Use of Medicare Data to Identify Coronary Heart Disease Outcomes In the Women's Health Initiative (WHI)

PubMed Central

Hlatky, Mark A; Ray, Roberta M; Burwen, Dale R; Margolis, Karen L; Johnson, Karen C; Kucharska-Newton, Anna; Manson, JoAnn E; Robinson, Jennifer G; Safford, Monika M; Allison, Matthew; Assimes, Themistocles L; Bavry, Anthony A; Berger, Jeffrey; Cooper-DeHoff, Rhonda M; Heckbert, Susan R; Li, Wenjun; Liu, Simin; Martin, Lisa W; Perez, Marco V; Tindle, Hilary A; Winkelmayer, Wolfgang C; Stefanick, Marcia L

2015-01-01

Background Data collected as part of routine clinical practice could be used to detect cardiovascular outcomes in pragmatic clinical trials, or in clinical registry studies. The reliability of claims data for documenting outcomes is unknown. Methods and Results We linked records of Women's Health Initiative (WHI) participants aged 65 years and older to Medicare claims data, and compared hospitalizations that had diagnosis codes for acute myocardial infarction (MI) or coronary revascularization with WHI outcomes adjudicated by study physicians. We then compared the hazard ratios for active versus placebo hormone therapy based solely on WHI adjudicated events with corresponding hazard ratios based solely on claims data for the same hormone trial participants. Agreement between WHI adjudicated outcomes and Medicare claims was good for the diagnosis for MI (kappa = 0.71 to 0.74), and excellent for coronary revascularization (kappa=0.88 to 0.91). The hormone:placebo hazard ratio for clinical MI was 1.31 (95% confidence interval (CI) 1.03 to 1.67) based on WHI outcomes, and 1.29 (CI 1.00 to 1.68) based on Medicare data. The hazard ratio for coronary revascularization was 1.09 (CI 0.88 to 1.35) based on WHI outcomes and 1.10 (CI 0.89 to 1.35) based on Medicare data. The differences between hazard ratios derived from WHI and Medicare data were not significant in 1,000 bootstrap replications. Conclusion Medicare claims may provide useful data on coronary heart disease outcomes among patients aged 65 years and older in clinical research studies. Clinical Trials Registration Information www.clinicaltrials.gov, Trial Number NCT00000611 PMID:24399330

How do outcomes compare between women and men living with HIV in Australia? An observational study

PubMed Central

Giles, Michelle L.; Zapata, Marin C.; Wright, Stephen T.; Petoumenos, Kathy; Grotowski, Miriam; Broom, Jennifer; Law, Matthew G.; O’Connor, Catherine C.

2018-01-01

Background Gender differences vary across geographical settings and are poorly reported in the literature. The aim of this study was to evaluate demographics and clinical characteristics of participants from the Australian HIV Observational Database (AHOD), and to explore any differences between females and males in the rate of new clinical outcomes, as well as initial immunological and virological response to antiretroviral therapy. Methods Time to a new clinical end-point, all-cause mortality and/or AIDS illness was analysed using standard survival methods. Univariate and covariate adjusted Cox proportional hazard models were used to evaluate the time to plasma viral load suppression in all patients that initiated antiretroviral therapy (ART) and time to switching from a first-line ART to a second-line ART regimen. Results There was no significant difference between females and males for the hazard of all-cause mortality [adjusted hazard ratio: 0.98 (0.51, 1.55), P = 0.67], new AIDS illness [adjusted hazard ratio: 0.75 (0.38, 1.48), P = 0.41] or a composite end-point [adjusted hazard ratio: 0.74 (0.45, 1.21), P = 0.23]. Incident rates of all-cause mortality were similar between females and males; 1.14 (0.61, 1.95) vs 1.28 (1.12, 1.45) per 100 person years. Virological response to ART was similar for females and males when measured as time to viral suppression and/or time to virological failure. Conclusion This study supports current Australian HIV clinical care as providing equivalent standards of care for male and female HIV-positive patients. Future studies should compare ART-associated toxicity differences between ART-associated toxicity differences between men and women living with HIV in Australia. PMID:26827052

Greater Volume but not Higher Density of Abdominal Aortic Calcium Is Associated With Increased Cardiovascular Disease Risk: MESA (Multi-Ethnic Study of Atherosclerosis).

PubMed

Forbang, Nketi I; Michos, Erin D; McClelland, Robyn L; Remigio-Baker, Rosemay A; Allison, Matthew A; Sandfort, Veit; Ix, Joachim H; Thomas, Isac; Rifkin, Dena E; Criqui, Michael H

2016-11-01

Abdominal aortic calcium (AAC) and coronary artery calcium (CAC) independently and similarly predict cardiovascular disease (CVD) events. The standard AAC and CAC score, the Agatston method, upweights for greater calcium density, thereby modeling higher calcium density as a CVD hazard. Computed tomography scans were used to measure AAC and CAC volume and density in a multiethnic cohort of community-dwelling individuals, and Cox proportional hazard was used to determine their independent association with incident coronary heart disease (CHD, defined as myocardial infarction, resuscitated cardiac arrest, or CHD death), cardiovascular disease (CVD, defined as CHD plus stroke and stroke death), and all-cause mortality. In 997 participants with Agatston AAC and CAC scores >0, the mean age was 66±9 years, and 58% were men. During an average follow-up of 9 years, there were 77 CHD, 118 CVD, and 169 all-cause mortality events. In mutually adjusted models, additionally adjusted for CVD risk factors, an increase in ln(AAC volume) per standard deviation was significantly associated with increased all-cause mortality (hazard ratio=1.20; 95% confidence interval, 1.08-1.33; P<0.01) and an increased ln(CAC volume) per standard deviation was significantly associated with CHD (hazard ratio=1.17; 95% confidence interval, 1.04-1.59; P=0.02) and CVD (hazard ratio=1.20; 95% confidence interval, 1.05-1.36; P<0.01). In contrast, both AAC and CAC density were not significantly associated with CVD events. The Agatston method of upweighting calcium scores for greater density may be inappropriate for CVD risk prediction in both the abdominal aorta and coronary arteries. © 2016 American Heart Association, Inc.

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

PubMed

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

2009-12-01

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

Effects of Changes in Potassium With Valsartan Use on Diabetes Risk: Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial

PubMed Central

Thomas, Laine; Svetkey, Laura; Brancati, Frederick L.; Califf, Robert M.; Edelman, David

2013-01-01

BACKGROUND Low and low-normal serum potassium is associated with an increased risk of diabetes. We hypothesized that the protective effect of valsartan on diabetes risk could be mediated by its effect of raising serum potassium. METHODS We analyzed data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, which randomized participants at risk for diabetes to either valsartan (up to 160mg daily) or no valsartan. Using Cox models, we evaluated the effect of valsartan on diabetes risk over a median of 4 years of follow-up and calculated the mediation effect of serum potassium as the difference in treatment hazard ratios from models excluding and including 1-year change in serum potassium. The 95% confidence interval (CI) for the difference in log hazard ratios was computed by bootstrapping. RESULTS The hazard ratio for developing diabetes among those on valsartan vs. no valsartan was 0.866 (95% CI = 0.795–0.943) vs. 0.868 (95% CI = 0.797–0.945), after controlling for 1-year change in potassium. The bootstrap 95% CI for a difference in these log hazard ratios was not statistically significant (−0.003 to 0.009). CONCLUSIONS Serum potassium does not appear to significantly mediate the protective effect of valsartan on diabetes risk. PMID:23417031

An apparatus and procedure for evaluating the toxic hazards of smoldering seating and bedding materials

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Brandt, D. L.; Brauer, D. P.

1978-01-01

An apparatus and procedure are described for evaluating the toxicity of the gases evolved from the smoldering combustion of seating and bedding materials. The method combines initiation of smoldering combustion in fabric/cushion combinations by a lighted cigarette and exposure of laboratory animals to the gases evolved. The ratio of the surface available for smoldering to the compartment volume in this apparatus is approximately five times the ratio expected in a California living room, and 100 times the ratio expected in a wide-body aircraft passenger cabin. Based on fabric/cushion combinations tested, the toxicity of gases from smoldering combustion does not appear to be a significant hazard in aircraft passenger cabins, but seems to be a basis for careful selection of materials for residential environments.

Prednisolone and Mycobacterium indicus pranii in Tuberculous Pericarditis

PubMed Central

Mayosi, Bongani M; Ntsekhe, Mpiko; Bosch, Jackie; Pandie, Shaheen; Jung, Hyejung; Gumedze, Freedom; Pogue, Janice; Thabane, Lehana; Smieja, Marek; Francis, Veronica; Joldersma, Laura; Thomas, Kandithalal M.; Thomas, Baby; Awotedu, Abolade A.; Magula, Nombulelo P.; Naidoo, Datshana P.; Damasceno, Albertino; Banda, Alfred Chitsa; Brown, Basil; Manga, Pravin; Kirenga, Bruce; Mondo, Charles; Mntla, Phindile; Tsitsi, Jacob M.; Peters, Ferande; Essop, Mohammed R.; Russell, James B.W.; Hakim, James; Matenga, Jonathan; Barasa, Ayub F.; Sani, Mahmoud U.; Olunuga, Taiwo; Ogah, Okechukwu; Ansa, Victor; Aje, Akinyemi; Danbauchi, Solomon; Ojji, Dike; Yusuf, Salim

2016-01-01

BACKGROUND Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis. METHODS Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. RESULTS There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P = 0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P = 0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P = 0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P = 0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P = 0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P = 0.03, respectively), owing mainly to an increase in HIV-associated cancer. CONCLUSIONS In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. (Funded by the Canadian Institutes of Health Research and others; IMPI ClinicalTrials.gov number, NCT00810849.) PMID:25178809

Different impacts of hypertension and diabetes mellitus on all-cause and cardiovascular mortality in community-dwelling older adults: the Rancho Bernardo Study.

PubMed

Oh, Jee-Young; Allison, Matthew A; Barrett-Connor, Elizabeth

2017-01-01

Although the prevalence rates of hypertension (HTN) and diabetes mellitus are slowing in some high-income countries, HTN and diabetes mellitus remain as the two major risk factors for atherosclerotic cardiovascular disease (CVD), the leading cause of death in the United States and worldwide. We aimed to observe the association of HTN and diabetes mellitus with all-cause and CVD mortality in older white adults. All community-dwelling Rancho Bernardo Study participants who were at least 55 years old and had carefully measured blood pressure and plasma glucose from 75-g oral glucose tolerance test at the baseline visit (1984-1987, n = 2186) were followed up until death or the last clinic visit in 2013 (median 14.3 years, interquartile range 8.4-21.3). In unadjusted analyses, diabetes mellitus was associated with all-cause mortality [hazard ratio 1.40, 95% confidence interval (CI) 1.23-1.60] and CVD mortality (hazard ratio 1.67, 95% CI 1.39-2.00); HTN with all-cause mortality [hazard ratio 1.93 (1.73-2.15)] and CVD mortality [hazard ratio 2.45 (2.10-2.93)]. After adjustment for cardiovascular risk factors, including age, BMI, triglycerides, HDL-cholesterol, smoking, exercise, and alcohol consumption, diabetes mellitus was associated with CVD mortality only (hazard ratio 1.25, P = 0.0213). Conversely, HTN was associated with both all-cause (hazard ratio 1.34, P < 0.0001) and CVD mortality (hazard ratio 1.40, P = 0.0003). Having both diabetes mellitus and HTN was associated with all-cause (hazard ratio 1.38, P = 0.0002) and CVD mortality (hazard ratio 1.70, P < 0.0001). We report the novel finding that HTN is more strongly associated with all-cause and CVD mortality than diabetes mellitus. Having both confers a modest increase in the hazards for these types of mortality.

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

PubMed

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

2017-12-01

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

Sickle Cell Trait, Rhabdomyolysis, and Mortality among U.S. Army Soldiers

PubMed Central

Nelson, D. Alan; Deuster, Patricia A.; Carter, Robert; Hill, Owen T.; Wolcott, Vickee L.; Kurina, Lianne M.

2016-01-01

Background Studies have suggested that sickle cell trait elevates the risks of exertional rhabdomyolysis and death. We conducted a study of sickle cell trait in relation to these outcomes, controlling for known risk factors for exertional rhabdomyolysis, in a large population of active persons who had undergone laboratory tests for hemoglobin AS (HbAS) and who were subject to exertional-injury precautions. Methods We used Cox proportional-hazards models to test whether the risks of exertional rhabdomyolysis and death varied according to sickle cell trait status among 47,944 black soldiers who had undergone testing for HbAS and who were on active duty in the U.S. Army between January 2011 and December 2014. We used the Stanford Military Data Repository, which contains comprehensive medical and administrative data on all active-duty soldiers. Results There was no significant difference in the risk of death among soldiers with sickle cell trait, as compared with those without the trait (hazard ratio, 0.99; 95% confidence interval [CI], 0.46 to 2.13; P = 0.97), but the trait was associated with a significantly higher adjusted risk of exertional rhabdomyolysis (hazard ratio, 1.54; 95% CI, 1.12 to 2.12; P = 0.008). This effect was similar in magnitude to that associated with tobacco use, as compared with no use (hazard ratio, 1.54; 95% CI, 1.23 to 1.94; P<0.001), and to that associated with having a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30.0 or more, as compared with a BMI of less than 25.0 (hazard ratio, 1.39; 95% CI, 1.04 to 1.86; P = 0.03). The effect was less than that associated with recent use of a statin, as compared with no use (hazard ratio, 2.89; 95% CI, 1.51 to 5.55; P = 0.001), or an antipsychotic agent (hazard ratio, 3.02; 95% CI, 1.34 to 6.82; P = 0.008). Conclusions Sickle cell trait was not associated with a higher risk of death than absence of the trait, but it was associated with a significantly higher risk of exertional rhabdomyolysis. (Funded by the National Heart, Lung, and Blood Institute and the Uniformed Services University of the Health Sciences.) PMID:27518662

Opioid Analgesics and Adverse Outcomes among Hemodialysis Patients.

PubMed

Ishida, Julie H; McCulloch, Charles E; Steinman, Michael A; Grimes, Barbara A; Johansen, Kirsten L

2018-05-07

Patients on hemodialysis frequently experience pain and may be particularly vulnerable to opioid-related complications. However, data evaluating the risks of opioid use in patients on hemodialysis are limited. Using the US Renal Data System, we conducted a cohort study evaluating the association between opioid use (modeled as a time-varying exposure and expressed in standardized oral morphine equivalents) and time to first emergency room visit or hospitalization for altered mental status, fall, and fracture among 140,899 Medicare-covered adults receiving hemodialysis in 2011. We evaluated risk according to average daily total opioid dose (>60 mg, ≤60 mg, and per 60-mg dose increment) and specific agents (per 60-mg dose increment). The median age was 61 years old, 52% were men, and 50% were white. Sixty-four percent received opioids, and 17% had an episode of altered mental status (15,658 events), fall (7646 events), or fracture (4151 events) in 2011. Opioid use was associated with risk for all outcomes in a dose-dependent manner: altered mental status (lower dose: hazard ratio, 1.28; 95% confidence interval, 1.23 to 1.34; higher dose: hazard ratio, 1.67; 95% confidence interval, 1.56 to 1.78; hazard ratio, 1.29 per 60 mg; 95% confidence interval, 1.26 to 1.33), fall (lower dose: hazard ratio, 1.28; 95% confidence interval, 1.21 to 1.36; higher dose: hazard ratio, 1.45; 95% confidence interval, 1.31 to 1.61; hazard ratio, 1.04 per 60 mg; 95% confidence interval, 1.03 to 1.05), and fracture (lower dose: hazard ratio, 1.44; 95% confidence interval, 1.33 to 1.56; higher dose: hazard ratio, 1.65; 95% confidence interval, 1.44 to 1.89; hazard ratio, 1.04 per 60 mg; 95% confidence interval, 1.04 to 1.05). All agents were associated with a significantly higher hazard of altered mental status, and several agents were associated with a significantly higher hazard of fall and fracture. Opioids were associated with adverse outcomes in patients on hemodialysis, and this risk was present even at lower dosing and for agents that guidelines have recommended for use. Copyright © 2018 by the American Society of Nephrology.

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

PubMed Central

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

2014-01-01

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

Best anthropometric discriminators of incident type 2 diabetes among white and black adults: A longitudinal ARIC study

PubMed Central

Stallings, Devita T.; Garvin, Jane T.; Xu, Hongyan; Racette, Susan B.

2017-01-01

Objective To determine which anthropometric measures are the strongest discriminators of incident type 2 diabetes (T2DM) among White and Black males and females in a large U.S. cohort. Methods We used Atherosclerosis Risk in Communities study data from 12,121 participants aged 45–64 years without diabetes at baseline who were followed for over 11 years. Anthropometric measures included a body shape index (ABSI), body adiposity index (BAI), body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), waist to height ratio (WHtR), and waist to hip to height ratio (WHHR). All anthropometric measures were repeated at each visit and converted to Z-scores. Hazard ratios and 95% confidence intervals adjusted for age were calculated using repeated measures Cox proportional hazard regression analysis. Akaike Information Criteria was used to select best-fit models. The magnitude of the hazard ratio effect sizes and the Harrell’s C-indexes were used to rank the highest associations and discriminators, respectively. Results There were 1,359 incident diabetes cases. Higher values of all anthropometric measures increased the risk for development of T2DM (p < 0.0001) except ABSI, which was not significant in White and Black males. Statistically significant hazard ratios ranged from 1.26–1.63 for males and 1.15–1.88 for females. In general, the largest hazard ratios were those that corresponded to the highest Harrell’s C-Index and lowest Akaike Information Criteria values. Among White and Black males and females, BMI, WC, WHR, and WHtR were comparable in discriminating cases from non-cases of T2DM. ABSI, BAI, and WHHR were inferior discriminators of incident T2DM across all race-gender groups. Conclusions BMI, the most commonly used anthropometric measure, and three anthropometric measures that included waist circumference (i.e., WC, WHR, WHtR) were the best anthropometric discriminators of incident T2DM across all race-gender groups in the ARIC cohort. PMID:28141847

Using Marginal Structural Measurement-Error Models to Estimate the Long-term Effect of Antiretroviral Therapy on Incident AIDS or Death

PubMed Central

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

2010-01-01

To estimate the net effect of imperfectly measured highly active antiretroviral therapy on incident acquired immunodeficiency syndrome or death, the authors combined inverse probability-of-treatment-and-censoring weighted estimation of a marginal structural Cox model with regression-calibration methods. Between 1995 and 2007, 950 human immunodeficiency virus–positive men and women were followed in 2 US cohort studies. During 4,054 person-years, 374 initiated highly active antiretroviral therapy, 211 developed acquired immunodeficiency syndrome or died, and 173 dropped out. Accounting for measured confounders and determinants of dropout, the weighted hazard ratio for acquired immunodeficiency syndrome or death comparing use of highly active antiretroviral therapy in the prior 2 years with no therapy was 0.36 (95% confidence limits: 0.21, 0.61). This association was relatively constant over follow-up (P = 0.19) and stronger than crude or adjusted hazard ratios of 0.75 and 0.95, respectively. Accounting for measurement error in reported exposure using external validation data on 331 men and women provided a hazard ratio of 0.17, with bias shifted from the hazard ratio to the estimate of precision as seen by the 2.5-fold wider confidence limits (95% confidence limits: 0.06, 0.43). Marginal structural measurement-error models can simultaneously account for 3 major sources of bias in epidemiologic research: validated exposure measurement error, measured selection bias, and measured time-fixed and time-varying confounding. PMID:19934191

Development of vulnerability curves to typhoon hazards based on insurance policy and claim dataset

NASA Astrophysics Data System (ADS)

Mo, Wanmei; Fang, Weihua; li, Xinze; Wu, Peng; Tong, Xingwei

2016-04-01

Vulnerability refers to the characteristics and circumstances of an exposure that make it vulnerable to the effects of some certain hazards. It can be divided into physical vulnerability, social vulnerability, economic vulnerabilities and environmental vulnerability. Physical vulnerability indicates the potential physical damage of exposure caused by natural hazards. Vulnerability curves, quantifying the loss ratio against hazard intensity with a horizontal axis for the intensity and a vertical axis for the Mean Damage Ratio (MDR), is essential to the vulnerability assessment and quantitative evaluation of disasters. Fragility refers to the probability of diverse damage states under different hazard intensity, revealing a kind of characteristic of the exposure. Fragility curves are often used to quantify the probability of a given set of exposure at or exceeding a certain damage state. The development of quantitative fragility and vulnerability curves is the basis of catastrophe modeling. Generally, methods for quantitative fragility and vulnerability assessment can be categorized into empirical, analytical and expert opinion or judgment-based ones. Empirical method is one of the most popular methods and it relies heavily on the availability and quality of historical hazard and loss dataset, which has always been a great challenge. Analytical method is usually based on the engineering experiments and it is time-consuming and lacks built-in validation, so its credibility is also sometimes criticized widely. Expert opinion or judgment-based method is quite effective in the absence of data but the results could be too subjective so that the uncertainty is likely to be underestimated. In this study, we will present the fragility and vulnerability curves developed with empirical method based on simulated historical typhoon wind, rainfall and induced flood, and insurance policy and claim datasets of more than 100 historical typhoon events. Firstly, an insurance exposure classification system is built according to structure type, occupation type and insurance coverage. Then MDR estimation method based on considering insurance policy structure and claim information is proposed and validated. Following that, fragility and vulnerability curves of the major exposure types for construction, homeowner insurance and enterprise property insurance are fitted with empirical function based on the historical dataset. The results of this study can not only help understand catastrophe risk and mange insured disaster risks, but can also be applied in other disaster risk reduction efforts.

Covariate Measurement Error Correction Methods in Mediation Analysis with Failure Time Data

PubMed Central

Zhao, Shanshan

2014-01-01

Summary Mediation analysis is important for understanding the mechanisms whereby one variable causes changes in another. Measurement error could obscure the ability of the potential mediator to explain such changes. This paper focuses on developing correction methods for measurement error in the mediator with failure time outcomes. We consider a broad definition of measurement error, including technical error and error associated with temporal variation. The underlying model with the ‘true’ mediator is assumed to be of the Cox proportional hazards model form. The induced hazard ratio for the observed mediator no longer has a simple form independent of the baseline hazard function, due to the conditioning event. We propose a mean-variance regression calibration approach and a follow-up time regression calibration approach, to approximate the partial likelihood for the induced hazard function. Both methods demonstrate value in assessing mediation effects in simulation studies. These methods are generalized to multiple biomarkers and to both case-cohort and nested case-control sampling design. We apply these correction methods to the Women's Health Initiative hormone therapy trials to understand the mediation effect of several serum sex hormone measures on the relationship between postmenopausal hormone therapy and breast cancer risk. PMID:25139469

Covariate measurement error correction methods in mediation analysis with failure time data.

PubMed

Zhao, Shanshan; Prentice, Ross L

2014-12-01

Mediation analysis is important for understanding the mechanisms whereby one variable causes changes in another. Measurement error could obscure the ability of the potential mediator to explain such changes. This article focuses on developing correction methods for measurement error in the mediator with failure time outcomes. We consider a broad definition of measurement error, including technical error, and error associated with temporal variation. The underlying model with the "true" mediator is assumed to be of the Cox proportional hazards model form. The induced hazard ratio for the observed mediator no longer has a simple form independent of the baseline hazard function, due to the conditioning event. We propose a mean-variance regression calibration approach and a follow-up time regression calibration approach, to approximate the partial likelihood for the induced hazard function. Both methods demonstrate value in assessing mediation effects in simulation studies. These methods are generalized to multiple biomarkers and to both case-cohort and nested case-control sampling designs. We apply these correction methods to the Women's Health Initiative hormone therapy trials to understand the mediation effect of several serum sex hormone measures on the relationship between postmenopausal hormone therapy and breast cancer risk. © 2014, The International Biometric Society.

Landslide susceptibility mapping by combining the three methods Fuzzy Logic, Frequency Ratio and Analytical Hierarchy Process in Dozain basin

NASA Astrophysics Data System (ADS)

Tazik, E.; Jahantab, Z.; Bakhtiari, M.; Rezaei, A.; Kazem Alavipanah, S.

2014-10-01

Landslides are among the most important natural hazards that lead to modification of the environment. Therefore, studying of this phenomenon is so important in many areas. Because of the climate conditions, geologic, and geomorphologic characteristics of the region, the purpose of this study was landslide hazard assessment using Fuzzy Logic, frequency ratio and Analytical Hierarchy Process method in Dozein basin, Iran. At first, landslides occurred in Dozein basin were identified using aerial photos and field studies. The influenced landslide parameters that were used in this study including slope, aspect, elevation, lithology, precipitation, land cover, distance from fault, distance from road and distance from river were obtained from different sources and maps. Using these factors and the identified landslide, the fuzzy membership values were calculated by frequency ratio. Then to account for the importance of each of the factors in the landslide susceptibility, weights of each factor were determined based on questionnaire and AHP method. Finally, fuzzy map of each factor was multiplied to its weight that obtained using AHP method. At the end, for computing prediction accuracy, the produced map was verified by comparing to existing landslide locations. These results indicate that the combining the three methods Fuzzy Logic, Frequency Ratio and Analytical Hierarchy Process method are relatively good estimators of landslide susceptibility in the study area. According to landslide susceptibility map about 51% of the occurred landslide fall into the high and very high susceptibility zones of the landslide susceptibility map, but approximately 26 % of them indeed located in the low and very low susceptibility zones.

Clinical Implications of the Tumor Volume Reduction Rate in Head-and-Neck Cancer During Definitive Intensity-Modulated Radiotherapy for Organ Preservation

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

Yang, Shih-Neng; Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan; Liao, Chih-Ying

2011-03-15

Purpose: To investigate the prognostic value of the volume reduction rate (VRR) in patients with head-and-neck cancer treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: Seventy-six patients with oropharyngeal cancer (OPC) and another 76 with hypopharyngeal cancer (HPC) were enrolled in volumetric analysis. All patients received allocated radiotherapy courses. Adaptive computed tomography was done 4 to 5 weeks after the start of IMRT. Primary tumor volume measurement was derived using separate images for the pretreatment gross tumor volume (pGTV) and the interval gross tumor volume. Results: In the OPC group, the pGTV ranged from 6.6 to 242.6 mL (mean, 49.9more » mL), whereas the value of the VRR ranged from 0.014 to 0.74 (mean, 0.43). In HPC patients, the pGTV ranged from 4.1 to 152.4 mL (mean, 35.6 mL), whereas the VRR ranged from -1.15 to 0.79 (mean, 0.33). Multivariate analysis of the primary tumor relapse-free survival for OPC revealed three prognostic factors: T4 tumor (p = 0.0001, hazard ratio 7.38), pGTV {>=}20 mL (p = 0.01, hazard ratio 10.61), and VRR <0.5 (p = 0.001, hazard ratio 6.49). Multivariate analysis of the primary tumor relapse-free survival for HPC showed two prognostic factors: pGTV {>=}30 mL (p = 0.001, hazard ratio 2.87) and VRR <0.5 (p = 0.03, hazard ratio 2.25). Conclusion: The VRR is an outcome predictor for local control in OPC and HPC patients treated with IMRT. Those with large tumor volumes or a VRR <0.5 should be considered for a salvage operation or a dose-escalation scheme.« less

A Bayesian Hybrid Adaptive Randomisation Design for Clinical Trials with Survival Outcomes.

PubMed

Moatti, M; Chevret, S; Zohar, S; Rosenberger, W F

2016-01-01

Response-adaptive randomisation designs have been proposed to improve the efficiency of phase III randomised clinical trials and improve the outcomes of the clinical trial population. In the setting of failure time outcomes, Zhang and Rosenberger (2007) developed a response-adaptive randomisation approach that targets an optimal allocation, based on a fixed sample size. The aim of this research is to propose a response-adaptive randomisation procedure for survival trials with an interim monitoring plan, based on the following optimal criterion: for fixed variance of the estimated log hazard ratio, what allocation minimizes the expected hazard of failure? We demonstrate the utility of the design by redesigning a clinical trial on multiple myeloma. To handle continuous monitoring of data, we propose a Bayesian response-adaptive randomisation procedure, where the log hazard ratio is the effect measure of interest. Combining the prior with the normal likelihood, the mean posterior estimate of the log hazard ratio allows derivation of the optimal target allocation. We perform a simulation study to assess and compare the performance of this proposed Bayesian hybrid adaptive design to those of fixed, sequential or adaptive - either frequentist or fully Bayesian - designs. Non informative normal priors of the log hazard ratio were used, as well as mixture of enthusiastic and skeptical priors. Stopping rules based on the posterior distribution of the log hazard ratio were computed. The method is then illustrated by redesigning a phase III randomised clinical trial of chemotherapy in patients with multiple myeloma, with mixture of normal priors elicited from experts. As expected, there was a reduction in the proportion of observed deaths in the adaptive vs. non-adaptive designs; this reduction was maximized using a Bayes mixture prior, with no clear-cut improvement by using a fully Bayesian procedure. The use of stopping rules allows a slight decrease in the observed proportion of deaths under the alternate hypothesis compared with the adaptive designs with no stopping rules. Such Bayesian hybrid adaptive survival trials may be promising alternatives to traditional designs, reducing the duration of survival trials, as well as optimizing the ethical concerns for patients enrolled in the trial.

Effect of Long Working Hours on Self-reported Hypertension among Middle-aged and Older Wage Workers

PubMed Central

2014-01-01

Objectives Many studies have reported an association between overwork and hypertension. However, research on the health effects of long working hours has yielded inconclusive results. The objective of this study was to identify an association between overtime work and hypertension in wage workers 45 years and over of age using prospective data. Methods Wage workers in Korea aged 45 years and over were selected for inclusion in this study from among 10,254 subjects from the Korean Longitudinal Study of Ageing. Workers with baseline hypertension and those with other major diseases were excluded. In the end, a total of 1,079 subjects were included. A Cox proportional hazards model was used to calculate hazard ratios and adjust for baseline characteristics such as sex, age, education, income, occupation, form of employment, body mass index, alcohol habit, smoking habit, regular exercise, and number of working days per week. Additional models were used to calculate hazard ratios after gender stratification. Results Among the 1,079 subjects, 85 workers were diagnosed with hypertension during 3974.2 person-months. The average number of working hours per week for all subjects was 47.68. The proportion of overtime workers was 61.0% (cutoff, 40 h per week). Compared with those working 40 h and less per week, the hazard ratio of subjects in the final model, which adjusted for all selected variables, working 41-50 h per week was 2.20 (95% confidence interval [CI], 1.19–4.06), that of subjects working 51-60 h per week was 2.40 (95% CI, 1.07–5.39), and that of subjects working 61 h and over per week was 2.87 (95% CI, 1.33–6.20). In gender stratification models, the hazard ratio of the females tended to be higher than that of the males. Conclusion As the number of working hours per week increased, the hazard ratio for diagnosis of hypertension significantly increased. This result suggests a positive association between overtime work and the risk of hypertension. PMID:25852938

Landslide hazard mapping with selected dominant factors: A study case of Penang Island, Malaysia

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

Tay, Lea Tien; Alkhasawneh, Mutasem Sh.; Ngah, Umi Kalthum

Landslide is one of the destructive natural geohazards in Malaysia. In addition to rainfall as triggering factos for landslide in Malaysia, topographical and geological factors play important role in the landslide susceptibility analysis. Conventional topographic factors such as elevation, slope angle, slope aspect, plan curvature and profile curvature have been considered as landslide causative factors in many research works. However, other topographic factors such as diagonal length, surface area, surface roughness and rugosity have not been considered, especially for the research work in landslide hazard analysis in Malaysia. This paper presents landslide hazard mapping using Frequency Ratio (FR) and themore » study area is Penang Island of Malaysia. Frequency ratio approach is a variant of probabilistic method that is based on the observed relationships between the distribution of landslides and each landslide-causative factor. Landslide hazard map of Penang Island is produced by considering twenty-two (22) landslide causative factors. Among these twenty-two (22) factors, fourteen (14) factors are topographic factors. They are elevation, slope gradient, slope aspect, plan curvature, profile curvature, general curvature, tangential curvature, longitudinal curvature, cross section curvature, total curvature, diagonal length, surface area, surface roughness and rugosity. These topographic factors are extracted from the digital elevation model of Penang Island. The other eight (8) non-topographic factors considered are land cover, vegetation cover, distance from road, distance from stream, distance from fault line, geology, soil texture and rainfall precipitation. After considering all twenty-two factors for landslide hazard mapping, the analysis is repeated with fourteen dominant factors which are selected from the twenty-two factors. Landslide hazard map was segregated into four categories of risks, i.e. Highly hazardous area, Hazardous area, Moderately hazardous area and Not hazardous area. The maps was assessed using ROC (Rate of Curve) based on the area under the curve method (AUC). The result indicates an increase of accuracy from 77.76% (with all 22 factors) to 79.00% (with 14 dominant factors) in the prediction of landslide occurrence.« less

Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal.

PubMed

Mocroft, Amanda; Sterne, Jonathan A C; Egger, Matthias; May, Margaret; Grabar, Sophie; Furrer, Hansjakob; Sabin, Caroline; Fatkenheuer, Gerd; Justice, Amy; Reiss, Peter; d'Arminio Monforte, Antonella; Gill, John; Hogg, Robert; Bonnet, Fabrice; Kitahata, Mari; Staszewski, Schlomo; Casabona, Jordi; Harris, Ross; Saag, Michael

2009-04-15

The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of antiretroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a "rare ADEs" category. During a median follow-up period of 43 months (interquartile range, 19-70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin's lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84-22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70-14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin's lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55-9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76-3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08-2.00]). In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in clinical end point trials, prognostic studies, and patient management.

Adverse health outcomes in women exposed in utero to diethylstilbestrol.

PubMed

Hoover, Robert N; Hyer, Marianne; Pfeiffer, Ruth M; Adam, Ervin; Bond, Brian; Cheville, Andrea L; Colton, Theodore; Hartge, Patricia; Hatch, Elizabeth E; Herbst, Arthur L; Karlan, Beth Y; Kaufman, Raymond; Noller, Kenneth L; Palmer, Julie R; Robboy, Stanley J; Saal, Robert C; Strohsnitter, William; Titus-Ernstoff, Linda; Troisi, Rebecca

2011-10-06

Before 1971, several million women were exposed in utero to diethylstilbestrol (DES) given to their mothers to prevent pregnancy complications. Several adverse outcomes have been linked to such exposure, but their cumulative effects are not well understood. We combined data from three studies initiated in the 1970s with continued long-term follow-up of 4653 women exposed in utero to DES and 1927 unexposed controls. We assessed the risks of 12 adverse outcomes linked to DES exposure, including cumulative risks to 45 years of age for reproductive outcomes and to 55 years of age for other outcomes, and their relationships to the baseline presence or absence of vaginal epithelial changes, which are correlated with a higher dose of, and earlier exposure to, DES in utero. Cumulative risks in women exposed to DES, as compared with those not exposed, were as follows: for infertility, 33.3% vs. 15.5% (hazard ratio, 2.37; 95% confidence interval [CI], 2.05 to 2.75); spontaneous abortion, 50.3% vs. 38.6% (hazard ratio, 1.64; 95% CI, 1.42 to 1.88); preterm delivery, 53.3% vs. 17.8% (hazard ratio, 4.68; 95% CI, 3.74 to 5.86); loss of second-trimester pregnancy, 16.4% vs. 1.7% (hazard ratio, 3.77; 95% CI, 2.56 to 5.54); ectopic pregnancy, 14.6% vs. 2.9% (hazard ratio, 3.72; 95% CI, 2.58 to 5.38); preeclampsia, 26.4% vs. 13.7% (hazard ratio 1.42; 95% CI, 1.07 to 1.89); stillbirth, 8.9% vs. 2.6% (hazard ratio, 2.45; 95% CI, 1.33 to 4.54); early menopause, 5.1% vs. 1.7% (hazard ratio, 2.35; 95% CI, 1.67 to 3.31); grade 2 or higher cervical intraepithelial neoplasia, 6.9% vs. 3.4% (hazard ratio, 2.28; 95% CI, 1.59 to 3.27); and breast cancer at 40 years of age or older, 3.9% vs. 2.2% (hazard ratio, 1.82; 95% CI, 1.04 to 3.18). For most outcomes, the risks among exposed women were higher for those with vaginal epithelial changes than for those without such changes. In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes. (Funded by the National Cancer Institute.).

Assessing the Impact of Analytical Error on Perceived Disease Severity.

PubMed

Kroll, Martin H; Garber, Carl C; Bi, Caixia; Suffin, Stephen C

2015-10-01

The perception of the severity of disease from laboratory results assumes that the results are free of analytical error; however, analytical error creates a spread of results into a band and thus a range of perceived disease severity. To assess the impact of analytical errors by calculating the change in perceived disease severity, represented by the hazard ratio, using non-high-density lipoprotein (nonHDL) cholesterol as an example. We transformed nonHDL values into ranges using the assumed total allowable errors for total cholesterol (9%) and high-density lipoprotein cholesterol (13%). Using a previously determined relationship between the hazard ratio and nonHDL, we calculated a range of hazard ratios for specified nonHDL concentrations affected by analytical error. Analytical error, within allowable limits, created a band of values of nonHDL, with a width spanning 30 to 70 mg/dL (0.78-1.81 mmol/L), depending on the cholesterol and high-density lipoprotein cholesterol concentrations. Hazard ratios ranged from 1.0 to 2.9, a 16% to 50% error. Increased bias widens this range and decreased bias narrows it. Error-transformed results produce a spread of values that straddle the various cutoffs for nonHDL. The range of the hazard ratio obscures the meaning of results, because the spread of ratios at different cutoffs overlap. The magnitude of the perceived hazard ratio error exceeds that for the allowable analytical error, and significantly impacts the perceived cardiovascular disease risk. Evaluating the error in the perceived severity (eg, hazard ratio) provides a new way to assess the impact of analytical error.

Daily home gardening improved survival for older people with mobility limitations: an 11-year follow-up study in Taiwan

PubMed Central

Lêng, Chhian Hūi; Wang, Jung-Der

2016-01-01

Aims To test the hypothesis that gardening is beneficial for survival after taking time-dependent comorbidities, mobility, and depression into account in a longitudinal middle-aged (50–64 years) and older (≥65 years) cohort in Taiwan. Methods The cohort contained 5,058 nationally sampled adults ≥50 years old from the Taiwan Longitudinal Study on Aging (1996–2007). Gardening was defined as growing flowers, gardening, or cultivating potted plants for pleasure with five different frequencies. We calculated hazard ratios for the mortality risks of gardening and adjusted the analysis for socioeconomic status, health behaviors and conditions, depression, mobility limitations, and comorbidities. Survival models also examined time-dependent effects and risks in each stratum contingent upon baseline mobility and depression. Sensitivity analyses used imputation methods for missing values. Results Daily home gardening was associated with a high survival rate (hazard ratio: 0.82; 95% confidence interval: 0.71–0.94). The benefits were robust for those with mobility limitations, but without depression at baseline (hazard ratio: 0.64, 95% confidence interval: 0.48–0.87) when adjusted for time-dependent comorbidities, mobility limitations, and depression. Chronic or relapsed depression weakened the protection of gardening. For those without mobility limitations and not depressed at baseline, gardening had no effect. Sensitivity analyses using different imputation methods yielded similar results and corroborated the hypothesis. Conclusion Daily gardening for pleasure was associated with reduced mortality for Taiwanese >50 years old with mobility limitations but without depression. PMID:27486315

Impaired fasting glucose, ancestry and waist-to-height ratio: main predictors of incident diagnosed diabetes in the Canary Islands.

PubMed

de León, A Cabrera; Coello, S Domínguez; González, D Almeida; Díaz, B Brito; Rodríguez, J C del Castillo; Hernández, A González; Aguirre-Jaime, A; Pérez, M del Cristo Rodríguez

2012-03-01

To estimate the incidence rate and risk factors for diabetes in the Canary Islands. A total of 5521 adults without diabetes were followed for a median of 3.5 years. Incident cases of diabetes were self-declared and validated in medical records. The following factors were assessed by Cox regression to estimate the hazard ratios for diabetes: impaired fasting glucose (5.6 mmol/l ≤ fasting glucose ≤ 6.9 mmol/l), BMI, waist-to-height ratio (≥ 0.55), insulin resistance (defined as triglycerides/HDL cholesterol ≥ 3), familial antecedents of diabetes, Canarian ancestry, smoking, alcohol intake, sedentary lifestyle, Mediterranean diet, social class and the metabolic syndrome. The incidence rate was 7.5/10(3) person-years (95% CI 6.4-8.8). The greatest risks were obtained for impaired fasting glucose (hazard ratio 2.6; 95% CI 1.8-3.8), Canarian ancestry (hazard ratio 1.9; 95% CI 1.0-3.4), waist-to-height ratio (hazard ratio 1.7; 95% CI 1.1-2.5), insulin resistance (hazard ratio 1.5; 95% CI 1.0-2.2) and paternal history of diabetes (hazard ratio 1.5; 95% CI 1.0-2.3). The metabolic syndrome (hazard ratio 1.9; 95% CI 1.3-2.8) and BMI ≥ 30 kg/m(2) (hazard ratio 1.7; 95% CI 1.0-2.7) were significant only when their effects were not adjusted for impaired fasting glucose and waist-to-height ratio, respectively. The incidence of diabetes in the Canary Islands is 1.5-fold higher than that in continental Spain and 1.7-fold higher than in the UK. The main predictors of diabetes were impaired fasting glucose, Canarian ancestry, waist-to-height ratio and insulin resistance. The metabolic syndrome predicted diabetes only when its effect was not adjusted for impaired fasting glucose. In individuals with Canarian ancestry, genetic susceptibility studies may be advisable. In order to propose preventive strategies, impaired fasting glucose, waist-to-height ratio and triglyceride/HDL cholesterol should be used to identify subjects with an increased risk of developing diabetes. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Correction of Selection Bias in Survey Data: Is the Statistical Cure Worse Than the Bias?

PubMed

Hanley, James A

2017-04-01

In previous articles in the American Journal of Epidemiology (Am J Epidemiol. 2013;177(5):431-442) and American Journal of Public Health (Am J Public Health. 2013;103(10):1895-1901), Masters et al. reported age-specific hazard ratios for the contrasts in mortality rates between obesity categories. They corrected the observed hazard ratios for selection bias caused by what they postulated was the nonrepresentativeness of the participants in the National Health Interview Study that increased with age, obesity, and ill health. However, it is possible that their regression approach to remove the alleged bias has not produced, and in general cannot produce, sensible hazard ratio estimates. First, we must consider how many nonparticipants there might have been in each category of obesity and of age at entry and how much higher the mortality rates would have to be in nonparticipants than in participants in these same categories. What plausible set of numerical values would convert the ("biased") decreasing-with-age hazard ratios seen in the data into the ("unbiased") increasing-with-age ratios that they computed? Can these values be encapsulated in (and can sensible values be recovered from) one additional internal variable in a regression model? Second, one must examine the age pattern of the hazard ratios that have been adjusted for selection. Without the correction, the hazard ratios are attenuated with increasing age. With it, the hazard ratios at older ages are considerably higher, but those at younger ages are well below one. Third, one must test whether the regression approach suggested by Masters et al. would correct the nonrepresentativeness that increased with age and ill health that I introduced into real and hypothetical data sets. I found that the approach did not recover the hazard ratio patterns present in the unselected data sets: the corrections overshot the target at older ages and undershot it at lower ages.

Estimation of age- and stage-specific Catalan breast cancer survival functions using US and Catalan survival data

PubMed Central

2009-01-01

Background During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On the other hand, we obtained detailed breast cancer survival functions that will be used for modeling the effect of screening and adjuvant treatments in Catalonia. PMID:19331670

[Relations of landslide and debris flow hazards to environmental factors].

PubMed

Zhang, Guo-ping; Xu, Jing; Bi, Bao-gui

2009-03-01

To clarify the relations of landslide and debris flow hazards to environmental factors is of significance to the prediction and evaluation of landslide and debris flow hazards. Base on the latitudinal and longitudinal information of 18431 landslide and debris flow hazards in China, and the 1 km x 1 km grid data of elevation, elevation difference, slope, slope aspect, vegetation type, and vegetation coverage, this paper analyzed the relations of landslide and debris flow hazards in this country to above-mentioned environmental factors by the analysis method of frequency ratio. The results showed that the landslide and debris flow hazards in China more occurred in lower elevation areas of the first and second transitional zones. When the elevation difference within a 1 km x 1 km grid cell was about 300 m and the slope was around 30 degree, there was the greatest possibility of the occurrence of landslide and debris hazards. Mountain forest land and slope cropland were the two land types the hazards most easily occurred. The occurrence frequency of the hazards was the highest when the vegetation coverage was about 80%-90%.

Changing tides: Adaptive monitoring, assessment, and management of pharmaceutical hazards in the environment through time.

PubMed

Gaw, Sally; Brooks, Bryan W

2016-04-01

Pharmaceuticals are ubiquitous contaminants in aquatic ecosystems. Adaptive monitoring, assessment, and management programs will be required to reduce the environmental hazards of pharmaceuticals of concern. Potentially underappreciated factors that drive the environmental dose of pharmaceuticals include regulatory approvals, marketing campaigns, pharmaceutical subsidies and reimbursement schemes, and societal acceptance. Sales data for 5 common antidepressants (duloxetine [Cymbalta], escitalopram [Lexapro], venlafaxine [Effexor], bupropion [Wellbutrin], and sertraline [Zoloft]) in the United States from 2004 to 2008 were modeled to explore how environmental hazards in aquatic ecosystems changed after patents were obtained or expired. Therapeutic hazard ratios for Effexor and Lexapro did not exceed 1; however, the therapeutic hazard ratio for Zoloft declined whereas the therapeutic hazard ratio for Cymbalta increased as a function of patent protection and sale patterns. These changes in therapeutic hazard ratios highlight the importance of considering current and future drivers of pharmaceutical use when prioritizing pharmaceuticals for water quality monitoring programs. When urban systems receiving discharges of environmental contaminants are examined, water quality efforts should identify, prioritize, and select target analytes presently in commerce for effluent monitoring and surveillance. © 2015 SETAC.

Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves.

PubMed

Guyot, Patricia; Ades, A E; Ouwens, Mario J N M; Welton, Nicky J

2012-02-01

The results of Randomized Controlled Trials (RCTs) on time-to-event outcomes that are usually reported are median time to events and Cox Hazard Ratio. These do not constitute the sufficient statistics required for meta-analysis or cost-effectiveness analysis, and their use in secondary analyses requires strong assumptions that may not have been adequately tested. In order to enhance the quality of secondary data analyses, we propose a method which derives from the published Kaplan Meier survival curves a close approximation to the original individual patient time-to-event data from which they were generated. We develop an algorithm that maps from digitised curves back to KM data by finding numerical solutions to the inverted KM equations, using where available information on number of events and numbers at risk. The reproducibility and accuracy of survival probabilities, median survival times and hazard ratios based on reconstructed KM data was assessed by comparing published statistics (survival probabilities, medians and hazard ratios) with statistics based on repeated reconstructions by multiple observers. The validation exercise established there was no material systematic error and that there was a high degree of reproducibility for all statistics. Accuracy was excellent for survival probabilities and medians, for hazard ratios reasonable accuracy can only be obtained if at least numbers at risk or total number of events are reported. The algorithm is a reliable tool for meta-analysis and cost-effectiveness analyses of RCTs reporting time-to-event data. It is recommended that all RCTs should report information on numbers at risk and total number of events alongside KM curves.

Dietary acrylamide intake and risk of breast cancer in the UK women's cohort

PubMed Central

Burley, V J; Greenwood, D C; Hepworth, S J; Fraser, L K; de Kok, T M; van Breda, S G; Kyrtopoulos, S A; Botsivali, M; Kleinjans, J; McKinney, P A; Cade, J E

2010-01-01

Background: No studies to date have demonstrated a clear association with breast cancer risk and dietary exposure to acrylamide. Methods: A 217-item food frequency questionnaire was used to estimate dietary acrylamide intake in 33 731 women aged 35–69 years from the UK Women's Cohort Study followed up for a median of 11 years. Results: In all, 1084 incident breast cancers occurred during follow-up. There was no evidence of an overall association between acrylamide intake and breast cancer (hazard ratio=1.08 per 10 μg day−1, 95% CI: 0.98–1.18, Ptrend=0.1). There was a suggestion of a possible weak positive association between dietary acrylamide intake and premenopausal breast cancer after adjustment for potential confounders (hazard ratio=1.2, 95% CI: 1.0–1.3, Ptrend=0.008). There was no suggestion of any association for postmenopausal breast cancer (hazard ratio=1.0, 95% CI: 0.9–1.1, Ptrend=0.99). Conclusions: There is no evidence of an association between dietary acrylamide intake and breast cancer. A weak association may exist with premenopausal breast cancer, but requires further investigation. PMID:20959829

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

PubMed Central

Wieder, Robert; Shafiq, Basit; Adam, Nabil

2016-01-01

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

A balanced hazard ratio for risk group evaluation from survival data.

PubMed

Branders, Samuel; Dupont, Pierre

2015-07-30

Common clinical studies assess the quality of prognostic factors, such as gene expression signatures, clinical variables or environmental factors, and cluster patients into various risk groups. Typical examples include cancer clinical trials where patients are clustered into high or low risk groups. Whenever applied to survival data analysis, such groups are intended to represent patients with similar survival odds and to select the most appropriate therapy accordingly. The relevance of such risk groups, and of the related prognostic factors, is typically assessed through the computation of a hazard ratio. We first stress three limitations of assessing risk groups through the hazard ratio: (1) it may promote the definition of arbitrarily unbalanced risk groups; (2) an apparently optimal group hazard ratio can be largely inconsistent with the p-value commonly associated to it; and (3) some marginal changes between risk group proportions may lead to highly different hazard ratio values. Those issues could lead to inappropriate comparisons between various prognostic factors. Next, we propose the balanced hazard ratio to solve those issues. This new performance metric keeps an intuitive interpretation and is as simple to compute. We also show how the balanced hazard ratio leads to a natural cut-off choice to define risk groups from continuous risk scores. The proposed methodology is validated through controlled experiments for which a prescribed cut-off value is defined by design. Further results are also reported on several cancer prognosis studies, and the proposed methodology could be applied more generally to assess the quality of any prognostic markers. Copyright © 2015 John Wiley & Sons, Ltd.

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

PubMed Central

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

2011-01-01

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

Daily home gardening improved survival for older people with mobility limitations: an 11-year follow-up study in Taiwan.

PubMed

Lêng, Chhian Hūi; Wang, Jung-Der

2016-01-01

To test the hypothesis that gardening is beneficial for survival after taking time-dependent comorbidities, mobility, and depression into account in a longitudinal middle-aged (50-64 years) and older (≥65 years) cohort in Taiwan. The cohort contained 5,058 nationally sampled adults ≥50 years old from the Taiwan Longitudinal Study on Aging (1996-2007). Gardening was defined as growing flowers, gardening, or cultivating potted plants for pleasure with five different frequencies. We calculated hazard ratios for the mortality risks of gardening and adjusted the analysis for socioeconomic status, health behaviors and conditions, depression, mobility limitations, and comorbidities. Survival models also examined time-dependent effects and risks in each stratum contingent upon baseline mobility and depression. Sensitivity analyses used imputation methods for missing values. Daily home gardening was associated with a high survival rate (hazard ratio: 0.82; 95% confidence interval: 0.71-0.94). The benefits were robust for those with mobility limitations, but without depression at baseline (hazard ratio: 0.64, 95% confidence interval: 0.48-0.87) when adjusted for time-dependent comorbidities, mobility limitations, and depression. Chronic or relapsed depression weakened the protection of gardening. For those without mobility limitations and not depressed at baseline, gardening had no effect. Sensitivity analyses using different imputation methods yielded similar results and corroborated the hypothesis. Daily gardening for pleasure was associated with reduced mortality for Taiwanese >50 years old with mobility limitations but without depression.

