11-01

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

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.

Access disparities to Magnet hospitals for patients undergoing neurosurgical operations

PubMed Central

Missios, Symeon; Bekelis, Kimon

2017-01-01

Background Centers of excellence focusing on quality improvement have demonstrated superior outcomes for a variety of surgical interventions. We investigated the presence of access disparities to hospitals recognized by the Magnet Recognition Program of the American Nurses Credentialing Center (ANCC) for patients undergoing neurosurgical operations. Methods We performed a cohort study of all neurosurgery patients who were registered in the New York Statewide Planning and Research Cooperative System (SPARCS) database from 2009–2013. We examined the association of African-American race and lack of insurance with Magnet status hospitalization for neurosurgical procedures. A mixed effects propensity adjusted multivariable regression analysis was used to control for confounding. Results During the study period, 190,535 neurosurgical patients met the inclusion criteria. Using a multivariable logistic regression, we demonstrate that African-Americans had lower admission rates to Magnet institutions (OR 0.62; 95% CI, 0.58–0.67). This persisted in a mixed effects logistic regression model (OR 0.77; 95% CI, 0.70–0.83) to adjust for clustering at the patient county level, and a propensity score adjusted logistic regression model (OR 0.75; 95% CI, 0.69–0.82). Additionally, lack of insurance was associated with lower admission rates to Magnet institutions (OR 0.71; 95% CI, 0.68–0.73), in a multivariable logistic regression model. This persisted in a mixed effects logistic regression model (OR 0.72; 95% CI, 0.69–0.74), and a propensity score adjusted logistic regression model (OR 0.72; 95% CI, 0.69–0.75). Conclusions Using a comprehensive all-payer cohort of neurosurgery patients in New York State we identified an association of African-American race and lack of insurance with lower rates of admission to Magnet hospitals. PMID:28684152

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.

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

PubMed

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

1992-01-01

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

Misspecification of Cox regression models with composite endpoints

PubMed Central

Wu, Longyang; Cook, Richard J

2012-01-01

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

[Negative prognostic impact of female gender on oncological outcomes following radical cystectomy].

PubMed

Dabi, Y; Rouscoff, Y; Delongchamps, N B; Sibony, M; Saighi, D; Zerbib, M; Peyraumore, M; Xylinas, E

2016-02-01

To confirm gender specific differences in pathologic factors and survival rates of urothelial bladder cancer patients treated with radical cystectomy. We conducted a retrospective monocentric study on 701 patients treated with radical cystectomy and pelvic lymphadenectomy for muscle invasive bladder cancer. Impact of gender on recurrence rate, specific and non-specific mortality rate were evaluated using Cox regression models in univariate and multivariate analysis. We collected data on 553 males (78.9%) and 148 females (21.1%) between 1998 and 2011. Both groups were comparable at inclusion regarding age, pathologic stage, nodal status and lymphovascular invasion. Mean follow-up time was 45 months (interquartile 23-73) and by that time, 163 patients (23.3%) had recurrence of their tumor and 127 (18.1%) died from their disease. In multivariable Cox regression analyses, female gender was independently associated with disease recurrence (RR: 1.73; 95% CI 1.22-2.47; P=0.02) and cancer-specific mortality (RR=2.50, 95% CI=1.71-3.68; P<0.001). We confirmed female gender to be an independent negative prognosis factor for patients following a radical cystectomy and lymphadenectomy for an invasive muscle bladder cancer. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Muscular strength and incident hypertension in normotensive and prehypertensive men.

PubMed

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

2010-02-01

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

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.

Association of chronic kidney disease with abnormal cardiac mechanics and adverse outcomes in patients with heart failure and preserved ejection fraction.

PubMed

Unger, Erin D; Dubin, Ruth F; Deo, Rajat; Daruwalla, Vistasp; Friedman, Julie L; Medina, Crystal; Beussink, Lauren; Freed, Benjamin H; Shah, Sanjiv J

2016-01-01

Chronic kidney disease (CKD) is associated with worse outcomes in heart failure with preserved ejection fraction (HFpEF). Whether this association is due the effect of CKD on intrinsic abnormalities in cardiac function is unknown. We hypothesized that CKD is independently associated with worse cardiac mechanics in HFpEF. We prospectively studied 299 patients enrolled in the Northwestern University HFpEF Program. Using the creatinine-based CKD-Epi equation to calculate estimated glomerular filtration rate (eGFR), study participants were analysed by CKD status (using eGFR <60 mL/min/1.73 m(2) to denote CKD). Indices of cardiac mechanics (longitudinal strain parameters) were measured using speckle-tracking echocardiography. Using multivariable-adjusted linear and Cox regression analyses, we determined the association between CKD and echocardiographic parameters and clinical outcomes (cardiovascular hospitalization or death). Of 299 study participants, 48% had CKD. CKD (dichotomous variable) and reduced eGFR (continuous variable) were both associated with worse cardiac mechanics indices including left atrial (LA) reservoir strain, LV longitudinal strain, and right ventricular free wall strain even after adjusting for potential confounders, including co-morbidities, EF, and volume status. For example, for each 1-SD decrease in eGFR, LA reservoir strain was 3.52% units lower (P < 0.0001) after multivariable adjustment. Reduced eGFR was also associated with worse outcomes [adjusted hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.61 per 1-SD decrease in eGFR; P = 0.039]. The association was attenuated after adjustment for indices of cardiac mechanics (P = 0.064). In HFpEF, CKD is independently associated with worse cardiac mechanics, which may explain why HFpEF patients with CKD have worse outcomes. NCT01030991. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

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.

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.

Birth by Caesarean Section and the Risk of Adult Psychosis: A Population-Based Cohort Study

PubMed Central

O’Neill, Sinéad M.; Curran, Eileen A.; Dalman, Christina; Kenny, Louise C.; Kearney, Patricia M.; Clarke, Gerard; Cryan, John F.; Dinan, Timothy G.; Khashan, Ali S.

2016-01-01

Despite the biological plausibility of an association between obstetric mode of delivery and psychosis in later life, studies to date have been inconclusive. We assessed the association between mode of delivery and later onset of psychosis in the offspring. A population-based cohort including data from the Swedish National Registers was used. All singleton live births between 1982 and 1995 were identified (n = 1 345 210) and followed-up to diagnosis at age 16 or later. Mode of delivery was categorized as: unassisted vaginal delivery (VD), assisted VD, elective Caesarean section (CS) (before onset of labor), and emergency CS (after onset of labor). Outcomes included any psychosis; nonaffective psychoses (including schizophrenia only) and affective psychoses (including bipolar disorder only and depression with psychosis only). Cox regression analysis was used reporting partially and fully adjusted hazard ratios (HR) with 95% confidence intervals (CI). Sibling-matched Cox regression was performed to adjust for familial confounding factors. In the fully adjusted analyses, elective CS was significantly associated with any psychosis (HR 1.13, 95% CI 1.03, 1.24). Similar findings were found for nonaffective psychoses (HR 1.13, 95% CI 0.99, 1.29) and affective psychoses (HR 1.17, 95% CI 1.05, 1.31) (χ2 for heterogeneity P = .69). In the sibling-matched Cox regression, this association disappeared (HR 1.03, 95% CI 0.78, 1.37). No association was found between assisted VD or emergency CS and psychosis. This study found that elective CS is associated with an increase in offspring psychosis. However, the association did not persist in the sibling-matched analysis, implying the association is likely due to familial confounding by unmeasured factors such as genetics or environment. PMID:26615187

Impact of Pacemaker Lead Characteristics on Pacemaker Related Infection and Heart Perforation: A Nationwide Population-Based Cohort Study.

PubMed

Lin, Yu-Sheng; Chen, Tien-Hsing; Hung, Sheng-Ping; Chen, Dong Yi; Mao, Chun-Tai; Tsai, Ming-Lung; Chang, Shih-Tai; Wang, Chun-Chieh; Wen, Ming-Shien; Chen, Mien-Cheng

2015-01-01

Several risk factors for pacemaker (PM) related complications have been reported. However, no study has investigated the impact of lead characteristics on pacemaker-related complications. Patients who received a new pacemaker implant from January 1997 to December 2011 were selected from the Taiwan National Health Insurance Database. This population was grouped according to the pacemaker lead characteristics in terms of fixation and insulation. The impact of the characteristics of leads on early heart perforation was analyzed by multivariable logistic regression analysis, while the impact of the lead characteristics on early and late infection and late heart perforation over a three-year period were analyzed using Cox regression. This study included 36,104 patients with a mean age of 73.4±12.5 years. In terms of both early and late heart perforations, there were no significant differences between groups across the different types of fixation and insulations. In the multivariable Cox regression analysis, the pacemaker-related infection rate was significantly lower in the active fixation only group compared to either the both fixation (OR, 0.23; 95% CI, 0.07-0.80; P = 0.020) or the passive fixation group (OR, 0.26; 95% CI, 0.08-0.83; P = 0.023). There was no difference in heart perforation between active and passive fixation leads. Active fixation leads were associated with reduced risk of pacemaker-related infection.

The influence of sarcopenia on survival and surgical complications in ovarian cancer patients undergoing primary debulking surgery.

PubMed

Rutten, I J G; Ubachs, J; Kruitwagen, R F P M; van Dijk, D P J; Beets-Tan, R G H; Massuger, L F A G; Olde Damink, S W M; Van Gorp, T

2017-04-01

Sarcopenia, severe skeletal muscle loss, has been identified as a prognostic factor in various malignancies. This study aims to investigate whether sarcopenia is associated with overall survival (OS) and surgical complications in patients with advanced ovarian cancer undergoing primary debulking surgery (PDS). Ovarian cancer patients (n = 216) treated with PDS were enrolled retrospectively. Total skeletal muscle surface area was measured on axial computed tomography at the level of the third lumbar vertebra. Optimum stratification was used to find the optimal skeletal muscle index cut-off to define sarcopenia (≤38.73 cm 2 /m 2 ). Cox-regression and Kaplan-Meier analysis were used to analyse the relationship between sarcopenia and OS. The effect of sarcopenia on the development of major surgical complications was studied with logistic regression. Kaplan-Meier analysis showed a significant survival disadvantage for patients with sarcopenia compared to patients without sarcopenia (p = 0.010). Sarcopenia univariably predicted OS (HR 1.536 (95% CI 1.105-2.134), p = 0.011) but was not significant in multivariable Cox-regression analysis (HR 1.362 (95% CI 0.968-1.916), p = 0.076). Significant predictors for OS in multivariable Cox-regression analysis were complete PDS, treatment in a specialised centre and the development of major complications. Sarcopenia was not predictive of major complications. Sarcopenia was not predictive of OS or major complications in ovarian cancer patients undergoing primary debulking surgery. However a strong trend towards a survival disadvantage for patients with sarcopenia was seen. Future prospective studies should focus on interventions to prevent or reverse sarcopenia and possibly increase ovarian cancer survival. Complete cytoreduction remains the strongest predictor of ovarian cancer survival. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Clinical impact of prolonged diagnosis to treatment interval (DTI) among patients with oropharyngeal squamous cell carcinoma.

PubMed

Sharma, Sonam; Bekelman, Justin; Lin, Alexander; Lukens, J Nicholas; Roman, Benjamin R; Mitra, Nandita; Swisher-McClure, Samuel

2016-05-01

We examined practice patterns using the National Cancer Data Base (NCDB) to determine risk factors for prolonged diagnosis to treatment interval (DTI) and survival outcomes in patients receiving chemoradiation for oropharyngeal squamous cell carcinoma (OPSCC). We identified 6606 NCDB patients with Stage III-IV OPSCC receiving chemoradiation from 2003 to 2006. We determined risk factors for prolonged DTI (>30days) using univariate and multivariable logistic regression models. We examined overall survival (OS) using Kaplan Meier and multivariable Cox proportional hazards models. 3586 (54.3%) patients had prolonged DTI. Race, IMRT, insurance status, and high volume facilities were significant risk factors for prolonged DTI. Patients with prolonged DTI had inferior OS compared to DTI⩽30days (Hazard Ratio (HR)=1.12, 95% CI 1.04-1.20, p=0.005). For every week increase in DTI there was a 2.2% (95% CI 1.1-3.3%, p<0.001) increase in risk of death. Patients receiving IMRT, treatment at academic, or high-volume facilities were more likely to experience prolonged DTI (High vs. Low volume: 61.5% vs. 51.8%, adjusted OR 1.38, 95% CI 1.21-1.58; Academic vs. Community: 59.5% vs. 50.6%, adjusted OR 1.26, 95% CI 1.13-1.42; non-IMRT vs. IMRT: 53.4% vs. 56.5%; adjusted OR 1.17, 95% CI 1.04-1.31). Our results suggest that prolonged DTI has a significant impact on survival outcomes. We observed disparities in DTI by socioeconomic factors. However, facility level factors such as academic affiliation, high volume, and IMRT also increased risk of DTI. These findings should be considered in developing efficient pathways to mitigate adverse effects of prolonged DTI. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gender Differences in Receipt of National Institutes of Health R01 Grants Among Junior Faculty at an Academic Medical Center: The Role of Connectivity, Rank, and Research Productivity.

PubMed

Warner, Erica T; Carapinha, René; Weber, Griffin M; Hill, Emorcia V; Reede, Joan Y

2017-10-01

To determine whether there were gender differences in likelihood of receiving a first National Institutes of Health (NIH) R01 award among 5445 instructors and assistant professors at Harvard Medical School (HMS). Data on R01 award principal investigators were obtained from NIH ExPORTER and linked with faculty data. Using Cox proportional hazard regression, we examined the association of gender with receipt of first R01 award between 2008 and 2015 accounting for demographics, research productivity metrics, and professional characteristics. Compared to males, females had fewer publications, lower h-index, smaller coauthor networks and were less likely to be assistant professors (p < 0.0001). Four hundred and thirteen of 5445 faculty (7.6%) received their first R01 award during the study period. There was no gender difference in receipt of R01 awards in age-adjusted (hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.70-1.08) or multivariable-adjusted models (HR: 1.07, 95% CI: 0.86-1.34). Compared to white males, there was a nonsignificant 10%, 18%, and 30% lower rate of R01 receipt among white, Asian or Pacific Islander, and underrepresented minority females, respectively. These differences were eliminated in the multivariable-adjusted model. Network reach, age, HMS start year, h-index, academic rank, previous K award, terminal degree, and HMS training were all significant predictors of receiving an R01 award. A relatively small proportion of HMS junior faculty obtained their first NIH R01 award during the study period. There was no significant gender difference in likelihood of award. However, we are unable to distinguish faculty that never applied from those who applied and were not successful.

Adherence to recommendations of the German food pyramid and risk of chronic diseases: results from the EPIC-Potsdam study.

PubMed

von Ruesten, A; Illner, A-K; Buijsse, B; Heidemann, C; Boeing, H

2010-11-01

The German food pyramid was set up to foster and communicate healthy food choices. The adherence to recommendations of the food pyramid was translated into an index (German Food Pyramid Index (GFPI)) by scoring the ratio of consumed and recommended daily servings of eight food groups, wherein higher scores indicated greater adherence. The GFPI was calculated for 23 531 subjects who participated in the European Prospective Investigation into Cancer and Nutrition-Potsdam study and were recruited between 1994 and 1998. Associations between quintiles of GFPI scores and risk of incident cardiovascular diseases (CVD), type-2 diabetes (T2D) and cancer were evaluated using Cox proportional hazard regression models. During 183 740 person-years of follow-up, 363 incident cases of CVD (myocardial infarction or stroke), 837 incident cases of T2D and 844 incident cases of cancer occurred. The GFPI was inversely related to CVD risk in men (multivariable-adjusted hazard ratio (HR) for highest versus lowest quintiles=0.56; 95% confidence interval (CI): 0.34-0.94) but not in women (HR=1.39; 95% CI: 0.76-2.55). No association between GFPI and cancer was observed. An inverse relation between GFPI and T2D (men: HR= 0.71 (0.52-0.97); women: HR= 0.69 (0.50-0.96)) in age-adjusted models was substantially attenuated after multivariable adjustments, particularly by body mass index (BMI) (men: HR=0.94 (0.69-1.30); women: HR=1.09 (0.77-1.54)). The same was observed for overall major chronic disease risk (CVD, T2D and total cancer). Adherence to the German food pyramid recommendations is not associated with a decreased risk of chronic diseases when considering BMI as confounder, except of CVD in men.

Socioeconomic deprivation and survival after stroke: findings from the prospective South London Stroke Register of 1995 to 2011.

PubMed

Chen, Ruoling; McKevitt, Christopher; Rudd, Anthony G; Wolfe, Charles D A

2014-01-01

Previous findings of the association between socioeconomic deprivation (SED) and survival after stroke are inconsistent. There is less investigation on long-term survival. We assessed the associations in a multi-ethnic population in England. We examined data from 4398 patients (3103 whites, 932 blacks, and 253 Asians/others) with first-ever stroke, collected by a population-based stroke register in South London from 1995 to 2011. SED was measured using the Carstairs index score-the higher score, the more deprived. It was analyzed in multivariate Cox regression models in relation to survival after stroke. During 17-year follow-up 2754 patients died. The quartile data of Carstairs score showed no significant association of SED with survival in patients, except for black Caribbeans and Africans. Black patients with the fourth quartile SED had a multivariate adjusted hazard ratio of 1.76 (95% confidence interval, 1.06-2.94) for 3-month mortality and 1.54 (1.00-2.37) for 1-year mortality. After adjustment for acute stroke care provisions, these were no longer significant. However, the sextile data of Carstairs score showed a consistent association of SED with survival after stroke; all patients with the sixth sextile had a fully adjusted hazard ratio of 1.23 (1.05-1.44) for 3-month mortality and 1.13 (1.01-1.25) for 17-year mortality. There is a weak but significant association of SED with reduced survival after stroke in England. SED in blacks may have a stronger impact on short-term survival when compared with white patients. Further efforts are required to achieve equality in survival among patients with stroke of different socioeconomic groups.

Dietary inflammatory index and risk of lung cancer and other respiratory conditions among heavy smokers in the COSMOS screening study.

PubMed

Maisonneuve, Patrick; Shivappa, Nitin; Hébert, James R; Bellomi, Massimo; Rampinelli, Cristiano; Bertolotti, Raffaella; Spaggiari, Lorenzo; Palli, Domenico; Veronesi, Giulia; Gnagnarella, Patrizia

2016-04-01

To test whether the inflammatory potential of diet, as measured using the dietary inflammatory index (DII), is associated with risk of lung cancer or other respiratory conditions and to compare results obtained with those based on the aMED score, an established dietary index that measures adherence to the traditional Mediterranean diet. In 4336 heavy smokers enrolled in a prospective, non-randomized lung cancer screening program, we measured participants' diets at baseline using a self-administered food frequency questionnaire from which dietary scores were calculated. Cox proportional hazards and logistic regression models were used to assess association between the dietary indices and lung cancer diagnosed during annual screening, and other respiratory outcomes that were recorded at baseline, respectively. In multivariable analysis, adjusted for baseline lung cancer risk (estimated from age, sex, smoking history, and asbestos exposure) and total energy, both DII and aMED scores were associated with dyspnoea (p trend = 0.046 and 0.02, respectively) and radiological evidence of emphysema (p trend = 0.0002 and 0.02). After mutual adjustment of the two dietary scores, only the association between DII and radiological evidence of emphysema (Q4 vs. Q1, OR 1.30, 95 % CI 1.01-1.67, p trend = 0.012) remained statistically significant. At univariate analysis, both DII and aMED were associated with lung cancer risk, but in fully adjusted multivariate analysis, only the association with aMED remained statistically significant (p trend = 0.04). Among heavy smokers, a pro-inflammatory diet, as indicated by increasing DII score, is associated with dyspnoea and radiological evidence of emphysema. A traditional Mediterranean diet, which is associated with a lower DII, may lower lung cancer risk.

Dietary inflammatory index and risk of lung cancer and other respiratory conditions among heavy smokers in the COSMOS screening study

PubMed Central

Shivappa, Nitin; Hébert, James R.; Bellomi, Massimo; Rampinelli, Cristiano; Bertolotti, Raffaella; Spaggiari, Lorenzo; Palli, Domenico; Veronesi, Giulia; Gnagnarella, Patrizia

2016-01-01

Purpose To test whether the inflammatory potential of diet, as measured using the dietary inflammatory index (DII), is associated with risk of lung cancer or other respiratory conditions and to compare results obtained with those based on the aMED score, an established dietary index that measures adherence to the traditional Mediterranean diet. Methods In 4336 heavy smokers enrolled in a prospective, non-randomized lung cancer screening program, we measured participants’ diets at baseline using a self-administered food frequency questionnaire from which dietary scores were calculated. Cox proportional hazards and logistic regression models were used to assess association between the dietary indices and lung cancer diagnosed during annual screening, and other respiratory outcomes that were recorded at baseline, respectively. Results In multivariable analysis, adjusted for baseline lung cancer risk (estimated from age, sex, smoking history, and asbestos exposure) and total energy, both DII and aMED scores were associated with dyspnoea (p trend = 0.046 and 0.02, respectively) and radiological evidence of emphysema (p trend = 0.0002 and 0.02). After mutual adjustment of the two dietary scores, only the association between DII and radiological evidence of emphysema (Q4 vs. Q1, OR 1.30, 95 % CI 1.01–1.67, p trend = 0.012) remained statistically significant. At univariate analysis, both DII and aMED were associated with lung cancer risk, but in fully adjusted multivariate analysis, only the association with aMED remained statistically significant (p trend = 0.04). Conclusions Among heavy smokers, a pro-inflammatory diet, as indicated by increasing DII score, is associated with dyspnoea and radiological evidence of emphysema. A traditional Mediterranean diet, which is associated with a lower DII, may lower lung cancer risk. PMID:25953452

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

Cystic Fibrosis Associated with Worse Survival After Liver Transplantation.

PubMed

Black, Sylvester M; Woodley, Frederick W; Tumin, Dmitry; Mumtaz, Khalid; Whitson, Bryan A; Tobias, Joseph D; Hayes, Don

2016-04-01

Survival in cystic fibrosis patients after liver transplantation and liver-lung transplantation is not well studied. To discern survival rates after liver transplantation and liver-lung transplantation in patients with and without cystic fibrosis. The United Network for Organ Sharing database was queried from 1987 to 2013. Univariate Cox proportional hazards, multivariate Cox models, and propensity score matching were performed. Liver transplant and liver-lung transplant were performed in 212 and 53 patients with cystic fibrosis, respectively. Univariate Cox proportional hazards regression identified lower survival in cystic fibrosis after liver transplant compared to a reference non-cystic fibrosis liver transplant cohort (HR 1.248; 95 % CI 1.012, 1.541; p = 0.039). Supplementary analysis found graft survival was similar across the 3 recipient categories (log-rank test: χ(2) 2.68; p = 0.262). Multivariate Cox models identified increased mortality hazard among cystic fibrosis patients undergoing liver transplantation (HR 2.439; 95 % CI 1.709, 3.482; p < 0.001) and liver-lung transplantation (HR 2.753; 95 % CI 1.560, 4.861; p < 0.001). Propensity score matching of cystic fibrosis patients undergoing liver transplantation to non-cystic fibrosis controls identified a greater mortality hazard in the cystic fibrosis cohort using a Cox proportional hazards model stratified on matched pairs (HR 3.167; 95 % CI 1.265, 7.929, p = 0.014). Liver transplantation in cystic fibrosis is associated with poorer long-term patient survival compared to non-cystic fibrosis patients, although the difference is not due to graft survival.

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

PubMed

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

2016-11-01

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

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

PubMed

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

2016-06-01

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

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

PubMed

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

2016-03-08

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

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.

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.

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.

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

PubMed

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

2018-05-01

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

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

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

Association of cigarette smoking with a past history and incidence of herpes zoster in the general Japanese population: the SHEZ Study.

PubMed

Ban, J; Takao, Y; Okuno, Y; Mori, Y; Asada, H; Yamanishi, K; Iso, H

2017-04-01

Few studies have examined the impact of cigarette smoking on the risk for herpes zoster. The Shozu Herpes Zoster (SHEZ) Study is a community-based prospective cohort study over 3 years in Japan aiming to clarify the incidence and predictive and immunological factors for herpes zoster. We investigated the associations of smoking status with past history and incidence of herpes zoster. A total of 12 351 participants provided valid information on smoking status and past history of herpes zoster at baseline survey. Smoking status was classified into three categories (current, former, never smoker), and if currently smoking, the number of cigarettes consumed per day was recorded. The participants were under the active surveillance for first-ever incident herpes zoster for 3 years. We used a logistic regression model for the cross-sectional study on the association between smoking status and past history of herpes zoster, and a Cox proportional hazards regression model for the cohort study on the association with risk of incidence. The multivariable adjusted odd ratios (95% CI) of past history of herpes zoster for current vs. never smokers were 0·67 (0·54-0·80) for total subjects, 0·72 (0·56-0·93) for men and 0·65 (0·44-0·96) for women. The multivariable adjusted hazard ratios (95% CI) of incident herpes zoster for current vs. never smokers were 0·52 (0·33-0·81) for total subjects, 0·49 (0·29-0·83) for men and 0·52 (0·19-1·39) for women. Smoking status was inversely associated with the prevalence and incidence of herpes zoster in the general population of men and women aged ⩾50 years.

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.

Genetic risk score and cardiovascular mortality in a southern european population with coronary artery disease.

PubMed

Pereira, Andreia; Mendonca, Maria Isabel; Sousa, Ana Célia; Borges, Sofia; Freitas, Sónia; Henriques, Eva; Rodrigues, Mariana; Freitas, Ana Isabel; Guerra, Graça; Ornelas, Ilídio; Pereira, Décio; Brehm, António; Palma Dos Reis, Roberto

2017-06-01

Several genetic risk scores (GRS) have been associated with cardiovascular disease; their role, however, in survival from proven coronary artery disease (CAD) have yielded conflicting results. The objective of this study was to evaluate long-term cardiovascular mortality according to the genetic risk score in a Southern European population with CAD. A cohort of 1464 CAD patients with angiographic proven CAD were followed up prospectively for up to 58.3 (interquartile range: 25.8-88.1) months. Genotyping of 32 single-nucleotide polymorphisms previously associated with CAD was performed using oligonucleotides probes marked with fluorescence for each allele. GRS was constructed according to the additive model assuming codominance and categorised using the median (=26). Cox Regression analysis was performed to determine independent multivariate predictors of cardiovascular mortality. Kaplan-Meier survival curves compared high vs low GRS using log-rank test. C-index was done for our population, as a measure of discrimination in survival analysis model. During a mean follow-up of 58.3 months, 156 patients (10.7%) died, 107 (7.3%) of CV causes. High GRS (≥26) was associated with reduced cardiovascular survival. Survival analysis with Cox regression model adjusted for 8 variables showed that high GRS, dyslipidemia, diabetes and 3-vessel disease were independent risk factors for cardiovascular mortality (HR=1.53, P=.037; HR=3.64, P=.012; HR=1.75, P=.004; HR=2.97, P<.0001, respectively). At the end of follow-up, the estimated survival probability was 70.8% for high GRS and 80.8% for low GRS (Log-rank test 5.6; P=.018). C-Index of 0.71 was found when GRS was added to a multivariate survival model of diabetes, dyslipidemia, smoking, hypertension and 3 vessel disease, stable angina and dual antiplatelet therapy. Besides the classical risk factors management, this work highlights the relevance of the genetic profile in survival from CAD. It is expected that new therapies will be dirsected to gene targets with proven value in cardiovascular survival. © 2017 John Wiley & Sons Ltd.

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

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

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

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

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

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

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

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

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

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

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.

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.

Adverse Outcomes After Initial Non-surgical Management of Subdural Hematoma: A Population-Based Study.

PubMed

Morris, Nicholas A; Merkler, Alexander E; Parker, Whitney E; Claassen, Jan; Connolly, E Sander; Sheth, Kevin N; Kamel, Hooman

2016-04-01

Little is known about the natural history of non-surgically managed subdural hematoma (SDH). The purpose of this study is to determine rates of adverse events after non-surgical management of SDH and whether these outcomes differ depending on traumatic versus nontraumatic etiology. A retrospective cohort study was conducted using administrative claims data on all emergency department visits and acute care hospitalizations at nonfederal facilities in California from 2005 to 2011, Florida from 2005 to 2012, and New York from 2006 to 2011. We included patients who were discharged home after hospitalization with a first-recorded diagnosis of SDH and no record of surgical hematoma evacuation. Patients were followed for readmission with SDH, readmission for surgical SDH evacuation, and fatal readmission with SDH. Survival statistics and the log-rank test were used to compare rates of these adverse events after traumatic versus nontraumatic SDH. Multivariable Cox regression analysis was used to compare hazards for traumatic versus nontraumatic etiology while adjusting for age, sex, race, insurance status, presence of dementia, alcohol use, acquired abnormalities in coagulation, acquired abnormalities in platelet function, hypertension, atrial fibrillation, venous thromboembolism, ischemic stroke, coronary heart disease, and valvular disease. We identified 27,502 conservatively treated patients with SDH, of which 70.9% were traumatic and 29.1% nontraumatic. Compared to patients with traumatic SDH, patients with nontraumatic SDH had significantly higher rates of subsequent hospitalization with SDH (cumulative 90-day rates: 15.3 % [95% CI 14.5-16.1%] vs. 10.3% [95% CI 9.9-10.8%]), surgical SDH evacuation (7.8% [95% CI 7.3-8.5%] vs. 5.5% [95% CI 5.2-5.8%]), and SDH-related in-hospital death (1.0% [95% CI 0.8-1.2%] vs. 0.4% [95 % CI 0.3-0.5%]). In multivariable Cox regression analysis, nontraumatic etiology was associated with a higher hazard of readmission with SDH (HR 1.4; 95% CI 1.3-1.5), surgery (HR 1.3; 95% CI 1.2-1.4), and in-hospital mortality (HR 1.9; 95% CI 1.4-2.5). Our findings were unchanged in sensitivity analyses that also adjusted for Elixhauser comorbidities. Approximately one in eight patients with a conservatively managed SDH was readmitted with SDH within 90 days. A substantial proportion of these readmissions involved surgical hematoma evacuation. These outcomes occurred significantly more often after nontraumatic as compared to traumatic SDH.

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

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.

Muscular Strength and Incident Hypertension in Normotensive and Prehypertensive Men

PubMed Central

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

2009-01-01

The protective effects of cardiorespiratory fitness (CRF) on hypertension (HTN) are well known; however, the association between muscular strength and incidence of HTN has yet to be examined. Purpose This study evaluated the strength-HTN association with and without accounting for CRF. Methods Participants were 4147 men (20–82 years) in the Aerobics Center Longitudinal Study for whom an age-specific composite muscular strength score was computed from measures of a 1-repetition maximal leg and a 1-repetition maximal bench press. CRF was quantified by maximal treadmill exercise test time in minutes. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals of incident HTN events according to exposure categories. Results During a mean follow-up of 19 years, there were 503 incident HTN cases. Multivariable-adjusted (excluding CRF) HRs of hypertension in normotensive men comparing middle and high strength thirds to the lowest third were not significant at 1.17 and 0.84, respectively. Multivariable-adjusted (excluding CRF) HRs of hypertension in baseline prehypertensive men comparing middle and high strength thirds to the lowest third were significant at 0.73 and 0.72 (p=.01 each), respectively. The association between muscular strength and incidence of HTN in baseline prehypertensive men was no longer significant after control for CRF (p=.26). Conclusions The study indicated that middle and high levels of muscular strength were associated with a reduced risk of HTN in prehypertensive men only. However, this relationship was no longer significant after controlling for CRF. PMID:19927030

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

PubMed

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

2014-08-01

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

Association of vegetable and fruit intake with gastric cancer risk among Japanese: a pooled analysis of four cohort studies.

PubMed

Shimazu, T; Wakai, K; Tamakoshi, A; Tsuji, I; Tanaka, K; Matsuo, K; Nagata, C; Mizoue, T; Inoue, M; Tsugane, S; Sasazuki, S

2014-06-01

Prospective evidence is inconsistent regarding the association between vegetable/fruit intake and the risk of gastric cancer. In an analysis of original data from four population-based prospective cohort studies encompassing 191 232 participants, we used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of gastric cancer incidence according to vegetable and fruit intake and conducted a meta-analysis of HRs derived from each study. During 2 094 428 person-years of follow-up, 2995 gastric cancer cases were identified. After adjustment for potential confounders, we found a marginally significant decrease in gastric cancer risk in relation to total vegetable intake but not total fruit intake: the multivariate-adjusted HR (95% CI; P for trend) for the highest versus the lowest quintile of total vegetable intake was 0.89 (0.77-1.03; P for trend = 0.13) among men and 0.83 (0.67-1.03; P for trend = 0.40) among women. For distal gastric cancer, the multivariate HR for the highest quintile of total vegetable intake was 0.78 (0.63-0.97; P for trend = 0.02) among men. This pooled analysis of data from large prospective studies in Japan suggests that vegetable intake reduces gastric cancer risk, especially the risk of distal gastric cancer among men. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Exercise Decreases and Smoking Increases Bladder Cancer Mortality.

PubMed

Liss, Michael A; White, Martha; Natarajan, Loki; Parsons, J Kellogg

2017-06-01

The aim of this study was to investigate modifiable lifestyle factors of smoking, exercise, and obesity with bladder cancer mortality. We used mortality-linked data from the National Health Information Survey from 1998 through 2006. The primary outcome was bladder cancer-specific mortality. The primary exposures were self-reported smoking status (never- vs. former vs. current smoker), self-reported exercise (dichotomized as "did no exercise" vs. "light, moderate, or vigorous exercise in ≥ 10-minute bouts"), and body mass index. We utilized multivariable adjusted Cox proportional hazards regression models, with delayed entry to account for age at survey interview. Complete data were available on 222,163 participants, of whom 96,715 (44%) were men and 146,014 (66%) were non-Hispanic whites, and among whom we identified 83 bladder cancer-specific deaths. In multivariate analyses, individuals who reported any exercise were 47% less likely (adjusted hazard ratio [HR adj ], 0.53; 95% confidence interval [CI], 0.29-0.96; P = .038) to die of bladder cancer than "no exercise". Compared with never-smokers, current (HR adj , 4.24; 95% CI, 1.89-9.65; P = .001) and former (HR adj , 2.95; 95% CI, 1.50-5.79; P = .002) smokers were 4 and 3 times more likely, respectively, to die of bladder cancer. There were no significant associations of body mass index with bladder cancer mortality. Exercise decreases and current smoking increases the risk of bladder cancer-specific mortality. These data suggest that exercise and smoking cessation interventions may reduce bladder cancer death. Published by Elsevier Inc.

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.

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 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.

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

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

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.

Appendectomy correlates with increased risk of pyogenic liver abscess

PubMed Central

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

2016-01-01

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

Dietary Sodium Consumption Predicts Future Blood Pressure and Incident Hypertension in the Japanese Normotensive General Population

PubMed Central

Takase, Hiroyuki; Sugiura, Tomonori; Kimura, Genjiro; Ohte, Nobuyuki; Dohi, Yasuaki

2015-01-01

Background Although there is a close relationship between dietary sodium and hypertension, the concept that persons with relatively high dietary sodium are at increased risk of developing hypertension compared with those with relatively low dietary sodium has not been studied intensively in a cohort. Methods and Results We conducted an observational study to investigate whether dietary sodium intake predicts future blood pressure and the onset of hypertension in the general population. Individual sodium intake was estimated by calculating 24-hour urinary sodium excretion from spot urine in 4523 normotensive participants who visited our hospital for a health checkup. After a baseline examination, they were followed for a median of 1143 days, with the end point being development of hypertension. During the follow-up period, hypertension developed in 1027 participants (22.7%). The risk of developing hypertension was higher in those with higher rather than lower sodium intake (hazard ratio 1.25, 95% CI 1.04 to 1.50). In multivariate Cox proportional hazards regression analysis, baseline sodium intake and the yearly change in sodium intake during the follow-up period (as continuous variables) correlated with the incidence of hypertension. Furthermore, both the yearly increase in sodium intake and baseline sodium intake showed significant correlations with the yearly increase in systolic blood pressure in multivariate regression analysis after adjustment for possible risk factors. Conclusions Both relatively high levels of dietary sodium intake and gradual increases in dietary sodium are associated with future increases in blood pressure and the incidence of hypertension in the Japanese general population. PMID:26224048

Outcomes following Kidney transplantation in IgA nephropathy: a UNOS/OPTN analysis.

PubMed

Kadiyala, Aditya; Mathew, Anna T; Sachdeva, Mala; Sison, Cristina P; Shah, Hitesh H; Fishbane, Steven; Jhaveri, Kenar D

2015-10-01

This study updates assessment of post-transplant outcomes in IgAN patients in the modern era of immunosuppression. Using UNOS/OPTN data, patients ≥18 yr of age with first kidney transplant (1/1/1999 to 12/31/2008) were analyzed. Multivariable Cox regression models and propensity score-based matching techniques were used to estimate hazard ratios (HRs) for death-censored allograft survival (DCGS) and patient survival in IgAN compared to non-IgAN. Results of multivariable regression were stratified by donor type (living vs. deceased). A total of 107, 747 recipients were included (4589 with IgAN and 103 158 with non-IgAN). Adjusted HR for DCGS showed no significant difference between IgAN and non-IgAN. IgAN had higher patient survival compared to non-IgAN (HR 0.54, 95% CI 0.47-0.62, p < 0.0001 for deceased donors; HR 0.42, 95% CI 0.33-0.54, p < 0.0001 for living donors). Propensity score-matched analysis was similar, with no significant difference in DCGS between matched groups and higher patient survival in IgAN patients compared to non-IgAN group (HR 0.54, 95% CI 0.47, 0.63; p-value <0.0001). IgAN patients with first kidney transplant have superior patient survival and similar graft survival compared to non-IgAN recipients. Results can be used in prognostication and informed decision-making about kidney transplantation in patients with IgAN. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cox proportional hazards model of myopic regression for laser in situ keratomileusis flap creation with a femtosecond laser and with a mechanical microkeratome.

PubMed

Lin, Meng-Yin; Chang, David C K; Hsu, Wen-Ming; Wang, I-Jong

2012-06-01

To compare predictive factors for postoperative myopic regression between laser in situ keratomileusis (LASIK) with a femtosecond laser and LASIK with a mechanical microkeratome. Nobel Eye Clinic, Taipei, Taiwan. Retrospective comparative study. Refractive outcomes were recorded 1 day, 1 week, and 1, 3, 6, 9, and 12 months after LASIK. A Cox proportional hazards model was used to evaluate the impact of the 2 flap-creating methods and other covariates on postoperative myopic regression. The femtosecond group comprised 409 eyes and the mechanical microkeratome group, 377 eyes. For both methods, significant predictors for myopic regression after LASIK included preoperative manifest spherical equivalent (P=.0001) and central corneal thickness (P=.027). Laser in situ keratomileusis with a mechanical microkeratome had a higher probability of postoperative myopic regression than LASIK with a femtosecond laser (P=.0002). After adjusting for other covariates in the Cox proportional hazards model, the cumulative risk for myopic regression with a mechanical microkeratome was higher than with a femtosecond laser 12 months postoperatively (P=.0002). With the definition of myopic regression as a myopic shift of 0.50 diopter (D) or more and residual myopia of -0.50 D or less, the risk estimate based on the mean covariates in all eyes in the femtosecond group and mechanical microkeratome group at 12 months was 43.6% and 66.9%, respectively. Laser in situ keratomileusis with a mechanical microkeratome had a higher risk for myopic regression than LASIK with a femtosecond laser through 12 months postoperatively. Copyright © 2012. Published by Elsevier Inc.

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

PubMed 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.

Remote-sensing data processing with the multivariate regression analysis method for iron mineral resource potential mapping: a case study in the Sarvian area, central Iran

NASA Astrophysics Data System (ADS)

Mansouri, Edris; Feizi, Faranak; Jafari Rad, Alireza; Arian, Mehran

2018-03-01

This paper uses multivariate regression to create a mathematical model for iron skarn exploration in the Sarvian area, central Iran, using multivariate regression for mineral prospectivity mapping (MPM). The main target of this paper is to apply multivariate regression analysis (as an MPM method) to map iron outcrops in the northeastern part of the study area in order to discover new iron deposits in other parts of the study area. Two types of multivariate regression models using two linear equations were employed to discover new mineral deposits. This method is one of the reliable methods for processing satellite images. ASTER satellite images (14 bands) were used as unique independent variables (UIVs), and iron outcrops were mapped as dependent variables for MPM. According to the results of the probability value (p value), coefficient of determination value (R2) and adjusted determination coefficient (Radj2), the second regression model (which consistent of multiple UIVs) fitted better than other models. The accuracy of the model was confirmed by iron outcrops map and geological observation. Based on field observation, iron mineralization occurs at the contact of limestone and intrusive rocks (skarn type).

Polymorphism in COX-2 modifies the inverse association between Helicobacter pylori seropositivity and esophageal squamous cell carcinoma risk in Taiwan: a case control study

PubMed Central

2009-01-01

Background Overexpression of Cyclooxygenase-2 (COX-2) was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC). One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori) was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP), H. pylori infection and the risk of developing ESCC. Methods One hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression. Results In analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 – 0.9). COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 – 7.3). The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 – 22.5). Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 – 0.9), and the effect was observed to be enhanced for the lower third ESCC patients (AOR ratio: 0.09, 95% CI: 0.02 – 0.47, p for multiplicative interaction 0.008) Conclusion H. pylori seropositivity is inversely associated with the risk of ESCC in Taiwan, and COX-2 -1195 polymorphism plays a role in modifying the influence between H. pylori and ESCC, especially in lower third esophagus. PMID:19463183

Polymorphism in COX-2 modifies the inverse association between Helicobacter pylori seropositivity and esophageal squamous cell carcinoma risk in Taiwan: a case control study.

PubMed

Hu, Huang-Ming; Kuo, Chao-Hung; Lee, Chien-Hung; Wu, I-Chen; Lee, Ka-Wo; Lee, Jang-Ming; Goan, Yih-Gang; Chou, Shah-Hwa; Kao, Ein-Long; Wu, Ming-Tsang; Wu, Deng-Chyang

2009-05-23

Overexpression of Cyclooxygenase-2 (COX-2) was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC). One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori) was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP), H. pylori infection and the risk of developing ESCC. One hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression. In analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 - 0.9). COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 - 7.3). The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 - 22.5). Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 - 0.9), and the effect was observed to be enhanced for the lower third ESCC patients (AOR ratio: 0.09, 95% CI: 0.02 - 0.47, p for multiplicative interaction 0.008) H. pylori seropositivity is inversely associated with the risk of ESCC in Taiwan, and COX-2 -1195 polymorphism plays a role in modifying the influence between H. pylori and ESCC, especially in lower third esophagus.

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

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.

Survival analysis of cervical cancer using stratified Cox regression

NASA Astrophysics Data System (ADS)

Purnami, S. W.; Inayati, K. D.; Sari, N. W. Wulan; Chosuvivatwong, V.; Sriplung, H.

2016-04-01

Cervical cancer is one of the mostly widely cancer cause of the women death in the world including Indonesia. Most cervical cancer patients come to the hospital already in an advanced stadium. As a result, the treatment of cervical cancer becomes more difficult and even can increase the death's risk. One of parameter that can be used to assess successfully of treatment is the probability of survival. This study raises the issue of cervical cancer survival patients at Dr. Soetomo Hospital using stratified Cox regression based on six factors such as age, stadium, treatment initiation, companion disease, complication, and anemia. Stratified Cox model is used because there is one independent variable that does not satisfy the proportional hazards assumption that is stadium. The results of the stratified Cox model show that the complication variable is significant factor which influent survival probability of cervical cancer patient. The obtained hazard ratio is 7.35. It means that cervical cancer patient who has complication is at risk of dying 7.35 times greater than patient who did not has complication. While the adjusted survival curves showed that stadium IV had the lowest probability of survival.

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.

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

Birth by Caesarean Section and the Risk of Adult Psychosis: A Population-Based Cohort Study.

PubMed

O'Neill, Sinéad M; Curran, Eileen A; Dalman, Christina; Kenny, Louise C; Kearney, Patricia M; Clarke, Gerard; Cryan, John F; Dinan, Timothy G; Khashan, Ali S

2016-05-01

Despite the biological plausibility of an association between obstetric mode of delivery and psychosis in later life, studies to date have been inconclusive. We assessed the association between mode of delivery and later onset of psychosis in the offspring. A population-based cohort including data from the Swedish National Registers was used. All singleton live births between 1982 and 1995 were identified (n= 1,345,210) and followed-up to diagnosis at age 16 or later. Mode of delivery was categorized as: unassisted vaginal delivery (VD), assisted VD, elective Caesarean section (CS) (before onset of labor), and emergency CS (after onset of labor). Outcomes included any psychosis; nonaffective psychoses (including schizophrenia only) and affective psychoses (including bipolar disorder only and depression with psychosis only). Cox regression analysis was used reporting partially and fully adjusted hazard ratios (HR) with 95% confidence intervals (CI). Sibling-matched Cox regression was performed to adjust for familial confounding factors. In the fully adjusted analyses, elective CS was significantly associated with any psychosis (HR 1.13, 95% CI 1.03, 1.24). Similar findings were found for nonaffective psychoses (HR 1.13, 95% CI 0.99, 1.29) and affective psychoses (HR 1.17, 95% CI 1.05, 1.31) (χ(2)for heterogeneityP= .69). In the sibling-matched Cox regression, this association disappeared (HR 1.03, 95% CI 0.78, 1.37). No association was found between assisted VD or emergency CS and psychosis. This study found that elective CS is associated with an increase in offspring psychosis. However, the association did not persist in the sibling-matched analysis, implying the association is likely due to familial confounding by unmeasured factors such as genetics or environment. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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

PubMed

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

2017-04-25

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

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

PubMed Central

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

2017-01-01

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

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.

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.

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.

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.

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.

Prediction of all-cause death in hemodialysis patients using elevated postdialysis pulse wave velocity.

PubMed

Fu, Xiaohong; Yang, Jihong; Fan, Zhaoxin; Chen, Xianguang; Wu, Jie; Li, Jie; Wu, Hua

2016-02-01

To identify the relationship between predialysis pulse wave velocity (PWV), postdialysis PWV during 1 hemodialysis (HD) session, and deaths in maintenance HD patients. 43 patients were recruited. PWV was measured before and after one HD session and dialysis- related data were recorded. Clinical data such as blood pressure, blood lipids, and blood glucose, were carefully observed and managed in a 5-year follow-up. The association between all-cause death, predialysis PWV, postdialysis PWV, change of PWV (ΔPWV), and other related variables were analyzed. After 5 years, 17 patients (39.5%) died. Univariate Cox regression analysis showed that all-cause death of the patients significantly correlated with age, postdialysis PWV, and ΔPWV. Multivariate Cox regression analysis revealed that postdialysis PWV was an independent predictor for all-cause death in these patients (HR: 1.377, 95% CI: 1.146 - 1.656, p = 0.001). Elevated postdialysis PWV significantly correlated with and was an independent predictor for all-cause death in maintenance HD patients.

Associations of ikigai as a positive psychological factor with all-cause mortality and cause-specific mortality among middle-aged and elderly Japanese people: findings from the Japan Collaborative Cohort Study.

PubMed

Tanno, Kozo; Sakata, Kiyomi; Ohsawa, Masaki; Onoda, Toshiyuki; Itai, Kazuyoshi; Yaegashi, Yumi; Tamakoshi, Akiko

2009-07-01

To determine whether presence of ikigai as a positive psychological factor is associated with decreased risks for all-cause and cause-specific mortality among middle-aged and elderly Japanese men and women. From 1988 to 1990, a total of 30,155 men and 43,117 women aged 40 to 79 years completed a lifestyle questionnaire including a question about ikigai. Mortality follow-up was available for a mean of 12.5 years and was classified as having occurred in the first 5 years or the subsequent follow-up period. Associations between ikigai and all-cause and cause-specific mortality were assessed using a Cox's regression model. Multivariate hazard ratios (HRs) were adjusted for age, body mass index, drinking and smoking status, physical activity, sleep duration, education, occupation, marital status, perceived mental stress, and medical history. During the follow-up period, 10,021 deaths were recorded. Men and women with ikigai had decreased risks of mortality from all causes in the long-term follow-up period; multivariate HRs (95% confidence intervals, CIs) were 0.85 (0.80-0.90) for men and 0.93 (0.86-1.00) for women. The risk of cardiovascular mortality was reduced in men with ikigai; the multivariate HR (95% CI) was 0.86 (0.76-0.97). Furthermore, men and women with ikigai had a decreased risk for mortality from external causes; multivariate HRs (95% CIs) were 0.74 (0.59-0.93) for men and 0.67 (0.51-0.88) for women. The findings suggest that a positive psychological factor such as ikigai is associated with longevity among Japanese people.

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.

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.

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.

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

PubMed

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

2017-11-01

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

A generalized multivariate regression model for modelling ocean wave heights

NASA Astrophysics Data System (ADS)

Wang, X. L.; Feng, Y.; Swail, V. R.

2012-04-01

In this study, a generalized multivariate linear regression model is developed to represent the relationship between 6-hourly ocean significant wave heights (Hs) and the corresponding 6-hourly mean sea level pressure (MSLP) fields. The model is calibrated using the ERA-Interim reanalysis of Hs and MSLP fields for 1981-2000, and is validated using the ERA-Interim reanalysis for 2001-2010 and ERA40 reanalysis of Hs and MSLP for 1958-2001. The performance of the fitted model is evaluated in terms of Pierce skill score, frequency bias index, and correlation skill score. Being not normally distributed, wave heights are subjected to a data adaptive Box-Cox transformation before being used in the model fitting. Also, since 6-hourly data are being modelled, lag-1 autocorrelation must be and is accounted for. The models with and without Box-Cox transformation, and with and without accounting for autocorrelation, are inter-compared in terms of their prediction skills. The fitted MSLP-Hs relationship is then used to reconstruct historical wave height climate from the 6-hourly MSLP fields taken from the Twentieth Century Reanalysis (20CR, Compo et al. 2011), and to project possible future wave height climates using CMIP5 model simulations of MSLP fields. The reconstructed and projected wave heights, both seasonal means and maxima, are subject to a trend analysis that allows for non-linear (polynomial) trends.

Glioblastoma multiforme (GBM) in the elderly: initial treatment strategy and overall survival.

PubMed

Glaser, Scott M; Dohopolski, Michael J; Balasubramani, Goundappa K; Flickinger, John C; Beriwal, Sushil

2017-08-01

The EORTC trial which solidified the role of external beam radiotherapy (EBRT) plus temozolomide (TMZ) in the management of GBM excluded patients over age 70. Randomized studies of elderly patients showed that hypofractionated EBRT (HFRT) alone or TMZ alone was at least equivalent to conventionally fractionated EBRT (CFRT) alone. We sought to investigate the practice patterns and survival in elderly patients with GBM. We identified patients age 65-90 in the National Cancer Data Base (NCDB) with histologically confirmed GBM from 1998 to 2012 and known chemotherapy and radiotherapy status. We analyzed factors predicting treatment with EBRT alone vs. EBRT plus concurrent single-agent chemotherapy (CRT) using multivariable logistic regression. Similarly, within the EBRT alone cohort we compared CFRT (54-65 Gy at 1.7-2.1 Gy/fraction) to HFRT (34-60 Gy at 2.5-5 Gy/fraction). Multivariable Cox proportional hazards model (MVA) with propensity score adjustment was used to compare survival. A total of 38,862 patients were included. Initial treatments for 1998 versus 2012 were: EBRT alone = 50 versus 10%; CRT = 6 versus 50%; chemo alone = 1.6% (70% single-agent) versus 3.2% (94% single-agent). Among EBRT alone patients, use of HFRT (compared to CFRT) increased from 13 to 41%. Numerous factors predictive for utilization of CRT over EBRT alone and for HFRT over CFRT were identified. Median survival and 1-year overall survival were higher in the CRT versus EBRT alone group at 8.6 months vs. 5.1 months and 36.0 versus 15.7% (p < 0.0005 by log-rank, multivariable HR 0.65 [95% CI = 0.61-0.68, p < 0.0005], multivariable HR with propensity adjustment 0.66 [95% CI = 0.63-0.70, p < 0.0005]). For elderly GBM patients in the United States, CRT is the most common initial treatment and appears to offer a survival advantage over EBRT alone. Adoption of hypofractionation has increased over time but continues to be low.

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

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.

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.

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

PubMed Central

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

2016-01-01

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

Comparison and validation of statistical methods for predicting power outage durations in the event of hurricanes.