The Cox proportional Hazard model on duration of birth process

NASA Astrophysics Data System (ADS)

Wuryandari, Triastuti; Haryatmi Kartiko, Sri; Danardono

2018-05-01

The duration of birth process, which is measured from the birth sign until baby born, is one important factor to the whole outcome of delivery process. There is a method of birth process that given relaxing and gentle treatment to the mother caled as gentlebirth. Gentlebirth is a method of birth process that combines brain science, birth science and technology to empower positive birth without pain. However the effect of method to the duration of birth process is still need empirical investigations. Therefore, the objective of this paper is to analyze the duration of birth process using the appropriate statistical methods for durational data, survival data or time to event data. Since there are many variables or factor that may affect the duration, a regression model is considerated. The flexibility of the Cox Proportional Hazard Model in the sense that there is no distributional assumption required, makes the Cox Model as the appropriate model and method to analyze the duration birth process. It is concluded that the Gentlebirth method affects on duration of birth process, with Hazard Ratio of 2.073, showing that the duration of birth process with gentlebirth method is faster than the other method.

Survivorship analysis when cure is a possibility: a Monte Carlo study.

PubMed

Goldman, A I

1984-01-01

Parametric survivorship analyses of clinical trials commonly involves the assumption of a hazard function constant with time. When the empirical curve obviously levels off, one can modify the hazard function model by use of a Gompertz or Weibull distribution with hazard decreasing over time. Some cancer treatments are thought to cure some patients within a short time of initiation. Then, instead of all patients having the same hazard, decreasing over time, a biologically more appropriate model assumes that an unknown proportion (1 - pi) have constant high risk whereas the remaining proportion (pi) have essentially no risk. This paper discusses the maximum likelihood estimation of pi and the power curves of the likelihood ratio test. Monte Carlo studies provide results for a variety of simulated trials; empirical data illustrate the methods.

Correction of Selection Bias in Survey Data: Is the Statistical Cure Worse Than the Bias?

PubMed

Hanley, James A

2017-03-15

In previous articles in the American Journal of Epidemiology (Am J Epidemiol. 2013;177(5):431-442) and American Journal of Public Health (Am J Public Health. 2013;103(10):1895-1901), Masters et al. reported age-specific hazard ratios for the contrasts in mortality rates between obesity categories. They corrected the observed hazard ratios for selection bias caused by what they postulated was the nonrepresentativeness of the participants in the National Health Interview Study that increased with age, obesity, and ill health. However, it is possible that their regression approach to remove the alleged bias has not produced, and in general cannot produce, sensible hazard ratio estimates. First, one must consider how many nonparticipants there might have been in each category of obesity and of age at entry and how much higher the mortality rates would have to be in nonparticipants than in participants in these same categories. What plausible set of numerical values would convert the ("biased") decreasing-with-age hazard ratios seen in the data into the ("unbiased") increasing-with-age ratios that they computed? Can these values be encapsulated in (and can sensible values be recovered from) 1 additional internal variable in a regression model? Second, one must examine the age pattern of the hazard ratios that have been adjusted for selection. Without the correction, the hazard ratios are attenuated with increasing age. With it, the hazard ratios at older ages are considerably higher, but those at younger ages are well below 1. Third, one must test whether the regression approach suggested by Masters et al. would correct the nonrepresentativeness that increased with age and ill health that I introduced into real and hypothetical data sets. I found that the approach did not recover the hazard ratio patterns present in the unselected data sets: The corrections overshot the target at older ages and undershot it at lower ages. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

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

NASA Astrophysics Data System (ADS)

Fatekurohman, Mohamat; Nurmala, Nita; Anggraeni, Dian

2018-04-01

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

Suicide rates across income levels: Retrospective cohort data on 1 million participants collected between 2003 and 2013 in South Korea.

PubMed

Lee, Sang-Uk; Oh, In-Hwan; Jeon, Hong Jin; Roh, Sungwon

2017-06-01

The relation of income and socioeconomic status with suicide rates remains unclear. Most previous studies have focused on the relationship between suicide rates and macroeconomic factors (e.g., economic growth rate). Therefore, we aimed to identify the relationship between individuals' socioeconomic position and suicide risk. We analyzed suicide mortality rates across socioeconomic positions to identify potential trends using observational data on suicide mortality collected between January 2003 and December 2013 from 1,025,340 national health insurance enrollees. We followed the subjects for 123.5 months on average. Socioeconomic position was estimated using insurance premium levels. To examine the hazard ratios of suicide mortality in various socioeconomic positions, we used Cox proportional hazard models. We found that the hazard ratios of suicide showed an increasing trend as socioeconomic position decreased. After adjusting for gender, age, geographic location, and disability level, Medicaid recipients had the highest suicide hazard ratio (2.28; 95% CI, 1.87-2.77). Among the Medicaid recipients, men had higher hazard ratios than women (2.79; 95% CI, 2.17-3.59 vs. 1.71; 95% CI, 1.25-2.34). Hazard ratios also varied across age groups. The highest hazard ratio was found in the 40-59-year-old group (3.19; 95% CI, 2.31-4.43), whereas the lowest ratio was found in those 60 years and older (1.44; 95% CI, 1.09-1.87). Our results illuminate the relationship between socioeconomic position and suicide rates and can be used to design and implement future policies on suicide prevention. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Bias in Hazard Ratios Arising From Misclassification According to Self-Reported Weight and Height in Observational Studies of Body Mass Index and Mortality.

PubMed

Flegal, Katherine M; Kit, Brian K; Graubard, Barry I

2018-01-01

Misclassification of body mass index (BMI) categories arising from self-reported weight and height can bias hazard ratios in studies of BMI and mortality. We examined the effects on hazard ratios of such misclassification using national US survey data for 1976 through 2010 that had both measured and self-reported weight and height along with mortality follow-up for 48,763 adults and a subset of 17,405 healthy never-smokers. BMI was categorized as <22.5 (low), 22.5-24.9 (referent), 25.0-29.9 (overweight), 30.0-34.9 (class I obesity), and ≥35.0 (class II-III obesity). Misreporting at higher BMI categories tended to bias hazard ratios upwards for those categories, but that effect was augmented, counterbalanced, or even reversed by misreporting in other BMI categories, in particular those that affected the reference category. For example, among healthy male never-smokers, misclassifications affecting the overweight and the reference categories changed the hazard ratio for overweight from 0.85 with measured data to 1.24 with self-reported data. Both the magnitude and direction of bias varied according to the underlying hazard ratios in measured data, showing that findings on bias from one study should not be extrapolated to a study with different underlying hazard ratios. Because of misclassification effects, self-reported weight and height cannot reliably indicate the lowest-risk BMI category. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

The effect of inter-unit HLA matching in double umbilical cord blood transplantation for acute leukemia

PubMed Central

Brunstein, Claudio; Zhang, Mei-Jie; Barker, Juliet; St. Martin, Andrew; Bashey, Asad; de Lima, Marcos; Dehn, Jason; Hematti, Peiman; Perales, Miguel-Angel; Rocha, Vanderson; Territo, Mary; Weisdorf, Daniel; Eapen, Mary

2017-01-01

The effects of inter-unit HLA-match on early outcomes with regards to double cord blood transplantation have not been established. Therefore, we studied the effect of inter-unit HLA-mismatching on the outcomes of 449 patients with acute leukemia after double cord blood transplantation. Patients were divided into two groups: one group that included transplantations with inter-unit mismatch at 2 or less HLA-loci (n=381) and the other group with inter-unit mismatch at 3 or 4 HLA-loci (n=68). HLA-match considered low resolution matching at HLA-A and -B loci and allele-level at HLA-DRB1, the accepted standard for selecting units for double cord blood transplants. Patients’, disease, and transplant characteristics were similar in the two groups. We observed no effect of the degree of inter-unit HLA-mismatch on neutrophil (Hazard Ratio 1.27, P=0.11) or platelet (Hazard Ratio 0.1.13, P=0.42) recovery, acute graft-versus-host disease (Hazard Ratio 1.17, P=0.36), treatment-related mortality (Hazard Ratio 0.92, P=0.75), relapse (Hazard Ratio 1.18, P=0.49), treatment failure (Hazard Ratio 0.99, P=0.98), or overall survival (Hazard Ratio 0.98, P=0.91). There were no differences in the proportion of transplants with engraftment of both units by three months (5% after transplantation of units with inter-unit mismatch at ≤2 HLA-loci and 4% after transplantation of units with inter-unit mismatch at 3 or 4 HLA-loci). Our observations support the elimination of inter-unit HLA-mismatch criterion when selecting cord blood units in favor of optimizing selection based on individual unit characteristics. PMID:28126967

Adapting Surface Ground Motion Relations to Underground conditions: A case study for the Sudbury Neutrino Observatory in Sudbury, Ontario, Canada

NASA Astrophysics Data System (ADS)

Babaie Mahani, A.; Eaton, D. W.

2013-12-01

Ground Motion Prediction Equations (GMPEs) are widely used in Probabilistic Seismic Hazard Assessment (PSHA) to estimate ground-motion amplitudes at Earth's surface as a function of magnitude and distance. Certain applications, such as hazard assessment for caprock integrity in the case of underground storage of CO2, waste disposal sites, and underground pipelines, require subsurface estimates of ground motion; at present, such estimates depend upon theoretical modeling and simulations. The objective of this study is to derive correction factors for GMPEs to enable estimation of amplitudes in the subsurface. We use a semi-analytic approach along with finite-difference simulations of ground-motion amplitudes for surface and underground motions. Spectral ratios of underground to surface motions are used to calculate the correction factors. Two predictive methods are used. The first is a semi-analytic approach based on a quarter-wavelength method that is widely used for earthquake site-response investigations; the second is a numerical approach based on elastic finite-difference simulations of wave propagation. Both methods are evaluated using recordings of regional earthquakes by broadband seismometers installed at the surface and at depths of 1400 m and 2100 m in the Sudbury Neutrino Observatory, Canada. Overall, both methods provide a reasonable fit to the peaks and troughs observed in the ratios of real data. The finite-difference method, however, has the capability to simulate ground motion ratios more accurately than the semi-analytic approach.

Long-term Survival Outcomes by Smoking Status in Surgical and Nonsurgical Patients With Non-small Cell Lung Cancer

PubMed Central

Meguid, Robert A.; Hooker, Craig M.; Harris, James; Xu, Li; Westra, William H.; Sherwood, J. Timothy; Sussman, Marc; Cattaneo, Stephen M.; Shin, James; Cox, Solange; Christensen, Joani; Prints, Yelena; Yuan, Nance; Zhang, Jennifer; Yang, Stephen C.

2010-01-01

Background: Survival outcomes of never smokers with non-small cell lung cancer (NSCLC) who undergo surgery are poorly characterized. This investigation compared surgical outcomes of never and current smokers with NSCLC. Methods: This investigation was a single-institution retrospective study of never and current smokers with NSCLC from 1975 to 2004. From an analytic cohort of 4,546 patients with NSCLC, we identified 724 never smokers and 3,822 current smokers. Overall, 1,142 patients underwent surgery with curative intent. For survival analysis by smoking status, hazard ratios (HRs) were estimated using Cox proportional hazard modeling and then further adjusted by other covariates. Results: Never smokers were significantly more likely than current smokers to be women (P < .01), older (P < .01), and to have adenocarcinoma (P < .01) and bronchioloalveolar carcinoma (P < .01). No statistically significant differences existed in stage distribution at presentation for the analytic cohort (P = .35) or for the subgroup undergoing surgery (P = .24). The strongest risk factors of mortality among patients with NSCLC who underwent surgery were advanced stage (adjusted hazard ratio, 3.43; 95% CI, 2.32-5.07; P < .01) and elevated American Society of Anesthesiologists classification (adjusted hazard ratio, 2.18; 95% CI, 1.40-3.40; P < .01). The minor trend toward an elevated risk of death on univariate analysis for current vs never smokers in the surgically treated group (hazard ratio, 1.20; 95% CI, 0.98-1.46; P = .07) was completely eliminated when the model was adjusted for covariates (P = .97). Conclusions: Our findings suggest that smoking status at time of lung cancer diagnosis has little impact on the long-term survival of patients with NSCLC, especially after curative surgery. Despite different etiologies between lung cancer in never and current smokers the prognosis is equally dismal. PMID:20507946

The effect of sibutramine prescribing in routine clinical practice on cardiovascular outcomes: a cohort study in the United Kingdom

PubMed Central

Hayes, J F; Bhaskaran, K; Batterham, R; Smeeth, L; Douglas, I

2015-01-01

Background/Objectives: The marketing authorization for the weight loss drug sibutramine was suspended in 2010 following a major trial that showed increased rates of non-fatal myocardial infarction and cerebrovascular events in patients with pre-existing cardiovascular disease. In routine clinical practice, sibutramine was already contraindicated in patients with cardiovascular disease and so the relevance of these influential clinical trial findings to the ‘real World' population of patients receiving or eligible for the drug is questionable. We assessed rates of myocardial infarction and cerebrovascular events in a cohort of patients prescribed sibutramine or orlistat in the United Kingdom. Subjects/Methods: A cohort of patients prescribed weight loss medication was identified within the Clinical Practice Research Datalink. Rates of myocardial infarction or cerebrovascular event, and all-cause mortality were compared between patients prescribed sibutramine and similar patients prescribed orlistat, using both a multivariable Cox proportional hazard model, and propensity score-adjusted model. Possible effect modification by pre-existing cardiovascular disease and cardiovascular risk factors was assessed. Results: Patients prescribed sibutramine (N=23 927) appeared to have an elevated rate of myocardial infarction or cerebrovascular events compared with those taking orlistat (N=77 047; hazard ratio 1.69, 95% confidence interval 1.12–2.56). However, subgroup analysis showed the elevated rate was larger in those with pre-existing cardiovascular disease (hazard ratio 4.37, 95% confidence interval 2.21–8.64), compared with those with no cardiovascular disease (hazard ratio 1.52, 95% confidence interval 0.92–2.48, P-interaction=0.0076). All-cause mortality was not increased in those prescribed sibutramine (hazard ratio 0.67, 95% confidence interval 0.34–1.32). Conclusions: Sibutramine was associated with increased rates of acute cardiovascular events in people with pre-existing cardiovascular disease, but there was a low absolute risk in those without. Sibutramine's marketing authorization may have, therefore, been inappropriately withdrawn for people without cardiovascular disease. PMID:25971925

Long-term cardiovascular mortality after procedure-related or spontaneous myocardial infarction in patients with non-ST-segment elevation acute coronary syndrome: a collaborative analysis of individual patient data from the FRISC II, ICTUS, and RITA-3 trials (FIR).

PubMed

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

2012-01-31

The present study was designed to investigate the long-term prognostic impact of procedure-related and spontaneous myocardial infarction (MI) on cardiovascular mortality in patients with non-ST-elevation acute coronary syndrome. Five-year follow-up after procedure-related or spontaneous MI was investigated in the individual patient pooled data set of the FRISC-II (Fast Revascularization During Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Randomized Intervention Trial of Unstable Angina 3) non-ST-elevation acute coronary syndrome trials. The principal outcome was cardiovascular death up to 5 years of follow-up. Cumulative event rates were estimated by the Kaplan-Meier method; hazard ratios were calculated with time-dependent Cox proportional hazards models. Adjustments were made for the variables associated with long-term outcomes. Among the 5467 patients, 212 experienced a procedure-related MI within 6 months after enrollment. A spontaneous MI occurred in 236 patients within 6 months. The cumulative cardiovascular death rate was 5.2% in patients who had a procedure-related MI, comparable to that for patients without a procedure-related MI (hazard ratio 0.66; 95% confidence interval, 0.36-1.20, P=0.17). In patients who had a spontaneous MI within 6 months, the cumulative cardiovascular death rate was 22.2%, higher than for patients without a spontaneous MI (hazard ratio 4.52; 95% confidence interval, 3.37-6.06, P<0.001). These hazard ratios did not change materially after risk adjustments. Five-year follow-up of patients with non-ST-elevation acute coronary syndrome from the 3 trials showed no association between a procedure-related MI and long-term cardiovascular mortality. In contrast, there was a substantial increase in long-term mortality after a spontaneous MI.

Increased risk of pernicious anemia following scabies: a nationwide population-based matched-cohort study

PubMed Central

Chang, Fung-Wei; Chiu, Feng-Hsiang; Yeh, Chia-Lun; Huang, Chun-Fa; Chang, Shu-Ting; Lee, Hung-Chang; Chi, Hsin; Lin, Chien-Yu

2017-01-01

Objectives Scabies is a common and annoying disorder. Pernicious anemia (PA) is a serious disease which, when untreated, leads to death. Mounting evidence suggests that immune-mediated inflammatory processes play a role in the pathophysiology of both diseases. The relationship between these two diseases has not been investigated. We conducted this study to explore the potential relationship between scabies and PA. Materials and methods This nationwide, population-based study was conducted using the National Health Insurance Research Database of Taiwan. In total, 5,407 patients with scabies were identified as a study group and 20,089 matched patients were randomly selected as a control group. We tracked patients in both groups for a 7-year period to identify the incidence of PA. The demographic characteristics and comorbidities of the patients were analyzed, and Cox proportional hazards regression was used to calculate the hazard ratios for PA. Results Of the 25,496 patients in this study, 183 (0.7%) patients with newly diagnosed PA were identified during the 7-year follow-up period; 71 of 5,407 (1.3%) from the scabies group and 112 of 20,089 (0.6%) from the control group. Patients with scabies had a higher risk of subsequent PA, with a crude hazard ratio of 2.368. After adjusting for covariates, the adjusted hazard ratio was 1.51 (95% confidence interval: 1.09–2.08). Conclusion This study demonstrated an increased risk of PA (adjusted hazard ratio 1.51) among patients with scabies. Immune-mediated inflammatory processes may contribute to this association. Further studies are warranted to investigate the entire pathological mechanisms between these two diseases. Physicians should pay attention to patients with history of scabies presented with anemia. Further confirmative tests of PA may contribute to correct diagnosis and initiation of vitamin B12 supplement. PMID:29066901

[Application of three risk assessment models in occupational health risk assessment of dimethylformamide].

PubMed

Wu, Z J; Xu, B; Jiang, H; Zheng, M; Zhang, M; Zhao, W J; Cheng, J

2016-08-20

Objective: To investigate the application of United States Environmental Protection Agency (EPA) inhalation risk assessment model, Singapore semi-quantitative risk assessment model, and occupational hazards risk assessment index method in occupational health risk in enterprises using dimethylformamide (DMF) in a certain area in Jiangsu, China, and to put forward related risk control measures. Methods: The industries involving DMF exposure in Jiangsu province were chosen as the evaluation objects in 2013 and three risk assessment models were used in the evaluation. EPA inhalation risk assessment model: HQ=EC/RfC; Singapore semi-quantitative risk assessment model: Risk= (HR×ER) 1/2 ; Occupational hazards risk assessment index=2 Health effect level ×2 exposure ratio ×Operation condition level. Results: The results of hazard quotient (HQ>1) from EPA inhalation risk assessment model suggested that all the workshops (dry method, wet method and printing) and work positions (pasting, burdening, unreeling, rolling, assisting) were high risk. The results of Singapore semi-quantitative risk assessment model indicated that the workshop risk level of dry method, wet method and printing were 3.5 (high) , 3.5 (high) and 2.8 (general) , and position risk level of pasting, burdening, unreeling, rolling, assisting were 4 (high) , 4 (high) , 2.8 (general) , 2.8 (general) and 2.8 (general) . The results of occupational hazards risk assessment index method demonstrated that the position risk index of pasting, burdening, unreeling, rolling, assisting were 42 (high) , 33 (high) , 23 (middle) , 21 (middle) and 22 (middle) . The results of Singapore semi-quantitative risk assessment model and occupational hazards risk assessment index method were similar, while EPA inhalation risk assessment model indicated all the workshops and positions were high risk. Conclusion: The occupational hazards risk assessment index method fully considers health effects, exposure, and operating conditions and can comprehensively and accurately evaluate occupational health risk caused by DMF.

On the Interpretation of the Hazard Ratio and Communication of Survival Benefit.

PubMed

Sashegyi, Andreas; Ferry, David

2017-04-01

This brief communication will clarify the difference between a relative hazard and a relative risk. We highlight the importance of this difference, and demonstrate in practical terms that 1 minus the hazard ratio should not be interpreted as a risk reduction in the commonly understood sense of the term. This article aims to provide a better understanding of the type of risk reduction that a hazard ratio implies, thereby clarifying the intent in the communication among practitioners and researchers and establishing an accurate and realistic foundation for communicating with patients. The Oncologist 2017;22:484-486. © AlphaMed Press 2017.

Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia

PubMed Central

Fitzhugh, Courtney D.; Hsieh, Matthew M.; Allen, Darlene; Coles, Wynona A.; Seamon, Cassie; Ring, Michael; Zhao, Xiongce; Minniti, Caterina P.; Rodgers, Griffin P.; Schechter, Alan N.; Tisdale, John F.; Taylor, James G.

2015-01-01

Background Adults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea. Objectives We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010. Methods An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648. Results Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003–1.006, p<0.0.0001), kidney dysfunction (elevated creatinine, Hazard Ratio = 1.13, 95% CI 1.00–1.27, p = 0.043), and cardiopulmonary dysfunction (elevated tricuspid jet velocity on echocardiogram, Hazard Ratio = 2.22, 1.23–4.02, p = 0.0082). Sixty-six percent of subjects were treated with hydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34–0.97, p = 0.040). This effect was most pronounced in those taking the recommended dose of 15–35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17–0.73, p = 0.0050). Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004). While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively), other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels. Conclusions Our data suggest that adults should be treated with the maximum tolerated hydroxyurea dose, ideally before organ damage occurs. Prospective studies are indicated to validate these findings. PMID:26576059

Peritoneal dialysis in rural Australia

PubMed Central

2013-01-01

Background Australians living in rural areas have lower incidence rates of renal replacement therapy and poorer dialysis survival compared with urban dwellers. This study compares peritoneal dialysis (PD) patient characteristics and outcomes in rural and urban Australia. Methods Non-indigenous Australian adults who commenced chronic dialysis between 1 January 2000 and 31 December 2010 according to the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) were investigated. Each patient’s residence was classified according to the Australian Bureau of Statistics remote area index as major city (MC), inner regional (IR), outer regional (OR), or remote/very remote (REM). Results A total of 7657 patients underwent PD treatment during the study period. Patient distribution was 69.0% MC, 19.6% IR, 9.5% OR, and 1.8% REM. PD uptake increased with increasing remoteness. Compared with MC, sub-hazard ratios [95% confidence intervals] for commencing PD were 1.70 [1.61-1.79] IR, 2.01 [1.87-2.16] OR, and 2.60 [2.21-3.06] REM. During the first 6 months of PD, technique failure was less likely outside MC (sub-hazard ratio 0.47 [95% CI: 0.35-0.62], P < 0.001), but no difference was seen after 6 months (sub-hazard ratio 1.05 [95% CI: 0.84-1.32], P = 0.6). Technique failure due to technical (sub-hazard ratio 0.57 [95% CI: 0.38-0.84], P = 0.005) and non-medical causes (sub-hazard ratio 0.52 [95% CI: 0.31-0.87], P = 0.01) was less likely outside MC. Time to first peritonitis episode was not associated with remoteness (P = 0.8). Patient survival while on PD or within 90 days of stopping PD did not differ by region (P = 0.2). Conclusions PD uptake increases with increasing remoteness. In rural areas, PD technique failure is less likely during the first 6 months and time to first peritonitis is comparable to urban areas. Mortality while on PD does not differ by region. PD is therefore a good dialysis modality choice for rural patients in Australia. PMID:24359341

Circulating active serum calcium reduces the risk of hypertension.

PubMed

Kunutsor, Setor K; Laukkanen, Jari A

2017-02-01

Purpose Calcium, which is one the most abundant mineral elements in the body, has been suggested to be involved in blood pressure regulation. We aimed to assess the association of active serum calcium (which is the ionised and physiologically active form of serum calcium) with the future risk of hypertension. Methods The active serum calcium concentration was assessed at baseline in the Finnish Kuopio Ischemic Heart Disease population-based prospective cohort study of 1562 normotensive men aged 42-61 years at baseline. Cox proportional hazard models were used to assess the hazard ratios (95% confidence intervals (CIs)) for incident hypertension. Results During a median follow-up of 24.9 years, 247 men developed new-onset hypertension. Active serum calcium was inversely associated with incident hypertension in an approximately linear fashion. In age-adjusted analysis, the hazard ratio for hypertension per 1 standard deviation increase in active serum calcium was 0.86 (95% CI 0.76-0.98), which remained consistent after adjustment for several established risk factors and potential confounders 0.82 (0.71-0.94). In a comparison of extreme quintiles of active serum calcium levels, the corresponding adjusted hazard ratios were 0.59 (95% CI 0.39-0.90) and 0.54 (95% CI 0.35-0.82), respectively. Conclusion Active serum calcium is protective of future hypertension in a middle-aged male Caucasian population. Further research is needed to confirm these findings and help unravel the mechanistic pathways of calcium in the pathogenesis of hypertension.

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

PubMed

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

2014-08-26

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

Rare opportunistic (non-Candida, non-Cryptococcus) Yeast Bloodstream Infections in Patients with Cancer

PubMed Central

Chitasombat, Maria N.; Kofteridis, Diamantis P.; Jiang, Ying; Tarrand, Jeffrey; Lewis, Russell E.; Kontoyiannis, Dimitrios P.

2013-01-01

Background Rare opportunistic (non-Candida, non-Cryptococcus) yeast bloodstream infections (ROYBSIs) are rare, even in cancer patients. Methods We retrospectively reviewed all episodes of ROYBSIs occurring from 1998 to 2010 in our cancer center. Results Of 2984 blood cultures positive for Candida and non-Candida yeasts, 94 (3.1%) were positive for non-Candida yeasts, representing 41 ROYBSIs (incidence, 2.1 cases/100,000 patient-days). Catheter-associated fungemia occurred in 21 (51%) patients. Breakthrough ROYBSIs occurred in 20 (49%) patients. The yeast species distribution was Rhodotorula in 21 (51%) patients, Trichosporon in 8 (20%) patients, Saccharomyces cerevisiae in 8 (20%) patients, Geotrichum in 2 (5%) patients, Pichia anomala, and Malassezia furfur in 1 patient each. All tested Trichosporon, Geotrichum, and Pichia isolates were azole-susceptible, whereas the Rhodotorula isolates were mostly azole-resistant. We noted echinocandin nonsusceptibility (minimal inhibitory concentration ≥ 2 mg/L) in all but the S. cerevisiae isolates. Most of the isolates (28/33 [85%]) were susceptible to amphotericin B. The mortality rate in all patients at 30 days after ROYBSIs diagnosis was 34%. Multivariate survival analysis revealed increased risk of death in patients with S. cerevisiae infections (hazard ratio, 3.7), Geotrichum infections (hazard ratio, 111.3), or disseminated infections (hazard ratio, 33.4) and reduced risk in patients who had catheter removal (hazard ratio, 0.1). Conclusions ROYBSIs are uncommon in patients with cancer, and catheters are common sources of them. Half of the ROYBSIs occurred as breakthrough infections, and in vitro species-specific resistance to echinocandins and azoles was common. Disseminated infections resulted in the high mortality rate. PMID:22101079

Retrograde pyelography predicts retrograde ureteral stenting failure and reduces unnecessary stenting trials in patients with advanced non-urological malignant ureteral obstruction

PubMed Central

Kim, Sung Han; Park, Boram; Joo, Jungnam; Joung, Jae Young; Seo, Ho Kyung; Chung, Jinsoo; Lee, Kang Hyun

2017-01-01

Objective To evaluate predictive factors for retrograde ureteral stent failure in patients with non-urological malignant ureteral obstruction. Materials and methods Between 2005 and 2014, medical records of 284 malignant ureteral obstruction patients with 712 retrograde ureteral stent trials including 63 (22.2%) having bilateral malignant ureteral obstruction were retrospectively reviewed. Retrograde ureteral stent failure was defined as the inability to place ureteral stents by cystoscopy, recurrent stent obstruction within one month, or non-relief of azotemia within one week from the prior retrograde ureteral stent. The clinicopathological parameters and first retrograde pyelographic findings were analyzed to investigate the predictive factors for retrograde ureteral stent failure and conversion to percutaneous nephrostomy in multivariate analysis with a statistical significance of p < 0.05. Results Retrograde ureteral stent failure was detected in 14.1% of patients. The mean number of retrograde ureteral stent placements and indwelling duration of the ureteral stents were 2.5 ± 2.6 times and 8.6 ± 4.0 months, respectively. Multivariate analyses identified several specific RGP findings as significant predictive factors for retrograde ureteral stent failure (p < 0.05). The significant retrograde pyelographic findings included grade 4 hydronephrosis (hazard ratio 4.10, 95% confidence interval 1.39–12.09), irreversible ureteral kinking (hazard ratio 2.72, confidence interval 1.03–7.18), presence of bladder invasion (hazard ratio 4.78, confidence interval 1.81–12.63), and multiple lesions of ureteral stricture (hazard ratio 3.46, confidence interval 1.35–8.83) (p < 0.05). Conclusion Retrograde pyelography might prevent unnecessary and ineffective retrograde ureteral stent trials in patients with advanced non-urological malignant ureteral obstruction. PMID:28931043

Phenotype at diagnosis predicts recurrence rates in Crohn's disease

PubMed Central

Wolters, F L; Russel, M G; Sijbrandij, J; Ambergen, T; Odes, S; Riis, L; Langholz, E; Politi, P; Qasim, A; Koutroubakis, I; Tsianos, E; Vermeire, S; Freitas, J; van Zeijl, G; Hoie, O; Bernklev, T; Beltrami, M; Rodriguez, D; Stockbrügger, R W; Moum, B

2006-01-01

Background In Crohn's disease (CD), studies associating phenotype at diagnosis and subsequent disease activity are important for patient counselling and health care planning. Aims To calculate disease recurrence rates and to correlate these with phenotypic traits at diagnosis. Methods A prospectively assembled uniformly diagnosed European population based inception cohort of CD patients was classified according to the Vienna classification for disease phenotype at diagnosis. Surgical and non‐surgical recurrence rates throughout a 10 year follow up period were calculated. Multivariate analysis was performed to classify risk factors present at diagnosis for recurrent disease. Results A total of 358 were classified for phenotype at diagnosis, of whom 262 (73.2%) had a first recurrence and 113 patients (31.6%) a first surgical recurrence during the first 10 years after diagnosis. Patients with upper gastrointestinal disease at diagnosis had an excess risk of recurrence (hazard ratio 1.54 (95% confidence interval (CI) 1.13–2.10)) whereas age ⩾40 years at diagnosis was protective (hazard ratio 0.82 (95% CI 0.70–0.97)). Colonic disease was a protective characteristic for resective surgery (hazard ratio 0.38 (95% CI 0.21–0.69)). More frequent resective surgical recurrences were reported from Copenhagen (hazard ratio 3.23 (95% CI 1.32–7.89)). Conclusions A mild course of disease in terms of disease recurrence was observed in this European cohort. Phenotype at diagnosis had predictive value for disease recurrence with upper gastrointestinal disease being the most important positive predictor. A phenotypic North‐South gradient in CD may be present, illustrated by higher surgery risks in some of the Northern European centres. PMID:16361306

Risk of high-grade cervical dysplasia and cervical cancer in women with systemic lupus erythematosus receiving immunosuppressive drugs.

PubMed

Feldman, C H; Liu, J; Feldman, S; Solomon, D H; Kim, S C

2017-06-01

Objective Prior studies suggest an increased risk of cervical cancer among women with systemic lupus erythematosus. However, the relationship with immunosuppressive drugs is not well studied in US nationwide cohorts. We compared the risk of high-grade cervical dysplasia and cervical cancer among women with systemic lupus erythematosus who started immunosuppressive drugs versus hydroxychloroquine. Methods We identified systemic lupus erythematosus patients initiating immunosuppressive drugs or hydroxychloroquine using claims data from two US commercial health plans and Medicaid (2000-2012). We used a validated claims-based algorithm to identify high-grade cervical dysplasia or cervical cancer. To account for potential confounders, including demographic factors, comorbidities, medication use, HPV vaccination status, and health care utilization, immunosuppressive drugs and hydroxychloroquine initiators were 1:1 matched on the propensity score. We used inverse variance-weighted, fixed effect models to pool hazard ratios from the propensity score-matched Medicaid and commercial cohorts. Results We included 2451 matched pairs of immunosuppressive drugs and hydroxychloroquine new users in the commercial cohort and 7690 matched pairs in Medicaid. In the commercial cohort, there were 14 cases of cervical dysplasia or cervical cancer among immunosuppressive drugs users and five cases among hydroxychloroquine users (hazard ratio 2.47, 95% CI 0.89-6.85, hydroxychloroquine = ref). In Medicaid, there were 46 cases among immunosuppressive drugs users and 29 cases in hydroxychloroquine users (hazard ratio 1.24, 95% CI 0.78-1.98, hydroxychloroquine = ref). The pooled hazard ratio of immunosuppressive drugs was 1.40 (95% CI 0.92-2.12). Conclusion Among women with systemic lupus erythematosus, immunosuppressive drugs may be associated with a greater, albeit not statistically significant, risk of high-grade cervical dysplasia and cervical cancer compared to patients receiving hydroxychloroquine alone.

Imaging growth and isocitrate dehydrogenase 1 mutation are independent predictors for diffuse low-grade gliomas

PubMed Central

Gozé, Catherine; Blonski, Marie; Le Maistre, Guillaume; Bauchet, Luc; Dezamis, Edouard; Page, Philippe; Varlet, Pascale; Capelle, Laurent; Devaux, Bertrand; Taillandier, Luc; Duffau, Hugues; Pallud, Johan

2014-01-01

Background We explored whether spontaneous imaging tumor growth (estimated by the velocity of diametric expansion) and isocitrate dehydrogenase 1 (IDH1) mutation (estimated by IDH1 immunoexpression) were independent predictors of long-term outcomes of diffuse low-grade gliomas in adults. Methods One hundred thirty-one adult patients with newly diagnosed supratentorial diffuse low-grade gliomas were retrospectively studied. Results Isocitrate dehydrogenase 1 mutations were present in 107 patients. The mean spontaneous velocity of diametric expansion was 5.40 ± 5.46 mm/y. During follow-up (mean, 70 ± 54.7 mo), 56 patients presented a malignant transformation and 23 died. The median malignant progression-free survival and the overall survival were significantly longer in cases of slow velocity of diametric expansion (149 and 198 mo, respectively) than in cases of fast velocity of diametric expansion (46 and 82 mo; P < .001 and P < .001, respectively) and in cases with IDH1 mutation (100 and 198 mo, respectively) than in cases without IDH1 mutation (72 mo and not reached; P = .028 and P = .001, respectively). In multivariate analyses, spontaneous velocity of diametric expansion and IDH1 mutation were independent prognostic factors for malignant progression-free survival (P < .001; hazard ratio, 4.23; 95% CI, 1.81–9.40 and P = .019; hazard ratio, 2.39; 95% CI, 1.19–4.66, respectively) and for overall survival (P < .001; hazard ratio, 26.3; 95% CI, 5.42–185.2 and P = .007; hazard ratio, 17.89; 95% CI, 2.15–200.1, respectively). Conclusions The spontaneous velocity of diametric expansion and IDH1 mutation status are 2 independent prognostic values that should be obtained at the beginning of the management of diffuse low-grade gliomas in adults. PMID:24847087

Neighborhood socioeconomic status at the age of 40 years and ischemic stroke before the age of 50 years: A nationwide cohort study from Sweden.

PubMed

Carlsson, Axel C; Li, Xinjun; Holzmann, Martin J; Ärnlöv, Johan; Wändell, Per; Gasevic, Danijela; Sundquist, Jan; Sundquist, Kristina

2017-10-01

Objective We aimed to study the association between neighborhood socioeconomic status at the age of 40 years and risk of ischemic stroke before the age of 50 years. Methods All individuals in Sweden were included if their 40th birthday occurred between 1998 and 2010. National registers were used to categorize neighborhood socioeconomic status into high, middle, and low and to retrieve information on incident ischemic strokes. Hazard ratios and their 95% confidence intervals were estimated. Results A total of 1,153,451 adults (women 48.9%) were followed for a mean of 5.5 years (SD 3.5 years), during which 1777 (0.30%) strokes among men and 1374 (0.24%) strokes among women were recorded. After adjustment for sex, marital status, education level, immigrant status, region of residence, and neighborhood services, there was a lower risk of stroke in residents from high-socioeconomic status neighborhoods (hazard ratio 0.87, 95% confidence interval 0.78-0.96), and an increased risk of stroke in adults from low-socioeconomic status neighborhoods (hazard ratio 1.16, 95% confidence interval 1.06-1.27), compared to their counterparts living in middle-socioeconomic status neighborhoods. After further adjustment for hospital diagnoses of hypertension, diabetes, heart failure, and atrial fibrillation prior to the age of 40, the higher risk in neighborhoods with low socioeconomic status was attenuated, but remained significant (hazard ratio 1.12, 95% confidence interval 1.02-1.23). Conclusions In a nationwide study of individuals between 40 and 50 years, we found that the risk of ischemic stroke differed depending on neighborhood socioeconomic status, which calls for increased efforts to prevent cardiovascular diseases in low socioeconomic status neighborhoods.

Edoxaban versus warfarin in patients with atrial fibrillation.

PubMed

Giugliano, Robert P; Ruff, Christian T; Braunwald, Eugene; Murphy, Sabina A; Wiviott, Stephen D; Halperin, Jonathan L; Waldo, Albert L; Ezekowitz, Michael D; Weitz, Jeffrey I; Špinar, Jindřich; Ruzyllo, Witold; Ruda, Mikhail; Koretsune, Yukihiro; Betcher, Joshua; Shi, Minggao; Grip, Laura T; Patel, Shirali P; Patel, Indravadan; Hanyok, James J; Mercuri, Michele; Antman, Elliott M

2013-11-28

Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.).

Granulopoietic Growth Factor Secretion in Ovarian Carcinoma as a Mechanism for the Emergence of Immune Suppressive Myeloid Subsets

DTIC Science & Technology

2013-06-01

rising IL-6 levels portended worse overall survival (hazard ratio = 1.525, P = 0.02). The following is a synopsis of year-2, followed by a summary...6 with patient outcome. Specifically, our data indicated that rising IL-6 levels portended worse overall survival (hazard ratio = 1.525, P = 0.02...portended worse overall survival (hazard ratio = 1.525, P = 0.02). 3. Key Research Accomplishments: Altogether, we identified… • A significant

CREATION OF A MODEL TO PREDICT SURVIVAL IN PATIENTS WITH REFRACTORY COELIAC DISEASE USING A MULTINATIONAL REGISTRY

PubMed Central

Rubio-Tapia, Alberto; Malamut, Georgia; Verbeek, Wieke H.M.; van Wanrooij, Roy L.J.; Leffler, Daniel A.; Niveloni, Sonia I.; Arguelles-Grande, Carolina; Lahr, Brian D.; Zinsmeister, Alan R.; Murray, Joseph A.; Kelly, Ciaran P.; Bai, Julio C.; Green, Peter H.; Daum, Severin; Mulder, Chris J.J.; Cellier, Christophe

2016-01-01

Background Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. Aim To create a prognostic model to estimate survival of patients with refractory coeliac disease. Methods We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap re-sampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. Results The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across 7 centers (range of 11–63 cases per center). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval: 1.38, 3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% confidence interval: 1.22, 6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% confidence interval: 0.61, 0.85). A simple weighted 3-factor risk score was created to estimate 5-year survival. Conclusions Using data from a multinational registry and previously-reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up. PMID:27485029

How do outcomes compare between women and men living with HIV in Australia? An observational study.

PubMed

Giles, Michelle L; Zapata, Marin C; Wright, Stephen T; Petoumenos, Kathy; Grotowski, Miriam; Broom, Jennifer; Law, Matthew G; O'Connor, Catherine C

2016-04-01

Background Gender differences vary across geographical settings and are poorly reported in the literature. The aim of this study was to evaluate demographics and clinical characteristics of participants from the Australian HIV Observational Database (AHOD), and to explore any differences between females and males in the rate of new clinical outcomes, as well as initial immunological and virological response to antiretroviral therapy. Time to a new clinical end-point, all-cause mortality and/or AIDS illness was analysed using standard survival methods. Univariate and covariate adjusted Cox proportional hazard models were used to evaluate the time to plasma viral load suppression in all patients that initiated antiretroviral therapy (ART) and time to switching from a first-line ART to a second-line ART regimen. There was no significant difference between females and males for the hazard of all-cause mortality [adjusted hazard ratio: 0.98 (0.51, 1.55), P=0.67], new AIDS illness [adjusted hazard ratio: 0.75 (0.38, 1.48), P=0.41] or a composite end-point [adjusted hazard ratio: 0.74 (0.45, 1.21), P=0.23]. Incident rates of all-cause mortality were similar between females and males; 1.14 (0.61, 1.95) vs 1.28 (1.12, 1.45) per 100 person years. Virological response to ART was similar for females and males when measured as time to viral suppression and/or time to virological failure. This study supports current Australian HIV clinical care as providing equivalent standards of care for male and female HIV-positive patients. Future studies should compare ART-associated toxicity differences between ART-associated toxicity differences between men and women living with HIV in Australia.

Understanding differences in results from literature-based and individual patient meta-analyses: an example from meta-analyses of observational data.

PubMed

Poppe, Katrina K; Doughty, Robert N; Yu, Cheuk-Man; Quintana, Miguel; Møller, Jacob E; Klein, Allan L; Gamble, Greg D; Dini, Frank L; Whalley, Gillian A

2011-04-14

Meta-analyses are increasingly used to summarise observational data however a literature meta-analysis (LMA) may give different results to the corresponding individual patient meta-analysis (IPMA). This study compares the published results of equivalent LMAs and IPMAs, highlighting factors that can affect the results and therefore impact on clinical interpretation of meta-analyses. Univariate results from published meta-analyses of prospective observational outcome data were compared, as were the number of studies, patients and length of follow-up. The absolute difference in survival was calculated. The association between severe diastolic dysfunction (RFP) and death post acute myocardial infarction (AMI) and in chronic heart failure (HF) were used as clinical examples. The IPMA hazard ratio was lower that the LMA odds ratio: AMI hazard ratio 2.67 (95% confidence interval 2.23 to 3.20), odds ratio 4.10 (3.38 to 4.99); HF hazard ratio 2.42 (2.06 to 2.83), odds ratio 4.36 (3.60 to 5.04). The IPMAs contained most of the studies from the LMAs as well as additional unpublished data, and a longer length of follow-up was available in the IPMAs (AMI 3.7 vs 2.6 yr, HF 4.0 vs 1.5 yr). Restricting analysis to the same studies in both the LMA and IPMA resulted in a similar difference in effect sizes between methods to those found in the published analyses. The result of a meta-analysis is affected by whether study level or individual patient data have been used, and the variant of analysis that is required. Awareness and consideration of these factors is important for clinical interpretation of meta-analyses. Copyright © 2009 Elsevier B.V. All rights reserved.

Angiotensin Receptor Blockers and Risk of Prostate Cancer among United States Veterans

PubMed Central

Rao, Gowtham A; Mann, Joshua R.; Bottai, Matteo; Uemura, Hiroji; Burch, James B; Bennett, Charles Lee; Haddock, Kathlyn Sue; Hébert, James R

2013-01-01

Objectives To address concerns regarding increased risk of prostate cancer (PrCA) among Angiotensin Receptor Blocker users, we used national retrospective data from the Department of Veterans Affairs (VA) through the Veterans Affairs Informatics and Computing Infrastructure (VINCI). Methods We identified a total of 543,824 unique Veterans who were classified into either ARB treated or not-treated in 1:15 ratio. The two groups were balanced using inverse probability of treatment weights. A double-robust cox-proportional hazards model was used to estimate the hazard ratio for PrCA incidence. To evaluate for a potential Gleason score stage migration we conducted weighted Cochrane-Armitage test. Results Post weighting, the rates of PrCA in treated and not-treated groups were 506 (1.5%) and 8,269 (1.6%), respectively; representing a hazard ratio of (0.91, p-value 0.049). There was no significant difference in Gleason scores between the two groups. Conclusions We found a small, but statistically significant, reduction in the incidence of clinically detected PrCA among patients assigned to receive ARB with no countervailing effect on degree of differentiation (as indicated by Gleason score). Findings from this study support FDA’s recent conclusion that ARB use does not increase risk of incident PrCA. PMID:23686462

Choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios together with age assemble a significant Cox's proportional-hazards regression model for prediction of survival in high-grade gliomas

PubMed Central

Rios, Camilo; Motola-Kuba, Daniel; Matus-Santos, Juan; Villa, Antonio R; Moreno-Jimenez, Sergio

2016-01-01

Objective: A long-lasting concern has prevailed for the identification of predictive biomarkers for high-grade gliomas (HGGs) using MRI. However, a consensus of which imaging parameters assemble a significant survival model is still missing in the literature; we investigated the significant positive or negative contribution of several MR biomarkers in this tumour prognosis. Methods: A retrospective cohort of supratentorial HGGs [11 glioblastoma multiforme (GBM) and 17 anaplastic astrocytomas] included 28 patients (9 females and 19 males, respectively, with a mean age of 50.4 years, standard deviation: 16.28 years; range: 13–85 years). Oedema and viable tumour measurements were acquired using regions of interest in T1 weighted, T2 weighted, fluid-attenuated inversion recovery, apparent diffusion coefficient (ADC) and MR spectroscopy (MRS). We calculated Kaplan–Meier curves and obtained Cox's proportional hazards. Results: During the follow-up period (3–98 months), 17 deaths were recorded. The median survival time was 1.73 years (range, 0.287–8.947 years). Only 3 out of 20 covariates (choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios and age) showed significance in explaining the variability in the survival hazards model; score test: χ2 (3) = 9.098, p = 0.028. Conclusion: MRS metabolites overcome volumetric parameters of peritumoral oedema and viable tumour, as well as tumour region ADC measurements. Specific MRS ratios (Cho/Naa, L-L/Cr) might be considered in a regular follow-up for these tumours. Advances in knowledge: Cho/Naa ratio is the strongest survival predictor with a log-hazard function of 2.672 in GBM. Low levels of lipids–lactate/Cr ratio represent up to a 41.6% reduction in the risk of death in GBM. PMID:27626830

Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL)

PubMed Central

Preston, Ioana R.; Roberts, Kari E.; Miller, Dave P.; Sen, Ginny P.; Selej, Mona; Benton, Wade W.; Hill, Nicholas S.

2015-01-01

Background— Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH. Methods and Results— Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients. Conclusions— No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214. PMID:26510696

Suicide After Deliberate Self-Harm in Adolescents and Young Adults.

PubMed

Olfson, Mark; Wall, Melanie; Wang, Shuai; Crystal, Stephen; Bridge, Jeffrey A; Liu, Shang-Min; Blanco, Carlos

2018-04-01

Among adolescents and young adults with nonfatal self-harm, our objective is to identify risk factors for repeated nonfatal self-harm and suicide death over the following year. A national cohort of patients in the Medicaid program, aged 12 to 24 years ( n = 32 395), was followed for up to 1 year after self-harm. Cause of death information was obtained from the National Death Index. Repeat self-harm per 1000 person-years and suicide deaths per 100 000 person-years were determined. Hazard ratios (HRs) of repeat self-harm and suicide were estimated by Cox proportional hazard models. Suicide standardized mortality rate ratios were derived by comparison with demographically matched general population controls. The 12-month suicide standardized mortality rate ratio after self-harm was significantly higher for adolescents (46.0, 95% confidence interval [CI]: 29.9-67.9) than young adults (19.2, 95% CI: 12.7-28.0). Hazards of suicide after self-harm were significantly higher for American Indians and Alaskan natives than non-Hispanic white patients (HR: 4.69, 95% CI: 2.41-9.13) and for self-harm patients who initially used violent methods (HR: 18.04, 95% CI: 9.92-32.80), especially firearms (HR: 35.73, 95% CI: 15.42-82.79), compared with nonviolent self-harm methods (1.00, reference). The hazards of repeat self-harm were higher for female subjects than male subjects (HR: 1.25, 95% CI: 1.18-1.33); patients with personality disorders (HR: 1.55, 95% CI: 1.42-1.69); and patients whose initial self-harm was treated in an inpatient setting (HR: 1.65, 95% CI: 1.49-1.83) compared with an emergency department (HR: 0.62, 95% CI: 0.55-0.69) or outpatient (1.00, reference) setting. After nonfatal self-harm, adolescents and young adults were at markedly elevated risk of suicide. Among these high-risk patients, those who used violent self-harm methods, particularly firearms, were at especially high risk underscoring the importance of follow-up care to help ensure their safety. Copyright © 2018 by the American Academy of Pediatrics.

Impact of immortal person-time and time scale in comparative effectiveness research for medical devices: a case for implantable cardioverter-defibrillators.

PubMed

Mi, Xiaojuan; Hammill, Bradley G; Curtis, Lesley H; Greiner, Melissa A; Setoguchi, Soko

2013-08-01

To assess the extent of immortal time bias in estimating the clinical effectiveness of implantable cardioverter-defibrillators (ICDs) and the impact of methods of handling immortal time bias. Retrospective population-based cohort study of patients with heart failure in a national registry linked to Medicare claims (2003-2008). We compared three methods of handling immortal time bias, namely the Mantel-Byar (or time-dependent exposure assignment), the landmark, and the exclusion methods. Of the 5,226 study patients, 1,274 (24.4%) received ICD therapy. Total person-years in the Mantel-Byar method were 2,639, or 490 more than that in the exclusion method, reflecting potential immortal time in the study. The exclusion method yielded a hazard ratio of 0.71 (95% confidence interval [CI]: 0.63-0.80), which was 16% lower than the Mantel-Byar method (0.84; 95% CI: 0.75-0.95). The 120-day landmark method yielded similar results to those produced by the Mantel-Byar method (0.82; 95% CI: 0.72-0.95). Immortal time bias was detected in the ICD clinical effectiveness study, which might have led to substantial bias overestimating the treatment effect if handled by exclusion. When an appropriate landmark was selected, that method yielded similar hazard ratios to those obtained by the Mantel-Byar method, supporting the validity of the landmark method. Copyright © 2013 Elsevier Inc. All rights reserved.

Use of External Beam Radiotherapy Is Associated With Reduced Incidence of Second Primary Head and Neck Cancer: A SEER Database Analysis

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

Rusthoven, Kyle; Chen Changhu; Raben, David

2008-05-01

Purpose: Patients with head and neck cancer have a significant risk of developing a second primary cancer of the head and neck. We hypothesized that treatment with external beam radiotherapy (RT) might reduce this risk, because RT can eradicate occult foci of second head and neck cancer (HNCA). Methods and Materials: The data of patients with Surveillance, Epidemiology, and End Results Historic Stage A localized squamous cell carcinoma of the oral cavity, larynx, and pharynx were queried using the Surveillance, Epidemiology, and End Results database. For patients treated with or without RT, the incidence of second HNCA was determined andmore » compared using the log-rank method. Cox proportional hazards analysis was performed for each site, evaluating the influence of covariates on the risk of second HNCA. Results: Between 1973 and 1997, 27,985 patients were entered with localized HNCA. Of these patients, 44% had received RT and 56% had not. The 15-year incidence of second HNCA was 7.7% with RT vs. 10.5% without RT (hazard ratio 0.71, p <0.0001). The effect of RT was more profound in patients diagnosed between 1988 and 1997 (hazard ratio 0.53, p <0.0001) and those with pharynx primaries (hazard ratio 0.47, p <0.0001). On multivariate analysis, RT was associated with a reduced risk of second HNCA for pharynx (p <0.0001) and larynx (p = 0.04) tumors. For oral cavity primaries, RT was associated with an increased risk of second HNCA in patients treated before 1988 (p <0.001), but had no influence on patients treated between 1988 and 1997 (p = 0.91). Conclusion: For localized HNCA, RT is associated with a reduced incidence of second HNCA. These observations are consistent with the eradication of microscopic foci of second HNCA with external beam RT.« less

The Nursing Home Pneumonia Risk Index: A Simple, Valid MDS-Based Method of Identifying 6-Month Risk for Pneumonia and Mortality.

PubMed

Sloane, Philip D; Zimmerman, Sheryl; Ward, Kimberly; Reed, David; Preisser, John S; Weber, David J

2017-09-01

Pneumonia is the leading infectious cause of hospitalization and death for nursing home (NH) residents; however, diagnosis is often delayed because classic signs of infection are not present. We sought to identify NH residents at high risk for pneumonia, to identify persons to target for more intensive surveillance and preventive measures. Based on a literature review, we identified key risk factors for pneumonia and compiled them for use as prediction tool, limiting risk factors to those available on the Minimum Data Set (MDS). Next, we tested the tool's ability to predict 6-month pneumonia incidence and mortality rates in a sample of 674 residents from 7 NHs, evaluating it both as a continuous and a dichotomous variable, and applying both logistic regression and survival analysis to calculate estimates. NH Pneumonia Risk Index scores ranged from -1 to 6, with a mean of 2.1, a median of 2, and a mode of 2. For the outcome of pneumonia, a 1-point increase in the index was associated with a risk odds ratio of 1.26 (P = .038) or a hazard ratio of 1.24 (P = .037); using it as a dichotomous variable (≤2 vs ≥3), the corresponding figures were a risk odds ratio of 1.78 (P = .045) and a hazard ratio of 1.82 (P = .025). For the outcome of mortality, a 1-point increase in the NH Pneumonia Risk Index was associated with a risk odds ratio of 1.58 (P = .002) and a hazard ratio of 1.45 (P = .013); using the index as a dichotomous variable, the corresponding figures were a risk odds ratio of 3.71 (P < .001) and a hazard ratio of 3.29 (P = .001). The NH Pneumonia Risk Index can be used by NH staff to identify residents for whom to apply especially intensive preventive measures and surveillance. Because of its strong association with mortality, the index may also be valuable in care planning and discussion of advance directives. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Divorce and the Onset of Alcohol Use Disorder: A Swedish Population-Based Longitudinal Cohort and Co-Relative Study.

PubMed

Kendler, Kenneth S; Lönn, Sara Larsson; Salvatore, Jessica; Sundquist, Jan; Sundquist, Kristina

2017-05-01

The purpose of this study was to clarify the magnitude and nature of the relationship between divorce and risk for alcohol use disorder (AUD). In a population-based Swedish sample of married individuals (N=942,366), the authors examined the association between divorce or widowhood and risk for first registration for AUD. AUD was assessed using medical, criminal, and pharmacy registries. Divorce was strongly associated with risk for first AUD onset in both men (hazard ratio=5.98, 95% CI=5.65-6.33) and women (hazard ratio=7.29, 95% CI=6.72-7.91). The hazard ratio was estimated for AUD onset given divorce among discordant monozygotic twins to equal 3.45 and 3.62 in men and women, respectively. Divorce was also associated with an AUD recurrence in those with AUD registrations before marriage. Furthermore, widowhood increased risk for AUD in men (hazard ratio=3.85, 95% CI=2.81-5.28) and women (hazard ratio=4.10, 95% CI=2.98-5.64). Among divorced individuals, remarriage was associated with a large decline in AUD in both sexes (men: hazard ratio=0.56, 95% CI=0.52-0.64; women: hazard ratio=0.61, 95% CI=0.55-0.69). Divorce produced a greater increase in first AUD onset in those with a family history of AUD or with prior externalizing behaviors. Spousal loss through divorce or bereavement is associated with a large enduring increased AUD risk. This association likely reflects both causal and noncausal processes. That the AUD status of the spouse alters this association highlights the importance of spouse characteristics for the behavioral health consequences of spousal loss. The pronounced elevation in AUD risk following divorce or widowhood, and the protective effect of remarriage against subsequent AUD, speaks to the profound impact of marriage on problematic alcohol use.

Failure of anticoagulant thromboprophylaxis: risk factors in medical-surgical critically ill patients*.

PubMed

Lim, Wendy; Meade, Maureen; Lauzier, Francois; Zarychanski, Ryan; Mehta, Sangeeta; Lamontagne, Francois; Dodek, Peter; McIntyre, Lauralyn; Hall, Richard; Heels-Ansdell, Diane; Fowler, Robert; Pai, Menaka; Guyatt, Gordon; Crowther, Mark A; Warkentin, Theodore E; Devereaux, P J; Walter, Stephen D; Muscedere, John; Herridge, Margaret; Turgeon, Alexis F; Geerts, William; Finfer, Simon; Jacka, Michael; Berwanger, Otavio; Ostermann, Marlies; Qushmaq, Ismael; Friedrich, Jan O; Cook, Deborah J

2015-02-01

To identify risk factors for failure of anticoagulant thromboprophylaxis in critically ill patients in the ICU. Multivariable regression analysis of thrombosis predictors from a randomized thromboprophylaxis trial. Sixty-seven medical-surgical ICUs in six countries. Three thousand seven hundred forty-six medical-surgical critically ill patients. All patients received anticoagulant thromboprophylaxis with low-molecular-weight heparin or unfractionated heparin at standard doses. Independent predictors for venous thromboembolism, proximal leg deep vein thrombosis, and pulmonary embolism developing during critical illness were assessed. A total of 289 patients (7.7%) developed venous thromboembolism. Predictors of thromboprophylaxis failure as measured by development of venous thromboembolism included a personal or family history of venous thromboembolism (hazard ratio, 1.64; 95% CI, 1.03-2.59; p = 0.04) and body mass index (hazard ratio, 1.18 per 10-point increase; 95% CI, 1.04-1.35; p = 0.01). Increasing body mass index was also a predictor for developing proximal leg deep vein thrombosis (hazard ratio, 1.25; 95% CI, 1.06-1.46; p = 0.007), which occurred in 182 patients (4.9%). Pulmonary embolism occurred in 47 patients (1.3%) and was associated with body mass index (hazard ratio, 1.37; 95% CI, 1.02-1.83; p = 0.035) and vasopressor use (hazard ratio, 1.84; 95% CI, 1.01-3.35; p = 0.046). Low-molecular-weight heparin (in comparison to unfractionated heparin) thromboprophylaxis lowered pulmonary embolism risk (hazard ratio, 0.51; 95% CI, 0.27-0.95; p = 0.034) while statin use in the preceding week lowered the risk of proximal leg deep vein thrombosis (hazard ratio, 0.46; 95% CI, 0.27-0.77; p = 0.004). Failure of standard thromboprophylaxis using low-molecular-weight heparin or unfractionated heparin is more likely in ICU patients with elevated body mass index, those with a personal or family history of venous thromboembolism, and those receiving vasopressors. Alternate management or incremental risk reduction strategies may be needed in such patients.

Robust inference in discrete hazard models for randomized clinical trials.

PubMed

Nguyen, Vinh Q; Gillen, Daniel L

2012-10-01

Time-to-event data in which failures are only assessed at discrete time points are common in many clinical trials. Examples include oncology studies where events are observed through periodic screenings such as radiographic scans. When the survival endpoint is acknowledged to be discrete, common methods for the analysis of observed failure times include the discrete hazard models (e.g., the discrete-time proportional hazards and the continuation ratio model) and the proportional odds model. In this manuscript, we consider estimation of a marginal treatment effect in discrete hazard models where the constant treatment effect assumption is violated. We demonstrate that the estimator resulting from these discrete hazard models is consistent for a parameter that depends on the underlying censoring distribution. An estimator that removes the dependence on the censoring mechanism is proposed and its asymptotic distribution is derived. Basing inference on the proposed estimator allows for statistical inference that is scientifically meaningful and reproducible. Simulation is used to assess the performance of the presented methodology in finite samples.

Albuminuria and Rapid Loss of GFR and Risk of New Hip and Pelvic Fractures

PubMed Central

Gao, Peggy; Clase, Catherine M.; Mente, Andrew; Mann, Johannes F.E.; Sleight, Peter; Yusuf, Salim; Teo, Koon K.

2013-01-01

Summary Background and objectives The microvascular circulation plays an important role in bone health. This study examines whether albuminuria, a marker of renal microvascular disease, is associated with incident hip and pelvic fractures. Design, setting, participants, & measurements This study reanalyzed data from the Ongoing Telmisartan Alone and in combination with Ramipril Global End Point Trial/Telmisartan Randomized Assessment Study in Angiotensin-Converting Enzyme Intolerant Subjects with Cardiovascular Disease trials, which examined the impact of renin angiotensin system blockade on cardiovascular outcomes (n=28,601). Albuminuria was defined as an albumin-to-creatinine ratio≥30 mg/g (n=4597). Cox proportional hazards models were used to determine the association of albuminuria with fracture risk adjusted for known risk factors for fractures, estimated GFR, and rapid decline in estimated GFR (≥5%/yr). Results There were 276 hip and pelvic fractures during a mean of 4.6 years of follow-up. Participants with baseline albuminuria had a significantly increased risk of fracture compared with participants without albuminuria (unadjusted hazard ratio=1.62 [1.22, 2.15], P<0.001; adjusted hazard ratio=1.36 [1.01, 1.84], P=0.05). A dose-dependent relationship was observed, with macroalbuminuria having a large fracture risk (unadjusted hazard ratio=2.01 [1.21, 3.35], P=0.007; adjusted hazard ratio=1.71 [1.007, 2.91], P=0.05) and microalbuminuria associating with borderline or no statistical significance (unadjusted hazard ratio=1.52 [1.10, 2.09], P=0.01; adjusted hazard ratio=1.28 [0.92, 1.78], P=0.15). Estimated GFR was not a predictor of fracture in any model, but rapid loss of estimated GFR over the first 2 years of follow-up predicted subsequent fracture (adjusted hazard ratio=1.47 [1.05, 2.04], P=0.02). Conclusions Albuminuria, especially macroalbuminuria, and rapid decline of estimated GFR predict hip and pelvic fractures. These findings support a theoretical model of a relationship between underlying causes of microalbuminuria and bone disease. PMID:23184565

Effect of a structured diabetes education programme in primary care on hospitalizations and emergency department visits among people with Type 2 diabetes mellitus: results from the Patient Empowerment Programme.

PubMed

Wong, C K H; Wong, W C W; Wan, Y F; Chan, A K C; Chan, F W K; Lam, C L K

2016-10-01

To assess whether a structured diabetes education programme, the Patient Empowerment Programme, was associated with a lower rate of all-cause hospitalization and emergency department visits in a population-based cohort of patients with Type 2 diabetes mellitus in primary care. A cohort of 24 250 patients was evaluated using a linked administrative database during 2009-2013. We selected 12 125 patients with Type 2 diabetes who had at least one Patient Empowerment Programme session attendance. Patients who did not participate in the Patient Empowerment Programme were matched one-to-one with patients who did, using the propensity score method. Hospitalization events and emergency department visits were the events of interest. Cox proportional hazard and negative binomial regressions were performed to estimate the hazard ratios for the initial event, and incidence rate ratios for the number of events. During a median 30.5 months of follow-up, participants in the Patient Empowerment Programme had a lower incidence of an initial hospitalization event (22.1 vs 25.2%; hazard ratio 0.879; P < 0.001) and emergency department visit (40.5 vs 44%; hazard ratio 0.901; P < 0.001) than those who did not participate in the Patient Empowerment Programme. Participation in the Patient Empowerment Programme was associated with a significantly lower number of emergency department visits (incidence rate ratio 0.903; P < 0.001): 40.4 visits per 100 patients annually in those who did not participate in the Patient Empowerment Programme vs. 36.2 per 100 patients annually in those who did. There were significantly fewer hospitalization episodes (incidence rate ratio 0.854; P < 0.001): 20.0 hospitalizations per 100 patients annually in those who did not participate in the Patient Empowerment Programme vs. 16.9 hospitalizations per 100 patients annually in those who did. Among patients with Type 2 diabetes, the Patient Empowerment Programme was shown to be effective in delaying the initial hospitalization event and in reducing their frequency. © 2015 Diabetes UK.

Family environment, hobbies and habits as psychosocial predictors of survival for surgically treated patients with breast cancer.

PubMed

Tominaga, K; Andow, J; Koyama, Y; Numao, S; Kurokawa, E; Ojima, M; Nagai, M

1998-01-01

Many psychosocial factors have been reported to influence the duration of survival of breast cancer patients. We have studied how family members, hobbies and habits of the patients may alter their psychosocial status. Female patients with surgically treated breast cancer diagnosed between 1986 and 1995 at the Tochigi Cancer Center Hospital, who provided information on the above-mentioned factors, were used. Their subsequent physical status was followed up in the outpatients clinic. The Cox regression model was used to evaluate the relationship between the results of the factors examined and the duration of the patients' survival, adjusting for the patients' age, stage of disease at diagnosis and curability, as judged by the physician in charge after the treatment. The following factors were revealed to be significant with regard to the survival of surgically treated breast cancer patients: being a widow (hazard ratio 3.29; 95% confidence interval 1.32-8.20), having a hobby (hazard ratio 0.43; 95% confidence interval 0.23-0.82), number of hobbies (hazard ratio 0.64; 95% confidence interval 0.41-1.00), number of female children (hazard ratio 0.64; 95% confidence interval 0.42-0.98), smoker (hazard ratio 2.08; 95% confidence interval 1.02-4.26) and alcohol consumption (hazard ratio 0.10; 95% confidence interval 0.01-0.72). These results suggest that psychosocial factors, including the family environment, where patients receive emotional support from their spouse and children, hobbies and the patients' habits, may influence the duration of survival in surgically treated breast cancer patients.

Effect of Donor and Recipient Factors on Corneal Graft Rejection

PubMed Central

Stulting, R. Doyle; Sugar, Alan; Beck, Roy; Belin, Michael; Dontchev, Mariya; Feder, Robert S.; Gal, Robin L.; Holland, Edward J.; Kollman, Craig; Mannis, Mark J.; Price, Francis; Stark, Walter; Verdier, David D.

2014-01-01

Purpose To assess the relationship between donor and recipient factors and corneal allograft rejection in eyes that underwent penetrating keratoplasty (PK) in the Cornea Donor Study. Methods 1090 subjects undergoing corneal transplantation for a moderate risk condition (principally Fuchs’ dystrophy or pseudophakic corneal edema) were followed for up to 5 years. Associations of baseline recipient and donor factors with the occurrence of a probable or definite rejection event were assessed in univariate and multivariate proportional hazards models. Results Eyes with pseudophakic or aphakic corneal edema (N=369) were more likely to experience a rejection event than eyes with Fuchs’ dystrophy (N=676) (34% ± 6% versus 22% ± 4%; hazard ratio = 1.56; 95% confidence interval 1.21 to 2.03). Among eyes with Fuchs’dystrophy, a higher probability of a rejection event was observed in phakic post-transplant eyes compared with eyes that underwent cataract extraction with or without intraocular lens implantation during PK (29% vs. 19%; hazard ratio = 0.54; 95% confidence interval 0.36 to 0.82). Female recipients had a higher probability of a rejection event than males (29% vs. 21%; hazard ratio=1.42; 95% confidence interval 1.08 to 1.87), after controlling for the effect of preoperative diagnosis and lens status. Donor age and donor recipient ABO compatibility were not associated with rejection. Conclusions There was a substantially higher graft rejection rate in eyes with pseudophakic or aphakic corneal edema compared with eyes with Fuchs’ dystrophy. Female recipients were more likely to have a rejection event than males. Graft rejection was not associated with donor age. PMID:22488114

Clinical impact of targeted therapies in patients with metastatic clear-cell renal cell carcinoma

PubMed Central

Nerich, Virginie; Hugues, Marion; Paillard, Marie Justine; Borowski, Laëtitia; Nai, Thierry; Stein, Ulrich; Nguyen Tan Hon, Thierry; Montcuquet, Philippe; Maurina, Tristan; Mouillet, Guillaume; Kleinclauss, François; Pivot, Xavier; Limat, Samuel; Thiery-Vuillemin, Antoine

2014-01-01

Introduction The aim of this retrospective clinical study was to assess, in the context of the recent evolution of systemic therapies, the potential effect of targeted therapies on overall survival (OS) of patients with metastatic clear-cell renal cell carcinoma (mccRCC) in daily practice. Patients and methods All consecutive patients with histologically confirmed mccRCC who received systemic therapy between January 2000 and December 2010 in two oncology treatment centers in our Franche-Comté region in eastern France were included in the analysis. The primary end point was OS. The analysis of prognostic factors was performed using a two-step approach: univariate then multivariate analysis with a stepwise Cox proportional hazards regression model. Results For the entire cohort of 111 patients, the median OS was 17 months (95% confidence interval [CI]; 13–22 months) and the two-year OS was 39%. Three prognostic factors were independent predictors of long survival: prior nephrectomy (hazard ratio =0.38 [0.22–0.64], P<0.0001); systemic therapy by targeted therapy (hazard ratio =0.50 [0.31–0.80], P=0.005); and lack of liver metastasis (hazard ratio =0.43 [0.22–0.82], P=0.002). Median OS was 21 months [14–29 months] for patients who received at least one targeted therapy compared with 12 months [7–15 months] for patients who were treated only by immunotherapy agents (P=0.003). Conclusion Our results suggest that targeted therapies are associated with improved OS in comparison with cytokines, which is in line with other publications. PMID:24600236

Carpal Tunnel Syndrome Associated with Oral Bisphosphonates. A Population-Based Cohort Study

PubMed Central

Carvajal, Alfonso; Martín Arias, Luis H.; Sáinz, María; Escudero, Antonio; Fierro, Inmaculada; Sauzet, Odile; Cornelius, Victoria R.; Molokhia, Mariam

2016-01-01

Background Bisphosphonates are widely used to prevent osteoporotic fractures. Some severe musculoskeletal reactions have been described with this medication; among them, some cases of carpal tunnel syndrome. Thus, the aim of this study was to explore whether bisphosphonates may be associated with this syndrome. Methods A cohort study was conducted to compare exposed to unexposed women; the exposed group was that composed of women having received at least one prescription of an oral bisphosphonate. For the purpose, we used information from The Health Improvement Network (THIN) database. The outcome of interest was defined as those women diagnosed with carpal tunnel syndrome. A survival analysis was performed; the Cox proportional hazard model was used to calculate hazard ratios and 95% confidence intervals, and to adjust for identified confounding variables. Results Out of a sample of 59,475 women older than 51 years, 19,825 were treated with bisphosphonates during the period studied. No differences in age distribution or mean follow-up time were observed between the two groups in comparison. Overall, there were 572 women diagnosed with carpal tunnel syndrome, 242 (1.2%) in the group exposed to bisphosphonates, and 330 (0.8%) in the unexposed. An adjusted hazard ratio of developing carpal tunnel syndrome of 1.38 (95%CI, 1.15–1.64) was found for women exposed to bisphosphonates; no significant changes in the hazard ratios were found when considering different levels of bisphosphonate exposure. Conclusions An increased risk of carpal tunnel syndrome is associated with the use of bisphosphonates in postmenopausal women. PMID:26765346

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

Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

PubMed

Huang, Yen-Tsung; Yang, Hwai-I

2017-05-01

Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.

Immune reconstitution inflammatory syndrome associated with Kaposi sarcoma: higher incidence and mortality in Africa than in the UK.

PubMed

Letang, Emilio; Lewis, James J; Bower, Mark; Mosam, Anisa; Borok, Margareth; Campbell, Thomas B; Naniche, Denise; Newsom-Davis, Tom; Shaik, Fahmida; Fiorillo, Suzanne; Miro, Jose M; Schellenberg, David; Easterbrook, Philippa J

2013-06-19

To assess the incidence, predictors, and outcomes of Kaposi sarcoma-associated paradoxical immune reconstitution inflammatory syndrome (KS-IRIS) in antiretroviral therapy (ART)-naive HIV-infected patients with Kaposi sarcoma initiating ART in both well resourced and limited-resourced settings. Pooled analysis of three prospective cohorts of ART-naive HIV-infected patients with Kaposi sarcoma from sub-Saharan Africa (SSA) and one from the UK. KS-IRIS case definition was standardized across sites. Cox regression and Kaplan-Meier survival analysis were used to identify the incidence and predictors of KS-IRIS and Kaposi sarcoma-associated mortality. Fifty-eight of 417 (13.9%) eligible individuals experienced KS-IRIS with an incidence 2.5 times higher in the African vs. European cohorts (P=0.001). ART alone as initial Kaposi sarcoma treatment (hazard ratio 2.97, 95% confidence interval (CI) 1.02-8.69); T1 Kaposi sarcoma stage (hazard ratio 2.96, 95% CI 1.26-6.94); and plasma HIV-1 RNA more than 5 log₁₀ copies/ml (hazard ratio 2.14, 95% CI 1.25-3.67) independently predicted KS-IRIS at baseline. Detectable plasma Kaposi sarcoma-associated herpes virus (KSHV) DNA additionally predicted KS-IRIS among the 259 patients with KSHV DNA assessed (hazard ratio 2.98, 95% CI 1.23-7.19). Nineteen KS-IRIS patients died, all in SSA. Kaposi sarcoma mortality was 3.3-fold higher in Africa, and was predicted by KS-IRIS (hazard ratio 19.24, CI 7.62-48.58), lack of chemotherapy (hazard ratio 2.35, 95% CI 1.09-5.05), pre-ART CD4 cell count less than 200 cells/μl (hazard ratio 2.04, 95% CI 0.99-4.2), and detectable baseline KSHV DNA (hazard ratio 2.12, 95% CI 0.94-4.77). KS-IRIS incidence and mortality are higher in SSA than in the UK. This is largely explained by the more advanced Kaposi sarcoma disease and lower chemotherapy availability. KS-IRIS is a major contributor to Kaposi sarcoma-associated mortality in Africa. Our results support the need to increase awareness on KS-IRIS, encourage earlier presentation, referral and diagnosis of Kaposi sarcoma, and advocate on access to systemic chemotherapy in Africa. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins

Double inverse-weighted estimation of cumulative treatment effects under nonproportional hazards and dependent censoring.

PubMed

Schaubel, Douglas E; Wei, Guanghui

2011-03-01

In medical studies of time-to-event data, nonproportional hazards and dependent censoring are very common issues when estimating the treatment effect. A traditional method for dealing with time-dependent treatment effects is to model the time-dependence parametrically. Limitations of this approach include the difficulty to verify the correctness of the specified functional form and the fact that, in the presence of a treatment effect that varies over time, investigators are usually interested in the cumulative as opposed to instantaneous treatment effect. In many applications, censoring time is not independent of event time. Therefore, we propose methods for estimating the cumulative treatment effect in the presence of nonproportional hazards and dependent censoring. Three measures are proposed, including the ratio of cumulative hazards, relative risk, and difference in restricted mean lifetime. For each measure, we propose a double inverse-weighted estimator, constructed by first using inverse probability of treatment weighting (IPTW) to balance the treatment-specific covariate distributions, then using inverse probability of censoring weighting (IPCW) to overcome the dependent censoring. The proposed estimators are shown to be consistent and asymptotically normal. We study their finite-sample properties through simulation. The proposed methods are used to compare kidney wait-list mortality by race. © 2010, The International Biometric Society.

The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region.

PubMed

Woodward, M; Zhang, X; Barzi, F; Pan, W; Ueshima, H; Rodgers, A; MacMahon, S

2003-02-01

To provide reliable age- and region-specific estimates of the associations between diabetes and major cardiovascular diseases and death in populations from the Asia-Pacific region. Twenty-four cohort studies from Asia, Australia, and New Zealand (median follow-up, 5.4 years) provided individual participant data from 161,214 people (58% from Asia) of whom 4,873 had a history of diabetes at baseline. The associations of diabetes with the risks of coronary heart disease, stroke, and cause-specific mortality during follow-up were estimated using time-dependent Cox models, stratified by study cohort and sex and adjusted for age at risk. In all, 9,277 deaths occurred (3,635 from cardiovascular disease). The hazard ratio (95% CI) associated with diabetes was 1.97 (1.72-2.25) for fatal cardiovascular disease; there were similar hazard ratios for fatal coronary heart disease, fatal stroke, and composites of fatal and nonfatal outcomes. For all cardiovascular outcomes, hazard ratios were similar in Asian and non-Asian populations and in men and women, but were greater in younger than older individuals. For noncardiovascular death, the hazard ratio was 1.56 (1.38-1.77), with separately significant increases in the risks of death from renal disease, cancer, respiratory infections, and other infective causes. The hazard ratio for all-causes mortality was 1.68 (1.55-1.84), with similar ratios in Asian and non-Asian populations, but with significantly higher ratios in younger than older individuals. The relative effect of diabetes on the risks of cardiovascular disease and death in Asian populations is much the same as that in the largely Caucasian populations of Australia and New Zealand. Hazard ratios were severalfold greater in younger people than older people. The rapidly growing prevalence of diabetes in Asia heralds a large increase in the incidence of diabetes-related death in the coming decades.

Conjugated Equine Estrogens and Breast Cancer Risk in the Women’s Health Initiative Clinical Trial and Observational Study

PubMed Central

Prentice, Ross L.; Chlebowski, Rowan T.; Stefanick, Marcia L.; Manson, JoAnn E.; Langer, Robert D.; Pettinger, Mary; Hendrix, Susan L.; Hubbell, F. Allan; Kooperberg, Charles; Kuller, Lewis H.; Lane, Dorothy S.; McTiernan, Anne; O’Sullivan, Mary Jo; Rossouw, Jacques E.; Anderson, Garnet L.

2009-01-01

The Women’s Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogenalone preparations. In 1993–2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women’s Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index. PMID:18448442

Risk of Nodal Metastasis in Major Salivary Gland Adenoid Cystic Carcinoma.

PubMed

Megwalu, Uchechukwu C; Sirjani, Davud

2017-04-01

Objective To determine the risk of nodal metastasis, examine risk factors for nodal metastasis, and evaluate the impact of nodal metastasis on survival in patients with major salivary gland adenoid cystic carcinoma. Study Design Retrospective cohort study from a large population- based cancer database. Methods Data were extracted from the SEER 18 database (Surveillance, Epidemiology, and End Results) of the National Cancer Institute. The study cohort included 720 patients diagnosed with major salivary gland adenoid cystic carcinoma between 1988 and 2013. Results The overall rate of lymph node metastasis was 17%. T3 disease (odds ratio, 4.74) and T4 disease (odds ratio, 9.24) were associated with increased risk of nodal metastasis. Age, sex, and site were not associated with nodal metastasis. Nodal metastasis was associated with worse overall survival (hazard ratio, 2.56) and disease-specific survival (hazard ratio, 3.27), after adjusting for T stage, presence of distant metastasis, site, surgical resection, radiotherapy, neck dissection, age, sex, race, marital status, and year of diagnosis. Conclusion Major salivary gland adenoid cystic carcinoma carries significant risk of nodal metastasis. Advanced T stage is associated with increased risk of nodal metastasis. Nodal metastasis is associated with worse survival.

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

Age Variation in the Association Between Obesity and Mortality in Adults.

PubMed

Wang, Zhiqiang; Peng, Yang; Liu, Meina

2017-12-01

The aim of this study was to evaluate the previously reported finding that the association between obesity and mortality strengthens with increasing age. The data were derived from the National Health Interview Survey. Age-specific hazard ratios of mortality for grade 2/3 obesity (BMI ≥ 35 kg/m 2 ), relative to a BMI of 18.5 kg/m 2 to < 25 kg/m 2 , were calculated by using a flexible parametric survival model (240,184 white men) and Cox proportional hazard models (51,697 matched pairs). When the model included interaction terms between obesity and age at the survey, hazard ratios appeared to increase with age if those interaction terms were ignored by fixing age at the survey as a single value. However, when recalculated for adults with various ages at the survey, according to model specifications, hazard ratios were higher for younger adults than for older adults with the same follow-up duration. Based on matched data, hazard ratios were also higher for younger adults (2.14 [95% CI: 1.90-2.40] for those 40-49 years of age) than for older adults (1.22 [95%: 0.91-1.63] for those 90+ years of age). For any given follow-up duration, the association between obesity and mortality weakens with age. The previously reported strengthening of the obesity-mortality association with increasing age was caused by the failure to take all the model specifications into consideration when calculating adjusted hazard ratios. © 2017 The Obesity Society.

Radiophysical methods of diagnostics the Earth's ionosphere and the underlying earth's surface by remote sensing in the short-wave range of radio waves

NASA Astrophysics Data System (ADS)

Belov, S. Yu.; Belova, I. N.

2017-11-01

Monitoring of the earth's surface by remote sensing in the short-wave band can provide quick identification of some characteristics of natural systems. This band range allows one to diagnose subsurface aspects of the earth, as the scattering parameter is affected by irregularities in the dielectric permittivity of subsurface structures. This method based on the organization of the monitoring probe may detect changes in these environments, for example, to assess seismic hazard, hazardous natural phenomena such as earthquakes, as well as some man-made hazards and etc. The problem of measuring and accounting for the scattering power of the earth's surface in the short-range of radio waves is important for a number of purposes, such as diagnosing properties of the medium, which is of interest for geological, environmental studies. In this paper, we propose a new method for estimating the parameters of incoherent signal/noise ratio. The paper presents the results of comparison of the measurement method from the point of view of their admissible relative analytical errors. The new method is suggested. Analysis of analytical error of estimation of this parameter allowed to recommend new method instead of standard method. A comparative analysis and shows that the analytical (relative) accuracy of the determination of this parameter new method on the order exceeds the widely-used standard method.

Pathologic Complete Response Predicts Recurrence-Free Survival More Effectively by Cancer Subset: Results From the I-SPY 1 TRIAL—CALGB 150007/150012, ACRIN 6657

PubMed Central

Esserman, Laura J.; Berry, Donald A.; DeMichele, Angela; Carey, Lisa; Davis, Sarah E.; Buxton, Meredith; Hudis, Cliff; Gray, Joe W.; Perou, Charles; Yau, Christina; Livasy, Chad; Krontiras, Helen; Montgomery, Leslie; Tripathy, Debasish; Lehman, Constance; Liu, Minetta C.; Olopade, Olufunmilayo I.; Rugo, Hope S.; Carpenter, John T.; Dressler, Lynn; Chhieng, David; Singh, Baljit; Mies, Carolyn; Rabban, Joseph; Chen, Yunn-Yi; Giri, Dilip; van 't Veer, Laura; Hylton, Nola

2012-01-01

Purpose Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers. Patients and Methods Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets. Results In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets. Conclusion In this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology. PMID:22649152

Five-Year Outcomes with PCI Guided by Fractional Flow Reserve.

PubMed

Xaplanteris, Panagiotis; Fournier, Stephane; Pijls, Nico H J; Fearon, William F; Barbato, Emanuele; Tonino, Pim A L; Engstrøm, Thomas; Kääb, Stefan; Dambrink, Jan-Henk; Rioufol, Gilles; Toth, Gabor G; Piroth, Zsolt; Witt, Nils; Fröbert, Ole; Kala, Petr; Linke, Axel; Jagic, Nicola; Mates, Martin; Mavromatis, Kreton; Samady, Habib; Irimpen, Anand; Oldroyd, Keith; Campo, Gianluca; Rothenbühler, Martina; Jüni, Peter; De Bruyne, Bernard

2018-05-22

Background We hypothesized that fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease. Methods Among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization. Results A total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical-therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical-therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval [CI], 0.34 to 0.63; P<0.001). The difference was driven by urgent revascularizations, which occurred in 6.3% of the patients in the PCI group as compared with 21.1% of those in the medical-therapy group (hazard ratio, 0.27; 95% CI, 0.18 to 0.41). There were no significant differences between the PCI group and the medical-therapy group in the rates of death (5.1% and 5.2%, respectively; hazard ratio, 0.98; 95% CI, 0.55 to 1.75) or myocardial infarction (8.1% and 12.0%; hazard ratio, 0.66; 95% CI, 0.43 to 1.00). There was no significant difference in the rate of the primary end point between the PCI group and the registry cohort (13.9% and 15.7%, respectively; hazard ratio, 0.88; 95% CI, 0.55 to 1.39). Relief from angina was more pronounced after PCI than after medical therapy. Conclusions In patients with stable coronary artery disease, an initial FFR-guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone. Patients without hemodynamically significant stenoses had a favorable long-term outcome with medical therapy alone. (Funded by St. Jude Medical and others; FAME 2 ClinicalTrials.gov number, NCT01132495 .).

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

Matching on the Disease Risk Score in Comparative Effectiveness Research of New Treatments

PubMed Central

Wyss, Richard; Ellis, Alan R.; Brookhart, M. Alan; Funk, Michele Jonsson; Girman, Cynthia J.; Simpson, Ross J.; Stürmer, Til

2016-01-01

Purpose We use simulations and an empirical example to evaluate the performance of disease risk score (DRS) matching compared with propensity score (PS) matching when controlling large numbers of covariates in settings involving newly introduced treatments. Methods We simulated a dichotomous treatment, a dichotomous outcome, and 100 baseline covariates that included both continuous and dichotomous random variables. For the empirical example, we evaluated the comparative effectiveness of dabigatran versus warfarin in preventing combined ischemic stroke and all-cause mortality. We matched treatment groups on a historically estimated DRS and again on the PS. We controlled for a high-dimensional set of covariates using 20% and 1% samples of Medicare claims data from October 2010 through December 2012. Results In simulations, matching on the DRS versus the PS generally yielded matches for more treated individuals and improved precision of the effect estimate. For the empirical example, PS and DRS matching in the 20% sample resulted in similar hazard ratios (0.88 and 0.87) and standard errors (0.04 for both methods). In the 1% sample, PS matching resulted in matches for only 92.0% of the treated population and a hazard ratio and standard error of 0.89 and 0.19, respectively, while DRS matching resulted in matches for 98.5% and a hazard ratio and standard error of 0.85 and 0.16, respectively. Conclusions When PS distributions are separated, DRS matching can improve the precision of effect estimates and allow researchers to evaluate the treatment effect in a larger proportion of the treated population. However, accurately modeling the DRS can be challenging compared with the PS. PMID:26112690

Peripheral CD4+ naïve/memory ratio is an independent predictor of survival in non-small cell lung cancer

PubMed Central

Yang, Peng; Ma, Junhong; Yang, Xin; Li, Wei

2017-01-01

Background To investigate the clinical significance of naïve T cells, memory T cells, CD45RA+CD45RO+ T cells, and naïve/memory ratio in non-small cell lung cancer (NSCLC) patients. Methods Pretreatment peripheral blood samples from 76 NSCLC patients and 28 age- and sex-matched healthy volunteers were collected and tested for immune cells by flow cytometry. We compared the expression of these immune cells between patients and healthy controls and evaluated their predictive roles for survival in NSCLC by cox proportional hazards model. Results Decreased naïve CD4+ T cells, naïve CD8+ T cells, CD4+ naïve/memory ratios and CD4+CD45RA+CD45RO+ T cells, and increased memory CD4+ T cells, were observed in 76 NSCLC patients compared to healthy volunteers. Univariate analysis revealed that elevated CD4+ naïve/memory ratio correlated with prolonged progression-free survival (P=0.013). Multivariate analysis confirmed its predictive role with a hazard ratio of 0.35 (95% confidence interval, 0.19-0.75, P=0.012). Conclusions Peripheral CD4+ naïve/memory ratio can be used as a predictive biomarker in NSCLC patients and used to optimize personalized treatment strategies. PMID:29137371

Risk of infective endocarditis in patients with systemic lupus erythematosus in Taiwan: a nationwide population-based study.

PubMed

Chang, Y S; Chang, C C; Chen, Y H; Chen, W S; Chen, J H

2017-10-01

Objectives Patients with systemic lupus erythematosus are considered vulnerable to infective endocarditis and prophylactic antibiotics are recommended before an invasive dental procedure. However, the evidence is insufficient. This nationwide population-based study evaluated the risk and related factors of infective endocarditis in systemic lupus erythematosus. Methods We identified 12,102 systemic lupus erythematosus patients from the National Health Insurance research-oriented database, and compared the incidence rate of infective endocarditis with that among 48,408 non-systemic lupus erythematosus controls. A Cox multivariable proportional hazards model was employed to evaluate the risk of infective endocarditis in the systemic lupus erythematosus cohort. Results After a mean follow-up of more than six years, the systemic lupus erythematosus cohort had a significantly higher incidence rate of infective endocarditis (42.58 vs 4.32 per 100,000 person-years, incidence rate ratio = 9.86, p < 0.001) than that of the control cohort. By contrast, the older systemic lupus erythematosus cohort had lower risk (adjusted hazard ratio 11.64) than that of the younger-than-60-years systemic lupus erythematosus cohort (adjusted hazard ratio 15.82). Cox multivariate proportional hazards analysis revealed heart disease (hazard ratio = 5.71, p < 0.001), chronic kidney disease (hazard ratio = 2.98, p = 0.034), receiving a dental procedure within 30 days (hazard ratio = 36.80, p < 0.001), and intravenous steroid therapy within 30 days (hazard ratio = 39.59, p < 0.001) were independent risk factors for infective endocarditis in systemic lupus erythematosus patients. Conclusions A higher risk of infective endocarditis was observed in systemic lupus erythematosus patients. Risk factors for infective endocarditis in the systemic lupus erythematosus cohort included heart disease, chronic kidney disease, steroid pulse therapy within 30 days, and a recent invasive dental procedure within 30 days.

Prognostic impact of metastatic pattern in stage IV breast cancer at initial diagnosis.

PubMed

Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro; Romero, Alberto Omar; Machiavelli, Mario Raúl; Pérez, Juan Eduardo; Leone, Julieta; Leone, José Pablo

2017-02-01

To analyze the prognostic influence of metastatic pattern (MP) compared with other biologic and clinical factors in stage IV breast cancer at initial diagnosis (BCID) and evaluate factors associated with specific sites of metastases (SSM). We evaluated women with stage IV BCID with known metastatic sites, reported to the Surveillance, Epidemiology and End Results program from 2010 to 2013. MP was categorized as bone-only, visceral, bone and visceral (BV), and other. Univariate and multivariate analyses determined the effects of each variable on overall survival (OS). Logistic regression examined factors associated with SSM. We included 9143 patients. Bone represented 37.5% of patients, visceral 21.9%, BV 28.8%, and other 11.9%. Median OS by MP was as follows: bone 38 months, visceral 21 months, BV 19 months, and other 33 months (P < 0.0001). Univariate analysis showed that higher number of metastatic sites had worse prognosis. In multivariate analysis, older age (hazard ratio 1.9), black race (hazard ratio 1.17), grade 3/4 tumors (hazard ratio 1.6), triple-negative (hazard ratio 2.24), BV MP (hazard ratio 2.07), and unmarried patients (hazard ratio 1.25) had significantly shorter OS. As compared with HR+/HER2- tumors, triple-negative and HR-/HER2+ had higher odds of brain, liver, lung, and other metastases. HR+/HER2+ had higher odds of liver metastases. All three subtypes had lower odds of bone metastases. There were substantial differences in OS according to MP. Tumor subtypes have a clear influence among other factors on SSM. We identified several prognostic factors that could guide therapy selection in treatment naïve patients.

Associations of Dietary Long-Chain ω-3 Polyunsaturated Fatty Acids and Fish Consumption With Endometrial Cancer Risk in the Black Women's Health Study

PubMed Central

Brasky, Theodore M.; Sponholtz, Todd R.; Palmer, Julie R.; Rosenberg, Lynn; Ruiz-Narváez, Edward A.; Wise, Lauren A.

2016-01-01

Dietary long-chain (LC) ω-3 polyunsaturated fatty acids (PUFAs), which derive primarily from intakes of fatty fish, are thought to inhibit inflammation and de novo estrogen synthesis. This study prospectively examined the associations of dietary LC ω-3 PUFAs and fish with endometrial cancer risk in 47,602 African-American women living in the United States, aged 21–69 years at baseline in 1995, and followed them until 2013 (n = 282 cases). Multivariable-adjusted Cox regression models estimated hazard ratios and 95% confidence intervals for associations of LC ω-3 PUFA (quintiled) and fish (quartiled) intake with endometrial cancer risk, overall and by body mass index (BMI; weight (kg)/height (m)2). The hazard ratio for quintile 5 of total dietary LC ω-3 PUFAs versus quintile 1 was 0.79 (95% confidence interval (CI): 0.51, 1.24); there was no linear trend. Hazard ratios for the association were smaller among normal-weight women (BMI <25: hazard ratio (HR) = 0.53, 95% CI: 0.18, 1.58) than among overweight/obese women (BMI ≥25: HR = 0.88, 95% CI: 0.54, 1.43), but these differences were not statistically significant. Fish intake was also not associated with risk (quartile 4 vs. quartile 1: HR = 0.86, 95% CI: 0.56, 1.31). Again hazard ratios were smaller among normal-weight women (HR = 0.65) than among overweight/obese women (HR = 0.94). While compatible with no association, the hazard ratios observed among leaner African-American women are similar to those from recent prospective studies conducted in predominantly white populations. PMID:26755676

Social risk or genetic liability for psychosis? A study of children born in Sweden and reared by adoptive parents.

PubMed

Wicks, Susanne; Hjern, Anders; Dalman, Christina

2010-10-01

Recent studies suggest a role for social factors during childhood in the later development of schizophrenia. Since social conditions in childhood are closely related to parental psychiatric illness, there is a need to disentangle how genes and social environmental factors interact. A total of 13,163 children born in Sweden between 1955 and 1984 and reared in Swedish adoptive families were linked to the National Patient Register until 2006 regarding admissions for non-affective psychoses, including schizophrenia. Hazard ratios for nonaffective psychoses were estimated in relation to three indicators of socioeconomic position in childhood (household data of the rearing family obtained via linkage to the National Censuses of 1960-1985) and in relation to indicator of genetic liability (biological parental inpatient care for psychosis). In addition, the total Swedish-born population was investigated. Increased risks for nonaffective psychosis were found among adoptees (without biological parental history of psychosis) reared in families with disadvantaged socioeconomic position, which consisted of adoptive parental unemployment (hazard ratio=2.0), single-parent household (hazard ratio=1.2), and living in apartments (hazard ratio=1.3). The risk was also increased among persons with genetic liability for psychosis alone (hazard ratio=4.7). Among those exposed to both genetic liability and a disadvantaged socioeconomic situation in childhood, the risk was considerably higher (hazard ratio=15.0, 10.3, and 5.7 for parental unemployment, single-parent household, and apartment living, respectively). Analyses in the larger population supported these results. The results indicate that children reared in families with a disadvantaged socioeconomic position have an increased risk for psychosis. There was also some support for an interaction effect, suggesting that social disadvantage increases this risk more in children with genetic liability for psychosis.

Relationships between exercise, smoking habit and mortality in more than 100,000 adults.

PubMed

O'Donovan, Gary; Hamer, Mark; Stamatakis, Emmanuel

2017-04-15

Exercise is associated with reduced risks of all-cause, cardiovascular disease (CVD) and cancer mortality; however, the benefits in smokers and ex-smokers are unclear. The aim of this study was to investigate associations between exercise, smoking habit and mortality. Self-reported exercise and smoking, and all-cause, CVD and cancer mortality were assessed in 106,341 adults in the Health Survey for England and the Scottish Health Survey. There were 9149 deaths from all causes, 2839 from CVD and 2634 from cancer during 999,948 person-years of follow-up. Greater amounts of exercise were associated with decreases and greater amounts of smoking were associated with increases in the risks of mortality from all causes, CVD and cancer. There was no statistically significant evidence of biological interaction; rather, the relative risks of all-cause mortality were additive. In the subgroup of 26,768 ex-smokers, the all-cause mortality hazard ratio was 0.70 (95% CI 0.60, 0.80), the CVD mortality hazard ratio was 0.71 (0.55, 092) and the cancer mortality hazard ratio was 0.66 (0.52, 0.84) in those who exercised compared to those who did not. In the subgroup of 28,440 smokers, the all-cause mortality hazard ratio was 0.69 (0.57, 0.83), the CVD mortality hazard ratio was 0.66 (0.45, 0.96) and the cancer mortality hazard ratio was 0.69 (0.51, 0.94) in those who exercised compared to those who did not. Given that an outright ban is unlikely, this study is important because it suggests exercise reduces the risks of all-cause, CVD and cancer mortality by around 30% in smokers and ex-smokers. © 2017 UICC.

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

PubMed

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

2011-04-01

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

Incidence and predictors of suicide attempts in DSM-IV major depressive disorder: a five-year prospective study.

PubMed

Holma, K Mikael; Melartin, Tarja K; Haukka, Jari; Holma, Irina A K; Sokero, T Petteri; Isometsä, Erkki T

2010-07-01

Prospective long-term studies of risk factors for suicide attempts among patients with major depressive disorder have not investigated the course of illness and state at the time of the act. Therefore, the importance of state factors, particularly time spent in risk states, for overall risk remains unknown. In the Vantaa Depression Study, a longitudinal 5-year evaluation of psychiatric patients with major depressive disorder, prospective information on 249 patients (92.6%) was available. Time spent in depressive states and the timing of suicide attempts were investigated with life charts. During the follow-up assessment period, there were 106 suicide attempts per 1,018 patient-years. The incidence rate per 1,000 patient-years during major depressive episodes was 21-fold (N=332 [95% confidence interval [CI]=258.6-419.2]), and it was fourfold during partial remission (N=62 [95% CI=34.6-92.4]) compared with full remission (N=16 [95% CI=11.2-40.2]). In the Cox proportional hazards model, suicide attempts were predicted by the months spent in a major depressive episode (hazard ratio=7.74 [95% CI=3.40-17.6]) or in partial remission (hazard ratio=4.20 [95% CI=1.71-10.3]), history of suicide attempts (hazard ratio=4.39 [95% CI=1.78-10.8]), age (hazard ratio=0.94 [95% CI=0.91-0.98]), lack of a partner (hazard ratio=2.33 [95% CI=0.97-5.56]), and low perceived social support (hazard ratio=3.57 [95% CI=1.09-11.1]). The adjusted population attributable fraction of the time spent depressed for suicide attempts was 78%. Among patients with major depressive disorder, incidence of suicide attempts varies markedly depending on the level of depression, being highest during major depressive episodes. Although previous attempts and poor social support also indicate risk, the time spent depressed is likely the major factor determining overall long-term risk.

Survival analysis using inverse probability of treatment weighted methods based on the generalized propensity score.

PubMed

Sugihara, Masahiro

2010-01-01

In survival analysis, treatment effects are commonly evaluated based on survival curves and hazard ratios as causal treatment effects. In observational studies, these estimates may be biased due to confounding factors. The inverse probability of treatment weighted (IPTW) method based on the propensity score is one of the approaches utilized to adjust for confounding factors between binary treatment groups. As a generalization of this methodology, we developed an exact formula for an IPTW log-rank test based on the generalized propensity score for survival data. This makes it possible to compare the group differences of IPTW Kaplan-Meier estimators of survival curves using an IPTW log-rank test for multi-valued treatments. As causal treatment effects, the hazard ratio can be estimated using the IPTW approach. If the treatments correspond to ordered levels of a treatment, the proposed method can be easily extended to the analysis of treatment effect patterns with contrast statistics. In this paper, the proposed method is illustrated with data from the Kyushu Lipid Intervention Study (KLIS), which investigated the primary preventive effects of pravastatin on coronary heart disease (CHD). The results of the proposed method suggested that pravastatin treatment reduces the risk of CHD and that compliance to pravastatin treatment is important for the prevention of CHD. (c) 2009 John Wiley & Sons, Ltd.

Social vulnerability of rural households to flood hazards in western mountainous regions of Henan province, China

NASA Astrophysics Data System (ADS)

Liu, Delin; Li, Yue

2016-05-01

Evaluating social vulnerability is a crucial issue in risk and disaster management. In this study, a household social vulnerability index (HSVI) to flood hazards was developed and used to assess the social vulnerability of rural households in western mountainous regions of Henan province, China. Eight key indicators were identified using existing literature and discussions with experts from multiple disciplines and local farmers, and their weights were determined using principle component analysis (PCA) and an expert scoring method. The results showed that (1) the ratio of perennial work in other places, hazard-related training and illiteracy ratio (15+) were the most dominant factors of social vulnerability. (2) The numbers of high, moderate and low vulnerability households were 14, 64 and 16, respectively, which accounted for 14.9, 68.1 and 17.0 % of the total interviewed rural households, respectively. (3) The correlation coefficient between household social vulnerability scores and casualties in a storm flood in July 2010 was significant at 0.05 significance level (r = 0.748), which indicated that the selected indicators and their weights were valid. (4) Some mitigation strategies to reduce household social vulnerability to flood hazards were proposed, which included (1) improving the local residents' income and their disaster-related knowledge and evacuation skills, (2) developing emergency plans and carrying out emergency drills and training, (3) enhancing the accuracy of disaster monitoring and warning systems and (4) establishing a specific emergency management department and comprehensive rescue systems. These results can provide useful information for rural households and local governments to prepare, mitigate and respond to flood hazards, and the corresponding strategies can help local households to reduce their social vulnerability and improve their ability to resist flood hazard.

Asymptomatic Intradialytic Supraventricular Arrhythmias and Adverse Outcomes in Patients on Hemodialysis

PubMed Central

Pérez de Prado, Armando; López-Gómez, Juan M.; Quiroga, Borja; Goicoechea, Marian; García-Prieto, Ana; Torres, Esther; Reque, Javier; Luño, José

2016-01-01

Background and objectives Supraventricular arrhythmias are associated with high morbidity and mortality. Nevertheless, this condition has received little attention in patients on hemodialysis. The objective of this study was to analyze the incidence of intradialysis supraventricular arrhythmia and its long–term prognostic value. Design, setting, participants, & measurements We designed an observational and prospective study in a cohort of patients on hemodialysis with a 10-year follow-up period. All patients were recruited for study participation and were not recruited for clinical indications. The study population comprised 77 patients (42 men and 35 women; mean age =58±15 years old) with sinus rhythm monitored using a Holter electrocardiogram over six consecutive hemodialysis sessions at recruitment. Results Hypertension was present in 68.8% of patients, and diabetes was present in 29.9% of patients. Supraventricular arrhythmias were recorded in 38 patients (49.3%); all of these were short, asymptomatic, and self-limiting. Age (hazard ratio, 1.04 per year; 95% confidence interval, 1.00 to 1.08) and right atrial enlargement (hazard ratio, 4.29; 95% confidence interval, 1.30 to 14.09) were associated with supraventricular arrhythmia in the multivariate analysis. During a median follow-up of 40 months, 57 patients died, and cardiovascular disease was the main cause of death (52.6%). The variables associated with all-cause mortality in the Cox model were age (hazard ratio, 1.04 per year; 95% confidence interval, 1.00 to 1.08), C-reactive protein (hazard ratio, 1.04 per 1 mg/L; 95% confidence interval, 1.00 to 1.08), and supraventricular arrhythmia (hazard ratio, 3.21; 95% confidence interval, 1.29 to 7.96). Patients with supraventricular arrhythmia also had a higher risk of nonfatal cardiovascular events (hazard ratio, 4.32; 95% confidence interval, 2.11 to 8.83) and symptomatic atrial fibrillation during follow-up (hazard ratio, 17.19; 95% confidence interval, 2.03 to 145.15). Conclusions The incidence of intradialysis supraventricular arrhythmia was high in our hemodialysis study population. Supraventricular arrhythmias were short, asymptomatic, and self-limiting, and although silent, these arrhythmias were independently associated with mortality and cardiovascular events. PMID:27697781

Asymptomatic Intradialytic Supraventricular Arrhythmias and Adverse Outcomes in Patients on Hemodialysis.