PubMed

Nateghi, Roshanak; Guikema, Seth D; Quiring, Steven M

2011-12-01

This article compares statistical methods for modeling power outage durations during hurricanes and examines the predictive accuracy of these methods. Being able to make accurate predictions of power outage durations is valuable because the information can be used by utility companies to plan their restoration efforts more efficiently. This information can also help inform customers and public agencies of the expected outage times, enabling better collective response planning, and coordination of restoration efforts for other critical infrastructures that depend on electricity. In the long run, outage duration estimates for future storm scenarios may help utilities and public agencies better allocate risk management resources to balance the disruption from hurricanes with the cost of hardening power systems. We compare the out-of-sample predictive accuracy of five distinct statistical models for estimating power outage duration times caused by Hurricane Ivan in 2004. The methods compared include both regression models (accelerated failure time (AFT) and Cox proportional hazard models (Cox PH)) and data mining techniques (regression trees, Bayesian additive regression trees (BART), and multivariate additive regression splines). We then validate our models against two other hurricanes. Our results indicate that BART yields the best prediction accuracy and that it is possible to predict outage durations with reasonable accuracy. © 2011 Society for Risk Analysis.

Fruit and vegetable consumption and mortality in Eastern Europe: Longitudinal results from the Health, Alcohol and Psychosocial Factors in Eastern Europe study.

PubMed

Stefler, Denes; Pikhart, Hynek; Kubinova, Ruzena; Pajak, Andrzej; Stepaniak, Urszula; Malyutina, Sofia; Simonova, Galina; Peasey, Anne; Marmot, Michael G; Bobak, Martin

2016-03-01

It is estimated that disease burden due to low fruit and vegetable consumption is higher in Central and Eastern Europe (CEE) and the former Soviet Union (FSU) than any other parts of the world. However, no large scale studies have investigated the association between fruit and vegetable (F&V) intake and mortality in these regions yet. The Health, Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE) study is a prospective cohort study with participants recruited from the Czech Republic, Poland and Russia. Dietary data was collected using food frequency questionnaire. Mortality data was ascertained through linkage with death registers. Multivariable adjusted hazard ratios were calculated by Cox regression models. Among 19,333 disease-free participants at baseline, 1314 died over the mean follow-up of 7.1 years. After multivariable adjustment, we found statistically significant inverse association between cohort-specific quartiles of F&V intake and stroke mortality: the highest vs lowest quartile hazard ratio (HR) was 0.52 (95% confidence interval (CI): 0.28-0.98). For total mortality, significant interaction (p = 0.008) between F&V intake and smoking was found. The associations were statistically significant in smokers, with HR 0.70 (0.53-0.91, p for trend: 0.011) for total mortality, and 0.62 (0.40-0.97, p for trend: 0.037) for cardiovascular disease (CVD) mortality. The association was appeared to be mediated by blood pressure, and F&V intake explained a considerable proportion of the mortality differences between the Czech and Russian cohorts. Our results suggest that increasing F&V intake may reduce CVD mortality in CEE and FSU, particularly among smokers and hypertensive individuals. © The European Society of Cardiology 2015.

Glycemic index, glycemic load and invasive breast cancer incidence in postmenopausal women: The PREDIMED study.

PubMed

Castro-Quezada, Itandehui; Sánchez-Villegas, Almudena; Martínez-González, Miguel Á; Salas-Salvadó, Jordi; Corella, Dolores; Estruch, Ramón; Schröder, Helmut; Álvarez-Pérez, Jacqueline; Ruiz-López, María D; Artacho, Reyes; Ros, Emilio; Bulló, Mónica; Sorli, Jose V; Fitó, Montserrat; Ruiz-Gutiérrez, Valentina; Toledo, Estefanía; Buil-Cosiales, Pilar; García Rodríguez, Antonio; Lapetra, José; Pintó, Xavier; Salaverría, Itziar; Tur, Josep A; Romaguera, Dora; Tresserra-Rimbau, Anna; Serra-Majem, Lluís

2016-11-01

The objective of this study was to evaluate the prospective associations between dietary glycemic index (GI) and glycemic load (GL) and the risk for invasive breast cancer incidence in postmenopausal women at high cardiovascular disease (CVD) risk. This study was conducted within the framework of the PREvención con DIeta MEDiterránea (PREDIMED) study, a nutritional intervention trial for primary cardiovascular prevention. We included 4010 women aged between 60 and 80 years who were initially free from breast cancer but at high risk for CVD disease. Dietary information was collected using a validated 137-item food frequency questionnaire. We assigned GI values using the International Tables of GI and GL values. Cases were ascertained through yearly consultation of medical records and through consultation of the National Death Index. Only cases confirmed by results from cytology tests or histological evaluation were included. We estimated multivariable-adjusted hazard ratios for invasive breast cancer risk across tertiles of energy-adjusted dietary GI/GL using Cox regression models. We repeated our analyses using yearly repeated measures of GI/GL intakes. No associations were found between baseline dietary GI/GL and invasive breast cancer incidence. The multivariable hazard ratio and 95% confidence interval (CI) for the top tertile of dietary GI was 1.02 (95% CI: 0.42-2.46) and for dietary GL was 1.00 (95% CI: 0.44-2.30) when compared with the bottom tertile. Repeated-measures analyses yielded similar results. In sensitivity analyses, no significant associations were observed for women with obesity or diabetes. Dietary GI and GL did not appear to be associated with an increased risk for invasive breast cancer in postmenopausal women at high CVD risk.

Menopause and postmenopausal hormone therapy and risk of hearing loss.

PubMed

Curhan, Sharon G; Eliassen, A Heather; Eavey, Roland D; Wang, Molin; Lin, Brian M; Curhan, Gary C

2017-09-01

Menopause may be a risk factor for hearing loss, and postmenopausal hormone therapy (HT) has been proposed to slow hearing decline; however, there are no large prospective studies. We prospectively examined the independent relations between menopause and postmenopausal HT and risk of self-reported hearing loss. Prospective cohort study among 80,972 women in the Nurses' Health Study II, baseline age 27 to 44 years, followed from 1991 to 2013. Baseline and updated information was obtained from detailed validated biennial questionnaires. Cox proportional-hazards regression models were used to examine independent associations between menopausal status and postmenopausal HT and risk of hearing loss. After 1,410,928 person-years of follow-up, 18,558 cases of hearing loss were reported. There was no significant overall association between menopausal status, natural or surgical, and risk of hearing loss. Older age at natural menopause was associated with higher risk. The multivariable-adjusted relative risk of hearing loss among women who underwent natural menopause at age 50+ years compared with those aged less than 50 years was 1.10 (95% confidence interval [CI] 1.03, 1.17). Among postmenopausal women, oral HT (estrogen therapy or estrogen plus progestogen therapy) was associated with higher risk of hearing loss, and longer duration of use was associated with higher risk (P trend < 0.001). Compared with women who never used HT, the multivariable-adjusted relative risk of hearing loss among women who used oral HT for 5 to 9.9 years was 1.15 (95% CI 1.06, 1.24) and for 10+ years was 1.21 (95% CI 1.07, 1.37). Older age at menopause and longer duration of postmenopausal HT are associated with higher risk of hearing loss.

Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes.

PubMed

Muraleedharan, Vakkat; Marsh, Hazel; Kapoor, Dheeraj; Channer, Kevin S; Jones, T Hugh

2013-12-01

Men with type 2 diabetes are known to have a high prevalence of testosterone deficiency. No long-term data are available regarding testosterone and mortality in men with type 2 diabetes or any effect of testosterone replacement therapy (TRT). We report a 6-year follow-up study to examine the effect of baseline testosterone and TRT on all-cause mortality in men with type 2 diabetes and low testosterone. A total of 581 men with type 2 diabetes who had testosterone levels performed between 2002 and 2005 were followed up for a mean period of 5.81.3 S.D. years. mortality rates were compared between total testosterone 10.4nmol/l (300ng/dl; n=343) and testosterone 10.4nmol/l (n=238). the effect of TRT (as per normal clinical practise: 85.9% testosterone gel and 14.1% intramuscular testosterone undecanoate) was assessed retrospectively within the low testosterone group. Mortality was increased in the low testosterone group (17.2%) compared with the normal testosterone group (9%; P=0.003) when controlled for covariates. In the Cox regression model, multivariate-adjusted hazard ratio (HR) for decreased survival was 2.02 (P=0.009, 95% CI 1.2-3.4). TRT (mean duration 41.6±20.7 months; n=64) was associated with a reduced mortality of 8.4% compared with 19.2% (P=0.002) in the untreated group (n=174). The multivariate-adjusted HR for decreased survival in the untreated group was 2.3 (95% CI 1.3-3.9, P=0.004). Low testosterone levels predict an increase in all-cause mortality during long-term follow-up. Testosterone replacement may improve survival in hypogonadal men with type 2 diabetes.

Discrete improvement in racial disparity in survival among patients with stage IV colorectal cancer: a 21-year population-based analysis.

PubMed

Castleberry, A W; Güller, U; Tarantino, I; Berry, M F; Brügger, L; Warschkow, R; Cerny, T; Mantyh, C R; Candinas, D; Worni, M

2014-06-01

Recently, multiple clinical trials have demonstrated improved outcomes in patients with metastatic colorectal cancer. This study investigated if the improved survival is race dependent. Overall and cancer-specific survival of 77,490 White and Black patients with metastatic colorectal cancer from the 1988-2008 Surveillance Epidemiology and End Results registry were compared using unadjusted and multivariable adjusted Cox proportional hazard regression as well as competing risk analyses. Median age was 69 years, 47.4 % were female and 86.0 % White. Median survival was 11 months overall, with an overall increase from 8 to 14 months between 1988 and 2008. Overall survival increased from 8 to 14 months for White, and from 6 to 13 months for Black patients. After multivariable adjustment, the following parameters were associated with better survival: White, female, younger, better educated and married patients, patients with higher income and living in urban areas, patients with rectosigmoid junction and rectal cancer, undergoing cancer-directed surgery, having well/moderately differentiated, and N0 tumors (p < 0.05 for all covariates). Discrepancies in overall survival based on race did not change significantly over time; however, there was a significant decrease of cancer-specific survival discrepancies over time between White and Black patients with a hazard ratio of 0.995 (95 % confidence interval 0.991-1.000) per year (p = 0.03). A clinically relevant overall survival increase was found from 1988 to 2008 in this population-based analysis for both White and Black patients with metastatic colorectal cancer. Although both White and Black patients benefitted from this improvement, a slight discrepancy between the two groups remained.

Conditional survival estimates improve over time for patients with advanced melanoma: results from a population-based analysis.

PubMed

Xing, Yan; Chang, George J; Hu, Chung-Yuan; Askew, Robert L; Ross, Merrick I; Gershenwald, Jeffrey E; Lee, Jeffrey E; Mansfield, Paul F; Lucci, Anthony; Cormier, Janice N

2010-05-01

Conditional survival (CS) has emerged as a clinically relevant measure of prognosis for cancer survivors. The objective of this analysis was to provide melanoma-specific CS estimates to help clinicians promote more informed patient decision making. Patients with melanoma and at least 5 years of follow-up were identified from the Surveillance Epidemiology and End Results registry (1988-2000). By using the methods of Kaplan and Meier, stage-specific, 5-year CS estimates were independently calculated for survivors for each year after diagnosis. Stage-specific multivariate Cox regression models including baseline survivor functions were used to calculate adjusted melanoma-specific CS for different subgroups of patients further stratified by age, gender, race, marital status, anatomic tumor location, and tumor histology. Five-year CS estimates for patients with stage I disease remained constant at 97% annually, while for patients with stages II, III, and IV disease, 5-year CS estimates from time 0 (diagnosis) to 5 years improved from 72% to 86%, 51% to 87%, and 19% to 84%, respectively. Multivariate CS analysis revealed that differences in stages II through IV CS based on age, gender, and race decreased over time. Five-year melanoma-specific CS estimates improve dramatically over time for survivors with advanced stages of disease. These prognostic data are critical to patients for both treatment and nontreatment related life decisions. (c) 2010 American Cancer Society.

Elevated red cell distribution width contributes to a poor prognosis in patients with esophageal carcinoma.

PubMed

Wan, Guo-Xing; Chen, Ping; Cai, Xiao-Jun; Li, Lin-Jun; Yu, Xiong-Jie; Pan, Dong-Feng; Wang, Xian-He; Wang, Xuan-Bin; Cao, Feng-Jun

2016-01-15

The red cell distribution width (RDW) has also been reported to reliably reflect the inflammation and nutrition status and predict the prognosis across several types of cancer, however, the prognostic value of RDW in esophageal carcinoma has seldom been studied. A retrospective study was performed to assess the prognostic value of RDW in patients with esophageal carcinoma by the Kaplan-Meier analysis and multivariate Cox regression proportional hazard model. All enrolled patients were divided into high RDW group (≧15%) and low RDW group (<15%) according to the detected RDW values. Clinical and laboratory data from a total of 179 patients with esophageal carcinoma were retrieved. With a median follow-up of 21months, the high RDW group exhibited a shorter disease-free survival (DFS) (p<0.001) and an unfavorable overall survival (OS) (p<0.001) in the univariate analysis. The multivariate analysis revealed that elevated RDW at diagnosis was an independent prognostic factor for shorter PFS (p=0.043, HR=1.907, 95% CI=1.020-3.565) and poor OS (p=0.042, HR=1.895, 95% CI=1.023-3.508) after adjustment with other cancer-related prognostic factors. The present study suggests that elevated preoperative RDW(≧15%) at the diagnosis may independently predict poorer disease-free and overall survival among patients with esophageal carcinoma. Copyright © 2015 Elsevier B.V. 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

Prediagnostic intake of dairy products and dietary calcium and colorectal cancer survival--results from the EPIC cohort study.

PubMed

Dik, Vincent K; Murphy, Neil; Siersema, Peter D; Fedirko, Veronika; Jenab, Mazda; Kong, So Y; Hansen, Camilla P; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Dossus, Laure; Racine, Antoine; Bastide, Nadia; Li, Kuanrong; Kühn, Tilman; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Barbitsioti, Antonia; Palli, Domenico; Contiero, Paolo; Vineis, Paolo; Tumino, Rosaria; Panico, Salvatore; Peeters, Petra H M; Weiderpass, Elisabete; Skeie, Guri; Hjartåker, Anette; Amiano, Pilar; Sánchez, María-José; Fonseca-Nunes, Ana; Barricarte, Aurelio; Chirlaque, María-Dolores; Redondo, Maria-Luisa; Jirström, Karin; Manjer, Jonas; Nilsson, Lena M; Wennberg, Maria; Bradbury, Kathryn E; Khaw, Kay-Tee; Wareham, Nicholas; Cross, Amanda J; Riboli, Elio; Bueno-de-Mesquita, H Bas

2014-09-01

We investigated whether prediagnostic reported intake of dairy products and dietary calcium is associated with colorectal cancer survival. Data from 3,859 subjects with colorectal cancer (42.1% male; mean age at diagnosis, 64.2 ± 8.1 years) in the European Investigation into Cancer and Nutrition cohort were analyzed. Intake of dairy products and dietary calcium was assessed at baseline (1992-2000) using validated, country-specific dietary questionnaires. Multivariable Cox regression models were used to calculate HR and corresponding 95% confidence intervals (CI) for colorectal cancer-specific death (n = 1,028) and all-cause death (n = 1,525) for different quartiles of intake. The consumption of total dairy products was not statistically significantly associated with risk of colorectal cancer-specific death (adjusted HR Q4 vs. Q1, 1.17; 95% CI, 0.97-1.43) nor that of all-cause death (Q4 vs. Q1, 1.16; 95% CI, 0.98-1.36). Multivariable-adjusted HRs for colorectal cancer-specific death (Q4 vs. Q1) were 1.21 (95% CI, 0.99-1.48) for milk, 1.09 (95% CI, 0.88-1.34) for yoghurt, and 0.93 (95% CI, 0.76-1.14) for cheese. The intake of dietary calcium was not associated with the risk of colorectal cancer-specific death (adjusted HR Q4 vs. Q1, 1.01; 95% CI, 0.81-1.26) nor that of all-cause death (Q4 vs. Q1, 1.01; 95% CI, 0.84-1.21). The prediagnostic reported intake of dairy products and dietary calcium is not associated with disease-specific or all-cause risk of death in patients diagnosed with colorectal cancer. The impact of diet on cancer survival is largely unknown. This study shows that despite its inverse association with colorectal cancer risk, the prediagnostic intake of dairy and dietary calcium does not affect colorectal cancer survival. ©2014 American Association for Cancer Research.

Combined high-intensity local treatment and systemic therapy in metastatic head and neck squamous cell carcinoma: An analysis of the National Cancer Data Base.

PubMed

Zumsteg, Zachary S; Luu, Michael; Yoshida, Emi J; Kim, Sungjin; Tighiouart, Mourad; David, John M; Shiao, Stephen L; Mita, Alain C; Scher, Kevin S; Sherman, Eric J; Lee, Nancy Y; Ho, Allen S

2017-12-01

There is increasing evidence that primary tumor ablation can improve survival for some cancer patients with distant metastases. This may be particularly applicable to head and neck squamous cell carcinoma (HNSCC) because of its tropism for locoregional progression. This study included patients with metastatic HNSCC undergoing systemic therapy identified in the National Cancer Data Base. High-intensity local treatment was defined as radiation doses ≥ 60 Gy or oncologic resection of the primary tumor. Multivariate Cox regression, propensity score matching, landmark analysis, and subgroup analysis were performed to account for imbalances in covariates, including adjustments for the number and location of metastatic sites in the subset of patients with this information available. In all, 3269 patients were included (median follow-up, 51.5 months). Patients undergoing systemic therapy with local treatment had improved survival in comparison with patients receiving systemic therapy alone in propensity score-matched cohorts (2-year overall survival, 34.2% vs 20.6%; P < .001). Improved survival was associated only with patients receiving high-intensity local treatment, whereas those receiving lower-intensity local treatment had survival similar to that of patients receiving systemic therapy without local treatment. The impact of high-intensity local therapy was time-dependent, with a stronger impact within the first 6 months after the diagnosis (adjusted hazard ratio [AHR], 0.255; 95% confidence interval [CI], 0.210-0.309; P < .001) in comparison with more than 6 months after the diagnosis (AHR, 0.622; 95% CI, 0.561-0.689; P < .001) in the multivariate analysis. A benefit was seen in all subgroups, in landmark analyses of 1-, 2-, and 3-year survivors, and when adjusting for the number and location of metastatic sites. Aggressive local treatment warrants prospective evaluation for select patients with metastatic HNSCC. Cancer 2017;123:4583-4593. © 2017 American Cancer Society. © 2017 American Cancer Society.

Dietary patterns and risk of death and progression to ESRD in individuals with CKD: a cohort study.

PubMed

Gutiérrez, Orlando M; Muntner, Paul; Rizk, Dana V; McClellan, William M; Warnock, David G; Newby, P K; Judd, Suzanne E

2014-08-01

Nutrition is linked strongly with health outcomes in chronic kidney disease (CKD). However, few studies have examined relationships between dietary patterns and health outcomes in persons with CKD. Observational cohort study. 3,972 participants with CKD (defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 or albumin-creatinine ratio ≥ 30 mg/g at baseline) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, a prospective cohort study of 30,239 black and white adults at least 45 years of age. 5 empirically derived dietary patterns identified by factor analysis: "convenience" (Chinese and Mexican foods, pizza, and other mixed dishes), "plant-based" (fruits and vegetables), "sweets/fats" (sugary foods), "Southern" (fried foods, organ meats, and sweetened beverages), and "alcohol/salads" (alcohol, green-leafy vegetables, and salad dressing). All-cause mortality and end-stage renal disease (ESRD). 816 deaths and 141 ESRD events were observed over approximately 6 years of follow-up. There were no statistically significant associations of convenience, sweets/fats, or alcohol/salads pattern scores with all-cause mortality after multivariable adjustment. In Cox regression models adjusted for sociodemographic factors, energy intake, comorbid conditions, and baseline kidney function, higher plant-based pattern scores (indicating greater consistency with the pattern) were associated with lower risk of mortality (HR comparing fourth to first quartile, 0.77; 95% CI, 0.61-0.97), whereas higher Southern pattern scores were associated with greater risk of mortality (HR comparing fourth to first quartile, 1.51; 95% CI, 1.19-1.92). There were no associations of dietary patterns with incident ESRD in multivariable-adjusted models. Missing dietary pattern data, potential residual confounding from lifestyle factors. A Southern dietary pattern rich in processed and fried foods was associated independently with mortality in persons with CKD. In contrast, a diet rich in fruits and vegetables appeared to be protective. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Hepatocellular Carcinoma Screening Associated with Early Tumor Detection and Improved Survival Among Patients with Cirrhosis in the US.

PubMed

Singal, Amit G; Mittal, Sahil; Yerokun, Olutola A; Ahn, Chul; Marrero, Jorge A; Yopp, Adam C; Parikh, Neehar D; Scaglione, Steve J

2017-09-01

Professional societies recommend hepatocellular carcinoma screening in patients with cirrhosis, but high-quality data evaluating its effectiveness to improve early tumor detection and survival in "real world" clinical practice are needed. We aim to characterize the association between hepatocellular carcinoma screening and early tumor detection, curative treatment, and overall survival among patients with cirrhosis. We performed a retrospective cohort study of patients diagnosed with hepatocellular carcinoma between June 2012 and May 2013 at 4 health systems in the US. Patients were categorized in the screening group if hepatocellular carcinoma was detected by imaging performed for screening purposes. Generalized linear models and multivariate Cox regression with frailty adjustment were used to compare early detection, curative treatment, and survival between screen-detected and non-screen-detected patients. Among 374 hepatocellular carcinoma patients, 42% (n = 157) were detected by screening. Screen-detected patients had a significantly higher proportion of early tumors (Barcelona Clinic Liver Cancer stage A 63.1% vs 36.4%, P <.001) and were more likely to undergo curative treatment (31% vs 13%, P = .02). Hepatocellular carcinoma screening was significantly associated with improved survival in multivariate analysis (hazards ratio 0.41; 95% confidence interval, 0.26-0.65) after adjusting for patient demographics, Child-Pugh class, and performance status. Median survival of screen-detected patients was 14.6 months, compared with 6.0 months for non-screen-detected patients, with the difference remaining significant after adjusting for lead-time bias (hazards ratio 0.59, 95% confidence interval, 0.37-0.93). Hepatocellular carcinoma screening is associated with increased early tumor detection and improved survival; however, a minority of hepatocellular carcinoma patients are detected by screening. Interventions to increase screening use in patients with cirrhosis may help curb hepatocellular carcinoma mortality rates. Copyright © 2017 Elsevier Inc. All rights reserved.

Anxiety, Depression, and Adverse Clinical Outcomes in Patients With Atrial Fibrillation Starting Warfarin: Cardiovascular Research Network WAVE Study.

PubMed

Baumgartner, Christine; Fan, Dongjie; Fang, Margaret C; Singer, Daniel E; Witt, Daniel M; Schmelzer, John R; Williams, Marc S; Gurwitz, Jerry H; Sung, Sue Hee; Go, Alan S

2018-04-14

Anxiety and depression are associated with worse outcomes in several cardiovascular conditions, but it is unclear whether they affect outcomes in atrial fibrillation (AF). In a large diverse population of adults with AF, we evaluated the association of diagnosed anxiety and/or depression with stroke and bleeding outcomes. The Cardiovascular Research Network WAVE (Community-Based Control and Persistence of Warfarin Therapy and Associated Rates and Predictors of Adverse Clinical Events in Atrial Fibrillation and Venous Thromboembolism) Study included adults with AF newly starting warfarin between 2004 and 2007 within 5 health delivery systems in the United States. Diagnosed anxiety and depression and other patient characteristics were identified from electronic health records. We identified stroke and bleeding outcomes from hospitalization databases using validated International Classification of Diseases, Ninth Revision ( ICD-9 ), codes. We used multivariable Cox regression to assess the relation between anxiety and/or depression with outcomes after adjustment for stroke and bleeding risk factors. In 25 570 adults with AF initiating warfarin, 490 had an ischemic stroke or intracranial hemorrhage (1.52 events per 100 person-years). In multivariable analyses, diagnosed anxiety was associated with a higher adjusted rate of combined ischemic stroke and intracranial hemorrhage (hazard ratio, 1.52; 95% confidence interval, 1.01-2.28). Results were not materially changed after additional adjustment for patient-level percentage of time in therapeutic anticoagulation range on warfarin (hazard ratio, 1.56; 95% confidence interval, 1.03-2.36). In contrast, neither isolated depression nor combined depression and anxiety were significantly associated with outcomes. Diagnosed anxiety was independently associated with increased risk of combined ischemic stroke and intracranial hemorrhage in adults with AF initiating warfarin that was not explained by differences in risk factors or achieved anticoagulation quality. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Egg consumption and risk of type 2 diabetes among African Americans: The Jackson Heart Study

PubMed Central

Djoussé, Luc; Petrone, Andrew B; Hickson, DeMarc A; Talegawkar, Sameera A.; Dubbert, Patricia M; Taylor, Herman; Tucker, Katherine L

2015-01-01

Background and Aims Type 2 diabetes (DM) disproportionally affects African Americans. Data on the association between egg consumption and risk of DM are sparse. We sought to examine whether egg consumption is associated with the prevalence and incidence of DM among African Americans. Methods We analyzed baseline data from 4,568 participants of the Jackson Heart Study. Egg consumption was obtained using a food frequency questionnaire designed for this population. We used generalized estimating equations to calculate adjusted prevalence ratios of DM and Cox regression to estimate hazard ratios of DM with corresponding 95% confidence intervals (CI). Results The average age was 55±13 years and 64% of subjects were women. The median frequency of egg consumption was 2/week for men and 1/week for women. The prevalence of DM was 22% overall (21% of men and 23% of women). Multivariable adjusted prevalence ratio [PR(95% CI)] for DM were: 1.00 (ref), 1.14 (0.90–1.44), 1.33 (1.04–1.70), 1.33 (1.06–1.68), 1.26 (0.99–1.61), and 1.52 (1.17–1.97) for egg consumption of <1/month, 1–3/month, 1/week, 2/week, 3–4/week, and 5+/week, respectively, p for linear trend 0.0024. Corresponding multivariable adjusted hazard ratios were 1.00 (ref), 0.88 (0.65–1.19), 0.94 (0.68–1.30), 0.91 (0.66–1.25), 1.11 (0.81–1.52), and 1.17 (0.81–1.70), respectively, during a mean follow up of 7.3 years (p for linear trend 0.22). Conclusions While egg consumption was positively associated with prevalent DM, prospective analysis did not show an association of egg intake with incidence of DM among African Americans. PMID:25971658

A Population-Based Observational Study of First-Course Treatment and Survival for Adolescent and Young Adult Females with Breast Cancer

PubMed Central

DeRouen, Mindy C.; Gomez, Scarlett L.; Press, David J.; Tao, Li; Kurian, Allison W.

2013-01-01

Purpose Young age at breast cancer diagnosis is associated with poor survival. However, little is known about factors associated with first-course treatment receipt or survival among adolescent and young adult (AYA) females aged 15–39 years. Methods Data regarding 19,906 eligible AYA breast cancers diagnosed in California during 1992–2009 were obtained from the population-based California Cancer Registry. Multivariable logistic regression was used to evaluate clinical and sociodemographic differences in treatment receipt. Multivariable Cox proportional hazards regression was used to examine differences in survival by initial treatment, and by patient and tumor characteristics. Results Black and Hispanic AYAs diagnosed with in situ or stages I–III breast cancer were more likely than White AYAs to receive breast-conserving surgery (BCS) without radiation; Asian and Hispanic AYAs were more likely than Whites to receive mastectomy. Women in lower socioeconomic status (SES) neighborhoods were more likely to omit radiation after BCS, more likely to receive mastectomy, and less likely to receive chemotherapy, compared to those in higher SES neighborhoods. Among patients with invasive disease, survival improved an average of 5% per year during 1992–2009. AYAs who received BCS with radiation experienced better survival than other surgery/radiation options. Black AYAs had poorer survival than Whites. AYAs who resided in higher SES neighborhoods had better survival. Conclusions Treatment receipt among AYAs with breast cancer varied by race/ethnicity and neighborhood SES. Poor survival for Black AYAs and AYAs living in low SES neighborhoods in models adjusted for treatment receipt suggests that factors other than treatment may also be important to disease outcome. PMID:24066271

Dietary Sodium Consumption Predicts Future Blood Pressure and Incident Hypertension in the Japanese Normotensive General Population.

PubMed

Takase, Hiroyuki; Sugiura, Tomonori; Kimura, Genjiro; Ohte, Nobuyuki; Dohi, Yasuaki

2015-07-29

Although there is a close relationship between dietary sodium and hypertension, the concept that persons with relatively high dietary sodium are at increased risk of developing hypertension compared with those with relatively low dietary sodium has not been studied intensively in a cohort. We conducted an observational study to investigate whether dietary sodium intake predicts future blood pressure and the onset of hypertension in the general population. Individual sodium intake was estimated by calculating 24-hour urinary sodium excretion from spot urine in 4523 normotensive participants who visited our hospital for a health checkup. After a baseline examination, they were followed for a median of 1143 days, with the end point being development of hypertension. During the follow-up period, hypertension developed in 1027 participants (22.7%). The risk of developing hypertension was higher in those with higher rather than lower sodium intake (hazard ratio 1.25, 95% CI 1.04 to 1.50). In multivariate Cox proportional hazards regression analysis, baseline sodium intake and the yearly change in sodium intake during the follow-up period (as continuous variables) correlated with the incidence of hypertension. Furthermore, both the yearly increase in sodium intake and baseline sodium intake showed significant correlations with the yearly increase in systolic blood pressure in multivariate regression analysis after adjustment for possible risk factors. Both relatively high levels of dietary sodium intake and gradual increases in dietary sodium are associated with future increases in blood pressure and the incidence of hypertension in the Japanese general population. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Cytologic anaplasia is a prognostic factor in osteosarcoma biopsies, but mitotic rate or extent of spontaneous tumor necrosis are not: a critique of the College of American Pathologists Bone Biopsy template.

PubMed

Cates, Justin Mm; Dupont, William D

2017-01-01

The current College of American Pathologists cancer template for reporting biopsies of bone tumors recommends including information that is of unproven prognostic significance for osteosarcoma, such as the presence of spontaneous tumor necrosis and mitotic rate. Conversely, the degree of cytologic anaplasia (degree of differentiation) is not reported in this template. This retrospective cohort study of 125 patients with high-grade osteosarcoma was performed to evaluate the prognostic impact of these factors in diagnostic biopsy specimens in predicting the clinical outcome and response to neoadjuvant chemotherapy. Multivariate Cox regression was performed to adjust survival analyses for well-established prognostic factors. Multivariate logistic regression was used to determine odds ratios for good chemotherapy response (≥90% tumor necrosis). Osteosarcomas with severe anaplasia were independently associated with increased overall and disease-free survival, but mitotic rate and spontaneous necrosis had no prognostic impact after controlling for other confounding factors. Mitotic rate showed a trend towards increased odds of a good histologic response, but this effect was diminished after controlling for other predictive factors. Neither spontaneous necrosis nor the degree of cytologic anaplasia observed in biopsy specimens was predictive of a good response to chemotherapy. Mitotic rate and spontaneous tumor necrosis observed in pretreatment biopsy specimens of high-grade osteosarcoma are not strong independent prognostic factors for clinical outcome or predictors of response to neoadjuvant chemotherapy. Therefore, reporting these parameters for osteosarcoma, as recommended in the College of American Pathologists Bone Biopsy template, does not appear to have clinical utility. In contrast, histologic grading schemes for osteosarcoma based on the degree of cytologic anaplasia may have independent prognostic value and should continue to be evaluated.

Surveillance and Radiation Therapy for Stage I Seminoma—Have We Learned From the Evidence?

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

Glaser, Scott M.; Vargo, John A.; Balasubramani, Goundappa K.

2016-01-01

Purpose: To analyze, in the setting of stage I seminoma, the factors affecting adjuvant treatment decisions and resulting survival outcomes, using a national dataset. Methods and Materials: We identified 33,094 stage I seminoma patients after orchiectomy from 1998 to 2012 from the National Cancer Data Base. Factors affecting treatment selection (active surveillance [AS] vs adjuvant treatment [AT]) were identified using a parsimonious multivariate logistic regression model. Propensity scores for treatment decision were generated and incorporated into a multivariate Cox regression analysis of overall survival. This process was then repeated within the AT cohort for factors predictive for chemotherapy [CT] versus radiationmore » therapy [RT]. Results: Only 33% of patients received AS, and 65% received AT (89% RT and 11% CT). From 1998 to 2012 the proportion receiving AS increased from 23% to 60%, whereas RT utilization decreased from 73% to 21%, and CT utilization increased from 2% to 17%. Utilization of low-dose RT increased from 1.5% in 1999 to 34% in 2012. There was a small absolute overall survival advantage to AT over AS at 10 years (95.0% vs 93.4%, propensity adjusted hazard ratio 0.58, P<.0005). Conclusions: There has been a significant increase in use of AS for stage I seminoma, influenced by both sociodemogrpahic and clinicopathologic factors. Between AT options, there has been significant increase in use of CT, mirrored by a decline in use of RT. Although overall survival remains high for all 3 treatment strategies, AT seems to be associated with a small absolute survival advantage over AS up to 10 years out from diagnosis.« less

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.

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.

Nutritional variables predict chances of returning home and activities of daily living in post-acute geriatric care

PubMed Central

Maeda, Keisuke; Koga, Takayuki; Akagi, Junji

2018-01-01

Background Little is known about the association between malnutrition and the chances of returning home from post-acute facilities in older adult patients. This study aimed to understand whether malnutrition and malnutrition-related factors would be determinants for returning home and activities of daily living (ADL) at discharge after post-acute care. Methods Patients aged ≥65 years living at home before the onset of an acute disease and admitted to a post-acute ward were enrolled (n=207) in this prospective observational study. Malnutrition was defined based on the criteria of the European Society for Clinical Nutrition and Metabolism. Nutritional parameters included the nutritional intake at the time of admission and oral conditions evaluated by the Oral Health Assessment Tool (OHAT). The Barthel Index was used to assess daily activities. A Cox regression analysis of the length of stay was performed. Multivariable linear regression analyses to determine associations between malnutrition, returning home, and ADL at discharge were performed, after adjusting the variables of acute care setting. Results The mean patient age was 84.7±6.7 years; 38% were men. European Society for Clinical Nutrition and Metabolism-defined malnutrition was observed in 129 (62.3%) patients, and 118 (57.0%) of all patients returned home. Multivariable regression analyses showed that malnutrition was a negative predictor of returning home (hazard ratio: 0.517 [0.351–0.761], p=0.001), and an increase in the nutritional intake (kcal/kg/d) was a positive predictor of the Barthel Index at discharge (coefficient: 0.34±0.15, p=0.021). The OHAT was not associated with returning home and ADL. Conclusion Malnutrition and nutritional intake are associated with returning home and ADL at discharge, respectively, after post-acute care. Further studies investigating the effects of a nutritional intervention for post-acute patients would be necessary. PMID:29416323

Impact of extent of resection and recurrent surgery on clinical outcome and overall survival in a consecutive series of 170 patients for glioblastoma in intraoperative high field magnetic resonance imaging.

PubMed

Coburger, Jan; Wirtz, Christian R; König, Ralph W

2017-06-01

In patients with a glioblastoma (GBM), few unselected data exists using actual standard adjuvant treatment and contemporary surgical techniques like iMRI. Aim of study is to assess impact of EoR and recurrent surgery on survival and outcome. We assessed a consecutive unselected series of 170 surgeries for GBM (2008-2014) applying intraoperative MRI (iMRI). All patients received adjuvant radio-chemo-therapy. Overall-survival (OS), progression free survival (PFS), complications and new permanent neurological deficits (nPND) were assessed. Uni- and multivariate-cox-regression-models were calculated. Mean follow-up was 40mo. GTR was intended in 82% and achieved in 77% of these cases. A nPND was found in 7% of patients. In multivariate cox-regression, GTR (HR:0.6, P<0.024) and absence of MGMT methylation (HR:1.6, P<0.042) was significantly associated with PFS. We found no difference in PFS after primary surgery and recurrent surgery. Concerning OS, in multivariate assessment an un-methylated MGMT-promotor (HR2.0, P<0.01) and presence of a complication (HR1.7, P<0.06) were negative prognosticators. Only GTR was significantly beneficial for OS (HR0.4, P<0.028) compared to a failed GTR and a STR. Repeated surgery for recurrent disease was positively associated with OS (HR0.6, P<0.06). Surgery in a contemporary setup using iMRI, brain mapping and modern adjuvant treatment, has a higher OS and lower complication rates as previously published. A maximum but safe resection should be the goal of surgery since a perioperative complication significantly decreases OS. Recurrent surgery has a beneficial effect on OS without an increase of complications.

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

PubMed

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

2015-05-01

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

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

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.

Survival in Alzheimer disease

PubMed Central

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

2008-01-01

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

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.

Association of computed tomography-derived left ventricular size with major cardiovascular events in the general population: the Heinz Nixdorf recall study.

PubMed

Dykun, Iryna; Geisel, Marie H; Kälsch, Hagen; Lehmann, Nils; Bauer, Marcus; Moebus, Susanne; Jöckel, Karl-Heinz; Möhlenkamp, Stefan; Erbel, Raimund; Mahabadi, Amir A

2015-05-01

To investigate the relationship between LV size as determined by non-contrast enhanced cardiac CT with incident cardiovascular disease in the general population free of clinical cardiovascular disease. LV axial area was quantified from non-contrast CT in axial, end-diastolic images at a mid-ventricular slice in participants from the population-based Heinz Nixdorf recall study, free of cardiovascular disease (n=3926, 59±8years, 53%female). LV size index (LVI) was defined as the quotient of LV area and body surface area. Major CV events (coronary events, stroke, CV death) were assessed during follow-up. Association of LVI with events was assessed using Cox regression analysis in unadjusted and multivariable adjusted models. During 8.0±1.5years of follow-up, 219 subjects developed a major CV event. Those with events had larger LVI at baseline (2258±352 vs. 2149±276 mm2/m2, p<0.0001). In univariate analysis, increase of LVI by 1 standard deviation was associated with 40% higher risk of events (HR(95%CI):1.41(1.26-1.59), p<0.0001). Associations remained statistically significant after adjustment for CV risk factors (1.24(1.10-1.40), p=0.0007) and when further adjusting for CAC (1.21(1.07-1.37), p=0.003). There was a trend towards stronger association for subjects with low CAC-score (CAC<100:1.41(1.16-1.71), p=0.0005, CAC≥100:1.24(1.06-1.44), p=0.006) in univariate analysis which persisted after multivariable adjustment (CAC<100: 1.41(1.14-1.73), p=0.001, CAC≥100: 1.12(0.96-1.31), p=0.16). CT-derived LV size is associated with incident major CV events independent of traditional risk factors and CAC-score in a population-based cohort and may improve the prediction of hard events especially in subjects with low CAC-scores. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The Number of Recalled Leads is Highly Predictive of Lead Failure: Results From the Pacemaker and Implantable Defibrillator Leads Survival Study ("PAIDLESS").

PubMed

Kersten, Daniel J; Yi, Jinju; Feldman, Alyssa M; Brahmbhatt, Kunal; Asheld, Wilbur J; Germano, Joseph; Islam, Shahidul; Cohen, Todd J

2016-12-01

The purpose of this study was to determine if implantation of multiple recalled defibrillator leads is associated with an increased risk of lead failure. The authors of the Pacemaker and Implantable Defibrillator Leads Survival Study ("PAIDLESS") have previously reported a relationship between recalled lead status, lead failure, and patient mortality. This substudy analyzes the relationship in a smaller subset of patients who received more than one recalled lead. The specific effects of having one or more recalled leads have not been previously examined. This study analyzed lead failure and mortality of 3802 patients in PAIDLESS and compared outcomes with respect to the number of recalled leads received. PAIDLESS includes all patients at Winthrop University Hospital who underwent defibrillator lead implantation between February 1, 1996 and December 31, 2011. Patients with no recalled ICD leads, one recalled ICD lead, and two recalled ICD leads were compared using the Kaplan-Meier method and log-rank test. Sidak adjustment method was used to correct for multiple comparisons. All calculations were performed using SAS 9.4. P-values <.05 were considered statistically significant. This study included 4078 total ICD leads implanted during the trial period. There were 2400 leads (59%) in the no recalled leads category, 1620 leads (40%) in the one recalled lead category, and 58 leads (1%) in the two recalled leads category. No patient received more than two recalled leads. Of the leads categorized in the two recalled leads group, 12 experienced lead failures (21%), which was significantly higher (P<.001) than in the no recalled leads group (60 failures, 2.5%) and one recalled lead group (81 failures; 5%). Multivariable Cox's regression analysis found a total of six significant predictive variables for lead failure including the number of recalled leads (P<.001 for one and two recalled leads group). The number of recalled leads is highly predictive of lead failure. Lead-based multivariable Cox's regression analysis produced a total of six predictive variable categories for lead failure, one of which was the number of recalled leads. Kaplan-Meier analysis showed that the leads in the two recalled leads category failed faster than both the no recalled lead and one recalled lead groups. The greater the number of recalled leads to which patients are exposed, the greater the risk of lead failure.

Very High-Risk Localized Prostate Cancer: Outcomes Following Definitive Radiation

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

Narang, Amol K.; Gergis, Carol; Robertson, Scott P.

Purpose: Existing definitions of high-risk prostate cancer consist of men who experience significant heterogeneity in outcomes. As such, criteria that identify a subpopulation of National Comprehensive Cancer Network (NCCN) high-risk prostate cancer patients who are at very high risk (VHR) for poor survival outcomes following prostatectomy were recently developed at our institution and include the presence of any of the following disease characteristics: multiple NCCN high-risk factors, primary Gleason pattern 5 disease and/or ≥5 biopsy cores with Gleason sums of 8 to 10. Whether these criteria also apply to men undergoing definitive radiation is unclear, as is the optimal treatment regimenmore » in these patients. Methods and Materials: All men consecutively treated with definitive radiation by a single provider from 1993 to 2006 and who fulfilled criteria for NCCN high-risk disease were identified (n=288), including 99 patients (34%) with VHR disease. Multivariate-adjusted competing risk regression models were constructed to assess associations between the VHR definition and biochemical failure (BF), distant metastasis (DM), and prostate cancer–specific mortality (PCSM). Multivariate-adjusted Cox regression analysis assessed the association of the VHR definition with overall mortality (OM). Cumulative incidences of failure endpoints were compared between VHR men and other NCCN high-risk men. Results: Men with VHR disease compared to other NCCN high-risk men experienced a higher 10-year incidence of BF (54.0% vs 35.4%, respectively, P<.001), DM (34.9% vs 13.4%, respectively, P<.001), PCSM (18.5% vs 5.9%, respectively, P<.001), and OM (36.4% vs 27.0%, respectively, P=.04). VHR men with a detectable prostate-specific antigen (PSA) concentration at the end of radiation (EOR) remained at high risk of 10-year PCSM compared to VHR men with an undetectable EOR PSA (31.0% vs 13.7%, respectively, P=.05). Conclusions: NCCN high-risk prostate cancer patients who meet VHR criteria experience distinctly worse outcomes following definitive radiation and long-term androgen deprivation therapy, particularly if an EOR PSA is detectable. Optimal use of local therapies for VHR patients should be explored further, as should novel agents.« less

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

PubMed

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

2011-08-01

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

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.

Risk of acute myocardial infarction in upper tract urothelial carcinoma patients receiving radical nephroureterectomy: a population-based cohort study

PubMed Central

Lin, Shih-Yi; Lin, Cheng-Li; Chang, Chao-Hsiang; Wu, His-Chin; Wang, I-Kuan; Chou, Che-Yi; Liang, Ji-An

2017-01-01

Background The outcomes of upper tract urothelial carcinoma (UTUC) receiving radical nephroureterectomy were usually limited to small sample size, case-control studies, and often focused on cancer progression. Risk of acute myocardial infarction (AMI) in these patients was never investigated. Results The overall incidences of AMI were 3.39, 1.44, and 1.70 per 10,000 person-years in the radical nephroureterectomy, nonnephroureterectomy, and non-UTUC cohorts, respectively. Multivariable Cox proportional hazard regression analysis revealed a significantly higher AMI risk in the radical nephroureterectomy cohort [adjusted HR (aHR) = 1.83, 95% confidence interval (CI) = 1.08–3.11], compared with non-UTUC cohorts. The risk of mortality were the highest in patients with UTUC who had undergone radical nephroureterectomy [adjusted HR (aHR) = 5.37, 95% confidence interval (CI) = 4.80–6.02]. Materials and Methods From the Taiwan National Health Insurance claims data, 1,359 patients with UTUC who had undergone radical nephroureterectomy and 3,154 patients with UTUC who had undergone nephron sparing surgery and were newly diagnosed between 2000 and 2010 were identified. For each patient, 4 individuals without UTUC were randomly selected and frequency matched by age, sex, and diagnosis year. Conclusions Patients with UTUC who have undergone radical nephroureterectomy are at a higher risk of developing AMI, compared with those receiving nephron sparing surgery. PMID:29108329

Soy food and isoflavone intake and endometrial cancer risk: the Japan Public Health Center-based prospective study.

PubMed

Budhathoki, S; Iwasaki, M; Sawada, N; Yamaji, T; Shimazu, T; Sasazuki, S; Inoue, M; Tsugane, S

2015-02-01

Compared with western populations, the consumption of soy foods among Japanese is very high and the incidence of endometrial cancer very low. We evaluated the association of soy food and isoflavone intake with endometrial cancer risk in Japanese women. Prospective cohort study. Ten public health centre areas in Japan. Forty nine thousand one hundred and twenty-one women of age 45-74 years who responded to a 5-year follow-up survey questionnaire. Intakes of soy foods as well as other covariates were assessed in 1995-1998 by a self-administered food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Incidence of endometrial cancer. During an average of 12.1 years of follow up, 112 newly diagnosed endometrial cancer cases were identified. Energy-adjusted intakes of soy food and isoflavone were not associated with the risk of endometrial cancer. The multivariate-adjusted HR per 25 g/day increase in the intake of soy food was 1.02 (95% CI 0.94-1.10), and the corresponding value for isoflavone intake per 15 mg/day was 1.01 (95% CI 0.84-1.22). In this population-based prospective cohort study of Japanese women, we observed no evidence of a protective association between soy food or isoflavone intake and endometrial cancer risk. © 2014 Royal College of Obstetricians and Gynaecologists.

Usefulness of the d-ROMs test for prediction of cardiovascular events.

PubMed

Masaki, Nobuyuki; Sato, Atsushi; Horii, Syumpei; Kimura, Toyokazu; Toya, Takumi; Yasuda, Risako; Namba, Takayuki; Yada, Hirotaka; Kawamura, Akio; Adachi, Takeshi

2016-11-01

d-ROMs test developed to determine the degree of individual oxidative stress may predict cardiovascular events. 265 patients (204 men, 61 women; age, 65±13years) who had been treated for cardiovascular disease were divided evenly by quartile of baseline d-ROMs levels, and were followed up. During the observation periods of 2.66±1.47years, there were 14 (5%) deaths, 8 (3%) cardiovascular deaths, 13 (5%) major adverse cardiovascular events (MACEs), and 51 (19%) all cardiovascular events including heart failure, cardiovascular surgery, and revascularization. Log-rank tests demonstrated that the patients in the 4th quartile (d-ROMs≧395.00U.CARR) had a higher incidence rate of cardiovascular death than those in the 2nd quartile (d-ROMs 286.00-335.00, p=0.022). In multivariate Cox regression analysis, even after adjustment for age, sex, coronary risk factors, C-reactive protein, and renal function, high d-ROMs was a risk factor for all-cause death [adjusted HR of 4th vs. 1st quartile, 10.791 (95% confidence interval 1.032-112.805), p=0.047], and all cardiovascular events [HR of 4th vs. 1st quartile, 2.651 (95% confidence interval 1.138-6.177), p=0.024]. Our results suggest that d-ROMs is a useful oxidative stress marker to assess prognosis and risk of further cardiovascular events. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Weight Cycling and Cancer Incidence in a Large Prospective US Cohort

PubMed Central

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

2015-01-01

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

Primary surgery versus primary radiation-based treatment for locally advanced oropharyngeal cancer.

PubMed

Kamran, Sophia C; Qureshi, Muhammad M; Jalisi, Scharukh; Salama, Andrew; Grillone, Gregory; Truong, Minh Tam

2018-06-01

Randomized data comparing surgery to radiation for locally advanced oropharyngeal cancer (OPC) are lacking. This study evaluated practice patterns and overall survival outcomes from the National Cancer Database. A total of 22,676 patients with stage III to IV, locally advanced OPC were treated between 2004 to 2013 with primary chemoradiation (CRT) or surgery with adjuvant radiotherapy with or without chemotherapy (aRT ± CT). Survival rates were estimated using the Kaplan-Meier method. Crude and adjusted hazard ratios (HR) were computed using Cox regression modeling. Median follow-up was 40.7 months; 8,555 and 14,121 patients received surgery with aRT ± CT and CRT, respectively. Corresponding 3-year survival was 85.4% and 72.6% (P < 0.0001). On multivariate analysis, adjusting for age, gender, race insurance status, median income, percentage with no high-school degree, Charlson-Deyo score, clinical tumor and node stage, tumor grade, facility type, treatment at > 1 facility, and human papillomavirus (HPV) status, surgery with aRT ± CT had a reduced hazard of death, HR, 0.79 (95% confidence interval 0.69-0.91), P = 0.001. Primary surgery with aRT ± CT for locally advanced OPC has an improved survival compared to primary radiation-based treatment even when stratified by HPV status. 2c. Laryngoscope, 128:1353-1364, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Accelerated death rate in population-based cohort of persons with traumatic brain injury.

PubMed

Selassie, Anbesaw W; Cao, Yue; Church, Elizabeth C; Saunders, Lee L; Krause, James

2014-01-01

To determine the influence of preexisting heart, liver, kidney, cancer, stroke, and mental health problems and examine the influence of low socioeconomic status on mortality after discharge from acute care facilities for individuals with traumatic brain injury. Population-based retrospective cohort study of 33695 persons discharged from acute care hospital with traumatic brain injury in South Carolina, 1999-2010. Days elapsing from the dates of injury to death established the survival time (T). Data were censored at the 145th month. Multivariable Cox regression was used to examine the independent effect of the variables on death. Age-adjusted cumulative probability of death for each chronic disease of interest was plotted. By the 70th month of follow-up, rate of death was accelerated from 10-fold for heart diseases to 2.5-fold for mental health problems. Adjusted hazard ratios for diseases of the heart (2.13), liver-renal (3.25), cancer (2.64), neurological diseases and stroke (2.07), diabetes (1.89), hypertension (1.43), and mental health problems (1.59) were highly significant (each with P < .001). Compared with persons with private insurance, the hazard ratio was significantly elevated with Medicaid (1.67), Medicare (1.54), and uninsured (1.27) (each with P < .001). Specific chronic diseases strongly influenced postdischarge mortality after traumatic brain injury. Low socioeconomic status as measured by the type of insurance elevated the risk of death.

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

Transplant center volume and outcomes in lung transplantation for cystic fibrosis.

PubMed

Hayes, Don; Sweet, Stuart C; Benden, Christian; Kopp, Benjamin T; Goldfarb, Samuel B; Visner, Gary A; Mallory, George B; Tobias, Joseph D; Tumin, Dmitry

2017-04-01

Transplant volume represents lung transplant (LTx) expertise and predicts outcomes, so we sought to determine outcomes related to center volumes in cystic fibrosis (CF). United Network for Organ Sharing data were queried for patients with CF in the United States (US) receiving bilateral LTx from 2005 to 2015. Multivariable Cox regression was used to model survival to 1 year and long-term (>1 year) survival, conditional on surviving at least 1 year. A total of 2025 patients and 67 centers were included in the analysis. The median annual LTx volumes were three in CF [interquartile range (IQR): 2, 6] and 17 in non-CF (IQR: 8, 33). Multivariable Cox regression in cases with complete data and surviving at least 1 year (n = 1510) demonstrated that greater annual CF LTx volume (HR per 10 LTx = 0.66; 95% CI: 0.49, 0.89; P = 0.006) but not greater non-CF LTx volume (HR = 1.00; 95% CI: 0.96, 1.05; P = 0.844) was associated with improved long-term survival in LTx recipients with CF. A Wald interaction test confirmed that CF LTx volume was more strongly associated with long-term outcomes than non-CF LTx volume (P = 0.012). In a US cohort, center volume was not associated with 1-year survival. CF-specific expertise predicted improved long-term outcomes of LTx for CF, whereas general LTx expertise was unassociated with CF patients' survival. © 2016 Steunstichting ESOT.

Perineural invasion is associated with increased relapse after external beam radiotherapy for men with low-risk prostate cancer and may be a marker for occult, high-grade cancer.