PubMed

Verde, Eduardo; Pérez de Prado, Armando; López-Gómez, Juan M; Quiroga, Borja; Goicoechea, Marian; García-Prieto, Ana; Torres, Esther; Reque, Javier; Luño, José

2016-12-07

Supraventricular arrhythmias are associated with high morbidity and mortality. Nevertheless, this condition has received little attention in patients on hemodialysis. The objective of this study was to analyze the incidence of intradialysis supraventricular arrhythmia and its long-term prognostic value. We designed an observational and prospective study in a cohort of patients on hemodialysis with a 10-year follow-up period. All patients were recruited for study participation and were not recruited for clinical indications. The study population comprised 77 patients (42 men and 35 women; mean age =58±15 years old) with sinus rhythm monitored using a Holter electrocardiogram over six consecutive hemodialysis sessions at recruitment. Hypertension was present in 68.8% of patients, and diabetes was present in 29.9% of patients. Supraventricular arrhythmias were recorded in 38 patients (49.3%); all of these were short, asymptomatic, and self-limiting. Age (hazard ratio, 1.04 per year; 95% confidence interval, 1.00 to 1.08) and right atrial enlargement (hazard ratio, 4.29; 95% confidence interval, 1.30 to 14.09) were associated with supraventricular arrhythmia in the multivariate analysis. During a median follow-up of 40 months, 57 patients died, and cardiovascular disease was the main cause of death (52.6%). The variables associated with all-cause mortality in the Cox model were age (hazard ratio, 1.04 per year; 95% confidence interval, 1.00 to 1.08), C-reactive protein (hazard ratio, 1.04 per 1 mg/L; 95% confidence interval, 1.00 to 1.08), and supraventricular arrhythmia (hazard ratio, 3.21; 95% confidence interval, 1.29 to 7.96). Patients with supraventricular arrhythmia also had a higher risk of nonfatal cardiovascular events (hazard ratio, 4.32; 95% confidence interval, 2.11 to 8.83) and symptomatic atrial fibrillation during follow-up (hazard ratio, 17.19; 95% confidence interval, 2.03 to 145.15). The incidence of intradialysis supraventricular arrhythmia was high in our hemodialysis study population. Supraventricular arrhythmias were short, asymptomatic, and self-limiting, and although silent, these arrhythmias were independently associated with mortality and cardiovascular events. Copyright © 2016 by the American Society of Nephrology.

Stereotactic Radiosurgery for the Treatment of Primary and Metastatic Spinal Sarcomas

PubMed Central

Balagamwala, Ehsan H.; Angelov, Lilyana; Suh, John H.; Djemil, Toufik; Magnelli, Anthony; Qi, Peng; Zhuang, Tingliang; Godley, Andrew

2016-01-01

Purpose: Despite advancements in local and systemic therapy, metastasis remains common in the natural history of sarcomas. Unfortunately, such metastases are the most significant source of morbidity and mortality in this heterogeneous disease. As a classically radioresistant histology, stereotactic radiosurgery has emerged to control spinal sarcomas and provide palliation. However, there is a lack of data regarding pain relief and relapse following stereotactic radiosurgery. Methods: We queried a retrospective institutional database of patients who underwent spine stereotactic radiosurgery for primary and metastatic sarcomas. The primary outcome was pain relief following stereotactic radiosurgery. Secondary outcomes included progression of pain, radiographic failure, and development of toxicities following treatment. Results: Forty treatment sites were eligible for inclusion; the median prescription dose was 16 Gy in a single fraction. Median time to radiographic failure was 14 months. At 6 and 12 months, radiographic control was 63% and 51%, respectively. Among patients presenting with pain, median time to pain relief was 1 month. Actuarial pain relief at 6 months was 82%. Median time to pain progression was 10 months; at 12 months, actuarial pain progression was 51%. Following multivariate analysis, presence of neurologic deficit at consult (hazard ratio: 2.48, P < .01) and presence of extraspinal bone metastases (hazard ratio: 2.83, P < .01) were associated with pain relief. Greater pain at consult (hazard ratio: 1.92, P < .01), prior radiotherapy (hazard ratio: 4.65, P = .02), and greater number of irradiated vertebral levels were associated with pain progression. Conclusions: Local treatment of spinal sarcomas has remained a challenge for decades, with poor rates of local control and limited pain relief following conventional radiotherapy. In this series, pain relief was achieved in 82% of treatments at 6 months, with half of patients experiencing pain progression by 12 months. Given minimal toxicity and suboptimal pain control at 12 months, dose escalation beyond 16 Gy is warranted. PMID:27074915

Factors associated with survival among patients with AIDS-related primary central nervous system lymphoma

PubMed Central

Uldrick, Thomas S.; Pipkin, Sharon; Scheer, Susan; Hessol, Nancy A.

2014-01-01

Objective AIDS-related primary central nervous system lymphoma (AR-PCNSL) has a poor prognosis. Improved understanding of specific patient, infectious, diagnostic, and treatment-related factors that affect overall survival (OS) are required to improve outcomes. Design Population-based registry linkage study. Methods Adult cases from the San Francisco AIDS registry (1990–2000) were matched with the California Cancer Registry (1985–2002) to ascertain AR-PCNSL data. Survival time was assessed through 31 December 2007. Risk factors and temporal trends for death were measured using two-sided Kaplan–Meier and Cox analyses. Results Two hundred and seven AR-PCNSL patients were identified: 68% were white, 20% Hispanic, 10% African–American, and 2% Asian. Nineteen percent of patients had central nervous system (CNS) opportunistic infections diagnosed prior to AR-PCNSL. Fifty seven percent of patients received radiation and/or chemotherapy and 12% used HAART prior to or within 30 days of AR-PCSNL diagnosis. One hundred and ninety-nine patients died (34 deaths/100 person-years). In adjusted analysis, prior CNS opportunistic infections diagnosis increased risk of death (hazard ratio 1.9, P = 0.0006) whereas radiation and/or chemotherapy decreased risk (hazard ratio 0.6, P <0.0001). AR-PCNSL diagnosis 1999–2002 had a lower mortality risk (hazard ratio = 0.4, P = 0.02) compared to 1990–1995. African–Americans had an increased risk of death compared to whites or Asians (hazard ratio = 2.0, P = 0.007). Conclusion OS among AR-PCSNL patients improved over time but remains poor, especially among African–Americans. Prospective evaluation of curative therapy in AR-PCNSL is urgently needed. Accurate diagnosis of CNS mass lesions in patients with AIDS is required and for those with AR-PCNSL, antiretroviral therapy with concomitant AR-PCNSL therapy, and antimicrobial supportive care may improve OS. PMID:24076659

Percentage of Cancer Volume in Biopsy Cores Is Prognostic for Prostate Cancer Death and Overall Survival in Patients Treated With Dose-Escalated External Beam Radiotherapy

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

Vance, Sean M.; Stenmark, Matthew H.; Blas, Kevin

2012-07-01

Purpose: To investigate the prognostic utility of the percentage of cancer volume (PCV) in needle biopsy specimens for prostate cancer patients treated with dose-escalated external beam radiotherapy. Methods and Materials: The outcomes were analyzed for 599 men treated for localized prostate cancer with external beam radiotherapy to a minimal planning target volume dose of 75 Gy (range, 75-79.2). We assessed the effect of PCV and the pretreatment and treatment-related factors on the freedom from biochemical failure, freedom from metastasis, cause-specific survival, and overall survival. Results: The median number of biopsy cores was 7 (interquartile range, 6-12), median PCV was 10%more » (interquartile range, 2.5-25%), and median follow-up was 62 months. The PCV correlated with the National Comprehensive Cancer Network risk group and individual risk features, including T stage, prostate-specific antigen level, Gleason score, and percentage of positive biopsy cores. On log-rank analysis, the PCV stratified by quartile was prognostic for all endpoints, including overall survival. In addition, the PCV was a stronger prognostic factor than the percentage of positive biopsy cores when the two metrics were analyzed together. On multivariate analysis, the PCV predicted a worse outcome for all endpoints, including freedom from biochemical failure, (hazard ratio, 1.9; p = .0035), freedom from metastasis (hazard ratio, 1.7, p = .09), cause-specific survival (hazard ratio, 3.9, p = .014), and overall survival (hazard ratio, 1.8, p = .02). Conclusions: For patients treated with dose-escalated external beam radiotherapy, the volume of cancer in the biopsy specimen adds prognostic value for clinically relevant endpoints, particularly in intermediate- and high-risk patients. Although the PCV determination is more arduous than the percentage of positive biopsy cores, it provides superior risk stratification.« less

Association of baseline level of physical activity and its temporal changes with incident hypertension and diabetes mellitus.

PubMed

Lee, Jong-Young; Ryu, Seungho; Sung, Ki-Chul

2018-01-01

Background The association between baseline and temporal changes in physical activity and incident hypertension or diabetes mellitus in initially non-hypertensive or non-diabetic subjects is rarely known. Methods Among individuals who underwent consecutive comprehensive health screenings, their physical activity level was measured using a self-reported international physical activity questionnaire. First, subjects were classified into four categories: no regular physical activity with a sedentary lifestyle; minimal physical activity (<75 min/week); insufficient physical activity (≥75 min but <150 min/week); and sufficient physical activity (≥150 min/week). Second, subjects were sub-grouped, based on temporal changes in physical activity level between baseline and consecutive follow-up: increase, no change, and decrease. Results Finally, among 174,314 subjects (mean age 36.7 ± 6.9 years), 5544 (3.18%) and 21,276 (12.2%) developed incident diabetes mellitus and arterial hypertension, respectively. After a multivariate adjustment, sufficient baseline physical activity was associated with significantly lower risk for incident hypertension (hazard ratio 0.89; 95% confidence interval (CI) 0.81 to 0.97), but the difference was not significant, and showed a lower trend in diabetes mellitus incidence (hazard ratio 0.87; 95% CI 0.69 to 1.04) in reference to no regular physical activity group. Regardless of the baseline physical activity level, subjects with a temporal increase in physical activity showed significantly decreased risk for incident hypertension (hazard ratio 0.93; 95% CI 0.87 to 0.99) and diabetes mellitus (hazard ratio 0.83; 95% CI 0.74 to 0.92) compared with those with a temporal decrease in their physical activity level. Conclusion Both sufficient baseline physical activity level and its temporal increase were associated with a lower risk of incident hypertension and diabetes mellitus in a large, relatively healthy, cohort.

AIDS-related and non-AIDS-related mortality in the Asia-Pacific region in the era of combination antiretroviral treatment.

PubMed

Falster, Kathleen; Choi, Jun Yong; Donovan, Basil; Duncombe, Chris; Mulhall, Brian; Sowden, David; Zhou, Jialun; Law, Matthew G

2009-11-13

Although studies have shown reductions in mortality from AIDS after the introduction of combination antiretroviral treatment (cART), little is known about cause-specific mortality in low-income settings in the cART era. We explored predictors of AIDS and non-AIDS mortality and compared cause-specific mortality across high-income and low-income settings in the Asia-Pacific region. We followed patients in the Asia Pacific HIV Observational Database from the date they started cART (or cohort enrolment if cART initiation was identified retrospectively), until the date of death or last follow-up visit. Competing risks methods were used to estimate the cumulative incidence, and to investigate predictors, of AIDS and non-AIDS mortality. Of 4252 patients, 215 died; 89 from AIDS, 97 from non-AIDS causes and 29 from unknown causes. Age more than 50 years [hazard ratio 4.29; 95% confidence interval (CI) 2.10-8.79] and CD4 cell counts less than or equal to 100 cells/microl (hazard ratio 8.59; 95% CI 5.66-13.03) were associated with an increased risk of non-AIDS mortality. Risk factors for AIDS mortality included CD4 cell counts less than or equal to 100 cells/microl (hazard ratio 34.97; 95% CI 18.01-67.90) and HIV RNA 10 001 or more (hazard ratio 4.21; 95% CI 2.07-8.55). There was some indication of a lower risk of non-AIDS mortality in Asian high-income, and possibly low-income, countries compared to Australia. Immune deficiency is associated with an increased risk of AIDS and non-AIDS mortality. Older age predicts non-AIDS mortality in the cART era. Less conclusive was the association between country-income level and cause-specific mortality because of the relatively high proportion of unknown causes of death in low-income settings.

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

PubMed

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

2016-07-15

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

Survival from skin cancer and its associated factors in Kurdistan province of Iran

PubMed Central

Ahmadi, Galavizh; Asadi-Lari, Mohsen; Amani, Saeid; Solaymani-Dodaran, Masoud

2015-01-01

Background: We explored survival of skin cancer and its determinants in Kurdistan province of Iran. Methods: In a retrospective cohort design, we identified all registered skin cancer patients in Kurdistan Cancer Registry from year 2000 to 2009. Information on time and cause of death were obtained from Registrar’s office and information on type, stage and anatomic locations were extracted from patients’ hospital records. Additional demographic information was collected via a telephone interview. We calculated the 3 and 5 years survival. Survival experiences in different groups were compared using log rank test. Cox proportional hazard model was built and hazard ratios and their 95% confidence intervals were calculated. Results: Of a total of 1353, contact information for 667 patients were available, all of which were followed up. 472 telephone interviews were conducted. Mean follow-up time was 34 months. We identified 78 deaths in this group of patients and 44 of them were because of skin cancer. After controlling for confounding, tumour type, anatomical location, and diseases stage remained significantly associated with survival. Hazard ratios for death because of squamous cell carcinoma was 74.5 (95%CI: 4.8-1146) and for melanoma was 24.4 (95%CI: 1.3-485) compared with basal cell carcinomas. Hazard ratio for tumours in stage 4 was 16.7 (95%CI: 1.8-156.6) and for stage 3 was 16.8 (95%CI: 1.07-260) compared with stage 1 and 2. Conclusion: Tumour stage is independently associated with survival. Relatively low survival rates suggest delayed diagnosis. Increasing public awareness through media about the warning signs of skin cancers could increase the chance of survival in these patients. PMID:26793668

Timing of pregnancy, postpartum risk of virologic failure and loss to follow-up among HIV-positive women

PubMed Central

Onoya, Dorina; Sineke, Tembeka; Brennan, Alana T.; Long, Lawrence; Fox, Matthew P.

2017-01-01

Objectives: We assessed the association between the timing of pregnancy with the risk of postpartum virologic failure and loss from HIV care in South Africa. Design: This is a retrospective cohort study of 6306 HIV-positive women aged 15–49 at antiretroviral therapy (ART) initiation, initiated on ART between January 2004 and December 2013 in Johannesburg, South Africa. Methods: The incidence of virologic failure (two consecutive viral load measurements of >1000 copies/ml) and loss to follow-up (>3 months late for a visit) during 24 months postpartum were assessed using Cox proportional hazards modelling. Results: The rate of postpartum virologic failure was higher following an incident pregnancy on ART [adjusted hazard ratio 1.8, 95% confidence interval (CI): 1.1–2.7] than among women who initiated ART during pregnancy. This difference was sustained among women with CD4+ cell count less than 350 cells/μl at delivery (adjusted hazard ratio 1.8, 95% CI: 1.1–3.0). Predictors of postpartum virologic failure were being viremic, longer time on ART, being 25 or less years old and low CD4+ cell count and anaemia at delivery, as well as initiating ART on stavudine-containing or abacavir-containing regimen. There was no difference postpartum loss to follow-up rates between the incident pregnancies group (hazard ratio 0.9, 95% CI: 0.7–1.1) and those who initiated ART in pregnancy. Conclusion: The risk of virologic failure remains high among postpartum women, particularly those who conceive on ART. The results highlight the need to provide adequate support for HIV-positive women with fertility intention after ART initiation and to strengthen monitoring and retention efforts for postpartum women to sustain the benefits of ART. PMID:28463877

Hazard ratio estimation and inference in clinical trials with many tied event times.

PubMed

Mehrotra, Devan V; Zhang, Yiwei

2018-06-13

The medical literature contains numerous examples of randomized clinical trials with time-to-event endpoints in which large numbers of events accrued over relatively short follow-up periods, resulting in many tied event times. A generally common feature across such examples was that the logrank test was used for hypothesis testing and the Cox proportional hazards model was used for hazard ratio estimation. We caution that this common practice is particularly risky in the setting of many tied event times for two reasons. First, the estimator of the hazard ratio can be severely biased if the Breslow tie-handling approximation for the Cox model (the default in SAS and Stata software) is used. Second, the 95% confidence interval for the hazard ratio can include one even when the corresponding logrank test p-value is less than 0.05. To help establish a better practice, with applicability for both superiority and noninferiority trials, we use theory and simulations to contrast Wald and score tests based on well-known tie-handling approximations for the Cox model. Our recommendation is to report the Wald test p-value and corresponding confidence interval based on the Efron approximation. The recommended test is essentially as powerful as the logrank test, the accompanying point and interval estimates of the hazard ratio have excellent statistical properties even in settings with many tied event times, inferential alignment between the p-value and confidence interval is guaranteed, and implementation is straightforward using commonly used software. Copyright © 2018 John Wiley & Sons, Ltd.

Allopurinol and Cardiovascular Outcomes in Adults With Hypertension.

PubMed

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

2016-03-01

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

Neighborhood disadvantage and ischemic stroke: the Cardiovascular Health Study (CHS).

PubMed

Brown, Arleen F; Liang, Li-Jung; Vassar, Stefanie D; Stein-Merkin, Sharon; Longstreth, W T; Ovbiagele, Bruce; Yan, Tingjian; Escarce, José J

2011-12-01

Neighborhood characteristics may influence the risk of stroke and contribute to socioeconomic disparities in stroke incidence. The objectives of this study were to examine the relationship between neighborhood socioeconomic status and incident ischemic stroke and examine potential mediators of these associations. We analyzed data from 3834 whites and 785 blacks enrolled in the Cardiovascular Health Study, a multicenter, population-based, longitudinal study of adults ages≥65 years from 4 US counties. The primary outcome was adjudicated incident ischemic stroke. Neighborhood socioeconomic status was measured using a composite of 6 census tract variables. Race-stratified multilevel Cox proportional hazard models were constructed adjusted for sociodemographic, behavioral, and biological risk factors. Among whites, in models adjusted for sociodemographic characteristics, stroke hazard was significantly higher among residents of neighborhoods in the lowest compared with the highest neighborhood socioeconomic status quartile (hazard ratio, 1.32; 95% CI, 1.01-1.72) with greater attenuation of the hazard ratio after adjustment for biological risk factors (hazard ratio, 1.16; 0.88-1.52) than for behavioral risk factors (hazard ratio, 1.30; 0.99-1.70). Among blacks, we found no significant associations between neighborhood socioeconomic status and ischemic stroke. Higher risk of incident ischemic stroke was observed in the most disadvantaged neighborhoods among whites, but not among blacks. The relationship between neighborhood socioeconomic status and stroke among whites appears to be mediated more strongly by biological than behavioral risk factors.

Parametric regression model for survival data: Weibull regression model as an example

PubMed Central

2016-01-01

Weibull regression model is one of the most popular forms of parametric regression model that it provides estimate of baseline hazard function, as well as coefficients for covariates. Because of technical difficulties, Weibull regression model is seldom used in medical literature as compared to the semi-parametric proportional hazard model. To make clinical investigators familiar with Weibull regression model, this article introduces some basic knowledge on Weibull regression model and then illustrates how to fit the model with R software. The SurvRegCensCov package is useful in converting estimated coefficients to clinical relevant statistics such as hazard ratio (HR) and event time ratio (ETR). Model adequacy can be assessed by inspecting Kaplan-Meier curves stratified by categorical variable. The eha package provides an alternative method to model Weibull regression model. The check.dist() function helps to assess goodness-of-fit of the model. Variable selection is based on the importance of a covariate, which can be tested using anova() function. Alternatively, backward elimination starting from a full model is an efficient way for model development. Visualization of Weibull regression model after model development is interesting that it provides another way to report your findings. PMID:28149846

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

PubMed

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

2017-09-01

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

Understanding the Risk Factors of Trauma Center Closures

PubMed Central

Shen, Yu-Chu; Hsia, Renee Y.; Kuzma, Kristen

2011-01-01

Objectives We analyze whether hazard rates of shutting down trauma centers are higher due to financial pressures or in areas with vulnerable populations (such as minorities or the poor). Materials and Methods This is a retrospective study of all hospitals with trauma center services in urban areas in the continental US between 1990 and 2005, identified from the American Hospital Association Annual Surveys. These data were linked with Medicare cost reports, and supplemented with other sources, including the Area Resource File. We analyze the hazard rates of trauma center closures among several dimensions of risk factors using discrete-time proportional hazard models. Results The number of trauma center closures increased from 1990 to 2005, with a total of 339 during this period. The hazard rate of closing trauma centers in hospitals with a negative profit margin is 1.38 times higher than those hospitals without the negative profit margin (P < 0.01). Hospitals receiving more generous Medicare reimbursements face a lower hazard of shutting down trauma centers (ratio: 0.58, P < 0.01) than those receiving below average reimbursement. Hospitals in areas with higher health maintenance organizations penetration face a higher hazard of trauma center closure (ratio: 2.06, P < 0.01). Finally, hospitals in areas with higher shares of minorities face a higher risk of trauma center closure (ratio: 1.69, P < 0.01). Medicaid load and uninsured populations, however, are not risk factors for higher rates of closure after we control for other financial and community characteristics. Conclusions Our findings give an indication on how the current proposals to cut public spending could exacerbate the trauma closure particularly among areas with high shares of minorities. In addition, given the negative effect of health maintenance organizations on trauma center survival, the growth of Medicaid managed care population should be monitored. Finally, high shares of Medicaid or uninsurance by themselves are not independent risk factors for higher closure as long as financial pressures are mitigated. Targeted policy interventions and further research on the causes, are needed to address these systems-level disparities. PMID:19704354

The spatiotemporal characteristics of environmental hazards caused by offshore oil and gas operations in the Gulf of Mexico.

PubMed

Meng, Qingmin

2016-09-15

Marine ecosystems are home to a host of numerous species ranging from tiny planktonic organisms, fishes, and birds, to large mammals such as the whales, manatees, and seals. However, human activities such as offshore oil and gas operations increasingly threaten marine and coastal ecosystems, for which there has been little exploration into the spatial and temporal risks of offshore oil operations. Using the Gulf of Mexico, one of the world's hottest spots of offshore oil and gas mining, as the study area, we propose a spatiotemporal approach that integrates spatial statistics and geostatistics in a geographic information system environment to provide insight to environmental management and decision making for oil and gas operators, coastal communities, local governments, and the federal government. We use the records from 1995 to 2015 of twelve types of hazards caused by offshore oil and gas operations, and analyze them spatially over a five year period. The spatial clusters of these hazards are analyzed and mapped using Getis-Ord Gi and local Moran's I statistics. We then design a spatial correlation coefficient matrix for multivariate spatial correlation, which is the ratio of the cross variogram of two types of hazards to the product of the variograms of the two hazards, showing a primary understanding of the degrees of spatial correlation among the twelve types hazards. To the best of our knowledge, it is the first application of spatiotemporal analysis methods to environmental hazards caused by offshore oil and gas operations; the proposed methods can be applied to other regions for the management and monitoring of environmental hazards caused by offshore oil operations. Copyright © 2016 Elsevier B.V. All rights reserved.

Ensemble of ground subsidence hazard maps using fuzzy logic

NASA Astrophysics Data System (ADS)

Park, Inhye; Lee, Jiyeong; Saro, Lee

2014-06-01

Hazard maps of ground subsidence around abandoned underground coal mines (AUCMs) in Samcheok, Korea, were constructed using fuzzy ensemble techniques and a geographical information system (GIS). To evaluate the factors related to ground subsidence, a spatial database was constructed from topographic, geologic, mine tunnel, land use, groundwater, and ground subsidence maps. Spatial data, topography, geology, and various ground-engineering data for the subsidence area were collected and compiled in a database for mapping ground-subsidence hazard (GSH). The subsidence area was randomly split 70/30 for training and validation of the models. The relationships between the detected ground-subsidence area and the factors were identified and quantified by frequency ratio (FR), logistic regression (LR) and artificial neural network (ANN) models. The relationships were used as factor ratings in the overlay analysis to create ground-subsidence hazard indexes and maps. The three GSH maps were then used as new input factors and integrated using fuzzy-ensemble methods to make better hazard maps. All of the hazard maps were validated by comparison with known subsidence areas that were not used directly in the analysis. As the result, the ensemble model was found to be more effective in terms of prediction accuracy than the individual model.

Non-detonable and non-explosive explosive simulators

DOEpatents

Simpson, Randall L.; Pruneda, Cesar O.

1997-01-01

A simulator which is chemically equivalent to an explosive, but is not detonable or explodable. The simulator is a combination of an explosive material with an inert material, either in a matrix or as a coating, where the explosive has a high surface ratio but small volume ratio. The simulator has particular use in the training of explosives detecting dogs, calibrating analytical instruments which are sensitive to either vapor or elemental composition, or other applications where the hazards associated with explosives is undesirable but where chemical and/or elemental equivalence is required. The explosive simulants may be fabricated by different techniques. A first method involves the use of standard slurry coatings to produce a material with a very high binder to explosive ratio without masking the explosive vapor, and a second method involves coating inert substrates with thin layers of explosive.

Disseminating Landslide Hazard Information for California Local Government

NASA Astrophysics Data System (ADS)

Wills, C. J.

2010-12-01

Since 1969, the California Geological Survey has produced numerous maps showing landslide features and delineating potential slope-stability problem areas. These maps have been provided to local governments to encourage consideration of landslide hazards in planning and development decisions. Maps produced from 1986 through 1995 under the Landslide Hazard Mapping Act were advisory only, and their use by local government was never consistent. By contrast, maps of Zones of Required Investigation for seismically induced landslides produced under the Seismic Hazard Zoning Act since 1997 come with detailed guidelines and legal requirements. A legislative act that required landslide hazards be mapped and hazard maps disseminated to local government proved ineffective in landslide hazard mitigation. A later act with requirements that the hazard zone maps be used by local government proved more effective. Planning scenarios have proven to be an effective way of transmitting scientific information about natural hazards to emergency response professionals. Numerous earthquake planning scenarios have been prepared and used as the basis for emergency response exercises. An advantage of scenarios that include loss estimates is that the effects can be put in units of measure that everyone understands, principally deaths and dollars. HAZUS software available from FEMA allows calculation of losses for earthquake scenarios, but similar methods for landslides have not been developed. As part of the USGS Multi-Hazard Demonstration Project, we have estimated the landslide losses for a major west-coast winter storm scenario by developing a system based loosely on HAZUS. Data on landslide damage in past storms has been sparse and inconsistent, but a few data sets are available. The most detailed and complete available data on landslide damage was gathered by the City of Los Angeles following the 1978 storms. We extrapolate from that data to the entire state by first generalizing a landslide susceptibility map to give a single value of susceptibility for each census tract. We then calculated the loss ratio, the cost of landslide damage from the 1978 storms divided by the value of light wood frame structures in the census tract. The comparison suggests three general categories of damage: tracts with low landslide susceptibility have no landslide damage: tracts with moderate susceptibility have loss ratios of about 0.016%: and tracts with high susceptibility have loss ratios of 0.096%. Using these values, the susceptibility map becomes a landslide loss ratio map for the average storm intensity and landslide vulnerability of Los Angeles in 1978. Generalization to other storm intensities uses differences in storm intensity and landslide damage data from the 1982 storm in the Bay Area. In Santa Cruz County, that storm had a recurrence interval of over 100 years, and over 3 times the damage as our projection from the 1978 data. In Sonoma County, that storm had a recurrence interval of only 10 years and damage that was only 2% of our projection. If a relationship between storm intensity and the projections from the 1978 Los Angeles data can be developed, we may be able to estimate landslide losses for any projected storm intensity.

Relationship between Early Physician Follow-Up and 30-Day Readmission after Acute Myocardial Infarction and Heart Failure

PubMed Central

Tung, Yu-Chi; Chang, Guann-Ming; Chang, Hsien-Yen

2017-01-01

Background Thirty-day readmission rates after acute myocardial infarction (AMI) and heart failure are important patient outcome metrics. Early post-discharge physician follow-up has been promoted as a method of reducing 30-day readmission rates. However, the relationships between early post-discharge follow-up and 30-day readmission for AMI and heart failure are inconclusive. We used nationwide population-based data to examine associations between 7-day physician follow-up and 30-day readmission, and further associations of 7-day same physician (during the index hospitalization and at follow-up) and cardiologist follow-up with 30-day readmission for non-ST-segment-elevation myocardial infarction (NSTEMI) or heart failure. Methods We analyzed all patients 18 years or older with NSTEMI and heart failure and discharged from hospitals in 2010 in Taiwan through Taiwan’s National Health Insurance Research Database. Cox proportional hazard models with robust sandwich variance estimates and propensity score weighting were performed after adjustment for patient and hospital characteristics to test associations between 7-day physician follow-up and 30-day readmission. Results The study population for NSTEMI and heart failure included 5,008 and 13,577 patients, respectively. Early physician follow-up was associated with a lower hazard ratio of readmission compared with no early physician follow-up for patients with NSTEMI (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.39–0.57), and for patients with heart failure (HR, 0.54; 95% CI, 0.48–0.60). Same physician follow-up was associated with a reduced hazard ratio of readmission compared with different physician follow-up for patients with NSTEMI (HR, 0.56; 95% CI, 0.48–0.65), and for patients with heart failure (HR, 0.69; 95% CI, 0.62–0.76). Conclusions For each condition, patients who have an outpatient visit with a physician within 7 days of discharge have a lower risk of 30-day readmission. Moreover, patients who have an outpatient visit with the same physician within 7 days of discharge have a much lower risk of 30-day readmission. PMID:28129332

Clinical Outcome of Degenerative Mitral Regurgitation: Critical Importance of Echocardiographic Quantitative Assessment in Routine Practice.

PubMed

Antoine, Clemence; Benfari, Giovanni; Michelena, Hector I; Malouf, Joseph F; Nkomo, Vuyisile T; Thapa, Prabin; Enriquez-Sarano, Maurice

2018-05-31

Background -Echocardiographic quantitation of degenerative mitral regurgitation (DMR) is recommended whenever possible in clinical guidelines but is criticized and its scalability to routine clinical practice doubted. We hypothesized that echocardiographic DMR quantitation, performed in routine clinical practice by multiple practitioners predicts independently long-term survival, and thus is essential to DMR management. Methods -We included patients diagnosed with isolated mitral-valve-prolapse 2003-2011 and any degree of MR quantified by any physician/sonographer in routine clinical practice. Clinical/echocardiographic data acquired at diagnosis were retrieved electronically. Endpoint was mortality under medical treatment analyzed by Kaplan-Meir method and Proportional-Hazard models. Results -The cohort included 3914 patients (55% male) aged 62±17 years, with left ventricular ejection fraction (LVEF) 63±8% and routinely measured effective regurgitant orifice area (EROA) 19[0-40] mm 2 During follow-up (6.7±3.1 years) 696 patients died under medical management and 1263 underwent mitral surgery. In multivariate analysis, routinely measured EROA was associated with mortality (adjusted-hazard-ratio 1.19[1.13-1.24] p<0.0001 per-10mm 2 ) independently of LVEF and end-systolic diameter, symptoms and age/comorbidities. The association between routinely measured EROA and mortality persisted with competitive risk modeling (adjusted hazard-ratio 1.15[1.10-1.20] per 10mm 2 p<0.0001), or in patients without guideline-based Class I/II surgical triggers (adjusted hazard ratio 1.19[1.10-1.28] per 10mm 2 p<0.0001) and in all subgroups examined (all p<0.01). Spline curve analysis showed that, compared with general population mortality, excess mortality appears for moderate DMR (EROA ≥20mm 2 ) becomes notable ≥EROA 30mm 2 and steadily increases with higher EROA levels, > 40 mm 2 threshold. Conclusions -Echocardiographic DMR quantitation is scalable to routine practice and is independently associated with clinical outcome. Routinely measured EROA is strongly associated with long-term survival under medical treatment. Excess mortality vs. the general population appears in the "moderate" DMR range and steadily increases with higher EROA. Hence, individual EROA values should be integrated into therapeutic considerations, additionally to categorical DMR grading.

Analysis of censored data.

PubMed

Lucijanic, Marko; Petrovecki, Mladen

2012-01-01

Analyzing events over time is often complicated by incomplete, or censored, observations. Special non-parametric statistical methods were developed to overcome difficulties in summarizing and comparing censored data. Life-table (actuarial) method and Kaplan-Meier method are described with an explanation of survival curves. For the didactic purpose authors prepared a workbook based on most widely used Kaplan-Meier method. It should help the reader understand how Kaplan-Meier method is conceptualized and how it can be used to obtain statistics and survival curves needed to completely describe a sample of patients. Log-rank test and hazard ratio are also discussed.

Apolipoprotein E and mortality in African-Americans and Yoruba.

PubMed

Lane, Kathleen A; Gao, Sujuan; Hui, Siu L; Murrell, Jill R; Hall, Kathleen S; Hendrie, Hugh C

2003-10-01

The literature on the association between apolipoprotein E (ApoE) and mortality across ethnic and age groups has been inconsistent. No studies have looked at this association in developing countries. We used data from the Indianapolis-Ibadan Dementia study to examine this association between APOE and mortality in 354 African-Americans from Indianapolis and 968 Yoruba from Ibadan, Nigeria. Participants were followed up to 9.5 years for Indianapolis and 8.7 years for Ibadan. Subjects from both sites were divided into 2 groups based upon age at baseline. A Cox proportional hazards regression model adjusting for age at baseline, education, hypertension, smoking history and gender in addition to time-dependent covariates of cancer, diabetes, heart disease, stroke, and dementia was fit for each cohort and age group. Having ApoE epsilon4 alleles significantly increased mortality risk in Indianapolis subjects under age 75 (hazard ratio: 2.00; 95% CI: 1.19-3.35; p = 0.0089). No association was found in Indianapolis subjects 75 and older (hazard ratio: 0.71; 95% CI: 0.45-1.10; p = 0.1238), Ibadan subjects under 75 (hazard ratio: 1.04; 95% CI: 0.78 to 1.40; p = 0.7782), or Ibadan subjects over 75 (hazard ratio: 1.21; 95% CI: 0.83 to 1.75; p = 0.3274).

Apolipoprotein E and mortality in African-Americans and Yoruba

PubMed Central

Lane, Kathleen A.; Gao, Sujuan; Hui, Siu L.; Murrell, Jill R.; Hall, Kathleen S.; Hendrie, Hugh C.

2011-01-01

The literature on the association between apolipoprotein E (ApoE) and mortality across ethnic and age groups has been inconsistent. No studies have looked at this association in developing countries. We used data from the Indianapolis-Ibadan Dementia study to examine this association between APOE and mortality in 354 African-Americans from Indianapolis and 968 Yoruba from Ibadan, Nigeria. Participants were followed up to 9.5 years for Indianapolis and 8.7 years for Ibadan. Subjects from both sites were divided into 2 groups based upon age at baseline. A Cox proportional hazards regression model adjusting for age at baseline, education, hypertension, smoking history and gender in addition to time-dependent covariates of cancer, diabetes, heart disease, stroke, and dementia was fit for each cohort and age group. Having ApoE ε4 alleles significantly increased mortality risk in Indianapolis subjects under age 75 ( hazard ratio: 2.00; 95% CI: 1.19–3.35; p = 0.0089). No association was found in Indianapolis subjects 75 and older (hazard ratio: 0.71; 95% CI: 0.45–1.10; p = 0.1238), Ibadan subjects under 75 (hazard ratio: 1.04; 95% CI: 0.78 to 1.40; p = 0.7782), or Ibadan subjects over 75 (hazard ratio: 1.21; 95% CI: 0.83 to 1.75; p = 0.3274). PMID:14646029

Coffee and risk of death from hepatocellular carcinoma in a large cohort study in Japan.

PubMed

Kurozawa, Y; Ogimoto, I; Shibata, A; Nose, T; Yoshimura, T; Suzuki, H; Sakata, R; Fujita, Y; Ichikawa, S; Iwai, N; Tamakoshi, A

2005-09-05

We examined the relation between coffee drinking and hepatocellular carcinoma (HCC) mortality in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). In total, 110,688 cohort members (46,399 male and 64,289 female subjects) aged 40-79 years were grouped by coffee intake into three categories: one or more cups per day, less than one cup per day and non-coffee drinkers. Cox proportional hazards model by SAS was used to obtain hazard ratio of HCC mortality for each coffee consumption categories. The hazard ratios were adjusted for age, gender, educational status, history of diabetes and liver diseases, smoking habits and alcohol. The hazard ratio of death due to HCC for drinkers of one and more cups of coffee per day, compared with non-coffee drinkers, was 0.50 (95% confidence interval 0.31-0.79), and the ratio for drinkers of less than one cup per day was 0.83 (95% confidence interval 0.54-1.25). Our data confirmed an inverse association between coffee consumption and HCC mortality.

Coffee and risk of death from hepatocellular carcinoma in a large cohort study in Japan

PubMed Central

Kurozawa, Y; Ogimoto, I; Shibata, A; Nose, T; Yoshimura, T; Suzuki, H; Sakata, R; Fujita, Y; Ichikawa, S; Iwai, N; Tamakoshi, A

2005-01-01

We examined the relation between coffee drinking and hepatocellular carcinoma (HCC) mortality in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). In total, 110 688 cohort members (46 399 male and 64 289 female subjects) aged 40–79 years were grouped by coffee intake into three categories: one or more cups per day, less than one cup per day and non-coffee drinkers. Cox proportional hazards model by SAS was used to obtain hazard ratio of HCC mortality for each coffee consumption categories. The hazard ratios were adjusted for age, gender, educational status, history of diabetes and liver diseases, smoking habits and alcohol. The hazard ratio of death due to HCC for drinkers of one and more cups of coffee per day, compared with non-coffee drinkers, was 0.50 (95% confidence interval 0.31–0.79), and the ratio for drinkers of less than one cup per day was 0.83 (95% confidence interval 0.54–1.25). Our data confirmed an inverse association between coffee consumption and HCC mortality. PMID:16091758

Survival Benefits of Invasive Versus Conservative Strategies in Heart Failure in Patients With Reduced Ejection Fraction and Coronary Artery Disease: A Meta-Analysis.

PubMed

Wolff, Georg; Dimitroulis, Dimitrios; Andreotti, Felicita; Kołodziejczak, Michalina; Jung, Christian; Scicchitano, Pietro; Devito, Fiorella; Zito, Annapaola; Occhipinti, Michele; Castiglioni, Battistina; Calveri, Giuseppe; Maisano, Francesco; Ciccone, Marco M; De Servi, Stefano; Navarese, Eliano P

2017-01-01

Heart failure with reduced ejection fraction caused by ischemic heart disease is associated with increased morbidity and mortality. It remains unclear whether revascularization by either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) carries benefits or risks in this group of stable patients compared with medical treatment. We performed a meta-analysis of available studies comparing different methods of revascularization (PCI or CABG) against each other or medical treatment in patients with coronary artery disease and left ventricular ejection fraction ≤40%. The primary outcome was all-cause mortality; myocardial infarction, revascularization, and stroke were also analyzed. Twenty-one studies involving a total of 16 191 patients were included. Compared with medical treatment, there was a significant mortality reduction with CABG (hazard ratio, 0.66; 95% confidence interval, 0.61-0.72; P<0.001) and PCI (hazard ratio, 0.73; 95% confidence interval, 0.62-0.85; P<0.001). When compared with PCI, CABG still showed a survival benefit (hazard ratio, 0.82; 95% confidence interval, 0.75-0.90; P<0.001). The present meta-analysis indicates that revascularization strategies are superior to medical treatment in improving survival in patients with ischemic heart disease and reduced ejection fraction. Between the 2 revascularization strategies, CABG seems more favorable compared with PCI in this particular clinical setting. © 2017 American Heart Association, Inc.

Chronic Use of Theophylline and Mortality in Chronic Obstructive Pulmonary Disease: A Meta-analysis.

PubMed

Horita, Nobuyuki; Miyazawa, Naoki; Kojima, Ryota; Inoue, Miyo; Ishigatsubo, Yoshiaki; Kaneko, Takeshi

2016-05-01

Theophylline has been shown to improve respiratory function and oxygenation in patients with chronic obstruction pulmonary disease (COPD). However, the impact of theophylline on mortality in COPD patients has not been not sufficiently evaluated. Two investigators independently searched for eligible articles in 4 databases. The eligibility criterion for this meta-analysis was an original research article that provided a hazard ratio for theophylline for all-cause mortality of COPD patients. Both randomized controlled trials and observational studies were accepted. After we confirmed no substantial heterogeneity (I(2)<50%), the fixed-model method with generic inverse variance was used for meta-analysis to estimate the pooled hazard ratio. We screened 364 potentially eligible articles. Of the 364 articles, 259 were excluded on the basis of title and abstract, and 99 were excluded after examination of the full text. Our final analysis included 6 observational studies and no randomized controlled trials. One study reported 2 cohorts. The number of patients in each cohort ranged from 47 to 46,403. Heterogeneity (I(2)=42%, P=.11) and publication bias (Begg's test r=0.21, P=.662) were not substantial. Fixed-model meta-analysis yielded a pooled hazard ratio for theophylline for all-cause death of 1.07 (95% confidence interval: 1.02-1.13, P=.003). This meta-analysis of 7 observational cohorts suggests that theophylline slightly increases all-cause death in COPD patients. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Prognostic impact of preoperative statin use after radical nephroureterectomy for upper urinary tract urothelial carcinoma

PubMed Central

Lim, Ju Hyun; Jeong, In Gab; Park, Jong Yeon; You, Dalsan; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong

2015-01-01

Purpose The objective was to investigate the impact of statin use on prognosis after radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC). Materials and Methods A retrospective review of medical records identified 277 patients who underwent radical nephroureterectomy for primary UTUC at Asan Medical Center between January 2006 and December 2011. Information on preoperative statin use was obtained from patient charts in an electronic database. We assessed the impact of statin use on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results Of these 277 patients, 62 (22.4%) were taking statin medications. Compared to the statin nonusers, the statin users were older, had a higher body mass index, and had higher rates of cardiovascular disease and diabetes. The 5-year RFS rates of statin users and nonusers were 78.5% and 72.5%, respectively (p=0.528); the 5-year CSS rates were 85.6% and 77.7%, respectively (p=0.516); and the 5-year OS rates were 74.5% and 71.4%, respectively (p=0.945). In the multivariate analysis, statin use was not an independent prognostic factor for RFS (hazard ratio, 0.47; p=0.056), CSS (hazard ratio, 0.46; p=0.093), or OS (hazard ratio, 0.59; p=0.144) in patients who underwent radical nephroureterectomy for UTUC. Conclusions Statin use was not associated with improved RFS, CSS, or OS in the sample population of patients with UTUC. PMID:26175868

Prior nonhip limb fracture predicts subsequent hip fracture in institutionalized elderly people.

PubMed

Nakamura, K; Takahashi, S; Oyama, M; Oshiki, R; Kobayashi, R; Saito, T; Yoshizawa, Y; Tsuchiya, Y

2010-08-01

This 1-year cohort study of nursing home residents revealed that historical fractures of upper limbs or nonhip lower limbs were associated with hip fracture (hazard ratio = 2.14), independent of activities of daily living (ADL), mobility, dementia, weight, and type of nursing home. Prior nonhip fractures are useful for predicting of hip fracture in institutional settings. The aim of this study was to evaluate the utility of fracture history for the prediction of hip fracture in nursing home residents. This was a cohort study with a 1-year follow-up. Subjects were 8,905 residents of nursing homes in Niigata, Japan (mean age, 84.3 years). Fracture histories were obtained from nursing home medical records. ADL levels were assessed by caregivers. Hip fracture diagnosis was based on hospital medical records. Subjects had fracture histories of upper limbs (5.0%), hip (14.0%), and nonhip lower limbs (4.6%). Among historical single fractures, only prior nonhip lower limbs significantly predicted subsequent fracture (adjusted hazard ratio, 2.43; 95% confidence interval (CI), 1.30-4.57). The stepwise method selected the best model, in which a combined historical fracture at upper limbs or nonhip lower limbs (adjusted hazard ratio, 2.14; 95% CI, 1.30-3.52), dependence, ADL levels, mobility, dementia, weight, and type of nursing home independently predicted subsequent hip fracture. A fracture history at upper or nonhip lower limbs, in combination with other known risk factors, is useful for the prediction of future hip fracture in institutional settings.

Usefulness of the Left Ventricular Myocardial Contraction Fraction in Healthy Men and Women to Predict Cardiovascular Morbidity and Mortality

PubMed Central

Chuang, Michael L.; Gona, Philimon; Salton, Carol J.; Yeon, Susan B.; Kissinger, Kraig V.; Blease, Susan J.; Levy, Daniel; O'Donnell, Christopher J.; Manning, Warren J.

2013-01-01

We sought to determine whether depressed myocardial contraction fraction (MCF, the ratio of left ventricular (LV) stroke volume to myocardial volume) predicts cardiovascular disease (CVD) events in initially healthy adults. A subset (N=318, 60±9 yrs, 158 men) of the Framingham Heart Study Offspring cohort free of clinical CVD underwent volumetric cardiovascular magnetic resonance (CMR) imaging in 1998–1999. LV ejection fraction (EF), mass and MCF were determined. “Hard” CVD events comprised cardiovascular death, myocardial infarction, stroke or new heart failure. A Cox proportional hazards model adjusting for Framingham Coronary Risk Score (FCRS) was used to estimate hazard ratios for incident hard CVD events for sex-specific quartiles of MCF, LV mass and LVEF. The lowest quartile of LV mass and highest quartiles of MCF and EF served as referent. Kaplan-Meier survival plots and the log rank test were used to compare event-free survival. MCF was greater in women (0.58±0.13) than men (0.52±0.11), p<0.01. Nearly all (99%) participants had EF ≥ 0.55. Over up to 9-year (median 5.2) follow-up, 31 participants (10%) experienced an incident hard CVD event. Lowest-quartile MCF was 7 times more likely to develop hard CVD (hazard ratio 7.11, p=0.010) compared to the lowest quartile, and the elevated hazards persisted even after adjustment for LV mass (hazard ratio=6.09, p=0.020). The highest-quartile LV mass/height2.7 had nearly five-fold risk (hazard ratio 4.68, p=0.016). Event-free survival was shorter in lowest-quartile MCF, p = 0.0006, but not in lowest-quartile LVEF. Conclusion: In a cohort of adults initially without clinical CVD, lowest-quartile MCF conferred an increased hazard for hard CVD events after adjustment for traditional CVD risk factors and LV mass. PMID:22381161

Usefulness of the left ventricular myocardial contraction fraction in healthy men and women to predict cardiovascular morbidity and mortality.

PubMed

Chuang, Michael L; Gona, Philimon; Salton, Carol J; Yeon, Susan B; Kissinger, Kraig V; Blease, Susan J; Levy, Daniel; O'Donnell, Christopher J; Manning, Warren J

2012-05-15

We sought to determine whether depressed myocardial contraction fraction (MCF; ratio of left ventricular [LV] stroke volume to myocardial volume) predicts cardiovascular disease (CVD) events in initially healthy adults. A subset (n = 318, 60 ± 9 years old, 158 men) of the Framingham Heart Study Offspring cohort free of clinical CVD underwent volumetric cardiovascular magnetic resonance imaging in 1998 through 1999. LV ejection fraction (EF), mass, and MCF were determined. "Hard" CVD events consisted of cardiovascular death, myocardial infarction, stroke, or new heart failure. A Cox proportional hazards model adjusting for Framingham Coronary Risk Score was used to estimate hazard ratios for incident hard CVD events for gender-specific quartiles of MCF, LV mass, and LVEF. The lowest quartile of LV mass and highest quartiles of MCF and EF served as referents. Kaplan-Meier survival plots and log-rank test were used to compare event-free survival. MCF was greater in women (0.58 ± 0.13) than in men (0.52 ± 0.11, p <0.01). Nearly all participants (99%) had EF ≥0.55. During an up to 9-year follow-up (median 5.2), 31 participants (10%) developed an incident hard CVD event. Lowest-quartile MCF was 7 times more likely to develop a hard CVD (hazard ratio 7.11, p = 0.010) compared to the remaining quartiles, and increased hazards persisted even after adjustment for LV mass (hazard ratio 6.09, p = 0.020). The highest-quartile LV mass/height 2.7 had a nearly fivefold risk (hazard ratio 4.68, p = 0.016). Event-free survival was shorter in lowest-quartile MCF (p = 0.0006) but not in lowest-quartile LVEF. In conclusion, in a cohort of adults initially without clinical CVD, lowest-quartile MCF conferred an increased hazard for hard CVD events after adjustment for traditional CVD risk factors and LV mass. Copyright © 2012 Elsevier Inc. All rights reserved.

Socioeconomic disparities in outcomes after acute myocardial infarction.

PubMed

Bernheim, Susannah M; Spertus, John A; Reid, Kimberly J; Bradley, Elizabeth H; Desai, Rani A; Peterson, Eric D; Rathore, Saif S; Normand, Sharon-Lise T; Jones, Philip G; Rahimi, Ali; Krumholz, Harlan M

2007-02-01

Patients of low socioeconomic status (SES) have higher mortality after acute myocardial infarction (AMI). Little is known about the underlying mechanisms or the relationship between SES and rehospitalization after AMI. We analyzed data from the PREMIER observational study, which included 2142 patients hospitalized with AMI from 18 US hospitals. Socioeconomic status was measured by self-reported household income and education level. Sequential multivariable modeling assessed the relationship of socioeconomic factors with 1-year all-cause mortality and all-cause rehospitalization after adjustment for demographics, clinical factors, and quality-of-care measures. Both household income and education level were associated with higher risk of mortality (hazard ratio 2.80, 95% CI 1.37-5.72, lowest to highest income group) and rehospitalization after AMI (hazard ratio 1.55, 95% CI 1.17-2.05). Patients with low SES had worse clinical status at admission and received poorer quality of care. In multivariable modeling, the relationship between household income and mortality was attenuated by adjustment for demographic and clinical factors (hazard ratio 1.19, 95% CI 0.54-2.62), with a further small decrement in the hazard ratio after adjustment for quality of care. The relationship between income and rehospitalization was only partly attenuated by demographic and clinical factors (hazard ratio 1.38, 95% CI 1.01-1.89) and was not influenced by adjustment for quality of care. Patients' baseline clinical status largely explained the relationship between SES and mortality, but not rehospitalization, among patients with AMI.

Transplantation Outcomes for Children with Hypodiploid Acute Lymphoblastic Leukemia.

PubMed

Mehta, Parinda A; Zhang, Mei-Jie; Eapen, Mary; He, Wensheng; Seber, Adriana; Gibson, Brenda; Camitta, Bruce M; Kitko, Carrie L; Dvorak, Christopher C; Nemecek, Eneida R; Frangoul, Haydar A; Abdel-Azim, Hisham; Kasow, Kimberly A; Lehmann, Leslie; Gonzalez Vicent, Marta; Diaz Pérez, Miguel A; Ayas, Mouhab; Qayed, Muna; Carpenter, Paul A; Jodele, Sonata; Lund, Troy C; Leung, Wing H; Davies, Stella M

2015-07-01

Children with hypodiploid acute lymphoblastic leukemia (ALL) have inferior outcomes despite intensive risk-adapted chemotherapy regimens. We describe 78 children with hypodiploid ALL who underwent hematopoietic stem cell transplantation between 1990 and 2010. Thirty-nine (50%) patients had ≤ 43 chromosomes, 12 (15%) had 44 chromosomes, and 27 (35%) had 45 chromosomes. Forty-three (55%) patients underwent transplantation in first remission (CR1) and 35 (45%) underwent transplantation in ≥ second remission (CR2). Twenty-nine patients (37%) received a graft from a related donor and 49 (63%) from an unrelated donor. All patients received a myeloablative conditioning regimen. The 5-year probabilities of leukemia-free survival, overall survival, relapse, and treatment-related mortality for the entire cohort were 51%, 56%, 27%, and 22%, respectively. Multivariate analysis confirmed that mortality risks were higher for patients who underwent transplantation in CR2 (hazard ratio, 2.16; P = .05), with number of chromosomes ≤ 43 (hazard ratio, 2.15; P = .05), and for those who underwent transplantation in the first decade of the study period (hazard ratio, 2.60; P = .01). Similarly, treatment failure risks were higher with number of chromosomes ≤ 43 (hazard ratio, 2.28; P = .04) and the earlier transplantation period (hazard ratio, 2.51; P = .01). Although survival is better with advances in donor selection and supportive care, disease-related risk factors significantly influence transplantation outcomes. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Association between chronic azotemic kidney disease and the severity of periodontal disease in dogs.