PubMed

Beard, C J; Chen, M H; Cote, K; Loffredo, M; Renshaw, A A; Hurwitz, M; D'Amico, A V

2004-01-01

To investigate the risk of postradiotherapy prostate-specific antigen (PSA) failure on the basis of pretreatment risk factors in prostate cancer patients with and without perineural invasion (PNI) in prostate biopsy specimens and to explain the observation that otherwise low-risk patients with PNI experience decreased freedom from PSA failure after external beam radiotherapy (RT). The study cohort consisted of 381 patients who underwent RT between 1989 and 2000 for clinically localized prostate cancer. A single genitourinary pathologist scored the absence or presence of PNI on all prostate biopsy specimens. Patients were divided into low-, intermediate- and high-risk subgroups on the basis of their 1992 American Joint Committee on Cancer T-stage, pretreatment PSA level, and Gleason score. Cox regression uni- and multivariate analyses were performed to evaluate whether the presence or absence of PNI in the biopsy specimen was a predictor of the time to post-RT PSA failure for patients in each pretreatment risk group. PSA failure was defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Actuarial PSA failure-free survival was estimated using the Kaplan-Meier method, and comparisons were performed using the log-rank test. Cox regression univariate analysis revealed that PNI was a significant predictor of the time to PSA failure in the low-risk (p = 0.04) and high-risk (p = 0.03) cohorts. The 5-year PSA failure-free survival rate was 50% vs. 80% (p = 0.04) in low-risk patients, 70% vs. 75% (p = 0.72) in intermediate-risk patients, and 29% vs. 53% (p = 0.03) in high-risk patients with and without PNI, respectively. Cox regression multivariate analysis within the high-risk group revealed that a PSA level > or =20 ng/mL (p = 0.01) and Gleason score > or =8 (p = 0.02), but not PNI, were the only significant predictors of the time to PSA failure after RT. However, an association was found between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 8-10 (p = 0.06). The association was stronger between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 7-10 (p = 0. 033). A decrement in PSA outcome after RT for low-risk patients with PNI-positive biopsy specimens was found. The association between PNI and high Gleason score provides a possible explanation for the loss of statistical significance of PNI in the Cox regression multivariate analysis of the high-risk cohort. The data suggest that PNI found in the biopsy specimen of an otherwise low-risk patient predicts for occult high-grade disease that is missed owing to the sampling error associated with prostate biopsy. The association between PNI and a high Gleason score argues for the use of more aggressive therapy, such as hormonal therapy with RT and/or dose escalation, in these select patients.

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.

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

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.

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.

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

Triglyceride and glucose (TyG) index as a predictor of incident hypertension: a 9-year longitudinal population-based study.

PubMed

Zheng, Rongjiong; Mao, Yushan

2017-09-13

Hypertension and the triglyceride and glucose index both have been associated with insulin resistance; however, the longitudinal association remains unclear. This study was designed to investigate the longitudinal association between the triglyceride and glucose index and incident hypertension among the Chinese population. We studied 4686 subjects (3177 males and 1509 females) and followed up for 9 years. The subjects were divided into four groups based on the triglyceride and glucose index. Univariate and multivariate Cox regression models were used to analyse the risk factors of hypertension. After 9 years of follow-up, 2047 subjects developed hypertension. The overall 9-year cumulative incidence of hypertension was 43.7%, ranging from 28.5% in quartile 1 to 36.9% in quartile 2, 49.2% in quartile 3 and 59.8% in quartile 4 (p for trend < 0.001). Cox regression analyses indicated that higher triglyceride and glucose index was associated with an increased risk of subsequent incident hypertension. The triglyceride and glucose index can predict the incident hypertension among the Chinese population.

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

A multivariate analysis of clinical and morphological prognostic factors in squamous cell carcinoma of the vulva.

PubMed

Smyczek-Gargya, B; Volz, B; Geppert, M; Dietl, J

1997-01-01

Clinical and histological data of 168 patients with squamous cell carcinoma of the vulva were analyzed with respect to survival. 151 patients underwent surgery, 12 patients were treated with primary radiation and in 5 patients no treatment was performed. Follow-up lasted from at least 2 up to 22 years' posttreatment. In univariate analysis, the following factors were highly significant: presurgery lymph node status, tumor infiltration beyond the vulva, tumor grading, histological inguinal lymph node status, pre- and postsurgery tumor stage, depth of invasion and tumor diameter. In the multivariate analysis (Cox regression), the most powerful factors were shown to be histological inguinal lymph node status, tumor diameter and tumor grading. The multivariate logistic regression analysis worked out as main prognostic factors for metastases of inguinal lymph nodes: presurgery inguinal lymph node status, tumor size, depth of invasion and tumor grading. Based on these results, tumor biology seems to be the decisive factor concerning recurrence and survival. Therefore, we suggest a more conservative treatment of vulvar carcinoma. Patients with confined carcinoma to the vulva, with a tumor diameter up to 3 cm and without clinical suspected lymph nodes, should be treated by wide excision/partial vulvectomy with ipsilateral lymphadenectomy.

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.

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.

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.

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.

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.

Lean body mass and risk of incident atrial fibrillation in post-menopausal women

PubMed Central

Azarbal, Farnaz; Stefanick, Marcia L.; Assimes, Themistocles L.; Manson, JoAnn E.; Bea, Jennifer W.; Li, Wenjun; Hlatky, Mark A.; Larson, Joseph C.; LeBlanc, Erin S.; Albert, Christine M.; Nassir, Rami; Martin, Lisa W.; Perez, Marco V.

2016-01-01

Aims High body mass index (BMI) is a risk factor for atrial fibrillation (AF). The aim of this study was to determine whether lean body mass (LBM) predicts AF. Methods and results The Women's Health Initiative is a study of post-menopausal women aged 50–79 enrolled at 40 US centres from 1994 to 1998. A subset of 11 393 participants at three centres underwent dual-energy X-ray absorptiometry. Baseline demographics and clinical histories were recorded. Incident AF was identified using hospitalization records and diagnostic codes from Medicare claims. A multivariable Cox hazard regression model adjusted for demographic and clinical risk factors was used to evaluate associations between components of body composition and AF risk. After exclusion for prevalent AF or incomplete data, 8832 participants with an average age of 63.3 years remained for analysis. Over the 11.6 years of average follow-up time, 1035 women developed incident AF. After covariate adjustment, all measures of LBM were independently associated with higher rates of AF: total LBM [hazard ratio (HR) 1.24 per 5 kg increase, 95% confidence intervals (CI) 1.14–1.34], central LBM (HR 1.51 per 5 kg increase, 95% CI 1.31–1.74), and peripheral LBM (HR 1.39 per 5 kg increase, 95% CI 1.19–1.63). The association between total LBM and AF remained significant after adjustment for total fat mass (HR 1.22 per 5 kg increase, 95% CI 1.13–1.31). Conclusion Greater LBM is a strong independent risk factor for AF. After adjusting for obesity-related risk factors, the risk of AF conferred by higher BMI is primarily driven by the association between LBM and AF. PMID:26371115

Non-recovery from dialysis-requiring acute kidney injury and short-term mortality and cardiovascular risk: a cohort study.

PubMed

Lee, Benjamin J; Hsu, Chi-Yuan; Parikh, Rishi V; Leong, Thomas K; Tan, Thida C; Walia, Sophia; Liu, Kathleen D; Hsu, Raymond K; Go, Alan S

2018-06-11

The high mortality and cardiovascular disease (CVD) burden in patients with end-stage renal disease (ESRD) is well-documented. Recent literature suggests that acute kidney injury is also associated with CVD. It is unknown whether patients with incident ESRD due to dialysis-requiring acute kidney injury (AKI-D) are at higher short-term risk for death and CVD events, compared with incident ESRD patients without preceding AKI-D. Few studies have examined the impact of recovery from AKI-D on subsequent CVD risk. In this retrospective cohort study, we evaluated adult members of Kaiser Permanente Northern California who initiated dialysis from January 2009 to September 2015. Preceding AKI-D and subsequent outcomes of death and CVD events (acute coronary syndrome, heart failure, ischemic stroke or transient ischemic attack) were identified from electronic health records. We performed multivariable Cox regression models adjusting for demographics, comorbidities, medication use, and laboratory results. Compared to incident ESRD patients who experienced AKI-D (n = 1865), patients with ESRD not due to AKI-D (n = 3772) had significantly lower adjusted rates of death (adjusted hazard ratio [aHR] 0.56, 95% CI: 0.47-0.67) and heart failure hospitalization (aHR 0.45, 0.30-0.70). Compared to AKI-D patients who did not recover and progressed to ESRD, AKI-D patients who recovered (n = 1347) had a 30% lower adjusted relative rate of death (aHR 0.70, 0.55-0.88). Patients who transition to ESRD via AKI-D are a high-risk subgroup that may benefit from aggressive monitoring and medical management, particularly for heart failure. Recovery from AKI-D is independently associated with lower short-term mortality.

Race and Survival Following Brachytherapy-Based Treatment for Men With Localized or Locally Advanced Adenocarcinoma of the Prostate

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

Winkfield, Karen M., E-mail: kwinkfield@partners.org; Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts; Chen Minghui

2011-11-15

Purpose: 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. Methods: 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, medianmore » income, and cardiovascular comorbidities. Results: 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). Conclusions: 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.« less

Impact of diabetes duration and chronic pancreatitis on the association between type 2 diabetes and pancreatic cancer risk.

PubMed

Brodovicz, K G; Kou, T D; Alexander, C M; O'Neill, E A; Engel, S S; Girman, C J; Goldstein, B J

2012-12-01

To examine the impact of diabetes duration, chronic pancreatitis and other factors on pancreatic cancer risk. This retrospective cohort study using the UK General Practice Research Database compared pancreatic cancer incidence and risk in patients with type 2 diabetes mellitus (T2DM) versus patients without diabetes. Multivariate Cox regression adjusting for age, sex, history of chronic pancreatitis, gallbladder disease, obesity, smoking and alcohol use and Charlson comorbidity index was used to estimate hazard ratio (HR) [95% confidence interval, CI]. Analyses were repeated using various time windows for diabetes duration. A total of 1903 incident pancreatic cancers were identified, 436 in patients with T2DM (78.76 per 100 000 person-years [95% CI: 71.54, 86.51]) and 1467 in patients without diabetes (11.46 per 100 000 person-years [10.88, 12.06]). Pancreatic cancer risk was significant for T2DM (adjusted HR 1.80 [1.52, 2.14]), increasing age, history of chronic pancreatitis and tobacco use. For patients with chronic pancreatitis and T2DM, the adjusted HR was 12.12 [6.02, 24.40]. Incidence was highest in patients with ≥5 year duration of T2DM. In patient populations with duration of T2DM ranging from ≥1 to ≥5 years, adjusted HRs remained significant but point estimates attenuated slightly with longer duration of T2DM. Patients with T2DM had an 80% increased risk of pancreatic cancer versus patients without diabetes. Patients with T2DM and chronic pancreatitis were 12 times more likely to develop pancreatic cancer. © 2012 Blackwell Publishing Ltd.

Recurrent Stroke in Minor Ischemic Stroke or Transient Ischemic Attack With Metabolic Syndrome and/or Diabetes Mellitus.

PubMed

Chen, Weiqi; Pan, Yuesong; Jing, Jing; Zhao, Xingquan; Liu, Liping; Meng, Xia; Wang, Yilong; Wang, Yongjun

2017-06-01

We aimed to determine the risk conferred by metabolic syndrome (METS) and diabetes mellitus (DM) to recurrent stroke in patients with minor ischemic stroke or transient ischemic attack from the CHANCE (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events) trial. In total, 3044 patients were included. Patients were stratified into 4 groups: neither, METS only, DM only, or both. METS was defined using the Chinese Diabetes Society (CDS) and International Diabetes Foundation (IDF) definitions. The primary outcome was new stroke (including ischemic and hemorrhagic) at 90 days. A multivariable Cox regression model was used to assess the relationship of METS and DM status to the risk of recurrent stroke adjusted for potential covariates. Using the CDS criteria of METS, 53.2%, 17.2%, 19.8%, and 9.8% of patients were diagnosed as neither, METS only, DM only, and both, respectively. After 90 days of follow-up, there were 299 new strokes (293 ischemic, 6 hemorrhagic). Patients with DM only (16.1% versus 6.8%; adjusted hazard ratio 2.50, 95% CI 1.89-3.39) and both (17.1% versus 6.8%; adjusted hazard ratio 2.76, 95% CI 1.98-3.86) had significantly increased rates of recurrent stroke. No interaction effect of antiplatelet therapy by different METS or DM status for the risk of recurrent stroke ( P =0.82 for interaction in the fully adjusted model of CDS) was observed. Using the METS (IDF) criteria demonstrated similar results. Concurrent METS and DM was associated with an increased risk of recurrent stroke in patients with minor stroke and transient ischemic attack. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Greater fluid overload and lower interdialytic weight gain are independently associated with mortality in a large international hemodialysis population.

PubMed

Hecking, Manfred; Moissl, Ulrich; Genser, Bernd; Rayner, Hugh; Dasgupta, Indranil; Stuard, Stefano; Stopper, Andrea; Chazot, Charles; Maddux, Franklin W; Canaud, Bernard; Port, Friedrich K; Zoccali, Carmine; Wabel, Peter

2018-04-20

Fluid overload and interdialytic weight gain (IDWG) are discrete components of the dynamic fluid balance in haemodialysis patients. We aimed to disentangle their relationship, and the prognostic importance of two clinically distinct, bioimpedance spectroscopy (BIS)-derived measures, pre-dialysis and post-dialysis fluid overload (FOpre and FOpost) versus IDWG. We conducted a retrospective cohort study on 38 614 incident patients with one or more BIS measurement within 90 days of haemodialysis initiation (1 October 2010 through 28 February 2015). We used fractional polynomial regression to determine the association pattern between FOpre, FOpost and IDWG, and multivariate adjusted Cox models with FO and/or IDWG as longitudinal and time-varying predictors to determine all-cause mortality risk. In analyses using 1-month averages, patients in quartiles 3 and 4 (Q3 and Q4) of FO had an incrementally higher adjusted mortality risk compared with reference Q2, and patients in Q1 of IDWG had higher adjusted mortality compared with Q2. The highest adjusted mortality risk was observed for patients in Q4 of FOpre combined with Q1 of IDWG [hazard ratio (HR) = 2.66 (95% confidence interval 2.21-3.20), compared with FOpre-Q2/IDWG-Q2 (reference)]. Using longitudinal means of FO and IDWG only slightly altered all HRs. IDWG associated positively with FOpre, but negatively with FOpost, suggesting a link with post-dialysis extracellular volume depletion. FOpre and FOpost were consistently positive risk factors for mortality. Low IDWG was associated with short-term mortality, suggesting perhaps an effect of protein-energy wasting. FOpost reflected the volume status without IDWG, which implies that this fluid marker is clinically most intuitive and may be best suited to guide volume management in haemodialysis patients.

Low Serum Magnesium and the Development of Atrial Fibrillation in the Community: The Framingham Heart Study

PubMed Central

Khan, Abigail May; Lubitz, Steven A.; Sullivan, Lisa M.; Sun, Jenny X.; Levy, Daniel; Vasan, Ramachandran S.; Magnani, Jared W.; Ellinor, Patrick T.; Benjamin, Emelia J.; Wang, Thomas J.

2012-01-01

Background Low serum magnesium has been linked to increased risk of atrial fibrillation (AF) following cardiac surgery. It is unknown whether hypomagnesemia predisposes to AF in the community. Methods and Results We studied 3,530 participants (mean age, 44 years; 52% women) from the Framingham Offspring Study who attended a routine examination, and were free of AF and cardiovascular disease. We used Cox proportional hazard regression analysis to examine the association between serum magnesium at baseline and risk of incident AF. Analyses were adjusted for conventional AF risk factors, use of antihypertensive medications, and serum potassium. During up to 20 years of follow-up, 228 participants developed AF. Mean serum magnesium was 1.88 mg/dl. The age- and sex-adjusted incidence rate of AF was 9.4 per 1,000 person-years (95% confidence interval, 6.7 to 11.9) in the lowest quartile of serum magnesium (≤1.77 mg/dl), compared with 6.3 per 1,000 person-years (95% confidence interval, 4.1 to 8.4) in the highest quartile (≥1.99 mg/dl). In multivariable-adjusted models, individuals in the lowest quartile of serum magnesium were approximately 50% more likely to develop AF (adjusted hazard ratio, 1.52, 1.00 to 2.31; P=0.05), compared with those in the upper quartiles. Results were similar after excluding individuals on diuretics. Conclusion Low serum magnesium is moderately associated with the development of AF in individuals without cardiovascular disease. Because hypomagnesemia is common in the general population, a link with AF may have potential clinical implications. Further studies are warranted to confirm our findings and elucidate the underlying mechanisms. PMID:23172839

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

PubMed

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

2012-06-01

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

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.

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.

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

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.

Serum uric acid levels contribute to new renal damage in systemic lupus erythematosus patients.

PubMed

Reátegui-Sokolova, C; Ugarte-Gil, Manuel F; Gamboa-Cárdenas, Rocío V; Zevallos, Francisco; Cucho-Venegas, Jorge M; Alfaro-Lozano, José L; Medina, Mariela; Rodriguez-Bellido, Zoila; Pastor-Asurza, Cesar A; Alarcón, Graciela S; Perich-Campos, Risto A

2017-04-01

This study aims to determine whether uric acid levels contribute to new renal damage in systemic lupus erythematosus (SLE) patients. This prospective study was conducted in consecutive patients seen since 2012. Patients had a baseline visit and follow-up visits every 6 months. Patients with ≥2 visits were included; those with end-stage renal disease (regardless of dialysis or transplantation) were excluded. Renal damage was ascertained using the SLICC/ACR damage index (SDI). Univariable and multivariable Cox-regression models were performed to determine the risk of new renal damage. Uric acid was included as a continuous and dichotomous (per receiving operating characteristic curve) variable. Multivariable models were adjusted for age at diagnosis, disease duration, socioeconomic status, SLEDAI, SDI, serum creatinine, baseline use of prednisone, antimalarials, and immunosuppressive drugs. One hundred and eighty-six patients were evaluated; their mean (SD) age at diagnosis was 36.8 (13.7) years; nearly all patients were mestizo. Disease duration was 7.7 (6.8) years. Follow-up time was 2.3 (1.1) years. The SLEDAI was 5.2 (4.3) and the SDI 0.8 (1.1). Uric acid levels were 4.5 (1.3) mg/dl. During follow-up, 16 (8.6%) patients developed at least one new point in the renal domain of the SDI. In multivariable analyses, uric acid levels (continuous and dichotomous) at baseline predicted the development of new renal damage (HR 3.21 (1.39-7.42), p 0.006; HR 18.28 (2.80-119.48), p 0.002; respectively). Higher uric acid levels contribute to the development of new renal damage in SLE patients independent of other well-known risk factors for such occurrence.

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

PubMed Central

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

2014-01-01

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

Skin autofluorescence predicts cardiovascular mortality in patients on chronic hemodialysis.

PubMed

Kimura, Hiroshi; Tanaka, Kenichi; Kanno, Makoto; Watanabe, Kimio; Hayashi, Yoshimitsu; Asahi, Koichi; Suzuki, Hodaka; Sato, Keiji; Sakaue, Michiaki; Terawaki, Hiroyuki; Nakayama, Masaaki; Miyata, Toshio; Watanabe, Tsuyoshi

2014-10-01

Tissue accumulation of advanced glycation end products (AGE) is thought to contribute to the progression of cardiovascular disease (CVD). Skin autofluorescence, a non-invasive measure of AGE accumulation using autofluorescence of the skin under ultraviolet light, has been reported to be an independent predictor of mortality associated with CVD in Caucasian patients on chronic hemodialysis. The aim of this study was to assess the predictive value of skin autofluorescence on all-cause and cardiovascular mortality in non-Caucasian (Japanese) patients on chronic hemodialysis. Baseline skin autofluorescence was measured with an autofluorescence reader in 128 non-Caucasian (Japanese) patients on chronic hemodialysis. All-cause and cardiovascular mortality was monitored prospectively during a period of 6 years. During the follow-up period, 42 of the 128 patients died; 19 of those patients died of CVD. Skin autofluorescence did not have a significant effect on all-cause mortality. However, age, carotid artery intima-media thickness (IMT), serum albumin, high-sensitivity C-reactive protein (hsCRP), skin autofluorescence and pre-existing CVD were significantly correlated with cardiovascular mortality. Multivariate Cox regression analysis showed skin autofluorescence (adjusted hazard ratio [HR] 3.97; 95% confidence interval [CI]1.67-9.43), serum albumin (adjusted HR 0.05; 95% CI 0.01-0.32), and hsCRP (adjusted HR 1.55; 95% CI 1.18-2.05) to be independent predictors of cardiovascular mortality. The present study suggests that skin autofluorescence is an independent predictor of cardiovascular mortality in non-Caucasian (Japanese) patients on chronic hemodialysis. © 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.

Sex Differences in the Relationship Between Amiodarone Use and the Need for Permanent Pacing in Patients With Atrial Fibrillation

PubMed Central

Essebag, Vidal; Reynolds, Matthew R.; Hadjis, Tom; Lemery, Robert; Olshansky, Brian; Buxton, Alfred E.; Josephson, Mark E.; Zimetbaum, Peter

2008-01-01

Background Amiodarone use was associated with an increased need for pacemaker insertion in a retrospective study of patients with atrial fibrillation (AF) and prior myocardial infarction. The aims of this study were to determine prospectively whether amiodarone increases the need for pacemakers in a general population of patients with AF and whether this effect is modified by sex. Methods The study included 1005 patients with new-onset AF who were enrolled in the Fibrillation Registry Assessing Costs, Therapies, Adverse events, and Lifestyle (FRACTAL). Multivariable Cox regression models, including time-dependent covariates accounting for medication exposure, were used to evaluate the risk of pacemaker insertion associated with amiodarone use. Results Amiodarone use was associated with an increased risk of pacemaker insertion (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.08–3.76) after adjustment for age, sex, atrial flutter, coronary artery disease, heart failure, and hypertension. The effect of amiodarone use was modified by sex, with a significant risk in women but not in men (HR, 4.69; 95% CI, 1.99–11.05 vs HR, 1.05; 95% CI, 0.42–2.58 [P = .02]). This interaction remained significant after adjustment for weight, body mass index, weight-adjusted amiodarone dose, and use of other antiarrhythmic or rate control drugs. Conclusion The risk of bradyarrhythmia requiring pacemaker insertion associated with amiodarone use for AF is significantly greater in women than in men, independent of weight or body mass index. PMID:17698688

Iron deficiency, anemia, and mortality in renal transplant recipients.

PubMed

Eisenga, Michele F; Minović, Isidor; Berger, Stefan P; Kootstra-Ros, Jenny E; van den Berg, Else; Riphagen, Ineke J; Navis, Gerjan; van der Meer, Peter; Bakker, Stephan J L; Gaillard, Carlo A J M

2016-11-01

Anemia, iron deficiency anemia (IDA), and iron deficiency (ID) are highly prevalent in renal transplant recipients (RTR). Anemia is associated with poor outcome, but the role of ID is unknown. Therefore, we aimed to investigate the association of ID, irrespective of anemia, with all-cause mortality in RTR. Cox regression analyses were used to investigate prospective associations. In 700 RTR, prevalences of anemia, IDA, and ID were 34%, 13%, and 30%, respectively. During follow-up for 3.1 (2.7-3.9) years, 81 (12%) RTR died. In univariable analysis, anemia [HR, 1.72 (95%CI: 1.11-2.66), P = 0.02], IDA [2.44 (1.48-4.01), P < 0.001], and ID [2.04 (1.31-3.16), P = 0.001] were all associated with all-cause mortality. In multivariable analysis, the association of anemia with mortality became weaker after adjustment for ID [1.52 (0.97-2.39), P = 0.07] and disappeared after adjustment for proteinuria and eGFR [1.09 (0.67-1.78), P = 0.73]. The association of IDA with mortality attenuated after adjustment for potential confounders. In contrast, the association of ID with mortality remained independent of potential confounders, including anemia [1.77 (1.13-2.78), P = 0.01]. In conclusion, ID is highly prevalent among RTR and is associated with an increased risk of mortality, independent of anemia. As ID is a modifiable factor, correction of ID could be a target to improve survival. © 2016 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.

Association of the Aspartate Aminotransferase to Alanine Aminotransferase Ratio with BNP Level and Cardiovascular Mortality in the General Population: The Yamagata Study 10-Year Follow-Up

PubMed Central

Yokoyama, Miyuki; Otaki, Yoichiro; Takahashi, Hiroki; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Shibata, Yoko; Daimon, Makoto; Kayama, Takamasa; Kubota, Isao

2016-01-01

Background. Early identification of high risk subjects for cardiovascular disease in health check-up is still unmet medical need. Cardiovascular disease is characterized by the superior increase in aspartate aminotransferase (AST) to alanine aminotransferase (ALT). However, the association of AST/ALT ratio with brain natriuretic peptide (BNP) levels and cardiovascular mortality remains unclear in the general population. Methods and Results. This longitudinal cohort study included 3,494 Japanese subjects who participated in a community-based health check-up, with a 10-year follow-up. The AST/ALT ratio increased with increasing BNP levels. And multivariate logistic analysis showed that the AST/ALT ratio was significantly associated with a high BNP (≥100 pg/mL). There were 250 all-cause deaths including 79 cardiovascular deaths. Multivariate Cox proportional hazard regression analysis revealed that a high AST/ALT ratio (>90 percentile) was an independent predictor of all-cause and cardiovascular mortality after adjustment for confounding factors. Kaplan-Meier analysis demonstrated that cardiovascular mortality was higher in subjects with a high AST/ALT ratio than in those without. Conclusions. The AST/ALT ratio was associated with an increase in BNP and was predictive of cardiovascular mortality in a general population. Measuring the AST/ALT ratio during routine health check-ups may be a simple and cost-effective marker for cardiovascular mortality. PMID:27872510

High coffee consumption and different brewing methods in relation to postmenopausal endometrial cancer risk in the Norwegian women and cancer study: a population-based prospective study.

PubMed

Gavrilyuk, Oxana; Braaten, Tonje; Skeie, Guri; Weiderpass, Elisabete; Dumeaux, Vanessa; Lund, Eiliv

2014-03-25

Coffee and its compounds have been proposed to inhibit endometrial carcinogenesis. Studies in the Norwegian population can be especially interesting due to the high coffee consumption and increasing incidence of endometrial cancer in the country. A total of 97 926 postmenopausal Norwegian women from the population-based prospective Norwegian Women and Cancer (NOWAC) Study, were included in the present analysis. We evaluated the general association between total coffee consumption and endometrial cancer risk as well as the possible impact of brewing method. Multivariate Cox regression analysis was used to estimate risks, and heterogeneity tests were performed to compare brewing methods. During an average of 10.9 years of follow-up, 462 incident endometrial cancer cases were identified. After multivariate adjustment, significant risk reduction was found among participants who drank ≥8 cups/day of coffee with a hazard ratio of 0.52 (95% confidence interval, CI 0.34-0.79). However, we did not observe a significant dose-response relationship. No significant heterogeneity in risk was found when comparing filtered and boiled coffee brewing methods. A reduction in endometrial cancer risk was observed in subgroup analyses among participants who drank ≥8 cups/day and had a body mass index ≥25 kg/m2, and in current smokers. These data suggest that in this population with high coffee consumption, endometrial cancer risk decreases in women consuming ≥8 cups/day, independent of brewing method.

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

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

PubMed Central

2014-01-01

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

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

PubMed

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

2014-05-23

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

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…

Racial Differences in Circulating Natriuretic Peptide Levels: The Atherosclerosis Risk in Communities Study

PubMed Central

Gupta, Deepak K; Claggett, Brian; Wells, Quinn; Cheng, Susan; Li, Man; Maruthur, Nisa; Selvin, Elizabeth; Coresh, Josef; Konety, Suma; Butler, Kenneth R; Mosley, Thomas; Boerwinkle, Eric; Hoogeveen, Ron; Ballantyne, Christie M; Solomon, Scott D

2015-01-01

Background Natriuretic peptides promote natriuresis, diuresis, and vasodilation. Experimental deficiency of natriuretic peptides leads to hypertension (HTN) and cardiac hypertrophy, conditions more common among African Americans. Hospital-based studies suggest that African Americans may have reduced circulating natriuretic peptides, as compared to Caucasians, but definitive data from community-based cohorts are lacking. Methods and Results We examined plasma N-terminal pro B-type natriuretic peptide (NTproBNP) levels according to race in 9137 Atherosclerosis Risk in Communities (ARIC) Study participants (22% African American) without prevalent cardiovascular disease at visit 4 (1996–1998). Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates. Among African Americans, percent European ancestry was determined from genetic ancestry informative markers and then examined in relation to NTproBNP levels in multivariable linear regression analysis. NTproBNP levels were significantly lower in African Americans (median, 43 pg/mL; interquartile range [IQR], 18, 88) than Caucasians (median, 68 pg/mL; IQR, 36, 124; P<0.0001). In multivariable models, adjusted log NTproBNP levels were 40% lower (95% confidence interval [CI], −43, −36) in African Americans, compared to Caucasians, which was consistent across subgroups of age, gender, HTN, diabetes, insulin resistance, and obesity. African-American race was also significantly associated with having nondetectable NTproBNP (adjusted OR, 5.74; 95% CI, 4.22, 7.80). In multivariable analyses in African Americans, a 10% increase in genetic European ancestry was associated with a 7% (95% CI, 1, 13) increase in adjusted log NTproBNP. Conclusions African Americans have lower levels of plasma NTproBNP than Caucasians, which may be partially owing to genetic variation. Low natriuretic peptide levels in African Americans may contribute to the greater risk for HTN and its sequalae in this population. PMID:25999400

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.

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

PubMed

Mulder, P G

1988-01-01

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

Prognostic factors in multiple myeloma: selection using Cox's proportional hazard model.

PubMed

Pasqualetti, P; Collacciani, A; Maccarone, C; Casale, R

1996-01-01

The pretreatment characteristics of 210 patients with multiple myeloma, observed between 1980 and 1994, were evaluated as potential prognostic factors for survival. Multivariate analysis according to Cox's proportional hazard model identified in the 160 dead patients with myeloma, among 26 different single prognostic variables, the following factors in order of importance: beta 2-microglobulin; bone marrow plasma cell percentage, hemoglobinemia, degree of lytic bone lesions, serum creatinine, and serum albumin. By analysis of these variables a prognostic index (PI), that considers the regression coefficients derived by Cox's model of all significant factors, was obtained. Using this it was possible to separate the whole patient group into three stages: stage I (PI < 1.485, 67 patients), stage II (PI: 1.485-2.090, 76 patients), and stage III (PI > 2.090, 67 patients), with a median survivals of 68, 36 and 13 months (P < 0.0001), respectively. Also the responses to therapy (P < 0.0001) and the survival curves (P < 0.00001) presented significant differences among the three subgroups. Knowledge of these factors could be of value in predicting prognosis and in planning therapy in patients with multiple myeloma.

Mid-arm muscle circumference as a significant predictor of all-cause mortality in male individuals

PubMed Central

Wu, Li-Wei; Lin, Yuan-Yung; Kao, Tung-Wei; Lin, Chien-Ming; Liaw, Fang-Yih; Wang, Chung-Ching; Peng, Tao-Chun; Chen, Wei-Liang

2017-01-01

Background Emerging evidences indicate that mid-arm muscle circumference (MAMC) is one of the anthropometric indicators that reflect health and nutritional status, but its correlative effectiveness in all-cause mortality prediction of United States individuals remains uncertain. Methods and findings design We investigated the joint association between MAMC and all-cause mortality in the US general population. A population-based longitudinal study of 6,769 participants aged 40 to 90 years in the third National Health and Nutrition Examination Survey (NHANES III) conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention. All participants were divided into two groups based on the gender: male and female group; each group was then divided into three subgroups depending on their MAMC level. The tertiles were as follows: T1 (18<27.3), T2 (27.3<29.6), T3 (29.6≤40.0) cm in the male group and T1 (15<22.3), T2 (22.3<24.6), T3 (24.6≤44.0) cm in the female group. Multivariable Cox regression analyses and Kaplan–Meier survival probabilities were utilized to jointly relate all-cause mortality risk to different MAMC level. For all-cause mortality in male participants, multivariable adjusted hazard ratios (HRs) were 0.83 (95% confidence interval (CI): 0.69–0.98; p = 0.033) for MAMC of 27.3–29.6 cm compared with 18–27.3 cm, and 0.76 (95% CI: 0.61–0.95; p = 0.018) for MAMC of 29.6–40 cm compared with 18–27.3 cm. For all-cause mortality in female participants, multivariable adjusted hazard ratios (HRs) were 0.84 (95% confidence interval (CI): 0.69–1.02; p = 0.075) for MAMC of 22.3–24.6 cm compared with 15–22.3 cm, and 0.94 (95% CI: 0.75–1.17; p = 0.583) for MAMC of 24.6–44 cm compared with 15–22.3 cm. Conclusion Results support a lower MAMC is associated with a higher mortality risk in male individuals. PMID:28196081

Cruciferous Vegetable Intake Is Inversely Associated with Lung Cancer Risk among Current Nonsmoking Men in the Japan Public Health Center (JPHC) Study.

PubMed

Mori, Nagisa; Shimazu, Taichi; Sasazuki, Shizuka; Nozue, Miho; Mutoh, Michihiro; Sawada, Norie; Iwasaki, Motoki; Yamaji, Taiki; Inoue, Manami; Takachi, Ribeka; Sunami, Ayaka; Ishihara, Junko; Sobue, Tomotaka; Tsugane, Shoichiro

2017-05-01

Background: Cruciferous vegetables, a rich source of isothiocyanates, have been reported to lower the risk of several types of cancer, including lung cancer. However, evidence from prospective observations of populations with a relatively high intake of cruciferous vegetables is sparse. Objective: We investigated the association between cruciferous vegetable intake and lung cancer risk in a large-scale population-based prospective study in Japan. Methods: We studied 82,330 participants (38,663 men; 43,667 women) aged 45-74 y without a past history of cancer. Participants were asked to respond to a validated questionnaire that included 138 food items. The association between cruciferous vegetable intake and lung cancer incidence was assessed with the use of Cox proportional hazard regression analysis to estimate HRs and 95% CIs (with adjustments for potential confounding factors). Results: After 14.9 y of follow-up, a total of 1499 participants (1087 men; 412 women) were diagnosed with lung cancer. After deleting early-diagnosed cancer and adjusting for confounding factors, we observed a nonsignificant inverse trend between cruciferous vegetable intake and lung cancer risk in men in the highest compared with the lowest quartiles (multivariate HR: 0.85; 95% CI: 0.69, 1.06; P -trend = 0.13). Stratified analysis by smoking status revealed a significant inverse association between cruciferous vegetable intake and lung cancer risk among those who were never smokers and those who were past smokers after deleting lung cancer cases in the first 3 y of follow-up [multivariate HR for never smokers: 0.49 (95% CI: 0.27, 0.87; P -trend = 0.04); multivariate HR for past smokers: 0.59 (95% CI: 0.35, 0.99; P -trend = 0.10)]. No association was noted in men who were current smokers and women who were never smokers. Conclusion: This study suggests that cruciferous vegetable intake may be associated with a reduction in lung cancer risk among men who are currently nonsmokers. © 2017 American Society for Nutrition.

Surgical treatment for women with breast cancer: do randomized clinical trials represent current medical practices?

PubMed

Frederick, Wayne A I; Ames, Sarah; Downing, Stephanie R; Oyetunji, Tolulope A; Chang, David C; Leffall, Lasalle D

2010-06-01

Randomized clinical trials have not shown survival differences between breast cancer patients who undergo breast-conserving surgery and those who undergo modified radical mastectomy (MRM). Recent studies however, have suggested that these randomized clinical trials findings may not be representative of the entire population or the nature of current patient care. A retrospective analysis of female invasive breast cancer patients who underwent surgery in the Surveillance, Epidemiology, and End Results database (1990-2003) was performed. Survival was compared amongst women who underwent partial mastectomy, partial mastectomy plus radiation (PMR), or MRM. Cox proportional hazards regressions were used to investigate the impact of method of treatment upon survival, after adjusting for patient and tumor characteristics. A total of 218,043 patients, mean age 62 years, were identified. MRM accounted for 51.5 per cent of the study population whereas PMR accounted for 34.9 per cent. On multivariate analyses, significant improvement was observed in patient survival associated with PMR when compared with MRM patients (hazard ratio = 0.71, 95% confidence interval = 0.67-0.74, P < 0.001). This population-based study suggests that there is a survival benefit for women undergoing PMR in the treatment of breast cancer.

Chronic Conditions and Mortality Among the Oldest Old

PubMed Central

Lee, Sei J.; Go, Alan S.; Lindquist, Karla; Bertenthal, Daniel; Covinsky, Kenneth E.

2008-01-01

Objectives. We sought to determine whether chronic conditions and functional limitations are equally predictive of mortality among older adults. Methods. Participants in the 1998 wave of the Health and Retirement Study (N=19430) were divided into groups by decades of age, and their vital status in 2004 was determined. We used multivariate Cox regression to determine the ability of chronic conditions and functional limitations to predict mortality. Results. As age increased, the ability of chronic conditions to predict mortality declined rapidly, whereas the ability of functional limitations to predict mortality declined more slowly. In younger participants (aged 50–59 years), chronic conditions were stronger predictors of death than were functional limitations (Harrell C statistic 0.78 vs. 0.73; P=.001). In older participants (aged 90–99 years), functional limitations were stronger predictors of death than were chronic conditions (Harrell C statistic 0.67 vs. 0.61; P=.004). Conclusions. The importance of chronic conditions as a predictor of death declined rapidly with increasing age. Therefore, risk-adjustment models that only consider comorbidities when comparing mortality rates across providers may be inadequate for adults older than 80 years. PMID:18511714

Locoregional treatments before liver transplantation for hepatocellular carcinoma: a study from the European Liver Transplant Registry.

PubMed

Pommergaard, Hans-Christian; Rostved, Andreas Arendtsen; Adam, René; Thygesen, Lau Caspar; Salizzoni, Mauro; Gómez Bravo, Miguel Angel; Cherqui, Daniel; De Simone, Paolo; Boudjema, Karim; Mazzaferro, Vincenzo; Soubrane, Olivier; García-Valdecasas, Juan Carlos; Fabregat Prous, Joan; Pinna, Antonio D; O'Grady, John; Karam, Vincent; Duvoux, Christophe; Rasmussen, Allan

2018-05-01

Locoregional treatment while on the waiting list for liver transplantation (Ltx) for hepatocellular carcinoma (HCC) has been shown to improve survival. However, the effect of treatment type has not been investigated. We investigate the effect of locoregional treatment type on survival after Ltx for HCC. We investigated patients registered in the European Liver Transplant Registry database using multivariate Cox regression survival analysis. Information on locoregional therapy was registered for 4978 of 23 124 patients and was associated with improved overall survival [hazard ratio (HR) 0.84 (0.73-0.96)] and HCC-specific survival [HR 0.76 (0.59-0.98)]. Radiofrequency ablation (RFA) was the one monotherapy associated with improved overall survival [HR 0.51 (0.40-0.65)]. In addition, the combination of RFA and transarterial chemoembolization also improved survival [HR 0.74 (0.55-0.99)]. Adjusting for factors related to prognosis, disease severity, and tumor aggressiveness, RFA was highly beneficial for overall and HCC-specific survival. The effect may represent a selection of patients with favorable tumor biology; however, the treatment may be effective per se by halting tumor progression. Clinicaltrials.gov number: NCT02995096. © 2018 Steunstichting ESOT.

Radical Surgery Improves Survival in Patients with Stage 4 Neuroblastoma.

PubMed

Vollmer, Katherin; Gfroerer, Stefan; Theilen, Till-Martin; Bochennek, Konrad; Klingebiel, Thomas; Rolle, Udo; Fiegel, Henning

2018-06-01

Neuroblastoma (NBL) is the most common extracranial solid tumor in children. Despite a good overall prognosis in NBL patients, the outcome of children with stage 4 disease, even with multimodal intensive therapy, remains poor. The role of extended surgical resection of the primary tumor is in numerous studies controversial. The aim of this study was to retrospectively analyze the impact of radical surgical resection on the overall- and event-free survival of stage 4 NBL patients. We retrospectively analyzed patient charts of 40 patients with stage 4 NBL treated in our institution between January 1990 and May 2012. All clinical and pathological findings of stage 4 NBL patients were included. Extent of surgery was assessed from the operation records and was classified as non-radical (tumor biopsy, partial 50-90% resection) or radical (near-complete >90% resection, complete resection). Overall- (OS) and event-free (EFS) survival was assessed using the Kaplan-Meier analysis and log-rank test. A multivariate Cox regression analysis was used to demonstrate independency. In total, 29/40 patients were operated radically (>90% resection), whereas 11 patients received subtotal resection or biopsy only. OS and EFS were significantly increased in patients with radical operation compared with non-radical resection (p = 0.0003 for OS, p = 0.004 for EFS; log-rank test). A multivariate Cox regression analysis revealed radical operation as a significant and independent parameter for OS and EFS. Our data indicate that radical (over 90% resection) surgery improves OS and EFS in stage 4 NBL patients.

Lack of Thy1 (CD90) expression in neuroblastomas is correlated with impaired survival.

PubMed

Fiegel, Henning C; Kaifi, Jussuf T; Quaas, Alexander; Varol, Emine; Krickhahn, Annika; Metzger, Roman; Sauter, Guido; Till, Holger; Izbicki, Jakob R; Erttmann, Rudolf; Kluth, Dietrich

2008-01-01

Neuroblastoma (NBL) is the most common solid tumor in children. Tumors in advanced stage or with positive risk factors still have a poor prognosis. Thy1 (CD90) is a membrane glycoprotein expressed in thymus, retinal ganglionic cells, and several types of stem cells. The aim of this study was to assess Thy1 expression in NBL and analyze the correlation with clinical outcome. Sixty-three specimens of NBL were stained for Thy1 on a tissue microarray by immunohistochemistry. Fresh frozen tumor tissues were used for RNA isolation, and RT-PCR analysis for Thy1-mRNA expression was performed. Patients' survival data were correlated with Thy1 status using a log rank test and a Cox regression multivariate analysis. Thy1 was expressed on 51 (81%) of the tumors. Kaplan-Meier survival analysis showed a significantly impaired survival in patients with NBL missing Thy1 (P < 0.005 by log-rank test). A multivariate Cox regression showed an independent prognostic value of Thy1 status for overall survival (P < 0.05). In addition, the frequency of events and deaths was significantly higher in the group of patients with Thy1 negative tumors, as assessed by ANOVA analysis (P < 0.05 by F-test). The data showed that Thy1-negative NBL patients have a significantly impaired overall survival compared with Thy1-positive NBL patients. Thus, Thy1 seemed to be a marker with a specific prognostic value in NBL patients. Future studies are aiming at the biological role of this marker in the tumor cell differentiation.

[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.

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

PubMed Central

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

2016-01-01

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

Anti-inflammatory use may not negatively impact oncologic outcomes following intravesical BCG for high-grade non-muscle-invasive bladder cancer.

PubMed

Singla, Nirmish; Haddad, Ahmed Q; Passoni, Niccolo M; Meissner, Matthew; Lotan, Yair

2017-01-01

To evaluate whether anti-inflammatory agents affect outcomes in patients receiving intravesical BCG therapy for high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). We reviewed the records of 203 patients in a prospective database of HG NMIBC from 2006 to 2012 at a single institution. Patients who had muscle-invasive disease (n = 32), low-grade pathology (n = 4), underwent early cystectomy within 3 months (n = 25), had <3 months of follow-up (n = 11), or did not receive an induction course of intravesical BCG (n = 32) were excluded. Clinicopathologic data were tabulated including demographics, comorbidities, pathologic stage and grades, intravesical therapy, and concomitant use of aspirin, NSAIDs, COX inhibitors, and statins. Multivariate Cox regression analysis explored predictive factors for recurrence, progression (stage progression or progression to cystectomy), cancer-specific survival (CSS), and overall survival (OS). Ninety-nine patients with HG NMIBC who received at least one induction course of intravesical BCG were identified, with median follow-up of 31.4 months. There were 20 (20.2 %) deaths, including 6 (6.1 %) patients with bladder cancer-related mortality. 13 % patients experienced tumor progression and 27 % underwent cystectomy following failure of intravesical therapy. Anti-inflammatory use included statins (65 %), aspirin (63 %), or non-aspirin NSAIDs/COX inhibitors (26 %). Anti-inflammatory use was not significantly predictive of recurrence, progression, or mortality outcomes on Cox regression. CIS stage was associated with higher progression, while age, BMI, and Charlson score were independent predictors of overall mortality. Despite speculation of inhibitory effects on BCG immunomodulation there was no evidence that anti-inflammatory agents impacted oncologic outcomes in patients receiving BCG for HG NMIBC.

Prognostic Impact of Neutrophil/Lymphocyte Ratio, Platelet Count, CRP, and Albumin Levels in Metastatic Colorectal Cancer Patients Treated with FOLFIRI-Bevacizumab.

PubMed

Artaç, Mehmet; Uysal, Mükremin; Karaağaç, Mustafa; Korkmaz, Levent; Er, Zehra; Güler, Tunç; Börüban, Melih Cem; Bozcuk, Hakan

2017-06-01

Metastatic colorectal cancer (mCRC) is a lethal disease and fluorouracil-leucovorin-irinotecan (FOLFIRI) plus bevacizumab (bev) is a standard approach. Hence, there is a strong need for identifying new prognostic factors to show the efficacy of FOLFIRI-bev. This is a retrospective study including patients (n = 90) with mCRC from two centers in Turkey. Neutrophil/lymphocyte (N/L) ratio, platelet count, albumin, and C-reactive protein (CRP) were recorded before FOLFIRI-bev therapy. The efficacy of these factors on progression-free survival (PFS) was analyzed with Kaplan Meier and Cox regression analysis. And the cutoff value of N/L ratio was analyzed with ROC analysis. The median age was 56 years (range 21-80). Forty-seven percent of patients with N/L ratio >2.5 showed progressive disease versus 43 % in patients with N/L ratio <2.5 (p = 0.025). The median PFS was 8.1 months for the patients with N/L ratio >2.5 versus 13.5 months for the patients with N/L ratio <2.5 (p = 0.025). At univariate Cox regression analysis, high baseline neutrophil count, LDH, N/L ratio, and CRP were all significantly associated with poor prognosis. At multivariate Cox regression analysis, CRP was confirmed to be a better independent prognostic factor. CRP variable was divided into above the upper limit of normal (ULN) and normal value. The median PFSs of the patients with normal and above ULN were 11.3 versus 5.8 months, respectively (p = 0.022). CRP and N/L ratio are potential predictors for advanced mCRC treated with FOLFIRI-bev.

Validation of a two-tier grading system in an unselected, consecutive cohort of serous ovarian cancer patients.

PubMed

Battista, Marco Johannes; Cotarelo, Cristina; Almstedt, Katrin; Heimes, Anne-Sophie; Makris, Georgios-Marios; Weyer, Veronika; Schmidt, Marcus

2016-09-01

New insights into the carcinogenesis of ovarian cancer (OC) lead to the definition of low-grade and high-grade serous OC. In this study, we validated the MD Anderson Cancer Center (MDACC) two-tier grading system and compared it with the traditional three-tier grading system as suggested by the International Federation of Gynecology and Obstetrics (FIGO). Consecutive patients with serous OC were enrolled. These two grading systems were assessed independently from each other. Kaplan-Meier estimates and Cox-regression analyses were performed to validate and compare their prognostic impact. 143 consecutive patients entered the study. According to the Kaplan-Meier estimates, the MDACC grading system (p = 0.001) predicted the progression free survival (PFS) more precisely than the FIGO system (p = 0.025). The MDACC grading system (p = 0.008) but not the FIGO system (p = 0.329) showed a statistically significant difference in terms of disease specific survival (DSS). Multivariable Cox-regression analyses revealed an independent prognostic impact of the MDACC grading system but not of the FIGO system for PFS (HR 1.570; 95 % CI 1.007-2.449; p = 0.047, and HR 0.712; 95 % CI 0.476-1.066; p = 0.099, respectively). Concerning DSS, the two-tier grading system but not the FIGO system showed a prognostic impact in a univariable Cox-regression analysis (HR 2.152; 95 % CI 1.207-3.835; p = 0.009, and HR 1.258; 95 % CI 0.801-1.975; p = 0.319, respectively). We were able to validate the MDACC grading system in serous OC. Moreover, this grading system was stronger associated with survival than the FIGO system.

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

PubMed

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

2016-12-01

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

Tunnelled haemodialysis catheter and haemodialysis outcomes: a retrospective cohort study in Zagreb, Croatia.

PubMed

Pašara, Vedran; Maksimović, Bojana; Gunjača, Mihaela; Mihovilović, Karlo; Lončar, Andrea; Kudumija, Boris; Žabić, Igor; Knotek, Mladen

2016-05-17

Studies have reported that the tunnelled dialysis catheter (TDC) is associated with inferior haemodialysis (HD) patient survival, in comparison with arteriovenous fistula (AVF). Since many cofactors may also affect survival of HD patients, it is unclear whether the greater risk for survival arises from TDC per se, or from associated conditions. Therefore, the aim of this study was to determine, in a multivariate analysis, the long-term outcome of HD patients, with respect to vascular access (VA). Retrospective cohort study. This retrospective cohort study included all 156 patients with a TDC admitted at University Hospital Merkur, from 2010 to 2012. The control group consisted of 97 patients dialysed via AVF. The groups were matched according to dialysis unit and time of VA placement. The site of choice for the placement of the TDC was the right jugular vein. Kaplan-Meier analysis with log-rank test was used to assess patient survival. Multivariate Cox regression analysis was used to determine independent variables associated with patient survival. Patient survival with respect to VA. The cumulative 1-year survival of patients who were dialysed exclusively via TDC was 86.4% and of those who were dialysed exclusively via AVF, survival was 97.1% (p=0.002). In multivariate Cox regression analysis, male sex and older age were independently negatively associated with the survival of HD patients, while shorter HD vintage before the creation of the observed VA, hypertensive renal disease and glomerulonephritis were positively associated with survival. TDC was an independent risk factor for survival of HD patients (HR 23.0, 95% CI 6.2 to 85.3). TDC may be an independent negative risk factor for HD patient survival. 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/

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

PubMed

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

2016-01-01

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

Dietary Patterns and Risk of Death and Progression to ESRD in Individuals With CKD: A Cohort Study

PubMed Central

Gutiérrez, Orlando M.; Muntner, Paul; Rizk, Dana V.; McClellan, William M.; Warnock, David G.; Newby, P.K.; Judd, Suzanne E.

2014-01-01

Background Nutrition is strongly linked with health outcomes in chronic kidney disease (CKD). However, few studies have examined relationships between dietary patterns and health outcomes in persons with CKD. Study Design Observational cohort study. Setting & Participants 3,972 participants with CKD (defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m2 or an albumin-creatinine ratio ≥30 mg/g at baseline) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a prospective cohort study of 30,239 black and white adults at least 45 years of age. Predictors Five empirically derived dietary patterns identified via factor analysis: “Convenience” (Chinese and Mexican foods, pizza, other mixed dishes), “Plant-Based” (fruits, vegetables), “Sweets/Fats” (sugary foods), “Southern” (fried foods, organ meats, sweetened beverages), and “Alcohol/Salads” (alcohol, green-leafy vegetables, salad dressing). Outcomes All-cause mortality and end-stage renal disease (ESRD). Results A total of 816 deaths and 141 ESRD events were observed over approximately 6 years of follow-up. There were no statistically significant associations of Convenience, Sweets/Fats or Alcohol/Salads pattern scores with all-cause mortality after multivariable adjustment. In Cox regression models adjusted for sociodemographic factors, energy intake, co-morbidities, and baseline kidney function, higher Plant-Based pattern scores (indicating greater consistency with the pattern) were associated with lower risk of mortality (HR comparing fourth to first quartile, 0.77; 95%CI, 0.61–0.97) whereas higher Southern pattern scores were associated with greater risk of mortality (HR comparing fourth to first quartile, 1.51; 95%CI, 1.19–1.92). There were no associations of dietary patterns with incident ESRD in multivariable-adjusted models. Limitations Missing dietary pattern data, potential residual confounding from lifestyle factors. Conclusions A Southern dietary pattern rich in processed and fried foods was independently associated with mortality in persons with CKD. In contrast, a diet rich in fruits and vegetables appeared to be protective. PMID:24679894

Contemporary use trends and survival outcomes in patients undergoing radical cystectomy or bladder-preservation therapy for muscle-invasive bladder cancer.