PubMed

Glickman, Lawrence T; Glickman, Nita W; Moore, George E; Lund, Elizabeth M; Lantz, Gary C; Pressler, Barrak M

2011-05-01

Naturally occurring periodontal disease affects >75% of dogs and has been associated with cardiac lesions and presumptive endocarditis. However, the relationships between periodontal disease and chronic kidney disease (CKD) in dogs have not been studied. In a retrospective longitudinal study the incidence of azotemic CKD was compared between a cohort of 164,706 dogs with periodontal disease and a cohort of age-matched dogs with no periodontal disease from a national primary care practice. These dogs contributed 415,971 dog-years of follow-up from 2002 to 2008. Hazard ratios and 95% confidence intervals from Cox regression were used to compare the incidence of azotemic CKD in dogs with stage 1, 2, or 3/4 periodontal disease to dogs with no periodontal disease. The hazard ratio for azotemic CKD increased with increasing severity of periodontal disease (stage 1 hazard ratio=1.8, 95% confidence interval: 1.6, 2.1; stage 2 hazard ratio=2.0, 95% confidence interval: 1.7, 2.3; stage 3/4 hazard ratio=2.7, 95% confidence interval: 2.3, 3.0; P(trend)=<0.0001) after adjustment for age, gender, neuter status, breed, body weight, number of hospital visits, and dental procedures. Increasing severity of periodontal disease was also associated with serum creatinine >1.4 mg/dl and blood urea nitrogen >36 mg/dl, independent of a veterinarian's clinical diagnosis of CKD. Copyright © 2011 Elsevier B.V. All rights reserved.

Two models for evaluating landslide hazards

USGS Publications Warehouse

Davis, J.C.; Chung, C.-J.; Ohlmacher, G.C.

2006-01-01

Two alternative procedures for estimating landslide hazards were evaluated using data on topographic digital elevation models (DEMs) and bedrock lithologies in an area adjacent to the Missouri River in Atchison County, Kansas, USA. The two procedures are based on the likelihood ratio model but utilize different assumptions. The empirical likelihood ratio model is based on non-parametric empirical univariate frequency distribution functions under an assumption of conditional independence while the multivariate logistic discriminant model assumes that likelihood ratios can be expressed in terms of logistic functions. The relative hazards of occurrence of landslides were estimated by an empirical likelihood ratio model and by multivariate logistic discriminant analysis. Predictor variables consisted of grids containing topographic elevations, slope angles, and slope aspects calculated from a 30-m DEM. An integer grid of coded bedrock lithologies taken from digitized geologic maps was also used as a predictor variable. Both statistical models yield relative estimates in the form of the proportion of total map area predicted to already contain or to be the site of future landslides. The stabilities of estimates were checked by cross-validation of results from random subsamples, using each of the two procedures. Cell-by-cell comparisons of hazard maps made by the two models show that the two sets of estimates are virtually identical. This suggests that the empirical likelihood ratio and the logistic discriminant analysis models are robust with respect to the conditional independent assumption and the logistic function assumption, respectively, and that either model can be used successfully to evaluate landslide hazards. ?? 2006.

Loss to follow-up in the Australian HIV Observational Database

PubMed Central

McManus, Hamish; Petoumenos, Kathy; Brown, Katherine; Baker, David; Russell, Darren; Read, Tim; Smith, Don; Wray, Lynne; Giles, Michelle; Hoy, Jennifer; Carr, Andrew; Law, Matthew

2015-01-01

Background Loss to follow-up (LTFU) in HIV-positive cohorts is an important surrogate for interrupted clinical care which can potentially influence the assessment of HIV disease status and outcomes. After preliminary evaluation of LTFU rates and patient characteristics, we evaluated the risk of mortality by LTFU status in a high resource setting. Methods Rates of LTFU were measured in the Australian HIV Observational Database for a range of patient characteristics. Multivariate repeated measures regression methods were used to identify determinants of LTFU. Mortality by LTFU status was ascertained using linkage to the National Death Index. Survival following combination antiretroviral therapy initiation was investigated using the Kaplan-Meier (KM) method and Cox proportional hazards models. Results Of 3,413 patients included in this analysis, 1,632 (47.8%) had at least one episode of LTFU after enrolment. Multivariate predictors of LTFU included viral load (VL)>10,000 copies/ml (Rate ratio (RR) 1.63 (95% confidence interval (CI):1.45–1.84) (ref ≤400)), time under follow-up (per year) (RR 1.03 (95% CI: 1.02–1.04)) and prior LTFU (per episode) (RR 1.15 (95% CI: 1.06–1.24)). KM curves for survival were similar by LTFU status (p=0.484). LTFU was not associated with mortality in Cox proportional hazards models (univariate hazard ratio (HR) 0.93 (95% CI: 0.69–1.26) and multivariate HR 1.04 (95% CI: 0.77–1.43)). Conclusions Increased risk of LTFU was identified amongst patients with potentially higher infectiousness. We did not find significant mortality risk associated with LTFU. This is consistent with timely re-engagement with treatment, possibly via high levels of unreported linkage to other health care providers. PMID:25377928

Meta-analysis of neutropenia or leukopenia as a prognostic factor in patients with malignant disease undergoing chemotherapy.

PubMed

Shitara, Kohei; Matsuo, Keitaro; Oze, Isao; Mizota, Ayako; Kondo, Chihiro; Nomura, Motoo; Yokota, Tomoya; Takahari, Daisuke; Ura, Takashi; Muro, Kei

2011-08-01

We performed a systematic review and meta-analysis to determine the impact of neutropenia or leukopenia experienced during chemotherapy on survival. Eligible studies included prospective or retrospective analyses that evaluated neutropenia or leukopenia as a prognostic factor for overall survival or disease-free survival. Statistical analyses were conducted to calculate a summary hazard ratio and 95% confidence interval (CI) using random-effects or fixed-effects models based on the heterogeneity of the included studies. Thirteen trials were selected for the meta-analysis, with a total of 9,528 patients. The hazard ratio of death was 0.69 (95% CI, 0.64-0.75) for patients with higher-grade neutropenia or leukopenia compared to patients with lower-grade or lack of cytopenia. Our analysis was also stratified by statistical method (any statistical method to decrease lead-time bias; time-varying analysis or landmark analysis), but no differences were observed. Our results indicate that neutropenia or leukopenia experienced during chemotherapy is associated with improved survival in patients with advanced cancer or hematological malignancies undergoing chemotherapy. Future prospective analyses designed to investigate the potential impact of chemotherapy dose adjustment coupled with monitoring of neutropenia or leukopenia on survival are warranted.

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

PubMed Central

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

2013-01-01

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

Serum cholesterol and risk of lower urinary tract symptoms progression: Results from the Reduction by Dutasteride of Prostate Cancer Events study.

PubMed

Feng, Tom; Howard, Lauren E; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

2017-02-01

To determine if cholesterol is a risk factor for the development of lower urinary tract symptoms in asymptomatic men. A post-hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study was carried out in 2323 men with baseline International Prostate Symptom Score <8 and not taking benign prostatic hyperplasia or cholesterol medications. Cox proportion models were used to test the association between cholesterol, high-density lipoprotein, low-density lipoprotein and the cholesterol : high-density lipoprotein ratio with incident lower urinary tract symptoms, defined as first report of medical treatment, surgery or two reports of an International Prostate Symptom Score >14. A total of 253 men (10.9%) developed incident lower urinary tract symptoms. On crude analysis, higher high-density lipoprotein was associated with a decreased lower urinary tract symptoms risk (hazard ratio 0.89, P = 0.024), whereas total cholesterol and low-density lipoprotein showed no association. After multivariable adjustment, the association between high-density lipoprotein and incident lower urinary tract symptoms remained significant (hazard ratio 0.89, P = 0.044), whereas no association was observed for low-density lipoprotein (P = 0.611). There was a trend for higher cholesterol to be linked with higher lower urinary tract symptoms risk, though this was not statistically significant (hazard ratio 1.04, P = 0.054). A higher cholesterol : high-density lipoprotein ratio was associated with increased lower urinary tract symptoms risk on crude (hazard ratio 1.11, P = 0.016) and adjusted models (hazard ratio 1.12, P = 0.012). Among asymptomatic men participating in the REDUCE study, higher cholesterol was associated with increased incident lower urinary tract symptoms risk, though the association was not significant. A higher cholesterol : high-density lipoprotein ratio was associated with increased incident lower urinary tract symptoms, whereas higher high-density lipoprotein was protective. These findings suggest dyslipidemia might play a role in lower urinary tract symptoms progression. © 2016 The Japanese Urological Association.

T-category remains an important prognostic factor for oropharyngeal carcinoma in the era of human papillomavirus.

PubMed

Mackenzie, P; Pryor, D; Burmeister, E; Foote, M; Panizza, B; Burmeister, B; Porceddu, S

2014-10-01

To determine prognostic factors for locoregional relapse (LRR), distant relapse and all-cause death in a contemporary cohort of locoregionally advanced oropharyngeal squamous cell carcinoma (OSCC) treated with definitive chemoradiotherapy or radiotherapy alone. OSCC patients treated with definitive radiotherapy between 2005 and 2010 were identified from a prospective head and neck database. Patient age, gender, smoking history, human papillomavirus (HPV) status, T- and N-category, lowest involved nodal level and gross tumour volume of the primary (GTV-p) and nodal (GTV-n) disease were analysed in relation to LRR, distant relapse and death by way of univariate and multivariate analysis. In total, 130 patients were identified, 88 HPV positive, with a median follow-up of 42 months. On multivariate analysis HPV status was a significant predictor of LRR (hazard ratio 0.15; 95% confidence interval 0.05-0.51) and death (hazard ratio 0.29; 95% confidence interval 0.14-0.59) but not distant relapse (hazard ratio 0.53, 95% confidence interval 0.22-1.27). Increasing T-category was associated with a higher risk of LRR (hazard ratio 1.80 for T3/4 versus T1/2; 95% confidence interval 1.08-2.99), death (hazard ratio 1.37, 95% confidence interval 1.06-1.77) and distant relapse (hazard ratio 1.35; 95% confidence interval 1.00-1.83). Increasing GTV-p was associated with increased risk of distant relapse and death. N3 disease and low neck nodes were significant for LRR, distant relapse and death on univariate analysis only. Tumour HPV status was the strongest predictor of LRR and death. T-category is more predictive of distant relapse and may provide additional prognostic value for LRR and death when accounting for HPV status. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Improving results of allogeneic hematopoietic cell transplantation for adults with acute lymphoblastic leukemia in first complete remission: an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

PubMed Central

Giebel, Sebastian; Labopin, Myriam; Socié, Gerard; Beelen, Dietrich; Browne, Paul; Volin, Liisa; Kyrcz-Krzemien, Slawomira; Yakoub-Agha, Ibrahim; Aljurf, Mahmoud; Wu, Depei; Michallet, Mauricette; Arnold, Renate; Mohty, Mohamad; Nagler, Arnon

2017-01-01

Allogeneic hematopoietic cell transplantation is widely used to treat adults with high-risk acute lymphoblastic leukemia. The aim of this study was to analyze whether the results changed over time and to identify prognostic factors. Adult patients treated between 1993 and 2012 with myeloablative allogeneic hematopoietic cell transplantation from HLA matched sibling (n=2681) or unrelated (n=2178) donors in first complete remission were included. For transplantations from sibling donors performed between 2008 and 2012, 2-year probabilities of overall survival were: 76% (18–25 years old), 69% (26–35 and 36–45 years old) and 60% (46–55 years old). Among recipients of transplantations from unrelated donors, the respective survival rates were 66%, 70%, 61%, and 62%. In comparison with the 1993–2007 period, significant improvements were observed for all age groups except for the 26–35-year old patients. In a multivariate model, transplantations performed between 2008 and 2012, when compared to 1993–2007, were associated with significantly reduced risks of non-relapse mortality (Hazard Ratio 0.77, P=0.00006), relapse (Hazard Ratio 0.85, P=0.007), treatment failure (Hazard Ratio 0.81, P<0.00001), and overall mortality (Hazard Ratio 0.79, P<0.00001). In the analysis restricted to transplantations performed between 2008 and 2012, the use of total body irradiation-based conditioning was associated with reduced risk of relapse (Hazard Ratio 0.48, P=0.004) and treatment failure (Hazard Ratio 0.63, P=0.02). We conclude that results of allogeneic hematopoietic cell transplantation for adults with acute lymphoblastic leukemia improved significantly over time. Total body irradiation should be considered as the preferable type of myeloablative conditioning. PMID:27686376

Predicting risk of cancer during HIV infection: the role of inflammatory and coagulation biomarkers.

PubMed

Borges, Álvaro H; Silverberg, Michael J; Wentworth, Deborah; Grulich, Andrew E; Fätkenheuer, Gerd; Mitsuyasu, Ronald; Tambussi, Giuseppe; Sabin, Caroline A; Neaton, James D; Lundgren, Jens D

2013-06-01

To investigate the relationship between inflammatory [interleukin-6 (IL-6) and C-reactive protein (CRP)] and coagulation (D-dimer) biomarkers and cancer risk during HIV infection. A prospective cohort. HIV-infected patients on continuous antiretroviral therapy (ART) in the control arms of three randomized trials (N=5023) were included in an analysis of predictors of cancer (any type, infection-related or infection-unrelated). Hazard ratios for IL-6, CRP and D-dimer levels (log2-transformed) were calculated using Cox models stratified by trial and adjusted for demographics and CD4+ cell counts and adjusted also for all biomarkers simultaneously. To assess the possibility that biomarker levels were elevated at entry due to undiagnosed cancer, analyses were repeated excluding early cancer events (i.e. diagnosed during first 2 years of follow-up). During approximately 24,000 person-years of follow-up (PYFU), 172 patients developed cancer (70 infection-related; 102 infection-unrelated). The risk of developing cancer was associated with higher levels (per doubling) of IL-6 (hazard ratio 1.38, P<0.001), CRP (hazard ratio 1.16, P=0.001) and D-dimer (hazard ratio 1.17, P=0.03). However, only IL-6 (hazard ratio 1.29, P=0.003) remained associated with cancer risk when all biomarkers were considered simultaneously. Results for infection-related and infection-unrelated cancers were similar to results for any cancer. Hazard ratios excluding 69 early cancer events were 1.31 (P=0.007), 1.14 (P=0.02) and 1.07 (P=0.49) for IL-6, CRP and D-dimer, respectively. Activated inflammation and coagulation pathways are associated with increased cancer risk during HIV infection. This association was stronger for IL-6 and persisted after excluding early cancer. Trials of interventions may be warranted to assess whether cancer risk can be reduced by lowering IL-6 levels in HIV-positive individuals.

Basophil-lineage commitment in acute promyelocytic leukemia predicts for severe bleeding after starting therapy.

PubMed

Matarraz, Sergio; Leoz, Pilar; Fernández, Carlos; Colado, Enrique; Chillón, María Carmen; Vidriales, María Belén; González, Marcos; Rivera, Daniel; Osuna, Carlos Salvador; Caballero-Velázquez, Teresa; Van Der Velden, Vincent; Jongen-Lavrencic, Mojca; Gutiérrez, Oliver; Bermejo, Ana Yeguas; Alonso, Luis García; García, Monique Bourgeois; De Ramón Sánchez, Cristina; García-Donas, Gloria; Mateo, Aránzazu García; Recio, Isabel; Sánchez-Real, Javier; Mayado, Andrea; Gutiérrez, María Laura; Bárcena, Paloma; Barrena, Susana; López, Antonio; Van Dongen, Jacques; Orfao, Alberto

2018-03-23

Severe hemorrhagic events occur in a significant fraction of acute promyelocytic leukemia patients, either at presentation and/or early after starting therapy, leading to treatment failure and early deaths. However, identification of independent predictors for high-risk of severe bleeding at diagnosis, remains a challenge. Here, we investigated the immunophenotype of bone marrow leukemic cells from 109 newly diagnosed acute promyelocytic leukemia patients, particularly focusing on the identification of basophil-related features, and their potential association with severe bleeding episodes and patient overall survival.From all phenotypes investigated on leukemic cells, expression of the CD203c and/or CD22 basophil-associated markers showed the strongest association with the occurrence and severity of bleeding (p ≤ 0.007); moreover, aberrant expression of CD7, coexpression of CD34 + /CD7 + and lack of CD71 was also more frequently found among patients with (mild and severe) bleeding at baseline and/or after starting treatment (p ≤ 0.009). Multivariate analysis showed that CD203c expression (hazard ratio: 26.4; p = 0.003) and older age (hazard ratio: 5.4; p = 0.03) were the best independent predictors for cumulative incidence of severe bleeding after starting therapy. In addition, CD203c expression on leukemic cells (hazard ratio: 4.4; p = 0.01), low fibrinogen levels (hazard ratio: 8.8; p = 0.001), older age (hazard ratio: 9.0; p = 0.002), and high leukocyte count (hazard ratio: 5.6; p = 0.02) were the most informative independent predictors for overall survival.In summary, our results show that the presence of basophil-associated phenotypic characteristics on leukemic cells from acute promyelocytic leukemia patients at diagnosis is a powerful independent predictor for severe bleeding and overall survival, which might contribute in the future to (early) risk-adapted therapy decisions.

Alcohol consumption is associated with reduced risk of Type 2 diabetes and autoimmune diabetes in adults: results from the Nord-Trøndelag health study.

PubMed

Rasouli, B; Ahlbom, A; Andersson, T; Grill, V; Midthjell, K; Olsson, L; Carlsson, S

2013-01-01

We investigated the influence of different aspects of alcohol consumption on the risk of Type 2 diabetes and autoimmune diabetes in adults. We used data from the Nord-Trøndelag Health Survey (HUNT) study, in which all adults aged ≥ 20 years from Nord-Trondelag County were invited to participate in three surveys in 1984-1986, 1995-1997 and 2006-2008. Patients with diabetes were identified using self-reports, and participants with onset age ≥ 35 years were classified as having Type 2 diabetes if they were negative for anti-glutamic acid decarboxylase (n = 1841) and as having autoimmune diabetes if they were positive for anti-glutamic acid decarboxylase (n = 140). Hazard ratios of amount and frequency of alcohol use, alcoholic beverage choice, and binge drinking and alcohol use disorders were estimated. Moderate alcohol consumption (adjusted for confounders) was associated with a reduced risk of Type 2 diabetes in men, but not in women (hazard ratio for men 10-15 g/day 0.48, 95% CI 0.28-0.77; hazard ratio for women ≥ 10 g/day 0.81, 95% CI 0.33-1.96). The reduced risk was primarily linked to consumption of wine [hazard ratio 0.93, 95% CI 0.87-0.99 (per g/day)]. No increased risk was seen in participants reporting binge drinking or in problem drinkers. The results were also compatible with a reduced risk of autoimmune diabetes associated with alcohol consumption [hazard ratio 0.70, 95% CI 0.45-1.08 (frequent consumption) and hazard ratio 0.36, 95% CI 0.13-0.97 (2-7 g/day)]. Moderate alcohol consumption associates with reduced risk of both Type 2 diabetes and autoimmune diabetes. A protective effect of alcohol intake may be limited to men. High alcohol consumption does not seem to carry an increased risk of diabetes. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Vascular Disease, ESRD, and Death: Interpreting Competing Risk Analyses

PubMed Central

Coresh, Josef; Segev, Dorry L.; Kucirka, Lauren M.; Tighiouart, Hocine; Sarnak, Mark J.

2012-01-01

Summary Background and objectives Vascular disease, a common condition in CKD, is a risk factor for mortality and ESRD. Optimal patient care requires accurate estimation and ordering of these competing risks. Design, setting, participants, & measurements This is a prospective cohort study of screened (n=885) and randomized participants (n=837) in the Modification of Diet in Renal Disease study (original study enrollment, 1989–1992), evaluating the association of vascular disease with ESRD and pre-ESRD mortality using standard survival analysis and competing risk regression. Results The method of analysis resulted in markedly different estimates. Cumulative incidence by standard analysis (censoring at the competing event) implied that, with vascular disease, the 15-year incidence was 66% and 51% for ESRD and pre-ESRD death, respectively. A more accurate representation of absolute risk was estimated with competing risk regression: 15-year incidence was 54% and 29% for ESRD and pre-ESRD death, respectively. For the association of vascular disease with pre-ESRD death, estimates of relative risk by the two methods were similar (standard survival analysis adjusted hazard ratio, 1.63; 95% confidence interval, 1.20–2.20; competing risk regression adjusted subhazard ratio, 1.57; 95% confidence interval, 1.15–2.14). In contrast, the hazard and subhazard ratios differed substantially for other associations, such as GFR and pre-ESRD mortality. Conclusions When competing events exist, absolute risk is better estimated using competing risk regression, but etiologic associations by this method must be carefully interpreted. The presence of vascular disease in CKD decreases the likelihood of survival to ESRD, independent of age and other risk factors. PMID:22859747

Vascular disease, ESRD, and death: interpreting competing risk analyses.

PubMed

Grams, Morgan E; Coresh, Josef; Segev, Dorry L; Kucirka, Lauren M; Tighiouart, Hocine; Sarnak, Mark J

2012-10-01

Vascular disease, a common condition in CKD, is a risk factor for mortality and ESRD. Optimal patient care requires accurate estimation and ordering of these competing risks. This is a prospective cohort study of screened (n=885) and randomized participants (n=837) in the Modification of Diet in Renal Disease study (original study enrollment, 1989-1992), evaluating the association of vascular disease with ESRD and pre-ESRD mortality using standard survival analysis and competing risk regression. The method of analysis resulted in markedly different estimates. Cumulative incidence by standard analysis (censoring at the competing event) implied that, with vascular disease, the 15-year incidence was 66% and 51% for ESRD and pre-ESRD death, respectively. A more accurate representation of absolute risk was estimated with competing risk regression: 15-year incidence was 54% and 29% for ESRD and pre-ESRD death, respectively. For the association of vascular disease with pre-ESRD death, estimates of relative risk by the two methods were similar (standard survival analysis adjusted hazard ratio, 1.63; 95% confidence interval, 1.20-2.20; competing risk regression adjusted subhazard ratio, 1.57; 95% confidence interval, 1.15-2.14). In contrast, the hazard and subhazard ratios differed substantially for other associations, such as GFR and pre-ESRD mortality. When competing events exist, absolute risk is better estimated using competing risk regression, but etiologic associations by this method must be carefully interpreted. The presence of vascular disease in CKD decreases the likelihood of survival to ESRD, independent of age and other risk factors.

Engagement and Nonusage Attrition With a Free Physical Activity Promotion Program: The Case of 10,000 Steps Australia.

PubMed

Guertler, Diana; Vandelanotte, Corneel; Kirwan, Morwenna; Duncan, Mitch J

2015-07-15

Data from controlled trials indicate that Web-based interventions generally suffer from low engagement and high attrition. This is important because the level of exposure to intervention content is linked to intervention effectiveness. However, data from real-life Web-based behavior change interventions are scarce, especially when looking at physical activity promotion. The aims of this study were to (1) examine the engagement with the freely available physical activity promotion program 10,000 Steps, (2) examine how the use of a smartphone app may be helpful in increasing engagement with the intervention and in decreasing nonusage attrition, and (3) identify sociodemographic- and engagement-related determinants of nonusage attrition. Users (N=16,948) were grouped based on which platform (website, app) they logged their physical activity: Web only, app only, or Web and app. Groups were compared on sociodemographics and engagement parameters (duration of usage, number of individual and workplace challenges started, and number of physical activity log days) using ANOVA and chi-square tests. For a subsample of users that had been members for at least 3 months (n=11,651), Kaplan-Meier survival curves were estimated to plot attrition over the first 3 months after registration. A Cox regression model was used to determine predictors of nonusage attrition. In the overall sample, user groups differed significantly in all sociodemographics and engagement parameters. Engagement with the program was highest for Web-and-app users. In the subsample, 50.00% (5826/11,651) of users stopped logging physical activity through the program after 30 days. Cox regression showed that user group predicted nonusage attrition: Web-and-app users (hazard ratio=0.86, 95% CI 0.81-0.93, P<.001) and app-only users (hazard ratio=0.63, 95% CI 0.58-0.68, P<.001) showed a reduced attrition risk compared to Web-only users. Further, having a higher number of individual challenges (hazard ratio=0.62, 95% CI 0.59-0.66, P<.001), workplace challenges (hazard ratio=0.94, 95% CI 0.90-0.97, P<.001), physical activity logging days (hazard ratio=0.921, 95% CI 0.919-0.922, P<.001), and steps logged per day (hazard ratio=0.99999, 95% CI 0.99998-0.99999, P<.001) were associated with reduced nonusage attrition risk as well as older age (hazard ratio=0.992, 95% CI 0.991-0.994, P<.001), being male (hazard ratio=0.85, 95% CI 0.82-0.89, P<.001), and being non-Australian (hazard ratio=0.87, 95% CI 0.82-0.91, P<.001). Compared to other freely accessible Web-based health behavior interventions, the 10,000 Steps program showed high engagement. The use of an app alone or in addition to the website can enhance program engagement and reduce risk of attrition. Better understanding of participant reasons for reducing engagement can assist in clarifying how to best address this issue to maximize behavior change.

Method for treating materials for solidification

DOEpatents

Jantzen, Carol M.; Pickett, John B.; Martin, Hollis L.

1995-01-01

A method for treating materials such as wastes for solidification to form a solid, substantially nonleachable product. Addition of reactive silica rather than ordinary silica to the material when bringing the initial molar ratio of its silica constituent to a desired ratio within a preselected range increases the solubility and retention of the materials in the solidified matrix. Materials include hazardous, radioactive, mixed, and heavy metal species. Amounts of other constituents of the material, in addition to its silica content are also added so that the molar ratio of each of these constituents is within the preselected ranges for the final solidified product. The mixture is then solidified by cement solidification or vitrification. The method can be used to treat a variety of wastes, including but not limited to spent filter aids from waste water treatment, waste sludges, combinations of spent filter aids and waste sludges, combinations of supernate and waste sludges, incinerator ash, incinerator offgas blowdown, combinations of incinerator ash and offgas blowdown, cementitious wastes and contaminated soils.

Health Insurance Trajectories and Long-Term Survival After Heart Transplantation.

PubMed

Tumin, Dmitry; Foraker, Randi E; Smith, Sakima; Tobias, Joseph D; Hayes, Don

2016-09-01

Health insurance status at heart transplantation influences recipient survival, but implications of change in insurance for long-term outcomes are unclear. Adults aged 18 to 64 receiving first-time orthotopic heart transplants between July 2006 and December 2013 were identified in the United Network for Organ Sharing registry. Patients surviving >1 year were categorized according to trajectory of insurance status (private compared with public) at wait listing, transplantation, and 1-year follow-up. The most common insurance trajectories were continuous private coverage (44%), continuous public coverage (27%), and transition from private to public coverage (11%). Among patients who survived to 1 year (n=9088), continuous public insurance (hazard ratio =1.36; 95% confidence interval 1.19, 1.56; P<0.001) and transition from private to public insurance (hazard ratio =1.25; 95% confidence interval 1.04, 1.50; P=0.017) were associated with increased mortality hazard relative to continuous private insurance. Supplementary analyses of 11 247 patients included all durations of post-transplant survival and examined post-transplant private-to-public and public-to-private transitions as time-varying covariates. In these analyses, transition from private to public insurance was associated with increased mortality hazard (hazard ratio =1.25; 95% confidence interval 1.07, 1.47; P=0.005), whereas transition from public to private insurance was associated with lower mortality hazard (hazard ratio =0.78; 95% confidence interval 0.62, 0.97; P=0.024). Transition from private to public insurance after heart transplantation is associated with worse long-term outcomes, compounding disparities in post-transplant survival attributed to insurance status at transplantation. By contrast, post-transplant gain of private insurance among patients receiving publicly funded heart transplants was associated with improved outcomes. © 2016 American Heart Association, Inc.

Assessment on the leakage hazard of landfill leachate using three-dimensional excitation-emission fluorescence and parallel factor analysis method.

PubMed

Pan, Hongwei; Lei, Hongjun; Liu, Xin; Wei, Huaibin; Liu, Shufang

2017-09-01

A large number of simple and informal landfills exist in developing countries, which pose as tremendous soil and groundwater pollution threats. Early warning and monitoring of landfill leachate pollution status is of great importance. However, there is a shortage of affordable and effective tools and methods. In this study, a soil column experiment was performed to simulate the pollution status of leachate using three-dimensional excitation-emission fluorescence (3D-EEMF) and parallel factor analysis (PARAFAC) models. Sum of squared residuals (SSR) and principal component analysis (PCA) were used to determine the optimal components for PARAFAC. A one-way analysis of variance showed that the component scores of the soil column leachate were significant influenced by landfill leachate (p<0.05). Therefore, the ratio of the component scores of the soil under the landfill to that of natural soil could be used to evaluate the leakage status of landfill leachate. Furthermore, a hazard index (HI) and a hazard evaluation standard were established. A case study of Kaifeng landfill indicated a low hazard (level 5) by the use of HI. In summation, HI is presented as a tool to evaluate landfill pollution status and for the guidance of municipal solid waste management. Copyright © 2017 Elsevier Ltd. All rights reserved.

Non-detonable and non-explosive explosive simulators

DOEpatents

Simpson, R.L.; Pruneda, C.O.

1997-07-15

A simulator which is chemically equivalent to an explosive, but is not detonable or explodable is disclosed. The simulator is a combination of an explosive material with an inert material, either in a matrix or as a coating, where the explosive has a high surface ratio but small volume ratio. The simulator has particular use in the training of explosives detecting dogs, calibrating analytical instruments which are sensitive to either vapor or elemental composition, or other applications where the hazards associated with explosives is undesirable but where chemical and/or elemental equivalence is required. The explosive simulants may be fabricated by different techniques. A first method involves the use of standard slurry coatings to produce a material with a very high binder to explosive ratio without masking the explosive vapor, and a second method involves coating inert substrates with thin layers of explosive. 11 figs.

Smoking and Schizophrenia in Population Cohorts of Swedish Women and Men: A Prospective Co-Relative Control Study

PubMed Central

Kendler, Kenneth S.; Lönn, Sara Larsson; Sundquist, Jan; Sundquist, Kristina

2015-01-01

Objective The purpose of this study was to clarify the causes of the smoking-schizophrenia association. Method Using Cox proportional hazard and co-relative control models, the authors predicted future risk for a diagnosis of schizophrenia or nonaffective psychosis from the smoking status of 1,413,849 women and 233,879 men from, respectively, the Swedish birth and conscript registries. Results Smoking was assessed in women at a mean age of 27 and in men at a mean age of 18. The mean age at end of follow-up was 46 for women and 26 for men. Hazard ratios for first-onset schizophrenia were elevated both for light smoking (2.21 [95% CI=1.90–2.56] for women and 2.15 [95% CI=1.25–3.44] for men) and heavy smoking (3.45 [95% CI=2.95–4.03] for women and 3.80 [95% CI=1.19–6.60] for men). These associations did not decline when schizophrenia onsets 3–5 years after smoking assessment were censored. When age, socioeconomic status, and drug abuse were controlled for, hazard ratios declined only modestly in both samples. Women who smoked into late pregnancy had a much higher risk for schizophrenia than those who quit early. Hazard ratios predicting nonaffective psychosis in the general population, in cousins, in half siblings, and in full siblings discordant for heavy smoking were, respectively, 2.67, 2.71, 2.54, and 2.18. A model utilizing all relative pairs predicted a hazard ratio of 1.69 (95% CI=1.17–2.44) for nonaffective psychosis in the heavy-smoking member of discordant monozygotic twin pairs. Conclusions Smoking prospectively predicts risk for schizophrenia. This association does not arise from smoking onset during a schizophrenic prodrome and demonstrates a clear dose-response relationship. While little of this association is explained by epidemiological confounders, a portion arises from common familial/genetic risk factors. However, in full siblings and especially monozygotic twins discordant for smoking, risk for nonaffective psychosis is appreciably higher in the smoking member. These results can help in evaluating the plausibility of various etiological hypotheses for the smoking-schizophrenia association. PMID:26046339

Sedation Intensity in the First 48 Hours of Mechanical Ventilation and 180-Day Mortality: A Multinational Prospective Longitudinal Cohort Study.

PubMed

Shehabi, Yahya; Bellomo, Rinaldo; Kadiman, Suhaini; Ti, Lian Kah; Howe, Belinda; Reade, Michael C; Khoo, Tien Meng; Alias, Anita; Wong, Yu-Lin; Mukhopadhyay, Amartya; McArthur, Colin; Seppelt, Ian; Webb, Steven A; Green, Maja; Bailey, Michael J

2018-06-01

In the absence of a universal definition of light or deep sedation, the level of sedation that conveys favorable outcomes is unknown. We quantified the relationship between escalating intensity of sedation in the first 48 hours of mechanical ventilation and 180-day survival, time to extubation, and delirium. Harmonized data from prospective multicenter international longitudinal cohort studies SETTING:: Diverse mix of ICUs. Critically ill patients expected to be ventilated for longer than 24 hours. Richmond Agitation Sedation Scale and pain were assessed every 4 hours. Delirium and mobilization were assessed daily using the Confusion Assessment Method of ICU and a standardized mobility assessment, respectively. Sedation intensity was assessed using a Sedation Index, calculated as the sum of negative Richmond Agitation Sedation Scale measurements divided by the total number of assessments. We used multivariable Cox proportional hazard models to adjust for relevant covariates. We performed subgroup and sensitivity analysis accounting for immortal time bias using the same variables within 120 and 168 hours. The main outcome was 180-day survival. We assessed 703 patients in 42 ICUs with a mean (SD) Acute Physiology and Chronic Health Evaluation II score of 22.2 (8.5) with 180-day mortality of 32.3% (227). The median (interquartile range) ventilation time was 4.54 days (2.47-8.43 d). Delirium occurred in 273 (38.8%) of patients. Sedation intensity, in an escalating dose-dependent relationship, independently predicted increased risk of death (hazard ratio [95% CI], 1.29 [1.15-1.46]; p < 0.001, delirium hazard ratio [95% CI], 1.25 [1.10-1.43]), p value equals to 0.001 and reduced chance of early extubation hazard ratio (95% CI) 0.80 (0.73-0.87), p value of less than 0.001. Agitation level independently predicted subsequent delirium hazard ratio [95% CI], of 1.25 (1.04-1.49), p value equals to 0.02. Delirium or mobilization episodes within 168 hours, adjusted for sedation intensity, were not associated with survival. Sedation intensity independently, in an ascending relationship, predicted increased risk of death, delirium, and delayed time to extubation. These observations suggest that keeping sedation level equivalent to a Richmond Agitation Sedation Scale 0 is a clinically desirable goal.

Application of decision tree model for the ground subsidence hazard mapping near abandoned underground coal mines.

PubMed

Lee, Saro; Park, Inhye

2013-09-30

Subsidence of ground caused by underground mines poses hazards to human life and property. This study analyzed the hazard to ground subsidence using factors that can affect ground subsidence and a decision tree approach in a geographic information system (GIS). The study area was Taebaek, Gangwon-do, Korea, where many abandoned underground coal mines exist. Spatial data, topography, geology, and various ground-engineering data for the subsidence area were collected and compiled in a database for mapping ground-subsidence hazard (GSH). The subsidence area was randomly split 50/50 for training and validation of the models. A data-mining classification technique was applied to the GSH mapping, and decision trees were constructed using the chi-squared automatic interaction detector (CHAID) and the quick, unbiased, and efficient statistical tree (QUEST) algorithms. The frequency ratio model was also applied to the GSH mapping for comparing with probabilistic model. The resulting GSH maps were validated using area-under-the-curve (AUC) analysis with the subsidence area data that had not been used for training the model. The highest accuracy was achieved by the decision tree model using CHAID algorithm (94.01%) comparing with QUEST algorithms (90.37%) and frequency ratio model (86.70%). These accuracies are higher than previously reported results for decision tree. Decision tree methods can therefore be used efficiently for GSH analysis and might be widely used for prediction of various spatial events. Copyright © 2013. Published by Elsevier Ltd.

An Analysis of Cumulative Risks Indicated by Biomonitoring Data of Six Phthalates Using the Maximum Cumulative Ratio

EPA Science Inventory

The Maximum Cumulative Ratio (MCR) quantifies the degree to which a single component of a chemical mixture drives the cumulative risk of a receptor.1 This study used the MCR, the Hazard Index (HI) and Hazard Quotient (HQ) to evaluate co-exposures to six phthalates using biomonito...

Brain function and structure and risk for incident diabetes: The Atherosclerosis Risk in Communities Study.

PubMed

Bancks, Michael P; Alonso, Alvaro; Gottesman, Rebecca F; Mosley, Thomas H; Selvin, Elizabeth; Pankow, James S

2017-12-01

Diabetes is prospectively associated with cognitive decline. Whether lower cognitive function and worse brain structure are prospectively associated with incident diabetes is unclear. We analyzed data for 10,133 individuals with cognitive function testing (1990-1992) and 1212 individuals with brain magnetic resonance imaging (1993-1994) from the Atherosclerosis Risk in Communities cohort. We estimated hazard ratios for incident diabetes through 2014 after adjustment for traditional diabetes risk factors and cohort attrition. Higher level of baseline cognitive function was associated with lower risk for diabetes (per 1 standard deviation, hazard ratio = 0.94; 95% confidence interval = 0.90, 0.98). This association did not persist after accounting for baseline glucose level, case ascertainment methods, and cohort attrition. No association was observed between any brain magnetic resonance imaging measure and incident diabetes. This is one of the first studies to prospectively evaluate the association between both cognitive function and brain structure and the incidence of diabetes. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Prechemotherapy neutrophil : lymphocyte ratio is superior to the platelet : lymphocyte ratio as a prognostic indicator for locally advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapy.

PubMed

Ji, W H; Jiang, Y H; Ji, Y L; Li, B; Mao, W M

2016-07-01

The study aimed to evaluate the prognostic significance of prechemotherapy neutrophil to lymphocyte ratio and platelet to lymphocyte ratio, and preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in locally advanced esophageal squamous cell cancer. We analyzed retrospectively locally advanced esophageal squamous cell cancer patients who had received neoadjuvant chemotherapy before undergoing a radical esophagectomy between 2009 and 2012. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio before chemotherapy and before the surgery were calculated. Univariate analyses showed that prechemotherapy neutrophil to lymphocyte ratio >5 (P = 0.048, hazard ratio = 2.86; 95% confidence interval: 1.01-8.12) and prechemotherapy platelet to lymphocyte ratio >130 (P = 0.025, hazard ratio = 5.50; 95% confidence interval: 1.23-24.55) were associated significantly with overall survival (OS), and prechemotherapy platelet to lymphocyte ratio >130 (P = 0.026, hazard ratio = 3.18; 95% confidence interval: 1.15-8.85) was associated significantly with progression-free survival. However, only prechemotherapy neutrophil to lymphocyte ratio >5 (P = 0.024, hazard ratio = 3.50; 95% confidence interval: 1.18-10.40) remained significantly associated with OS in multivariate analyses. Neither preoperative neutrophil to lymphocyte ratio nor platelet to lymphocyte ratio was associated with OS or progression-free survival. The prechemotherapy neutrophil to lymphocyte ratio >5 to preoperative neutrophil to lymphocyte ratio ≤5 group showed significantly worse OS than the prechemotherapy neutrophil to lymphocyte ratio ≤5 to preoperative neutrophil to lymphocyte ratio ≤5 group (P = 0.050). The prechemotherapy platelet to lymphocyte ratio >130 to preoperative platelet to lymphocyte ratio ≤130 group (P = 0.016) and platelet to lymphocyte ratio >130 to preoperative platelet to lymphocyte ratio >130 group (P = 0.042) showed significantly worse OS than the prechemotherapy platelet to lymphocyte ratio ≤30 to preoperative platelet to lymphocyte ratio ≤130 group. In conclusions, prechemotherapy neutrophil to lymphocyte ratio is an independent prognostic factor for OS in patients with advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapy, and, as an adverse prognostic predictor, increased prechemotherapy neutrophil to lymphocyte ratio is superior to platelet to lymphocyte ratio. Maintaining a low neutrophil to lymphocyte ratio and platelet to lymphocyte ratio throughout treatment is a predictor of better OS. © 2015 International Society for Diseases of the Esophagus.

Problems Related to Alcohol Consumption among Youth in Jujuy Province, Argentina

PubMed Central

Alderete, Ethel; Kaplan, Celia P; Nah, Gregory; Pérez-Stable, Eliseo J

2014-01-01

Objective To examine drinking patterns and alcohol-related problems among youth in Jujuy, Argentina. Material and Methods A survey was conducted in 2005 with a representative sample of 9th grade youth (12 to 17 years old) including sociodemographic and consumption data, and the AUDIT-C test. Results Nine percent of girls and 11% of boys reported hazardous drinking; 12% of girls and 19% of boys reported dependence symptoms. The odds ratio for dependence symptoms (adjusted OR 0.7; 95%CI: 0.6-0.8) and for hazardous drinking (adjusted OR 0.7; 95%CI: 0.6-0.8) was significantly lower for girls compared with boys. Older age, working, and attending night school were risk factors for hazardous drinking, dependence symptoms, and harmful drinking. Conclusions A significant proportion of youth reported problematic patterns of alcohol drinking, highlighting the need to implement prevention and treatment interventions tailored to the adolescent population. PMID:18670721

Depression and Risk of Incident Asthma in Adults. The CARDIA Study

PubMed Central

Schreiner, Pamela J.; Sood, Akshay; Jacobs, David R.

2014-01-01

Rationale: Asthma is associated with depression, but the temporality of the association has not been established. Objectives: To examine the association between prevalent elevated depressive symptoms and incident asthma, and between prevalent asthma and incident elevated depressive symptoms in a cohort of young and middle-aged adults. Methods: We examined the longitudinal association between asthma and depressive symptoms bidirectionally in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. First, 3,614 participants, free of asthma, were classified by elevated depressive symptoms at the CARDIA Year-5 exam (n = 856 elevated vs. 2,758 not elevated; ages 23–35 yr) and followed for 20 years to incident asthma. Then, 3,016 participants, free of elevated depressive symptoms, were classified by self-reported current asthma status (n = 188 prevalent vs. 2,828 not prevalent) at the CARDIA Year-5 exam and followed for 20 years until onset of elevated depressive symptoms. Measurements and Main Results: The relative hazard of incident asthma among those with elevated depressive symptoms was 1.26 (95% confidence interval [CI] = 1.02–1.56) after adjustment for covariates. When depressive status was modeled as the total number of reports of elevated depressive symptoms before the onset of asthma, the adjusted hazard ratio was 1.15 (95% CI = 1.02–1.29). The hazard of incident elevated depressive symptoms for those with asthma was no different than the hazard in those without asthma (adjusted hazard ratio = 0.92; 95% CI = 0.70–1.20). Conclusions: This longitudinal observational study points to depression as a marker of risk for incident adult-onset asthma. On the other hand, prevalent asthma is not associated with incident adult-onset depression. PMID:24456492

Body Adiposity in Later Life and the Incidence of Dementia: The Health in Men Study

PubMed Central

Power, Brian D.; Alfonso, Helman; Flicker, Leon; Hankey, Graeme J.; Yeap, Bu B.; Almeida, Osvaldo P.

2011-01-01

Objective To determine if adiposity in later life increases dementia hazard. Methods Cohort study of 12,047 men aged 65–84 years living in Perth, Australia. Adiposity exposures were baseline body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR). We used the Western Australian Data Linkage System (WADLS) to establish the presence of new cases of dementia between 1996 and 2009 according to the International Classification of Diseases (ICD). Crude and adjusted hazard ratio (HR, 95% confidence interval, 95%CI) of dementia for each adiposity marker was calculated using Cox regression models. Other measured factors included age, marital status, education, alcohol use, smoking, diet, physical activity, and prevalent hypertension, diabetes, dyslipidaemia and cardiovascular disease. Results Compared with men with BMI<25, participants with BMI between 25–30 had lower adjusted HR of dementia (HR = 0.82, 95% CI = 0.70–0.95). The HR of dementia for men with BMI≥30 was comparable to men with BMI<25 (HR = 0.82, 95%CI = 0.67–1.01). Waist circumference showed no obvious association with dementia hazard. Men with WHR≥0.9 had lower adjusted HR of dementia than men with WHR <0.9 (HR = 0.82, 95%CI = 0.69–0.98). We found a “J” shape association between measures of obesity and the hazard of dementia, with the nadir of risk being in the overweight range of BMI and about 1 for WHR. Conclusions Higher adiposity is not associated with incident dementia in this Australian cohort of older men. Overweight men and those with WHR≥0.9 have lower hazard of dementia than men with normal weight and with WHR<0.9. PMID:21464984

Thermal co-treatment of combustible hazardous waste and waste incineration fly ash in a rotary kiln.

PubMed

Huber, Florian; Blasenbauer, Dominik; Mallow, Ole; Lederer, Jakob; Winter, Franz; Fellner, Johann

2016-12-01

As current disposal practices for municipal solid waste incineration (MSWI) fly ash are either associated with significant costs or negative environmental impacts, an alternative treatment was investigated in a field scale experiment. Thereto, two rotary kilns were fed with hazardous waste, and moistened MSWI fly ash (water content of 23%) was added to the fuel of one kiln with a ratio of 169kg/Mg hazardous waste for 54h and 300kg/Mg hazardous waste for 48h while the other kiln was used as a reference. It was shown that the vast majority (>90%) of the inserted MSWI fly ash was transferred to the bottom ash of the rotary kiln. This bottom ash complied with the legal limits for non-hazardous waste landfills, thereby demonstrating the potential of the investigated method to transfer hazardous waste (MSWI fly ash) into non-hazardous waste (bottom ash). The results of a simple mixing test (MSWI fly ash and rotary kiln bottom ash have been mixed accordingly without thermal treatment) revealed that the observed transformation of hazardous MSWI fly ash into non-hazardous bottom ash during thermal co-treatment cannot be referred to dilution, as the mixture did not comply with legal limits for non-hazardous waste landfills. For the newly generated fly ash of the kiln, an increase in the concentration of Cd, K and Pb by 54%, 57% and 22%, respectively, was observed. In general, the operation of the rotary kiln was not impaired by the MSWI fly ash addition. Copyright © 2016 Elsevier Ltd. All rights reserved.

Determinants of variations in initial treatment strategies for stable ischemic heart disease

PubMed Central

Bennell, Maria C.; Qiu, Feng; Kingsbury, Kori J.; Austin, Peter C.; Wijeysundera, Harindra C.

2015-01-01

Background: The ratio of revascularization to medical therapy (referred to herein as the revascularization ratio) for the initial treatment of stable ischemic heart disease varies considerably across hospitals. We conducted a comprehensive study to identify patient, physician and hospital factors associated with variations in the revascularization ratio across 18 cardiac centres in the province of Ontario. We also explored whether clinical outcomes differed between hospitals with high, medium and low ratios. Methods: We identified all patients in Ontario who had stable ischemic heart disease documented by index angiography performed between Oct. 1, 2008, and Sept. 30, 2011, at any of the 18 cardiac centres in the province. We classified patients by initial treatment strategy (medical therapy or revascularization). Hospitals were classified into equal tertiles based on their revascularization ratio. The primary outcome was all-cause mortality. Patient follow-up was until Dec. 31, 2012. Hierarchical logistic regression models identified predictors of revascularization. Multivariable Cox proportional hazards models, with a time-varying covariate for actual treatment received, were used to evaluate the impact of the revascularization ratio on clinical outcomes. Results: Variation in revascularization ratios was twofold across the hospitals. Patient factors accounted for 67.4% of the variation in revascularization ratios. Physician and hospital factors were not significantly associated with the variation. Significant patient-level predictors of revascularization were history of smoking, multivessel disease, high-risk findings on noninvasive stress testing and more severe symptoms of angina (v. no symptoms). Treatment at hospitals with a high revascularization ratio was associated with increased mortality compared with treatment at hospitals with a low ratio (hazard ratio 1.12, 95% confidence interval 1.03–1.21). Interpretation: Most of the variation in revascularization ratios across hospitals was warranted, in that it was driven by patient factors. Nonetheless, the variation was associated with potentially important differences in mortality. PMID:25991840

A comprehensive analysis of the content of heavy rare-earth elements and platinum in snow samples to assess the ecological hazard of air pollution in urban areas

NASA Astrophysics Data System (ADS)

Vinokurov, S. F.; Tarasova, N. P.; Trunova, A. N.; Sychkova, V. A.

2017-07-01

Snow samples from the territory of the Setun River Valley Wildlife Sanctuary are analyzed for the content of rare-earth elements, heavy metals, and other hazardous elements by the inductively coupled plasma mass-spectrometry method. The changes in the concentrations of rare-earth elements, Pt, Pd, and indicator ratios of elements in the solid fractions of snow are revealed. A trend toward a decrease in the content of several elements northeastward of the Moscow Ring Road (MRR) is established. The level of seasonal atmospheric contamination of the area under study is assessed, and a possible source is identified.

Air Pollution and Nonmalignant Respiratory Mortality in 16 Cohorts within the ESCAPE Project

PubMed Central

Dimakopoulou, Konstantina; Samoli, Evangelia; Beelen, Rob; Stafoggia, Massimo; Andersen, Zorana Jovanovic; Hoffmann, Barbara; Fischer, Paul; Nieuwenhuijsen, Mark; Vineis, Paolo; Xun, Wei; Hoek, Gerard; Raaschou-Nielsen, Ole; Oudin, Anna; Forsberg, Bertil; Modig, Lars; Jousilahti, Pekka; Lanki, Timo; Turunen, Anu; Oftedal, Bente; Nafstad, Per; Schwarze, Per E.; Penell, Johanna; Fratiglioni, Laura; Andersson, Niklas; Pedersen, Nancy; Korek, Michal; De Faire, Ulf; Eriksen, Kirsten Thorup; Tjønneland, Anne; Becker, Thomas; Wang, Meng; Bueno-de-Mesquita, Bas; Tsai, Ming-Yi; Eeftens, Marloes; Peeters, Petra H.; Meliefste, Kees; Marcon, Alessandro; Krämer, Ursula; Kuhlbusch, Thomas A.J.; Vossoughi, Mohammad; Key, Timothy; de Hoogh, Kees; Hampel, Regina; Peters, Annette; Heinrich, Joachim; Weinmayr, Gudrun; Concin, Hans; Nagel, Gabriele; Ineichen, Alex; Jacquemin, Bénédicte; Stempfelet, Morgane; Vilier, Alice; Ricceri, Fulvio; Sacerdote, Carlotta; Pedeli, Xanthi; Katsoulis, Michalis; Trichopoulou, Antonia; Brunekreef, Bert

2014-01-01

Rationale: Prospective cohort studies have shown that chronic exposure to particulate matter and traffic-related air pollution is associated with reduced survival. However, the effects on nonmalignant respiratory mortality are less studied, and the data reported are less consistent. Objectives: We have investigated the relationship of long-term exposure to air pollution and nonmalignant respiratory mortality in 16 cohorts with individual level data within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE). Methods: Data from 16 ongoing cohort studies from Europe were used. The total number of subjects was 307,553. There were 1,559 respiratory deaths during follow-up. Measurements and Main Results: Air pollution exposure was estimated by land use regression models at the baseline residential addresses of study participants and traffic-proximity variables were derived from geographical databases following a standardized procedure within the ESCAPE study. Cohort-specific hazard ratios obtained by Cox proportional hazard models from standardized individual cohort analyses were combined using metaanalyses. We found no significant associations between air pollution exposure and nonmalignant respiratory mortality. Most hazard ratios were slightly below unity, with the exception of the traffic-proximity indicators. Conclusions: In this study of 16 cohorts, there was no association between air pollution exposure and nonmalignant respiratory mortality. PMID:24521254

Site response in the eastern United States: A comparison of Vs30 measurements with estimates from horizontal:vertical spectral ratios

USGS Publications Warehouse

McNamara, Daniel E.; Stephenson, William J.; Odum, Jackson K.; Williams, Robert; Gee, Lind

2014-01-01

Earthquake damage is often increased due to local ground-motion amplification caused by soft soils, thick basin sediments, topographic effects, and liquefaction. A critical factor contributing to the assessment of seismic hazard is detailed information on local site response. In order to address and quantify the site response at seismograph stations in the eastern United States, we investigate the regional spatial variation of horizontal:vertical spectral ratios (HVSR) using ambient noise recorded at permanent regional and national network stations as well as temporary seismic stations deployed in order to record aftershocks of the 2011 Mineral, Virginia, earthquake. We compare the HVSR peak frequency to surface measurements of the shear-wave seismic velocity to 30 m depth (Vs30) at 21 seismograph stations in the eastern United States and find that HVSR peak frequency increases with increasing Vs30. We use this relationship to estimate the National Earthquake Hazards Reduction Program soil class at 218 ANSS (Advanced National Seismic System), GSN (Global Seismographic Network), and RSN (Regional Seismograph Networks) locations in the eastern United States, and suggest that this seismic station–based HVSR proxy could potentially be used to calibrate other site response characterization methods commonly used to estimate shaking hazard.

Confounding by dietary patterns of the inverse association between alcohol consumption and type 2 diabetes risk.

PubMed

Imamura, Fumiaki; Lichtenstein, Alice H; Dallal, Gerard E; Meigs, James B; Jacques, Paul F

2009-07-01

The ability to interpret epidemiologic observations is limited because of potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome the limitation. To examine confounding by dietary pattern as well as standard risk factors and selected nutrients, the authors modeled the longitudinal association between alcohol consumption and 7-year risk of type 2 diabetes mellitus in 2,879 healthy adults enrolled in the Framingham Offspring Study (1991-2001) by Cox proportional hazard models. After adjustment for standard risk factors, consumers of > or =9.0 drinks/week had a significantly lower risk of type 2 diabetes mellitus compared with abstainers (hazard ratio = 0.47, 95% confidence interval (CI): 0.27, 0.81). Adjustment for selected nutrients had little effect on the hazard ratio, whereas adjustment for dietary pattern variables by factor analysis significantly shifted the hazard ratio away from null (hazard ratio = 0.33, 95% CI: 0.17, 0.64) by 40.0% (95% CI: 16.8, 57.0; P = 0.002). Dietary pattern variables by partial least squares showed similar results. Therefore, the observed inverse association, consistent with past studies, was confounded by dietary patterns, and this confounding was not captured by individual nutrient adjustment. The data suggest that alcohol intake, not dietary patterns associated with alcohol intake, is responsible for the observed inverse association with type 2 diabetes mellitus risk.

Asymptomatic embolisation for prediction of stroke in the Asymptomatic Carotid Emboli Study (ACES): a prospective observational study

PubMed Central

Markus, Hugh S; King, Alice; Shipley, Martin; Topakian, Raffi; Cullinane, Marisa; Reihill, Sheila; Bornstein, Natan M; Schaafsma, Arjen

2010-01-01

Summary Background Whether surgery is beneficial for patients with asymptomatic carotid stenosis is controversial. Better methods of identifying patients who are likely to develop stroke would improve the risk–benefit ratio for carotid endarterectomy. We aimed to investigate whether detection of asymptomatic embolic signals by use of transcranial doppler (TCD) could predict stroke risk in patients with asymptomatic carotid stenosis. Methods The Asymptomatic Carotid Emboli Study (ACES) was a prospective observational study in patients with asymptomatic carotid stenosis of at least 70% from 26 centres worldwide. To detect the presence of embolic signals, patients had two 1 h TCD recordings from the ipsilateral middle cerebral artery at baseline and one 1 h recording at 6, 12, and 18 months. Patients were followed up for 2 years. The primary endpoint was ipsilateral stroke and transient ischaemic attack. All recordings were analysed centrally by investigators masked to patient identity. Findings 482 patients were recruited, of whom 467 had evaluable recordings. Embolic signals were present in 77 of 467 patients at baseline. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack from baseline to 2 years in patients with embolic signals compared with those without was 2·54 (95% CI 1·20–5·36; p=0·015). For ipsilateral stroke alone, the hazard ratio was 5·57 (1·61–19·32; p=0·007). The absolute annual risk of ipsilateral stroke or transient ischaemic attack between baseline and 2 years was 7·13% in patients with embolic signals and 3·04% in those without, and for ipsilateral stroke was 3·62% in patients with embolic signals and 0·70% in those without. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack for patients who had embolic signals on the recording preceding the next 6-month follow-up compared with those who did not was 2·63 (95% CI 1·01–6·88; p=0·049), and for ipsilateral stroke alone the hazard ratio was 6·37 (1·59–25·57; p=0·009). Controlling for antiplatelet therapy, degree of stenosis, and other risk factors did not alter the results. Interpretation Detection of asymptomatic embolisation on TCD can be used to identify patients with asymptomatic carotid stenosis who are at a higher risk of stroke and transient ischaemic attack, and also those with a low absolute stroke risk. Assessment of the presence of embolic signals on TCD might be useful in the selection of patients with asymptomatic carotid stenosis who are likely to benefit from endarterectomy. Funding British Heart Foundation. PMID:20554250

METHODOLOGY AND CALCULATIONS FOR THE ASSIGNMENT OF WASTE GROUPS FOR THE LARGE UNDERGROUND WASTE STORAGE TANKS AT THE HANFORD SITE

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

WEBER RA

2009-01-16

The Hanford Site contains 177 large underground radioactive waste storage tanks (28 double-shell tanks and 149 single-shell tanks). These tanks are categorized into one of three waste groups (A, B, and C) based on their waste and tank characteristics. These waste group assignments reflect a tank's propensity to retain a significant volume of flammable gases and the potential of the waste to release retained gas by a buoyant displacement gas release event. Assignments of waste groups to the 177 double-shell tanks and single-shell tanks, as reported in this document, are based on a Monte Carlo analysis of three criteria. Themore » first criterion is the headspace flammable gas concentration following release of retained gas. This criterion determines whether the tank contains sufficient retained gas such that the well-mixed headspace flammable gas concentration would reach 100% of the lower flammability limit if the entire tank's retained gas were released. If the volume of retained gas is not sufficient to reach 100% of the lower flammability limit, then flammable conditions cannot be reached and the tank is classified as a waste group C tank independent of the method the gas is released. The second criterion is the energy ratio and considers whether there is sufficient supernatant on top of the saturated solids such that gas-bearing solids have the potential energy required to break up the material and release gas. Tanks that are not waste group C tanks and that have an energy ratio < 3.0 do not have sufficient potential energy to break up material and release gas and are assigned to waste group B. These tanks are considered to represent a potential induced flammable gas release hazard, but no spontaneous buoyant displacement flammable gas release hazard. Tanks that are not waste group C tanks and have an energy ratio {ge} 3.0, but that pass the third criterion (buoyancy ratio < 1.0, see below) are also assigned to waste group B. Even though the designation as a waste group B (or A) tank identifies the potential for an induced flammable gas release hazard, the hazard only exists for specific operations that can release the retained gas in the tank at a rate and quantity that results in reaching 100% of the lower flammability limit in the tank headspace. The identification and evaluation of tank farm operations that could cause an induced flammable gas release hazard in a waste group B (or A) tank are included in other documents. The third criterion is the buoyancy ratio. This criterion addresses tanks that are not waste group C double-shell tanks and have an energy ratio {ge} 3.0. For these double-shell tanks, the buoyancy ratio considers whether the saturated solids can retain sufficient gas to exceed neutral buoyancy relative to the supernatant layer and therefore have buoyant displacement gas release events. If the buoyancy ratio is {ge} 1.0, that double-shell tank is assigned to waste group A. These tanks are considered to have a potential spontaneous buoyant displacement flammable gas release hazard in addition to a potential induced flammable gas release hazard. This document categorizes each of the large waste storage tanks into one of several categories based on each tank's waste characteristics. These waste group assignments reflect a tank's propensity to retain a significant volume of flammable gases and the potential of the waste to release retained gas by a buoyant displacement event. Revision 8 is the annual update of the calculations of the flammable gas Waste Groups for DSTs and SSTs.« less

Prevalence and Correlates of Hazardous Drinking among Female Sex Workers in 13 Mexican Cities

PubMed Central

Semple, Shirley J.; Pitpitan, Eileen V.; Chavarin, Claudia V.; Strathdee, Steffanie A.; Zavala, Rosa Icela; Aarons, Gregory A.; Patterson, Thomas L.

2016-01-01

Aims To describe the prevalence and correlates of hazardous drinking among female sex workers (FSWs) at 13 sites throughout Mexico. Methods FSWs (N = 1089) who were enrolled in a brief sexual risk reduction intervention (Mujer Segura) were queried about their sexual risk and substance use practices and their work contexts. Participants were classified as hazardous or non-hazardous drinkers based on the Alcohol Use Disorders test (AUDIT-C). Logistic regression models were used to examine individual, contextual, and community-level factors as correlates of hazardous drinking. Results Ninety-two percent of participants reported alcohol consumption in the past month. Among drinkers (N = 1001), 83% met AUDIT-C criteria for hazardous drinking. Factors that were independently associated with hazardous drinking included: drug use in the past month (adjusted odds ratio (AOR) = 3.31; 95% CI 1.29—8.45), being a cigarette smoker (AOR = 1.71; 95% CI 1.13—2.58), being a barmaid or dance hostess (AOR = 3.40; 95% CI 1.95–5.91), alcohol use before or during sex with clients (AOR = 7.78; 95% CI 4.84–12.52), and working in a city with a higher marginalization index (AOR = 1.07; 95% CI 1.04–1.11). Conclusions Findings support the high prioritization by public health authorities of alcohol prevention and treatment programs for FSWs. PMID:26546017

Association between obstructive sleep apnea and optic neuropathy: a Taiwanese population-based cohort study.

PubMed

Sun, Ming-Hui; Liao, Yaping Joyce; Lin, Che-Chen; Chiang, Rayleigh Ping-Ying; Wei, James Cheng-Chung

2018-04-26

Obstructive sleep apnea (OSA) is associated with many systemic diseases including diabetes, hypertension, stroke, and cardiovascular disease. The aim of our study was to investigate the association between OSA and optic neuropathy (ON), and to evaluate the efficacy of treatment for OSA on the risk of ON. We used the data from the Longitudinal Health Insurance Database, which involved one million insurants from Taiwan National Health Insurance program (Taiwan NHI). OSA patients had a 1.95-fold higher risk of ON compared with non-OSA patients in all age group. The risk was significantly higher (adjusted hazard ratio: 4.21) in the group aged <45 years and male individuals (adjusted hazard ratio: 1.93). Meanwhile, sleep apnea was associated with ON regardless of the existence of comorbidity or not. OSA patients treated with continuous positive airway pressure (CPAP) had an adjusted 2.31-fold higher hazard of developing ON compared to controls, and those without any treatment had an adjusted 1.82-fold higher hazard of developing ON compared to controls. Moreover, ON patients had a 1.45-fold higher risk of OSA, and those aged between 45 and 64 years (hazard ratio: 1.76) and male individuals (hazard ratio: 1.55) had highest risk. Our study showed that OSA increased the risk of developing ON after controlling the comorbidities; however, treatment with CPAP did not reduce the risk of ON. Further large population study accessing to medical records about the severity of OSA and treatment for OSA is needed to clarify the efficacy of treatment for OSA in reducing the risk of ON.

Surgical excision of anal sac apocrine gland adenocarcinomas with and without adjunctive chemotherapy in dogs: 42 cases (2005-2011).

PubMed

Potanas, Christopher P; Padgett, Sheldon; Gamblin, Rance M

2015-04-15

Objective-To identify variables associated with prognosis in dogs undergoing surgical excision of anal sac apocrine gland adenocarcinomas (ASACs) with and without adjunctive chemotherapy. Design-Retrospective case series. Animals-42 dogs with ASACs. Procedures-Information on signalment, clinical signs, diagnostic procedures, surgical procedures, adjunctive therapies, survival time, and disease-free interval was obtained from the medical records. Results-Survival time was significantly associated with the presence of sublumbar lymphadenopathy and sublumbar lymph node extirpation, with median survival time significantly shorter for dogs with sublumbar lymphadenopathy (hazard ratio, 2.31) than for those without and for dogs that underwent lymph node extirpation (hazard ratio, 2.31) than for those that did not. Disease-free interval was significantly associated with the presence of sublumbar lymphadenopathy, lymph node extirpation, and administration of platinum-containing chemotherapeutic agents, with median disease-free interval significantly shorter for dogs with sublumbar lymphadenopathy (hazard ratio, 2.47) than for those without, for dogs that underwent lymph node extirpation (hazard ratio, 2.47) than for those that did not, and for dogs that received platinum-containing chemotherapeutic agents (hazard ratio, 2.69) than for those that did not. Survival time and disease-free interval did not differ among groups when dogs were grouped on the basis of histopathologic margins (complete vs marginal vs incomplete excision). Conclusions and Clinical Relevance-Results suggested that in dogs with ASAC undergoing surgical excision, the presence of sublumbar lymphadenopathy and lymph node extirpation were both negative prognostic factors. However, completeness of surgical excision was not associated with survival time or disease-free interval.

Best anthropometric discriminators of incident type 2 diabetes among white and black adults: A longitudinal ARIC study.

PubMed

Hardy, Dale S; Stallings, Devita T; Garvin, Jane T; Xu, Hongyan; Racette, Susan B

2017-01-01

To determine which anthropometric measures are the strongest discriminators of incident type 2 diabetes (T2DM) among White and Black males and females in a large U.S. cohort. We used Atherosclerosis Risk in Communities study data from 12,121 participants aged 45-64 years without diabetes at baseline who were followed for over 11 years. Anthropometric measures included a body shape index (ABSI), body adiposity index (BAI), body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), waist to height ratio (WHtR), and waist to hip to height ratio (WHHR). All anthropometric measures were repeated at each visit and converted to Z-scores. Hazard ratios and 95% confidence intervals adjusted for age were calculated using repeated measures Cox proportional hazard regression analysis. Akaike Information Criteria was used to select best-fit models. The magnitude of the hazard ratio effect sizes and the Harrell's C-indexes were used to rank the highest associations and discriminators, respectively. There were 1,359 incident diabetes cases. Higher values of all anthropometric measures increased the risk for development of T2DM (p < 0.0001) except ABSI, which was not significant in White and Black males. Statistically significant hazard ratios ranged from 1.26-1.63 for males and 1.15-1.88 for females. In general, the largest hazard ratios were those that corresponded to the highest Harrell's C-Index and lowest Akaike Information Criteria values. Among White and Black males and females, BMI, WC, WHR, and WHtR were comparable in discriminating cases from non-cases of T2DM. ABSI, BAI, and WHHR were inferior discriminators of incident T2DM across all race-gender groups. BMI, the most commonly used anthropometric measure, and three anthropometric measures that included waist circumference (i.e., WC, WHR, WHtR) were the best anthropometric discriminators of incident T2DM across all race-gender groups in the ARIC cohort.

National Cancer Database Analysis of Proton Versus Photon Radiation Therapy in Non-Small Cell Lung Cancer

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

Higgins, Kristin A., E-mail: kristin.higgins@emory.edu; Winship Cancer Institute, Emory University, Atlanta, Georgia; O'Connell, Kelli

Purpose: To analyze outcomes and predictors associated with proton radiation therapy for non-small cell lung cancer (NSCLC) in the National Cancer Database. Methods and Materials: The National Cancer Database was queried to capture patients with stage I-IV NSCLC treated with thoracic radiation from 2004 to 2012. A logistic regression model was used to determine the predictors for utilization of proton radiation therapy. The univariate and multivariable association with overall survival were assessed by Cox proportional hazards models along with log–rank tests. A propensity score matching method was implemented to balance baseline covariates and eliminate selection bias. Results: A total of 243,822more » patients (photon radiation therapy: 243,474; proton radiation therapy: 348) were included in the analysis. Patients in a ZIP code with a median income of <$46,000 per year were less likely to receive proton treatment, with the income cohort of $30,000 to $35,999 least likely to receive proton therapy (odds ratio 0.63 [95% confidence interval (CI) 0.44-0.90]; P=.011). On multivariate analysis of all patients, non-proton therapy was associated with significantly worse survival compared with proton therapy (hazard ratio 1.21 [95% CI 1.06-1.39]; P<.01). On propensity matched analysis, proton radiation therapy (n=309) was associated with better 5-year overall survival compared with non-proton radiation therapy (n=1549), 22% versus 16% (P=.025). For stage II and III patients, non-proton radiation therapy was associated with worse survival compared with proton radiation therapy (hazard ratio 1.35 [95% CI 1.10-1.64], P<.01). Conclusions: Thoracic radiation with protons is associated with better survival in this retrospective analysis; further validation in the randomized setting is needed to account for any imbalances in patient characteristics, including positron emission tomography–computed tomography staging.« less

The Prescription Pattern of Chinese Herbal Products That Contain Dang-Qui and Risk of Endometrial Cancer among Tamoxifen-Treated Female Breast Cancer Survivors in Taiwan: A Population-Based Study

PubMed Central

Wu, Chien-Tung; Lai, Jung-Nien; Tsai, Yueh-Ting

2014-01-01

Purpose The increased practice of traditional Chinese medicine worldwide has raised concerns regarding herb-drug interactions. We analyzed the usage of Chinese herbal products containing dang-qui and investigated whether dang-qui therapy increases endometrial cancer risk among tamoxifen-treated breast cancer survivors in Taiwan. Methods All patients newly diagnosed with invasive breast cancer who received tamoxifen treatment from January 1, 1998, to December 31, 2008 were selected from the National Health Insurance Research Database. The usage, frequency of service and type of Chinese herbal products containing dang-qui prescribed across the 31,970 survivors were evaluated. Logistic regression method was employed to estimate the odds ratios for utilization of Chinese herbal products containing dang-qui. Cox proportional hazard regression was performed to calculate the hazard ratio of endometrial cancer associated with dang-qui use within the cohort. Results Almost one in two study subjects had used dang-qui. Among 31,938 tamoxifen-treated breast cancer survivors, 157 cases of subsequent endometrial cancer were identified. The hazard ratio for development of endometrial cancer among breast cancer survivors aged 20–79 years who had taken dang-qui after tamoxifen treatment was decreased compared to survivors who had never used dang-qui (HR: 0.61, 95%CI: 0.44–0.84). To minimise potential confounding factors, women with breast cancer in the reproductive age were excluded from further analysis, and the negative relationship between dang-qui consumption and subsequent endometrial cancer among breast cancer survivors aged 55–79 years was still observed, although not significantly (HR: 0.74, 95%CI: 0.46–1.17). Conclusions Dang-qui consumption is common among breast cancer survivors aged 20–79 years and seems decrease the risk of subsequent endometrial cancer after less than a cumulative dose of 7,500 mg of tamoxifen treatment. PMID:25485843

Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin’s lymphoma responding to prior salvage therapy

PubMed Central

Devillier, Raynier; Coso, Diane; Castagna, Luca; Brenot Rossi, Isabelle; Anastasia, Antonella; Chiti, Arturo; Ivanov, Vadim; Schiano, Jean Marc; Santoro, Armando; Chabannon, Christian; Balzarotti, Monica; Blaise, Didier; Bouabdallah, Reda

2012-01-01

Background High-dose chemotherapy followed by autologous stem cell transplantation is the standard treatment for relapsed and/or refractory Hodgkin’s lymphoma although half of patients relapse after transplantation. Predictive factors, such as relapse within 12 months, Ann-Arbor stage at relapse, and relapse in previously irradiated fields are classically used to identify patients with poor outcome. Recently, 18-fluorodeoxyglucose positron emission tomography has emerged as a new method for providing information to predict outcome. The aim of this study was to confirm the predictive value of positron emission tomography status after salvage therapy and to compare single versus tandem autologous stem cell transplantation in patients with relapsed and/or refractory Hodgkin’s lymphoma. Design and Methods We report a series of 111 consecutive patients with treatment-sensitive relapsed and/or treatment-refractory Hodgkin’s lymphoma who achieved complete (positron emission tomography-negative group) or partial remission (positron emission tomography-positive group) at positron emission tomography evaluation after salvage chemotherapy and who underwent single or tandem autologous stem cell transplantation. Results Five-year overall and progression-free survival rates were 81% and 64%, respectively. There were significant differences in 5-year progression-free survival (79% versus 23%; P<0.001) and 5-year overall survival (90% versus 55%, P=0.001) between the positron emission tomography-negative and -positive groups, respectively. A complete response, as determined by positron emission tomography evaluation, after salvage therapy predicted significantly better 5-year overall survival rates in both intermediate (91% versus 50%; P=0.029) and unfavorable (89% versus 58%; P=0.026) risk subgroup analyses. In the positron emission tomography-positive subgroup, tandem transplantation improved 5-year progression-free survival from 0% (in the single transplantation group) to 43% (P=0.034). Multivariate analysis showed that positron emission tomography status (hazard ratio: 5.26 [2.57–10.73]) and tandem transplantation (hazard ratio: 0.39 [0.19–0.78]) but not risk factors at relapse (hazard ratio: 1.77 [0.80–3.92]) significantly influenced progression-free survival, while only tomography status significantly influenced overall survival (hazard ratio: 4.03 [1.38–11.75]). Conclusions In patients with relapsed/refractory Hodgkin’s lymphoma responding to prior salvage therapy, positron emission tomography response at time of autologous stem cell transplantation favorably influences outcome and enables identification of patients requiring single or tandem transplantation. PMID:22271893

Abdominal aortic atherosclerosis at MR imaging is associated with cardiovascular events: the Dallas heart study.

PubMed

Maroules, Christopher D; Rosero, Eric; Ayers, Colby; Peshock, Ronald M; Khera, Amit

2013-10-01

To determine the value of two abdominal aortic atherosclerosis measurements at magnetic resonance (MR) imaging for predicting future cardiovascular events. This study was approved by the institutional review board and complied with HIPAA regulations. The study consisted of 2122 participants from the multiethnic, population-based Dallas Heart Study who underwent abdominal aortic MR imaging at 1.5 T. Aortic atherosclerosis was measured by quantifying mean aortic wall thickness (MAWT) and aortic plaque burden. Participants were monitored for cardiovascular death, nonfatal cardiac events, and nonfatal extracardiac vascular events over a mean period of 7.8 years ± 1.5 (standard deviation [SD]). Cox proportional hazards regression was used to assess independent associations of aortic atherosclerosis and cardiovascular events. Increasing MAWT was positively associated with male sex (odds ratio, 3.66; P < .0001), current smoking (odds ratio, 2.53; P < .0001), 10-year increase in age (odds ratio, 2.24; P < .0001), and hypertension (odds ratio, 1.66; P = .0001). A total of 143 participants (6.7%) experienced a cardiovascular event. MAWT conferred an increased risk for composite events (hazard ratio, 1.28 per 1 SD; P = .001). Aortic plaque was not associated with increased risk for composite events. Increasing MAWT and aortic plaque burden both conferred an increased risk for nonfatal extracardiac events (hazard ratio of 1.52 per 1 SD [P < .001] and hazard ratio of 1.46 per 1 SD [P = .03], respectively). MR imaging measures of aortic atherosclerosis are predictive of future adverse cardiovascular events. © RSNA, 2013.

Heterogeneity in Early Responses in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

PubMed

Dhruva, Sanket S; Huang, Chenxi; Spatz, Erica S; Coppi, Andreas C; Warner, Frederick; Li, Shu-Xia; Lin, Haiqun; Xu, Xiao; Furberg, Curt D; Davis, Barry R; Pressel, Sara L; Coifman, Ronald R; Krumholz, Harlan M

2017-07-01

Randomized trials of hypertension have seldom examined heterogeneity in response to treatments over time and the implications for cardiovascular outcomes. Understanding this heterogeneity, however, is a necessary step toward personalizing antihypertensive therapy. We applied trajectory-based modeling to data on 39 763 study participants of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) to identify distinct patterns of systolic blood pressure (SBP) response to randomized medications during the first 6 months of the trial. Two trajectory patterns were identified: immediate responders (85.5%), on average, had a decreasing SBP, whereas nonimmediate responders (14.5%), on average, had an initially increasing SBP followed by a decrease. Compared with those randomized to chlorthalidone, participants randomized to amlodipine (odds ratio, 1.20; 95% confidence interval [CI], 1.10-1.31), lisinopril (odds ratio, 1.88; 95% CI, 1.73-2.03), and doxazosin (odds ratio, 1.65; 95% CI, 1.52-1.78) had higher adjusted odds ratios associated with being a nonimmediate responder (versus immediate responder). After multivariable adjustment, nonimmediate responders had a higher hazard ratio of stroke (hazard ratio, 1.49; 95% CI, 1.21-1.84), combined cardiovascular disease (hazard ratio, 1.21; 95% CI, 1.11-1.31), and heart failure (hazard ratio, 1.48; 95% CI, 1.24-1.78) during follow-up between 6 months and 2 years. The SBP response trajectories provided superior discrimination for predicting downstream adverse cardiovascular events than classification based on difference in SBP between the first 2 measurements, SBP at 6 months, and average SBP during the first 6 months. Our findings demonstrate heterogeneity in response to antihypertensive therapies and show that chlorthalidone is associated with more favorable initial response than the other medications. © 2017 American Heart Association, Inc.

Comparative safety of direct oral anticoagulants and warfarin in venous thromboembolism: multicentre, population based, observational study.

PubMed

Jun, Min; Lix, Lisa M; Durand, Madeleine; Dahl, Matt; Paterson, J Michael; Dormuth, Colin R; Ernst, Pierre; Yao, Shenzhen; Renoux, Christel; Tamim, Hala; Wu, Cynthia; Mahmud, Salaheddin M; Hemmelgarn, Brenda R

2017-10-17

Objective  To determine the safety of direct oral anticoagulant (DOAC) use compared with warfarin use for the treatment of venous thromboembolism. Design  Retrospective matched cohort study conducted between 1 January 2009 and 31 March 2016. Setting  Community based, using healthcare data from six jurisdictions in Canada and the United States. Participants  59 525 adults (12 489 DOAC users; 47 036 warfarin users) with a new diagnosis of venous thromboembolism and a prescription for a DOAC or warfarin within 30 days of diagnosis. Main outcome measures  Outcomes included hospital admission or emergency department visit for major bleeding and all cause mortality within 90 days after starting treatment. Propensity score matching and shared frailty models were used to estimate adjusted hazard ratios of the outcomes comparing DOACs with warfarin. Analyses were conducted independently at each site, with meta-analytical methods used to estimate pooled hazard ratios across sites. Results  Of the 59 525 participants, 1967 (3.3%) had a major bleed and 1029 (1.7%) died over a mean follow-up of 85.2 days. The risk of major bleeding was similar for DOAC compared with warfarin use (pooled hazard ratio 0.92, 95% confidence interval 0.82 to 1.03), with the overall direction of the association favouring DOAC use. No difference was found in the risk of death (pooled hazard ratio 0.99, 0.84 to 1.16) for DOACs compared with warfarin use. There was no evidence of heterogeneity across centres, between patients with and without chronic kidney disease, across age groups, or between male and female patients. Conclusions  In this analysis of adults with incident venous thromboembolism, treatment with DOACs, compared with warfarin, was not associated with an increased risk of major bleeding or all cause mortality in the first 90 days of treatment. Trial registration  Clinical trials NCT02833987. 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.

Effect of Socioeconomic Status on Mortality after Bacteremia in Working-Age Patients. A Danish Population-Based Cohort Study

PubMed Central

Koch, Kristoffer; Nørgaard, Mette; Schønheyder, Henrik Carl; Thomsen, Reimar Wernich; Søgaard, Mette

2013-01-01

Objectives To examine the effect of socioeconomic status (SES) on mortality in patients with bacteremia and the underlying factors that may mediate differences in mortality. Methods We conducted a population-based cohort study in two Danish regions. All patients 30 to 65 years of age with first time bacteremia from 2000 through 2008 were identified in a population-based microbiological bacteremia database (n = 8,653). Individual-level data on patients’ SES (educational level and personal income) and comorbid conditions were obtained from public and medical registries. We used Cox regression to examine mortality within 30 days after bacteremia with and without cumulative adjustment for potential mediators. Results Bacteremia patients of low SES were more likely to live alone and be unmarried than patients of high SES. They also had more pre-existing comorbidity, more substance abuse, more Staphylococcus aureus and nosocomial infections, and more admissions to small nonteaching hospitals. Overall, 1,374 patients (15.9%) died within 30 days of follow-up. Patients of low SES had consistently higher mortality after bacteremia than those of high SES crude hazard ratio for low vs. high education, 1.38 [95% confidence interval (CI), 1.18–1.61]; crude hazard ratio for low-income vs. high-income tertile, 1.58 [CI, 1.39–1.80]. Adjustment for differences in social support, pre-existing comorbidity, substance abuse, place of acquisition of the infection, and microbial agent substantially attenuated the effect of SES on mortality (adjusted hazard ratio for low vs. high education, 1.15 [95% CI, 0.98–1.36]; adjusted hazard ratio for low-income vs. high-income tertile, 1.29 [CI, 1.12–1.49]). Further adjustment for characteristics of the admitting hospital had minimal effect on observed mortality differences. Conclusions Low SES was strongly associated with increased 30-day mortality after bacteremia. Less social support, more pre-existing comorbidity, more substance abuse, and differences in place of acquisition and agent of infection appeared to mediate much of the observed disparities in mortality. PMID:23936145

Associations of Conventional Echocardiographic Measures with Incident Heart Failure and Mortality: The Chronic Renal Insufficiency Cohort.

PubMed

Dubin, Ruth F; Deo, Rajat; Bansal, Nisha; Anderson, Amanda H; Yang, Peter; Go, Alan S; Keane, Martin; Townsend, Ray; Porter, Anna; Budoff, Matthew; Malik, Shaista; He, Jiang; Rahman, Mahboob; Wright, Jackson; Cappola, Thomas; Kallem, Radhakrishna; Roy, Jason; Sha, Daohang; Shlipak, Michael G

2017-01-06

Heart failure is the most frequent cardiac complication of CKD. Left ventricular hypertrophy is common and develops early in CKD, but studies have not adequately evaluated the association of left ventricular mass index with heart failure incidence among men and women with CKD. We evaluated echocardiograms of 2567 participants without self-reported heart failure enrolled in the Chronic Renal Insufficiency Cohort Study. Two-dimensional echocardiograms were performed at the year 1 study visit and interpreted at a central core laboratory. Left ventricular mass index was calculated using the linear method, indexed to height 2.7 , and analyzed using sex-specific quartiles. The primary outcomes of incident heart failure and all-cause mortality were adjudicated over a median of 6.6 (interquartile range, 5.7-7.6) years. Among 2567 participants, 45% were women, and 54% were nonwhite race; mean (SD) age was 59±11 years old, and mean eGFR was 44±17 ml/min per 1.73 m 2 . During a median follow-up period of 6.6 years, 262 participants developed heart failure, and 470 participants died. Compared with participants in the first quartile of left ventricular mass index, those in the highest quartile had higher rates of incident heart failure (hazard ratio, 3.96; 95% confidence interval, 1.96 to 8.02) and mortality (hazard ratio, 1.86; 95% confidence interval, 1.22 to 2.85), even after adjustment for B-type natriuretic peptide, troponin T, mineral metabolism markers, and other cardiovascular disease risk factors. Those in the lowest quartile of ejection fraction had higher rates of incident heart failure (hazard ratio, 3.01; 95% confidence interval, 1.94 to 4.67) but similar mortality rates (hazard ratio, 1.18; 95% confidence interval, 0.89 to 1.57) compared with those in the highest quartile. Diastolic dysfunction was not significantly associated with heart failure or death. Among persons with CKD and without history of cardiovascular disease, left ventricular mass index is strongly associated with incident heart failure, even after adjustment for major cardiovascular risk factors and biomarkers. Copyright © 2016 by the American Society of Nephrology.

Associations of Conventional Echocardiographic Measures with Incident Heart Failure and Mortality: The Chronic Renal Insufficiency Cohort

PubMed Central

Deo, Rajat; Bansal, Nisha; Anderson, Amanda H.; Yang, Peter; Go, Alan S.; Keane, Martin; Townsend, Ray; Porter, Anna; Budoff, Matthew; Malik, Shaista; He, Jiang; Rahman, Mahboob; Wright, Jackson; Cappola, Thomas; Kallem, Radhakrishna; Roy, Jason; Sha, Daohang; Shlipak, Michael G.

2017-01-01

Background and objectives Heart failure is the most frequent cardiac complication of CKD. Left ventricular hypertrophy is common and develops early in CKD, but studies have not adequately evaluated the association of left ventricular mass index with heart failure incidence among men and women with CKD. Design, setting, participants, & measurements We evaluated echocardiograms of 2567 participants without self–reported heart failure enrolled in the Chronic Renal Insufficiency Cohort Study. Two-dimensional echocardiograms were performed at the year 1 study visit and interpreted at a central core laboratory. Left ventricular mass index was calculated using the linear method, indexed to height2.7, and analyzed using sex-specific quartiles. The primary outcomes of incident heart failure and all-cause mortality were adjudicated over a median of 6.6 (interquartile range, 5.7–7.6) years. Results Among 2567 participants, 45% were women, and 54% were nonwhite race; mean (SD) age was 59±11 years old, and mean eGFR was 44±17 ml/min per 1.73 m2. During a median follow-up period of 6.6 years, 262 participants developed heart failure, and 470 participants died. Compared with participants in the first quartile of left ventricular mass index, those in the highest quartile had higher rates of incident heart failure (hazard ratio, 3.96; 95% confidence interval, 1.96 to 8.02) and mortality (hazard ratio, 1.86; 95% confidence interval, 1.22 to 2.85), even after adjustment for B–type natriuretic peptide, troponin T, mineral metabolism markers, and other cardiovascular disease risk factors. Those in the lowest quartile of ejection fraction had higher rates of incident heart failure (hazard ratio, 3.01; 95% confidence interval, 1.94 to 4.67) but similar mortality rates (hazard ratio, 1.18; 95% confidence interval, 0.89 to 1.57) compared with those in the highest quartile. Diastolic dysfunction was not significantly associated with heart failure or death. Conclusions Among persons with CKD and without history of cardiovascular disease, left ventricular mass index is strongly associated with incident heart failure, even after adjustment for major cardiovascular risk factors and biomarkers. PMID:28062676

Factors associated with reporting results for pulmonary clinical trials in ClinicalTrials.gov.

PubMed

Riley, Isaretta L; Boulware, L Ebony; Sun, Jie-Lena; Chiswell, Karen; Que, Loretta G; Kraft, Monica; Todd, Jamie L; Palmer, Scott M; Anderson, Monique L

2018-02-01

Background/aims The Food and Drug Administration Amendments Act mandates that applicable clinical trials report basic summary results to the ClinicalTrials.gov database within 1 year of trial completion or termination. We aimed to determine the proportion of pulmonary trials reporting basic summary results to ClinicalTrials.gov and assess factors associated with reporting. Methods We identified pulmonary clinical trials subject to the Food and Drug Administration Amendments Act (called highly likely applicable clinical trials) that were completed or terminated between 2008 and 2012 and reported results by September 2013. We estimated the cumulative percentage of applicable clinical trials reporting results by pulmonary disease category. Multivariable Cox regression modeling identified characteristics independently associated with results reporting. Results Of 1450 pulmonary highly likely applicable clinical trials, 380 (26%) examined respiratory neoplasms, 238 (16%) asthma, 175 (12%) chronic obstructive pulmonary disease, and 657 (45%) other respiratory diseases. Most (75%) were pharmaceutical highly likely applicable clinical trials and 71% were industry-funded. Approximately 15% of highly likely applicable clinical trials reported results within 1 year of trial completion, while 55% reported results over the 5-year study period. Earlier phase highly likely applicable clinical trials were less likely to report results compared to phase 4 highly likely applicable clinical trials (phases 1/2 and 2 (adjusted hazard ratio 0.41 (95% confidence interval: 0.31-0.54)), phases 2/3 and 3 (adjusted hazard ratio 0.55 (95% confidence interval: 0.42-0.72)) and phase not applicable (adjusted hazard ratio 0.43 (95% confidence interval: 0.29-0.63)). Pulmonary highly likely applicable clinical trials without Food and Drug Administration oversight were less likely to report results compared with those with oversight (adjusted hazard ratio 0.65 (95% confidence interval: 0.51-0.83)). Conclusion A total of 15% of pulmonary clinical highly likely applicable clinical trials report basic summary results to ClinicalTrials.gov within 1 year of trial completion. Strategies to improve reporting are needed within the pulmonary community.

The Diesel Exhaust in Miners Study: A Cohort Mortality Study With Emphasis on Lung Cancer

PubMed Central

Schleiff, Patricia L.; Lubin, Jay H.; Blair, Aaron; Stewart, Patricia A.; Vermeulen, Roel; Coble, Joseph B.; Silverman, Debra T.

2012-01-01

Background Current information points to an association between diesel exhaust exposure and lung cancer and other mortality outcomes, but uncertainties remain. Methods We undertook a cohort mortality study of 12 315 workers exposed to diesel exhaust at eight US non-metal mining facilities. Historical measurements and surrogate exposure data, along with study industrial hygiene measurements, were used to derive retrospective quantitative estimates of respirable elemental carbon (REC) exposure for each worker. Standardized mortality ratios and internally adjusted Cox proportional hazard models were used to evaluate REC exposure–associated risk. Analyses were both unlagged and lagged to exclude recent exposure such as that occurring in the 15 years directly before the date of death. Results Standardized mortality ratios for lung cancer (1.26, 95% confidence interval [CI] = 1.09 to 1.44), esophageal cancer (1.83, 95% CI = 1.16 to 2.75), and pneumoconiosis (12.20, 95% CI = 6.82 to 20.12) were elevated in the complete cohort compared with state-based mortality rates, but all-cause, bladder cancer, heart disease, and chronic obstructive pulmonary disease mortality were not. Differences in risk by worker location (ever-underground vs surface only) initially obscured a positive diesel exhaust exposure–response relationship with lung cancer in the complete cohort, although it became apparent after adjustment for worker location. The hazard ratios (HRs) for lung cancer mortality increased with increasing 15-year lagged cumulative REC exposure for ever-underground workers with 5 or more years of tenure to a maximum in the 640 to less than 1280 μg/m3-y category compared with the reference category (0 to <20 μg/m3-y; 30 deaths compared with eight deaths of the total of 93; HR = 5.01, 95% CI = 1.97 to 12.76) but declined at higher exposures. Average REC intensity hazard ratios rose to a plateau around 32 μg/m3. Elevated hazard ratios and evidence of exposure–response were also seen for surface workers. The association between diesel exhaust exposure and lung cancer risk remained after inclusion of other work-related potentially confounding exposures in the models and were robust to alternative approaches to exposure derivation. Conclusions The study findings provide further evidence that exposure to diesel exhaust increases risk of mortality from lung cancer and have important public health implications. PMID:22393207

Leucocyte telomere length and risk of type 2 diabetes mellitus: new prospective cohort study and literature-based meta-analysis.

PubMed

Willeit, Peter; Raschenberger, Julia; Heydon, Emma E; Tsimikas, Sotirios; Haun, Margot; Mayr, Agnes; Weger, Siegfried; Witztum, Joseph L; Butterworth, Adam S; Willeit, Johann; Kronenberg, Florian; Kiechl, Stefan

2014-01-01

Short telomeres have been linked to various age-related diseases. We aimed to assess the association of telomere length with incident type 2 diabetes mellitus (T2DM) in prospective cohort studies. Leucocyte relative telomere length (RTL) was measured using quantitative polymerase chain reaction in 684 participants of the prospective population-based Bruneck Study (1995 baseline), with repeat RTL measurements performed in 2005 (n = 558) and 2010 (n = 479). Hazard ratios for T2DM were calculated across quartiles of baseline RTL using Cox regression models adjusted for age, sex, body-mass index, smoking, socio-economic status, physical activity, alcohol consumption, high-density lipoprotein cholesterol, log high-sensitivity C-reactive protein, and waist-hip ratio. Separate analyses corrected hazard ratios for within-person variability using multivariate regression calibration of repeated measurements. To contextualise findings, we systematically sought PubMed, Web of Science and EMBASE for relevant articles and pooled results using random-effects meta-analysis. Over 15 years of follow-up, 44 out of 606 participants free of diabetes at baseline developed incident T2DM. The adjusted hazard ratio for T2DM comparing the bottom vs. the top quartile of baseline RTL (i.e. shortest vs. longest) was 2.00 (95% confidence interval: 0.90 to 4.49; P = 0.091), and 2.31 comparing the bottom quartile vs. the remainder (1.21 to 4.41; P = 0.011). The corresponding hazard ratios corrected for within-person RTL variability were 3.22 (1.27 to 8.14; P = 0.014) and 2.86 (1.45 to 5.65; P = 0.003). In a random-effects meta-analysis of three prospective cohort studies involving 6,991 participants and 2,011 incident T2DM events, the pooled relative risk was 1.31 (1.07 to 1.60; P = 0.010; I2 = 69%). Low RTL is independently associated with the risk of incident T2DM. To avoid regression dilution biases in observed associations of RTL with disease risk, future studies should implement methods correcting for within-person variability in RTL. The causal role of short telomeres in T2DM development remains to be determined.

C-reactive protein-to-albumin ratio is a predictor of hepatitis B virus related decompensated cirrhosis: time-dependent receiver operating characteristics and decision curve analysis.

PubMed

Huang, Si-Si; Xie, Dong-Mei; Cai, Yi-Jing; Wu, Jian-Min; Chen, Rui-Chong; Wang, Xiao-Dong; Song, Mei; Zheng, Ming-Hua; Wang, Yu-Qun; Lin, Zhuo; Shi, Ke-Qing

2017-04-01

Hepatitis B virus (HBV) infection remains a major health problem and HBV-related-decompensated cirrhosis (HBV-DC) usually leads to a poor prognosis. Our aim was to determine the utility of inflammatory biomarkers in predicting mortality of HBV-DC. A total of 329 HBV-DC patients were enrolled. Survival estimates for the entire study population were generated using the Kaplan-Meier method. The prognostic values for model for end-stage liver disease (MELD) score, Child-Pugh score, and inflammatory biomarkers neutrophil/lymphocyte ratio, C-reactive protein-to-albumin ratio (CAR), and lymphocyte-to-monocyte ratio (LMR) for HBV-DC were compared using time-dependent receiver operating characteristic curves and time-dependent decision curves. The survival time was 23.1±15.8 months. Multivariate analysis identified age, CAR, LMR, and platelet count as prognostic independent risk factors. Kaplan-Meier analysis indicated that CAR of at least 1.0 (hazard ratio, 7.19; 95% confidence interval, 4.69-11.03), and LMR less than 1.9 (hazard ratio, 2.40; 95% confidence interval, 1.69-3.41) were independently associated with mortality of HBV-DC. The time-dependent receiver operating characteristic indicated that CAR showed the best performance in predicting mortality of HBV-DC compared with LMR, MELD score, and Child-Pugh score. The results were also confirmed by time-dependent decision curves. CAR and LMR were associated with the prognosis of HBV-DC. CAR was superior to LMR, MELD score, and Child-Pugh score in HBV-DC mortality prediction.

Derivation and interpretation of hazard quotients to assess ecological risks from the cultivation of insect-resistant transgenic crops.

PubMed

Raybould, Alan; Caron-Lormier, Geoffrey; Bohan, David A

2011-06-08

Cost-effective and rigorous risk assessments for chemicals may be based on hazard quotients (HQs): the ratio of a measure of exposure to a substance and a measure of the effect of that substance. HQs have been used for many years in ecological risk assessments for the use of synthetic pesticides in agriculture, and methods for calculating pesticide HQs have been adapted for use with transgenic crops. This paper describes how laboratory methods for assessing the ecotoxicological effects of synthetic pesticides have been modified for the measurement of effects of insecticidal proteins, and how these effect measures are combined with exposure estimates to derive HQs for assessing the ecological risks from the cultivation of insect-resistant transgenic crops. The potential for ecological modeling to inform the design of laboratory effects tests for insecticidal proteins is also discussed.

Characterization of airborne float coal dust emitted during continuous mining, longwall mining and belt transport.

PubMed

Shahan, M R; Seaman, C E; Beck, T W; Colinet, J F; Mischler, S E

2017-09-01

Float coal dust is produced by various mining methods, carried by ventilating air and deposited on the floor, roof and ribs of mine airways. If deposited, float dust is re-entrained during a methane explosion. Without sufficient inert rock dust quantities, this float coal dust can propagate an explosion throughout mining entries. Consequently, controlling float coal dust is of critical interest to mining operations. Rock dusting, which is the adding of inert material to airway surfaces, is the main control technique currently used by the coal mining industry to reduce the float coal dust explosion hazard. To assist the industry in reducing this hazard, the Pittsburgh Mining Research Division of the U.S. National Institute for Occupational Safety and Health initiated a project to investigate methods and technologies to reduce float coal dust in underground coal mines through prevention, capture and suppression prior to deposition. Field characterization studies were performed to determine quantitatively the sources, types and amounts of dust produced during various coal mining processes. The operations chosen for study were a continuous miner section, a longwall section and a coal-handling facility. For each of these operations, the primary dust sources were confirmed to be the continuous mining machine, longwall shearer and conveyor belt transfer points, respectively. Respirable and total airborne float dust samples were collected and analyzed for each operation, and the ratio of total airborne float coal dust to respirable dust was calculated. During the continuous mining process, the ratio of total airborne float coal dust to respirable dust ranged from 10.3 to 13.8. The ratios measured on the longwall face were between 18.5 and 21.5. The total airborne float coal dust to respirable dust ratio observed during belt transport ranged between 7.5 and 21.8.

Near-Earth object hazardous impact: A Multi-Criteria Decision Making approach.

PubMed

Sánchez-Lozano, J M; Fernández-Martínez, M

2016-11-16

The impact of a near-Earth object (NEO) may release large amounts of energy and cause serious damage. Several NEO hazard studies conducted over the past few years provide forecasts, impact probabilities and assessment ratings, such as the Torino and Palermo scales. These high-risk NEO assessments involve several criteria, including impact energy, mass, and absolute magnitude. The main objective of this paper is to provide the first Multi-Criteria Decision Making (MCDM) approach to classify hazardous NEOs. Our approach applies a combination of two methods from a widely utilized decision making theory. Specifically, the Analytic Hierarchy Process (AHP) methodology is employed to determine the criteria weights, which influence the decision making, and the Technique for Order Performance by Similarity to Ideal Solution (TOPSIS) is used to obtain a ranking of alternatives (potentially hazardous NEOs). In addition, NEO datasets provided by the NASA Near-Earth Object Program are utilized. This approach allows the classification of NEOs by descending order of their TOPSIS ratio, a single quantity that contains all of the relevant information for each object.

Risk of metachronous ovarian cancer after ovarian conservation in young women with stage I cervical cancer.

PubMed

Matsuo, Koji; Machida, Hiroko; Horowitz, Max P; Shahzad, Mian M K; Guntupalli, Saketh R; Roman, Lynda D; Wright, Jason D

2017-11-01

While there is an increasing trend of ovarian conservation at the time of surgical treatment for young women with stage I cervical cancer, the risk for subsequent ovarian cancer after ovarian conservation has not been well studied. We sought to examine the incidence of and risk factors for metachronous ovarian cancer among young women with stage I cervical cancer who had ovarian conservation at the time of hysterectomy. The Surveillance, Epidemiology, and End Results Program was used to identify women aged <50 years who underwent hysterectomy with ovarian conservation for stage I cervical cancer from 1983 through 2013 (n = 4365). Time-dependent analysis was performed for ovarian cancer risk after cervical cancer diagnosis. Mean age at cervical cancer diagnosis was 37 years, and the majority of patients had stage IA disease (68.2%) and squamous histology (72.9%). Median follow-up time was 10.8 years, and there were 13 women who developed metachronous ovarian cancer. The 10- and 20-year cumulative incidences of metachronous ovarian cancer were 0.2% (95% confidence interval, 0.1-0.4) and 0.5% (95% confidence interval, 0.2-0.8), respectively. Mean age at the time of diagnosis of metachronous ovarian cancer was 47.5 years, and stage III-IV disease was seen in 55.6%. Age (≥45 vs <45 years, hazard ratio, 4.22; 95% confidence interval, 1.16-15.4; P = .018), ethnicity (non-white vs white, hazard ratio, 4.29; 95% confidence interval, 1.31-14.0; P = .009), cervical cancer histology (adenocarcinoma or adenosquamous vs squamous, hazard ratio, 3.50; 95% confidence interval, 1.17-10.5; P = .028), and adjuvant radiotherapy use (yes vs no, hazard ratio, 3.69; 95% confidence interval, 1.01-13.4; P = .034) were significantly associated with metachronous ovarian cancer risk. The presence of multiple risk factors was associated with a significantly increased risk of metachronous ovarian cancer compared to the no risk factor group: 1 risk factor (hazard ratio range, 2.96-8.43), 2 risk factors (hazard ratio range, 16.6-31.0), and 3-4 risk factors (hazard ratio range, 62.3-109), respectively. Metachronous ovarian cancer risk after ovarian conservation for women with stage I cervical cancer is <1%. Older age, non-white ethnicity, adenocarcinoma or adenosquamous histology, and adjuvant radiotherapy may be associated with an increased metachronous ovarian cancer risk. Copyright © 2017 Elsevier Inc. All rights reserved.

Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.

PubMed

Patel, Anushka; MacMahon, Stephen; Chalmers, John; Neal, Bruce; Billot, Laurent; Woodward, Mark; Marre, Michel; Cooper, Mark; Glasziou, Paul; Grobbee, Diederick; Hamet, Pavel; Harrap, Stephen; Heller, Simon; Liu, Lisheng; Mancia, Giuseppe; Mogensen, Carl Erik; Pan, Changyu; Poulter, Neil; Rodgers, Anthony; Williams, Bryan; Bompoint, Severine; de Galan, Bastiaan E; Joshi, Rohina; Travert, Florence

2008-06-12

In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain. We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately. After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001). A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.) 2008 Massachusetts Medical Society

Analysis of tsunami disaster map by Geographic Information System (GIS): Aceh Singkil-Indonesia

NASA Astrophysics Data System (ADS)

Farhan, A.; Akhyar, H.

2017-02-01

Tsunami risk map is used by stakeholder as a base to decide evacuation plan and evaluates from disaster. Aceh Singkil district of Aceh- Indonesia’s disaster maps have been developed and analyzed by using GIS tool. Overlay methods through algorithms are used to produce hazard map, vulnerability, capacity and finally created disaster risk map. Spatial maps are used topographic maps, administrative map, SRTM. The parameters are social, economic, physical environmental vulnerability, a level of exposed people, parameters of houses, public building, critical facilities, productive land, population density, sex ratio, poor ratio, disability ratio, age group ratio, the protected forest, natural forest, and mangrove forest. The results show high-risk tsunami disaster at nine villages; moderate levels are seventeen villages, and other villages are shown in the low level of tsunami risk disaster.