PubMed

Cahn, David B; Handorf, Elizabeth A; Ghiraldi, Eric M; Ristau, Benjamin T; Geynisman, Daniel M; Churilla, Thomas M; Horwitz, Eric M; Sobczak, Mark L; Chen, David Y T; Viterbo, Rosalia; Greenberg, Richard E; Kutikov, Alexander; Uzzo, Robert G; Smaldone, Marc C

2017-11-15

The current study was performed to examine temporal trends and compare overall survival (OS) in patients undergoing radical cystectomy (RC) or bladder-preservation therapy (BPT) for muscle-invasive urothelial carcinoma of the bladder. The authors reviewed the National Cancer Data Base to identify patients with AJCC stage II to III urothelial carcinoma of the bladder from 2004 through 2013. Patients receiving BPT were stratified as having received any external-beam radiotherapy (any XRT), definitive XRT (50-80 grays), and definitive XRT with chemotherapy (CRT). Treatment trends and OS outcomes for the BPT and RC cohorts were evaluated using Cochran-Armitage tests, unadjusted Kaplan-Meier curves, adjusted Cox multivariate regression, and propensity score matching, using increasingly stringent selection criteria. A total of 32,300 patients met the inclusion criteria and were treated with RC (22,680 patients) or BPT (9620 patients). Of the patients treated with BPT, 26.4% (2540 patients) and 15.5% (1489 patients), respectively, were treated with definitive XRT and CRT. Improved OS was observed for RC in all groups. After adjustments with more rigorous statistical models controlling for confounders and with more restrictive BPT cohorts, the magnitude of the OS benefit became attenuated on multivariate (any XRT: hazard ratio [HR], 2.115 [95% confidence interval [95% CI], 2.045-2.188]; definitive XRT: HR, 1.870 [95% CI, 1.773-1.972]; and CRT: HR, 1.578 [95% CI, 1.474-1.691]) and propensity score (any XRT: HR, 2.008 [95% CI, 1.871-2.154]; definitive XRT: HR, 1.606 [95% CI, 1.453-1.776]; and CRT: HR, 1.406 [95% CI, 1.235-1.601]) analyses. In the National Cancer Data Base, receipt of BPT was associated with decreased OS compared with RC in patients with stage II to III urothelial carcinoma. Increasingly stringent definitions of BPT and more rigorous statistical methods adjusting for selection biases attenuated observed survival differences. Cancer 2017;123:4337-45. © 2017 American Cancer Society. © 2017 American Cancer Society.

Impact of Time Since Last Childbirth on Survival of Women with Premenopausal and Postmenopausal Breast Cancers.

PubMed

Balakrishnan, Nanthini; Teo, Soo-Hwang; Sinnadurai, Siamala; Bhoo Pathy, Nanthini Thevi; See, Mee-Hoong; Taib, Nur Aishah; Yip, Cheng-Har; Bhoo Pathy, Nirmala

2017-11-01

Reproductive factors are associated with risk of breast cancer, but the association with breast cancer survival is less well known. Previous studies have reported conflicting results on the association between time since last childbirth and breast cancer survival. We determined the association between time since last childbirth (LCB) and survival of women with premenopausal and postmenopausal breast cancers in Malaysia. A historical cohort of 986 premenopausal, and 1123 postmenopausal, parous breast cancer patients diagnosed from 2001 to 2012 in University Malaya Medical Centre were included in the analyses. Time since LCB was categorized into quintiles. Multivariable Cox regression was used to determine whether time since LCB was associated with survival following breast cancer, adjusting for demographic, tumor, and treatment characteristics. Premenopausal breast cancer patients with the most recent childbirth (LCB quintile 1) were younger, more likely to present with unfavorable prognostic profiles and had the lowest 5-year overall survival (OS) (66.9; 95% CI 60.2-73.6%), compared to women with longer duration since LCB (quintile 2 thru 5). In univariable analysis, time since LCB was inversely associated with risk of mortality and the hazard ratio for LCB quintile 2, 3, 4, and 5 versus quintile 1 were 0.53 (95% CI 0.36-0.77), 0.49 (95% CI 0.33-0.75), 0.61 (95% CI 0.43-0.85), and 0.64 (95% CI 0.44-0.93), respectively; P trend  = 0.016. However, this association was attenuated substantially following adjustment for age at diagnosis and other prognostic factors. Similarly, postmenopausal breast cancer patients with the most recent childbirth were also more likely to present with unfavorable disease profiles. Compared to postmenopausal breast cancer patients in LCB quintile 1, patients in quintile 5 had a higher risk of mortality. This association was not significant following multivariable adjustment. Time since LCB is not independently associated with survival in premenopausal or postmenopausal breast cancers. The apparent increase in risks of mortality in premenopausal breast cancer patients with a recent childbirth, and postmenopausal patients with longer duration since LCB, appear to be largely explained by their age at diagnosis.

Prognostic significance of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with stage III and IV colorectal cancer

PubMed Central

Kim, Jae Hyun; Lee, Jun Yeop; Kim, Hae Koo; Lee, Jin Wook; Jung, Sung Gyu; Jung, Kyoungwon; Kim, Sung Eun; Moon, Won; Park, Moo In; Park, Seun Ja

2017-01-01

AIM To evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with colorectal cancer (CRC). METHODS Between April 1996 and December 2010, medical records from a total of 1868 patients with CRC were retrospectively reviewed. The values of simple inflammatory markers including NLR and PLR in predicting the long-term outcomes of these patients were evaluated using Kaplan-Meier curves and Cox regression models. RESULTS The median follow-up duration was 46 mo (interquartile range, 22-73). The estimation of NLR and PLR was based on the time of diagnosis. In multivariate Cox regression analysis, high NLR (≥ 3.0) and high PLR (≥ 160) were independent risk factors predicting poor long-term outcomes in patients with stage III and IV CRC. However, high NLR and high PLR were not prognostic factors in patients with stage I and II CRC. CONCLUSION In this study, we identified that high NLR (≥ 3.0) and high PLR (≥ 160) are useful prognostic factors to predict long-term outcomes in patients with stage III and IV CRC. PMID:28210087

Aspergillus Colonization of the Lung Allograft is a Risk Factor for Bronchiolitis Obliterans Syndrome

PubMed Central

Weigt, S. Samuel; Elashoff, Robert M.; Huang, Cathy; Ardehali, Abbas; Gregson, Aric L.; Kubak, Bernard; Fishbein, Michael C.; Saggar, Rajeev; Keane, Michael P.; Saggar, Rajan; Lynch, Joseph P.; Zisman, David A.; Ross, David J.; Belperio, John A.

2014-01-01

Multiple infections have been linked with the development of bronchiolitis obliterans syndrome (BOS) post-lung transplantation. Lung allograft airway colonization by Aspergillus species is common among lung transplant recipients. We hypothesized that Aspergillus colonization may promote the development of BOS and may decrease survival post-lung transplantation. We reviewed all lung transplant recipients transplanted in our center between 1/2000 and 6/2006. Bronchoscopy was performed according to a surveillance protocol and when clinically indicated. Aspergillus colonization was defined as a positive culture from bronchoalveolar lavage or two sputum cultures positive for the same Aspergillus species, in the absence of invasive pulmonary Aspergillosis. We found that Aspergillus colonization was strongly associated with BOS and BOS related mortality in Cox regression analyses. Aspergillus colonization typically preceded the development of BOS by a median of 261 days (95% CI 87 to 520). Furthermore, in a multivariate Cox regression model, Aspergillus colonization was a distinct risk factor for BOS, independent of acute rejection. These data suggest a potential causative role for Aspergillus colonization in the development of BOS post-lung transplantation and raise the possibility that strategies aimed to prevent Aspergillus colonization may help delay or reduce the incidence of BOS. PMID:19459819

Prognostic value of inflammation-based scores in patients with osteosarcoma

PubMed Central

Liu, Bangjian; Huang, Yujing; Sun, Yuanjue; Zhang, Jianjun; Yao, Yang; Shen, Zan; Xiang, Dongxi; He, Aina

2016-01-01

Systemic inflammation responses have been associated with cancer development and progression. C-reactive protein (CRP), Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and neutrophil-platelet score (NPS) have been shown to be independent risk factors in various types of malignant tumors. This retrospective analysis of 162 osteosarcoma cases was performed to estimate their predictive value of survival in osteosarcoma. All statistical analyses were performed by SPSS statistical software. Receiver operating characteristic (ROC) analysis was generated to set optimal thresholds; area under the curve (AUC) was used to show the discriminatory abilities of inflammation-based scores; Kaplan-Meier analysis was performed to plot the survival curve; cox regression models were employed to determine the independent prognostic factors. The optimal cut-off points of NLR, PLR, and LMR were 2.57, 123.5 and 4.73, respectively. GPS and NLR had a markedly larger AUC than CRP, PLR and LMR. High levels of CRP, GPS, NLR, PLR, and low level of LMR were significantly associated with adverse prognosis (P < 0.05). Multivariate Cox regression analyses revealed that GPS, NLR, and occurrence of metastasis were top risk factors associated with death of osteosarcoma patients. PMID:28008988

Dietary Intake of α-Linolenic Acid Is Not Appreciably Associated with Risk of Ischemic Stroke among Middle-Aged Danish Men and Women.

PubMed

Bork, Christian S; Venø, Stine K; Lundbye-Christensen, Søren; Jakobsen, Marianne U; Tjønneland, Anne; Schmidt, Erik B; Overvad, Kim

2018-06-01

Intake of the plant-derived omega-3 (n-3) fatty acid α-linolenic acid (ALA) may reduce the risk of ischemic stroke. We have investigated the associations between dietary intake of ALA and the risk of ischemic stroke and ischemic stroke subtypes. This was a follow-up study. A total of 57,053 participants aged 50-64 y were enrolled into the Danish Diet, Cancer and Health cohort between 1993 and 1997. Intake of ALA was assessed by a validated semiquantitative food frequency questionnaire. Potential incident cases of ischemic stroke were identified in the Danish National Patient Register, validated, and classified into subtypes based on assumed etiology. Statistical analyses were performed via Cox proportional hazard regression with adjustment for established ischemic stroke risk factors. A total of 1859 ischemic stroke cases were identified during a median of 13.5 y of follow-up. In multivariable analyses using restricted cubic splines adjusting for traditional risk factors for ischemic stroke, we observed no clear associations between dietary intake of ALA and the risk of total ischemic stroke or any of its subtypes including ischemic stroke due to large artery atherosclerosis, ischemic stroke due to small-vessel occlusion, and ischemic stroke due to cardio-embolism. Dietary intake of ALA was neither consistently nor appreciably associated with the risk of ischemic stroke or ischemic stroke subtypes among middle-aged Danish men and women. This study was registered at clinicaltrials.gov as NCT03258983.

Duodenal localization is a negative predictor of survival after small bowel adenocarcinoma resection: A population-based, propensity score-matched analysis.

PubMed

Wilhelm, Alexander; Galata, Christian; Beutner, Ulrich; Schmied, Bruno M; Warschkow, Rene; Steffen, Thomas; Brunner, Walter; Post, Stefan; Marti, Lukas

2018-03-01

This study assessed the influence of tumor localization of small bowel adenocarcinoma on survival after surgical resection. Patients with resected small bowel adenocarcinoma, ACJJ stage I-III, were identified from the Surveillance, Epidemiology, and End Results database from 2004 to 2013. The impact of tumor localization on overall and cancer-specific survival was assessed using Cox proportional hazard regression models with and without risk-adjustment and propensity score methods. Adenocarcinoma was localized to the duodenum in 549 of 1025 patients (53.6%). There was no time trend for duodenal localization (P = 0.514). The 5-year cancer-specific survival rate was 48.2% (95%CI: 43.3-53.7%) for patients with duodenal carcinoma and 66.6% (95%CI: 61.6-72.1%) for patients with cancer located in the jejunum or ileum. Duodenal localization was associated with worse overall and cancer-specific survival in univariable (HR = 1.73; HR = 1.81, respectively; both P < 0.001), multivariable (HR = 1.52; HR = 1.65; both P < 0.001), and propensity score-adjusted analyses (HR = 1.33, P = 0.012; HR = 1.50, P = 0.002). Furthermore, young age, retrieval of more than 12 regional lymph nodes, less advanced stage, and married matrimonial status were positive, independent prognostic factors. Duodenal localization is an independent risk factor for poor survival after resection of adenocarcinoma. © 2017 Wiley Periodicals, Inc.

Type of Resection (Whipple vs. Distal) Does Not Affect the National Failure to Provide Post-resection Adjuvant Chemotherapy in Localized Pancreatic Cancer.

PubMed

Bergquist, John R; Ivanics, Tommy; Shubert, Christopher R; Habermann, Elizabeth B; Smoot, Rory L; Kendrick, Michael L; Nagorney, David M; Farnell, Michael B; Truty, Mark J

2017-06-01

Adjuvant chemotherapy improves survival after curative intent resection for localized pancreatic adenocarcinoma (PDAC). Given the differences in perioperative morbidity, we hypothesized that patients undergoing distal partial pancreatectomy (DPP) would receive adjuvant therapy more often those undergoing pancreatoduodenectomy (PD). The National Cancer Data Base (2004-2012) identified patients with localized PDAC undergoing DPP and PD, excluding neoadjuvant cases, and factors associated with receipt of adjuvant therapy were identified. Overall survival (OS) was analyzed using multivariable Cox proportional hazards regression. Overall, 13,501 patients were included (DPP, n = 1933; PD, n = 11,568). Prognostic characteristics were similar, except DPP patients had fewer N1 lesions, less often positive margins, more minimally invasive resections, and shorter hospital stay. The proportion of patients not receiving adjuvant chemotherapy was equivalent (DPP 33.7%, PD 32.0%; p = 0.148). The type of procedure was not independently associated with adjuvant chemotherapy (hazard ratio 0.96, 95% confidence interval 0.90-1.02; p = 0.150), and patients receiving adjuvant chemotherapy had improved unadjusted and adjusted OS compared with surgery alone. The type of resection did not predict adjusted mortality (p = 0.870). Receipt of adjuvant chemotherapy did not vary by type of resection but improved survival independent of procedure performed. Factors other than type of resection appear to be driving the nationwide rates of post-resection adjuvant chemotherapy in localized PDAC.

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

PubMed

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

2017-06-01

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

Word Memory Test Predicts Recovery in Claimants With Work-Related Head Injury.

PubMed

Colangelo, Annette; Abada, Abigail; Haws, Calvin; Park, Joanne; Niemeläinen, Riikka; Gross, Douglas P

2016-05-01

To investigate the predictive validity of the Word Memory Test (WMT), a verbal memory neuropsychological test developed as a performance validity measure to assess memory, effort, and performance consistency. Cohort study with 1-year follow-up. Workers' compensation rehabilitation facility. Participants included workers' compensation claimants with work-related head injury (N=188; mean age, 44y; 161 men [85.6%]). Not applicable. Outcome measures for determining predictive validity included days to suspension of wage replacement benefits during the 1-year follow-up and work status at discharge in claimants undergoing rehabilitation. Analysis included multivariable Cox and logistic regression. Better WMT performance was significantly but weakly correlated with younger age (r=-.30), documented brain abnormality (r=.28), and loss of consciousness at the time of injury (r=.25). Claimants with documented brain abnormalities on diagnostic imaging scans performed better (∼9%) on the WMT than those without brain abnormalities. The WMT predicted days receiving benefits (adjusted hazard ratio, 1.13; 95% confidence interval, 1.04-1.24) and work status outcome at program discharge (adjusted odds ratio, 1.62; 95% confidence interval, 1.13-2.34). Our results provide evidence for the predictive validity of the WMT in workers' compensation claimants. Younger claimants and those with more severe brain injuries performed better on the WMT. It may be that financial incentives or other factors related to the compensation claim affected the performance. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Survival in Adult Lung Transplant Recipients Receiving Pediatric Versus Adult Donor Allografts.

PubMed

Hayes, Don; Whitson, Bryan A; Ghadiali, Samir N; Lloyd, Eric A; Tobias, Joseph D; Mansour, Heidi M; Black, Sylvester M

2015-10-01

Recent evidence showed that pediatric donor lungs increased rates of allograft failure in adult lung transplant recipients; however, the influence on survival is unclear. The United Network for Organ Sharing (UNOS) database was queried from 2005 to 2013 for adult lung transplant recipients (≥18 years) to assess survival differences among donor age categories (<18 years, 18 to 29 years, 30 to 59 years, ≥60 years). Of 12,297 adult lung transplants, 12,209 were used for univariate Cox models and Kaplan-Meier (KM) analysis and 11,602 for multivariate Cox models. A total of 1,187 adult recipients received pediatric donor lungs compared with 11,110 receiving adult donor organs. Univariate and multivariate Cox models found no difference in survival between donor ages 0 to 17 and donor ages 18 to 29, whereas donor ages 60 and older were significantly associated with increased mortality hazard, relative to the modal category of donor ages 30 to 59 (adjusted hazard ratio = 1.381; 95% confidence interval = 1.188% to 1.606%; p < 0.001). Interactions between recipient and donor age range found that the oldest donor age range was negatively associated with survival among middle-aged (30 to 59) and older (≥60) lung transplant recipients. Pediatric donor lung allografts were not negatively associated with survival in adult lung transplant recipients; however, the oldest donor age range was associated with increased mortality hazard for adult lung transplant recipients. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Bayesian multivariate hierarchical transformation models for ROC analysis.

PubMed

O'Malley, A James; Zou, Kelly H

2006-02-15

A Bayesian multivariate hierarchical transformation model (BMHTM) is developed for receiver operating characteristic (ROC) curve analysis based on clustered continuous diagnostic outcome data with covariates. Two special features of this model are that it incorporates non-linear monotone transformations of the outcomes and that multiple correlated outcomes may be analysed. The mean, variance, and transformation components are all modelled parametrically, enabling a wide range of inferences. The general framework is illustrated by focusing on two problems: (1) analysis of the diagnostic accuracy of a covariate-dependent univariate test outcome requiring a Box-Cox transformation within each cluster to map the test outcomes to a common family of distributions; (2) development of an optimal composite diagnostic test using multivariate clustered outcome data. In the second problem, the composite test is estimated using discriminant function analysis and compared to the test derived from logistic regression analysis where the gold standard is a binary outcome. The proposed methodology is illustrated on prostate cancer biopsy data from a multi-centre clinical trial.

Bayesian multivariate hierarchical transformation models for ROC analysis

PubMed Central

O'Malley, A. James; Zou, Kelly H.

2006-01-01

SUMMARY A Bayesian multivariate hierarchical transformation model (BMHTM) is developed for receiver operating characteristic (ROC) curve analysis based on clustered continuous diagnostic outcome data with covariates. Two special features of this model are that it incorporates non-linear monotone transformations of the outcomes and that multiple correlated outcomes may be analysed. The mean, variance, and transformation components are all modelled parametrically, enabling a wide range of inferences. The general framework is illustrated by focusing on two problems: (1) analysis of the diagnostic accuracy of a covariate-dependent univariate test outcome requiring a Box–Cox transformation within each cluster to map the test outcomes to a common family of distributions; (2) development of an optimal composite diagnostic test using multivariate clustered outcome data. In the second problem, the composite test is estimated using discriminant function analysis and compared to the test derived from logistic regression analysis where the gold standard is a binary outcome. The proposed methodology is illustrated on prostate cancer biopsy data from a multi-centre clinical trial. PMID:16217836

Disparities in Adherence to National Comprehensive Cancer Network Treatment Guidelines and Survival for Stage IB-IIA Cervical Cancer in California.

PubMed

Pfaendler, Krista S; Chang, Jenny; Ziogas, Argyrios; Bristow, Robert E; Penner, Kristine R

2018-05-01

To evaluate the association of sociodemographic and hospital characteristics with adherence to National Comprehensive Cancer Network treatment guidelines for stage IB-IIA cervical cancer and to analyze the relationship between adherent care and survival. This is a retrospective population-based cohort study of patients with stage IB-IIA invasive cervical cancer reported to the California Cancer Registry from January 1, 1995, through December 31, 2009. Adherence to National Comprehensive Cancer Network guideline care was defined by year- and stage-appropriate surgical procedures, radiation, and chemotherapy. Multivariate logistic regression, Kaplan-Meier estimate, and Cox proportional hazard models were used to examine associations between patient, tumor, and treatment characteristics and National Comprehensive Cancer Network guideline adherence and cervical cancer-specific 5-year survival. A total of 6,063 patients were identified. Forty-seven percent received National Comprehensive Cancer Network guideline-adherent care, and 18.8% were treated in high-volume centers (20 or more patients/year). On multivariate analysis, lowest socioeconomic status (adjusted odds ratio [OR] 0.69, 95% CI 0.57-0.84), low-middle socioeconomic status (adjusted OR 0.76, 95% CI 0.64-0.92), and Charlson-Deyo comorbidity score 1 or higher (adjusted OR 0.78, 95% CI 0.69-0.89) were patient characteristics associated with receipt of nonguideline care. Receiving adherent care was less common in low-volume centers (45.9%) than in high-volume centers (50.9%) (effect size 0.90, 95% CI 0.84-0.96). Death from cervical cancer was more common in the nonadherent group (13.3%) than in the adherent group (8.6%) (effect size 1.55, 95% CI 1.34-1.80). Black race (adjusted hazard ratio 1.56, 95% CI 1.08-2.27), Medicaid payer status (adjusted hazard ratio 1.47, 95% CI 1.15-1.87), and Charlson-Deyo comorbidity score 1 or higher (adjusted hazard ratio 2.07, 95% CI 1.68-2.56) were all associated with increased risk of dying from cervical cancer. Among patients with early-stage cervical cancer, National Comprehensive Cancer Network guideline-nonadherent care was independently associated with increased cervical cancer-specific mortality along with black race and Medicaid payer status. Nonadherence was more prevalent in patients with older age, lower socioeconomic status, and receipt of care in low-volume centers. Attention should be paid to increase guideline adherence.

Chronic Pancreatitis Correlates With Increased Risk of Cerebrovascular Disease: A Retrospective Population-Based Cohort Study in Taiwan.

PubMed

Wong, Tuck-Siu; Liao, Kuan-Fu; Lin, Chi-Ming; Lin, Cheng-Li; Chen, Wen-Chi; Lai, Shih-Wei

2016-04-01

The aim of this study is to explore whether there is a relationship between chronic pancreatitis and cerebrovascular disease in Taiwan. Using the claims data of the Taiwan National Health Insurance Program, we identified 16,672 subjects aged 20 to 84 years with a new diagnosis of chronic pancreatitis from 2000 to 2010 as the chronic pancreatitis group. We randomly selected 65,877 subjects aged 20 to 84 years without chronic pancreatitis as the nonchronic pancreatitis group. Both groups were matched by sex, age, comorbidities, and the index year of diagnosing chronic pancreatitis. The incidence of cerebrovascular disease at the end of 2011 was measured. The multivariable Cox proportional hazards regression model was used to measure the hazard ratio (HR) and 95% confidence interval (CI) for cerebrovascular disease risk associated with chronic pancreatitis and other comorbidities. The overall incidence of cerebrovascular disease was 1.24-fold greater in the chronic pancreatitis group than that in the nonchronic pancreatitis group (14.2 vs. 11.5 per 1000 person-years, 95% CI = 1.19-1.30). After controlling for confounding factors, the adjusted HR of cerebrovascular disease was 1.27 (95% CI = 1.19-1.36) for the chronic pancreatitis group as compared with the nonchronic pancreatitis group. Woman (adjusted HR = 1.41, 95% CI = 1.31-1.51), age (every 1 year, HR = 1.04, 95% CI = 1.04-1.05), atrial fibrillation (adjusted HR = 1.23, 95% CI = 1.02-1.48), chronic kidney disease (adjusted HR = 1.48, 95% CI = 1.31-1.67), chronic obstructive pulmonary disease (adjusted HR = 1.27, 95% CI = 1.16-1.40), diabetes mellitus (adjusted HR = 1.82, 95% CI = 1.72-1.92), hypertension (adjusted HR = 1.66, 95% CI = 1.56-1.76), and peripheral atherosclerosis (adjusted HR = 1.26, 95% CI = 1.06-1.51) were other factors significantly associated with cerebrovascular disease. Chronic pancreatitis is associated with increased hazard of subsequent cerebrovascular disease.

Chronic Pancreatitis Correlates With Increased Risk of Cerebrovascular Disease

PubMed Central

Wong, Tuck-Siu; Liao, Kuan-Fu; Lin, Chi-Ming; Lin, Cheng-Li; Chen, Wen-Chi; Lai, Shih-Wei

2016-01-01

Abstract The aim of this study is to explore whether there is a relationship between chronic pancreatitis and cerebrovascular disease in Taiwan. Using the claims data of the Taiwan National Health Insurance Program, we identified 16,672 subjects aged 20 to 84 years with a new diagnosis of chronic pancreatitis from 2000 to 2010 as the chronic pancreatitis group. We randomly selected 65,877 subjects aged 20 to 84 years without chronic pancreatitis as the nonchronic pancreatitis group. Both groups were matched by sex, age, comorbidities, and the index year of diagnosing chronic pancreatitis. The incidence of cerebrovascular disease at the end of 2011 was measured. The multivariable Cox proportional hazards regression model was used to measure the hazard ratio (HR) and 95% confidence interval (CI) for cerebrovascular disease risk associated with chronic pancreatitis and other comorbidities. The overall incidence of cerebrovascular disease was 1.24-fold greater in the chronic pancreatitis group than that in the nonchronic pancreatitis group (14.2 vs. 11.5 per 1000 person-years, 95% CI = 1.19–1.30). After controlling for confounding factors, the adjusted HR of cerebrovascular disease was 1.27 (95% CI = 1.19–1.36) for the chronic pancreatitis group as compared with the nonchronic pancreatitis group. Woman (adjusted HR = 1.41, 95% CI = 1.31–1.51), age (every 1 year, HR = 1.04, 95% CI = 1.04–1.05), atrial fibrillation (adjusted HR = 1.23, 95% CI = 1.02–1.48), chronic kidney disease (adjusted HR = 1.48, 95% CI = 1.31–1.67), chronic obstructive pulmonary disease (adjusted HR = 1.27, 95% CI = 1.16–1.40), diabetes mellitus (adjusted HR = 1.82, 95% CI = 1.72–1.92), hypertension (adjusted HR = 1.66, 95% CI = 1.56–1.76), and peripheral atherosclerosis (adjusted HR = 1.26, 95% CI = 1.06–1.51) were other factors significantly associated with cerebrovascular disease. Chronic pancreatitis is associated with increased hazard of subsequent cerebrovascular disease. PMID:27082563

A national cohort study of parental socioeconomic status and non-fatal suicidal behaviour-the mediating role of school performance

PubMed Central

2012-01-01

Background A link between low parental socioeconomic status and mental health problems in offspring is well established in previous research. The mechanisms that explain this link are largely unknown. The present study investigated whether school performance was a mediating and/or moderating factor in the path between parental socioeconomic status and the risk of hospital admission for non-fatal suicidal behaviour. Methods A national cohort of 447 929 children born during 1973-1977 was followed prospectively in the National Patient Discharge Register from the end of their ninth and final year of compulsory school until 2001. Multivariate Cox proportional hazards and linear regression analyses were performed to test whether the association between parental socioeconomic status and non-fatal suicidal behaviour was mediated or moderated by school performance. Results The results of a series of multiple regression analyses, adjusted for demographic variables, revealed that school performance was as an important mediator in the relationship between parental socioeconomic status and risk of non-fatal suicidal behaviour, accounting for 60% of the variance. The hypothesized moderation of parental socioeconomic status-non-fatal suicidal behaviour relationship by school performance was not supported. Conclusions School performance is an important mediator through which parental socioeconomic status translates into a risk for non-fatal suicidal behaviour. Prevention efforts aimed to reduce socioeconomic inequalities in non-fatal suicidal behaviour among young people will need to consider socioeconomic inequalities in school performance. PMID:22230577

Coffee Consumption and Lung Cancer Risk: The Japan Public Health Center-Based Prospective Study.

PubMed

Narita, Saki; Saito, Eiko; Sawada, Norie; Shimazu, Taichi; Yamaji, Taiki; Iwasaki, Motoki; Sasazuki, Shizuka; Noda, Mitsuhiko; Inoue, Manami; Tsugane, Shoichiro

2018-04-05

Many epidemiological studies have indicated a positive association between coffee intake and lung cancer risk, but such findings were suggested to be confounded by smoking. Furthermore, only a few of these studies have been conducted in Asia. Here, we investigated the association between coffee intake and lung cancer risk in one of the largest prospective cohort studies in Japan. We investigated the association of coffee drinking and subsequent incidence of lung cancer among 41,727 men and 45,352 women in the Japan Public Health Center-based Prospective Study using Cox proportional hazards regression, with adjustment for potential confounders and by strata of smoking status. Coffee and other dietary intakes were assessed once at baseline with a food frequency questionnaire (FFQ). During 1,481,887 person-years of follow-up between 1990 and 2011, a total of 1,668 lung cancer cases were identified. In a multivariate regression model, coffee consumption was not associated with risk of lung cancer (HR 1.16; 95% CI, 0.82-1.63; P trend = 0.285 for men and HR 1.49; 95% CI, 0.79-2.83; P trend = 0.942 for women). However, there was a significant increase in the risk for small cell carcinoma (HR 3.52; 95% CI, 1.49-8.28; P trend < 0.001). Our prospective study suggests that habitual consumption of coffee is not associated with an increased risk of lung cancer incidence, despite observing a significant increase in the risk for small cell carcinoma.

Paleolithic and Mediterranean Diet Pattern Scores Are Inversely Associated with All-Cause and Cause-Specific Mortality in Adults123

PubMed Central

Whalen, Kristine A; Judd, Suzanne; McCullough, Marjorie L; Flanders, W Dana; Hartman, Terryl J; Bostick, Roberd M

2017-01-01

Background: Poor diet quality is associated with a higher risk of many chronic diseases that are among the leading causes of death in the United States. It has been hypothesized that evolutionary discordance may account for some of the higher incidence and mortality from these diseases. Objective: We investigated associations of 2 diet pattern scores, the Paleolithic and the Mediterranean, with all-cause and cause-specific mortality in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, a longitudinal cohort of black and white men and women ≥45 y of age. Methods: Participants completed questionnaires, including a Block food-frequency questionnaire (FFQ), at baseline and were contacted every 6 mo to determine their health status. Of the analytic cohort (n = 21,423), a total of 2513 participants died during a median follow-up of 6.25 y. We created diet scores from FFQ responses and assessed their associations with mortality using multivariable Cox proportional hazards regression models adjusting for major risk factors. Results: For those in the highest relative to the lowest quintiles of the Paleolithic and Mediterranean diet scores, the multivariable adjusted HRs for all-cause mortality were, respectively, 0.77 (95% CI: 0.67, 0.89; P-trend < 0.01) and 0.63 (95% CI: 0.54, 0.73; P-trend < 0.01). The corresponding HRs for all-cancer mortality were 0.72 (95% CI: 0.55, 0.95; P-trend = 0.03) and 0.64 (95% CI: 0.48, 0.84; P-trend = 0.01), and for all-cardiovascular disease mortality they were 0.78 (95% CI: 0.61, 1.00; P-trend = 0.06) and HR: 0.68 (95% CI: 0.53, 0.88; P-trend = 0.01). Conclusions: Findings from this biracial prospective study suggest that diets closer to Paleolithic or Mediterranean diet patterns may be inversely associated with all-cause and cause-specific mortality. PMID:28179490

Paleolithic and Mediterranean Diet Pattern Scores Are Inversely Associated with All-Cause and Cause-Specific Mortality in Adults.

PubMed

Whalen, Kristine A; Judd, Suzanne; McCullough, Marjorie L; Flanders, W Dana; Hartman, Terryl J; Bostick, Roberd M

2017-04-01

Background: Poor diet quality is associated with a higher risk of many chronic diseases that are among the leading causes of death in the United States. It has been hypothesized that evolutionary discordance may account for some of the higher incidence and mortality from these diseases. Objective: We investigated associations of 2 diet pattern scores, the Paleolithic and the Mediterranean, with all-cause and cause-specific mortality in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, a longitudinal cohort of black and white men and women ≥45 y of age. Methods: Participants completed questionnaires, including a Block food-frequency questionnaire (FFQ), at baseline and were contacted every 6 mo to determine their health status. Of the analytic cohort ( n = 21,423), a total of 2513 participants died during a median follow-up of 6.25 y. We created diet scores from FFQ responses and assessed their associations with mortality using multivariable Cox proportional hazards regression models adjusting for major risk factors. Results: For those in the highest relative to the lowest quintiles of the Paleolithic and Mediterranean diet scores, the multivariable adjusted HRs for all-cause mortality were, respectively, 0.77 (95% CI: 0.67, 0.89; P- trend < 0.01) and 0.63 (95% CI: 0.54, 0.73; P- trend < 0.01). The corresponding HRs for all-cancer mortality were 0.72 (95% CI: 0.55, 0.95; P- trend = 0.03) and 0.64 (95% CI: 0.48, 0.84; P- trend = 0.01), and for all-cardiovascular disease mortality they were 0.78 (95% CI: 0.61, 1.00; P- trend = 0.06) and HR: 0.68 (95% CI: 0.53, 0.88; P- trend = 0.01). Conclusions: Findings from this biracial prospective study suggest that diets closer to Paleolithic or Mediterranean diet patterns may be inversely associated with all-cause and cause-specific mortality. © 2017 American Society for Nutrition.

Comparison of adherence and persistence among adults with type 2 diabetes mellitus initiating saxagliptin or linagliptin.

PubMed

Farr, Amanda M; Sheehan, John J; Davis, Brian M; Smith, David M

2016-01-01

Adherence and persistence to antidiabetes medications are important to control blood glucose levels among individuals with type 2 diabetes mellitus (T2D). The objective of this study was to compare adherence and persistence over a 12-month period between patients initiating saxagliptin and patients initiating linagliptin, two dipeptidyl peptidase-4 inhibitors. This retrospective cohort study was conducted in MarketScan(®) Commercial and Medicare Supplemental claims databases. Patients with T2D initiating saxagliptin or linagliptin between January 1, 2009, and June 30, 2013, were selected. Patients were required to be at least 18 years old and have 12 months of continuous enrollment prior to and following initiation. Adherence and persistence to initiated medication were measured over the 12 months after initiation using outpatient pharmacy claims. Patients were considered adherent if the proportion of days covered was ≥0.80. Patients were considered nonpersistent (or to have discontinued) if there was a gap of >60 days without initiated medication on hand. Multivariable logistic regression and multivariable Cox proportional hazard models were fit to compare adherence and persistence, respectively, between the two cohorts. There were 21,599 saxagliptin initiators (mean age 55 years; 53% male) and 5,786 linagliptin initiators (mean age 57 years; 54% male) included in the study sample. Over the 12-month follow-up, 46% of saxagliptin initiators and 42% of linagliptin initiators were considered adherent and 47% of saxagliptin initiators and 51% of linagliptin initiators discontinued their initiated medication. After controlling for patient characteristics, saxagliptin initiation was associated with significantly greater odds of being adherent (adjusted odds ratio =1.212, 95% CI 1.140-1.289) and significantly lower hazards of discontinuation (adjusted hazard ratio =0.887, 95% CI 0.850-0.926) compared with linagliptin initiation. Compared with patients with T2D who initiated linagliptin, patients with T2D who initiated saxagliptin had significantly better adherence and persistence.

Prognostic value of the new Grade Groups in Prostate Cancer: a multi-institutional European validation study.

PubMed

Mathieu, R; Moschini, M; Beyer, B; Gust, K M; Seisen, T; Briganti, A; Karakiewicz, P; Seitz, C; Salomon, L; de la Taille, A; Rouprêt, M; Graefen, M; Shariat, S F

2017-06-01

We aimed to assess the prognostic relevance of the new Grade Groups in Prostate Cancer (PCa) within a large cohort of European men treated with radical prostatectomy (RP). Data from 27 122 patients treated with RP at seven European centers were analyzed. We investigated the prognostic performance of the new Grade Groups (based on Gleason score 3+3, 3+4, 4+3, 8 and 9-10) on biopsy and RP specimen, adjusted for established clinical and pathological characteristics. Multivariable Cox proportional hazards regression models assessed the association of new Grade Groups with biochemical recurrence (BCR). Prognostic accuracies of the models were assessed using Harrell's C-index. Median follow-up was 29 months (interquartile range, 13-54). The 4-year estimated BCR-free survival (bRFS) for biopsy Grade Groups 1-5 were 91.3, 81.6, 69.8, 60.3 and 44.4%, respectively. The 4-year estimated bRFS for RP Grade Groups 1-5 were 96.1%, 86.7%, 67.0%, 63.1% and 41.0%, respectively. Compared with Grade Group 1, all other Grade Groups based both on biopsy and RP specimen were independently associated with a lower bRFS (all P<0.01). Adjusted pairwise comparisons revealed statistically differences between all Grade Groups, except for group 3 and 4 on RP specimen (P=0.10). The discriminations of the multivariable base prognostic models based on the current three-tier and the new five-tier systems were not clinically different (0.3 and 0.9% increase in discrimination for clinical and pathological model). We validated the independent prognostic value of the new Grade Groups on biopsy and RP specimen from European PCa men. However, it does not improve the accuracies of prognostic models by a clinically significant margin. Nevertheless, this new classification may help physicians and patients estimate disease aggressiveness with a user-friendly, clinically relevant and reproducible method.

Adjuvant Chemotherapy After Radical Cystectomy for Urothelial Bladder Cancer: Outcome and Prognostic Factors for Survival in a French Multicenter, Contemporary Cohort.

PubMed

Pouessel, Damien; Bastuji-Garin, Sylvie; Houédé, Nadine; Vordos, Dimitri; Loriot, Yohann; Chevreau, Christine; Sevin, Emmanuel; Beuzeboc, Philippe; Taille, Alexandre de la; Le Thuaut, Aurélie; Allory, Yves; Culine, Stéphane

2017-02-01

In the past decade, adjuvant chemotherapy (AC) after radical cystectomy (RC) was preferred worldwide for patients with muscle-invasive urothelial bladder cancer. In this study we aimed to determine the outcome of patients who received AC and evaluated prognostic factors associated with survival. We retrospectively analyzed 226 consecutive patients treated in 6 academic hospitals between 2000 and 2009. Multivariate Cox proportional hazards regression adjusted for center to estimate adjusted hazard ratios (HRs) with 95% confidence intervals were used. The median age was 62.4 (range, 35-82) years. Patients had pT3/pT4 and/or pN+ in 180 (79.6%) and 168 patients (74.3%), respectively. Median lymph node (LN) density was 25% (range, 3.1-100). Median time between RC and AC was 61.5 (range, 18-162) days. Gemcitabine with cisplatin, gemcitabine with carboplatin, and MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimens were delivered in 161 (71.2%), 49 (21.7%), and 12 patients (5.3%) of patients, respectively. The median number of cycles was 4 (range, 1-6). Thirteen patients (5.7%) with LN metastases also received adjuvant pelvic radiotherapy (ART). After a median follow-up of 4.2 years, 5-year overall survival (OS) was 40.7%. In multivariate analysis, pT ≥3 stage (HR, 1.73; P = .05), LN density >50% (HR, 1.94; P = .03), and number of AC cycles <4 (HR, 4.26; P = .001) were adverse prognostic factors for OS. ART (HR, 0.30; P = .05) tended to provide survival benefit. Classical prognostic features associated with survival are not modified by the use of AC. Patients who derived benefit from AC had a low LN density and received at least 4 cycles of treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of uric acid levels on the risk of long-term cardiovascular mortality in patients with type 2 diabetes mellitus.

PubMed

Ilundain-González, Ana Isabel; Gimeno-Orna, José Antonio; Sáenz-Abad, Daniel; Pons-Dolset, Jordi; Cebollada-Del Hoyo, Jesús; Lahoza-Pérez, María Del Carmen

Hyperuricemia is associated to cardiovascular disease. However, the contribution of uric acid (UA) to cardiovascular mortality in diabetic patients is controversial. To assess the impact of UA levels on the risk of cardiovascular mortality risk in a cohort of patients with type 2 diabetes mellitus (T2DM). A prospective cohort study on outpatients with T2DM. The clinical endpoint was cardiovascular death. Anthropometric, demographic, clinical, and biochemical variables were collected, including UA levels, urinary albumin excretion and estimated glomerular filtration rate. The independent contribution of UA levels to cardiovascular mortality was assessed using multivariate Cox regression models, progressively adjusted for potential confounders. A total of 452 patients with a mean age of 65.9 (SD 9.5) years were enrolled. Mean UA level was 4.2mg/dL. Quartiles of UA levels were Q1 < 3.3; Q2: 3.3-4.2; Q3: 4.3-5.1; Q4 > 5.1mg/dL. UA levels significantly correlated with estimated glomerular filtration rate (Rho=-0.227; p<0.001). During a median follow-up time of 13 years, cardiovascular mortality rates were higher in Q4 of the UA distribution (Q1: 10.7; Q2: 11.7; Q3: 10.7; Q4: 21.6 per 1000 patient-years; p = 0.027). UA was a predictor of cardiovascular mortality in the univariate analysis (HR1mg/dL = 1.30; p=0.002), but not in a multivariate analysis adjusted for urinary albumin excretion and eGFR (HR1mg/dL=1.20; p=0.12). High UA levels are associated to cardiovascular mortality in patients with T2DM. However, the role of UA may be mediated by impaired kidney function in patients with hyperuricemia. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Mediterranean Diet, Retinopathy, Nephropathy, and Microvascular Diabetes Complications: A Post Hoc Analysis of a Randomized Trial.

PubMed

Díaz-López, Andrés; Babio, Nancy; Martínez-González, Miguel A; Corella, Dolores; Amor, Antonio J; Fitó, Montse; Estruch, Ramon; Arós, Fernando; Gómez-Gracia, Enrique; Fiol, Miquel; Lapetra, José; Serra-Majem, Lluís; Basora, Josep; Basterra-Gortari, F Javier; Zanon-Moreno, Vicente; Muñoz, Miguel Ángel; Salas-Salvadó, Jordi

2015-11-01

To date no clinical trials have evaluated the role of dietary patterns on the incidence of microvascular diabetes complications. We hypothesized that a nutritional intervention based on the Mediterranean diet (MedDiet) would have greater protective effect on diabetic retinopathy and nephropathy than a low-fat control diet. This was a post hoc analysis of a cohort of patients with type 2 diabetes participating in the PREvención con DIeta MEDiterránea (PREDIMED) study, a multicenter randomized nutritional intervention trial conducted in a population at high cardiovascular risk. Individuals with type 2 diabetes who were free of microvascular complications at enrollment (n = 3,614, aged 55-80 years) were randomly assigned to one of three dietary interventions: MedDiet supplemented with extravirgin olive oil (MedDiet+EVOO), MedDiet supplemented with mixed nuts (MedDiet+Nuts), or a low-fat control diet. Two independent outcomes were considered: new onset of diabetic retinopathy and nephropathy. Hazard ratios (HRs) were calculated using multivariable-adjusted Cox regression. During a median follow-up of 6.0 years, we identified 74 new cases of retinopathy and 168 of nephropathy. Compared with the control diet, multivariable-adjusted HRs for diabetic retinopathy were 0.56 (95% CI 0.32-0.97) for the MedDiet+EVOO and 0.63 (0.35-1.11) for the MedDiet+Nuts. No between-group differences were found for nephropathy. When the yearly updated information on adherence to the MedDiet was considered, the HR for retinopathy in the highest versus the lowest quintile was 0.34 (0.13-0.89; P = 0.001 for trend). No significant associations were found for nephropathy. A MedDiet enriched with EVOO may protect against diabetic retinopathy but not diabetic nephropathy. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Residual pathological stage at radical cystectomy significantly impacts outcomes for initial T2N0 bladder cancer.

PubMed

Isbarn, Hendrik; Karakiewicz, Pierre I; Shariat, Shahrokh F; Capitanio, Umberto; Palapattu, Ganesh S; Sagalowsky, Arthur I; Lotan, Yair; Schoenberg, Mark P; Amiel, Gilad E; Lerner, Seth P; Sonpavde, Guru

2009-08-01

We hypothesized that in patients with T2N0 stage disease at transurethral bladder tumor resection a lower residual cancer stage (P1N0 or less) at radical cystectomy may correlate with improved outcomes relative to those with residual P2N0 disease. We analyzed 208 patients with T2N0 stage disease at transurethral bladder tumor resection whose tumors were organ confined at radical cystectomy (P2 or lower, pN0). None received perioperative chemotherapy. Kaplan-Meier as well as univariable and multivariable Cox regression models addressed the effect of residual pT stage at radical cystectomy on recurrence and cancer specific mortality rates. Covariates consisted of age, gender, grade, lymphovascular invasion, carcinoma in situ, number of lymph nodes removed and year of surgery. Residual pT stage at radical cystectomy was P0 in 24 (11.5%) patients, Pa in 9 (4.3%), PCIS in 22 (10.6%), P1 in 35 (16.8%) and P2 in 118 (56.7%). Median followup of censored patients was 55.7 months for recurrence and 52.1 months for cancer specific mortality analyses. The 5-year recurrence-free survival rates of patients with P0/Pa/PCIS, P1 and P2 stage disease were 100%, 85% and 75%, respectively. The 5-year cancer specific survival rates for the same cohorts were 100%, 93% and 81%, respectively. On multivariable analysis the effect of residual stage P1 or lower at radical cystectomy achieved independent predictor status for recurrence (adjusted HR 0.20, p = 0.002) and cancer specific mortality (adjusted HR 0.24, p = 0.02). Down staging from initial T2N0 bladder cancer at transurethral bladder tumor resection to lower stage at radical cystectomy significantly reduces recurrence and cancer specific mortality. Further validation of this finding is warranted.

Associations between tooth loss and prognostic biomarkers and the risk for cardiovascular events in patients with stable coronary heart disease.

PubMed

Vedin, Ola; Hagström, Emil; Östlund, Ollie; Avezum, Alvaro; Budaj, Andrzej; Flather, Marcus D; Harrington, Robert A; Koenig, Wolfgang; Soffer, Joseph; Siegbahn, Agneta; Steg, Philippe Gabriel; Stewart, Ralph A H; Wallentin, Lars; White, Harvey D; Held, Claes

2017-10-15

Underlying mechanisms behind the hypothesized relationship between periodontal disease (PD) and coronary heart disease (CHD) have been insufficiently explored. We evaluated associations between self-reported tooth loss- a marker of PD- and prognostic biomarkers in 15,456 (97%) patients with stable CHD in the global STABILITY trial. Baseline blood samples were obtained and patients reported their number of teeth according to the following tooth loss levels: "26-32 (All)" [lowest level], "20-25", "15-19", "1-14", and "No Teeth" [highest level]. Linear and Cox regression models assessed associations between tooth loss levels and biomarker levels, and the relationship between tooth loss levels and outcomes, respectively. After multivariable adjustment, the relative biomarker increase between the highest and the lowest tooth loss level was: high-sensitivity C-reactive protein 1.21 (95% confidence interval, 1.14-1.29), interleukin 6 1.14 (1.10-1.18), lipoprotein-associated phospholipase A 2 activity 1.05 (1.03-1.06), growth differentiation factor 15 1.11 (1.08-1.14), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1.18 (1.11-1.25). No association was detected for high-sensitivity troponin T 1.02 (0.98-1.05). Some attenuation of the relationship between tooth loss and outcomes resulted from the addition of biomarkers to the multivariable analysis, of which NT-proBNP had the biggest impact. A graded and independent association between tooth loss and several prognostic biomarkers was observed, suggesting that tooth loss and its underlying mechanisms may be involved in multiple pathophysiological pathways also implicated in the development and prognosis of CHD. The association between tooth loss and cardiovascular death and stroke persisted despite comprehensive adjustment including prognostic biomarkers. www.clinicaltrials.gov; NCT00799903. Copyright © 2017 Elsevier B.V. All rights reserved.

All-cause mortality in asymptomatic persons with extensive Agatston scores above 1000.

PubMed

Patel, Jaideep; Blaha, Michael J; McEvoy, John W; Qadir, Sadia; Tota-Maharaj, Rajesh; Shaw, Leslee J; Rumberger, John A; Callister, Tracy Q; Berman, Daniel S; Min, James K; Raggi, Paolo; Agatston, Arthur A; Blumenthal, Roger S; Budoff, Matthew J; Nasir, Khurram

2014-01-01

Risk assessment in the extensive calcified plaque phenotype has been limited by small sample size. We studied all-cause mortality rates among asymptomatic patients with markedly elevated Agatston scores > 1000. We studied a clinical cohort of 44,052 asymptomatic patients referred for coronary calcium scans. Mean follow-up was 5.6 years (range, 1-13 years). All-cause mortality rates were calculated after stratifying by Agatston score (0, 1-1000, 1001-1500, 1500-2000, and >2000). A multivariable Cox regression model adjusting for self-reported traditional risk factors was created to assess the relative mortality hazard of Agatston scores 1001 to 1500, 1501 to 2000, and >2000. With the use of post-estimation modeling, we assessed for the presence of an upper threshold of risk with high Agatston scores. A total of 1593 patients (4% of total population) had Agatston score > 1000. There was a continuous graded decrease in estimated 10-year survival across increasing Agatston score, continuing when Agatston score > 1000 (Agatston score 1001-1500, 78%; Agatston score 1501-2000, 74%; Agatston score > 2000, 51%). After multivariable adjustment, Agatston scores 1001 to 1500, 1501 to 2000, and >2000 were associated with an 8.05-, 7.45-, and 13.26-fold greater mortality risk, respectively, than for Agatston score of 0. Compared with Agatston score 1001 to 1500, Agatston score 1501 to 2000 had a similar all-cause mortality risk, whereas Agatston score > 2000 had an increased relative risk (Agatston score 1501-2000: hazard ratio [HR], 1.01 [95% CI, 0.67-1.51]; Agatston score > 2000: HR, 1.79 [95% CI, 1.30-2.46]). Graphical assessment of the predicted survival model suggests no upper threshold for risk associated with calcified plaque in coronary arteries. Increasing calcified plaque in coronary arteries continues to predict a graded decrease in survival among patients with extensive Agatston score > 1000 with no apparent upper threshold. Published by Elsevier Inc.