Critical review of methods for risk ranking of food-related hazards, based on risks for human health.

PubMed

Van der Fels-Klerx, H J; Van Asselt, E D; Raley, M; Poulsen, M; Korsgaard, H; Bredsdorff, L; Nauta, M; D'agostino, M; Coles, D; Marvin, H J P; Frewer, L J

2018-01-22

This study aimed to critically review methods for ranking risks related to food safety and dietary hazards on the basis of their anticipated human health impacts. A literature review was performed to identify and characterize methods for risk ranking from the fields of food, environmental science and socio-economic sciences. The review used a predefined search protocol, and covered the bibliographic databases Scopus, CAB Abstracts, Web of Sciences, and PubMed over the period 1993-2013. All references deemed relevant, on the basis of predefined evaluation criteria, were included in the review, and the risk ranking method characterized. The methods were then clustered-based on their characteristics-into eleven method categories. These categories included: risk assessment, comparative risk assessment, risk ratio method, scoring method, cost of illness, health adjusted life years (HALY), multi-criteria decision analysis, risk matrix, flow charts/decision trees, stated preference techniques and expert synthesis. Method categories were described by their characteristics, weaknesses and strengths, data resources, and fields of applications. It was concluded there is no single best method for risk ranking. The method to be used should be selected on the basis of risk manager/assessor requirements, data availability, and the characteristics of the method. Recommendations for future use and application are provided.

Two-Step Screening for Depressive Symptoms and Prediction of Mortality in Patients With Heart Failure.

PubMed

Lee, Kyoung Suk; Moser, Debra K; Pelter, Michele; Biddle, Martha J; Dracup, Kathleen

2017-05-01

Comorbid depression in patients with heart failure is associated with increased risk for death. In order to effectively identify depressed patients with cardiac disease, the American Heart Association suggests a 2-step screening method: administering the 2-item Patient Health Questionnaire first and then the 9-item Patient Health Questionnaire. However, whether the 2-step method is better for predicting poor prognosis in heart failure than is either the 2-item or the 9-item tool alone is not known. To determine whether the 2-step method is better than either the 2-item or the 9-item questionnaire alone for predicting all-cause mortality in heart failure. During a 2-year period, 562 patients with heart failure were assessed for depression by using the 2-step method. With the 2-step method, results are considered positive if patients endorse either depressed mood or anhedonia on the 2-item screen and have scores of 10 or higher on the 9-item screen. Screening results with the 2-step method were not associated with all-cause mortality. Patients with scores positive for depression on either the 2-item or 9-item screen alone had 53% and 60% greater risk, respectively, for all-cause death than did patients with scores negative for depression after adjustments for covariates (hazard ratio, 1.530; 95% CI, 1.029-2.274 for the 2-item screen; hazard ratio, 1.603; 95% CI, 1.079-2.383 for the 9-item screen). The 2-step method has no clear advantages compared with the 2-item screen alone or the 9-item screen alone for predicting adverse prognostic effects of depressive symptoms in heart failure. ©2017 American Association of Critical-Care Nurses.

Normalization of Testosterone Levels After Testosterone Replacement Therapy Is Associated With Decreased Incidence of Atrial Fibrillation.

PubMed

Sharma, Rishi; Oni, Olurinde A; Gupta, Kamal; Sharma, Mukut; Sharma, Ram; Singh, Vikas; Parashara, Deepak; Kamalakar, Surineni; Dawn, Buddhadeb; Chen, Guoqing; Ambrose, John A; Barua, Rajat S

2017-05-09

Atrial fibrillation (AF) is the most common cardiac dysrhythmia associated with significant morbidity and mortality. Several small studies have reported that low serum total testosterone (TT) levels were associated with a higher incidence of AF. In contrast, it is also reported that anabolic steroid use is associated with an increase in the risk of AF. To date, no study has explored the effect of testosterone normalization on new incidence of AF after testosterone replacement therapy (TRT) in patients with low testosterone. Using data from the Veterans Administrations Corporate Data Warehouse, we identified a national cohort of 76 639 veterans with low TT levels and divided them into 3 groups. Group 1 had TRT resulting in normalization of TT levels (normalized TRT), group 2 had TRT without normalization of TT levels (nonnormalized TRT), and group 3 did not receive TRT (no TRT). Propensity score-weighted stabilized inverse probability of treatment weighting Cox proportional hazard methods were used for analysis of the data from these groups to determine the association between post-TRT levels of TT and the incidence of AF. Group 1 (40 856 patients, median age 66 years) had significantly lower risk of AF than group 2 (23 939 patients, median age 65 years; hazard ratio 0.90, 95% CI 0.81-0.99, P =0.0255) and group 3 (11 853 patients, median age 67 years; hazard ratio 0.79, 95% CI 0.70-0.89, P =0.0001). There was no statistical difference between groups 2 and 3 (hazard ratio 0.89, 95% CI 0.78- 1.0009, P =0.0675) in incidence of AF. These novel results suggest that normalization of TT levels after TRT is associated with a significant decrease in the incidence of AF. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

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

PubMed Central

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

2015-01-01

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

Concepts for risk-based surveillance in the field of veterinary medicine and veterinary public health: Review of current approaches

PubMed Central

Stärk, Katharina DC; Regula, Gertraud; Hernandez, Jorge; Knopf, Lea; Fuchs, Klemens; Morris, Roger S; Davies, Peter

2006-01-01

Background Emerging animal and zoonotic diseases and increasing international trade have resulted in an increased demand for veterinary surveillance systems. However, human and financial resources available to support government veterinary services are becoming more and more limited in many countries world-wide. Intuitively, issues that present higher risks merit higher priority for surveillance resources as investments will yield higher benefit-cost ratios. The rapid rate of acceptance of this core concept of risk-based surveillance has outpaced the development of its theoretical and practical bases. Discussion The principal objectives of risk-based veterinary surveillance are to identify surveillance needs to protect the health of livestock and consumers, to set priorities, and to allocate resources effectively and efficiently. An important goal is to achieve a higher benefit-cost ratio with existing or reduced resources. We propose to define risk-based surveillance systems as those that apply risk assessment methods in different steps of traditional surveillance design for early detection and management of diseases or hazards. In risk-based designs, public health, economic and trade consequences of diseases play an important role in selection of diseases or hazards. Furthermore, certain strata of the population of interest have a higher probability to be sampled for detection of diseases or hazards. Evaluation of risk-based surveillance systems shall prove that the efficacy of risk-based systems is equal or higher than traditional systems; however, the efficiency (benefit-cost ratio) shall be higher in risk-based surveillance systems. Summary Risk-based surveillance considerations are useful to support both strategic and operational decision making. This article highlights applications of risk-based surveillance systems in the veterinary field including food safety. Examples are provided for risk-based hazard selection, risk-based selection of sampling strata as well as sample size calculation based on risk considerations. PMID:16507106

Renal Cell Carcinoma: Comparison of RENAL Nephrometry and PADUA Scores with Maximum Tumor Diameter for Prediction of Local Recurrence after Thermal Ablation.

PubMed

Maxwell, Aaron W P; Baird, Grayson L; Iannuccilli, Jason D; Mayo-Smith, William W; Dupuy, Damian E

2017-05-01

Purpose To evaluate the performance of the radius, exophytic or endophytic, nearness to collecting system or sinus, anterior or posterior, and location relative to polar lines (RENAL) nephrometry and preoperative aspects and dimensions used for anatomic classification (PADUA) scoring systems and other tumor biometrics for prediction of local tumor recurrence in patients with renal cell carcinoma after thermal ablation. Materials and Methods This HIPAA-compliant study was performed with a waiver of informed consent after institutional review board approval was obtained. A retrospective evaluation of 207 consecutive patients (131 men, 76 women; mean age, 71.9 years ± 10.9) with 217 biopsy-proven renal cell carcinoma tumors treated with thermal ablation was conducted. Serial postablation computed tomography (CT) or magnetic resonance (MR) imaging was used to evaluate for local tumor recurrence. For each tumor, RENAL nephrometry and PADUA scores were calculated by using imaging-derived tumor morphologic data. Several additional tumor biometrics and combinations thereof were also measured, including maximum tumor diameter. The Harrell C index and hazard regression techniques were used to quantify associations with local tumor recurrence. Results The RENAL (hazard ratio, 1.43; P = .003) and PADUA (hazard ratio, 1.80; P < .0001) scores were found to be significantly associated with recurrence when regression techniques were used but demonstrated only poor to fair discrimination according to Harrell C index results (C, 0.68 and 0.75, respectively). Maximum tumor diameter showed the highest discriminatory strength of any individual variable evaluated (C, 0.81) and was also significantly predictive when regression techniques were used (hazard ratio, 2.98; P < .0001). For every 1-cm increase in diameter, the estimated rate of recurrence risk increased by 198%. Conclusion Maximum tumor diameter demonstrates superior performance relative to existing tumor scoring systems and other evaluated biometrics for prediction of local tumor recurrence after renal cell carcinoma ablation. © RSNA, 2016.

Financial Insolvency as a Risk Factor for Early Mortality Among Patients With Cancer

PubMed Central

Bansal, Aasthaa; Fedorenko, Catherine R.; Blough, David K.; Overstreet, Karen A.; Shankaran, Veena; Newcomb, Polly

2016-01-01

Purpose Patients with cancer are more likely to file for bankruptcy than the general population, but the impact of severe financial distress on health outcomes among patients with cancer is not known. Methods We linked Western Washington SEER Cancer Registry records with federal bankruptcy records for the region. By using propensity score matching to account for differences in several demographic and clinical factors between patients who did and did not file for bankruptcy, we then fit Cox proportional hazards models to examine the relationship between bankruptcy filing and survival. Results Between 1995 and 2009, 231,596 persons were diagnosed with cancer. Patients who filed for bankruptcy (n = 4,728) were more likely to be younger, female, and nonwhite, to have local- or regional- (v distant-) stage disease at diagnosis, and have received treatment. After propensity score matching, 3,841 patients remained in each group (bankruptcy v no bankruptcy). In the matched sample, mean age was 53.0 years, 54% were men, mean income was $49,000, and majorities were white (86%), married (60%), and urban (91%) and had local- or regional-stage disease at diagnosis (84%). Both groups received similar initial treatments. The adjusted hazard ratio for mortality among patients with cancer who filed for bankruptcy versus those who did not was 1.79 (95% CI, 1.64 to 1.96). Hazard ratios varied by cancer type: colorectal, prostate, and thyroid cancers had the highest hazard ratios. Excluding patients with distant-stage disease from the models did not have an effect on results. Conclusion Severe financial distress requiring bankruptcy protection after cancer diagnosis appears to be a risk factor for mortality. Further research is needed to understand the process by which extreme financial distress influences survival after cancer diagnosis and to find strategies that could mitigate this risk. PMID:26811521

Cardiovascular mortality and exposure to extremely low frequency magnetic fields: a cohort study of Swiss railway workers

PubMed Central

Röösli, Martin; Egger, Matthias; Pfluger, Dominik; Minder, Christoph

2008-01-01

Background Exposure to intermittent magnetic fields of 16 Hz has been shown to reduce heart rate variability, and decreased heart rate variability predicts cardiovascular mortality. We examined mortality from cardiovascular causes in railway workers exposed to varying degrees to intermittent 16.7 Hz magnetic fields. Methods We studied a cohort of 20,141 Swiss railway employees between 1972 and 2002, including highly exposed train drivers (median lifetime exposure 120.5 μT-years), and less or little exposed shunting yard engineers (42.1 μT-years), train attendants (13.3 μT-years) and station masters (5.7 μT-years). During 464,129 person-years of follow up, 5,413 deaths were recorded and 3,594 deaths were attributed to cardio-vascular diseases. We analyzed data using Cox proportional hazards models. Results For all cardiovascular mortality the hazard ratio compared to station masters was 0.99 (95%CI: 0.91, 1.08) in train drivers, 1.13 (95%CI: 0.98, 1.30) in shunting yard engineers, and 1.09 (95%CI: 1.00, 1.19) in train attendants. Corresponding hazard ratios for arrhythmia related deaths were 1.04 (95%CI: 0.68, 1.59), 0.58 (95%CI: 0.24, 1.37) and 10 (95%CI: 0.87, 1.93) and for acute myocardial infarction 1.00 (95%CI: 0.73, 1.36), 1.56 (95%CI: 1.04, 2.32), and 1.14 (95%CI: 0.85, 1.53). The hazard ratio for arrhythmia related deaths per 100 μT-years of cumulative exposure was 0.94 (95%CI: 0.71, 1.24) and 0.91 (95%CI: 0.75, 1.11) for acute myocardial infarction. Conclusion This study provides evidence against an association between long-term occupational exposure to intermittent 16.7 Hz magnetic fields and cardiovascular mortality. PMID:18593477

Long-term outcomes in patients with rheumatologic disorders undergoing percutaneous coronary intervention: a BAsel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination (BASKET-PROVE) sub-study.

PubMed

Nochioka, Kotaro; Biering-Sørensen, Tor; Hansen, Kim Wadt; Sørensen, Rikke; Pedersen, Sune; Jørgensen, Peter Godsk; Iversen, Allan; Shimokawa, Hiroaki; Jeger, Raban; Kaiser, Christoph; Pfisterer, Matthias; Galatius, Søren

2017-12-01

Rheumatologic disorders are characterised by inflammation and an increased risk of coronary artery disease (CAD). However, the association between rheumatologic disorders and long-term prognosis in CAD patients undergoing percutaneous coronary intervention (PCI) is unknown. Thus, we aimed to examine the association between rheumatologic disorders and long-term prognosis in CAD patients undergoing PCI. A post-hoc analysis was performed in 4605 patients (age: 63.3 ± 11.0 years; male: 76.6%) with ST-segment elevation myocardial infarction (STEMI; n = 1396), non-STEMI ( n = 1541), and stable CAD ( n = 1668) from the all-comer stent trials, the BAsel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination (BASKET-PROVE) I and II trials. We evaluated the association between rheumatologic disorders and 2-year major adverse cardiac events (MACEs; cardiac death, nonfatal myocardial infarction (MI), and target vessel revascularisation (TVR)) by Cox regression analysis. Patients with rheumatologic disorders ( n = 197) were older, more often female, had a higher prevalence of renal disease, multi-vessel coronary disease, and bifurcation lesions, and had longer total stent lengths. During the 2-year follow-up, the MACE rate was 8.6% in the total cohort. After adjustment for potential confounders, rheumatologic disorders were associated with MACEs in the total cohort (adjusted hazard ratio: 1.55; 95% confidence interval (CI): 1.04-2.31) driven by the STEMI subgroup (adjusted hazard ratio: 2.38; 95% CI: 1.26-4.51). In all patients, rheumatologic disorders were associated with all-cause death (adjusted hazard ratio: 2.05; 95% CI: 1.14-3.70), cardiac death (adjusted hazard ratio: 2.63; 95% CI: 1.27-5.43), and non-fatal MI (adjusted hazard ratio: 2.64; 95% CI: 1.36-5.13), but not with TVR (adjusted hazard ratio: 0.81; 95% CI: 0.41-1.58). The presence of rheumatologic disorders appears to be independently associated with worse outcome in CAD patients undergoing PCI. This calls for further studies and focus on this high-risk group of patients following PCI.

Impact of disability status on suicide risks in South Korea: Analysis of National Health Insurance cohort data from 2003 to 2013.

PubMed

Lee, Sang-Uk; Roh, Sungwon; Kim, Young-Eun; Park, Jong-Ik; Jeon, Boyoung; Oh, In-Hwan

2017-01-01

The elevated risk of suicide in people with disability has been suggested in the previous studies; however, the majority of study results have been limited to specific disability types, and there is a lack of research comparing the risk of suicide in people with disability in general. To examine the hazard ratio of suicide according to the presence and the types of disability and identify patterns in the results. In this study, we used National Health Insurance Service-National Sample Cohort data on 990,598 people, and performed analysis on the cause of death from 2003 through 2013. A Cox proportional hazard model was used to estimate the hazard ratio of suicide associated with disability and its types. The hazard ratio of suicide among people with disability was 1.9-folds higher compared to people without disability. The risk of suicide among different disability types was higher in mental disorder, renal failure, brain injury and physical disability. The hazard ratio of suicide in people with disability was not varied by income. The time to death by suicide for people with disability from the onset of their disability was 39.8 months on average. Our findings suggest that when the government plans suicide prevention policies, early and additional interventions specific to people with disability are needed. Disability due to mental disorder, renal failure should be given priority. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Performance of a Fuel-Injection Spark-Ignition Engine Using a Hydrogenated Safety Fuel

NASA Technical Reports Server (NTRS)

Schey, Oscar W; Young, Alfred W

1934-01-01

This report presents the performance of a single-cylinder test engine using a hydrogenated safety fuel. The safety fuel has a flash point of 125 degrees f. (Cleveland open-dup method), which is high enough to remove most of the fire hazard, and an octane number of 95, which permits higher compression ratios to be used than are permissible with most undoped gasolines.

Hazard evaluation of inorganics, singly and in mixtures, to Flannelmouth Sucker Catostomus latipinnis in the San Juan River, New Mexico

USGS Publications Warehouse

Hamilton, S.J.; Buhl, K.J.

1997-01-01

Larval flannelmouth sucker (Catostomus latipinnis) were exposed to arsenate, boron, copper, molybdenum, selenate, selenite, uranium, vanadium, and zinc singly, and to five mixtures of five to nine inorganics. The exposures were conducted in reconstituted water representative of the San Juan River near Shiprock, New Mexico. The mixtures simulated environmental ratios reported for sites along the San Juan River (San Juan River backwater, Fruitland marsh, Hogback East Drain, Mancos River, and McElmo Creek). The rank order of the individual inorganics, from most to least toxic, was: copper > zinc > vanadium > selenite > selenate > arsenate > uranium > boron > molybdenum. All five mixtures exhibited additive toxicity to flannelmouth sucker. In a limited number of tests, 44-day-old and 13-day-old larvae exhibited no difference in sensitivity to three mixtures. Copper was the major toxic component in four mixtures (San Juan backwater, Hogback East Drain, Mancos River, and McElmo Creek), whereas zinc was the major toxic component in the Fruitland marsh mixture, which did not contain copper. The Hogback East Drain was the most toxic mixture tested. Comparison of 96-h LC50values with reported environmental water concentrations from the San Juan River revealed low hazard ratios for arsenic, boron, molybdenum, selenate, selenite, uranium, and vanadium, moderate hazard ratios for zinc and the Fruitland marsh mixture, and high hazard ratios for copper at three sites and four environmental mixtures representing a San Juan backwater, Hogback East Drain, Mancos River, and McElmo Creek. The high hazard ratios suggest that inorganic contaminants could adversely affect larval flannelmouth sucker in the San Juan River at four sites receiving elevated inorganics.

Use of the quality management system "JACIE" and outcome after hematopoietic stem cell transplantation.

PubMed

Gratwohl, Alois; Brand, Ronald; McGrath, Eoin; van Biezen, Anja; Sureda, Anna; Ljungman, Per; Baldomero, Helen; Chabannon, Christian; Apperley, Jane

2014-05-01

Competent authorities, healthcare payers and hospitals devote increasing resources to quality management systems but scientific analyses searching for an impact of these systems on clinical outcome remain scarce. Earlier data indicated a stepwise improvement in outcome after allogeneic hematopoietic stem cell transplantation with each phase of the accreditation process for the quality management system "JACIE". We therefore tested the hypothesis that working towards and achieving "JACIE" accreditation would accelerate improvement in outcome over calendar time. Overall mortality of the entire cohort of 107,904 patients who had a transplant (41,623 allogeneic, 39%; 66,281 autologous, 61%) between 1999 and 2006 decreased over the 14-year observation period by a factor of 0.63 per 10 years (hazard ratio: 0.63; 0.58-0.69). Considering "JACIE"-accredited centers as those with programs having achieved accreditation by November 2012, at the latest, this improvement was significantly faster in "JACIE"-accredited centers than in non-accredited centers (approximately 5.3% per year for 49,459 patients versus approximately 3.5% per year for 58,445 patients, respectively; hazard ratio: 0.83; 0.71-0.97). As a result, relapse-free survival (hazard ratio 0.85; 0.75-0.95) and overall survival (hazard ratio 0.86; 0.76-0.98) were significantly higher at 72 months for those patients transplanted in the 162 "JACIE"-accredited centers. No significant effects were observed after autologous transplants (hazard ratio 1.06; 0.99-1.13). Hence, working towards implementation of a quality management system triggers a dynamic process associated with a steeper reduction in mortality over the years and a significantly improved survival after allogeneic stem cell transplantation. Our data support the use of a quality management system for complex medical procedures.

Prognostic factors for survival in 676 consecutive patients with newly diagnosed primary glioblastoma.

PubMed

Filippini, Graziella; Falcone, Chiara; Boiardi, Amerigo; Broggi, Giovanni; Bruzzone, Maria G; Caldiroli, Dario; Farina, Rita; Farinotti, Mariangela; Fariselli, Laura; Finocchiaro, Gaetano; Giombini, Sergio; Pollo, Bianca; Savoiardo, Mario; Solero, Carlo L; Valsecchi, Maria G

2008-02-01

Reliable data on large cohorts of patients with glioblastoma are needed because such studies differ importantly from trials that have a strong bias toward the recruitment of younger patients with a higher performance status. We analyzed the outcome of 676 patients with histologically confirmed newly diagnosed glioblastoma who were treated consecutively at a single institution over a 7-year period (1997-2003) with follow-up to April 30, 2006. Survival probabilities were 57% at 1 year, 16% at 2 years, and 7% at 3 years. Progression-free survival was 15% at 1 year. Prolongation of survival was significantly associated with surgery in patients with a good performance status, whatever the patient's age, with an adjusted hazard ratio of 0.55 (p < 0.001) or a 45% relative decrease in the risk of death. Radiotherapy and chemotherapy improved survival, with adjusted hazard ratios of 0.61 (p = 0.001) and 0.89 (p = 0.04), respectively, regardless of age, performance status, or residual tumor volume. Recurrence occurred in 99% of patients throughout the follow-up. Reoperation was performed in one-fourth of these patients but was not effective, whether performed within 9 months (hazard ratio, 0.86; p = 0.256) or after 9 months (hazard ratio, 0.98; p = 0.860) of initial surgery, whereas second-line chemotherapy with procarbazine, lomustine, and vincristine (PCV) or with temozolomide improved survival (hazard ratio, 0.77; p = 0.008). Surgery followed by radiotherapy and chemotherapy should be considered in all patients with glioblastoma, and these treatments should not be withheld because of increasing age alone. The benefit of second surgery at recurrence is uncertain, and new trials are needed to assess its effectiveness. Chemotherapy with PCV or temozolomide seems to be a reasonable option at tumor recurrence.

Prognostic factors for survival in 676 consecutive patients with newly diagnosed primary glioblastoma

PubMed Central

Filippini, Graziella; Falcone, Chiara; Boiardi, Amerigo; Broggi, Giovanni; Bruzzone, Maria G.; Caldiroli, Dario; Farina, Rita; Farinotti, Mariangela; Fariselli, Laura; Finocchiaro, Gaetano; Giombini, Sergio; Pollo, Bianca; Savoiardo, Mario; Solero, Carlo L.; Valsecchi, Maria G.

2008-01-01

Reliable data on large cohorts of patients with glioblastoma are needed because such studies differ importantly from trials that have a strong bias toward the recruitment of younger patients with a higher performance status. We analyzed the outcome of 676 patients with histologically confirmed newly diagnosed glioblastoma who were treated consecutively at a single institution over a 7-year period (1997 – 2003) with follow-up to April 30, 2006. Survival probabilities were 57% at 1 year, 16% at 2 years, and 7% at 3 years. Progression-free survival was 15% at 1 year. Prolongation of survival was significantly associated with surgery in patients with a good performance status, whatever the patient’s age, with an adjusted hazard ratio of 0.55 (p < 0.001) or a 45% relative decrease in the risk of death. Radiotherapy and chemotherapy improved survival, with adjusted hazard ratios of 0.61 (p = 0.001) and 0.89 (p = 0.04), respectively, regardless of age, performance status, or residual tumor volume. Recurrence occurred in 99% of patients throughout the follow-up. Reoperation was performed in one-fourth of these patients but was not effective, whether performed within 9 months (hazard ratio, 0.86; p = 0.256) or after 9 months (hazard ratio, 0.98; p = 0.860) of initial surgery, whereas second-line chemotherapy with procarbazine, lomustine, and vincristine (PCV) or with temozolomide improved survival (hazard ratio, 0.77; p = 0.008). Surgery followed by radiotherapy and chemotherapy should be considered in all patients with glioblastoma, and these treatments should not be withheld because of increasing age alone. The benefit of second surgery at recurrence is uncertain, and new trials are needed to assess its effectiveness. Chemotherapy with PCV or temozolomide seems to be a reasonable option at tumor recurrence. PMID:17993634

Prognostic factors and survival according to tumour subtype in women presenting with breast cancer brain metastases at initial diagnosis.

PubMed

Leone, José Pablo; Leone, Julieta; Zwenger, Ariel Osvaldo; Iturbe, Julián; Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro

2017-03-01

The presence of brain metastases at the time of initial breast cancer diagnosis (BMIBCD) is uncommon. Hence, the prognostic assessment and management of these patients is very challenging. The aim of this study was to analyse the influence of tumour subtype compared with other prognostic factors in the survival of patients with BMIBCD. We evaluated women with BMIBCD, reported to Surveillance, Epidemiology and End Results program from 2010 to 2013. Patients with other primary malignancy were excluded. Univariate and multivariate analyses were performed to determine the effects of each variable on overall survival (OS). We included 740 patients. Median OS for the whole population was 10 months, and 20.7% of patients were alive at 36 months. Tumour subtype distribution was: 46.6% hormone receptor (HR)+/HER2-, 17% HR+/HER2+, 14.1% HR-/HER2+ and 22.3% triple-negative. Univariate analysis showed that the presence of liver metastases, lung metastases and triple-negative patients (median OS 6 months) had worse prognosis. The HR+/HER2+ subtype had the longest OS with a median of 22 months. In multivariate analysis, older age (hazard ratio 1.8), lobular histology (hazard ratio 2.08), triple-negative subtype (hazard ratio 2.25), liver metastases (hazard ratio 1.6) and unmarried patients (hazard ratio 1.39) had significantly shorter OS. Although the prognosis of patients with BMIBCD is generally poor, 20.7% were still alive 3 years after the diagnosis. There were substantial differences in OS according to tumour subtype. In addition to tumour subtype, other independent predictors of OS are age at diagnosis, marital status, histology and liver metastases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Risk of lung cancer and consumption of vegetables and fruit in Japanese: A pooled analysis of cohort studies in Japan.

PubMed

Wakai, Kenji; Sugawara, Yumi; Tsuji, Ichiro; Tamakoshi, Akiko; Shimazu, Taichi; Matsuo, Keitaro; Nagata, Chisato; Mizoue, Tetsuya; Tanaka, Keitaro; Inoue, Manami; Tsugane, Shoichiro; Sasazuki, Shizuka

2015-08-01

International reviews have concluded that consumption of fruit and vegetables might decrease the risk of lung cancer. However, the relevant epidemiological evidence still remains insufficient in Japan. Therefore, we performed a pooled analysis of data from four population-based cohort studies in Japan with >200 000 participants and >1700 lung cancer cases. We computed study-specific hazard ratios by quintiles of vegetable and fruit consumption as assessed by food frequency questionnaires. Summary hazard ratios were estimated by pooling the study-specific hazard ratios with a fixed-effect model. In men, we found inverse associations between fruit consumption and the age-adjusted and area-adjusted risk of mortality or incidence of lung cancer. However, the associations were largely attenuated after adjustment for smoking and energy intake. The significant decrease in risk among men remained only for a moderate level of fruit consumption; the lowest summary hazard ratios were found in the third quintile of intake (mortality: 0.71, 95% confidence interval 0.60-0.84; incidence: 0.83, 95% confidence interval 0.70-0.98). This decrease in risk was mainly detected in ever smokers. Conversely, vegetable intake was positively correlated with the risk of incidence of lung cancer after adjustment for smoking and energy intake in men (trend P, 0.024); the summary hazard ratio for the highest quintile was 1.26 (95% confidence interval 1.05-1.50). However, a similar association was not detected for mortality from lung cancer. In conclusion, a moderate level of fruit consumption is associated with a decreased risk of lung cancer in men among the Japanese population. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Kaplan-Meier Meets Chemical Kinetics: Intrinsic Rate of SOD1 Amyloidogenesis Decreased by Subset of ALS Mutations and Cannot Fully Explain Age of Disease Onset.

PubMed

Abdolvahabi, Alireza; Shi, Yunhua; Rasouli, Sanaz; Croom, Corbin M; Aliyan, Amir; Martí, Angel A; Shaw, Bryan F

2017-06-21

Over 150 mutations in SOD1 (superoxide dismutase-1) cause amyotrophic lateral sclerosis (ALS), presumably by accelerating SOD1 amyloidogenesis. Like many nucleation processes, SOD1 fibrillization is stochastic (in vitro), which inhibits the determination of aggregation rates (and obscures whether rates correlate with patient phenotypes). Here, we diverged from classical chemical kinetics and used Kaplan-Meier estimators to quantify the probability of apo-SOD1 fibrillization (in vitro) from ∼10 3 replicate amyloid assays of wild-type (WT) SOD1 and nine ALS variants. The probability of apo-SOD1 fibrillization (expressed as a Hazard ratio) is increased by certain ALS-linked SOD1 mutations but is decreased or remains unchanged by other mutations. Despite this diversity, Hazard ratios of fibrillization correlated linearly with (and for three mutants, approximately equaled) Hazard ratios of patient survival (R 2 = 0.67; Pearson's r = 0.82). No correlation exists between Hazard ratios of fibrillization and age of initial onset of ALS (R 2 = 0.09). Thus, Hazard ratios of fibrillization might explain rates of disease progression but not onset. Classical kinetic metrics of fibrillization, i.e., mean lag time and propagation rate, did not correlate as strongly with phenotype (and ALS mutations did not uniformly accelerate mean rate of nucleation or propagation). A strong correlation was found, however, between mean ThT fluorescence at lag time and patient survival (R 2 = 0.93); oligomers of SOD1 with weaker fluorescence correlated with shorter survival. This study suggests that SOD1 mutations trigger ALS by altering a property of SOD1 or its oligomers other than the intrinsic rate of amyloid nucleation (e.g., oligomer stability; rates of intercellular propagation; affinity for membrane surfaces; and maturation rate).

Unrelated alternative donor transplantation for severe acquired aplastic anemia: a study from the French Society of Bone Marrow Transplantation and Cell Therapies and the EBMT Severe Aplastic Anemia Working Party.

PubMed

Devillier, Raynier; Dalle, Jean-Hugues; Kulasekararaj, Austin; D'aveni, Maud; Clément, Laurence; Chybicka, Alicja; Vigouroux, Stéphane; Chevallier, Patrice; Koh, Mickey; Bertrand, Yves; Michallet, Mauricette; Zecca, Marco; Yakoub-Agha, Ibrahim; Cahn, Jean-Yves; Ljungman, Per; Bernard, Marc; Loiseau, Pascale; Dubois, Valérie; Maury, Sébastien; Socié, Gérard; Dufour, Carlo; Peffault de Latour, Regis

2016-07-01

Unrelated allogeneic transplantation for severe aplastic anemia is a treatment option after immunosuppressive treatment failure in the absence of a matched sibling donor. Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. Using the French Society of Bone Marrow Transplantation and Cell Therapies registry, we analyzed all consecutive patients (n=139) who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age over 30 years (Hazard Ratio=2.39; P=0.011), time from diagnosis to transplantation over 12 months (Hazard Ratio=2.18; P=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; P=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, we built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; P<0.001). The score was then confirmed on an independent cohort from the European Group for Blood and Marrow Transplantation database of 296 patients, with shorter survival in patients with at least 2 risk factors (Hazard Ratio=2.13; P=0.005) In conclusion, a simple score using age, transplantation timing and HLA matching would appear useful to help physicians in the daily care of patients with severe aplastic anemia. Copyright© Ferrata Storti Foundation.

Risk of lung cancer and consumption of vegetables and fruit in Japanese: A pooled analysis of cohort studies in Japan

PubMed Central

Wakai, Kenji; Sugawara, Yumi; Tsuji, Ichiro; Tamakoshi, Akiko; Shimazu, Taichi; Matsuo, Keitaro; Nagata, Chisato; Mizoue, Tetsuya; Tanaka, Keitaro; Inoue, Manami; Tsugane, Shoichiro; Sasazuki, Shizuka

2015-01-01

International reviews have concluded that consumption of fruit and vegetables might decrease the risk of lung cancer. However, the relevant epidemiological evidence still remains insufficient in Japan. Therefore, we performed a pooled analysis of data from four population-based cohort studies in Japan with >200 000 participants and >1700 lung cancer cases. We computed study-specific hazard ratios by quintiles of vegetable and fruit consumption as assessed by food frequency questionnaires. Summary hazard ratios were estimated by pooling the study-specific hazard ratios with a fixed-effect model. In men, we found inverse associations between fruit consumption and the age-adjusted and area-adjusted risk of mortality or incidence of lung cancer. However, the associations were largely attenuated after adjustment for smoking and energy intake. The significant decrease in risk among men remained only for a moderate level of fruit consumption; the lowest summary hazard ratios were found in the third quintile of intake (mortality: 0.71, 95% confidence interval 0.60–0.84; incidence: 0.83, 95% confidence interval 0.70–0.98). This decrease in risk was mainly detected in ever smokers. Conversely, vegetable intake was positively correlated with the risk of incidence of lung cancer after adjustment for smoking and energy intake in men (trend P, 0.024); the summary hazard ratio for the highest quintile was 1.26 (95% confidence interval 1.05–1.50). However, a similar association was not detected for mortality from lung cancer. In conclusion, a moderate level of fruit consumption is associated with a decreased risk of lung cancer in men among the Japanese population. PMID:26033436

Increased Rate of Hospitalization for Diabetes and Residential Proximity of Hazardous Waste Sites

PubMed Central

Kouznetsova, Maria; Huang, Xiaoyu; Ma, Jing; Lessner, Lawrence; Carpenter, David O.

2007-01-01

Background Epidemiologic studies suggest that there may be an association between environmental exposure to persistent organic pollutants (POPs) and diabetes. Objective The aim of this study was to test the hypothesis that residential proximity to POP-contaminated waste sites result in increased rates of hospitalization for diabetes. Methods We determined the number of hospitalized patients 25–74 years of age diagnosed with diabetes in New York State exclusive of New York City for the years 1993–2000. Descriptive statistics and negative binomial regression were used to compare diabetes hospitalization rates in individuals who resided in ZIP codes containing or abutting hazardous waste sites containing POPs (“POP” sites); ZIP codes containing hazardous waste sites but with wastes other than POPs (“other” sites); and ZIP codes without any identified hazardous waste sites (“clean” sites). Results Compared with the hospitalization rates for diabetes in clean sites, the rate ratios for diabetes discharges for people residing in POP sites and “other” sites, after adjustment for potential confounders were 1.23 [95% confidence interval (CI), 1.15–1.32] and 1.25 (95% CI, 1.16–1.34), respectively. In a subset of POP sites along the Hudson River, where there is higher income, less smoking, better diet, and more exercise, the rate ratio was 1.36 (95% CI, 1.26–1.47) compared to clean sites. Conclusions After controlling for major confounders, we found a statistically significant increase in the rate of hospitalization for diabetes among the population residing in the ZIP codes containing toxic waste sites. PMID:17366823

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

PubMed Central

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

2017-01-01

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

Effect of liquid-to-solid ratio on semi-solid Fenton process in hazardous solid waste detoxication.

PubMed

Hu, Li-Fang; Feng, Hua-Jun; Long, Yu-Yang; Zheng, Yuan-Ge; Fang, Cheng-Ran; Shen, Dong-Sheng

2011-01-01

The liquid-to-solid ratio (L/S) of semi-solid Fenton process (SSFP) designated for hazardous solid waste detoxication was investigated. The removal and minimization effects of o-nitroaniline (ONA) in simulate solid waste residue (SSWR) from organic arsenic industry was evaluated by total organic carbon (TOC) and ONA removal efficiency, respectively. Initially, Box-Behnken design (BBD) and response surface methodology (RSM) were used to optimize the key factors of SSFP. Results showed that the removal rates of TOC and ONA decreased as L/S increased. Subsequently, four target initial ONA concentrations including 100 mg kg(-1), 1 g kg(-1), 10 g kg(-1), and 100 gk g(-1) on a dry basis were evaluated for the effect of L/S. A significant cubic empirical model between the initial ONA concentration and L/S was successfully developed to predict the optimal L/S for given initial ONA concentration for SSFP. Moreover, an optimized operation strategy of multi-SSFP for different cases was determined based on the residual target pollutant concentration and the corresponding environmental conditions. It showed that the total L/S of multi-SSFP in all tested scenarios was no greater than 3.8, which is lower than the conventional slurry systems (L/S ≥ 5). The multi-SSFP is environment-friendly when it used for detoxication of hazardous solid waste contaminated by ONA and provides a potential method for the detoxication of hazardous solid waste contaminated by organics. Copyright © 2010 Elsevier Ltd. All rights reserved.

Correlation of 18F-FDG PET and MRI Apparent Diffusion Coefficient Histogram Metrics with Survival in Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium.

PubMed

Zukotynski, Katherine A; Vajapeyam, Sridhar; Fahey, Frederic H; Kocak, Mehmet; Brown, Douglas; Ricci, Kelsey I; Onar-Thomas, Arzu; Fouladi, Maryam; Poussaint, Tina Young

2017-08-01

The purpose of this study was to describe baseline 18 F-FDG PET voxel characteristics in pediatric diffuse intrinsic pontine glioma (DIPG) and to correlate these metrics with baseline MRI apparent diffusion coefficient (ADC) histogram metrics, progression-free survival (PFS), and overall survival. Methods: Baseline brain 18 F-FDG PET and MRI scans were obtained in 33 children from Pediatric Brain Tumor Consortium clinical DIPG trials. 18 F-FDG PET images, postgadolinium MR images, and ADC MR images were registered to baseline fluid attenuation inversion recovery MR images. Three-dimensional regions of interest on fluid attenuation inversion recovery MR images and postgadolinium MR images and 18 F-FDG PET and MR ADC histograms were generated. Metrics evaluated included peak number, skewness, and kurtosis. Correlation between PET and MR ADC histogram metrics was evaluated. PET pixel values within the region of interest for each tumor were plotted against MR ADC values. The association of these imaging markers with survival was described. Results: PET histograms were almost always unimodal (94%, vs. 6% bimodal). None of the PET histogram parameters (skewness or kurtosis) had a significant association with PFS, although a higher PET postgadolinium skewness tended toward a less favorable PFS (hazard ratio, 3.48; 95% confidence interval [CI], 0.75-16.28 [ P = 0.11]). There was a significant association between higher MR ADC postgadolinium skewness and shorter PFS (hazard ratio, 2.56; 95% CI, 1.11-5.91 [ P = 0.028]), and there was the suggestion that this also led to shorter overall survival (hazard ratio, 2.18; 95% CI, 0.95-5.04 [ P = 0.067]). Higher MR ADC postgadolinium kurtosis tended toward shorter PFS (hazard ratio, 1.30; 95% CI, 0.98-1.74 [ P = 0.073]). PET and MR ADC pixel values were negatively correlated using the Pearson correlation coefficient. Further, the level of PET and MR ADC correlation was significantly positively associated with PFS; tumors with higher values of ADC-PET correlation had more favorable PFS (hazard ratio, 0.17; 95% CI, 0.03-0.89 [ P = 0.036]), suggesting that a higher level of negative ADC-PET correlation leads to less favorable PFS. A more significant negative correlation may indicate higher-grade elements within the tumor leading to poorer outcomes. Conclusion: 18 F-FDG PET and MR ADC histogram metrics in pediatric DIPG demonstrate different characteristics with often a negative correlation between PET and MR ADC pixel values. A higher negative correlation is associated with a worse PFS, which may indicate higher-grade elements within the tumor. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Retinal injury from simultaneous exposure to 532-nm and 860-nm laser irradiation

NASA Astrophysics Data System (ADS)

Schuster, Kurt; Roach, William P.; Polhamus, Garrett; Notabartolo, John; DiCarlo, Cheryl; Stockton, Kevin; Stolarski, David; Carothers, Val; Rockwell, Benjamin A.; Cain, Clarence

2004-07-01

To properly assess the retinal hazards from several lasers using multiple wavelengths, the retinal effects of 10-second laser irradiation from 532 and 860 nm were determined in non-human primates for several different power combinations of these wavelengths. A total of 12 eyes were exposed using four different ratios of power levels to determine the contribution to the damage levels from each wavelength. The data are compared to the calculations resulting from use of the currently accepted method of predicting hazards from simultaneous laser. The ANSI-Z136 - 2000 standard was used to calculate the combined maximum permissible exposure (MPE) and for comparison with the measured visible lesion thresholds, i.e., ED50s.

Dietary Sodium to Potassium Ratio and Risk of Stroke in a Multiethnic Urban Population: The Northern Manhattan Study.

PubMed

Willey, Joshua; Gardener, Hannah; Cespedes, Sandino; Cheung, Ying K; Sacco, Ralph L; Elkind, Mitchell S V

2017-11-01

There is growing evidence that increased dietary sodium (Na) intake increases the risk of vascular diseases, including stroke, at least in part via an increase in blood pressure. Higher dietary potassium (K), seen with increased intake of fruits and vegetables, is associated with lower blood pressure. The goal of this study was to determine the association of a dietary Na:K with risk of stroke in a multiethnic urban population. Stroke-free participants from the Northern Manhattan Study, a population-based cohort study of stroke incidence, were followed-up for incident stroke. Baseline food frequency questionnaires were analyzed for Na and K intake. We estimated the hazard ratios and 95% confidence intervals for the association of Na:K with incident total stroke using multivariable Cox proportional hazards models. Among 2570 participants with dietary data (mean age, 69±10 years; 64% women; 21% white; 55% Hispanic; 24% black), the mean Na:K ratio was 1.22±0.43. Over a mean follow-up of 12 years, there were 274 strokes. In adjusted models, a higher Na:K ratio was associated with increased risk for stroke (hazard ratio, 1.6; 95% confidence interval, 1.2-2.1) and specifically ischemic stroke (hazard ratio, 1.6; 95% confidence interval, 1.2-2.1). Na:K intake is an independent predictor of stroke risk. Further studies are required to understand the joint effect of Na and K intake on risk of cardiovascular disease. © 2017 American Heart Association, Inc.

A more powerful test based on ratio distribution for retention noninferiority hypothesis.

PubMed

Deng, Ling; Chen, Gang

2013-03-11

Rothmann et al. ( 2003 ) proposed a method for the statistical inference of fraction retention noninferiority (NI) hypothesis. A fraction retention hypothesis is defined as a ratio of the new treatment effect verse the control effect in the context of a time to event endpoint. One of the major concerns using this method in the design of an NI trial is that with a limited sample size, the power of the study is usually very low. This makes an NI trial not applicable particularly when using time to event endpoint. To improve power, Wang et al. ( 2006 ) proposed a ratio test based on asymptotic normality theory. Under a strong assumption (equal variance of the NI test statistic under null and alternative hypotheses), the sample size using Wang's test was much smaller than that using Rothmann's test. However, in practice, the assumption of equal variance is generally questionable for an NI trial design. This assumption is removed in the ratio test proposed in this article, which is derived directly from a Cauchy-like ratio distribution. In addition, using this method, the fundamental assumption used in Rothmann's test, that the observed control effect is always positive, that is, the observed hazard ratio for placebo over the control is greater than 1, is no longer necessary. Without assuming equal variance under null and alternative hypotheses, the sample size required for an NI trial can be significantly reduced if using the proposed ratio test for a fraction retention NI hypothesis.

Candida transmission and sexual behaviors as risks for a repeat episode of Candida vulvovaginitis.

PubMed

Reed, Barbara D; Zazove, Philip; Pierson, Carl L; Gorenflo, Daniel W; Horrocks, Julie

2003-12-01

To assess associations between female and male factors and the risk of recurring Candida vulvovaginitis. A prospective cohort study of 148 women with Candida vulvovaginitis and 78 of their male sexual partners was conducted at two primary care practices in the Ann Arbor, Michigan, area. Thirty-three of 148 women developed at least one further episode of Candida albicans vulvovaginitis within 1 year of follow-up. Cultures of Candida species from various sites of the woman (tongue, feces, vulva, and vagina) and from her partner (tongue, feces, urine, and semen) did not predict recurrences. Female factors associated with recurrence included recent masturbating with saliva (hazard ratio 2.66 [95% CI 1.17-6.06]) or cunnilingus (hazard ratio 2.94 [95% CI 1.12-7.68]) and ingestion of two or more servings of bread per day (p

Quantifying the relative risk of sex offenders: risk ratios for static-99R.

PubMed

Hanson, R Karl; Babchishin, Kelly M; Helmus, Leslie; Thornton, David

2013-10-01

Given the widespread use of empirical actuarial risk tools in corrections and forensic mental health, it is important that evaluators and decision makers understand how scores relate to recidivism risk. In the current study, we found strong evidence for a relative risk interpretation of Static-99R scores using 8 samples from Canada, United Kingdom, and Western Europe (N = 4,037 sex offenders). Each increase in Static-99R score was associated with a stable and consistent increase in relative risk (as measured by an odds ratio or hazard ratio of approximately 1.4). Hazard ratios from Cox regression were used to calculate risk ratios that can be reported for Static-99R. We recommend that evaluators consider risk ratios as a useful, nonarbitrary metric for quantifying and communicating risk information. To avoid misinterpretation, however, risk ratios should be presented with recidivism base rates.

Evaluating MoE and its Uncertainty and Variability for Food Contaminants (EuroTox presentation)

EPA Science Inventory

Margin of Exposure (MoE), is a metric for quantifying the relationship between exposure and hazard. Ideally, it is the ratio of the dose associated with hazard and an estimate of exposure. For example, hazard may be characterized by a benchmark dose (BMD), and, for food contami...

Does Quitting Smoking Make a Difference Among Newly Diagnosed Head and Neck Cancer Patients?

PubMed Central

Choi, Seung Hee; Terrell, Jeffrey E.; Bradford, Carol R.; Ghanem, Tamer; Spector, Matthew E.; Wolf, Gregory T.; Lipkus, Isaac M.

2016-01-01

Introduction: To determine if smoking after a cancer diagnosis makes a difference in mortality among newly diagnosed head and neck cancer patients. Methods: Longitudinal data were collected from newly diagnosed head and neck cancer patients with a median follow-up time of 1627 days (N = 590). Mortality was censored at 8 years or September 1, 2011, whichever came first. Based on smoking status, all patients were categorized into four groups: continuing smokers, quitters, former smokers, or never-smokers. A broad range of covariates were included in the analyses. Kaplan–Meier curves, bivariate and multivariate Cox proportional hazards models were constructed. Results: Eight-year overall mortality and cancer-specific mortality were 40.5% (239/590) and 25.4% (150/590), respectively. Smoking status after a cancer diagnosis predicted overall mortality and cancer-specific mortality. Compared to never-smokers, continuing smokers had the highest hazard ratio (HR) of dying from all causes (HR = 2.71, 95% confidence interval [CI] = 1.48–4.98). Those who smoked at diagnosis, but quit and did not relapse—quitters—had an improved hazard ratio of dying (HR = 2.38, 95% CI = 1.29–4.36) and former smokers at diagnosis with no relapse after diagnosis—former smokers—had the lowest hazard ratio of dying from all causes (HR = 1.68, 95% CI = 1.12–2.56). Similarly, quitters had a slightly higher hazard ratio of dying from cancer-specific reasons (HR = 2.38, 95% CI = 1.13–5.01) than never-smokers, which was similar to current smokers (HR = 2.07, 95% CI = 0.96–4.47), followed by former smokers (HR = 1.70, 95% CI = 1.00–2.89). Conclusions: Compared to never-smokers, continuing smokers have the highest HR of overall mortality followed by quitters and former smokers, which indicates that smoking cessation, even after a cancer diagnosis, may improve overall mortality among newly diagnosed head and neck cancer patients. Health care providers should consider incorporating smoking cessation interventions into standard cancer treatment to improve survival among this population. Implications: Using prospective observational longitudinal data from 590 head and neck cancer patients, this study showed that continuing smokers have the highest overall mortality relative to never-smokers, which indicates that smoking cessation, even after a cancer diagnosis, may have beneficial effects on long-term overall mortality. Health care providers should consider incorporating smoking cessation interventions into standard cancer treatment to improve survival among this population. PMID:27613928

Comparison of Fuzzy-Based Models in Landslide Hazard Mapping

NASA Astrophysics Data System (ADS)

Mijani, N.; Neysani Samani, N.

2017-09-01

Landslide is one of the main geomorphic processes which effects on the development of prospect in mountainous areas and causes disastrous accidents. Landslide is an event which has different uncertain criteria such as altitude, slope, aspect, land use, vegetation density, precipitation, distance from the river and distance from the road network. This research aims to compare and evaluate different fuzzy-based models including Fuzzy Analytic Hierarchy Process (Fuzzy-AHP), Fuzzy Gamma and Fuzzy-OR. The main contribution of this paper reveals to the comprehensive criteria causing landslide hazard considering their uncertainties and comparison of different fuzzy-based models. The quantify of evaluation process are calculated by Density Ratio (DR) and Quality Sum (QS). The proposed methodology implemented in Sari, one of the city of Iran which has faced multiple landslide accidents in recent years due to the particular environmental conditions. The achieved results of accuracy assessment based on the quantifier strated that Fuzzy-AHP model has higher accuracy compared to other two models in landslide hazard zonation. Accuracy of zoning obtained from Fuzzy-AHP model is respectively 0.92 and 0.45 based on method Precision (P) and QS indicators. Based on obtained landslide hazard maps, Fuzzy-AHP, Fuzzy Gamma and Fuzzy-OR respectively cover 13, 26 and 35 percent of the study area with a very high risk level. Based on these findings, fuzzy-AHP model has been selected as the most appropriate method of zoning landslide in the city of Sari and the Fuzzy-gamma method with a minor difference is in the second order.

Repeated measures of inflammation and oxidative stress biomarkers in preeclamptic and normotensive pregnancies.