Association of chemokine receptor gene (CCR2-CCR5) haplotypes with acquisition and control of HIV-1 infection in Zambians

PubMed Central

2011-01-01

Background Polymorphisms in chemokine (C-C motif) receptors 2 and 5 genes (CCR2 and CCR5) have been associated with HIV-1 infection and disease progression. We investigated the impact of CCR2-CCR5 haplotypes on HIV-1 viral load (VL) and heterosexual transmission in an African cohort. Between 1995 and 2006, cohabiting Zambian couples discordant for HIV-1 (index seropositive and HIV-1 exposed seronegative {HESN}) were monitored prospectively to determine the role of host genetic factors in HIV-1 control and heterosexual transmission. Genotyping for eight CCR2 and CCR5 variants resolved nine previously recognized haplotypes. By regression and survival analytic techniques, controlling for non-genetic factors, we estimated the effects of these haplotypic variants on a) index partner VL, b) seroconverter VL, c) HIV-1 transmission by index partners, d) HIV-1 acquisition by HESN partners. Results Among 567 couples, 240 virologically linked transmission events had occurred through 2006. HHF*2 homozygosity was associated with significantly lower VL in seroconverters (mean beta = -0.58, log10 P = 0.027) and the HHD/HHE diplotype was associated with significantly higher VL in the seroconverters (mean beta = 0.54, log10 P = 0.014) adjusted for age and gender in multivariable model. HHD/HHE was associated with more rapid acquisition of infection by the HESNs (HR = 2.0, 95% CI = 1.20-3.43, P = 0.008), after adjustments for index partner VL and the presence of genital ulcer or inflammation in either partner in Cox multivariable models. The HHD/HHE effect was stronger in exposed females (HR = 2.1, 95% CI = 1.14-3.95, P = 0.018). Conclusions Among Zambian discordant couples, HIV-1 coreceptor gene haplotypes and diplotypes appear to modulate HIV-1 VL in seroconverters and alter the rate of HIV-1 acquisition by HESNs. These associations replicate or resemble findings reported in other African and European populations. PMID:21429204

Exercise Decreases and Smoking Increases Bladder Cancer Mortality

PubMed Central

Liss, Michael A.; White, Martha; Natarajan, Loki; Parsons, J. Kellogg

2018-01-01

Modifiable lifestyle factors play an important role regarding the development and outcomes in solid tumors. Whereas smoking has been attributed to bladder cancer and cessation leads to better outcome, we show that exercise may provide similar benefits regarding bladder cancer mortality Background The aim of this study was to investigate modifiable lifestyle factors of smoking, exercise, and obesity with bladder cancer mortality. Patients and Methods We used mortality-linked data from the National Health Information Survey from 1998 through 2006. The primary outcome was bladder cancer-specific mortality. The primary exposures were self-reported smoking status (never- vs. former vs. current smoker), self-reported exercise (dichotomized as “did no exercise” vs. “light, moderate, or vigorous exercise in ≥ 10-minute bouts”), and body mass index. We utilized multivariable adjusted Cox proportional hazards regression models, with delayed entry to account for age at survey interview. Results Complete data were available on 222,163 participants, of whom 96,715 (44%) were men and 146,014 (66%) were non-Hispanic whites, and among whom we identified 83 bladder cancer-specific deaths. In multivariate analyses, individuals who reported any exercise were 47% less likely (adjusted hazard ratio [HRadj], 0.53; 95% confidence interval [CI], 0.29–0.96; P = .038) to die of bladder cancer than “no exercise”. Compared with never-smokers, current (HRadj, 4.24; 95% CI, 1.89–9.65; P = .001) and former (HRadj, 2.95; 95% CI, 1.50–5.79; P = .002) smokers were 4 and 3 times more likely, respectively, to die of bladder cancer. There were no significant associations of body mass index with bladder cancer mortality. Conclusion Exercise decreases and current smoking increases the risk of bladder cancer-specific mortality. These data suggest that exercise and smoking cessation interventions may reduce bladder cancer death. PMID:28007367

Meat consumption, ornithine decarboxylase gene polymorphism, and outcomes after colorectal cancer diagnosis

PubMed Central

Zell, Jason A.; Lin, Bruce S.; Ziogas, Argyrios; Anton-Culver, Hoda

2012-01-01

Background: Dietary arginine and meat consumption are implicated in colorectal cancer (CRC) progression via polyamine-dependent processes. Polymorphism in the polyamine-regulatory gene, ornithine decarboxylase 1 (Odc1, rs2302615) is prognostic for CRC-specific mortality. Here, we examined joint effects of meat consumption and Odc1 polymorphism on CRC-specific mortality. Materials and Methods: The analytic cohort was comprised of 329 incident stage I-III CRC cases diagnosed 1994-1996 with follow- up through March 2008. Odc1 genotyping was conducted using primers that amplify a 172-bp fragment containing the polymorphic base at +316. Dietary questionnaires were administered at cohort entry. Multivariate Cox proportional hazards regression analysis for CRC-specific mortality was stratified by tumor, node, metastasis (TNM) stage, and adjusted for clinically relevant variables, plus meat consumption (as a continuous variable, i.e., the number of medium-sized servings/week), Odc1 genotype, and a term representing the meat consumption and Odc1 genotype interaction. The primary outcome was the interaction of Odc1 and meat intake on CRC-specific mortality, as assessed by departures from multiplicative joint effects. Results: Odc1 genotype distribution was 51% GG, 49% GA/AA. In the multivariate model, there was a significant interaction between meat consumption and Odc1 genotype, P-int = 0.01. Among Odc1 GA/AA CRC cases in meat consumption Quartiles 1-3, increased mortality risk was observed when compared to GG cases (adjusted hazards ratio (HR) = 7.06 [95% CI 2.34-21.28]) – a difference not found among cases in the highest dietary meat consumption Quartile 4. Conclusions: Effects of meat consumption on CRC-specific mortality risk differ based on genetic polymorphism at Odc1. These results provide further evidence that polyamine metabolism and its modulation by dietary factors such as meat may have relevance to CRC outcomes. PMID:23233821

Association between preoperative erectile dysfunction and prostate cancer features--an analysis from the Duke Prostate Center Database.

PubMed

Kimura, Masaki; Bañez, Lionel L; Gerber, Leah; Qi, Jim; Tsivian, Matvey; Freedland, Stephen J; Satoh, Takefumi; Polascik, Thomas J; Baba, Shiro; Moul, Judd W

2012-04-01

Erectile dysfunction (ED) is related to several co-morbidities including obesity, metabolic syndrome, cigarette smoking, and low testosterone, all of which have been reported to be associated with adverse prostate cancer features. To examine whether preoperative ED has a relationship with adverse prostate cancer features in patients who underwent radical prostatectomy (RP). We analyzed data from our institution on 676 patients who underwent RP between 2001 and 2010. Crude and adjusted logistic regression models were used to investigate the association between preoperative ED and several pathological parameters. The log-rank test and multivariate proportional hazards model were conducted to determine the association of preoperative ED with biochemical recurrence (BCR). The expanded prostate cancer index composite (EPIC) instrument was used to evaluate preoperative erectile function (EF). Preoperative normal EF was defined as EPIC-SF ≥ 60 points while ED was defined as preoperative EPIC-SF lower than 60 points. Preoperatively, a total of 343 (50.7%) men had normal EF and 333 (49.3%) men had ED. After adjusting for covariates, preoperative ED was identified a risk factor for positive extracapsular extension (OR 1.57; P = 0.029) and high percentage of tumor involvement (OR 1.56; P = 0.047). In a Kaplan-Meier curve, a trend was identified that patients with ED had higher incidence of BCR than men with normal EF (P = 0.091). Moreover, using a multivariate Cox model, higher preoperative EF was negatively associated with BCR (HR 0.99; P = 0.014). These results suggest that the likelihood for adverse pathological outcomes as well as BCR following prostatectomy is higher among men with preoperative ED, though these results require validation in larger datasets. The present study indicates that preoperative ED might be a surrogate for adverse prostate cancer outcomes following RP. © 2011 International Society for Sexual Medicine.

Fasting and 2-hour plasma glucose, and HbA1c in pregnancy and the postpartum risk of diabetes among Chinese women with gestational diabetes.

PubMed

Liu, Huikun; Zhang, Shuang; Wang, Leishen; Leng, Junhong; Li, Weiqin; Li, Nan; Li, Min; Qiao, Yijuan; Tian, Huiguang; Tuomilehto, Jaakko; Yang, Xilin; Yu, Zhijie; Hu, Gang

2016-02-01

Very few studies have assessed the association of fasting and 2h glucose, and HbA1c during pregnancy with postpartum diabetes risk among women with prior gestational diabetes mellitus (GDM). We assessed the association of fasting glucose, 2h glucose and HbA1c at 26-30 gestational weeks with postpartum diabetes risk among women with prior GDM. A cohort study in 1263 GDM women at 1-5 years after delivery was performed. Cox proportional hazards regression models were used to evaluate the association of fasting and 2h plasma glucose, and HbA1c at 26-30 gestational weeks with the risk of diabetes at postpartum. The multivariable-adjusted (age, pre-pregnancy body mass index, weight gain during pregnancy, current body mass index, family history of diabetes, marital status, education, family income, smoking status, passive smoking, leisure-time physical activity, alcohol drinking, and intake of energy, saturated fat, and dietary fiber) hazard ratios of postpartum diabetes were 1.61 (95% confidence interval [CI]: 1.36-1.91) for each 1 mmol/l increase in fasting glucose during pregnancy, 1.63 (95% CI: 1.45-1.84) for each 1 mmol/l increase in 2h glucose during pregnancy, 2.11 (95% CI: 1.50-2.97) for each 1 unit (%) increase in HbA1c during pregnancy. When fasting glucose, 2h glucose and HbA1c during pregnancy were entered multivariable-adjusted model simultaneously, 2h glucose and HbA1c but not fasting glucose remained to be significant and positive predictors for postpartum diabetes. For women with prior GDM, 2h plasma glucose and HbA1c during pregnancy are independent predictors of postpartum diabetes, but fasting plasma glucose during pregnancy is not. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Symptoms of Insomnia and Sleep Duration and Their Association with Incident Strokes: Findings from the Population-Based MONICA/KORA Augsburg Cohort Study.

PubMed

Helbig, A Katharina; Stöckl, Doris; Heier, Margit; Ladwig, Karl-Heinz; Meisinger, Christa

2015-01-01

To examine the relationship between symptoms of insomnia and sleep duration and incident total (non-fatal plus fatal) strokes, non-fatal strokes, and fatal strokes in a large cohort of men and women from the general population in Germany. In four population-based MONICA (monitoring trends and determinants in cardiovascular disease)/KORA (Cooperative Health Research in the Region of Augsburg) surveys conducted between 1984 and 2001, 17,604 men and women (aged 25 to 74 years) were asked about issues like sleep, health behavior, and medical history. In subsequent surveys and mortality follow-ups, incident stroke cases (cerebral hemorrhage, ischemic stroke, transient ischemic attack, unknown stroke type) were gathered prospectively until 2009. Sex-specific hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using sequential Cox proportional hazards regression models. During a mean follow-up of 14 years, 917 strokes (710 non-fatal strokes and 207 fatal strokes) were observed. Trouble falling asleep and difficulty staying asleep were not significantly related to any incident stroke outcome in either sex in the multivariable models. Among men, the HR for the association between short (≤5 hours) and long (≥10 hours) daily sleep duration and total strokes were 1.44 (95% CI: 1.01-2.06) and 1.63 (95% CI: 1.16-2.29), after adjustment for basic confounding variables. As for non-fatal strokes and fatal strokes, in the analyses adjusted for age, survey, education, physical activity, alcohol consumption, smoking habits, body mass index, hypertension, diabetes, and dyslipidemia, the increased risks persisted, albeit somewhat attenuated, but no longer remained significant. Among women, in the multivariable analyses the quantity of sleep was also not related to any stroke outcome. In the present study, symptoms of insomnia and exceptional sleep duration were not significantly predictive of incident total strokes, non-fatal strokes, and fatal strokes in either sex.

Symptoms of Insomnia and Sleep Duration and Their Association with Incident Strokes: Findings from the Population-Based MONICA/KORA Augsburg Cohort Study

PubMed Central

Helbig, A. Katharina; Stöckl, Doris; Heier, Margit; Ladwig, Karl-Heinz; Meisinger, Christa

2015-01-01

Objective To examine the relationship between symptoms of insomnia and sleep duration and incident total (non-fatal plus fatal) strokes, non-fatal strokes, and fatal strokes in a large cohort of men and women from the general population in Germany. Methods In four population-based MONICA (monitoring trends and determinants in cardiovascular disease)/KORA (Cooperative Health Research in the Region of Augsburg) surveys conducted between 1984 and 2001, 17,604 men and women (aged 25 to 74 years) were asked about issues like sleep, health behavior, and medical history. In subsequent surveys and mortality follow-ups, incident stroke cases (cerebral hemorrhage, ischemic stroke, transient ischemic attack, unknown stroke type) were gathered prospectively until 2009. Sex-specific hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using sequential Cox proportional hazards regression models. Results During a mean follow-up of 14 years, 917 strokes (710 non-fatal strokes and 207 fatal strokes) were observed. Trouble falling asleep and difficulty staying asleep were not significantly related to any incident stroke outcome in either sex in the multivariable models. Among men, the HR for the association between short (≤5 hours) and long (≥10 hours) daily sleep duration and total strokes were 1.44 (95% CI: 1.01–2.06) and 1.63 (95% CI: 1.16–2.29), after adjustment for basic confounding variables. As for non-fatal strokes and fatal strokes, in the analyses adjusted for age, survey, education, physical activity, alcohol consumption, smoking habits, body mass index, hypertension, diabetes, and dyslipidemia, the increased risks persisted, albeit somewhat attenuated, but no longer remained significant. Among women, in the multivariable analyses the quantity of sleep was also not related to any stroke outcome. Conclusion In the present study, symptoms of insomnia and exceptional sleep duration were not significantly predictive of incident total strokes, non-fatal strokes, and fatal strokes in either sex. PMID:26230576

Fasting and 2-hour plasma glucose, and HbA1c in pregnancy and the postpartum risk of diabetes among Chinese women with gestational diabetes

PubMed Central

Liu, Huikun; Zhang, Shuang; Wang, Leishen; Leng, Junhong; Li, Weiqi; Li, Nan; Li, Min; Qiao, Yijuan; Tian, Huiguang; Tuomilehto, Jaakko; Yang, Xilin; Yu, Zhijie; Hu, Gang

2015-01-01

Aims Very few studies have assessed the association of fasting and 2-hour glucose, and HbA1c during pregnancy with postpartum diabetes risk among women with prior gestational diabetes (GDM). We assessed the association of fasting glucose, 2-hour glucose and HbA1c at 26-30 gestational weeks with postpartum diabetes risk among women with prior GDM. Methods A cohort study in 1,263 GDM women at 1–5 years after delivery was performed. Cox proportional hazards regression models were used to evaluate the association of fasting and 2-hour plasma glucose, and HbA1c at 26-30 gestational weeks with the risk of diabetes at postpartum. Results The multivariable-adjusted (age, pre-pregnancy body mass index, weight gain during pregnancy, current body mass index, family history of diabetes, marital status, education, family income, smoking status, passive smoking, leisure-time physical activity, alcohol drinking, and intake of energy, saturated fat, and dietary fiber) hazard ratios of postpartum diabetes were 1.61 (95% confidence interval [CI]: 1.36–1.91) for each 1 mmol/l increase in fasting glucose during pregnancy, 1.63 (95% CI: 1.45–1.84) for each 1 mmol/l increase in 2-hour glucose during pregnancy, 2.11 (95% CI: 1.50–2.97) for each 1 unit (%) increase in HbA1c during pregnancy. When fasting glucose, 2-hour glucose and HbA1c during pregnancy were entered multivariable-adjusted model simultaneously, 2-hour glucose and HbA1c but not fasting glucose remained to be significant and positive predictors for postpartum diabetes. Conclusions For women with prior GDM, 2-hour plasma glucose and HbA1c during pregnancy are independent predictors of postpartum diabetes, but fasting plasma glucose during pregnancy is not. PMID:26686048

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

PubMed

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

2015-01-01

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

Cumulative HIV viremia and non-AIDS-defining malignancies among a sample of HIV-infected male veterans.

PubMed

Kowalkowski, Marc A; Day, Rena S; Du, Xianglin L; Chan, Wenyaw; Chiao, Elizabeth Y

2014-10-01

Research suggests that cumulative measurement of HIV exposure is associated with mortality, AIDS, and AIDS-defining malignancies. However, the relationship between cumulative HIV and non-AIDS-defining malignancies (NADMs) remains unclear. The aim of this study was to evaluate the effect of different HIV measures on NADM hazard among HIV-infected male veterans. We performed a retrospective cohort study using Veterans Affairs HIV Clinical Case Registry data from 1985 to 2010. We analyzed the relationship between HIV exposure (recent HIV RNA, % undetectable HIV RNA, and HIV copy-years viremia) and NADM. To evaluate the effect of HIV, we calculated hazard ratios for 3 common virally associated NADM [ie, hepatocarcinoma (HCC), Hodgkin lymphoma (HL), and squamous cell carcinoma of the anus (SCCA)] in multivariable Cox regression models. Among 31,576 HIV-infected male veterans, 383 HCC, 211 HL, and 373 SCCA cases were identified. In multivariable regression models, cross-sectional HIV measurement was not associated with NADM. However, compared with <20% undetectable HIV, individuals with ≥80% had decreased HL [adjusted hazard ratio (aHR) = 0.62; 95% confidence interval (CI): 0.37 to 1.02] and SCCA (aHR = 0.64; 95% CI: 0.44 to 0.93). Conversely, each log10 increase in HIV copy-years was associated with elevated HL (aHR = 1.22; 95% CI: 1.06 to 1.40) and SCCA (aHR = 1.36; 95% CI: 1.21 to 1.52). Model fit was best with HIV copy-years. Cumulative HIV was not associated with HCC. Cumulative HIV was associated with certain virally associated NADM (ie, HL and SCCA), independent of measured covariates. Findings underline the importance of early treatment initiation and durable medication adherence to reduce cumulative HIV burden. Future research should prioritize how to best apply cumulative HIV measures in screening for these cancers.

Possible Protective Effect of Hydroxychloroquine on Retarding the Occurrence of Integument Damage in Lupus: Data from LUMINA, a Multiethnic Cohort

PubMed Central

Pons-Estel, Guillermo J.; Alarcón, Graciela S.; González, Luis A.; Zhang, Jie; Vilá, Luis M.; Reveille, John D.; McGwin, Gerald

2010-01-01

Objective To determine the features predictive of time-to-integument damage in patients with systemic lupus erythematosus (SLE) from a multiethnic cohort (LUMINA). Methods SLE LUMINA patients (n=580), age ≥16 years, disease duration ≤5 years at baseline (T0), of African American, Hispanic and Caucasian ethnicity were studied. Integument damage was defined per the SLICC damage index (scarring alopecia, extensive skin scarring and skin ulcers lasting at least six months); factors associated with time-to-its occurrence were examined by Cox proportional univariable and multivariable (main model) hazards regression analyses. Two alternative models were also examined; in model 1 all patients, regardless of when integument damage occurred (n=94), were included; in model 2 a time-varying approach (GEE) was employed. Results Thirty-nine (6.7%) of 580 patients developed integument damage over a mean (SD) total disease duration of 5.9 (3.7) years and were included in the main multivariable regression model. After adjusting for discoid rash, nailfold infarcts, photosensitivity and Raynaud’s phenomenon (significant in the univariable analyses), disease activity over time [Hazard ratio (HR)=1.17; 95% Confidence interval (CI) 1.09–1.26)] was associated with a shorter time-to-integument damage whereas hydroxychloroquine use (HR=0.23, 95% CI 0.12–0.47) and Texan-Hispanic (HR=0.35; 95% CI 0.14–0.87) and Caucasian ethnicities (HR=0.37; 95% CI 0.14–0.99) were associated with a longer time. Results of the alternative models were consistent with those of the main model albeit in model 2 the association with hydroxychloroquine was not significant. Conclusions Our data indicate that hydroxychloroquine use is possibly associated with a delay in integument damage development in patients with SLE. PMID:20391486

Ethnicity Modifies Associations between Cardiovascular Risk Factors and Disease Severity in Parallel Dutch and Singapore Coronary Cohorts

PubMed Central

Gijsberts, Crystel M.; Seneviratna, Aruni; de Carvalho, Leonardo P.; den Ruijter, Hester M.; Vidanapthirana, Puwalani; Sorokin, Vitaly; Stella, Pieter; Agostoni, Pierfrancesco; Asselbergs, Folkert W.; Richards, A. Mark; Low, Adrian F.; Lee, Chi-Hang; Tan, Huay Cheem; Hoefer, Imo E.; Pasterkamp, Gerard; de Kleijn, Dominique P. V.; Chan, Mark Y.

2015-01-01

Background In 2020 the largest number of patients with coronary artery disease (CAD) will be found in Asia. Published epidemiological and clinical reports are overwhelmingly derived from western (White) cohorts and data from Asia are scant. We compared CAD severity and all-cause mortality among 4 of the world’s most populous ethnicities: Whites, Chinese, Indians and Malays. Methods The UNIted CORoNary cohort (UNICORN) simultaneously enrolled parallel populations of consecutive patients undergoing coronary angiography or intervention for suspected CAD in the Netherlands and Singapore. Using multivariable ordinal regression, we investigated the independent association of ethnicity with CAD severity and interactions between risk factors and ethnicity on CAD severity. Also, we compared all-cause mortality among the ethnic groups using multivariable Cox regression analysis. Results We included 1,759 White, 685 Chinese, 201 Indian and 224 Malay patients undergoing coronary angiography. We found distinct inter-ethnic differences in cardiovascular risk factors. Furthermore, the associations of gender and diabetes with severity of CAD were significantly stronger in Chinese than Whites. Chinese (OR 1.3 [1.1–1.7], p = 0.008) and Malay (OR 1.9 [1.4–2.6], p<0.001) ethnicity were independently associated with more severe CAD as compared to White ethnicity. Strikingly, when stratified for diabetes status, we found a significant association of all three Asian ethnic groups as compared to White ethnicity with more severe CAD among diabetics, but not in non-diabetics. Crude all-cause mortality did not differ, but when adjusted for covariates mortality was higher in Malays than the other ethnic groups. Conclusion In this population of individuals undergoing coronary angiography, ethnicity is independently associated with the severity of CAD and modifies the strength of association between certain risk factors and CAD severity. Furthermore, mortality differs among ethnic groups. Our data provide insight in inter-ethnic differences in CAD risk factors, CAD severity and mortality. PMID:26147693

Adjustment of geochemical background by robust multivariate statistics

USGS Publications Warehouse

Zhou, D.

1985-01-01

Conventional analyses of exploration geochemical data assume that the background is a constant or slowly changing value, equivalent to a plane or a smoothly curved surface. However, it is better to regard the geochemical background as a rugged surface, varying with changes in geology and environment. This rugged surface can be estimated from observed geological, geochemical and environmental properties by using multivariate statistics. A method of background adjustment was developed and applied to groundwater and stream sediment reconnaissance data collected from the Hot Springs Quadrangle, South Dakota, as part of the National Uranium Resource Evaluation (NURE) program. Source-rock lithology appears to be a dominant factor controlling the chemical composition of groundwater or stream sediments. The most efficacious adjustment procedure is to regress uranium concentration on selected geochemical and environmental variables for each lithologic unit, and then to delineate anomalies by a common threshold set as a multiple of the standard deviation of the combined residuals. Robust versions of regression and RQ-mode principal components analysis techniques were used rather than ordinary techniques to guard against distortion caused by outliers Anomalies delineated by this background adjustment procedure correspond with uranium prospects much better than do anomalies delineated by conventional procedures. The procedure should be applicable to geochemical exploration at different scales for other metals. ?? 1985.

Arteriopathy after transarterial chemo-lipiodolization for hepatocellular carcinoma.

PubMed

Matsui, Y; Figi, A; Horikawa, M; Jahangiri Noudeh, Y; Tomozawa, Y; Hashimoto, K; Kaufman, J A; Farsad, K

2017-12-01

The purpose of this study was to investigate the incidence of and the risk factors for arteriopathy in hepatic arteries after transarterial chemo-lipiodolization in patients with hepatocellular carcinoma and the subsequent treatment strategy changes due to arteriopathy. A total of 365 arteries in 167 patients (126 men and 41 women; mean age, 60.4±15.0 [SD] years [range: 18-87 years]) were evaluated for the development of arteriopathy after chemo-lipiodolization with epirubicin- or doxorubicin-Lipiodol ® emulsion. The development of arteriopathy after chemo-lipiodolization was assessed on arteriograms performed during subsequent transarterial treatments. The treatment strategy changes due to arteriopathy, including change in the chemo-lipiodolization method and the application of alternative therapies was also investigated. Univariate and multivariate binary logistic regression models were used to identify risk factors for arteriopathy and subsequent treatment strategy change. One hundred two (27.9%) arteriopathies were detected in 62/167 (37.1%) patients (45 men, 17 women) with a mean age of 63.3±7.1 [SD] years (age range, 50-86 years). The incidence of arteriopathy was highly patient dependent, demonstrating significant correlation in a fully-adjusted multivariate regression model (P<0.0001). Multivariate-adjusted regression analysis with adjustment for the patient effect showed a statistically significant association of super-selective chemo-lipiodolization (P=0.003) with the incidence of arteriopathy. Thirty of the 102 arteriopathies (29.4%) caused a change in treatment strategy. No factors were found to be significantly associated with the treatment strategy change. The incidence of arteriopathy after chemo-lipiodolization is 27.9%. Among them, 29.4% result in a change in treatment strategy. Copyright © 2017 Editions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Serum phosphorus and mortality in the Third National Health and Nutrition Examination Survey (NHANES III): effect modification by fasting.

PubMed

Chang, Alex R; Grams, Morgan E

2014-10-01

Serum phosphorus levels have been associated with mortality in some but not all studies. Because dietary intake prior to measurement can affect serum phosphorus levels, we hypothesized that the association between serum phosphorus level and mortality is strongest in those who have fasted longer. Prospective cohort study. Nationally representative sample of 12,984 participants 20 years or older in the Third National Health and Nutrition Examination Survey (1988-1994). Serum phosphorus level, fasting duration (dichotomized as ≥ 12 or < 12 hours). All-cause and cardiovascular mortality determined by death certificate data from the National Death Index. Serum phosphorus measured in a central laboratory and fasting duration recorded as time since food or drink other than water was consumed. Individuals fasting 12 or more hours had lower serum phosphorus levels than those fasting less than 12 hours (3.34 vs 3.55 mg/dL; P < 0.001) and higher correlation with repeat measurement (0.66 vs 0.53; P = 0.002). In multivariable-adjusted Cox regression models, the highest quartile of serum phosphorus was associated with increased mortality in participants fasting 12 or more hours (adjusted HR, 1.74; 95% CI, 1.38-2.20; reference, lowest quartile) but not in participants fasting less than 12 hours (adjusted HR, 1.08; 95% CI, 0.89-1.32; P for interaction = 0.002). Relationships were consistent using 8 hours as the fasting cutoff point or cardiovascular mortality as the outcome. Observational study, lack of fibroblast growth factor 23 or intact parathyroid hormone measurements. Fasting but not nonfasting serum phosphorus levels were associated with increased mortality. Risk prognostication based on serum phosphorus may be improved using fasting levels. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Association between direct measurement of active serum calcium and risk of type 2 diabetes mellitus: A prospective study.

PubMed

Zaccardi, F; Webb, D R; Carter, P; Pitocco, D; Khunti, K; Davies, M J; Kurl, S; Laukkanen, J A

2015-06-01

Previous prospective studies showing a positive association between serum calcium and incidence of type 2 diabetes mellitus (T2DM) have relied on total calcium or an indirect estimate of active, ionized calcium (iCa). We aimed to assess this relationship using a direct measurement of iCa. iCa and cardiometabolic risk factors were measured in a population-based sample of 2350 men without a known history of T2DM at baseline. Associations between iCa levels and incident cases of T2DM (self-reported, ascertained with a glucose tolerance test, or determined by record linkage to national registers) were estimated using Cox regression analyses adjusted for potential confounders. At baseline, mean (standard deviation) age was 53 (5) years and mean iCa 1.18 (0.05) mmol/L. During a median follow-up of 23.1 years, 140 new cases of T2DM were recorded. In a multivariable analysis adjusted for age, body mass index, systolic blood pressure, serum HDL-cholesterol, and family history of T2DM, there was no association comparing second (hazard ratio 0.84; 95% confidence interval 0.59-1.18), third (0.77; 0.52-1.14), or fourth (0.98; 0.69-1.39) vs first quartile of iCa (p for trend 0.538); further adjustment for C-reactive protein, physical activity level, and triglycerides did not change the estimates (p for trend 0.389). In this study, we did not find evidence of an association between direct measurement of active calcium and risk of T2DM. Further studies are needed to confirm our findings and define the relationship between factors influencing indirect calcium estimation and incident T2DM. Copyright © 2015 Elsevier B.V. All rights reserved.

Pulmonary function and adverse cardiovascular outcomes: Can cardiac function explain the link?

PubMed

Burroughs Peña, Melissa S; Dunning, Allison; Schulte, Phillip J; Durheim, Michael T; Kussin, Peter; Checkley, William; Velazquez, Eric J

2016-12-01

The complex interaction between pulmonary function, cardiac function and adverse cardiovascular events has only been partially described. We sought to describe the association between pulmonary function with left heart structure and function, all-cause mortality and incident cardiovascular hospitalization. This study is a retrospective analysis of patients evaluated in a single tertiary care medical center. We used multivariable linear regression analyses to examine the relationship between FVC and FEV1 with left ventricular ejection fraction (LVEF), left ventricular internal dimension in systole and diastole (LVIDS, LVIDD) and left atrial diameter, adjusting for baseline characteristics, right ventricular function and lung hyperinflation. We also used Cox proportional hazards models to examine the relationship between FVC and FEV1 with all-cause mortality and cardiac hospitalization. A total of 1807 patients were included in this analysis with a median age of 61 years and 50% were female. Decreased FVC and FEV1 were both associated with decreased LVEF. In individuals with FVC less than 2.75 L, decreased FVC was associated with increased all-cause mortality after adjusting for left and right heart echocardiographic variables (hazard ratio [HR] 0.49, 95% CI 0.29, 0.82, respectively). Decreased FVC was associated with increased cardiac hospitalization after adjusting for left heart size (HR 0.80, 95% CI 0.67, 0.96), even in patients with normal LVEF (HR 0.75, 95% CI 0.57, 0.97). In a tertiary care center reduced pulmonary function was associated with adverse cardiovascular events, a relationship that is not fully explained by left heart remodeling or right heart dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Survival after acute hemodialysis in Pennsylvania, 2005-2007: a retrospective cohort study.

PubMed

Ramer, Sarah J; Cohen, Elan D; Chang, Chung-Chou H; Unruh, Mark L; Barnato, Amber E

2014-01-01

Little is known about acute hemodialysis in the US. Here we describe predictors of receipt of acute hemodialysis in one state and estimate the marginal impact of acute hemodialysis on survival after accounting for confounding due to illness severity. This is a retrospective cohort study of acute-care hospitalizations in Pennsylvania from October 2005 to December 2007 using data from the Pennsylvania Health Care Cost Containment Council. Exposure variable is acute hemodialysis; dependent variable is survival following acute hemodialysis. We used multivariable logistic regression to determine propensity to receive acute hemodialysis and then, for a Cox proportional hazards model, matched acute hemodialysis and non-acute hemodialysis patients 1∶5 on this propensity. In 2,131,248 admissions of adults without end-stage renal disease, there were 6,657 instances of acute hemodialysis. In analyses adjusted for predicted probability of death upon admission plus other covariates and stratified on age, being male, black, and insured were independent predictors of receipt of acute hemodialysis. One-year post-admission mortality was 43% for those receiving acute hemodialysis, compared to 13% among those not receiving acute hemodialysis. After matching on propensity to receive acute hemodialysis and adjusting for predicted probability of death upon admission, patients who received acute hemodialysis had a higher risk of death than patients who did not over at least 1 year of follow-up (hazard ratio 1·82, 95% confidence interval 1·68-1·97). In a populous US state, receipt of acute hemodialysis varied by age, sex, race, and insurance status even after adjustment for illness severity. In a comparison of patients with similar propensity to receive acute hemodialysis, those who did receive it were less likely to survive than those who did not. These findings raise questions about reasons for lack of benefit.

Additive effect of congenital heart disease and early developmental disorders on attention-deficit/hyperactivity disorder and autism spectrum disorder: a nationwide population-based longitudinal study.

PubMed

Tsao, Pei-Chen; Lee, Yu-Sheng; Jeng, Mei-Jy; Hsu, Ju-Wei; Huang, Kai-Lin; Tsai, Shih-Jen; Chen, Mu-Hong; Soong, Wen-Jue; Kou, Yu Ru

2017-11-01

In this retrospective nationwide population-based case-control study, we investigated the impact of congenital heart disease (CHD) on the development of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), which remains unclear. Children aged <18 years that were diagnosed with CHD (n = 3552) between January 1, 1997 and December 31, 2009 were identified from the National Health Insurance Research Database in Taiwan. Non-CHD controls (n = 14,208) matched for age and sex (1:4) were selected from the same dataset. All subjects were observed until December 31, 2011 or their death. Comorbid perinatal conditions and early developmental disorders (EDD) that were diagnosed before ADHD and ASD diagnosis were also analyzed. The incidence rates of perinatal comorbidities, EDD, ADHD, and ASD were higher in the CHD group than in the control group. Multivariate Cox regression analysis revealed that the CHD group had an increased risk of developing ADHD (adjusted hazard ratio [aHR] 2.52, 95% confidence interval CI 1.96-3.25) and ASD (aHR 1.97, 95% CI 1.11-3.52) after adjusting for confounding comorbidities. EDD, but not perinatal comorbidities were also independent risk factors for ADHD and ASD after adjustment. Subgroup analysis indicated that the risk for ADHD (HR 16.59, 95% CI 12.17-22.60) and ASD (HR 80.68, 95% CI 39.96-176.12) was greatly increased in CHD subjects with EDD than in non-CHD subjects without EDD. These findings suggested that CHD at birth and EDD during early childhood were two independent risk factors for ADHD and ASD and that concurrent CHD and EDD might additively increase these risks.

Impact of individual and neighborhood factors on disparities in prostate cancer survival.

PubMed

DeRouen, Mindy C; Schupp, Clayton W; Koo, Jocelyn; Yang, Juan; Hertz, Andrew; Shariff-Marco, Salma; Cockburn, Myles; Nelson, David O; Ingles, Sue A; John, Esther M; Gomez, Scarlett L

2018-04-01

We addressed the hypothesis that individual-level factors act jointly with social and built environment factors to influence overall survival for men with prostate cancer and contribute to racial/ethnic and socioeconomic (SES) survival disparities. We analyzed multi-level data, combining (1) individual-level data from the California Collaborative Prostate Cancer Study, a population-based study of non-Hispanic White (NHW), Hispanic, and African American prostate cancer cases (N = 1800) diagnosed from 1997 to 2003, with (2) data on neighborhood SES (nSES) and social and built environment factors from the California Neighborhoods Data System, and (3) data on tumor characteristics, treatment and follow-up through 2009 from the California Cancer Registry. Multivariable, stage-stratified Cox proportional hazards regression models with cluster adjustments were used to assess education and nSES main and joint effects on overall survival, before and after adjustment for social and built environment factors. African American men had worse survival than NHW men, which was attenuated by nSES. Increased risk of death was associated with residence in lower SES neighborhoods (quintile 1 (lowest nSES) vs. 5: HR = 1.56, 95% CI: 1.11-2.19) and lower education (

Direct transport to a PCI-capable hospital is associated with improved survival after adult out-of-hospital cardiac arrest of medical aetiology.

PubMed

McKenzie, Nicole; Williams, Teresa A; Ho, Kwok M; Inoue, Madoka; Bailey, Paul; Celenza, Antonio; Fatovich, Daniel; Jenkins, Ian; Finn, Judith

2018-05-02

To compare survival outcomes of adults with out-of-hospital cardiac arrest (OHCA) of medical aetiology directly transported to a percutaneous-coronary-intervention capable (PCI-capable) hospital (direct transport) with patients transferred to a PCI-capable hospital via another hospital without PCI services available (indirect transport) by emergency medical services (EMS). This retrospective cohort study used the St John Ambulance Western Australia OHCA Database and medical chart review. We included OHCA patients (≥18 years) admitted to any one of five PCI-capable hospitals in Perth between January 2012 and December 2015. Survival to hospital discharge (STHD) and survival up to 12-months after OHCA were compared between the direct and indirect transport groups using multivariable logistic and Cox-proportional hazards regression, respectively, while adjusting for so-called "Utstein variables" and other potential confounders. Of the 509 included patients, 404 (79.4%) were directly transported to a PCI-capable hospital and 105 (20.6%) transferred via another hospital to a PCI-capable hospital; 274/509 (53.8%) patients STHD and 253/509 (49.7%) survived to 12-months after OHCA. Direct transport patients were twice as likely to STHD (adjusted odds ratio 1.97, 95% confidence interval [CI] 1.13-3.43) than those transferred via another hospital. Indirect transport was also associated with a possible increased risk of death, up to 12-months, compared to direct transport (adjusted hazard ratio 1.36, 95% CI 1.00-1.84). Direct transport to a PCI-capable hospital for post-resuscitation care is associated with a survival advantage for adults with OHCA of medical aetiology. This has implications for EMS transport protocols for patients with OHCA. Copyright © 2018 Elsevier B.V. All rights reserved.

Electrocardiographic repolarization-related variables as predictors of coronary heart disease death in the women's health initiative study.

PubMed

Rautaharju, Pentti M; Zhang, Zhu-Ming; Vitolins, Mara; Perez, Marco; Allison, Matthew A; Greenland, Philip; Soliman, Elsayed Z

2014-07-28

We evaluated 25 repolarization-related ECG variables for the risk of coronary heart disease (CHD) death in 52 994 postmenopausal women from the Women's Health Initiative study. Hazard ratios from Cox regression were computed for subgroups of women with and without cardiovascular disease (CVD). During the average follow-up of 16.9 years, 941 CHD deaths occurred. Based on electrophysiological considerations, 2 sets of ECG variables with low correlations were considered as candidates for independent predictors of CHD death: Set 1, Ѳ(Tp|Tref), the spatial angle between T peak (Tp) and normal T reference (Tref) vectors; Ѳ(Tinit|Tterm), the angle between the initial and terminal T vectors; STJ depression in V6 and rate-adjusted QTp interval (QTpa); and Set 2, TaVR and TV1 amplitudes, heart rate, and QRS duration. Strong independent predictors with over 2-fold increased risk for CHD death in women with and without CVD were Ѳ(Tp|Tref) >42° from Set 1 and TaVR amplitude >-100 μV from Set 2. The risk for these CHD death predictors remained significant after multivariable adjustment for demographic/clinical factors. Other significant predictors for CHD death in fully adjusted risk models were Ѳ(Tinit|Tterm) >30°, TV1 >175 μV, and QRS duration >100 ms. Ѳ(Tp|Tref) angle and TaVR amplitude are associated with CHD mortality in postmenopausal women. The use of these measures to identify high-risk women for further diagnostic evaluation or more intense preventive intervention warrants further study. http://www.clinicaltrials.gov. Unique identifier: NCT00000611. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Diabetes Mellitus is Associated With Higher Risk of Developing Decompensated Cirrhosis in Chronic Hepatitis C Patients.

PubMed

Saeed, Mohammed J; Olsen, Margaret A; Powderly, William G; Presti, Rachel M

2017-01-01

To investigate the association of diabetes with risk of decompensated cirrhosis in patients with chronic hepatitis C (CHC). Direct-acting antivirals are highly effective in treating CHC but very expensive. CHC patients at high risk of progression to symptomatic liver disease may benefit most from early treatment. We conducted a retrospective cohort study using the 2006 to 2013 Truven Health Analytics MarketScan Commercial Claims and Encounters database including inpatient, outpatient, and pharmacy claims from private insurers. CHC and cirrhosis were identified using ICD-9-CM diagnosis codes; baseline diabetes was identified by diagnosis codes or antidiabetic medications. CHC patients were followed to identify decompensated cirrhosis. Multivariable Cox proportional hazards regression was used to model the risk of decompensated cirrhosis by baseline cirrhosis. There were 75,805 CHC patients with median 1.9 years follow-up. A total of 10,317 (13.6%) of the CHC population had diabetes. The rates of decompensated cirrhosis per 1000 person-years were: 185.5 for persons with baseline cirrhosis and diabetes, 119.8 for persons with cirrhosis and no diabetes, 35.3 for persons with no cirrhosis and diabetes, and 17.1 for persons with no cirrhosis and no diabetes. Diabetes was associated with increased risk of decompensated cirrhosis in persons with baseline cirrhosis (adjusted hazard ratio=1.4; 95% confidence interval, 1.3-1.6) and in persons without baseline cirrhosis (adjusted hazard ratio=1.9; 95% confidence interval, 1.7-2.1). In a privately insured US population with CHC, the adjusted risk of decompensated cirrhosis was higher in diabetic compared with nondiabetic patients. Diabetes status should be included in prioritization of antiviral treatment.

Self-Reported Physical Quality of Life Before Thoracic Operations Is Associated With Long-Term Survival.

PubMed

Al-Ameri, Mamdoh; Bergman, Per; Franco-Cereceda, Anders; Sartipy, Ulrik

2017-02-01

The aim was to analyze the association between baseline self-reported health-related quality of life and long-term survival after thoracic operations. In a prospective population-based cohort study, we included patients scheduled for thoracic operations and obtained information about preoperative health-related quality of life using the validated quality-of-life instrument Short Form-36. Patients were categorized according to higher or lower physical and mental component scores, compared with an age- and sex-matched reference population. The primary outcome measure was all-cause mortality and was ascertained from Swedish national registers. We used Cox regression for estimation of hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between preoperative physical/mental quality of life and long-term survival while adjusting for differences in baseline characteristics, cancer stage, histopathologic process, and other factors. We included 249 patients between 2006 and 2008. During a median follow-up time of 8.0 years, 119 patients (48%) died. Having a physical component summary score less than reference was significantly associated with mortality (multivariable adjusted HR 2.02, 95% CI: 1.34 to 3.06, p = 0.001). A mental component summary score less than reference was not associated with mortality (adjusted HR 1.32, 95% CI: 0.84 to 3.06, p = 0.233). In patients who underwent thoracic operations, a self-reported physical quality of life lower than reference value was associated with significantly worse survival independent of histopathologic process, cancer stage, extent of operations, and other patient-related factors. The preoperative mental component of quality of life was not associated with long-term survival. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Impact of Home Health Care on Health Care Resource Utilization Following Hospital Discharge: A Cohort Study.

PubMed

Xiao, Roy; Miller, Jacob A; Zafirau, William J; Gorodeski, Eiran Z; Young, James B

2018-04-01

As healthcare costs rise, home health care represents an opportunity to reduce preventable adverse events and costs following hospital discharge. No studies have investigated the utility of home health care within the context of a large and diverse patient population. A retrospective cohort study was conducted between 1/1/2013 and 6/30/2015 at a single tertiary care institution to assess healthcare utilization after discharge with home health care. Control patients discharged with "self-care" were matched by propensity score to home health care patients. The primary outcome was total healthcare costs in the 365-day post-discharge period. Secondary outcomes included follow-up readmission and death. Multivariable linear and Cox proportional hazards regression were used to adjust for covariates. Among 64,541 total patients, 11,266 controls were matched to 6,363 home health care patients across 11 disease-based Institutes. During the 365-day post-discharge period, home health care was associated with a mean unadjusted savings of $15,233 per patient, or $6,433 after adjusting for covariates (p < 0.0001). Home health care independently decreased the hazard of follow-up readmission (HR 0.82, p < 0.0001) and death (HR 0.80, p < 0.0001). Subgroup analyses revealed that home health care most benefited patients discharged from the Digestive Disease (death HR 0.72, p < 0.01), Heart & Vascular (adjusted savings of $11,453, p < 0.0001), Medicine (readmission HR 0.71, p < 0.0001), and Neurological (readmission HR 0.67, p < 0.0001) Institutes. Discharge with home health care was associated with significant reduction in healthcare utilization and decreased hazard of readmission and death. These data inform development of value-based care plans. Copyright © 2018 Elsevier Inc. All rights reserved.

Increase in relative skeletal muscle mass over time and its inverse association with metabolic syndrome development: a 7-year retrospective cohort study.

PubMed

Kim, Gyuri; Lee, Seung-Eun; Jun, Ji Eun; Lee, You-Bin; Ahn, Jiyeon; Bae, Ji Cheol; Jin, Sang-Man; Hur, Kyu Yeon; Jee, Jae Hwan; Lee, Moon-Kyu; Kim, Jae Hyeon

2018-02-05

Skeletal muscle mass was negatively associated with metabolic syndrome prevalence in previous cross-sectional studies. The aim of this study was to investigate the impact of baseline skeletal muscle mass and changes in skeletal muscle mass over time on the development of metabolic syndrome in a large population-based 7-year cohort study. A total of 14,830 and 11,639 individuals who underwent health examinations at the Health Promotion Center at Samsung Medical Center, Seoul, Korea were included in the analyses of baseline skeletal muscle mass and those changes from baseline over 1 year, respectively. Skeletal muscle mass was estimated by bioelectrical impedance analysis and was presented as a skeletal muscle mass index (SMI), a body weight-adjusted appendicular skeletal muscle mass value. Using Cox regression models, hazard ratio for developing metabolic syndrome associated with SMI values at baseline or changes of SMI over a year was analyzed. During 7 years of follow-up, 20.1% of subjects developed metabolic syndrome. Compared to the lowest sex-specific SMI tertile at baseline, the highest sex-specific SMI tertile showed a significant inverse association with metabolic syndrome risk (adjusted hazard ratio [AHR] = 0.61, 95% confidence interval [CI] 0.54-0.68). Furthermore, compared with SMI changes < 0% over a year, multivariate-AHRs for metabolic syndrome development were 0.87 (95% CI 0.78-0.97) for 0-1% changes and 0.67 (0.56-0.79) for > 1% changes in SMI over 1 year after additionally adjusting for baseline SMI and glycometabolic parameters. An increase in relative skeletal muscle mass over time has a potential preventive effect on developing metabolic syndrome, independently of baseline skeletal muscle mass and glycometabolic parameters.

Associations of Coffee, Tea, and Caffeine Intake with Coronary Artery Calcification and Cardiovascular Events.

PubMed

Miller, P Elliott; Zhao, Di; Frazier-Wood, Alexis C; Michos, Erin D; Averill, Michelle; Sandfort, Veit; Burke, Gregory L; Polak, Joseph F; Lima, Joao A C; Post, Wendy S; Blumenthal, Roger S; Guallar, Eliseo; Martin, Seth S

2017-02-01

Coffee and tea are 2 of the most commonly consumed beverages in the world. The association of coffee and tea intake with coronary artery calcium and major adverse cardiovascular events remains uncertain. We examined 6508 ethnically diverse participants with available coffee and tea data from the Multi-Ethnic Study of Atherosclerosis. Intake for each was classified as never, occasional (<1 cup per day), and regular (≥1 cup per day). A coronary artery calcium progression ratio was derived from mixed effect regression models using loge(calcium score+1) as the outcome, with coefficients exponentiated to reflect coronary artery calcium progression ratio versus the reference. Cox proportional hazards analyses were used to evaluate the association between beverage intake and incident cardiovascular events. Over a median follow-up of 5.3 years for coronary artery calcium and 11.1 years for cardiovascular events, participants who regularly drank tea (≥1 cup per day) had a slower progression of coronary artery calcium compared with never drinkers after multivariable adjustment. This correlated with a statistically significant lower incidence of cardiovascular events for ≥1 cup per day tea drinkers (adjusted hazard ratio 0.71; 95% confidence interval 0.53-0.95). Compared with never coffee drinkers, regular coffee intake (≥1 cup per day) was not statistically associated with coronary artery calcium progression or cardiovascular events (adjusted hazard ratio 0.97; 95% confidence interval 0.78-1.20). Caffeine intake was marginally inversely associated with coronary artery calcium progression. Moderate tea drinkers had slower progression of coronary artery calcium and reduced risk for cardiovascular events. Future research is needed to understand the potentially protective nature of moderate tea intake. Published by Elsevier Inc.

Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

PubMed

Westenbrink, B Daan; Alings, Marco; Granger, Christopher B; Alexander, John H; Lopes, Renato D; Hylek, Elaine M; Thomas, Laine; Wojdyla, Daniel M; Hanna, Michael; Keltai, Matyas; Steg, P Gabriel; De Caterina, Raffaele; Wallentin, Lars; van Gilst, Wiek H

2017-03-01

Patients with atrial fibrillation (AF) are prone to cardiovascular events and anticoagulation-related bleeding complications. We hypothesized that patients with anemia are at increased risk for these outcomes. We performed a post hoc analysis of the ARISTOTLE trial, which included >18,000 patients with AF randomized to warfarin (target international normalized ratio, 2.0-3.0) or apixaban 5 mg twice daily. Multivariable Cox regression analysis was used to determine if anemia (defined as hemoglobin <13.0 in men and <12.0 g/dL in women) was associated with future stroke, major bleeding, or mortality. Anemia was present at baseline in 12.6% of the ARISTOTLE population. Patients with anemia were older, had higher mean CHADS 2 and HAS-BLED scores, and were more likely to have experienced previous bleeding events. Anemia was associated with major bleeding (adjusted hazard ratio [HR], 1.92; 95% CI, 1.62-2.28; P<.0001) and all-cause mortality (adjusted HR, 1.68; 95% CI, 1.46-1.93; P<.0001) but not stroke or systemic embolism (adjusted HR, 0.92; 95% CI, 0.70-1.21). The benefits of apixaban compared with warfarin on the rates of stroke, mortality, and bleeding events were consistent in patients with and without anemia. Chronic anemia is associated with a higher incidence of bleeding complications and mortality, but not of stroke, in anticoagulated patients with AF. Apixaban is an attractive anticoagulant for stroke prevention in patients with AF with or without anemia. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Sleep disorders and an increased risk of Parkinson's disease in individuals with non-apnea sleep disorders: a population-based cohort study.

PubMed

Hsiao, Yi-Han; Chen, Yung-Tai; Tseng, Ching-Ming; Wu, Li-An; Perng, Diahn-Warng; Chen, Yuh-Min; Chen, Tzeng-Ji; Chang, Shi-Chuan; Chou, Kun-Ta

2017-10-01

Sleep disorders are common non-motor symptoms in patients with Parkinson's disease. Our study aims to explore the relationship between non-apnea sleep disorders and future Parkinson's disease. This is a cohort study using a nationwide database. The participants were recruited from the Taiwan National Health Insurance Research Database between 2000 and 2003. A total of 91 273 adult patients who had non-apnea sleep disorders without pre-existing Parkinson's disease were enrolled. An age-, gender-, income-, urbanization- and Charlson comorbidity index score-matched control cohort consisting of 91 273 participants was selected for comparison. The two cohorts were followed for the occurrence of Parkinson's disease, death or until the end of 2010, whichever came first. The Kaplan-Meier analyses revealed patients with non-apnea sleep disorders tended to develop Parkinson's disease (log-rank test, P < 0.001). After a multivariate adjustment in a Cox regression model, non-apnea sleep disorders was an independent risk factor for the development of Parkinson's disease [crude hazard ratio: 1.63, 95% confidence interval (CI): 1.54-1.73, P < 0.001; adjusted hazard ratio: 1.18, 95% CI: 1.11-1.26, P < 0.001]. In the subgroup analysis, patients with chronic insomnia (lasting more than 3 months) had the greatest risk (crude hazard ratio: 2.91, 95% CI: 2.59-3.26, P < 0.001; adjusted hazard ratio: 1.37, 95% CI: 1.21-1.55, P < 0.001). In conclusion, this study revealed that non-apnea sleep disorders, especially chronic insomnia, are associated with a higher risk for future Parkinson's disease. © 2017 European Sleep Research Society.

Prenatal Exposure to the Pesticide DDT and Hypertension Diagnosed in Women before Age 50: A Longitudinal Birth Cohort Study

PubMed Central

Cirillo, Piera M.; Terry, Mary Beth; Krigbaum, Nickilou Y.; Flom, Julie D.; Cohn, Barbara A.

2013-01-01

Background: Elevated levels of the pesticide DDT (dichlorodiphenyltrichloroethane) have been positively associated with blood pressure and hypertension in studies among adults. Accumulating epidemiologic and toxicologic evidence suggests that hypertension during adulthood may also be affected by earlier life and possibly the prenatal environment. Objectives: We assessed whether prenatal exposure to the pesticide DDT increases risk of adult hypertension. Methods: We examined concentrations of DDT (p,p´- and o,p´-) and its metabolite p,p´-DDE (dichlorodiphenyldichloroethylene) in prenatal serum samples from a subset of women (n = 527) who had participated in the prospective Child Health and Development Studies birth cohort in the San Francisco Bay area while they were pregnant between 1959 and 1967. We surveyed daughters 39–47 years of age by telephone interview from 2005 to 2008 to obtain information on self-reported physician-diagnosed hypertension and use of hypertensive medication. We used multivariable regression analysis of time to hypertension based on the Cox proportional hazards model to estimate relative rates for the association between prenatal DDT exposures and hypertension treated with medication in adulthood, with adjustment for potential confounding by maternal, early-life, and adult exposures. Results: Prenatal p,p´-DDT exposure was associated with hypertension [adjusted hazard ratio (aHR) = 3.6; 95% CI: 1.8, 7.2 and aHR = 2.5; 95% CI: 1.2, 5.3 for middle and high tertiles of p,p´-DDT relative to the lowest tertile, respectively]. These associations between p,p´-DDT and hypertension were robust to adjustment for independent hypertension risk factors as well as sensitivity analyses. Conclusions: These findings suggest that the association between DDT exposure and hypertension may have its origins early in development. PMID:23591545

Late-Onset Asthma Predicts Cardiovascular Disease Events: The Wisconsin Sleep Cohort.

PubMed

Tattersall, Matthew C; Barnet, Jodi H; Korcarz, Claudia E; Hagen, Erika W; Peppard, Paul E; Stein, James H

2016-08-24

Asthma is a heterogeneous syndrome with different clinical subtypes that is associated with an increased risk for cardiovascular disease (CVD). We hypothesized that the late-onset subtype of asthma is associated with a higher risk of incident CVD. Participants from the Wisconsin Sleep Cohort free of CVD at baseline were followed for a mean (SD) of 13.9 (5.9) years for development of CVD (myocardial infarction, angina, stroke, coronary revascularization, heart failure, or CVD death). Late-onset asthma was defined as physician-diagnosed asthma at age ≥18 years. Multivariable Cox regression models adjusted for age, sex, and CVD risk factors were used to assess associations of late-onset asthma and incident CVD. The 1269 participants were 47.3 (8.0) years old; 166 participants had asthma (111 late-onset, 55 early-onset). Participants with late-onset asthma compared to nonasthmatics were more likely to be female (67% versus 44%) and to have a higher body-mass index (32.2 versus 29.4 kg/m(2)) (P<0.05). Mean age of asthma diagnosis in the late-onset group was 39.5 (9.6) years versus 8.9 (5.7) years in the early-onset group (P<0.0001). Late-onset asthmatics had a higher adjusted risk of incident CVD than nonasthmatics (hazard ratio 1.57, 95% CI 1.01-2.45, P=0.045). There was no interaction between body-mass index and age of asthma diagnosis on incident CVD (P=0.83). In a large cohort study of adults followed prospectively for over a decade, late-onset asthmatics had an increased risk of incident CVD events that persisted after adjustment for age, sex, and CVD risk factors. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Screening frequency and atypical cells and the prediction of cervical cancer risk.

PubMed

Chen, Yun-Yuan; You, San-Lin; Koong, Shin-Lan; Liu, Jessica; Chen, Chi-An; Chen, Chien-Jen

2014-05-01

To evaluate the screening efficacy and importance of atypical squamous cells and atypical glandular cells in predicting subsequent cervical cancer risk. This national cohort study in Taiwan analyzed associations between Pap test screening frequency and findings in 1995-2000 and subsequent risk of squamous cell carcinoma and adenocarcinoma after 2002. Women aged 30 years or older in 1995 without a cervical cancer history were included. Multivariate-adjusted hazard ratios and their 95% confidence intervals (CIs) were assessed using Cox regression analysis. During a total follow-up of 31,693,980 person-years in 2002-2008, 9,471 squamous cell carcinoma and 1,455 adenocarcinoma cases were newly diagnosed, resulting in 2,067 deaths. The risk of developing and dying from squamous cell carcinoma decreased significantly with increasing attendance frequency between 1995 and 2000 (all P values for trend<.001). Women who attended more than three screenings in 1995-2000 had 0.69-fold and 0.35-fold decrease in incidence and mortality of adenocarcinoma, respectively, compared with women who never attended any screenings. Abnormal cytologic findings were significant predictors of the incidence and mortality of cervical cancers. The adjusted hazard ratio (95% CI) of developing squamous cell carcinoma was 29.94 (22.83-39.25) for atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions, and the adjusted hazard ratio (95% CI) of developing adenocarcinoma was 49.43 (36.49-66.97) for atypical glandular cells. Significant reductions in cervical adenocarcinoma occurred in women who attend three or more annual screenings in 6 years. High-grade atypical squamous cells and atypical glandular cells are important predictors of subsequent adenocarcinoma and squamous cell carcinoma. II.

Irregularity and lack of p waves in short tachycardia episodes predict atrial fibrillation and ischemic stroke.

PubMed

Johnson, Linda S B; Persson, Anders P; Wollmer, Per; Juul-Möller, Steen; Juhlin, Tord; Engström, Gunnar

2018-02-13

Atrial fibrillation (AF) is defined as an irregular supraventricular tachycardia (SVT) without p waves, with duration >30 seconds. Whether AF characteristics during short SVT episodes predict AF and stroke is not known. The purpose of this study was to determine whether irregularity and lack of p waves, alone or in combination, during short SVT episodes increase the risk of incident AF and ischemic stroke. The population-based Malmö Diet and Cancer study includes 24-hour ECG screening of 377 AF-free individuals (mean age 64.5 years; 43% men) who were prospectively followed for >13 years. There were 65 AF events and 25 ischemic stroke events during follow-up. Subjects with an SVT episode ≥5 beats were identified, and the longest SVT episode was assessed for irregularity and lack of p waves. The association between SVT classification and AF and stroke was assessed using multivariable adjusted Cox regression. The incidence of AF increased with increasing abnormality of the SVTs. The risk-factor adjusted hazard ratio for AF was 4.95 (95% confidence interval 2.06-11.9; P <.0001) for those with short irregular SVTs (<70 beats) without p waves. The incidence of ischemic stroke was highest in the group with regular SVT episodes without p waves (hazard ratio 14.2; 95% confidence interval 3.76-57.6; P <.0001, adjusted for age and sex). Characteristics of short SVT episodes detected at 24-hour ECG screening are associated with incident AF and ischemic stroke. Short irregular SVTs without p waves likely represent early stages of AF or atrial myopathy. Twenty-four-hour ECG could identify subjects suitable for primary prevention efforts. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Serious Infections among Adult Medicaid Beneficiaries with Systemic Lupus Erythematosus and Lupus Nephritis

PubMed Central

Feldman, Candace H.; Hiraki, Linda T.; Winkelmayer, Wolfgang C.; Marty, Francisco M.; Franklin, Jessica M.; Kim, Seoyoung C.; Costenbader, Karen H.

2015-01-01

Objective While serious infections are significant causes of morbidity and mortality in systemic lupus erythematosus (SLE), the epidemiology in a nationwide cohort of SLE and lupus nephritis (LN) patients has not been examined. Methods Using the Medicaid Analytic eXtract (MAX) database, 2000-2006, we identified patients 18-64 years with SLE and a subset with LN. We ascertained hospitalized serious infections using validated algorithms, and 30-day mortality rates. We used Poisson regression to calculate infection incidence rates (IR), and multivariable Cox proportional hazards models to calculate hazard ratios (HR) for first infection, adjusted for sociodemographics, medication use, and a SLE-specific risk adjustment index. Results We identified 33,565 patients with SLE and 7,113 with LN. There were 9,078 serious infections in 5,078 SLE patients and 3,494 infections in 1,825 LN patients. The infection IR per 100 person-years was 10.8 in SLE and 23.9 in LN. In adjusted models, in SLE, we observed increased risks of infection among males compared to females (HR 1.33, 95% CI 1.20-1.47), in Blacks compared to Whites (HR 1.14, 95% CI 1.06-1.21), and glucocorticoid users (HR 1.51, 95% CI 1.43-1.61) and immunosuppressive users (HR 1.11, 95% CI 1.03-1.20) compared with non-users. Hydroxychloroquine users had a reduced risk of infection compared to non-users (HR 0.73, 95% CI 0.68-0.77). The 30-day mortality rate per 1,000 person-years among those hospitalized with infections was 21.4 in SLE and 38.7 in LN. Conclusion In this diverse, nationwide cohort of SLE patients, we observed a substantial burden of serious infections with many subsequent deaths. PMID:25772621

Associations between Coffee, Tea, and Caffeine Intake with Coronary Artery Calcification and Cardiovascular Events

PubMed Central

Miller, P. Elliott; Zhao, Di; Frazier-Wood, Alexis C.; Michos, Erin D.; Averill, Michelle; Sandfort, Veit; Burke, Gregory L.; Polak, Joseph F.; Lima, Joao A.C.; Post, Wendy S.; Blumenthal, Roger S.; Guallar, Eliseo; Martin, Seth S.

2016-01-01

Background Coffee and tea are two of the most commonly consumed beverages in the world. The association of coffee and tea intake with coronary artery calcium and major adverse cardiovascular events remains uncertain. Methods We examined 6,508 ethnically-diverse participants with available coffee and tea data from the Multi-Ethnic Study of Atherosclerosis. Intake for each was classified as never, occasional (<1 cup/day), and regular (≥1 cup/day). A coronary artery calcium progression ratio was derived from mixed effect regression models using loge(calcium score+1) as the outcome with coefficients exponentiated to reflect coronary artery calcium progression ratio vs. the reference. Cox proportional hazards analyses were used to evaluate the association between beverage intake and incident cardiovascular events. Results Over a median follow-up of 5.3 years for coronary artery calcium and 11.1 years for cardiovascular events, participants who regularly drank tea (≥1 cup/day) had a slower progression of coronary artery calcium compared with never drinkers after multivariable adjustment. This correlated with a statistically significant lower incidence of cardiovascular events for ≥1 cup/day tea drinkers (adjusted HR 0.71; 95% CI 0.53–0.95). Compared to never coffee drinkers, regular coffee intake (≥1 cup/day) was not statistically associated with coronary artery calcium progression or cardiovascular events (adjusted HR 0.97 [0.78, 1.20]). Caffeine intake was marginally inversely associated with coronary artery calcium progression. Conclusions Moderate tea drinkers had slower progression of coronary artery calcium and reduced risk for cardiovascular events. Future research is needed to understand the potentially protective nature of moderate tea intake. PMID:27640739

Adiposity and breast cancer risk in postmenopausal women: Results from the UK Biobank prospective cohort.

PubMed

Guo, Wenji; Key, Timothy J; Reeves, Gillian K

2018-03-23

Body size is an important modifiable risk factor for postmenopausal breast cancer. However, it remains unclear whether direct measures of fat mass are better indicators of risk than anthropometric measures, or whether central adiposity may contribute to risk beyond overall adiposity. We analyzed data from 162,691 postmenopausal women in UK Biobank followed from 2006 to 2014. Body size was measured by trained technicians. Multivariable-adjusted Cox regression was used to estimate relative risks. Analyses were stratified by age at recruitment, region and socioeconomic status, and adjusted for family history of breast cancer, age at menarche, age at first birth, parity, age at menopause, previous hormone replacement therapy use, smoking, alcohol intake, height, physical activity and ethnicity. We observed 2,913 incident invasive breast cancers during a mean 5.7 years of follow-up. There was a continuous increase in risk of postmenopausal breast cancer with increasing adiposity, across all measures. The point estimate, comparing women in the top (median 37.6 kg) to bottom (median 17.6 kg) quartile of body fat mass was 1.70 (95% confidence interval 1.52-1.90). The magnitudes of the associations between per SD increase in BMI and body fat mass with breast cancer risk were similar, suggesting impedance measures of fat were not substantially better indicators of risk than anthropometric measures. After adjusting for body fat mass, the associations between anthropometric measures of central adiposity and breast cancer risk were attenuated. The magnitude of risk, across all measures of adiposity, was greater in women who had been postmenopausal for 12 or more years. © 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein evaluates liver function and predicts prognosis in liver cirrhosis.

PubMed

Xu, Wen Ping; Wang, Ze Rui; Zou, Xia; Zhao, Chen; Wang, Rui; Shi, Pei Mei; Yuan, Zong Li; Yang, Fang; Zeng, Xin; Wang, Pei Qin; Sultan, Sakhawat; Zhang, Yan; Xie, Wei Fen

2018-04-01

Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA + -M2BP) is a novel glycobiomarker for evaluating liver fibrosis, but less is known about its role in liver cirrhosis (LC). This study aimed to investigate the utility of WFA + -M2BP in evaluating liver function and predicting prognosis of cirrhotic patients. We retrospectively included 197 patients with LC between 2013 and 2016. Serum WFA + -M2BP and various biochemical parameters were measured in all patients. With a median follow-up of 23 months, liver-related complications and deaths of 160 patients were recorded. The accuracy of WFA + -M2BP in evaluating liver function, predicting decompensation and mortality were measured by the receiver operating characteristic (ROC) curve, logistic and Cox's regression analyses, respectively. WFA + -M2BP levels increased with elevated Child-Pugh classification, especially in patients with hepatitis B virus (HBV) infection. ROC analysis confirmed the high reliability of WFA + -M2BP for the assessment of liver function using Child-Pugh classification. WFA + -M2BP was also significantly positively correlated with the model for end-stage liver disease (MELD) score. Multivariate logistic regression analysis indicated WFA + -M2BP as an independent predictor of clinical decompensation for compensated patients (odds ratio 11.958, 95% confidence interval [CI] 1.876-76.226, P = 0.009), and multivariate Cox's regression analysis verified WFA + -M2BP as an independent risk factor for liver-related death in patients with HBV infection (hazards ratio 10.596, 95% CI 1.356-82.820, P = 0.024). Serum WFA + -M2BP is a reliable predictor of liver function and prognosis in LC and could be incorporated into clinical surveillance strategies for LC patients, especially those with HBV infection. © 2018 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

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

PubMed

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

2008-07-01

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

The relationship of age-adjusted Charlson comorbidity ındex and diurnal variation of blood pressure.

PubMed

Kalaycı, Belma; Erten, Yunus Turgay; Akgün, Tunahan; Karabag, Turgut; Kokturk, Furuzan

2018-03-05

Charlson Comorbidity index (CCI) is a scoring system to predict prognosis and mortality. It exhibits better utility when combined with age, age-adjusted Charlson Comorbidity Index (ACCI). The aim of this study was to evaluate the relationship between ACCI and diurnal variation of blood pressure parameters in hypertensive patients and normotensive patients. We enrolled 236 patients. All patients underwent a 24-h ambulatory blood pressure monitoring (ABPM) for evaluation of dipper or non-dipper pattern. We searched the correlation between ACCI and dipper or non-dipper pattern and other ABPM parameters. To further investigate the role of these parameters in predicting survival, a multivariate analysis using the Cox proportional hazard model was performed. 167 patients were in the hypertensive group (87 patients in non-dipper status) and 69 patients were in the normotensive group (41 patients in non-dipper status) of all study patients. We found a significant difference and negative correlation between AACI and 24-h diastolic blood pressure (DBP), awake DBP, awake mean blood pressure (MBP) and 24-h MBP and awake systolic blood pressure(SBP). Night decrease ratio of blood pressure had also a negative correlation with ACCI (p = 0.003, r = -0.233). However, we found a relationship with non-dipper pattern and ACCI in the hypertensive patients (p = 0.050). In multivariate Cox analysis sleep MBP was found related to mortality like ACCI (p = 0.023, HR = 1.086, %95 CI 1.012-1.165) Conclusion: ACCI was statistically significantly higher in non-dipper hypertensive patients than dipper hypertensive patients while ACCI had a negative correlation with blood pressure. Sleep MBP may predict mortality.

Risk of type 2 diabetes mellitus in patients with acute critical illness: a population-based cohort study.

PubMed

Hsu, Chin-Wang; Lin, Chin-Sheng; Chen, Sy-Jou; Lin, Shih-Hua; Lin, Cheng-Li; Kao, Chia-Hung

2016-01-01

This large population-based cohort study evaluated the association between certain critical illnesses and the incidence of newly diagnosed type 2 diabetes mellitus (T2DM) in Taiwan. Data were obtained from the Taiwan National Health Insurance Research Database. According to age, sex, and propensity score-matching, a cohort comprising 9528 patients with critical illness, including septicemia, septic shock, acute myocardial infarction (AMI), and stroke, and a control cohort of 9528 patients with no critical illness were identified. Cox proportional-hazard regression and competing-risk regression models were employed to evaluate the risk of developing T2DM. With the median follow-up periods (interquartile range) of 3.86 (1.64-6.93) and 5.12 (2.51-8.13) years for the patients in the critical illness and control cohorts, respectively, the risk of developing T2DM in the critical illness cohort was significantly higher than in the control cohort (adjusted hazard ratio, aHR = 1.32; 95% confidence interval, CI 1.16-1.50). In the multivariate competing-risk regression models, the aHR of T2DM was 1.58 (95% CI 1.45-1.72) in the critical illness cohort. Moreover, among the patients with these critical illnesses, those with septicemia or septic shock exhibited the highest risk of developing T2DM (aHR = 1.51, 95% CI 1.37-1.67), followed by AMI compared with the control cohort. Our results suggest that patients with certain critical illnesses are associated with a high risk of developing T2DM. Clinicians should be aware of this association and intensively screen for T2DM in patients following diagnosis of critical illness.

Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.

PubMed

Brennan, Donal J; Brändstedt, Jenny; Rexhepaj, Elton; Foley, Michael; Pontén, Fredrik; Uhlén, Mathias; Gallagher, William M; O'Connor, Darran P; O'Herlihy, Colm; Jirstrom, Karin

2010-04-01

Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer

PubMed Central

2010-01-01

Background Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. Methods HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Results Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. Conclusion HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens. PMID:20359358

Disparities in Mortality of Hispanic Cystic Fibrosis Patients in the United States: A National and Regional Cohort Study.

PubMed

Rho, Jason; Ahn, Chul; Gao, Ang; Sawicki, Gregory S; Keller, Ashley; Jain, Raksha

2018-05-09

Cystic Fibrosis (CF) patients of Hispanic origin are the largest growing minority, representing 8.5% of CF patients in the United States. No national survival analysis of this group has ever been undertaken. We aimed to determine whether Hispanic ethnicity within the CF population is associated with worse outcomes and whether any geographic differences exist. Using U.S. CF Foundation Patient Registry data from 2010-2014, we performed a retrospective cohort analysis comparing survival rates between Hispanics and non-Hispanics using Kaplan-Meier and Cox regression analysis. A subject's residence was categorized into geographic regions based on U.S. Census Bureau data: Northeast, Midwest, West and South. 29,637 patients were included in the study; 2,493 identified themselves as Hispanic. Hispanics had a lower survival probability overall, with a mean age of death of 22.4 ± 9.9 years compared to non-Hispanics of 28.1 ± 10.0 years (p < 0.0001). Multivariate cox proportional hazards modeling revealed that Hispanic CF patients had a 1.27 times higher rate of death compared to non-Hispanics (95% CI: 1.05 - 1.53) after adjusting for covariates including age, sex, genetic mutations, bacterial cultures, lung function, body mass index, use of CF respiratory therapies, low socioeconomic status, pancreatic enzyme use, and CF-related diabetes. When analyzed by region, Hispanics in the Midwest, Northeast, and West had shorter median survivals compared to Non-Hispanics, which was not demonstrated in the South. CF patients of Hispanic origin have a higher mortality rate than non-Hispanic CF patients. This pattern was seen in the Midwest, Northeast, and West but not in the South.

Long-QT Syndrome and Therapy for Attention Deficit/Hyperactivity Disorder.

PubMed

Zhang, Claire; Kutyifa, Valentina; Moss, Arthur J; McNitt, Scott; Zareba, Wojciech; Kaufman, Elizabeth S

2015-10-01

Stimulants are the mainstay therapy for attention deficit/hyperactivity disorder (ADHD) and are associated with adrenergic side effects. There are limited data on the clinical course of patients treated for ADHD who have long-QT syndrome (LQTS), for which β-blockade is the goal of therapy. LQTS patients from the Rochester-based LQTS Registry (open-enrollment between 1979 and 2003; follow-up from 1979 to present) treated with stimulant or nonstimulant ADHD medications (n = 48) were compared to a 2:1 age-, gender-, and QTc-duration matched LQTS control group not exposed to ADHD medications (n = 96). Kaplan-Meier and Cox proportional hazards regression analyses were used to evaluate risk of cardiac events (syncope, aborted cardiac arrest, and sudden cardiac death) in LQTS patients treated with ADHD medications. During a mean follow-up of 7.9 ± 5.4 years after initiation of ADHD medication at a mean age 10.7 ±7.3 years, there was a 62% cumulative probability of cardiac events in the ADHD treatment group compared to 28% in the matched LQTS control group (P < 0.001). Time-dependent use of ADHD medication was associated with an increased risk for cardiac events (HR = 3.07; P = 0.03) in the multivariate Cox model adjusted for time-dependent β-blocker use and prior cardiac events. Subgroup gender analyses showed that time-dependent ADHD medication was associated with an increased risk in male LQTS patients (HR = 6.80, P = 0.04). LQTS patients treated with ADHD medications have increased risk for cardiac events, particularly syncope, and this risk is augmented in males. The findings highlight the importance of heightened surveillance for LQTS patients on ADHD medications. © 2015 Wiley Periodicals, Inc.

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

PubMed

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

2011-11-03

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

High coffee consumption and different brewing methods in relation to postmenopausal endometrial cancer risk in the Norwegian Women and Cancer Study: a population-based prospective study

PubMed Central

2014-01-01

Background Coffee and its compounds have been proposed to inhibit endometrial carcinogenesis. Studies in the Norwegian population can be especially interesting due to the high coffee consumption and increasing incidence of endometrial cancer in the country. Methods A total of 97 926 postmenopausal Norwegian women from the population-based prospective Norwegian Women and Cancer (NOWAC) Study, were included in the present analysis. We evaluated the general association between total coffee consumption and endometrial cancer risk as well as the possible impact of brewing method. Multivariate Cox regression analysis was used to estimate risks, and heterogeneity tests were performed to compare brewing methods. Results During an average of 10.9 years of follow-up, 462 incident endometrial cancer cases were identified. After multivariate adjustment, significant risk reduction was found among participants who drank ≥8 cups/day of coffee with a hazard ratio of 0.52 (95% confidence interval, CI 0.34-0.79). However, we did not observe a significant dose-response relationship. No significant heterogeneity in risk was found when comparing filtered and boiled coffee brewing methods. A reduction in endometrial cancer risk was observed in subgroup analyses among participants who drank ≥8 cups/day and had a body mass index ≥25 kg/m2, and in current smokers. Conclusions These data suggest that in this population with high coffee consumption, endometrial cancer risk decreases in women consuming ≥8 cups/day, independent of brewing method. PMID:24666820

Effect of previous history of cancer on survival of patients with a second cancer of the head and neck.

PubMed

Jégu, Jérémie; Belot, Aurélien; Borel, Christian; Daubisse-Marliac, Laetitia; Trétarre, Brigitte; Ganry, Olivier; Guizard, Anne-Valérie; Bara, Simona; Troussard, Xavier; Bouvier, Véronique; Woronoff, Anne-Sophie; Colonna, Marc; Velten, Michel

2015-05-01

To provide head and neck squamous cell carcinoma (HNSCC) survival estimates with respect to patient previous history of cancer. Data from ten French population-based cancer registries were used to establish a cohort of all male patients presenting with a HNSCC diagnosed between 1989 and 2004. Vital status was updated until December 31, 2007. The 5-year overall and net survival estimates were assessed using the Kaplan-Meier and Pohar-Perme estimators, respectively. Multivariate Cox regression models were used to assess the effect of cancer history adjusted for age and year of HNSCC diagnosis. Among the cases of HNSCC, 5553 were localized in the oral cavity, 3646 in the oropharynx, 3793 in the hypopharynx and 4550 in the larynx. From 11.0% to 16.8% of patients presented with a previous history of cancer according to HNSCC. Overall and net survival were closely tied to the presence, or not, of a previous cancer. For example, for carcinoma of the oral cavity, the five-year overall survival was 14.0%, 5.9% and 36.7% in case of previous lung cancer, oesophagus cancer or no cancer history, respectively. Multivariate analyses showed that previous history of cancer was a prognosis factor independent of age and year of diagnosis (p<.001). Previous history of cancer is strongly associated with survival among HNSCC patients. Survival estimates based on patients' previous history of cancer will enable clinicians to assess more precisely the prognosis of their patients with respect to this major comorbid condition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Processed and unprocessed red meat consumption and hypertension in women.

PubMed

Lajous, Martin; Bijon, Anne; Fagherazzi, Guy; Rossignol, Emilie; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise

2014-09-01

High processed red meat consumption is associated with increased risk of cardiovascular disease. The high sodium content of processed red meat could increase blood pressure and explain the association with cardiovascular disease. We evaluated the relation between the consumption of unprocessed and processed red meat and incident hypertension. In a prospective cohort of 44,616 disease-free French women who responded to a validated dietary questionnaire, we observed 10,256 incident cases of hypertension between 1993 and 2008. Cases were identified through self-reports of diagnosed or treated hypertension. Multivariate Cox regression models were adjusted for age, education, smoking, physical activity, body mass index, menopause, menopausal hormone therapy, and alcohol, bread, coffee, and fruit and vegetable consumption. Women who consumed ≥5 servings of processed red meat/wk (50 g = 1 serving) had a 17% higher rate of hypertension than that of women who consumed <1 serving/wk (HR: 1.17; 95% CI: 1.09, 1.26; P-trend = 0.0002). No association was observed between unprocessed red meat consumption and hypertension. When women who consumed ≥5 servings of unprocessed red meat/wk (100 g = 1 serving) were compared with women who consumed <1 serving unprocessed red meat/wk, the multivariate HR was 0.99 (95% CI: 0.91, 1.08; P-trend = 0.63). In this large prospective cohort of French women, we observed an association between the consumption of processed red meat and hypertension. We observed no association for unprocessed red meat consumption and hypertension. © 2014 American Society for Nutrition.

Carotid intima-media thickness is a novel predictor of new onset of hypertension in normotensive subjects.

PubMed

Takase, Hiroyuki; Sugiura, Tonomori; Murai, Shunsuke; Yamashita, Sumiyo; Ohte, Nobuyuki; Dohi, Yasuaki

2017-08-01

Increased carotid intima-media thickness (IMT) in individuals without hypertension might indicate other factors promoting the atherosclerotic process that are often simultaneously clustered in individuals. The present study tested the hypothesis that carotid IMT predicts new onset of hypertension in the normotensive subjects.A total of 867 participants were enrolled from our yearly physical checkup program and their carotid IMT was measured. After a baseline examination, the subjects were followed up for a median of 1091 days with the endpoint being the development of hypertension.At baseline, the carotid IMT value was 0.75 ± 0.16 mm. Hypertension developed in 184 subjects during the follow-up (76.9/1000 person-years). The incidence of hypertension was increased across the tertiles of the carotid IMT value (39.6, 70.0, and 134.5/1000 person-years in the first, second, and third tertiles, respectively, P < .001 by log-rank test). Multivariate Cox-hazard analysis after adjustment identified carotid IMT, taken as a continuous variable, as a significant predictor of new-onset hypertension (hazard ratio = 7.08, 95% confidence interval = 3.06-15.39). Furthermore, multivariate linear regression analyses indicated a significant correlation between the carotid IMT at baseline and yearly increases in systolic blood pressure during the follow-up period (β = 0.189, P < .001).Carotid IMT is an independent predictor of hypertension onset in normotensive subjects. The findings also suggested a close association between increased carotid IMT and blood pressure.

Carotid intima-media thickness is a novel predictor of new onset of hypertension in normotensive subjects

PubMed Central

Takase, Hiroyuki; Sugiura, Tonomori; Murai, Shunsuke; Yamashita, Sumiyo; Ohte, Nobuyuki; Dohi, Yasuaki

2017-01-01

Abstract Increased carotid intima-media thickness (IMT) in individuals without hypertension might indicate other factors promoting the atherosclerotic process that are often simultaneously clustered in individuals. The present study tested the hypothesis that carotid IMT predicts new onset of hypertension in the normotensive subjects. A total of 867 participants were enrolled from our yearly physical checkup program and their carotid IMT was measured. After a baseline examination, the subjects were followed up for a median of 1091 days with the endpoint being the development of hypertension. At baseline, the carotid IMT value was 0.75 ± 0.16 mm. Hypertension developed in 184 subjects during the follow-up (76.9/1000 person-years). The incidence of hypertension was increased across the tertiles of the carotid IMT value (39.6, 70.0, and 134.5/1000 person-years in the first, second, and third tertiles, respectively, P < .001 by log-rank test). Multivariate Cox-hazard analysis after adjustment identified carotid IMT, taken as a continuous variable, as a significant predictor of new-onset hypertension (hazard ratio = 7.08, 95% confidence interval = 3.06–15.39). Furthermore, multivariate linear regression analyses indicated a significant correlation between the carotid IMT at baseline and yearly increases in systolic blood pressure during the follow-up period (β = 0.189, P < .001). Carotid IMT is an independent predictor of hypertension onset in normotensive subjects. The findings also suggested a close association between increased carotid IMT and blood pressure. PMID:28767608

Predictors of Mortality among United States Veterans with Human Immunodeficiency Virus and Hepatitis C Virus Coinfection

PubMed Central

Murtaza Kasi, Pashtoon; Butt, Adeel A.

2014-01-01

Background. Understanding the predictors of mortality in individuals with human immunodeficiency virus and hepatitis C virus (HIV/HCV) coinfection can be useful in management of these patients. Methods. We used the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) for these analyses. Multivariate Cox-regression models were used to determine predictors of mortality. Results. Among 8,039 HIV infected veterans, 5251 (65.3%) had HCV coinfection. The all-cause mortality rate was 74.1 (70.4–77.9) per 1000 person-years (PY) among veterans with HIV/HCV coinfection and 39.8 (36.3–43.6) per 1000 PY for veterans with HIV monoinfection. The multivariable adjusted hazard ratio (95% confidence interval) of all-cause mortality for HCV infection was 1.58 (1.36–1.84). Positive predictors of mortality included decompensated liver disease (2.33 (1.98–2.74)), coronary artery disease (1.74 (1.32–2.28)), chronic kidney disease (1.62 (1.36–1.92)), and anemia (1.58 (1.31–1.89)). Factors associated with reduced mortality included HCV treatment (0.41 (0.27–0.63)) and higher CD4 count (0.90 (0.87–0.93) per 100 cells/μL higher count). Data were insufficient to make informative analyses of the role of HCV virologic response. Conclusion. HCV coinfection was associated with substantial increased risk of mortality among HIV infected veterans. HCV treatment was associated with significantly lower risk of mortality. PMID:25006471

Impact of preexisting tumor necrosis on the efficacy of stereotactic radiosurgery in the treatment of brain metastases in women with breast cancer.

PubMed

Xu, Zhiyuan; Marko, Nicholas F; Angelov, Lilyana; Barnett, Gene H; Chao, Samuel T; Vogelbaum, Michael A; Suh, John H; Weil, Robert J

2012-03-01

Breast cancer is the second most common source of brain metastasis. Stereotactic radiosurgery (SRS) can be an effective treatment for some patients with brain metastasis (BM). Necrosis is a common feature of many brain tumors, including BM; however, the influence of tumor necrosis on treatment efficacy of SRS in women with breast cancer metastatic to the brain is unknown. A cohort of 147 women with breast cancer and BM treated consecutively with SRS over 10 years were studied. Of these, 80 (54.4%) had necrosis identified on pretreatment magnetic resonance images and 67 (46.4%) did not. Survival times were computed using the Kaplan-Meier method. Log-rank tests were used to compare groups with respect to survival times, Cox proportional hazards regression models were used to perform univariate and multivariate analyses, and chi-square and Fisher exact tests were used to compare clinicopathologic covariates. Neurological survival (NS) and survival after SRS were decreased in BM patients with necrosis at the time of SRS compared with patients without necrosis by 32% and 27%, respectively (NS median survival, 25 vs 17 months [log-rank test, P = .006]; SRS median survival, 15 vs 11 months [log-rank test, P = .045]). On multivariate analysis, HER2 amplification status and necrosis influenced NS and SRS after adjusting for standard clinical features, including BM number, size, and volume as well as Karnofsky performance status. Neuroimaging evidence of necrosis at the time of SRS significantly diminished the efficacy of therapy and was a potent prognostic marker. Copyright © 2011 American Cancer Society.

Effect of Cobicistat on Tenofovir Disoproxil Fumarate (TDF): What Is True for TAF May Also Be True for TDF.

PubMed

Cattaneo, Dario; Minisci, Davide; Baldelli, Sara; Mazzali, Cristina; Giacomelli, Andrea; Milazzo, Laura; Meraviglia, Paola; Resnati, Chiara; Rizzardini, Giuliano; Clementi, Emilio; Galli, Massimo; Gervasoni, Cristina

2018-01-01

The dose of tenofovir alafenamide is reduced from 25 to 10 mg daily when given with boosting agents. However, such dose reduction has never been adopted for tenofovir disoproxil fumarate (TDF). In this study, we aim to quantify the effect of cobicistat (COBI) both on tenofovir concentrations and TDF durability in real life setting. HIV-positive patients receiving TDF-containing antiretroviral therapies with at least 1 assessment of tenofovir plasma trough concentrations were included in the study. Univariate and multivariate regression analyses were performed considering tenofovir concentration as the dependent variable and clinical characteristics as independent covariates. Subsequently, survival and Cox analyses were performed considering as the primary outcome TDF discontinuation for any reasons. Patients were given TDF with protease inhibitors/ritonavir (n = 212), non-nucleoside reverse transcriptase inhibitors (n = 176), integrase inhibitors (dolutegravir or raltegravir, n = 46), or with elvitegravir/COBI (ELV/COBI) (n = 76). By multivariate analysis, concomitant antiretroviral therapies resulted significantly associated with tenofovir levels, with the highest drug concentrations measured in patients given ELV/COBI. By survival analysis, we found that patients given TDF with ELV/COBI had the lowest rate of drug durability. Overall, these patients had a 2.3-fold increased risk to experience TDF discontinuation. Coadministration with COBI resulted in significantly higher tenofovir concentrations and higher TDF discontinuation compared with other antiretroviral regimens. Accordingly, the possibility that the lack of proper dose adjustment for TDF when given with COBI might have biased the safety comparisons with tenofovir alafenamide during registrative trials cannot be ruled out.

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.

Malignant Peritoneal Mesothelioma: Prognostic Factors and Oncologic Outcome Analysis

PubMed Central

Magge, Deepa; Zenati, Mazen S.; Austin, Frances; Mavanur, Arun; Sathaiah, Magesh; Ramalingam, Lekshmi; Jones, Heather; Zureikat, Amer H.; Holtzman, Matthew; Ahrendt, Steven; Pingpank, James; Zeh, Herbert J.; Bartlett, David L.; Choudry, Haroon A.

2014-01-01

Background Most patients with malignant peritoneal mesothelioma (MPM) present with late-stage, unresectable disease that responds poorly to systemic chemotherapy while, at the same time, effective targeted therapies are lacking. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in MPM. Methods We prospectively analyzed 65 patients with MPM undergoing CRS/HIPEC between 2001 and 2010. Kaplan–Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes. Results Adequate CRS was achieved in 56 patients (CC-0 = 35; CC-1 = 21), and median simplified peritoneal cancer index (SPCI) was 12. Pathologic assessment revealed predominantly epithelioid histology (81 %) and biphasic histology (8 %), while lymph node involvement was uncommon (8 %). Major postoperative morbidity (grade III/IV) occurred in 23 patients (35 %), and 60-day mortality rate was 6 %. With median follow-up of 37 months, median overall survival was 46.2 months, with 1-, 2-, and 5-year overall survival probability of 77, 57, and 39 %, respectively. Median progression-free survival was 13.9 months, with 1-, 2-, and 5-year disease failure probability of 47, 68, and 83 %, respectively. In a multivariate Cox-regression model, age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), aggressive histology (epithelioid, biphasic), and postoperative sepsis were joint significant predictors of poor survival (chi square = 42.8; p = 0.00001), while age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), and aggressive histology (epithelioid, biphasic) were joint significant predictors of disease progression (Chi square = 30.6; p = 0.00001). Conclusions Tumor histology, disease burden, and the ability to achieve adequate surgical cytoreduction are essential prognostic factors in MPM patients undergoing CRS/HIPEC. PMID:24322529

Reformed smokers have survival benefits after head and neck cancer.

PubMed

Cao, Wei; Liu, Zheqi; Gokavarapu, Sandhya; Chen, YiMing; Yang, Rong; Ji, Tong

2016-09-01

Smoking tobacco is the main risk factor for head and neck cancer, is proportional to the number of pack years (number of packs smoked/day x number of years of smoking), and is reduced when the patient stops smoking. Current molecular evidence has suggested that tobacco-related cancers could be clinically more aggressive than cancers in non-smokers, particularly in the head and neck. However, clinical studies have not uniformly reproduced the relation between survival and tobacco, possibly because they ignore the health benefit that reformed smokers obtain during the period between giving up smoking and the diagnosis of cancer, which is not shared by those who continue to smoke and develop cancer. We have investigated the survival of reformed smokers, non-smokers, and continuing smokers after a diagnosis of head and neck cancer. The data of patients with head and neck cancer from 1992 -2013 from the Cancer Genome Atlas database were analysed using a multivariate Cox's regression model for survival, and Kaplan-Meier curves were produced for smoking history. A total of 521 patients were treated for head and neck cancer, and there was a significant difference in survival between reformed and non-smokers on the one hand, and current smokers on the other (p=0.02). The significance increased when reformed smokers were grouped according to their duration of abstinence and time of diagnosis of cancer (>15 and ≤15 years, p<0.01). Smoking history was a significant prognostic factor in the multivariate Cox's regression model when analysed with age, stage, grade, and site. We conclude that reformed smokers have a survival benefit in head and neck cancer. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Aggressive Management of Peritoneal Carcinomatosis from Mucinous Appendiceal Neoplasms

PubMed Central

Austin, Frances; Mavanur, Arun; Sathaiah, Magesh; Steel, Jennifer; Lenzner, Diana; Ramalingam, Lekshmi; Holtzman, Matthew; Ahrendt, Steven; Pingpank, James; Zeh, Herbert J.; Bartlett, David L.; Choudry, Haroon A.

2014-01-01

Background Peritoneal carcinomatosis (PC) in the setting of mucinous appendiceal neoplasms is characterized by the intraperitoneal accumulation of mucinous ascites and mucin-secreting epithelial cells that leads to progressive compression of intra-abdominal organs, morbidity, and eventual death. We assessed postoperative and oncologic outcomes after aggressive surgical management by experienced surgeons. Methods We analyzed clinicopathologic, perioperative, and oncologic outcome data in 282 patients with PC from appendiceal adenocarcinomas between 2001 and 2010 from a prospective database. Kaplan–Meier survival curves and multivariate Cox-regression models were used to identify prognostic factors affecting oncologic outcomes. Results Adequate cytoreduction was achieved in 82% of patients (completeness of cytoreduction score (CC)-0: 49%; CC-1: 33%). Median simplified peritoneal cancer index (SPCI), operative time, and estimated blood loss were 14 (range, 0–21), 483.5 min (range, 46–1,402), and 800 ml (range, 0–14,000), respectively. Pathology assessment demonstrated high-grade tumors in 36% of patients and lymph node involvement in 23% of patients. Major postoperative morbidity occurred in 70 (25%) patients. Median overall survival was 6.72 years (95% confidence interval (CI), 4.17 years not reached), with 5 year overall survival probability of 52.7% (95% CI, 42.4, 62%). In a multivariate Cox-regression model, tumor grade, age, preoperative SPCI and chemo-naïve status at surgery were joint significant predictors of overall survival. Tumor grade, postoperative CC-score, prior chemotherapy, and preoperative SPCI were joint significant predictors of time to progression. Conclusions Aggressive management of PC from mucinous appendiceal neoplasms, by experienced surgeons, to achieve complete cytoreduction provides long-term survival with low major morbidity. PMID:22302270

Primary Cryotherapy for High-Grade Clinically Localized Prostate Cancer: Oncologic and Functional Outcomes from the COLD Registry.

PubMed

Tay, Kae Jack; Polascik, Thomas J; Elshafei, Ahmed; Cher, Michael L; Given, Robert W; Mouraviev, Vladimir; Ross, Ashley E; Jones, J Stephen

2016-01-01

To evaluate the oncological and functional outcomes of primary cryotherapy in men with clinically localized, high-grade prostate cancer. We included all men with biopsy Gleason score ≥8, localized (cT1-2) disease with a serum prostate-specific antigen (PSA) ≤50 ng/mL from the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression free survival (BPFS) as defined by the Phoenix criteria (nadir PSA +2 ng/mL). Secondary outcomes of continence (defined as strictly no leak) and potency (able to have intercourse) were patient reported. Factors influencing BPFS were evaluated individually using Kaplan Meier and in a multivariate model using Cox regression. Altogether, 300 men were included for analysis. The median follow-up was 18.2 months (mean 28.4) and median BPFS was 69.8 months. Based on Kaplan-Meier analysis, the estimated 2- and 5-year BPFS rate was 77.2% and 59.1%, respectively. Neoadjuvant hormonal therapy was administered to 41% of men and this tended to occur in men with larger prostates, likely as a technical consideration for downsizing before cryosurgery. At multivariate analysis, the presence of Gleason score 9 or 10 (Hazard Ratio [HR] 1.9) and a posttreatment PSA nadir of ≥0.4 ng/mL (HR 5.7) were the only significant variables associated with biochemical progression using Cox regression. Complete continence was noted in 90.5% of men and potency in 17% of men at the 12-month follow-up. The incidence of rectourethral fistulae and urinary retention requiring intervention beyond temporary catheterization was 1.3% and 3.3%, respectively. Primary cryotherapy appears to be effective and safe in the community setting for high-grade, clinically localized prostate cancer in the short term.

Survival of aggressive variants of papillary thyroid carcinoma in patients under 55 years old: a SEER population-based retrospective analysis.

PubMed

Feng, Jianhua; Shen, Fei; Cai, Wensong; Gan, Xiaoxiong; Deng, Xingyan; Xu, Bo

2018-06-16

Patients younger than 55 years of age with papillary thyroid carcinoma (PTC) have excellent survival. Diffuse sclerosing variant (DSV) and tall cell variant (TCV) of PTC are associated with aggressiveness; the survival of patients <55 years of age with these variants is still unclear. We aim to investigate the clinicopathological features and survival of these variants in the age group <55 years. All adult patients (<55 years old) with DSV, TCV and conventional PTC (CPTC) came from the Surveillance, Epidemiology, and End Results program (1988-2013). Kaplan-Meier method and log-rank test were used to analyze the survival. Prognostic factors associated with survival were analyzed by Cox multivariate regression. There were 280 DSV, 615 TCV, and 56287 CPTC in the age group <55 years. DSV and TCV were associated with multifocality, extrathyroidal extension, lymph node and distant metastasis (all p < 0.05). The 10-year disease-specific survival (DSS) of TCV was worse than CPTC (96.3 vs. 99.4%, p < 0.01), but there was no significant difference between DSV and CPTC (99.5 vs. 99.4%, p > 0.05). Cox multivariate regression showed TCV was the independent predictor of DSS (HR: 5.39, p < 0.01). In the age group <55 years, DSV and TCV are more likely to exhibit aggressive characteristics than CPTC. Patient <55 years of age with DSV have excellent survival likewise, while patients <55 years of age with TCV carry worse survival. Further investigation for the recurrence risk of patients <55 years with these variants would contribute to optimal clinical management making.

Advanced interatrial block predicts new-onset atrial fibrillation and ischemic stroke in patients with heart failure: The "Bayes' Syndrome-HF" study.

PubMed

Escobar-Robledo, Luis Alberto; Bayés-de-Luna, Antoni; Lupón, Josep; Baranchuk, Adrian; Moliner, Pedro; Martínez-Sellés, Manuel; Zamora, Elisabet; de Antonio, Marta; Domingo, Mar; Cediel, Germán; Núñez, Julio; Santiago-Vacas, Evelyn; Bayés-Genís, Antoni

2018-05-18

Advanced interatrial block (IAB) is characterized by a prolonged (≥120 ms) and bimodal P wave in the inferior leads. The association between advanced IAB and atrial fibrillation (AF) is known as "Bayes' Syndrome", and there is scarce information about it in heart failure (HF). We examined the prevalence of IAB and whether advanced IAB could predict new-onset AF and/or stroke in HF patients. The prospective observational "Bayes' Syndrome-HF" study included consecutive outpatients with chronic HF. The primary endpoints were new-onset AF, ischemic stroke, and the composite of both. A secondary endpoint included all-cause death alone or in combination with the primary endpoint. Comprehensive multivariable Cox regression analyses were performed. Among 1050 consecutive patients, 536 (51.0%) were in sinus rhythm, 464 with a measurable P wave are the focus of this study. Two-hundred and sixty patients (56.0%) had normal atrial conduction, 95 (20.5%) partial IAB, and 109 (23.5%) advanced IAB. During a mean follow-up of 4.5 ± 2.1 years, 235 patients experienced all-cause death, new-onset AF, or stroke. In multivariable comprehensive Cox regression analyses, advanced IAB was associated with new-onset AF (HR 2.71 [1.61-4.56], P < 0.001), ischemic stroke (HR 3.02 [1.07-8.53], P = 0.04), and the composite of both (HR 2.42 [1.41-4.15], P < 0.001). In patients with HF advanced IAB predicts new-onset AF and ischemic stroke. Future studies must assess whether anticoagulant treatment in Bayes' Syndrome leads to better outcomes in HF. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2017-08-01

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

Decoy receptor 3 is a prognostic factor in renal cell cancer.

PubMed

Macher-Goeppinger, Stephan; Aulmann, Sebastian; Wagener, Nina; Funke, Benjamin; Tagscherer, Katrin E; Haferkamp, Axel; Hohenfellner, Markus; Kim, Sunghee; Autschbach, Frank; Schirmacher, Peter; Roth, Wilfried

2008-10-01

Decoy receptor 3 (DcR3) is a soluble protein that binds to and inactivates the death ligand CD95L. Here, we studied a possible association between DcR3 expression and prognosis in patients with renal cell carcinomas (RCCs). A tissue microarray containing RCC tumor tissue samples and corresponding normal tissue samples was generated. Decoy receptor 3 expression in tumors of 560 patients was examined by immunohistochemistry. The effect of DcR3 expression on disease-specific survival and progression-free survival was assessed using univariate analysis and multivariate Cox regression analysis. Decoy receptor 3 serum levels were determined by ELISA. High DcR3 expression was associated with high-grade (P = .005) and high-stage (P = .048) RCCs. The incidence of distant metastasis (P = .03) and lymph node metastasis (P = .002) was significantly higher in the group with high DcR3 expression. Decoy receptor 3 expression correlated negatively with disease-specific survival (P < .001) and progression-free survival (P < .001) in univariate analyses. A multivariate Cox regression analysis retained DcR3 expression as an independent prognostic factor that outperformed the Karnofsky performance status. In patients with high-stage RCCs expressing DcR3, the 2-year survival probability was 25%, whereas in patients with DcR3-negative tumors, the survival probability was 65% (P < .001). Moreover, DcR3 serum levels were significantly higher in patients with high-stage localized disease (P = .007) and metastatic disease (P = .001). DcR3 expression is an independent prognostic factor of RCC progression and mortality. Therefore, the assessment of DcR3 expression levels offers valuable prognostic information that could be used to select patients for adjuvant therapy studies.

Brain volume reduction after whole-brain radiotherapy: quantification and prognostic relevance.

PubMed

Hoffmann, Christian; Distel, Luitpold; Knippen, Stefan; Gryc, Thomas; Schmidt, Manuel Alexander; Fietkau, Rainer; Putz, Florian

2018-01-22

Recent studies have questioned the value of adding whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) for brain metastasis treatment. Neurotoxicity, including radiation-induced brain volume reduction, could be one reason why not all patients benefit from the addition of WBRT. In this study, we quantified brain volume reduction after WBRT and assessed its prognostic significance. Brain volumes of 91 patients with cerebral metastases were measured during a 150-day period after commencing WBRT and were compared with their pretreatment volumes. The average daily relative change in brain volume of each patient, referred to as the "brain volume reduction rate," was calculated. Univariate and multivariate Cox regression analyses were performed to assess the prognostic significance of the brain volume reduction rate, as well as of 3 treatment-related and 9 pretreatment factors. A one-way analysis of variance was used to compare the brain volume reduction rate across recursive partitioning analysis (RPA) classes. On multivariate Cox regression analysis, the brain volume reduction rate was a significant predictor of overall survival after WBRT (P < 0.001), as well as the number of brain metastases (P = 0.002) and age (P = 0.008). Patients with a relatively favorable prognosis (RPA classes 1 and 2) experienced significantly less brain volume decrease after WBRT than patients with a poor prognosis (RPA class 3) (P = 0.001). There was no significant correlation between delivered radiation dose and brain volume reduction rate (P = 0.147). In this retrospective study, a smaller decrease in brain volume after WBRT was an independent predictor of longer overall survival. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The incidence and prevalence of pterygium in South Korea: A 10-year population-based Korean cohort study.

PubMed

Rim, Tyler Hyungtaek; Kang, Min Jae; Choi, Moonjung; Seo, Kyoung Yul; Kim, Sung Soo

2017-01-01

Although numerous population-based studies have reported the prevalences and risk factors for pterygium, information regarding the incidence of pterygium is scarce. This population-based cohort study aimed to evaluate the South Korean incidence and prevalence of pterygium. We retrospectively obtained data from a nationally representative sample of 1,116,364 South Koreans in the Korea National Health Insurance Service National Sample Cohort (NHIS-NSC). The associated sociodemographic factors were evaluated using multivariable Cox regression analysis, and the hazard ratios and confidence intervals were calculated. Pterygium was defined based on the Korean Classification of Diseases code, and surgically removed pterygium was defined as cases that required surgical removal. We identified 21,465 pterygium cases and 8,338 surgically removed pterygium cases during the study period. The overall incidences were 2.1 per 1,000 person-years for pterygium and 0.8 per 1,000 person-years for surgically removed pterygium. Among subjects who were ≥40 years old, the incidences were 4.3 per 1,000 person-years for pterygium and 1.7 per 1,000 person-years for surgically removed pterygium. The overall prevalences were 1.9% for pterygium and 0.6% for surgically removed pterygium, and the prevalences increased to 3.8% for pterygium and 1.4% for surgically removed pterygium among subjects who were ≥40 years old. The incidences of pterygium decreased according to year. The incidence and prevalence of pterygium were highest among 60-79-year-old individuals. Increasing age, female sex, and living in a relatively rural area were associated with increased risks of pterygium and surgically removed pterygium in the multivariable Cox regression analysis. Our analyses of South Korean national insurance claims data revealed a decreasing trend in the incidence of pterygium during the study period.

Comparison between imported versus domestic drug-eluting stents in China: A large single-center data.

PubMed

Liu, Ru; Gao, Zhan; Chen, Jue; Gao, Lijian; Song, Lei; Qiao, Shubin; Yang, Yuejin; Gao, Runlin; Xu, Bo; Yuan, Jinqing

2017-08-01

In recent years, most drug-eluting stents (DESs) were domestically produced in China, but how domestic DESs perform compared to imported DESs was still unknown. A total of 9011 consecutive cases with DESs implantation in a single center throughout 2013 were prospectively collected. Two-year clinical outcomes were evaluated between patients implanted with imported and domestic DESs. During 2-year follow-up, the rates of all-cause death, cardiac death, myocardial infarction, stroke, and stent thrombosis were not significantly different between two groups. However, the rate of revascularization was significantly higher in domestic DES group, shown as higher rates of overall revascularization, target vessel revascularization (TVR), and target lesion revascularization (TLR) (9.7% vs 6.4%, P < 0.001; 5.6% vs 3.2%, P < 0.001; 4.5% vs 2.2%, P < 0.001, respectively). Accordingly, major adverse cardiac events (MACE) rate was significantly higher in domestic DES group (12.1% vs 8.5%, P < 0.001). Multivariable Cox regression analysis indicated that domestic DES was an independent risk factor of MACE (HR [95%CI]: 1.22 [1.05-1.41]), overall revascularization (HR [95%CI]: 1.29 [1.09-1.53]), TVR (HR [95%CI]: 1.54 [1.22-1.94]), and TLR (HR [95%CI]: 1.85 [1.41-2.42]). After propensity score matching, the rates of overall revascularization, TVR, and TLR were still significantly higher in domestic DES group, and domestic DES was still predictive of overall revascularization, TVR, and TLR in multivariate Cox regression analysis. Domestic DESs showed the same safety as imported DESs in this real-world cohort. But, patients implanted with domestic DESs had a higher risk of revascularization than imported DESs. © 2017, Wiley Periodicals, Inc.

Racial differences in circulating natriuretic peptide levels: the atherosclerosis risk in communities study.

PubMed

Gupta, Deepak K; Claggett, Brian; Wells, Quinn; Cheng, Susan; Li, Man; Maruthur, Nisa; Selvin, Elizabeth; Coresh, Josef; Konety, Suma; Butler, Kenneth R; Mosley, Thomas; Boerwinkle, Eric; Hoogeveen, Ron; Ballantyne, Christie M; Solomon, Scott D

2015-05-21

Natriuretic peptides promote natriuresis, diuresis, and vasodilation. Experimental deficiency of natriuretic peptides leads to hypertension (HTN) and cardiac hypertrophy, conditions more common among African Americans. Hospital-based studies suggest that African Americans may have reduced circulating natriuretic peptides, as compared to Caucasians, but definitive data from community-based cohorts are lacking. We examined plasma N-terminal pro B-type natriuretic peptide (NTproBNP) levels according to race in 9137 Atherosclerosis Risk in Communities (ARIC) Study participants (22% African American) without prevalent cardiovascular disease at visit 4 (1996-1998). Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates. Among African Americans, percent European ancestry was determined from genetic ancestry informative markers and then examined in relation to NTproBNP levels in multivariable linear regression analysis. NTproBNP levels were significantly lower in African Americans (median, 43 pg/mL; interquartile range [IQR], 18, 88) than Caucasians (median, 68 pg/mL; IQR, 36, 124; P<0.0001). In multivariable models, adjusted log NTproBNP levels were 40% lower (95% confidence interval [CI], -43, -36) in African Americans, compared to Caucasians, which was consistent across subgroups of age, gender, HTN, diabetes, insulin resistance, and obesity. African-American race was also significantly associated with having nondetectable NTproBNP (adjusted OR, 5.74; 95% CI, 4.22, 7.80). In multivariable analyses in African Americans, a 10% increase in genetic European ancestry was associated with a 7% (95% CI, 1, 13) increase in adjusted log NTproBNP. African Americans have lower levels of plasma NTproBNP than Caucasians, which may be partially owing to genetic variation. Low natriuretic peptide levels in African Americans may contribute to the greater risk for HTN and its sequalae in this population. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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.

Mediterranean Diet and Hip Fracture in Swedish Men and Women.

PubMed

Byberg, Liisa; Bellavia, Andrea; Larsson, Susanna C; Orsini, Nicola; Wolk, Alicja; Michaëlsson, Karl

2016-12-01

A Mediterranean diet, known to have beneficial effects on cardiovascular health, may also influence the risk of hip fracture although previous studies present discrepant results. We therefore aimed to determine whether the rate of hip fracture was associated with degree of adherence to a Mediterranean diet. We combined two Swedish cohort studies consisting of 37,903 men and 33,403 women (total n = 71,333, mean age 60 years) free of previous cardiovascular disease and cancer who answered a medical and a food-frequency questionnaire in 1997. A modified Mediterranean diet score (mMED; range, 0 to 8 points) was created based on high consumption of fruits and vegetables, legumes and nuts, whole grains, fermented dairy products, fish, and olive/rapeseed oil, moderate intake of alcohol, and low intake of red and processed meat. Incident hip fractures between January 1, 1998, and December 31, 2012, were retrieved from the National Patient Register. Hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for potential confounders were calculated using Cox proportional hazards regression. Differences in age at hip fracture were calculated using multivariable Laplace regression. During follow-up, 3175 hip fractures occurred at a median age of 73.3 years. One unit increase in the mMED was associated with 6% lower hip fracture rate (adjusted HR = 0.94; 95% CI, 0.92 to 0.96) and with a 3-month higher median age at hip fracture (50th percentile difference = 2.8 months; 95% CI, 1.4 to 4.2). Comparing the highest quintile of adherence to the mMED (6 to 8 points) with the lowest (0 to 2 points) conferred an adjusted HR of hip fracture of 0.78 (95% CI, 0.69 to 0.89) and a 12-month higher median age of hip fracture (50th percentile difference = 11.6 months; 95% CI, 4.2 to 19.0). Results were similar in men and women. We conclude that higher adherence to a Mediterranean-like diet is associated with lower risk of future hip fracture. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Starting Dose of Sorafenib for the Treatment of Hepatocellular Carcinoma: A Retrospective, Multi-Institutional Study.

PubMed

Reiss, Kim A; Yu, Shun; Mamtani, Ronac; Mehta, Rajni; D'Addeo, Kathryn; Wileyto, E Paul; Taddei, Tamar H; Kaplan, David E

2017-11-01

Purpose Sorafenib is currently the only Food and Drug Administration-approved first-line therapy for patients with advanced hepatocellular carcinoma. There are few data examining how sorafenib starting dose may influence patient outcomes and costs. Patients and Methods We retrospectively evaluated 4,903 patients from 128 Veterans Health Administration hospitals who were prescribed sorafenib for hepatocellular carcinoma between January 2006 and April 2015. After 1:1 propensity score matching to account for potential treatment bias, hazard ratios (HRs) were calculated using Cox regression and were tested against a noninferiority margin of HR = 1.1. A matched multivariate logistic regression was performed to adjust for potential confounders. The primary end point was overall survival (OS) of patients who were prescribed standard starting dosage sorafenib (800 mg/d per os) versus that of patients who were prescribed reduced starting dose sorafenib (< 800 mg/d per os). Results There were 3,094 standard dose sorafenib patients (63%) and 1,809 reduced starting dose sorafenib patients (37%). Reduced starting dose sorafenib patients had more Barcelona Clinic Liver Cancer stage D ( P < .001), higher Model for End-Stage Liver Disease Sodium scores ( P < .001), higher Child-Turcotte-Pugh scores ( P < .001), and higher Cirrhosis Comorbidity Index scores ( P = .01). Consequently, reduced starting dose sorafenib patients had lower OS (median, 200 v 233 days, HR = 1.10). After propensity score matching and adjusting for potential confounders, there was no longer a significant OS difference (adjusted hazard ratio [HR adj ], 0.92; 95% CI, 0.83 to 1.01), and this fell significantly below the noninferiority margin ( P < .001). Reduced starting dose sorafenib patients experienced significantly lower total cumulative sorafenib cost and were less likely to discontinue sorafenib because of gastrointestinal adverse effects (8.7% v 10.8%; P = .047). Conclusion The initiation of sorafenib therapy at reduced dosages was associated with reduced pill burden, reduced treatment costs, and a trend toward a decreased rate of discontinuing sorafenib because of adverse events. Reduced dosing was not associated with inferior OS relative to standard dosing.

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

PubMed Central

2010-01-01

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

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

PubMed

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

2018-02-01

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

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

PubMed

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

2018-01-01

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

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.

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

PubMed

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

2018-05-07

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

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.

Quality of initial HIV care in Canada: extension of a composite programmatic assessment tool for HIV therapy.

PubMed

Kesselring, S; Cescon, A; Colley, G; Osborne, C; Zhang, W; Raboud, J M; Hosein, S R; Burchell, A N; Cooper, C; Klein, M B; Loutfy, M; Machouf, N; Montaner, Jsg; Rachlis, A; Tsoukas, C; Hogg, R S; Lima, V D

2017-03-01

To document the quality of initial HIV care in Canada using the Programmatic Compliance Score (PCS), to explore the association of the PCS with mortality, and to identify factors associated with higher quality of care. We analysed data from the Canadian Observational Cohort Collaboration (CANOC), a multisite Canadian cohort of HIV-positive adults initiating combination antiretroviral therapy (ART) from 2000 to 2011. PCS indicators of noncompliance with HIV treatment guidelines include: fewer than three CD4 count tests in the first year of ART; fewer than three viral load tests in the first year of ART; no drug resistance testing before initiation; baseline CD4 count < 200 cells/mm 3 ; starting a nonrecommended ART regimen; and not achieving viral suppression within 6 months of initiation. Indicators are summed for a score from 0 to 6; higher scores indicate poorer care. Cox regression was used to assess the association between PCS and mortality and ordinal logistic regression was used to explore factors associated with higher quality of care. Of the 7460 participants (18% female), the median score was 1.0 (Q1-Q3 1.0-2.0); 21% scored 0 and 8% scored ≥ 4. In multivariable analysis, compared with a score of 0, poorer PCS was associated with mortality for scores > 1 [score = 2: adjusted hazard ratio (AHR) 1.64; 95% confidence interval (CI) 1.13-2.36; score = 3: AHR 2.02; 95% CI 1.38-2.97; score ≥ 4: AHR 2.14; 95% CI 1.43-3.21], after adjustments for age, sex, province, ART start year, hepatitis C virus (HCV) coinfection, and baseline viral load. Women, individuals with HCV coinfection, younger people, and individuals starting ART earlier (2000-2003) had poorer scores. Our findings further validate the PCS as a predictor of all-cause mortality. Disparities identified suggest that further efforts are needed to ensure that care is equitably accessible. © 2016 British HIV Association.

Harmonic scalpel versus electrocautery dissection in modified radical mastectomy: a randomized controlled trial.

PubMed

Khan, Salma; Khan, Shaista; Chawla, Tabish; Murtaza, Ghulam

2014-03-01

To test the hypothesis that the use of a harmonic scalpel increases operative time but results in less estimated blood loss, postoperative pain, drainage volume, and duration of surgery, as well as fewer complications, such as flap necrosis, seroma, and surgical site infection (SSI), than electrocautery. This parallel-group, single-institution blinded randomized controlled trial was conducted at the department of surgery of our institute between April 2010 and July 2011. Women undergoing modified radical mastectomy were randomly allocated to either harmonic dissection (n = 76) or electrocautery (n = 76). Both the groups were comparable for baseline variables with age of 50.5 ± 12.2 and 48.5 ± 14.5 years in the harmonic and electrocautery groups, respectively. Harmonic dissection yielded better outcomes compared to electrocautery with lower estimated blood loss (100 ± 62 vs. 182 ± 92, p < 0.001), less drain volume (631 ± 275 ml vs. 1035 ± 413 ml, p < 0.001), fewer drain days (12 ± 3 vs. 17 ± 4, p < 0.001), less seroma formation (21.3 vs. 33.3 %, p = 0.071), and less postoperative pain [median (interquartile range) 2 (2-2) vs. 3 (3-4), p < 0.001], whereas mean operative time (191 ± 44 vs. 187 ± 36 min, p = 0.49) and SSI (0 vs. 4 %, p = 0.122) did not differ. On multivariable Cox regression analysis, harmonic dissection was associated with lower risk of significant postoperative pain [adjusted relative risk 0.028 (95 % confidence interval (CI) 0.004-0.2)] and overall complications [adjusted relative risk 0.47, (95 % CI 0.26-0.86)]. On multiple linear regression, duration of drains in the harmonic dissection group was 4.5 days less than electrocautery (r2 = 0.28, β = 11.8, p < 0.001). The harmonic scalpel significantly reduces postoperative discomfort and morbidity to the patient without increasing operating time. We thus recommend preferential use of harmonic dissection in modified radical mastectomy. (ClinicalTrials.gov NCT01587248).

Diabetes Reduces the Rate of Sputum Culture Conversion in Patients With Newly Diagnosed Multidrug-Resistant Tuberculosis

PubMed Central

Salindri, Argita D.; Kipiani, Maia; Kempker, Russell R.; Gandhi, Neel R.; Darchia, Lasha; Tukvadze, Nestani; Blumberg, Henry M.; Magee, Matthew J.

2016-01-01

Background. Diabetes is a risk factor for active tuberculosis (TB), but little is known about the relationship between diabetes and multidrug-resistant (MDR) TB. We aimed to assess risk factors for primary MDR TB, including diabetes, and determine whether diabetes reduced the rate of sputum culture conversion among patients with MDR TB. Methods. From 2011 to 2014, we conducted a cohort study at the National Center for Tuberculosis and Lung Diseases in Tbilisi, Georgia. Adult (≥35 years) patients with primary TB were eligible. Multidrug-resistant TB was defined as resistance to at least rifampicin and isoniazid. Patients with capillary glycosylated hemoglobin (HbA1c) ≥ 6.5% or previous diagnosis were defined to have diabetes. Polytomous regression was used to estimate the association of patient characteristics with drug resistance. Cox regression was used to compare rates of sputum culture conversion in patients with and without diabetes. Results. Among 318 patients with TB, 268 had drug-susceptibility test (DST) results. Among patients with DST results, 19.4% (52 of 268) had primary MDR TB and 13.4% (36 of 268) had diabetes. In multivariable analyses, diabetes (adjusted odds ratio [aOR], 2.51; 95% confidence interval [CI], 1.00–6.31) and lower socioeconomic status (aOR, 3.51; 95% CI, 1.56–8.20) were associated with primary MDR TB. Among patients with primary MDR TB, 44 (84.6%) converted sputum cultures to negative. The rate of sputum culture conversion was lower among patients with diabetes (adjusted hazard ratio [aHR], 0.34; 95% CI, .13–.87) and among smokers (aHR, 0.16; 95% CI, .04–.61). Conclusions. We found diabetes was associated with an increased risk of primary MDR TB; both diabetes and smoking were associated with a longer time to sputum culture conversion. PMID:27419188

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.

Results of therapy for acute lymphoblastic leukemia in black and white children.

PubMed

Pui, Ching-Hon; Sandlund, John T; Pei, Deqing; Rivera, Gaston K; Howard, Scott C; Ribeiro, Raul C; Rubnitz, Jeffrey E; Razzouk, Bassem I; Hudson, Melissa M; Cheng, Cheng; Raimondi, Susana C; Behm, Frederick G; Downing, James R; Relling, Mary V; Evans, William E

2003-10-15

Treatment results for acute lymphoblastic leukemia (ALL) clearly have improved over the past decade, but black children have not fared as well as white children in large national trials. To compare the clinical outcomes of therapy for black and white children with ALL treated at a single institution. A retrospective analysis of 412 children and adolescents (68 black, 338 white, and 6 other race) with newly diagnosed ALL who were treated consecutively at a pediatric cancer center in Memphis, Tenn. Patients were enrolled from December 1991 to July 1998 in successive Total Therapy studies regardless of race, ethnicity, or ability to pay and received risk-directed therapy according to stringent criteria. All patients received the same intensive, remission-induction therapy followed by 120 weeks of risk-assigned postremission therapy that included reinduction treatment, pulses of high-dose methotrexate, and early intensification of intrathecal chemotherapy. Event-free and overall survival rates for black and white children were estimated by the method of Kaplan and Meier and compared with the Mantel-Haenszel test and by Cox proportional hazards regression analysis, adjusting for known prognostic factors. The 68 black children were significantly more likely than the 338 white children to have higher-risk prognostic features, including an initial leukocyte count greater than 100 x 10(3)/ microL, a T-cell immunophenotype, and the t(1;19) chromosomal translocation with E2A-PBX1 fusion, and were less likely to have hyperdiploid blast cells, a favorable prognostic factor in childhood ALL. However, the clinical outcomes for these 2 cohorts were not significantly different: 5-year event-free and overall survival rates were 80.7% (95% confidence interval [CI], 70.3%-91.1%) and 86.2% (95% CI, 77.2%-95.2%) for black children vs 79.4% (95% CI, 74.7%-84.1%) and 85.0% (95% CI, 80.9%-89.1%) for white children. Ten-year results also were comparable, but the CIs were wide because of the small numbers of patients who had been followed up for 10 years or more. The lack of a racial effect on the long-term outcome of therapy was still apparent in a multivariate Cox regression analysis, adjusting for sex, age, presenting leukocyte count, leukemic cell DNA index, immunophenotype, and central nervous system status. With equal access to effective antileukemic therapy, black and white children with ALL can expect the same high rate of cure.

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

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

Psychosocial Correlates of Dating Violence Victimization among Latino Youth

ERIC Educational Resources Information Center

Howard, Donna E.; Beck, Kenneth; Kerr, Melissa Hallmark; Shattuck, Teresa

2005-01-01

To examine the association between physical dating violence victimization and risk and protective factors, an anonymous, cross-sectional, self-reported survey was administered to Latino youth (n = 446) residing in suburban Washington, DC. Multivariate logistic regression models were constructed, and adjusted OR and 95% CI were examined.…

Applying Additive Hazards Models for Analyzing Survival in Patients with Colorectal Cancer in Fars Province, Southern Iran

PubMed

Madadizadeh, Farzan; Ghanbarnejad, Amin; Ghavami, Vahid; Zare Bandamiri, Mohammad; Mohammadianpanah, Mohammad

2017-04-01

Introduction: Colorectal cancer (CRC) is a commonly fatal cancer that ranks as third worldwide and third and the fifth in Iranian women and men, respectively. There are several methods for analyzing time to event data. Additive hazards regression models take priority over the popular Cox proportional hazards model if the absolute hazard (risk) change instead of hazard ratio is of primary concern, or a proportionality assumption is not made. Methods: This study used data gathered from medical records of 561 colorectal cancer patients who were admitted to Namazi Hospital, Shiraz, Iran, during 2005 to 2010 and followed until December 2015. The nonparametric Aalen’s additive hazards model, semiparametric Lin and Ying’s additive hazards model and Cox proportional hazards model were applied for data analysis. The proportionality assumption for the Cox model was evaluated with a test based on the Schoenfeld residuals and for test goodness of fit in additive models, Cox-Snell residual plots were used. Analyses were performed with SAS 9.2 and R3.2 software. Results: The median follow-up time was 49 months. The five-year survival rate and the mean survival time after cancer diagnosis were 59.6% and 68.1±1.4 months, respectively. Multivariate analyses using Lin and Ying’s additive model and the Cox proportional model indicated that the age of diagnosis, site of tumor, stage, and proportion of positive lymph nodes, lymphovascular invasion and type of treatment were factors affecting survival of the CRC patients. Conclusion: Additive models are suitable alternatives to the Cox proportionality model if there is interest in evaluation of absolute hazard change, or no proportionality assumption is made. Creative Commons Attribution License

Dental Health and Mortality in People With End-Stage Kidney Disease Treated With Hemodialysis: A Multinational Cohort Study.

PubMed

Palmer, Suetonia C; Ruospo, Marinella; Wong, Germaine; Craig, Jonathan C; Petruzzi, Massimo; De Benedittis, Michele; Ford, Pauline; Johnson, David W; Tonelli, Marcello; Natale, Patrizia; Saglimbene, Valeria; Pellegrini, Fabio; Celia, Eduardo; Gelfman, Ruben; Leal, Miguel R; Torok, Marietta; Stroumza, Paul; Bednarek-Skublewska, Anna; Dulawa, Jan; Frantzen, Luc; Ferrari, Juan Nin; Del Castillo, Domingo; Bernat, Amparo G; Hegbrant, Jorgen; Wollheim, Charlotta; Gargano, Letizia; Bots, Casper P; Strippoli, Giovanni F M

2015-10-01

Dental disease is more extensive in adults with chronic kidney disease, but whether dental health and behaviors are associated with survival in the setting of hemodialysis is unknown. Prospective multinational cohort. 4,205 adults treated with long-term hemodialysis, 2010 to 2012 (Oral Diseases in Hemodialysis [ORAL-D] Study). Dental health as assessed by a standardized dental examination using World Health Organization guidelines and personal oral care, including edentulousness; decayed, missing, and filled teeth index; teeth brushing and flossing; and dental health consultation. All-cause and cardiovascular mortality at 12 months after dental assessment. Multivariable-adjusted Cox proportional hazards regression models fitted with shared frailty to account for clustering of mortality risk within countries. During a mean follow-up of 22.1 months, 942 deaths occurred, including 477 cardiovascular deaths. Edentulousness (adjusted HR, 1.29; 95% CI, 1.10-1.51) and decayed, missing, or filled teeth score ≥ 14 (adjusted HR, 1.70; 95% CI, 1.33-2.17) were associated with early all-cause mortality, while dental flossing, using mouthwash, brushing teeth daily, spending at least 2 minutes on oral hygiene daily, changing a toothbrush at least every 3 months, and visiting a dentist within the past 6 months (adjusted HRs of 0.52 [95% CI, 0.32-0.85], 0.79 [95% CI, 0.64-0.97], 0.76 [95% CI, 0.58-0.99], 0.84 [95% CI, 0.71-0.99], 0.79 [95% CI, 0.65-0.95], and 0.79 [95% CI, 0.65-0.96], respectively) were associated with better survival. Results for cardiovascular mortality were similar. Convenience sample of clinics. In adults treated with hemodialysis, poorer dental health was associated with early death, whereas preventive dental health practices were associated with longer survival. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Higher Serum Direct Bilirubin Levels Were Associated with a Lower Risk of Incident Chronic Kidney Disease in Middle Aged Korean Men

PubMed Central

Ryu, Seungho; Chang, Yoosoo; Zhang, Yiyi; Woo, Hee-Yeon; Kwon, Min-Jung; Park, Hyosoon; Lee, Kyu-Beck; Son, Hee Jung; Cho, Juhee; Guallar, Eliseo

2014-01-01

Background The association between serum bilirubin levels and incident chronic kidney disease (CKD) in the general population is unknown. We aimed to examine the association between serum bilirubin concentration (total, direct, and indirect) and the risk of incident CKD. Methods and Findings Longitudinal cohort study of 12,823 Korean male workers 30 to 59 years old without CKD or proteinuria at baseline participating in medical health checkup program in a large worksite. Study participants were followed for incident CKD from 2002 through 2011. Estimated glomerular filtration rate (eGFR) was estimated by using the CKD-EPI equation. CKD was defined as eGFR <60 mL/min per 1.73 m2. Parametric Cox models and pooled logistic regression models were used to estimate adjusted hazard ratios for incident CKD. We observed 238 incident cases of CKD during 70,515.8 person-years of follow-up. In age-adjusted models, the hazard ratios for CKD comparing quartiles 2–4 vs. quartile 1 of serum direct bilirubin were 0.93 (95% CI 0.67–1.28), 0.88 (0.60–1.27) and 0.60 (0.42–0.88), respectively. In multivariable models, the adjusted hazard ratio for CKD comparing the highest to the lowest quartile of serum direct bilirubin levels was 0.60 (95% CI 0.41–0.87; P trend = 0.01). Neither serum total nor indirect bilirubin levels were significantly associated with the incidence of CKD. Conclusions Higher serum direct bilirubin levels were significantly associated with a lower risk of developing CKD, even adjusting for a variety of cardiometabolic parameters. Further research is needed to elucidate the mechanisms underlying this association and to establish the role of serum direct bilirubin as a marker for CKD risk. PMID:24586219

Lean body mass and risk of incident atrial fibrillation in post-menopausal women.

PubMed

Azarbal, Farnaz; Stefanick, Marcia L; Assimes, Themistocles L; Manson, JoAnn E; Bea, Jennifer W; Li, Wenjun; Hlatky, Mark A; Larson, Joseph C; LeBlanc, Erin S; Albert, Christine M; Nassir, Rami; Martin, Lisa W; Perez, Marco V

2016-05-21

High body mass index (BMI) is a risk factor for atrial fibrillation (AF). The aim of this study was to determine whether lean body mass (LBM) predicts AF. The Women's Health Initiative is a study of post-menopausal women aged 50-79 enrolled at 40 US centres from 1994 to 1998. A subset of 11 393 participants at three centres underwent dual-energy X-ray absorptiometry. Baseline demographics and clinical histories were recorded. Incident AF was identified using hospitalization records and diagnostic codes from Medicare claims. A multivariable Cox hazard regression model adjusted for demographic and clinical risk factors was used to evaluate associations between components of body composition and AF risk. After exclusion for prevalent AF or incomplete data, 8832 participants with an average age of 63.3 years remained for analysis. Over the 11.6 years of average follow-up time, 1035 women developed incident AF. After covariate adjustment, all measures of LBM were independently associated with higher rates of AF: total LBM [hazard ratio (HR) 1.24 per 5 kg increase, 95% confidence intervals (CI) 1.14-1.34], central LBM (HR 1.51 per 5 kg increase, 95% CI 1.31-1.74), and peripheral LBM (HR 1.39 per 5 kg increase, 95% CI 1.19-1.63). The association between total LBM and AF remained significant after adjustment for total fat mass (HR 1.22 per 5 kg increase, 95% CI 1.13-1.31). Greater LBM is a strong independent risk factor for AF. After adjusting for obesity-related risk factors, the risk of AF conferred by higher BMI is primarily driven by the association between LBM and AF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Lansoprazole use and tuberculosis incidence in the United Kingdom Clinical Practice Research Datalink: A population based cohort

PubMed Central

Yates, Tom A.; Tomlinson, Laurie A.; Bhaskaran, Krishnan; Langan, Sinead; Thomas, Sara; Smeeth, Liam

2017-01-01

Background Recent in vitro and animal studies have found the proton pump inhibitor (PPI) lansoprazole to be highly active against Mycobacterium tuberculosis. Omeprazole and pantoprazole have no activity. There is no evidence that, in clinical practice, lansoprazole can treat or prevent incident tuberculosis (TB) disease. Methods and findings We studied a cohort of new users of lansoprazole, omeprazole, or pantoprazole from the United Kingdom Clinical Practice Research Datalink to determine whether lansoprazole users have a lower incidence of TB disease than omeprazole or pantoprazole users. Negative control outcomes of myocardial infarction (MI) and herpes zoster were also studied. Multivariable Cox proportional hazards regression was used to adjust for potential confounding by a wide range of factors. We identified 527,364 lansoprazole initiators and 923,500 omeprazole or pantoprazole initiators. Lansoprazole users had a lower rate of TB disease (n = 86; 10.0 cases per 100,000 person years; 95% confidence interval 8.1–12.4) than omeprazole or pantoprazole users (n = 193; 15.3 cases per 100,000 person years; 95% confidence interval 13.3–17.7), with an adjusted hazard ratio (HR) of 0.68 (0.52–0.89). No association was found with MI (adjusted HR 1.04; 95% confidence interval 1.00–1.08) or herpes zoster (adjusted HR 1.03; 95% confidence interval 1.00–1.06). Limitations of this study are that we could not determine whether TB disease was due to reactivation of latent infection or a result of recent transmission, nor could we determine whether lansoprazole would have a beneficial effect if given to people presenting with TB disease. Conclusions In this study, use of the commonly prescribed and cheaply available PPI lansoprazole was associated with reduced incidence of TB disease. Given the serious problem of drug resistance and the adverse side effect profiles of many TB drugs, further investigation of lansoprazole as a potential antituberculosis agent is warranted. PMID:29161254

Potentially modifiable factors contributing to sepsis-associated encephalopathy.

PubMed

Sonneville, Romain; de Montmollin, Etienne; Poujade, Julien; Garrouste-Orgeas, Maïté; Souweine, Bertrand; Darmon, Michael; Mariotte, Eric; Argaud, Laurent; Barbier, François; Goldgran-Toledano, Dany; Marcotte, Guillaume; Dumenil, Anne-Sylvie; Jamali, Samir; Lacave, Guillaume; Ruckly, Stéphane; Mourvillier, Bruno; Timsit, Jean-François

2017-08-01

Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) <15 or when features of delirium were noted. Potentially modifiable risk factors for SAE at ICU admission and its impact on mortality were investigated using multivariate logistic regression analysis and Cox proportional hazard modeling, respectively. We included 2513 patients with sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19-1.67], hypoglycemia <3 mmol/l (aOR = 2.66, 95% CI 1.27-5.59), hyperglycemia >10 mmol/l (aOR = 1.37, 95% CI 1.09-1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53-2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48-3.57), and S. aureus (aOR = 1.54, 95% CI 1.05-2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13-14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09-1.76). Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

Associations Between Complex PCI and Prasugrel or Clopidogrel Use in Patients With Acute Coronary Syndrome Who Undergo PCI: From the PROMETHEUS Study.

PubMed

Chandrasekhar, Jaya; Baber, Usman; Sartori, Samantha; Aquino, Melissa; Kini, Annapoorna S; Rao, Sunil; Weintraub, William; Henry, Timothy D; Farhan, Serdar; Vogel, Birgit; Sorrentino, Sabato; Ge, Zhen; Kapadia, Samir; Muhlestein, Joseph B; Weiss, Sandra; Strauss, Craig; Toma, Catalin; DeFranco, Anthony; Effron, Mark B; Keller, Stuart; Baker, Brian A; Pocock, Stuart; Dangas, George; Mehran, Roxana

2018-03-01

Potent P2Y 12 inhibitors might offer enhanced benefit against thrombotic events in complex percutaneous coronary intervention (PCI). We examined prasugrel use and outcomes according to PCI complexity, as well as analyzing treatment effects according to thienopyridine type. PROMETHEUS was a multicentre observational study that compared clopidogrel vs prasugrel in acute coronary syndrome patients who underwent PCI (n = 19,914). Complex PCI was defined as PCI of the left main, bifurcation lesion, moderate-severely calcified lesion, or total stent length ≥ 30 mm. Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke, or unplanned revascularization. Outcomes were adjusted using multivariable Cox regression for effect of PCI complexity and propensity-stratified analysis for effect of thienopyridine type. The study cohort included 48.9% (n = 9735) complex and 51.1% (n = 10,179) noncomplex patients. Second generation drug-eluting stents were used in 70.1% complex and 66.2% noncomplex PCI patients (P < 0.0001). Complex PCI was associated with greater adjusted risk of 1-year MACE (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.20-1.39; P < 0.001). Prasugrel was prescribed in 20.7% of complex and 20.1% of noncomplex PCI patients (P = 0.30). Compared with clopidogrel, prasugrel significantly decreased adjusted risk for 1-year MACE in complex PCI (HR, 0.79; 95% CI, 0.68-0.92) but not noncomplex PCI (HR, 0.91; 95% CI, 0.77-1.08), albeit there was no evidence of interaction (P interaction = 0.281). Despite the use of contemporary techniques, acute coronary syndrome patients who undergo complex PCI had significantly higher rates of 1-year MACE. Adjusted magnitude of treatment effects with prasugrel vs clopidogrel were consistent in complex and noncomplex PCI without evidence of interaction. Copyright © 2018. Published by Elsevier Inc.

Post-Transplant Hypophosphatemia and the Risk of Death-Censored Graft Failure and Mortality after Kidney Transplantation.

PubMed

van Londen, Marco; Aarts, Brigitte M; Deetman, Petronella E; van der Weijden, Jessica; Eisenga, Michele F; Navis, Gerjan; Bakker, Stephan J L; de Borst, Martin H

2017-08-07

Hypophosphatemia is common in the first year after kidney transplantation, but its clinical implications are unclear. We investigated the relationship between the severity of post-transplant hypophosphatemia and mortality or death-censored graft failure in a large cohort of renal transplant recipients with long-term follow-up. We performed a longitudinal cohort study in 957 renal transplant recipients who were transplanted between 1993 and 2008 at a single center. We used a large real-life dataset containing 28,178 phosphate measurements (median of 27; first to third quartiles, 23-34) serial measurements per patient) and selected the lowest intraindividual phosphate level during the first year after transplantation. The primary outcomes were all-cause mortality, cardiovascular mortality, and death-censored graft failure. The median (interquartile range) intraindividual lowest phosphate level was 1.58 (1.30-1.95) mg/dl, and it was reached at 33 (21-51) days post-transplant. eGFR was the main correlate of the lowest serum phosphate level (model R 2 =0.32). During 9 (5-12) years of follow-up, 181 (19%) patients developed graft failure, and 295 (35%) patients died, of which 94 (32%) deaths were due to cardiovascular disease. In multivariable Cox regression analysis, more severe hypophosphatemia was associated with a lower risk of death-censored graft failure (fully adjusted hazard ratio, 0.61; 95% confidence interval, 0.43 to 0.88 per 1 mg/dl lower serum phosphate) and cardiovascular mortality (fully adjusted hazard ratio, 0.37; 95% confidence interval, 0.22 to 0.62) but not noncardiovascular mortality (fully adjusted hazard ratio, 1.33; 95% confidence interval, 0.9 to 1.96) or all-cause mortality (fully adjusted hazard ratio, 1.15; 95% confidence interval, 0.81 to 1.61). Post-transplant hypophosphatemia develops early after transplantation. These data connect post-transplant hypophosphatemia with favorable long-term graft and patient outcomes. Copyright © 2017 by the American Society of Nephrology.

Sugar-sweetened and artificially sweetened beverage consumption and risk of type 2 diabetes in men123

PubMed Central

de Koning, Lawrence; Malik, Vasanti S; Rimm, Eric B; Willett, Walter C

2011-01-01

Background: Sugar-sweetened beverages are risk factors for type 2 diabetes; however, the role of artificially sweetened beverages is unclear. Objective: The objective was to examine the associations of sugar- and artificially sweetened beverages with incident type 2 diabetes. Design: An analysis of healthy men (n = 40,389) from the Health Professionals Follow-Up Study, a prospective cohort study, was performed. Cumulatively averaged intakes of sugar-sweetened (sodas, fruit punches, lemonades, fruit drinks) and artificially sweetened (diet sodas, diet drinks) beverages from food-frequency questionnaires were tested for associations with type 2 diabetes by using Cox regression. Results: There were 2680 cases over 20 y of follow-up. After age adjustment, the hazard ratio (HR) for the comparison of the top with the bottom quartile of sugar-sweetened beverage intake was 1.25 (95% CI: 1.11, 1.39; P for trend < 0.01). After adjustment for confounders, including multivitamins, family history, high triglycerides at baseline, high blood pressure, diuretics, pre-enrollment weight change, dieting, total energy, and body mass index, the HR was 1.24 (95% CI: 1.09, 1.40; P for trend < 0.01). Intake of artificially sweetened beverages was significantly associated with type 2 diabetes in the age-adjusted analysis (HR: 1.91; 95% CI: 1.72, 2.11; P for trend < 0.01) but not in the multivariate-adjusted analysis (HR: 1.09; 95% CI: 0.98, 1.21; P for trend = 0.13). The replacement of one serving of sugar-sweetened beverage with 1 cup (≈237 mL) of coffee was associated with a risk reduction of 17%. Conclusion: Sugar-sweetened beverage consumption is associated with a significantly elevated risk of type 2 diabetes, whereas the association between artificially sweetened beverages and type 2 diabetes was largely explained by health status, pre-enrollment weight change, dieting, and body mass index. PMID:21430119

Serum Uric Acid and Renal Transplantation Outcomes: At Least 3-Year Post-transplant Retrospective Multivariate Analysis

PubMed Central

Zhang, Kun; Gao, Baoshan; Wang, Yuantao; Wang, Gang; Wang, Weigang; Zhu, Yaxiang; Yao, Liyu; Gu, Yiming; Chen, Mo; Zhou, Honglan; Fu, Yaowen

2015-01-01

Since the association of serum uric acid and kidney transplant graft outcome remains disputable, we sought to evaluate the predictive value of uric acid level for graft survival/function and the factors could affect uric acid as time varies. A consecutive cohort of five hundred and seventy three recipients transplanted during January 2008 to December 2011 were recruited. Data and laboratory values of our interest were collected at 1, 3, 6, 12, 24 and 36 months post-transplant for analysis. Cox proportional hazard model, and multiple regression equation were built to adjust for the possible confounding variables and meet our goals as appropriate. The current cohort study lasts for 41.86 ± 15.49 months. Uric acid level is proven to be negatively associated with eGFR at different time point after adjustment for age, body mass index and male gender (standardized β ranges from -0.15 to -0.30 with all P<0.001).Males with low eGFR but high level of TG were on CSA, diuretics and RAS inhibitors and experienced at least one episode of acute rejection and diabetic issue were associated with a higher mean uric acid level. Hyperuricemia was significantly an independent predictor of pure graft failure (hazard ratio=4.01, 95% CI: 1.25-12.91, P=0.02) after adjustment. But it was no longer an independent risk factor for graft loss after adjustment. Interestingly, higher triglyceride level can make incidence of graft loss (hazard ratio=1.442, for each unit increase millimoles per liter 95% CI: 1.008-2.061, P=0.045) and death (hazard ratio=1.717, 95% CI: 1.105-2.665, P=0.016) more likely. The results of our study suggest that post-transplant elevated serum uric acid level is an independent predictor of long-term graft survival and graft function. Together with the high TG level impact on poor outcomes, further investigations for therapeutic effect are needed. PMID:26208103

The Impact of the Crown-Root Ratio on Survival of Abutment Teeth for Dentures.

PubMed

Tada, S; Allen, P F; Ikebe, K; Zheng, H; Shintani, A; Maeda, Y

2015-09-01

Crown-root ratio (CRR) is commonly recorded when planning prosthodontic procedures. However, there is a lack of longitudinal clinical data evaluating the association between CRR and tooth survival. The aim of this longitudinal practice-based study was to assess the impact of CRR on the survival of abutment teeth for removable partial dentures (RPDs). Data were collected from 147 patients provided with RPDs at a dental hospital in Japan. In total, 236 clasp-retained RPDs and 856 abutment teeth were analyzed. Survival of abutment teeth was assessed using Kaplan-Meier methods and Cox's proportional hazard (PH) regression. The Cox PH regression was used to assess the prognostic significance of initial CRR value with adjustments for clinically relevant factors, including age, sex, frequency of periodontal maintenance programs, occlusal support area, type of abutment tooth, status of endodontic treatment, and probing pocket depth. Abutment teeth were divided into 1 of 5 risk groups according to CRR: A (≤0.75), B (0.76-1.00), C (1.01-1.25), D (1.26-1.50) and E (≥1.51). The 7-year survival rate was 89.1% for group A, 85.9% for group B, 86.5% for group C, 76.9% for group D, and 46.7% for group E. The survival curves of groups A, B, and C were illustrated to be quite similar and favorable. The multivariable analysis treating CRR as a continuous variable allowed estimation of the hazard ratio at any specific CRR value. When CRR = 0.80 was set as a reference, the estimated hazard ratio was 0.58 for CRR = 0.50 (95% confidence interval [CI], 0.36-0.91), 1.13 for CRR = 1.00 (95% CI, 0.93-1.37), 1.35 for CRR = 1.25 (95% CI, 1.02-1.80), 1.53 for CRR = 1.50 (95% CI, 1.15-2.08), or 1.95 for CRR = 2.00 (95% CI, 1.44-2.65). These practice-based longitudinal data provide information to improve the evidence-based prognosis of teeth in providing prosthodontic procedures. © International & American Associations for Dental Research.

Inflammatory Biomarkers Predict Heart Failure Severity and Prognosis in Patients With Heart Failure With Preserved Ejection Fraction: A Holistic Proteomic Approach.

PubMed

Hage, Camilla; Michaëlsson, Erik; Linde, Cecilia; Donal, Erwan; Daubert, Jean-Claude; Gan, Li-Ming; Lund, Lars H

2017-02-01

Underlying mechanisms in heart failure (HF) with preserved ejection fraction remain unknown. We investigated cardiovascular plasma biomarkers in HF with preserved ejection fraction and their correlation to diastolic dysfunction, functional class, pathophysiological processes, and prognosis. In 86 stable patients with HF and EF ≥45% in the Karolinska Rennes (KaRen) biomarker substudy, biomarkers were quantified by a multiplex immunoassay. Orthogonal projection to latent structures by partial least square analysis was performed on 87 biomarkers and 240 clinical variables, ranking biomarkers associated with New York Heart Association (NYHA) Functional class and the composite outcome (all-cause mortality and HF hospitalization). Biomarkers significantly correlated with outcome were analyzed by multivariable Cox regression and correlations with echocardiographic measurements performed. The orthogonal partial least square outcome-predicting biomarker pattern was run against the Ingenuity Pathway Analysis (IPA) database, containing annotated data from the public domain. The orthogonal partial least square analyses identified 32 biomarkers correlated with NYHA class and 28 predicting outcomes. Among outcome-predicting biomarkers, growth/differentiation factor-15 was the strongest and an additional 7 were also significant in Cox regression analyses when adjusted for age, sex, and N-terminal probrain natriuretic peptide: adrenomedullin (hazard ratio per log increase 2.53), agouti-related protein; (1.48), chitinase-3-like protein 1 (1.35), C-C motif chemokine 20 (1.35), fatty acid-binding protein (1.33), tumor necrosis factor receptor 1 (2.29), and TNF-related apoptosis-inducing ligand (0.34). Twenty-three of them correlated with diastolic dysfunction (E/e') and 5 with left atrial volume index. The IPA suggested that increased inflammation, immune activation with decreased necrosis and apoptosis preceded poor outcome. In HF with preserved ejection fraction, novel biomarkers of inflammation predict HF severity and prognosis that may complement or even outperform traditional markers, such as N-terminal probrain natriuretic peptide. These findings lend support to a hypothesis implicating global systemic inflammation in HF with preserved ejection fraction. URL: http://www.clinicaltrials.gov; Unique identifier: NCT00774709. © 2017 American Heart Association, Inc.

Statin treatment may lower the risk of postradiation epilepsy in patients with nasopharyngeal carcinoma.

PubMed

Rong, Xiaoming; Yin, Jing; Wang, Hongxuan; Zhang, Xiaoni; Peng, Ying

2017-12-01

This study aimed to clarify the effect of statins on preventing the risk of postradiation epilepsy. We performed a retrospective analysis of neurological nasopharyngeal carcinoma patients with a history of radiotherapy. Patients with a history of epilepsy before radiation and those who received prophylactically antiepileptic treatment were excluded. The demographic and clinical data of these patients were collected through chart review. We used Kaplan-Meier analysis (log-rank test) to examine the effect of statins on epilepsy-free survival. Cox regression analysis was utilized to identify independent predictive variables. Our study included 532 patients (405 males and 127 females) with a mean follow-up of 28.1 months. During follow-up, 471 (88.5%) patients developed radiation-induced brain necrosis (RN). Within a mean latency of 24.1 months, 88 (16.5%) patients experienced epilepsy, of whom 27 (27 of 88, 30.7%) patients suffered from epilepsy before the diagnosis of RN. Thirty-six (36 of 88, 40.9%) cases of epilepsy occurred after RN onset, and in 22 cases (22 of 88, 25.0%) epilepsy was the first presentation of RN. Three patients suffered from epilepsy but did not have RN. Eighty-eight patients in our cohort were treated with statins because of hyperlipidemia or prevention of cardiocerebrovascular diseases, of whom six (6.8%) developed epilepsy, whereas in those without statin, the epileptic rate was 18.5%. Log-rank test found that there was a significant difference in epilepsy-free survival between patients who used statins and those who did not (p = 0.016). After adjusting for confounding variables, multivariate Cox regression analysis revealed that statin use could still significantly reduce the risk of epilepsy after radiation (hazard ratio = 0.36, 95% confidence interval = 0.15-0.82, p = 0.015). However, for the patients who already suffered from RN, statin treatment did not lower the risk of post-RN epilepsy. Early statin use may reduce the risk of postradiotherapy epilepsy in patients with nasopharyngeal carcinoma. © 2017 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Dual oxidase 1: A predictive tool for the prognosis of hepatocellular carcinoma patients.

PubMed

Chen, Shengsen; Ling, Qingxia; Yu, Kangkang; Huang, Chong; Li, Ning; Zheng, Jianming; Bao, Suxia; Cheng, Qi; Zhu, Mengqi; Chen, Mingquan

2016-06-01

Dual oxidase 1 (DUOX1), which is the main source of reactive oxygen species (ROS) production in the airway, can be silenced in human lung cancer and hepatocellular carcinomas. However, the prognostic value of DUOX1 expression in hepatocellular carcinoma patients is still unclear. We investigated the prognostic value of DUOX1 expression in liver cancer patients. DUOX1 mRNA expression was determined in tumor tissues and non-tumor tissues by real‑time PCR. For evaluation of the prognostic value of DUOX1 expression, Kaplan-Meier method and Cox's proportional hazards model (univariate analysis and multivariate analysis) were employed. A simple risk score was devised by using significant variables obtained from the Cox's regression analysis to further predict the HCC patient prognosis. We observed a reduced DUOX1 mRNA level in the cancer tissues in comparison to the non‑cancer tissues. More importantly, Kaplan-Meier analysis showed that patients with high DUOX1 expression had longer disease-free survival and overall survival compared with those with low expression of DUOX1. Cox's regression analysis indicated that DUOX1 expression, age, and intrahepatic metastasis may be significant prognostic factors for disease-free survival and overall survival. Finally, we found that patients with total scores of >2 and >1 were more likely to relapse and succumb to the disease than patients whose total scores were ≤2 and ≤1. In conclusion, DUOX1 expression in liver tumors is a potential prognostic tool for patients. The risk scoring system is useful for predicting the survival of liver cancer patients after tumor resection.

Does liver damage explain the inverse association between vitamin D status and mortality?

PubMed

Skaaby, Tea; Husemoen, Lise Lotte N; Linneberg, Allan

2013-12-01

Several observational studies have linked vitamin D deficiency with an increased risk of all cause mortality. Vitamin D deficiency is common among patients with liver diseases. In a random sample of the general population, we investigated whether the inverse association between vitamin D status and all-cause mortality could be explained by liver damage as reflected by increased levels of liver enzymes. We included a total of 2649 persons examined in 1993e1994. Vitamin D status was assessed as serum 25-hydroxyvitamin D and liver enzyme levels were measured. Information on all-cause mortality was obtained from the Danish Central Personal Register until July 2011. Median follow-up time was 17.0 years, and there were 736 deaths. Multivariable Cox regression analyses with age as underlying time axis and delayed entry showed lower mortality risk with higher vitamin D levels and this was essentially unaffected by adjustment for liver enzyme levels with hazard ratio, 0.96 (95% confidence interval, 0.93e0.99) for a 10 nmol/L higher vitamin D level. The present study did not support our hypothesis that the well-known association between low vitamin D status and mortality is explained by liver damage as reflected by levels of liver enzymes. 2013 Elsevier Inc. All rights reserved.

Association between HOMA-IR, fasting insulin and fasting glucose with coronary heart disease mortality in nondiabetic men: a 20-year observational study.

PubMed

Kurl, Sudhir; Zaccardi, Francesco; Onaemo, Vivian N; Jae, Sae Young; Kauhanen, Jussi; Ronkainen, Kimmo; Laukkanen, Jari A

2015-02-01

Whether glucose and insulin are differently associated with the risk of coronary heart disease (CHD) mortality is unclear. We aimed to estimate the association between insulin resistance (estimated by the homeostasis model assessment for insulin resistance, HOMA-IR), fasting serum insulin (FI) and fasting plasma glucose (FPG) with incident CHD mortality in a prospective study including middle-aged nondiabetic Finnish men. During an average follow-up of 20 years, 273 (11 %) CHD deaths occurred. In a multivariable Cox regression analysis adjusted for age, body mass index, systolic blood pressure, serum LDL-cholesterol, cigarette smoking, history of CHD, alcohol consumption, blood leukocytes and plasma fibrinogen, the hazard ratios (HRs) for CHD mortality comparing top versus bottom quartiles were as follows: 1.69 (95 % CI: 1.15-2.48; p = 0.008) for HOMA-IR; 1.59 (1.09-2.32; p = 0.016) for FI; and 1.26 (0.90-1.76; p = 0.173) for FPG. These findings suggest that IR and FI, but not FPG, are independent risk factors for CHD mortality. Further studies could help clarify these results in terms of screening and risk stratification, causality of the associations, and therapeutical implications.

Red wine consumption not associated with reduced risk of colorectal cancer.

PubMed

Chao, Chun; Haque, Reina; Caan, Bette J; Poon, Kwun-Yee T; Tseng, Hung-Fu; Quinn, Virginia P

2010-01-01

Red wine contains polyphenol antioxidants that inhibit colorectal cancer (CRC) development in animal studies. We investigated the effect of red wine intake on risk of CRC in the California Men's Health Study (CMHS). CMHS is a prospective, multiethnic cohort of middle-aged men who were members of the Kaiser Permanente (KP) California Health Plans and completed study questionnaires between 2002-2003. Incident CRC were identified from the health plan cancer registries through the end of 2007 (n = 287). To properly account for potential confounding by previous endoscopy screening, we restricted the primary analyses to CMHS men continuously enrolled in KP between 1998-2002 (n = 43,483 and CRC = 176). We used multivariable Cox regression to adjust for important confounders. We did not find an inverse association between moderate red wine intake and risk of CRC. The hazard ratio for consuming >/=1 drink/day (average = 2 drinks/day) was 1.16, 95% confidence intervals 0.56-2.40. There was no linear dose-response. The lack of clear association for red wine intake was consistently observed when we stratified the analyses by CRC stage at diagnosis and cancer site (colon or rectum). Moderate red wine consumption was not associated with reduced risk of colorectal cancer in this population of middle-aged men.

Tumour mutation status and melanoma recurrence following a negative sentinel lymph node biopsy.

PubMed

Adler, Nikki R; Wolfe, Rory; McArthur, Grant A; Kelly, John W; Haydon, Andrew; McLean, Catriona A; Mar, Victoria J

2018-05-14

A proportion of patients develop recurrence following a tumour-negative sentinel lymph node biopsy (SLNB). This study aimed to explore whether melanoma patients with BRAF or NRAS mutant tumours have an increased risk of developing disease recurrence following a negative SLNB compared to patients with wild-type tumours. Prospective cohort study of melanoma patients at three tertiary referral centres in Melbourne, who underwent SLNB. Clinical, pathological and molecular characteristics and recurrence data were prospectively recorded. Multivariate Cox proportional hazards regression models estimated the adjusted hazard ratio (aHR) and corresponding 95% confidence interval (CI) for the association between mutation status and development of recurrence following a negative-SLNB. Overall, 344/477 (72.1%) patients had a negative SLNB. Of these, 54 (15.7%) developed subsequent recurrence. The risk of disease recurrence following a negative SLNB was increased for patients with either a BRAF or NRAS mutant tumour compared to wild-type tumours (aHR 1.92, 95% CI: 1.02-3.60, p = 0.04). Melanoma patients with BRAF or NRAS mutant tumours had an increased risk compared to patients with BRAF/NRAS wild-type tumours of developing disease recurrence following a tumour-negative SLNB. The findings also confirm the importance of continued surveillance to monitor for disease recurrence among SLNB-negative patients.

The Influence of Race and Comorbidity on the Timely Initiation of Antiretroviral Therapy Among Older Persons Living With HIV/AIDS

PubMed Central

Smith, Lerissa; Zhang, Shun; Fairchild, Amanda J.; Heiman, Harry J.; Rust, George

2014-01-01

Objectives. We examined whether the timely initiation of antiretroviral therapy (ART) differed by race and comorbidity among older (≥ 50 years) people living with HIV/AIDS (PLWHA). Methods. We conducted frequency and descriptive statistics analysis to characterize our sample, which we drew from 2005–2007 Medicaid claims data from 14 states. We employed univariate and multivariable Cox regression analyses to evaluate the relationship between race, comorbidity, and timely ART initiation (≤ 90 days post-HIV/AIDS diagnosis). Results. Approximately half of the participants did not commence ART promptly. After we adjusted for covariates, we found that older PLWHA who reported a comorbidity were 40% (95% confidence interval = 0.26, 0.61) as likely to commence ART promptly. We found no racial differences in the timely initiation of ART among older PLWHA. Conclusions. Comorbidities affect timely ART initiation in older PLWHA. Older PLWHA may benefit from integrating and coordinating HIV care with care for other comorbidities and the development of ART treatment guidelines specific to older PLWHA. Consistent Medicaid coverage helps ensure consistent access to HIV treatment and care and may eliminate racial disparities in timely ART initiation among older PLWHA. PMID:25211735

Kidney transplantation from deceased donors with elevated serum creatinine.

PubMed

Gallinat, Anja; Leerhoff, Sabine; Paul, Andreas; Molmenti, Ernesto P; Schulze, Maren; Witzke, Oliver; Sotiropoulos, Georgios C

2016-12-01

Elevated donor serum creatinine has been associated with inferior graft survival in kidney transplantation (KT). The aim of this study was to evaluate the impact of elevated donor serum creatinine on short and long-term outcomes and to determine possible ways to optimize the use of these organs. All kidney transplants from 01-2000 to 12-2012 with donor creatinine ≥ 2 mg/dl were considered. Risk factors for delayed graft function (DGF) were explored with uni- and multivariate regression analyses. Donor and recipient data were analyzed with uni- and multivariate cox proportional hazard analyses. Graft and patient survival were calculated using the Kaplan-Meier method. Seventy-eight patients were considered. Median recipient age and waiting time on dialysis were 53 years and 5.1 years, respectively. After a median follow-up of 6.2 years, 63 patients are alive. 1, 3, and 5-year graft and patient survival rates were 92, 89, and 89 % and 96, 93, and 89 %, respectively. Serum creatinine level at procurement and recipient's dialysis time prior to KT were predictors of DGF in multivariate analysis (p = 0.0164 and p = 0.0101, respectively). Charlson comorbidity score retained statistical significance by multivariate regression analysis for graft survival (p = 0.0321). Recipient age (p = 0.0035) was predictive of patient survival by multivariate analysis. Satisfactory long-term kidney transplant outcomes in the setting of elevated donor serum creatinine ≥2 mg/dl can be achieved when donor creatinine is <3.5 mg/dl, and the recipient has low comorbidities, is under 56 years of age, and remains in dialysis prior to KT for <6.8 years.

Community-Based Management of Child Malnutrition in Zambia: HIV/AIDS Infection and Other Risk Factors on Child Survival.

PubMed

Moramarco, Stefania; Amerio, Giulia; Ciarlantini, Clarice; Chipoma, Jean Kasengele; Simpungwe, Matilda Kakungu; Nielsen-Saines, Karin; Palombi, Leonardo; Buonomo, Ersilia

2016-07-01

(1) BACKGROUND: Supplementary feeding programs (SFPs) are effective in the community-based treatment of moderate acute malnutrition (MAM) and prevention of severe acute malnutrition (SAM); (2) METHODS: A retrospective study was conducted on a sample of 1266 Zambian malnourished children assisted from 2012 to 2014 in the Rainbow Project SFPs. Nutritional status was evaluated according to WHO/Unicef methodology. We performed univariate and multivariate Cox proportional risk regression to identify the main predictors of mortality. In addition, a time-to event analysis was performed to identify predictors of failure and time to cure events; (3) RESULTS: The analysis included 858 malnourished children (19 months ± 9.4; 49.9% males). Program outcomes met international standards with a better performance for MAM compared to SAM. Cox regression identified SAM (3.8; 2.1-6.8), HIV infection (3.1; 1.7-5.5), and WAZ <-3 (3.1; 1.6-5.7) as predictors of death. Time to event showed 80% of children recovered by SAM/MAM at 24 weeks. (4) CONCLUSIONS: Preventing deterioration of malnutrition, coupled to early detection of HIV/AIDS with adequate antiretroviral treatment, and extending the duration of feeding supplementation, could be crucial elements for ensuring full recovery and improve child survival in malnourished Zambian children.

Impact of immunotherapy among patients with melanoma brain metastases managed with radiotherapy.

PubMed

Stokes, William A; Binder, David C; Jones, Bernard L; Oweida, Ayman J; Liu, Arthur K; Rusthoven, Chad G; Karam, Sana D

2017-12-15

Patients with melanoma brain metastases (MBM) have been excluded from trials evaluating immunotherapy in melanoma. As such, immunotherapy's role in MBM is poorly understood, particularly in combination with radiotherapy. The National Cancer Database was queried for patients with MBM receiving brain radiotherapy. They were classified according to immunotherapy receipt. Multivariate Cox regression was performed to identify factors associated with survival. Among 1287 patients, 185 received immunotherapy. Factors associated with improved survival included younger age, academic facility, lower extracranial disease burden, stereotactic radiotherapy, chemotherapy, and immunotherapy. Adding immunotherapy to radiotherapy for MBM is associated with improved survival. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of Diuretics is not associated with mortality in patients admitted to the emergency department: results from a cross-sectional study.

PubMed

Haider, Dominik G; Lindner, Gregor; Wolzt, Michael; Leichtle, Alexander Benedikt; Fiedler, Georg-Martin; Sauter, Thomas C; Fuhrmann, Valentin; Exadaktylos, Aristomenis K

2016-02-01

Patients with diuretic therapy are at risk for drug-induced adverse reactions. It is unknown if presence of diuretic therapy at hospital emergency room admission is associated with mortality. In this cross sectional analysis, all emergency room patients 2010 and 2011 at the Inselspital Bern, Switzerland were included. A multivariable logistic regression model was performed to assess the association between pre-existing diuretic medication and 28 day mortality. Twenty-two thousand two hundred thirty-nine subjects were included in the analysis. A total of 8.5%, 2.5%, and 0.4% of patients used one, two, or three or more diuretics. In univariate analysis spironolactone, torasemide and chlortalidone use were associated with 28 day mortality (all p < 0.05). In a multivariate cox regression model no association with mortality was detectable (p > 0.05). No difference existed between patients with or without diuretic therapy (P > 0.05). Age and creatinine were independent risk factors for mortaliy (both p < 0.05). Use of diuretics is not associated with mortality in an unselected cohort of patients presenting in an emergency room.

Interval to Testosterone Recovery After Hormonal Therapy for Prostate Cancer and Risk of Death

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

D'Amico, Anthony V.; Chen, M.-H.; Renshaw, Andrew A.

Purpose: To assess whether the risk of death is associated with the time to testosterone recovery (TTR) after radiotherapy (RT) and hormonal therapy (HT) for prostate cancer (PCa). Patients and Methods: Between 1995 and 2001, 206 men with localized, unfavorable-risk PCa were randomized to receive RT or RT plus 6 months of HT. A multivariate postrandomization Cox regression analysis was used to assess whether the TTR in years was associated with the risk of death after adjusting for the known prognostic factors, age, Adult Comorbidity Evaluation-27 score, and the use of HT for recurrence. Results: Of the 102 men randomizedmore » to receive RT and HT, 57 (56%) had a TTR of >2 years, and none of these men had died of PCa after a median follow-up of 7.6 years. As the TTR increased, the risk of death decreased significantly (adjusted hazard ratio, 0.60; 95% confidence interval, 0.43-0.84; p = .003). A significant interaction was noted between the TTR and the comorbidity score (p = .002). The survival estimates were similar (p = 0.17) across the TTR values in men with moderate to severe comorbidity; however, these estimates increased significantly (p < .001) with decreasing PCa-specific mortality (p = .006) as the TTR increased in men with no or minimal comorbidity. Conclusion: The results of our study have shown that a longer TTR after RT plus 6 months of HT for unfavorable-risk PCa is associated with a lower risk of death in men with no or minimal comorbidity.« less

Increased Risk of Restless Legs Syndrome in Patients With Migraine

PubMed Central

Yang, Fu-Chi; Lin, Te-Yu; Chen, Hsuan-Ju; Lee, Jiunn-Tay; Lin, Chun-Chieh; Huang, Wen-Yen; Chen, Hsin-Hung; Kao, Chia-Hung

2016-01-01

Abstract Previous studies suggest that an association between restless legs syndrome (RLS) and migraine exists. However, population-based data are unavailable in Asian cohorts. Our study thus aims to evaluate the association between migraine and RLS in a nationwide, population-based cohort in Taiwan and to examine the effects of age, sex, migraine subtype, and comorbidities on RLS development. Data from the Taiwan National Health Insurance Research Database were used. Patients aged 20 years or older with newly diagnosed migraine from 2000 to 2008 were included; 23,641 patients with newly diagnosed migraine and 94,564 subjects without migraine were randomly selected and followed until RLS development, withdrawal from the National Health Insurance, or until the end of 2011. A multivariate Cox proportional hazards regression model was used to explore the risk of RLS in patients with migraine after adjustment for demographic characteristics and comorbidities. Both cohorts were followed for a mean of 7.38 years. After adjustment for covariates, the risk of RLS was 1.42-fold higher (95% confidence interval = 1.13–1.79) in the migraine cohort than in the nonmigraine cohort (7.19 versus 3.42 years per 10,000 person-years). The increased risk was more prominent in males in the migraine cohort (1.87-fold increased risk, 95% confidence interval 1.22–2.85). Neither comorbidity status nor migraine subtype influenced the RLS risk. This population-based study demonstrated that migraine is associated with an increased risk of RLS compared with those without migraine, particularly in male patients with migraine and regardless of the comorbidity status. PMID:26844484

Effects of Statin Intensity and Adherence on the Long-Term Prognosis After Acute Ischemic Stroke.

PubMed

Kim, Jinkwon; Lee, Hye Sun; Nam, Chung Mo; Heo, Ji Hoe

2017-10-01

Statin is an established treatment for secondary prevention after ischemic stroke. However, the effects of statin intensity and adherence on the long-term prognosis after acute stroke are not well known. This retrospective cohort study using a nationwide health insurance claim data in South Korea included patients admitted with acute ischemic stroke between 2002 and 2012. Statin adherence and intensity were determined from the prescription data for a period of 1 year after the index stroke. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. We performed multivariate Cox proportional regression analyses. We included 8001 patients with acute ischemic stroke. During the mean follow-up period of 4.69±2.72 years, 2284 patients developed a primary outcome. Compared with patients with no statin, adjusted hazard ratios (95% confidence interval) were 0.74 (0.64-0.84) for good adherence, 0.93 (0.79-1.09) for intermediate adherence, and 1.07 (0.95-1.20) for poor adherence to statin. Among the 1712 patients with good adherence, risk of adverse events was lower in patients with high-intensity statin (adjusted hazard ratio [95% confidence interval], 0.48 [0.24-0.96]) compared with those with low-intensity statin. Neither good adherence nor high intensity of statin was associated with an increased risk of hemorrhagic stroke. After acute ischemic stroke, high-intensity statin therapy with good adherence was significantly associated with a lower risk of adverse events. © 2017 American Heart Association, Inc.

Six minute walk test predicts long-term all-cause mortality and heart failure rehospitalization in African-American patients hospitalized with acute decompensated heart failure.

PubMed

Alahdab, M Tarek; Mansour, Ibrahim N; Napan, Sirikarn; Stamos, Thomas D

2009-03-01

The prognostic value of the 6-minute walk test (6MWT) has been described in patients with heart failure (HF); however, limited data are available in an African-American (AA) population. We prospectively evaluated the usefulness of the 6MWT in predicting mortality and HF rehospitalization in AA patients with acute decompensated HF. Two hundred AA patients (63.1% men, mean age 55.7 +/- 12.9 years) with acute decompensated HF were prospectively studied. Patients were followed to assess 40-month all-cause mortality and 18-month HF rehospitalization. The median distance walked on the 6MWT was 213 m. Of the 198 patients with available mortality data, 59 patients (29.8%) died. Of the 191 patients with available rehospitalization data, 114 (59.7%) were rehospitalized for worsening HF. For patients who walked 200 m (P = .001). For patients who walked 200 m (P = .027). Multivariate Cox regression analysis showed that 6MWT distance

Electrocardiographic Left Ventricular Hypertrophy as a Predictor of Cardiovascular Disease Independent of Left Ventricular Anatomy in Persons ≥ 65 Years of Age

PubMed Central

Leigh, J. Adam; O’Neal, Wesley T.; Soliman, Elsayed Z.

2016-01-01

Left ventricular hypertrophy (LVH) diagnosed by electrocardiography (ECG-LVH) and echocardiography (echo-LVH) are independently associated with an increased risk of cardiovascular disease (CVD) events. However, it is unknown if ECG-LVH retains its predictive properties independent of left ventricular anatomy. We compared the risk of CVD associated with ECG-LVH and echo-LVH in 4,076 participants (41% male, 86% white) from the Cardiovascular Health Study (CHS), who were free of baseline CVD. ECG-LVH was defined with Minnesota ECG Classification criteria from baseline ECG data. Echo-LVH was defined by sex-specific left ventricular mass values normalized to body surface area (male: >102 g/m2; female: >88 g/m2). ECG-LVH was detected in 144 (3.5%) participants and echo-LVH in 430 (11%) participants. Over a median follow-up of 10.6 years, 2,274 CVD events occurred. In a multivariable Cox regression analysis adjusted for common CVD risk factors, ECG-LVH (HR=1.84, 95%CI=1.51, 2.24) and echo-LVH (HR=1.35, 95%CI=1.19, 1.54) were associated with an increased risk for CVD events. The association between ECG-LVH and CVD events was not substantively altered with further adjustment for echo-LVH (HR=1.76, 95%CI=1.45, 2.15). In conclusion, the association of ECG-LVH with CVD events is not dependent on echo-LVH. This finding provides support to the concept that ECG-LVH is an electrophysiologic marker with predictive properties independent of left ventricular anatomy. PMID:27067620

Ileostomy creation in colorectal cancer surgery: risk of acute kidney injury and chronic kidney disease.

PubMed

Li, Linda; Lau, Kelsey S; Ramanathan, Venkat; Orcutt, Sonia T; Sansgiry, Shubhada; Albo, Daniel; Berger, David H; Anaya, Daniel A

2017-04-01

Ileostomy creation is associated with postoperative dehydration and readmission; however, the effect on renal function is unknown. Our goal was to characterize the impact of ileostomy creation on acute and chronic renal function. A retrospective cohort study with patients undergoing colorectal cancer surgery at a tertiary referral institution (2005-2011). The relationship between ileostomy creation and acute kidney injury (AKI)-related readmission, severe chronic kidney disease (CKD) at 12 mo (glomerular filtration rate <30 mL/min/1.73 m 2 ), and onset of severe CKD over time was evaluated using multivariable logistic and Cox regression and adjusted using propensity score stratification. Among 619 patients, 84 (13%) had ileostomy. AKI-related readmission and severe CKD at 12 mo were more common among ileostomy patients (17% versus 2%, P < 0.01 and 13.3% versus 5%, P = 0.02, respectively). After propensity score adjustment, ileostomy was a significant predictor of AKI-related readmissions (odds ratio: 10.3; 95% confidence interval [CI], 3.9-27.2), severe CKD at 12 mo (odds ratio: 4.1; 95% CI, 1.4-11.9), and onset of severe CKD over time (hazard ratio: 4.2; 95% CI, 2.3-6.6). Ileostomy creation is associated with increased risk of AKI-related readmissions and development of severe CKD. Future studies must focus on strategies to minimize kidney injury when ileostomy is a necessary component of colorectal cancer surgery and revisiting current indications for ileostomy creation. Copyright © 2016 Elsevier Inc. All rights reserved.

Circulating uric acid levels and subsequent development of cancer in 493,281 individuals: findings from the AMORIS Study.

PubMed

Yiu, Andrew; Van Hemelrijck, Mieke; Garmo, Hans; Holmberg, Lars; Malmström, Håkan; Lambe, Mats; Hammar, Niklas; Walldius, Göran; Jungner, Ingmar; Wulaningsih, Wahyu

2017-06-27

Serum uric acid has been suggested to be associated with cancer risk. We aimed to study the association between serum uric acid and cancer incidence in a large Swedish cohort. A positive association was found between uric acid levels and overall cancer risk, and results were similar with adjustment for glucose, triglycerides and BMI. Hazard ratio (HR) for overall cancer for the 4th quartile of uric acid compared to the 1st was 1.08 (95% CI: 1.05-1.11) in men and 1.12 (1.09 - 1.16) in women. Site-specific analysis showed a positive association between uric acid and risk of colorectal, hepatobiliary, kidney, non-melanoma skin, and other cancers in men and of head and neck and other cancers in women. An inverse association was observed for pulmonary and central nervous system (CNS) cancers in men and breast, lymphatic and haematological, and CNS malignancies in women. We included 493,281 persons aged 20 years and older who had a measurement of serum uric acid and were cancer-free at baseline in the AMORIS study. Multivariable Cox proportional hazards regression was used to investigate sex-specific quartiles of serum uric acid in relation to cancer risk in men and women. Analysis was further adjusted for serum glucose, triglycerides and, where available, BMI. Site-specific analysis was performed for major cancers. Altered uric acid levels were associated with risk of overall and some specific cancers, further indicating the potential role of uric acid metabolism in carcinogenesis.

Circulating uric acid levels and subsequent development of cancer in 493,281 individuals: findings from the AMORIS Study

PubMed Central

Yiu, Andrew; Van Hemelrijck, Mieke; Garmo, Hans; Holmberg, Lars; Malmström, Håkan; Lambe, Mats; Hammar, Niklas; Walldius, Göran; Jungner, Ingmar; Wulaningsih, Wahyu

2017-01-01

Objectives Serum uric acid has been suggested to be associated with cancer risk. We aimed to study the association between serum uric acid and cancer incidence in a large Swedish cohort. Results A positive association was found between uric acid levels and overall cancer risk, and results were similar with adjustment for glucose, triglycerides and BMI. Hazard ratio (HR) for overall cancer for the 4th quartile of uric acid compared to the 1st was 1.08 (95% CI: 1.05–1.11) in men and 1.12 (1.09 – 1.16) in women. Site-specific analysis showed a positive association between uric acid and risk of colorectal, hepatobiliary, kidney, non-melanoma skin, and other cancers in men and of head and neck and other cancers in women. An inverse association was observed for pulmonary and central nervous system (CNS) cancers in men and breast, lymphatic and haematological, and CNS malignancies in women. Materials and Methods We included 493,281 persons aged 20 years and older who had a measurement of serum uric acid and were cancer-free at baseline in the AMORIS study. Multivariable Cox proportional hazards regression was used to investigate sex-specific quartiles of serum uric acid in relation to cancer risk in men and women. Analysis was further adjusted for serum glucose, triglycerides and, where available, BMI. Site-specific analysis was performed for major cancers. Conclusions Altered uric acid levels were associated with risk of overall and some specific cancers, further indicating the potential role of uric acid metabolism in carcinogenesis. PMID:28418841

The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide

PubMed Central

Williams, Robert C.; Opelz, Gerhard; Weil, E. Jennifer; McGarvey, Chelsea J.; Chakkera, Harini A.

2017-01-01

Background Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years. Methods Using the United Network for Organ Sharing data, we identified first kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches and stratified by donor origin. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine impact of HLA compatibility on kidney allograft survival for all living donors and for living related and living unrelated subsets. Results There were 66 596 first adult transplants from living donors with 348 960 years of follow-up. We found a linear relationship between HLA mismatch and allograft survival. In adjusted analyses, among all living donors, 1 mismatch conferred a 44% higher risk, whereas 6 mismatches conferred a twofold higher risk of allograft failure. When using 0-mismatched full siblings as a reference, living-donor kidneys reduce the hazard of failure by approximately 34% when compared with deceased donors. Twenty-five years of transplant experience, stratified by donor source, was summarized and presented as a guide for allocation. Conclusions These data reinforce the importance of optimizing HLA matching to further improve survival in first adult kidney allografts in the future, especially in living unrelated donations, when possible. PMID:28573187

The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts From Deceased Donors.

PubMed

Williams, Robert C; Opelz, Gerhard; McGarvey, Chelsea J; Weil, E Jennifer; Chakkera, Harini A

2016-05-01

Since the beginning of the technology, there has been active debate about the role of human leucocyte antigen (HLA) matching in kidney allograft survival. Recent studies have reported diminishing importance of HLA matching, which have, in turn, been challenged by reports that suggest the continuing importance of these loci. Given the controversies, we examined the effect of HLA compatibility on kidney allograft survival by studying all first adult kidney transplants in the United States from a deceased donor. Using the United Network for Organ Sharing data, we identified first deceased donor kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine the impact of HLA compatibility on kidney allograft survival. Study cohort included 189 141 first adult kidney alone transplants, with a total of 994 558 years of kidney allograft follow-up time. Analyses adjusted for recipient and donor characteristics demonstrated a 13% higher risk (hazard ratio, 1.13; 95% confidence interval, 1.06-1.21) with 1 mismatch and a 64% higher risk (hazard ratio, 1.64, 95% confidence interval, 1.56-1.73) with 6 mismatches. Dividing the mismatch categories into 27 ordered permutations, and testing their 57 within mismatch category differences, demonstrated that all but 1 were equal, independent of locus. A significant linear relationship of hazard ratios was associated with HLA mismatch and affects allograft survival even during the recent periods of increasing success in renal transplantation.

The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide.

PubMed

Williams, Robert C; Opelz, Gerhard; Weil, E Jennifer; McGarvey, Chelsea J; Chakkera, Harini A

2017-05-01

Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years. Using the United Network for Organ Sharing data, we identified first kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches and stratified by donor origin. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine impact of HLA compatibility on kidney allograft survival for all living donors and for living related and living unrelated subsets. There were 66 596 first adult transplants from living donors with 348 960 years of follow-up. We found a linear relationship between HLA mismatch and allograft survival. In adjusted analyses, among all living donors, 1 mismatch conferred a 44% higher risk, whereas 6 mismatches conferred a twofold higher risk of allograft failure. When using 0-mismatched full siblings as a reference, living-donor kidneys reduce the hazard of failure by approximately 34% when compared with deceased donors. Twenty-five years of transplant experience, stratified by donor source, was summarized and presented as a guide for allocation. These data reinforce the importance of optimizing HLA matching to further improve survival in first adult kidney allografts in the future, especially in living unrelated donations, when possible.

Concurrent Anemia and Elevated C-Reactive Protein Predicts HIV Clinical Treatment Failure, Including Tuberculosis, After Antiretroviral Therapy Initiation

PubMed Central

Shivakoti, Rupak; Yang, Wei-Teng; Gupte, Nikhil; Berendes, Sima; Rosa, Alberto La; Cardoso, Sandra W.; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Sugandhavesa, Patcharaphan; Santos, Brento; Poongulali, Selvamuthu; Tripathy, Srikanth; Bollinger, Robert C.; Currier, Judith S.; Tang, Alice M.; Semba, Richard D.; Christian, Parul; Campbell, Thomas B.; Gupta, Amita

2015-01-01

Background. Anemia is a known risk factor for clinical failure following antiretroviral therapy (ART). Notably, anemia and inflammation are interrelated, and recent studies have associated elevated C-reactive protein (CRP), an inflammation marker, with adverse human immunodeficiency virus (HIV) treatment outcomes, yet their joint effect is not known. The objective of this study was to assess prevalence and risk factors of anemia in HIV infection and to determine whether anemia and elevated CRP jointly predict clinical failure post-ART. Methods. A case-cohort study (N = 470 [236 cases, 234 controls]) was nested within a multinational randomized trial of ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings [PEARLS]). Cases were incident World Health Organization stage 3, 4, or death by 96 weeks of ART treatment (clinical failure). Multivariable logistic regression was used to determine risk factors for pre-ART (baseline) anemia (females: hemoglobin <12.0 g/dL; males: hemoglobin <13.0 g/dL). Association of anemia as well as concurrent baseline anemia and inflammation (CRP ≥10 mg/L) with clinical failure were assessed using multivariable Cox models. Results. Baseline anemia prevalence was 51% with 15% prevalence of concurrent anemia and inflammation. In analysis of clinical failure, multivariate-adjusted hazard ratios were 6.41 (95% confidence interval [CI], 2.82–14.57) for concurrent anemia and inflammation, 0.77 (95% CI, .37–1.58) for anemia without inflammation, and 0.45 (95% CI, .11–1.80) for inflammation without anemia compared to those without anemia and inflammation. Conclusions. ART-naive, HIV-infected individuals with concurrent anemia and inflammation are at particularly high risk of failing treatment, and understanding the pathogenesis could lead to new interventions. Reducing inflammation and anemia will likely improve HIV disease outcomes. Alternatively, concurrent anemia and inflammation could represent individuals with occult opportunistic infections in need of additional screening. PMID:25828994

Impact of biliary stent-related events in patients diagnosed with advanced pancreatobiliary tumours receiving palliative chemotherapy.

PubMed

Lamarca, Angela; Rigby, Christina; McNamara, Mairéad G; Hubner, Richard A; Valle, Juan W

2016-07-14

To determine the impact (morbidity/mortality) of biliary stent-related events (SRE) (cholangitis or stent obstruction) in chemotherapy-treated pancreatico-biliary patients. All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records (Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE (defined as time from first stenting before chemotherapy to date of SRE). Progression-free survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, Cox and Fine-Gray regression (univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing event. Ninety-six out of 693 screened patients were eligible; 89% had a metal stent (the remainder were plastic). The median time of follow-up was 9.6 mo (range 2.2 to 26.4). Forty-one patients (43%) developed a SRE during follow-up [cholangitis (39%), stent obstruction (29%), both (32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none (37%), chemotherapy delay (24%), discontinuation (17%) and death (22%). The median time-to-SRE was 4.4 mo (95%CI: 3.6-5.5). Patients with severe comorbidities (P < 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3 (95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival (P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE (SRE group vs no-SRE group). SREs are common and impact on patient's morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/delay SREs.

Impact of biliary stent-related events in patients diagnosed with advanced pancreatobiliary tumours receiving palliative chemotherapy

PubMed Central

Lamarca, Angela; Rigby, Christina; McNamara, Mairéad G; Hubner, Richard A; Valle, Juan W

2016-01-01

AIM: To determine the impact (morbidity/mortality) of biliary stent-related events (SRE) (cholangitis or stent obstruction) in chemotherapy-treated pancreatico-biliary patients. METHODS: All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records (Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE (defined as time from first stenting before chemotherapy to date of SRE). Progression-free survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, Cox and Fine-Gray regression (univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing event. RESULTS: Ninety-six out of 693 screened patients were eligible; 89% had a metal stent (the remainder were plastic). The median time of follow-up was 9.6 mo (range 2.2 to 26.4). Forty-one patients (43%) developed a SRE during follow-up [cholangitis (39%), stent obstruction (29%), both (32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none (37%), chemotherapy delay (24%), discontinuation (17%) and death (22%). The median time-to-SRE was 4.4 mo (95%CI: 3.6-5.5). Patients with severe comorbidities (P < 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3 (95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival (P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE (SRE group vs no-SRE group). CONCLUSION: SREs are common and impact on patient’s morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/delay SREs. PMID:27468198

Predictive factors for the regression of canine transmissible venereal tumor during vincristine therapy.

PubMed

Scarpelli, Karime C; Valladão, Maria L; Metze, Konradin

2010-03-01

Canine transmissible venereal tumor (CTVT) is a neoplasm transmitted by transplantation. Monochemotherapy with vincristine is considered to be effective, but treatment time until complete clinical remission may vary. The aim of this study was to determine which clinical data at diagnosis could predict the responsiveness of CTVT to vincristine chemotherapy. One hundred dogs with CTVT entered this prospective study. The animals were treated with vincristine sulfate (0.025 mg/kg) at weekly intervals until the tumor had macroscopically disappeared. The time to complete remission was recorded. A multivariate Cox regression model indicated that larger tumor mass, increased age and therapy during hot and rainy months were independent significant unfavorable predictive factors retarding remission, whereas sex, weight, status as owned dog or breed were of no predictive relevance. Further studies are necessary to investigate whether these results are due to changes in immunological response mechanisms in animals with a diminished immune surveillance, resulting in delays in tumor regression. 2008 Elsevier Ltd. All rights reserved.

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 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.

Multivariate analysis of prognostic factors in synovial sarcoma.

PubMed

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

2009-11-01

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

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.

Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy.

PubMed

Ruben, Jeremy D; Dally, Michael; Bailey, Michael; Smith, Robin; McLean, Catriona A; Fedele, Pasqual

2006-06-01

To investigate radiation necrosis in patients treated for glioma in terms of incidence, outcomes, predictive and prognostic factors. Records were reviewed for 426 patients followed up until death or for at least 3 years. Logistic regression analysis was performed to identify predictive and prognostic factors. Multivariate survival analysis was conducted using Cox proportional hazards regression. Separate analyses were performed for the subset of 352 patients who received a biologically effective dose (BED) > or =85.5 Gy2 (> or =45 Gy/25 fractions) who were at highest risk for radionecrosis. Twenty-one patients developed radionecrosis (4.9%). Actuarial incidence plateaued at 13.3% after 3 years. In the high-risk subset, radiation parameters confirmed as risk factors included total dose (p < 0.001), BED (p < 0.005), neuret (p < 0.001), fraction size (p = 0.028), and the product of total dose and fraction size (p = 0.001). No patient receiving a BED <96 Gy2 developed radionecrosis. Subsequent chemotherapy significantly increased the risk of cerebral necrosis (p = 0.001) even when adjusted for BED (odds ratio [OR], 5.8; 95% confidence interval [CI], 1.6-20.3) or length of follow-up (OR, 5.4; 95% CI, 1.5-19.3). Concurrent use of valproate appeared to delay the onset of necrosis (p = 0.013). The development of radionecrosis did not affect survival (p = 0.09). Cerebral necrosis is unlikely at doses below 50 Gy in 25 fractions. The risk increases significantly with increasing radiation dose, fraction size, and the subsequent administration of chemotherapy.

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

PubMed Central

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

2013-01-01

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

Voxelwise multivariate analysis of multimodality magnetic resonance imaging

PubMed Central

Naylor, Melissa G.; Cardenas, Valerie A.; Tosun, Duygu; Schuff, Norbert; Weiner, Michael; Schwartzman, Armin

2015-01-01

Most brain magnetic resonance imaging (MRI) studies concentrate on a single MRI contrast or modality, frequently structural MRI. By performing an integrated analysis of several modalities, such as structural, perfusion-weighted, and diffusion-weighted MRI, new insights may be attained to better understand the underlying processes of brain diseases. We compare two voxelwise approaches: (1) fitting multiple univariate models, one for each outcome and then adjusting for multiple comparisons among the outcomes and (2) fitting a multivariate model. In both cases, adjustment for multiple comparisons is performed over all voxels jointly to account for the search over the brain. The multivariate model is able to account for the multiple comparisons over outcomes without assuming independence because the covariance structure between modalities is estimated. Simulations show that the multivariate approach is more powerful when the outcomes are correlated and, even when the outcomes are independent, the multivariate approach is just as powerful or more powerful when at least two outcomes are dependent on predictors in the model. However, multiple univariate regressions with Bonferroni correction remains a desirable alternative in some circumstances. To illustrate the power of each approach, we analyze a case control study of Alzheimer's disease, in which data from three MRI modalities are available. PMID:23408378

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.

Citrus consumption and incident dementia in elderly Japanese: the Ohsaki Cohort 2006 Study.

PubMed

Zhang, Shu; Tomata, Yasutake; Sugiyama, Kemmyo; Sugawara, Yumi; Tsuji, Ichiro

2017-04-01

Although some experimental biological studies have indicated that citrus may have preventive effects against cognitive impairment, no cohort study has yet examined the relationship between citrus consumption and incident dementia. In a baseline survey, we collected data on daily citrus intake (categorised as ≤2, 3-4 times/week or almost every day) and consumption of other foods using a FFQ, and used a self-reported questionnaire to collect data on other covariates. Data on incident dementia were retrieved from the Japanese Long-term Care Insurance database. A multivariate-adjusted Cox model was used to estimate the hazard ratios (HR) and 95 % CI for incident dementia according to citrus consumption. Among 13 373 participants, the 5·7-year incidence of dementia was 8·6 %. In comparison with participants who consumed citrus ≤2 times/week, the multivariate-adjusted HR for incident dementia among those did so 3-4 times/week and almost every day was 0·92 (95 % CI 0·80, 1·07) and 0·86 (95 % CI 0·73, 1·01), respectively (P trend=0·065). The inverse association persisted after excluding participants whose dementia events had occurred in the first 2 years of follow-up. The multivariate HR was 1·00 (reference) for ≤2 times/week, 0·82 (95 % CI 0·69, 0·98) for 3-4 times/week and 0·77 (95 % CI 0·64, 0·93) for almost every day (P trend=0·006). The present findings suggest that frequent citrus consumption was associated with a lower risk of incident dementia, even after adjustment for possible confounding factors.

Menopause and Risk of Kidney Stones.

PubMed

Prochaska, Megan; Taylor, Eric N; Curhan, Gary

2018-05-03

Metabolic changes due to menopause may alter urine composition and kidney stone risk but results from prior work on this association have been mixed. We examined menopause and risk of incident kidney stones and changes in 24-hour urine composition in the Nurses' Health Study II. We conducted a prospective analysis of 108,639 Nurses' Health Study II participants who provided information on menopause and kidney stones. We used multivariate adjusted Cox proportional hazards models. We also analyzed 24-hour urine collections from 658 participants who performed a collection while pre-menopausal and a repeat collection after menopause. During 22 years of follow-up, there were 3,456 incident kidney stones. The multivariate adjusted relative risk for an incident kidney stone for post-menopausal participants compared with pre-menopause was 1.27 (95% CI 1.08 to 1.46). In a stratified analysis, compared with pre-menopause, the multivariate adjusted relative risk of natural menopause was 1.27 (95% CI 1.09 to 1.48) and surgically induced menopause was 1.43 (95% CI 1.19 to 1.73). Among 74,505 post-menopausal participants, there were 1,041 incident stone events. Compared with no hormone therapy use, neither current nor past use was significantly associated with kidney stone risk. Compared with pre-menopause, the post-menopausal urine collections had lower mean calcium, citrate, phosphorus, and uric acid, and higher mean volume. Post-menopausal status is associated with higher risk of incident kidney stone. Natural and surgical menopause are each independently associated with higher risk. There are small but significant differences in urine composition between pre- and post-menopausal urine collections. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Outcomes of deliveries by family physicians or obstetricians: a population-based cohort study using an instrumental variable

PubMed Central

Aubrey-Bassler, Kris; Cullen, Richard M.; Simms, Alvin; Asghari, Shabnam; Crane, Joan; Wang, Peizhong Peter; Godwin, Marshall

2015-01-01

Background: Previous research has suggested that obstetric outcomes are similar for deliveries by family physicians and obstetricians, but many of these studies were small, and none of them adjusted for unmeasured selection bias. We compared obstetric outcomes between these provider types using an econometric method designed to adjust for unobserved confounding. Methods: We performed a retrospective population-based cohort study of all Canadian (except Quebec) hospital births with delivery by family physicians and obstetricians at more than 20 weeks gestational age, with birth weight greater than 500 g, between Apr. 1, 2006, and Mar. 31, 2009. The primary outcomes were the relative risks of in-hospital perinatal death and a composite of maternal mortality and major morbidity assessed with multivariable logistic regression and instrumental variable–adjusted multivariable regression. Results: After exclusions, there were 3600 perinatal deaths and 14 394 cases of maternal morbidity among 799 823 infants and 793 053 mothers at 390 hospitals. For deliveries by family physicians v. obstetricians, the relative risk of perinatal mortality was 0.98 (95% confidence interval [CI] 0.85–1.14) and of maternal morbidity was 0.81 (95% CI 0.70–0.94) according to logistic regression. The respective relative risks were 0.97 (95% CI 0.58–1.64) and 1.13 (95% CI 0.65–1.95) according to instrumental variable methods. Interpretation: After adjusting for both observed and unobserved confounders, we found a similar risk of perinatal mortality and adverse maternal outcome for obstetric deliveries by family physicians and obstetricians. Whether there are differences between these groups for other outcomes remains to be seen. PMID:26303244

The Association Between Immigration Status and Office-based Medical Provider Visits for Cancer Patients in the United States.

PubMed

Wang, Yang; Wilson, Fernando A; Chen, Li-Wu

2017-06-01

We examined differences in cancer-related office-based provider visits associated with immigration status in the United States. Data from the 2007-2012 Medical Expenditure Panel Survey and National Health Interview Survey included adult patients diagnosed with cancer. Univariate analyses described distributions of cancer-related office-based provider visits received, expenditures, visit characteristics, as well as demographic, socioeconomic, and health covariates, across immigration groups. We measured the relationships of immigrant status to number of visits and associated expenditure within the past 12 months, adjusting for age, sex, educational attainment, race/ethnicity, self-reported health status, time since cancer diagnosis, cancer remission status, marital status, poverty status, insurance status, and usual source of care. We finally performed sensitivity analyses for regression results by using the propensity score matching method to adjust for potential selection bias. Noncitizens had about 2 fewer visits in a 12-month period in comparison to US-born citizens (4.0 vs. 5.9). Total expenditure per patient was higher for US-born citizens than immigrants (not statistically significant). Noncitizens (88.3%) were more likely than US-born citizens (76.6%) to be seen by a medical doctor during a visit. Multivariate regression results showed that noncitizens had 42% lower number of visiting medical providers at office-based settings for cancer care than US-born citizens, after adjusting for all the other covariates. There were no significant differences in expenditures across immigration groups. The propensity score matching results were largely consistent with those in multivariate-adjusted regressions. Results suggest targeted interventions are needed to reduce disparities in utilization between immigrants and US-born citizen cancer patients.

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

ERIC Educational Resources Information Center

Kirisci, Levent; Hsu, Tse-Chi

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

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

PubMed Central

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

2015-01-01

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

High Maternal Blood Mercury Level Is Associated with Low Verbal IQ in Children.

PubMed

Jeong, Kyoung Sook; Park, Hyewon; Ha, Eunhee; Shin, Jiyoung; Hong, Yun Chul; Ha, Mina; Park, Hyesook; Kim, Bung Nyun; Lee, Boeun; Lee, Soo Jeong; Lee, Kyung Yeon; Kim, Ja Hyeong; Kim, Yangho

2017-07-01

The objective of the present study was to investigate the relationship of IQ in children with maternal blood mercury concentration during late pregnancy. The present study is a component of the Mothers and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project in Korea that began in 2006. The study cohort consisted of 553 children whose mothers underwent testing for blood mercury during late pregnancy. The children were given the Korean language version of the Wechsler Preschool and Primary Scale of Intelligence, revised edition (WPPSI-R) at 60 months of age. Multivariate linear regression analysis, with adjustment for covariates, was used to assess the relationship between verbal, performance, and total IQ in children and blood mercury concentration of mothers during late pregnancy. The results of multivariate linear regression analysis indicated that a doubling of blood mercury was associated with the decrease in verbal and total IQ by 2.482 (95% confidence interval [CI], 0.749-4.214) and 2.402 (95% CI, 0.526-4.279), respectively, after adjustment. This inverse association remained after further adjustment for blood lead concentration. Fish intake is an effect modifier of child IQ. In conclusion, high maternal blood mercury level is associated with low verbal IQ in children. © 2017 The Korean Academy of Medical Sciences.

Racial Differences in the Overall Survival of Hairy Cell Leukemia in the United States: A Population-Based Analysis of the Surveillance, Epidemiology, and End Results Database.

PubMed

Giri, Smith; Shrestha, Rajesh; Pathak, Ranjan; Bhatt, Vijaya Raj

2015-08-01

Several studies have reported excellent long-term overall survival (OS) of patients with hairy cell leukemia (HCL) without racial disparity. Studies in other cancers have demonstrated worse mortality among African American (AA) individuals. We used the Surveillance, Epidemiology, and End Results 18 database to identify HCL patients diagnosed between 1978 and 2011. Kaplan-Meier curves were plotted to estimate OS. Univariate analysis using the life table method and multivariate Cox regression model were used to determine the independent effect of race on OS. The study population included 78% men and had a median age of 56 years. Race included 93% white, 3.5% Asian/Pacific Islander, and 3.5% AA. The 10-year OS was significantly less for AA as compared with white and Asian/Pacific Islander individuals (54% vs. 72% vs. 75%; P < .001). A Kaplan-Meier survival curve showed a significantly worse OS for AA versus other races (P < .001). In a multivariate analysis, AA race remained an independent predictor for a worse OS (hazard ratio 1.77; 95% confidence interval, 1.30-2.40; P < .001) after adjusting for age, sex, year of diagnosis, and marital status. In this population-based study, only half of AA patients but more than two-thirds of HCL patients from other racial groups were alive at 10 years. Such drastic racial differences in OS of HCL patients at the population level mandates further evaluation of the contributory biological, socioeconomic, health system, and other factors. Understanding and overcoming such racial disparities might close the racial differences in OS of this potentially curable disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Exclusive breastfeeding practices among mothers in urban slum settlements: pooled analysis from three prospective birth cohort studies in South India.

PubMed

Velusamy, Vasanthakumar; Premkumar, Prasanna S; Kang, Gagandeep

2017-01-01

The World Health Organization (WHO) recommends six months of exclusive breastfeeding. Despite documented health, social and economic benefits, the practice of exclusive breastfeeding is quite low and information on influencing factors is limited especially from slum settlements. Our goal is to assess the prevalence and evaluate factors associated with early cessation of exclusive breastfeeding in the first six months of life among mothers in urban slums of Vellore, Southern India. We pooled data from three similar birth cohort studies ( n = 1088) conducted between 2002 and 2009. Breastfeeding information was obtained soon after birth and then from follow-up home visits conducted once every two weeks by the field workers. Multivariable Cox regression analyses were used to assess factors associated with early cessation of exclusive breastfeeding. The prevalence of exclusive breastfeeding for the first six months was 11.4%, based on prospective data since birth. Results from multivariable analyses revealed maternal education (Adjusted Hazard Ratio [AHR] 1.18 , 95% CI 1.03, 1.35), pucca type of house (AHR 1.25 , 95% CI 1.10, 1.43), two or more number of children in the family (AHR 1.26 , 95% CI 1.10, 1.43), joint family structure (AHR 1.20 , 95% CI 1.02, 1.40) and birth during summer (AHR 1.16, 95% CI 1.01, 1.31) were associated with early cessation of exclusive breastfeeding in the first six months. Our results indicate that exclusive breastfeeding rates are well below the recommended levels. Educational interventions providing comprehensive breastfeeding information to mothers and their families can be evaluated to assess its effect on improving infant feeding practices.

Features associated with, and the impact of, hemolytic anemia in patients with systemic lupus erythematosus: LX, results from a multiethnic cohort.

PubMed

Durán, Sergio; Apte, Mandar; Alarcón, Graciela S; Marion, Miranda C; Edberg, Jeffrey C; Kimberly, Robert P; Zhang, Jie; Langefeld, Carl D; Vilá, Luis M; Reveille, John D

2008-09-15

To examine the clinical and genetic correlates of hemolytic anemia and its impact on damage accrual and mortality in systemic lupus erythematosus (SLE) patients. SLE patients (American College of Rheumatology [ACR] criteria) of Hispanic (Texan or Puerto Rican), African American, and Caucasian ethnicity from the LUMINA (LUpus in MInorities, NAture versus nurture) cohort were studied. Hemolytic anemia was defined as anemia with reticulocytosis (ACR criterion). The association between degrees of hemolytic anemia and socioeconomic/demographic, clinical, pharmacologic, immunologic, psychological, and behavioral variables was examined by univariable and multivariable (proportional odds model) analyses. Genetic variables (FCGR and Fas/Fas ligand polymorphisms) were examined by 2 degrees of freedom test of association and Cochran-Armitage trend tests. The impact of hemolytic anemia on damage accrual and mortality was examined by multivariable linear and Cox regression analyses, respectively. Of 628 patients studied, 90% were women, 19% were Texan Hispanic, 16% were Puerto Rican Hispanic, 37% were African American, and 28% were Caucasian. Sixty-five (10%) patients developed hemolytic anemia at some time during the disease course, 83% at or before diagnosis. Variables independently associated with degrees of hemolytic anemia were African American ethnicity, thrombocytopenia, and the use of azathioprine. Hemolytic anemia was associated with damage accrual after adjusting for variables known to affect this outcome; however, hemolytic anemia was not associated with mortality. The association of hemolytic anemia with thrombocytopenia suggests a common mechanism in their pathophysiology. Hemolytic anemia is an early disease manifestation and is associated with African American ethnicity and the use of azathioprine; it appears to exert an impact on damage but not on mortality.

Multicenter Analysis of Long-Term Oncologic Impact of Anastomotic Leakage After Laparoscopic Total Mesorectal Excision

PubMed Central

Kang, Jeonghyun; Choi, Gyu-Seog; Oh, Jae Hwan; Kim, Nam Kyu; Park, Jun Seok; Kim, Min Jung; Lee, Kang Young; Baik, Seung Hyuk

2015-01-01

Abstract This study aims to validate the oncologic outcomes of anastomotic leakage (AL) after laparoscopic total mesorectal excision (TME) in a large multicenter cohort. The impact of AL after laparoscopic TME for rectal cancer surgery has not yet been clearly described. This was a multicenter retrospective study of 1083 patients who underwent laparoscopic TME for nonmetastatic rectal cancer (stage 0–III). AL was defined as an anastomotic complication within 30 days of surgery irrespective of requiring a reoperation or interventional radiology. Estimated local recurrence (LR), disease-free survival (DFS), and overall survival (OS) were compared between the leakage group and the no leakage group using the log-rank method. Multivariate Cox-regression analysis was used to adjust confounding for survival. The incidence of AL was 6.4%. Mortality within 30 days of surgery occurred in 1 patient (1.4%) in the leakage group and 2 patients (0.2%) in the no leakage group. The leakage group showed a higher LR rate (6.4% vs 1.8%, P = 0.011). Five-year DFS and OS were significantly lower in the leakage group than the no leakage group (DFS 71.7% vs 82.1%, P = 0.016, OS 81.8% vs 93.5%, P = 0.007). Multivariate analysis showed that AL was an independent poor prognostic factor for DFS and OS (hazard ratio [HR] = 1.6; 95% confidence intervals [CI]: 1.0–2.6; P = 0.042, HR = 2.1; 95% CI: 1.0–4.2; P = 0.028, respectively). AL after laparoscopic TME was significantly associated with an increased rate of LR, systemic recurrence and poor OS. PMID:26200636

Long-term follow-up after near-infrared spectroscopy coronary imaging: Insights from the lipid cORe plaque association with CLinical events (ORACLE-NIRS) registry.

PubMed

Danek, Barbara Anna; Karatasakis, Aris; Karacsonyi, Judit; Alame, Aya; Resendes, Erica; Kalsaria, Pratik; Nguyen-Trong, Phuong-Khanh J; Rangan, Bavana V; Roesle, Michele; Abdullah, Shuaib; Banerjee, Subhash; Brilakis, Emmanouil S

Coronary lipid core plaque may be associated with the incidence of subsequent cardiovascular events. We analyzed outcomes of 239 patients who underwent near-infrared spectroscopy (NIRS) coronary imaging between 2009-2011. Multivariable Cox regression was used to identify variables independently associated with the incidence of major adverse cardiovascular events (MACE; cardiac mortality, acute coronary syndromes (ACS), stroke, and unplanned revascularization) during follow-up. Mean patient age was 64±9years, 99% were men, and 50% were diabetic, presenting with stable coronary artery disease (61%) or an acute coronary syndrome (ACS, 39%). Target vessel pre-stenting median lipid core burden index (LCBI) was 88 [interquartile range, IQR 50-130]. Median LCBI in non-target vessels was 57 [IQR 26-94]. Median follow-up was 5.3years. The 5-year MACE rate was 37.5% (cardiac mortality was 15.0%). On multivariable analysis the following variables were associated with MACE: diabetes mellitus, prior percutaneous coronary intervention performed at index angiography, and non-target vessel LCBI. Non-target vessel LCBI of 77 was determined using receiver-operating characteristic curve analysis to be a threshold for prediction of MACE in our cohort. The adjusted hazard ratio (HR) for non-target vessel LCBI ≥77 was 14.05 (95% confidence interval (CI) 2.47-133.51, p=0.002). The 5-year cumulative incidence of events in the above-threshold group was 58.0% vs. 13.1% in the below-threshold group. During long-term follow-up of patients who underwent NIRS imaging, high LCBI in a non-PCI target vessel was associated with increased incidence of MACE. Published by Elsevier Inc.

Symptom clusters predict mortality among dialysis patients in Norway: a prospective observational cohort study.

PubMed

Amro, Amin; Waldum, Bård; von der Lippe, Nanna; Brekke, Fredrik Barth; Dammen, Toril; Miaskowski, Christine; Os, Ingrid

2015-01-01

Patients with end-stage renal disease on dialysis have reduced survival rates compared with the general population. Symptoms are frequent in dialysis patients, and a symptom cluster is defined as two or more related co-occurring symptoms. The aim of this study was to explore the associations between symptom clusters and mortality in dialysis patients. In a prospective observational cohort study of dialysis patients (n = 301), Kidney Disease and Quality of Life Short Form and Beck Depression Inventory questionnaires were administered. To generate symptom clusters, principal component analysis with varimax rotation was used on 11 kidney-specific self-reported physical symptoms. A Beck Depression Inventory score of 16 or greater was defined as clinically significant depressive symptoms. Physical and mental component summary scores were generated from Short Form-36. Multivariate Cox regression analysis was used for the survival analysis, Kaplan-Meier curves and log-rank statistics were applied to compare survival rates between the groups. Three different symptom clusters were identified; one included loading of several uremic symptoms. In multivariate analyses and after adjustment for health-related quality of life and depressive symptoms, the worst perceived quartile of the "uremic" symptom cluster independently predicted all-cause mortality (hazard ratio 2.47, 95% CI 1.44-4.22, P = 0.001) compared with the other quartiles during a follow-up period that ranged from four to 52 months. The two other symptom clusters ("neuromuscular" and "skin") or the individual symptoms did not predict mortality. Clustering of uremic symptoms predicted mortality. Assessing co-occurring symptoms rather than single symptoms may help to identify dialysis patients at high risk for mortality. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Incidence and predictors of mental health disorder diagnoses among people who inject drugs in a Canadian setting.

PubMed

Reddon, Hudson; Pettes, Tyler; Wood, Evan; Nosova, Ekaterina; Milloy, Michael-John; Kerr, Thomas; Hayashi, Kanna

2018-04-01

Limited attention has been given to the predictors of mental health diagnoses among people who inject drugs (PWID) in community settings. Therefore, we sought to longitudinally examine the prevalence, incidence and predictors of mental disorder diagnosis among a community-recruited cohort of PWID. Data were derived from two prospective cohort studies of PWID (VIDUS and ACCESS) in Vancouver, Canada between December 2005 and May 2015. We used multivariable extended Cox regression to identify factors independently associated with self-reported mental disorder diagnosis during follow-up among those without a history of such diagnoses at baseline. Among the 923 participants who did not report a mental disorder at baseline, 206 (22.3%) reported a first diagnosis of a mental disorder during follow-up for an incidence density of 4.29 [95% confidence interval (CI) 3.72-4.91] per 100 person-years. In the multivariable analysis, female sex [adjusted hazards ratio (AHR) = 1.74, 95% CI 1.29-2.33], experiencing non-fatal overdose (AHR = 2.33, 95% CI 1.38-3.94), accessing any drug or alcohol treatment (AHR = 1.68, 95% CI 1.24-2.27), accessing any community health or social services (AHR = 1.53, 95% CI 1.02-2.28) and experiencing violence (AHR = 1.60, 95% CI 1.12-2.29) were independently associated with a mental disorder diagnosis at follow-up. We observed a high prevalence and incidence of mental disorders among our community-recruited sample of PWID. The validity and implication of these diagnoses for key substance use and public health outcomes are an urgent priority. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Characteristics and risk of syphilis diagnosis among HIV-infected male cohort: a population-based study in Houston, Texas.

PubMed

Yang, Biru; Hallmark, Camden J; Huang, Jamie S; Wolverton, Marcia L; McNeese-Ward, Marlene; Arafat, Raouf R

2013-12-01

This population-based study assessed the characteristics, timing, and risk of syphilis diagnoses among HIV-infected males in Houston, Texas. A retrospective cohort of males newly diagnosed as having HIV between January 2000 and December 2002 was constructed using HIV surveillance data. These individuals were cross-referenced to sexually transmitted disease surveillance data to ascertain early syphilis diagnoses for the subsequent 10 years. Multivariable Cox regression was used to identify risk factors for syphilis diagnosis while controlling for the effects of covariates. Approximately 6% of the HIV-infected male cohort received early syphilis diagnoses during a 10-year period. Of these comorbid individuals, 40.8% received an incident syphilis diagnosis 5 years or more after their HIV diagnosis. Men who have sex with men (MSM) transmission risk was associated with significantly increased hazard of having a syphilis diagnosis in multivariable analysis (adjusted hazard ratio [HR] of a syphilis diagnosis, 5.24; 95% confidence interval, 3.41-8.05). Compared with men who were older than 40 years at HIV diagnosis, those 13 to 19 years old were 4.06 (2.18-7.55) times more likely to obtain a syphilis diagnosis. The HRs of having an HIV-syphilis comorbidity decreased as age increased. Compared with whites, non-Hispanic African Americans had 1.59 (1.11-2.26) times increased risk of having a subsequent syphilis diagnosis. Risk-stratified HRs showed that MSM had an increased risk of contracting syphilis in all race/ethnicity and age groups. This study suggests that HIV-positive African Americans, youth, and MSM had increased risk of having a subsequent syphilis diagnosis. Targeting these groups with STI prevention messaging may be beneficial to reducing comorbidity.

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

PubMed Central

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

2014-01-01

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

Heterogeneous impact of alcohol consumption according to treatment method on survival in head and neck cancer: A prospective study.

PubMed

Sawabe, Michi; Ito, Hidemi; Oze, Isao; Hosono, Satoyo; Kawakita, Daisuke; Tanaka, Hideo; Hasegawa, Yasuhisa; Murakami, Shingo; Matsuo, Keitaro

2017-01-01

Alcohol consumption is an established risk factor, and also a potential prognostic factor, for squamous cell carcinoma of the head and neck (HNSCC). However, little is known about whether the prognostic impact of alcohol consumption differs by treatment method. We evaluated the association between alcohol drinking and survival by treatment method to the primary site in 427 patients with HNSCC treated between 2005 and 2013 at Aichi Cancer Center Central Hospital (Nagoya, Japan). The impact of alcohol on prognosis was measured by multivariable Cox regression analysis adjusted for established prognostic factors. Among all HNSCC patients, the overall survival rate was significantly poorer with increased levels of alcohol consumption in multivariable analysis (trend P = 0.038). Stratification by treatment method and primary site revealed that the impact of drinking was heterogeneous. Among laryngopharyngeal cancer (laryngeal, oropharyngeal, and hypopharyngeal cancer) patients receiving radiotherapy (n = 141), a significant dose-response relationship was observed (trend P = 0.034). In contrast, among laryngopharyngeal cancer patients treated with surgery (n = 80), no obvious impact of alcohol was observed. This heterogeneity in the impact of alcohol between surgery and radiotherapy was significant (for interaction, P = 0.048). Furthermore, among patients with oral cavity cancer treated by surgery, a significant impact of drinking on survival was seen with tongue cancer, but not with non-tongue oral cancer. We observed a significant inverse association between alcohol drinking and prognosis among HNSCC patients, and its impact was heterogeneous by treatment method and primary site. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Comparison of rehospitalization rates and associated costs among patients with schizophrenia receiving paliperidone palmitate or oral antipsychotics.

PubMed

Lafeuille, Marie-Hélène; Grittner, Amanda Melina; Fortier, Jonathan; Muser, Erik; Fasteneau, John; Duh, Mei Sheng; Lefebvre, Patrick

2015-03-01

Comparative data on rehospitalization patterns and associated institutional costs after inpatient treatment with paliperidone palmitate or oral antipsychotic therapy are reported. A retrospective cohort study was conducted using discharge and billing records from a large hospital database. Selected clinical and cost outcomes were compared in a cohort of adult patients who received the long-acting antipsychotic paliperidone palmitate during a schizophrenia-related index hospital stay and a cohort of patients who received oral antipsychotic therapy during their index admission. Inverse probability-of-treatment weights based on propensity scores were used to reduce confounding. Rates of all-cause and schizophrenia-related rehospitalization and emergency room (ER) use in the two cohorts over periods of up to 12 months were analyzed using a multivariate Cox proportional hazard model. Institutional costs for the evaluated postdischarge events were compared via multivariate linear regression analysis. In the first 12 months after index hospital discharge, the risk of all-cause rehospitalization and ER use was significantly lower in the paliperidone palmitate cohort than in the oral antipsychotic cohort (hazard ratio, 0.61; 95% confidence interval [CI], 0.59-0.63; p < 0.0001); institutional costs during the first 6 months after discharge were significantly lower in the paliperidone palmitate cohort than in the comparator group (adjusted mean monthly cost difference -$404; 95% CI, -$781 to -$148; p < 0.0001). The use of paliperidone palmitate therapy during patients' index hospital admission for schizophrenia was associated with a reduced risk of hospital readmission or ER use and lower postdischarge institutional costs. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.