PubMed

Ferguson, Kelly K; Meeker, John D; McElrath, Thomas F; Mukherjee, Bhramar; Cantonwine, David E

2017-05-01

Preeclampsia is a prevalent and enigmatic disease, in part characterized by poor remodeling of the spiral arteries. However, preeclampsia does not always clinically present when remodeling has failed to occur. Hypotheses surrounding the "second hit" that is necessary for the clinical presentation of the disease focus on maternal inflammation and oxidative stress. Yet, the studies to date that have investigated these factors have used cross-sectional study designs or small study populations. In the present study, we sought to explore longitudinal trajectories, beginning early in gestation, of a panel of inflammation and oxidative stress markers in women who went on to have preeclamptic or normotensive pregnancies. We examined 441 subjects from the ongoing LIFECODES prospective birth cohort, which included 50 mothers who experienced preeclampsia and 391 mothers with normotensive pregnancies. Participants provided urine and plasma samples at 4 time points during gestation (median, 10, 18, 26, and 35 weeks) that were analyzed for a panel of oxidative stress and inflammation markers. Oxidative stress biomarkers included 8-isoprostane and 8-hydroxydeoxyguanosine. Inflammation biomarkers included C-reactive protein, the cytokines interleukin-1β, -6, and -10, and tumor necrosis factor-α. We created Cox proportional hazard models to calculate hazard ratios based on time of preeclampsia diagnosis in association with biomarker concentrations at each of the 4 study visits. In adjusted models, hazard ratios of preeclampsia were significantly (P<.01) elevated in association with all inflammation biomarkers that were measured at visit 2 (median, 18 weeks; hazard ratios, 1.31-1.83, in association with an interquartile range increase in biomarker). Hazard ratios at this time point were the most elevated for C-reactive protein, for interleukin-1β, -6, and -10, and for the oxidative stress biomarker 8-isoprostane (hazard ratio, 1.68; 95% confidence interval, 1.14-2.48) compared to other time points. Hazard ratios for tumor necrosis factor-α were consistently elevated at all 4 of the study visits (hazard ratios, 1.49-1.63; P<.01). In sensitivity analyses, we observed that these associations were attenuated within groups typically at higher risk of experiencing preeclampsia, which include African American mothers, mothers with higher body mass index at the beginning of gestation, and pregnancies that ended preterm. This study provides the most robust data to date on repeated measures of inflammation and oxidative stress in preeclamptic compared with normotensive pregnancies. Within these groups, inflammation and oxidative stress biomarkers show different patterns across gestation, beginning as early as 10 weeks. The start of the second trimester appears to be a particularly important time point for the measurement of these biomarkers. Although biomarkers alone do not appear to be useful in the prediction of preeclampsia, these data are useful in understanding the maternal inflammatory profile in pregnancy before the development of the disease and may be used to further develop an understanding of potentially preventative measures. Published by Elsevier Inc.

Red meat consumption and risk of heart failure in male physicians

PubMed Central

Ashaye, A; Gaziano, J; Djoussé, L

2010-01-01

Background and Aims Heart failure (HF) remains a major public health issue. Red meat and dietary heme iron have been associated with an increased risk of coronary heart disease and hypertension, two major risk factors for HF. However, it is not known whether red meat intake influences the risk of HF. We therefore examined the association between red meat consumption and incident HF. Methods and Results We prospectively studied 21,120 apparently healthy men (mean age 54.6 y) from the Physicians’ Health Study (1982–2008). Red meat was assessed by an abbreviated food questionnaire and incident HF was ascertained through annual follow-up questionnaires. We used Cox proportional hazard models to estimate hazard ratios. In a multivariable model, there was a positive and graded relation between red meat consumption and HF [hazard ratio (95% CI) of 1.0 (reference), 1.02 (0.85–1.22), 1.08 (0.90–1.30), 1.17 (0.97–1.41), and 1.24 (1.03–1.48) from the lowest to the highest quintile of red meat, respectively (p for trend 0.007)]. This association was observed for HF with (p for trend 0. 035) and without (p for trend 0.038) antecedent myocardial infarction. Conclusion Our data suggest that higher intake of red meat is associated with an increased risk of HF. PMID:20675107

Is Genetic Background Important in Lung Cancer Survival?

PubMed Central

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

2009-01-01

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

Healthy eating and reduced risk of cognitive decline

PubMed Central

Dehghan, Mahshid; O'Donnell, Martin; Anderson, Craig; Teo, Koon; Gao, Peggy; Sleight, Peter; Dagenais, Gilles; Probstfield, Jeffrey L.; Mente, Andrew; Yusuf, Salim

2015-01-01

Objective: We sought to determine the association of dietary factors and risk of cognitive decline in a population at high risk of cardiovascular disease. Methods: Baseline dietary intake and measures of the Mini-Mental State Examination were recorded in 27,860 men and women who were enrolled in 2 international parallel trials of the ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease) studies. We measured diet quality using the modified Alternative Healthy Eating Index. Cox proportional hazards regression was used to determine the association between diet quality and risk of ≥3-point decline in Mini-Mental State Examination score, and reported as hazard ratio with 95% confidence intervals with adjustment for covariates. Results: During 56 months of follow-up, 4,699 cases of cognitive decline occurred. We observed lower risk of cognitive decline among those in the healthiest dietary quintile of modified Alternative Healthy Eating Index compared with lowest quintile (hazard ratio 0.76, 95% confidence interval 0.66–0.86, Q5 vs Q1). Lower risk of cognitive decline was consistent regardless of baseline cognitive level. Conclusion: We found that higher diet quality was associated with a reduced risk of cognitive decline. Improved diet quality represents an important potential target for reducing the global burden of cognitive decline. PMID:25948720

Symptom-Hemodynamic Mismatch and Heart Failure Event Risk

PubMed Central

Lee, Christopher S.; Hiatt, Shirin O.; Denfeld, Quin E.; Mudd, James O.; Chien, Christopher; Gelow, Jill M.

2014-01-01

Background Heart failure (HF) is a heterogeneous condition of both symptoms and hemodynamics. Objective The goal of this study was to identify distinct profiles among integrated data on physical and psychological symptoms and hemodynamics, and quantify differences in 180-day event-risk among observed profiles. Methods A secondary analysis of data collected during two prospective cohort studies by a single group of investigators was performed. Latent class mixture modeling was used to identify distinct symptom-hemodynamic profiles. Cox proportional hazards modeling was used to quantify difference in event-risk (HF emergency visit, hospitalization or death) among profiles. Results The mean age (n=291) was 57±13 years, 38% were female, and 61% had class III/IV HF. Three distinct symptom-hemodynamic profiles were identified. 17.9% of patients had concordant symptoms and hemodynamics (i.e. moderate physical and psychological symptoms matched the comparatively hemodynamic profile), 17.9% had severe symptoms and average hemodynamics, and 64.2% had poor hemodynamics and mild symptoms. Compared to those in the concordant profile, both profiles of symptom-hemodynamic mismatch were associated with a markedly increased event-risk (severe symptoms hazards ratio = 3.38, p=0.033; poor hemodynamics hazards ratio = 3.48, p=0.016). Conclusions A minority of adults with HF have concordant symptoms and hemodynamics. Either profile of symptom-hemodynamic mismatch in HF is associated with a greater risk of healthcare utilization for HF or death. PMID:24988323

Association of Time between Surgery and Adjuvant Therapy with Survival in Oral Cavity Cancer.

PubMed

Chen, Michelle M; Harris, Jeremy P; Orosco, Ryan K; Sirjani, Davud; Hara, Wendy; Divi, Vasu

2018-06-01

Objective The National Cancer Center Network recommends starting radiation therapy within 6 weeks after surgery for oral cavity squamous cell carcinoma (OCSCC), but there is limited evidence of the importance of the total time from surgery to completion of radiation therapy (package time). We set out to determine if there was an association between package time and survival in OCSCC and to evaluate the impact of treatment location on outcomes. Study Design Retrospective cohort study. Setting Tertiary academic medical center. Subjects and Methods We reviewed the records of patients with OCSCC who completed postoperative radiation therapy at an academic medical center from 2008 to 2016. The primary endpoints were overall survival and recurrence-free survival. Statistical analysis included χ 2 tests and Cox proportional hazards regressions. Results We identified 132 patients with an average package time of 12.6 weeks. On multivariate analysis, package time >11 weeks was independently associated with decreased overall survival (hazard ratio, 6.68; 95% CI, 1.42-31.44) and recurrence-free survival (hazard ratio, 2.94; 95% CI, 1.20-7.18). Patients who received radiation therapy at outside facilities were more likely to have treatment delays (90.2% vs 62.9%, P = .001). Conclusions Prolonged package times are associated with decreased overall and recurrence-free survival among patients with OCSCC. Patients who received radiation therapy at outside facilities are more likely to have prolonged package times.

Justice at Work and Metabolic Syndrome: the Whitehall II Study

PubMed Central

Gimeno, David; Tabák, Ádám G.; Ferrie, Jane E.; Shipley, Martin J.; De Vogli, Roberto; Elovainio, Marko; Vahtera, Jussi; Marmot, Michael G.; Kivimäki, Mika

2011-01-01

Objectives Growing evidence shows that high levels of justice are beneficial for employee health, although biological mechanisms underlying this association are yet to be clarified. We aim to test whether high justice at work protects against metabolic syndrome. Methods A prospective cohort study of 20 civil service departments in London (the Whitehall II study) including 6123 male and female British civil servants aged 35 to 55 years without prevalent CHD at baseline (1985-1990). Perceived justice at work was determined by means of questionnaire on two occasions between 1985 and 1990. Follow-up for metabolic syndrome and its components occurring from 1990 through 2004 was based on clinical assessments on three occasions over more than 18 years. Results Cox proportional hazard models adjusted for age, ethnicity and employment grade showed that men who experienced a high level of justice at work had a lower risk of incident metabolic syndrome than employees with a low level of justice (hazard ratio 0.75; 95% confidence interval: 0.63-0.89). There was little evidence of an association between organizational justice and metabolic syndrome or its components in women (hazard ratio 0.88; 95%CI: 0.67-1.17). Conclusions Our prospective findings provide evidence of an association between high levels of justice at work and the development of metabolic syndrome in men. PMID:19819861

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

PubMed

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

2018-03-01

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

Cardiac Calcifications on Echocardiography Are Associated with Mortality and Stroke.

PubMed

Lu, Marvin Louis Roy; Gupta, Shuchita; Romero-Corral, Abel; Matejková, Magdaléna; De Venecia, Toni; Obasare, Edinrin; Bhalla, Vikas; Pressman, Gregg S

2016-12-01

Calcium deposits in the aortic valve and mitral annulus have been associated with cardiovascular events and mortality. However, there is no accepted standard method for scoring such cardiac calcifications, and most existing methods are simplistic. The aim of this study was to test the hypothesis that a semiquantitative score, one that accounts for all visible calcium on echocardiography, could predict all-cause mortality and stroke in a graded fashion. This was a retrospective study of 443 unselected subjects derived from a general echocardiography database. A global cardiac calcium score (GCCS) was applied that assigned points for calcification in the aortic root and valve, mitral annulus and valve, and submitral apparatus, and points for restricted leaflet mobility. The primary outcome was all-cause mortality, and the secondary outcome was stroke. Over a mean 3.8 ± 1.7 years of follow-up, there were 116 deaths and 34 strokes. Crude mortality increased in a graded fashion with increasing GCCS. In unadjusted proportional hazard analysis, the GCCS was significantly associated with total mortality (hazard ratio, 1.26; 95% CI, 1.17-1.35; P < .0001) and stroke (hazard ratio, 1.23; 95% CI, 1.07-1.40; P = .003). After adjusting for demographic and clinical factors (age, gender, body mass index, diabetes, hypertension, dyslipidemia, smoking, family history of coronary disease, chronic kidney disease, history of atrial fibrillation, and history of stroke), these associations remained significant. The GCCS is easily applied to routinely acquired echocardiograms and has clinically significant associations with total mortality and stroke. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

CD8+ T cells and Risk for Bacterial Pneumonia and All-Cause Mortality Among HIV-infected Women

PubMed Central

Gohil, Shruti; Heo, Moonseong; Schoenbaum, Ellie; Celentano, David; Pirofski, Liise-anne

2012-01-01

Background Bacterial pneumonia risk is disproportionately high among those infected with Human Immunodeficiency Virus (HIV). This risk is present across all CD4+ T cell levels (TCL), suggesting additional factors govern susceptibility. This study examines CD8+ TCL and risk for HIV-associated bacterial pneumonia and all-cause mortality. Methods Demographic, clinical, and laboratory data were obtained for 885 HIV-infected (HIV+) women enrolled in the HIV Epidemiologic Research Study (HERS). Bacterial pneumonia cases were identified using clinical, microbiologic, and radiographic criteria. CD8+ TCLs were assessed at 6-month intervals. Statistical methods included Cox proportional hazards regression modeling and covariate-adjusted survival estimates. Results Relative to a referent CD8+ TCL 401–800 cells/mm3, risk for bacterial pneumonia was significantly higher when CD8+ TCLs were ≤ 400 (hazard ratio 1.65, p=0.017, 95% CI 1.10–2.49), after adjusting for age, CD4+ TCL, viral load, and antiretroviral use. There was also a significantly higher risk of death when CD8+ TCLs were ≤ 400 cells/mm3 (hazard ratio 1.45, p=0.04, 95% CI 1.02–2.06). Covariate-adjusted survival estimates revealed shorter time to pneumonia and death in this CD8+ TCL category and the overall association of the categorized CD8+TCL with bacterial pneumonia and all-cause mortality were each statistically significant (p=0.017 and p<0.0001, respectively). Conclusions CD8+ TCL ≤ 400 cells/mm3 was associated with increased risk for pneumonia and all-cause mortality in HIV-infected women in the HERS Cohort, suggesting that CD8+ TCL could serve as an adjunctive biomarker of pneumonia risk and mortality in HIV-infected individuals. PMID:22334070

Evaluation of Rainfall-induced Landslide Potential

NASA Astrophysics Data System (ADS)

Chen, Y. R.; Tsai, K. J.; Chen, J. W.; Chue, Y. S.; Lu, Y. C.; Lin, C. W.

2016-12-01

Due to Taiwan's steep terrain, rainfall-induced landslides often occur and lead to human causalities and properties loss. Taiwan's government has invested huge reconstruction funds to the affected areas. However, after rehabilitation they still face the risk of secondary sediment disasters. Therefore, this study assessed rainfall-induced landslide potential and spatial distribution in some watersheds of Southern Taiwan to configure reasonable assessment process and methods for landslide potential. This study focused on the multi-year multi-phase heavy rainfall events after 2009 Typhoon Morakot and applied the analysis techniques for the classification of satellite images of research region before and after rainfall to obtain surface information and hazard log data. GIS and DEM were employed to obtain the ridge and water system and to explore characteristics of landslide distribution. A multivariate hazards evaluation method was applied to quantitatively analyze the weights of various hazard factors. Furthermore, the interaction between rainfall characteristic, slope disturbance and landslide mechanism was analyzed. The results of image classification show that the values of coefficient of agreement are at medium-high level. The agreement of landslide potential map is at around 80% level compared with historical disaster sites. The relations between landslide potential level, slope disturbance degree, and the ratio of number and area of landslide increment corresponding heavy rainfall events are positive. The ratio of landslide occurrence is proportional to the value of instability index. Moreover, for each rainfall event, the number and scale of secondary landslide sites are much more than those of new landslide sites. The greater the slope land disturbance, the more likely it is that the scale of secondary landslide become greater. The spatial distribution of landslide depends on the interaction of rainfall patterns, slope, and elevation of the research area.

Loss to follow-up in the Australian HIV Observational Database.

PubMed

McManus, Hamish; Petoumenos, Kathy; Brown, Katherine; Baker, David; Russell, Darren; Read, Tim; Smith, Don; Wray, Lynne; Giles, Michelle; Hoy, Jennifer; Carr, Andrew; Law, Matthew G

2015-01-01

Loss to follow-up (LTFU) in HIV-positive cohorts is an important surrogate for interrupted clinical care, which can potentially influence the assessment of HIV disease status and outcomes. After preliminary evaluation of LTFU rates and patient characteristics, we evaluated the risk of mortality by LTFU status in a high-resource setting. Rates of LTFU were measured in the Australian HIV Observational Database for a range of patient characteristics. Multivariate repeated measures regression methods were used to identify determinants of LTFU. Mortality by LTFU status was ascertained using linkage to the National Death Index. Survival following combination antiretroviral therapy initiation was investigated using the Kaplan-Meier (KM) method and Cox proportional hazards models. Of 3,413 patients included in this analysis, 1,632 (47.8%) had at least one episode of LTFU after enrolment. Multivariate predictors of LTFU included viral load (VL)>10,000 copies/ml (rate ratio [RR] 1.63; 95% CI 1.45, 1.84; ref ≤400), time under follow-up (per year; RR 1.03; 95% CI 1.02, 1.04) and prior LTFU (per episode; RR 1.15; 95% CI 1.06, 1.24). KM curves for survival were similar by LTFU status (P=0.484). LTFU was not associated with mortality in Cox proportional hazards models (univariate hazard ratio [HR] 0.93; 95% CI 0.69, 1.26) and multivariate HR 1.04 (95% CI 0.77, 1.43). Increased risk of LTFU was identified amongst patients with potentially higher infectiousness. We did not find significant mortality risk associated with LTFU. This is consistent with timely re-engagement with treatment, possibly via high levels of unreported linkage to other health-care providers.

Prognostic value of long noncoding RNA MALAT1 in digestive system malignancies

PubMed Central

Zhai, Hui; Li, Xiao-Mei; Maimaiti, Ailifeire; Chen, Qing-Jie; Liao, Wu; Lai, Hong-Mei; Liu, Fen; Yang, Yi-Ning

2015-01-01

Background: MALAT1, a newly discovered long noncoding RNA (lncRNA), has been reported to be highly expressed in many types of cancers. This meta-analysis summarizes its potential prognostic value in digestive system malignancies. Methods: A quantitative meta-analysis was performed through a systematic search in PubMed, Cochrane Library, Web of Science and Chinese National Knowledge Infrastructure (CNKI) for eligible papers on the prognostic impact of MALAT1 in digestive system malignancies from inception to Apr. 25, 2015. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to summarize the effect. Results: Five studies were included in the study, with a total of 527 patients. A significant association was observed between MALAT1 abundance and poor overall survival (OS) of patients with digestive system malignancies, with pooled hazard ratio (HR) of 7.68 (95% confidence interval [CI]: 4.32-13.66, P<0.001). Meta sensitivity analysis suggested the reliability of our findings. No publication bias was observed. Conclusions: MALAT1 abundance may serve as a novel predictive factor for poor prognosis in patients with digestive system malignancies. PMID:26770406

Cause-specific mortality according to urine albumin creatinine ratio in the general population.

PubMed

Skaaby, Tea; Husemoen, Lise Lotte Nystrup; Ahluwalia, Tarunveer Singh; Rossing, Peter; Jørgensen, Torben; Thuesen, Betina Heinsbæk; Pisinger, Charlotta; Rasmussen, Knud; Linneberg, Allan

2014-01-01

Urine albumin creatinine ratio, UACR, is positively associated with all-cause mortality, cardiovascular disease and diabetes in observational studies. Whether a high UACR is also associated with other causes of death is unclear. We investigated the association between UACR and cause-specific mortality. We included a total of 9,125 individuals from two population-based studies, Monica10 and Inter99, conducted in 1993-94 and 1999-2001, respectively. Urine albumin creatinine ratio was measured from spot urine samples by standard methods. Information on causes of death was obtained from The Danish Register of Causes of Death until 31 December 2010. There were a total of 920 deaths, and the median follow-up was 11.3 years. Multivariable Cox regression analyses with age as underlying time axis showed statistically significant positive associations between UACR status and risk of all-cause mortality, endocrine nutritional and metabolic diseases, mental and behavioural disorders, diseases of the circulatory system, and diseases of the respiratory system with hazard ratios 1.56, 6.98, 2.34, 2.03, and 1.91, for the fourth UACR compared with the first, respectively. Using UACR as a continuous variable, we also found a statistically significant positive association with risk of death caused by diseases of the digestive system with a hazard ratio of 1.02 per 10 mg/g higher UACR. We found statistically significant positive associations between baseline UACR and death from all-cause mortality, endocrine nutritional and metabolic diseases, and diseases of the circulatory system and possibly mental and behavioural disorders, and diseases of the respiratory and digestive system.

Gender differences in hazardous drinking among middle-aged in Europe: the role of social context and women’s empowerment

PubMed Central

Bosque-Prous, Marina; Borrell, Carme; Bartroli, Montse; Guitart, Anna M.; Villalbí, Joan R.; Brugal, M. Teresa

2015-01-01

Background: The aim of this study was to estimate the magnitude of gender differences in hazardous drinking among middle-aged people and to analyse whether these differences are associated with contextual factors, such as public policies or socioeconomic factors. Methods: Cross-sectional design. The study population included 50- to 64-year-old residents of 16 European countries who participated in the Survey of Health, Ageing and Retirement in Europe project conducted in 2010–12 (n = 26 017). We estimated gender differences in hazardous drinking in each country. To determine whether different social context or women’s empowerment variables were associated with gender differences in hazardous drinking, we fitted multilevel Poisson regression models adjusted for various individual and country-level variables, which yielded prevalence ratios and their 95% confidence intervals (95% CI). Results: Prevalence of hazardous drinking was significantly higher in men than women [30.2% (95% CI: 29.1–31.4%) and 18.6% (95% CI: 17.7–19.4%), respectively] in most countries, although the extent of these differences varied between countries. Among individuals aged 50–64 years in Europe, risk of becoming a hazardous drinker was 1.69 times higher (95% CI: 1.45–1.97) in men, after controlling for individual and country-level variables. We also found that lower values of the gender empowerment measure and higher unemployment rates were associated with higher gender differences in hazardous drinking. Conclusion: Countries with the greatest gender differences in hazardous drinking were those with the most restrictions on women’s behaviour, and the greatest gender inequalities in daily life. Lower gender differences in hazardous drinking seem to be related to higher consumption among women. PMID:25616593

Utility of serum lipid ratios for predicting incident type 2 diabetes: the Isfahan Diabetes Prevention Study.

PubMed

Janghorbani, Mohsen; Amini, Masoud

2016-09-01

In this study, we evaluate the association between triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio and total cholesterol (TC) to HDL (TC/HDL) ratio and the risks of type 2 diabetes (T2D) in an Iranian high-risk population. We analysed 7-year follow-up data (n = 1771) in non-diabetic first-degree relatives of consecutive patients with T2D 30-70 years old. The primary outcome was the diagnosis of T2D based on repeated oral glucose tolerance tests. We used Cox proportional hazard models to estimate hazard ratio for incident T2D across tertiles of TG/HDL and TC/HDL ratios and plotted a receiver operating characteristic (ROC) curve to assess discrimination. The highest tertile of TG/HDL and TC/HDL ratios compared with the lowest tertile was not associated with T2D in age- and gender-adjusted models (HR 0.99, 95% CI: 0.88, 1.11 for TG/HDL ratio and 1.10, 95% CI: 0.97, 1.23 for TC/HDL ratio). Further adjustment for waist circumference or body mass index, fasting plasma glucose, and low-density lipoprotein cholesterol did not appreciably alter the hazard ratio compared with the age- and gender-adjusted model. The area under the ROC curve for TG/HDL ratio was 57.7% (95% CI: 54.0, 61.5) and for TC/HDL ratio was 55.1% (95% CI: 51.2, 59.0). TG/HDL and TC/HDL ratios were not robust predictors of T2D in high-risk individuals in Iran. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Considerations for analysis of time-to-event outcomes measured with error: Bias and correction with SIMEX.

PubMed

Oh, Eric J; Shepherd, Bryan E; Lumley, Thomas; Shaw, Pamela A

2018-04-15

For time-to-event outcomes, a rich literature exists on the bias introduced by covariate measurement error in regression models, such as the Cox model, and methods of analysis to address this bias. By comparison, less attention has been given to understanding the impact or addressing errors in the failure time outcome. For many diseases, the timing of an event of interest (such as progression-free survival or time to AIDS progression) can be difficult to assess or reliant on self-report and therefore prone to measurement error. For linear models, it is well known that random errors in the outcome variable do not bias regression estimates. With nonlinear models, however, even random error or misclassification can introduce bias into estimated parameters. We compare the performance of 2 common regression models, the Cox and Weibull models, in the setting of measurement error in the failure time outcome. We introduce an extension of the SIMEX method to correct for bias in hazard ratio estimates from the Cox model and discuss other analysis options to address measurement error in the response. A formula to estimate the bias induced into the hazard ratio by classical measurement error in the event time for a log-linear survival model is presented. Detailed numerical studies are presented to examine the performance of the proposed SIMEX method under varying levels and parametric forms of the error in the outcome. We further illustrate the method with observational data on HIV outcomes from the Vanderbilt Comprehensive Care Clinic. Copyright © 2017 John Wiley & Sons, Ltd.

Environmental risk assessment of selected pharmaceuticals in Turkey.

PubMed

Oğuz, Merve; Mihçiokur, Hamdi

2014-07-01

In this study, environmental risks of selected pharmaceuticals were investigated to assess potential hazards. Ciprofloxacin, Clarithromycin, Cefuroxime axetil, antibiotics, Benzalkoniuman antiseptic, Paracetamol, an analgesic, and Naproxen, an anti-inflammatory, were selected due to their high rate of usage in Turkey. Ciprofloxacin was found to have the highest risk due to its high PEC/PNEC ratio (28.636). Benzalkonium, Paracetamol and Clarithromycin have a potential to cause environmental hazards. The biodegradation and biological concentration factors (BCF) of the drugs were also determined using EPA/STWIN and EPA/BCFWIN programs. The results illustrated that these pharmaceuticals are nonbiodegradable in wastewater treatment plants. The BCFs of Benzalkonium and Clarithromycin were found to be very high, 70.790 L/kg and 56.490 L/kg, respectively. It was suggested that alternative treatment methods other than biological ones should be investigated for these pharmaceuticals because of their low biodegradability. Also, unnecessary use of antibiotics is supposed to be discouraged to reduce environmental hazards. Copyright © 2014 Elsevier B.V. All rights reserved.

Risk factors for UK Plasmodium falciparum cases

PubMed Central

2014-01-01

Background An increasing proportion of malaria cases diagnosed in UK residents with a history of travel to malaria endemic areas are due to Plasmodium falciparum. Methods In order to identify travellers at most risk of acquiring malaria a proportional hazards model was used to estimate the risk of acquiring malaria stratified by purpose of travel and age whilst adjusting for entomological inoculation rate (EIR) and duration of stay in endemic countries. Results Travellers visiting friends and relatives and business travellers were found to have significantly higher hazard of acquiring malaria (adjusted hazard ratio (HR) relative to that of holiday makers 7.4, 95% CI 6.4–8.5, p < 0. 0001 and HR 3.4, 95% CI 2.9-3.8, p < 0. 0001, respectively). All age-groups were at lower risk than children aged 0–15 years. Conclusions These estimates of the increased risk for business travellers and those visiting friends and relatives should be used to inform programmes to improve awareness of the risks of malaria when travelling. PMID:25091803

A safer disposal of hazardous phosphate coating sludge by formation of an amorphous calcium phosphate matrix.

PubMed

Navarro-Blasco, I; Duran, A; Pérez-Nicolás, M; Fernández, J M; Sirera, R; Alvarez, J I

2015-08-15

Phosphate coating hazardous wastes originated from the automotive industry were efficiently encapsulated by an acid-base reaction between phosphates present in the sludge and calcium aluminate cement, yielding very inert and stable monolithic blocks of amorphous calcium phosphate (ACP). Two different compositions of industrial sludge were characterized and loaded in ratios ranging from 10 to 50 wt.%. Setting times and compressive strengths were recorded to establish the feasibility of this method to achieve a good handling and a safe landfilling of these samples. Short solidification periods were found and leaching tests showed an excellent retention for toxic metals (Zn, Ni, Cu, Cr and Mn) and for organic matter. Retentions over 99.9% for Zn and Mn were observed even for loadings as high as 50 wt.% of the wastes. The formation of ACP phase of low porosity and high stability accounted for the effective immobilization of the hazardous components of the wastes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preconception B-vitamin and homocysteine status, conception, and early pregnancy loss.

PubMed

Ronnenberg, Alayne G; Venners, Scott A; Xu, Xiping; Chen, Changzhong; Wang, Lihua; Guang, Wenwei; Huang, Aiqun; Wang, Xiaobin

2007-08-01

Maternal vitamin status contributes to clinical spontaneous abortion, but the role of B-vitamin and homocysteine status in subclinical early pregnancy loss is unknown. Three-hundred sixty-four textile workers from Anqing, China, who conceived at least once during prospective observation (1996-1998), provided daily urine specimens for up to 1 year, and urinary human chorionic gonadotropin was assayed to detect conception and early pregnancy loss. Homocysteine, folate, and vitamins B6 and B12 were measured in preconception plasma. Relative to women in the lowest quartile of vitamin B6, those in the third and fourth quartiles had higher adjusted proportional hazard ratios of conception (hazard ratio (HR)=2.2, 95% confidence interval (CI): 1.3, 3.4; HR=1.6, 95% CI: 1.1, 2.3, respectively), and the adjusted odds ratio for early pregnancy loss in conceptive cycles was lower in the fourth quartile (odds ratio=0.5, 95% CI: 0.3, 1.0). Women with sufficient vitamin B6 had a higher adjusted hazard ratio of conception (HR=1.4, 95% CI: 1.1, 1.9) and a lower adjusted odds ratio of early pregnancy loss in conceptive cycles (odds ratio=0.7, 95% CI: 0.4, 1.1) than did women with vitamin B6 deficiency. Poor vitamin B6 status appears to decrease the probability of conception and to contribute to the risk of early pregnancy loss in this population.

Integrating Behavioral Health in Primary Care Using Lean Workflow Analysis: A Case Study.

PubMed

van Eeghen, Constance; Littenberg, Benjamin; Holman, Melissa D; Kessler, Rodger

2016-01-01

Primary care offices are integrating behavioral health (BH) clinicians into their practices. Implementing such a change is complex, difficult, and time consuming. Lean workflow analysis may be an efficient, effective, and acceptable method for use during integration. The objectives of this study were to observe BH integration into primary care and to measure its impact. This was a prospective, mixed-methods case study in a primary care practice that served 8,426 patients over a 17-month period, with 652 patients referred to BH services. Secondary measures included primary care visits resulting in BH referrals, referrals resulting in scheduled appointments, time from referral to the scheduled appointment, and time from the referral to the first visit. Providers and staff were surveyed on the Lean method. Referrals increased from 23 to 37 per 1000 visits (P < .001). Referrals resulted in more scheduled (60% to 74%; P < .001) and arrived visits (44% to 53%; P = .025). Time from referral to the first scheduled visit decreased (hazard ratio, 1.60; 95% confidence interval, 1.37-1.88) as did time to first arrived visit (hazard ratio, 1.36; 95% confidence interval, 1.14-1.62). Survey responses and comments were positive. This pilot integration of BH showed significant improvements in treatment initiation and other measures. Strengths of Lean analysis included workflow improvement, system perspective, and project success. Further evaluation is indicated. © Copyright 2016 by the American Board of Family Medicine.

Cerebrovascular Outcomes With Proton Pump Inhibitors and Thienopyridines: A Systematic Review and Meta-Analysis.

PubMed

Malhotra, Konark; Katsanos, Aristeidis H; Bilal, Mohammad; Ishfaq, Muhammad Fawad; Goyal, Nitin; Tsivgoulis, Georgios

2018-02-01

Pharmacokinetic and prior studies on thienopyridine and proton pump inhibitors (PPI) coadministration provide conflicting data for cardiovascular outcomes, whereas there is no established evidence on the association of concomitant use of PPI and thienopyridines with adverse cerebrovascular outcomes. We conducted a systematic review and meta-analysis of randomized controlled trials and cohort studies from inception to July 2017, reporting following outcomes among patients treated with thienopyridine and PPI versus thienopyridine alone (1) ischemic stroke, (2) combined ischemic or hemorrhagic stroke, (3) composite outcome of stroke, myocardial infarction (MI), and cardiovascular death, (4) MI, (5) all-cause mortality, and (6) major or minor bleeding events. After the unadjusted analyses of risk ratios, we performed additional analyses of studies reporting hazard ratios adjusted for potential confounders. We identified 22 studies (12 randomized controlled trials and 10 cohort studies) comprising 131 714 patients. Concomitant use of PPI with thienopyridines was associated with increased risk of ischemic stroke (risk ratio, 1.74; 95% confidence interval [CI], 1.41-2.16; P <0.001), composite stroke/MI/cardiovascular death (risk ratio, 1.14; 95% CI, 1.01-1.29; P =0.04), and MI (risk ratio, 1.19; 95% CI, 1.00-1.40; P =0.05). Likewise, in adjusted analyses concomitant use of PPI with thienopyridines was again associated with increased risk of stroke (hazard ratios adjusted, 1.30; 95% CI, 1.04-1.61; P =0.02), composite stroke/MI/cardiovascular death (hazard ratios adjusted, 1.23; 95% CI, 1.03-1.47; P =0.02), but not with MI (hazard ratios adjusted, 1.19; 95% CI, 0.93-1.52; P =0.16). Co-prescription of PPI and thienopyridines increases the risk of incident ischemic strokes and composite stroke/MI/cardiovascular death. Our findings corroborate the current guidelines for PPI deprescription and pharmacovigilance, especially in patients treated with thienopyridines. © 2018 American Heart Association, Inc.

All-Cause, Cardiovascular, and Cancer Mortality Rates in Postmenopausal White, Black, Hispanic, and Asian Women With and Without Diabetes in the United States

PubMed Central

Ma, Yunsheng; Hébert, James R.; Balasubramanian, Raji; Wedick, Nicole M.; Howard, Barbara V.; Rosal, Milagros C.; Liu, Simin; Bird, Chloe E.; Olendzki, Barbara C.; Ockene, Judith K.; Wactawski-Wende, Jean; Phillips, Lawrence S.; LaMonte, Michael J.; Schneider, Kristin L.; Garcia, Lorena; Ockene, Ira S.; Merriam, Philip A.; Sepavich, Deidre M.; Mackey, Rachel H.; Johnson, Karen C.; Manson, JoAnn E.

2013-01-01

Using data from the Women's Health Initiative (1993–2009; n = 158,833 participants, of whom 84.1% were white, 9.2% were black, 4.1% were Hispanic, and 2.6% were Asian), we compared all-cause, cardiovascular, and cancer mortality rates in white, black, Hispanic, and Asian postmenopausal women with and without diabetes. Cox proportional hazard models were used for the comparison from which hazard ratios and 95% confidence intervals were computed. Within each racial/ethnic subgroup, women with diabetes had an approximately 2–3 times higher risk of all-cause, cardiovascular, and cancer mortality than did those without diabetes. However, the hazard ratios for mortality outcomes were not significantly different between racial/ethnic subgroups. Population attributable risk percentages (PARPs) take into account both the prevalence of diabetes and hazard ratios. For all-cause mortality, whites had the lowest PARP (11.1, 95% confidence interval (CI): 10.1, 12.1), followed by Asians (12.9, 95% CI: 4.7, 20.9), blacks (19.4, 95% CI: 15.0, 23.7), and Hispanics (23.2, 95% CI: 14.8, 31.2). To our knowledge, the present study is the first to show that hazard ratios for mortality outcomes were not significantly different between racial/ethnic subgroups when stratified by diabetes status. Because of the “amplifying” effect of diabetes prevalence, efforts to reduce racial/ethnic disparities in the rate of death from diabetes should focus on prevention of diabetes. PMID:24045960

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

PubMed

Ishikawa, Joji; Ishikawa, Shizukiyo; Kario, Kazuomi

2015-03-01

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

Prognostic value of the frequency of vascular invasion in stage I non-small cell lung cancer.

PubMed

Okada, Satoshi; Mizuguchi, Shinjiro; Izumi, Nobuhiro; Komatsu, Hiroaki; Toda, Michihito; Hara, Kantaro; Okuno, Takahiro; Shibata, Toshihiko; Wanibuchi, Hideki; Nishiyama, Noritoshi

2017-01-01

There is no standard pathological method for determining vessel invasion in lung cancer. Herein, we examine whether vessel invasion can be accurately assessed using hematoxylin-eosin staining alone, and investigate the prognostic impact of the presence and frequency of vessel invasion in lung cancer. Vessel invasion was assessed by hematoxylin-eosin, Victoria blue, and D2-40 in 251 completely resected stage I non-small cell lung cancer patients. Vessel invasion was classified into 3 grades according to the number of invaded vessels. Using hematoxylin-eosin and Victoria blue, vascular invasion was detected in 27 (10.8 %) and 75 (29.9 %) of patients, respectively. Lymphatic permeation was detected in 126 (50.2 %) and 70 (27.9 %) of patients using hematoxylin-eosin and D2-40 staining. Hematoxylin-eosin staining did not accurately detect a high frequency of vessel invasion; only 5 and 21.7 % of high-frequency vascular invasion and lymphatic permeation cases diagnosed with Victoria blue and D2-40 were detected. Multivariate analysis based on elastic stain and immunostaining indicated that plural invasion, a high frequency of vascular invasion (hazard ratio 4.00), and a high frequency of lymphatic permeation (hazard ratio 2.30) were independent predictors of cancer recurrence within 3 years. Likewise, an age ≥70 years, male, and a high frequency of vascular invasion (hazard ratio 3.41) were independent predictors of overall survival. Vascular invasion should be confirmed by elastic stains, and the frequency, not but the presence, of vascular invasion is a powerful independent prognostic factor in completely resected stage I non-small cell lung cancer patients.

Impact of Viral Status on Survival in Patients Receiving Sorafenib for Advanced Hepatocellular Cancer: A Meta-Analysis of Randomized Phase III Trials.

PubMed

Jackson, Richard; Psarelli, Eftychia-Eirini; Berhane, Sarah; Khan, Harun; Johnson, Philip

2017-02-20

Purpose Following the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial, sorafenib has become the standard of care for patients with advanced unresectable hepatocellular carcinoma, but the relation between survival advantage and disease etiology remains unclear. To address this, we undertook an individual patient data meta-analysis of three large prospective randomized trials in which sorafenib was the control arm. Methods Of a total of 3,256 patients, 1,643 (50%) who received sorafenib were available. The primary end point was overall survival (OS). A Bayesian hierarchical approach for individual patient data meta-analyses was applied using a piecewise exponential model. Results are presented in terms of hazard ratios comparing sorafenib with alternative therapies according to hepatitis C virus (HCV) or hepatitis B virus (HBV) status. Results Hazard ratios show improved OS for sorafenib in patients who are both HBV negative and HCV positive (log [hazard ratio], -0.27; 95% CI, -0.46 to -0.06). Median unadjusted survival is 12.6 (11.15 to 13.8) months for sorafenib and 10.2 (8.88 to 12.2) months for "other" treatments in this subgroup. There was no evidence of improvement in OS for any other patient subgroups defined by HBV and HCV. Results were consistent across all trials with heterogeneity assessed using Cochran's Q statistic. Conclusion There is consistent evidence that the effect of sorafenib on OS is dependent on patients' hepatitis status. There is an improved OS for patients negative for HBV and positive for HCV when treated with sorafenib. There was no evidence of any improvement in OS attributable to sorafenib for patients positive for HBV and negative for HCV.

Register-based data of psychosocial working conditions and occupational groups as predictors of disability pension due to musculoskeletal diagnoses: a prospective cohort study of 24 543 Swedish twins

PubMed Central

2013-01-01

Background Occupations and psychosocial working conditions have rarely been investigated as predictors of disability pension in population-based samples. This study investigated how occupational groups and psychosocial working conditions are associated with future disability pension due to musculoskeletal diagnoses, accounting for familial factors in the associations. Methods A sample of 24 543 same-sex Swedish twin individuals was followed from 1993 to 2008 using nationwide registries. Baseline data on occupations were categorized into eight sector-defined occupational groups. These were further used to reflect psychosocial working conditions by applying the job strain scores of a Job Exposure Matrix. Cox proportional hazard ratios (HR) were estimated. Results During the 12-year (average) follow-up, 7% of the sample was granted disability pension due to musculoskeletal diagnoses. Workers in health care and social work; agriculture, forestry and fishing; transportation; production and mining; and the service and military work sectors were two to three times more likely to receive a disability pension than those in the administration and management sector. Each single unit decrease in job demands and each single unit increase in job control and social support significantly predicted disability pension. Individuals with high work strain or an active job had a lower hazard ratio of disability pension, whereas a passive job predicted a significantly higher hazard ratio. Accounting for familial confounding did not alter these results. Conclusion Occupational groups and psychosocial working conditions seem to be independent of familial confounding, and hence represent risk factors for disability pension due to musculoskeletal diagnoses. This means that preventive measures in these sector-defined occupational groups and specific psychosocial working conditions might prevent disability pension due to musculoskeletal diagnoses. PMID:24040914

Association between physical fitness, cardiovascular risk factors, and Parkinson's disease.

PubMed

Müller, Jan; Myers, Jonathan

2018-01-01

Objective Exercise is a cornerstone of therapy for Parkinson's disease. This study addressed the association between physical fitness and the onset of Parkinson's disease and association with cardiovascular risk factors. Patients and methods Male veterans ( N = 7347, 59.0 ± 11.2 years) from the Veterans Exercise Testing Study cohort were evaluated. Physical fitness was measured objectively by maximal exercise testing. Onset of Parkinson's disease was abstracted from the Veterans Affairs computerized patient records system. Results After a mean follow-up of 12.5 ± 6.3 years, a total of 94 (1.3%) developed Parkinson's disease. Incidence was 86 cases per 100,000 person-years. The strongest multivariate factors associated with incidence of Parkinson's disease were higher age (hazard ratio: 1.067, 95% confidence interval (CI): 1.043-1.093, p < .001), current smoking (hazard ratio: 0.511, 95% CI: 0.274-0.953, p = .035) and physical fitness (high vs. low: hazard ratio: 0.239, 95% CI: 0.079-0.725, p = .011). Compared with patients with no or only one of these risk factors, patients with two risk factors had a 3.7-fold ( p < .001) increased risk for incidence of Parkinson's disease; those with all three risk factors had a 7.8-fold ( p < .001) higher risk. Conclusions High physical fitness, current smoking and younger age were associated with a lower incidence of Parkinson's disease. These findings parallel those of several epidemiological studies focusing on physical activity and the onset of Parkinson's disease. Together, these observations provide strong support for recommending physical activity to diminish risk of Parkinson's disease.

Matching on the disease risk score in comparative effectiveness research of new treatments.

PubMed

Wyss, Richard; Ellis, Alan R; Brookhart, M Alan; Jonsson Funk, Michele; Girman, Cynthia J; Simpson, Ross J; Stürmer, Til

2015-09-01

We use simulations and an empirical example to evaluate the performance of disease risk score (DRS) matching compared with propensity score (PS) matching when controlling large numbers of covariates in settings involving newly introduced treatments. We simulated a dichotomous treatment, a dichotomous outcome, and 100 baseline covariates that included both continuous and dichotomous random variables. For the empirical example, we evaluated the comparative effectiveness of dabigatran versus warfarin in preventing combined ischemic stroke and all-cause mortality. We matched treatment groups on a historically estimated DRS and again on the PS. We controlled for a high-dimensional set of covariates using 20% and 1% samples of Medicare claims data from October 2010 through December 2012. In simulations, matching on the DRS versus the PS generally yielded matches for more treated individuals and improved precision of the effect estimate. For the empirical example, PS and DRS matching in the 20% sample resulted in similar hazard ratios (0.88 and 0.87) and standard errors (0.04 for both methods). In the 1% sample, PS matching resulted in matches for only 92.0% of the treated population and a hazard ratio and standard error of 0.89 and 0.19, respectively, while DRS matching resulted in matches for 98.5% and a hazard ratio and standard error of 0.85 and 0.16, respectively. When PS distributions are separated, DRS matching can improve the precision of effect estimates and allow researchers to evaluate the treatment effect in a larger proportion of the treated population. However, accurately modeling the DRS can be challenging compared with the PS. Copyright © 2015 John Wiley & Sons, Ltd.

Primary prevention of cardiovascular disease in patients with systemic lupus erythematosus: case series and literature review.

PubMed

Fasano, S; Margiotta, D P; Navarini, L; Pierro, L; Pantano, I; Riccardi, A; Afeltra, A; Valentini, G

2017-12-01

Background Systemic lupus erythematosus is associated with an increased risk of cardiovascular disease. Low-dose aspirin, hydroxychloroquine and statins have been suggested to play a prophylactic role of cardiovascular events. This study is devoted to reviewing the literature on the topic and assessing the effects of these drugs in preventing a first cardiovascular event in a two-centre Italian series. Methods A PubMed search on cardiovascular prevention in systemic lupus erythematosus was performed. Moreover, systemic lupus erythematosus patients admitted to two centres from 2000-2015, who at admission had not experienced any cardiovascular event, were investigated. Aspirin, hydroxychloroquine and statin use, and the occurrence of any cardiovascular event, were recorded at each visit. Kaplan-Meier and Cox regression analyses were performed to evaluate the role of traditional, disease-related cardiovascular risk factors and of each of the three drugs in the occurrence of new cardiovascular events. Results The literature search produced conflicting results. Two hundred and ninety-one systemic lupus erythematosus patients were included in the study and followed for a median of eight years. During follow-up, 16 cardiovascular events occurred. At multivariate analysis, taking aspirin (hazard ratio: 0.24) and hydroxychloroquine for more than five years (hazard ratio: 0.27) reduced, while antiphospholipid antibody positivity (hazard ratio: 4.32) increased, the risk of a first cardiovascular event. No effect of statins emerged. Conclusion Our study confirms an additive role of aspirin and hydroxychloroquine in the primary prophylaxis of cardiovascular events in Italian patients with systemic lupus erythematosus. The lack of any detected effect in previous reports may depend on the design of studies and their short follow-up period.

The COPD Helplessness Index

PubMed Central

Katz, Patricia P.; Yelin, Edward H.; Iribarren, Carlos; Knight, Sara J.; Blanc, Paul D.; Eisner, Mark D.

2010-01-01

Background: Psychologic factors affect how patients with COPD respond to attempts to improve their self-management skills. Learned helplessness may be one such factor, but there is no validated measure of helplessness in COPD. Methods: We administered a new COPD Helplessness Index (CHI) to 1,202 patients with COPD. Concurrent validity was assessed through association of the CHI with established psychosocial measures and COPD severity. The association of helplessness with incident COPD exacerbations was then examined by following subjects over a median 2.1 years, defining COPD exacerbations as COPD-related hospitalizations or ED visits. Results: The CHI demonstrated internal consistency (Cronbach α = 0.75); factor analysis was consistent with the CHI representing a single construct. Greater CHI-measured helplessness correlated with greater COPD severity assessed by the BODE (Body-mass, Obstruction, Dyspnea, Exercise) Index (r = 0.34; P < .001). Higher CHI scores were associated with worse generic (Short Form-12, Physical Component Summary Score) and respiratory-specific (Airways Questionnaire 20) health-related quality of life, greater depressive symptoms, and higher anxiety (all P < .001). Controlling for sociodemographics and smoking status, helplessness was prospectively associated with incident COPD exacerbations (hazard ratio = 1.31; P < .001). After also controlling for the BODE Index, helplessness remained predictive of COPD exacerbations among subjects with BODE Index ≤ median (hazard ratio = 1.35; P = .01), but not among subjects with higher BODE Index values (hazard ratio = 0.93; P = .34). Conclusions: The CHI is an internally consistent and valid measure, concurrently associated with health status and predictively associated with COPD exacerbations. The CHI may prove a useful tool in analyzing differential clinical responses mediated by patient-centered attributes. PMID:19837823

Long-Term Incidence of Female-Specific Cancer after Bariatric Surgery or Usual Care in the Swedish Obese Subjects Study

PubMed Central

Anveden, Åsa; Taube, Magdalena; Peltonen, Markku; Jacobson, Peter; Andersson-Assarsson, Johanna C.; Sjöholm, Kajsa; Svensson, Per-Arne; Carlsson, Lena M.S.

2017-01-01

Summary Objective To examine the long-term effects of bariatric surgery on female-specific cancer in women with obesity. Methods The prospective, matched Swedish Obese Subjects (SOS) study was designed to examine outcomes after bariatric surgery. This study includes 1420 women from the SOS cohort that underwent bariatric surgery and 1447 contemporaneously matched controls who received conventional obesity treatment. Age was 37–60 years and BMI was ≥38 kg/m2. Information on cancer events was obtained from the Swedish National Cancer Registry. Median follow-up time was 18.1 years (interquartile range 14.8–20.9 years, maximum 26 years). This study is registered with ClinicalTrials.gov, NCT01479452. Results Bariatric surgery was associated with reduced risk of overall cancer (hazard ratio=0.71; 95% CI 0.59–0.85; p<0.001). About half of the observed cancers were female-specific, and the incidence of these were lower in the surgery group compared with the control group (hazard ratio=0.68; 95% CI 0.52–0·88; p=0.004). The surgical treatment benefit with respect to female-specific cancer was significantly associated with baseline serum insulin (interaction p value=0.022), with greater relative treatment benefit in patients with medium or high insulin levels. Separate analyses of different types of female-specific cancers showed that bariatric surgery was associated with reduced risk of endometrial cancer (hazard ratio=0.56: 95% CI 0.35–0.89; p=0.014). Conclusions In this long-term study, bariatric surgery was associated with reduced risk of female-specific cancer, especially in women with hyperinsulinemia at baseline. PMID:28259424

Western-Style Fast Food Intake and Cardiometabolic Risk in an Eastern Country

PubMed Central

Odegaard, Andrew O.; Koh, Woon Puay; Yuan, Jian-Min; Gross, Myron D.; Pereira, Mark A.

2014-01-01

Background Western-style fast food contributes to a dietary pattern portending poor cardiometabolic health in the United States. With globalization, this way of eating is becoming more common in developing and recently developed populations. Methods and Results We examined the association of Western-style fast food intake with risk of incident type 2 diabetes mellitus and coronary heart disease mortality in Chinese Singaporeans. This analysis included men and women 45 to 74 years of age who enrolled in the Singapore Chinese Health Study from 1993 to 1998. For CHD mortality, 52 584 participants were included and 1397 deaths were identified through December 31, 2009, via registry linkage. For type 2 diabetes mellitus, 43 176 participants were included and 2252 cases were identified during the follow-up interview (1999 –2004) and validated. Hazard ratios for incident type 2 diabetes mellitus and coronary heart disease mortality were estimated with thorough adjustment for demographic, lifestyle, and dietary factors. Chinese Singaporeans with relatively frequent intake of Western-style fast food items (≥2 times per week) had an increased risk of developing type 2 diabetes mellitus (hazard ratio, 1.27; 95% confidence interval, 1.03–1.54) and dying of coronary heart disease (hazard ratio, 1.56; 95% confidence interval, 1.18 –2.06) relative to their peers with little or no reported intake. These associations were not materially altered by adjustments for overall dietary pattern, energy intake, and body mass index. Conclusions Western-style fast food intake is associated with increased risk of developing type 2 diabetes mellitus and of coronary heart disease mortality in an Eastern population. These findings suggest the need for further attention to global dietary acculturation in the context of ongoing epidemiological and nutrition transitions. PMID:22753304

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

PubMed Central

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

2016-01-01

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

Twelve-month contraceptive continuation among women initiating short- and long-acting reversible contraceptives in North Kivu, Democratic Republic of the Congo.

PubMed

Casey, Sara E; Cannon, Amy; Mushagalusa Balikubirhi, Benjamin; Muyisa, Jean-Bosco; Amsalu, Ribka; Tsolka, Maria

2017-01-01

Despite the inclusion of sexual and reproductive health (SRH) services in the minimum standards of health care in humanitarian settings, access to SRH services, and especially to contraception, is often compromised in war. Very little is known about continuation and switching of contraceptive methods in these settings. An evaluation of a contraceptive services program in North Kivu, Democratic Republic of the Congo (DRC) was conducted to measure 12-month contraceptive continuation by type of contraceptive method (short-acting or long-acting). A stratified systematic sample of women who initiated a contraceptive method 12-18 months prior to data collection was selected retrospectively from facility registers. A total of 548 women was interviewed about their contraceptive use: 304 who began a short-acting method (pills, injectables) and 244 who began a long-acting method (intra-uterine devices, implants). Key characteristics of short-acting method versus long-acting method acceptors were compared using chi-square statistics for categorical data and t-tests for continuous data. Unadjusted and adjusted Cox proportional hazard ratios were estimated to assess factors associated with discontinuation. At 12 months, 81.6% women reported using their baseline contraceptive method continuously, with more long-acting than short-acting contraceptive acceptors (86.1% versus 78.0%, p = .02) continuing contraceptive use. Use of a short-acting method (Hazard ratio (HR) 1.74 [95%CI 1.13-2.67]) and desiring a child within two years (HR 2.58 [95%CI 1.45-4.54]) were associated with discontinuation within the first 12 months of use. The vast majority (88.3%) of women reported no prior contraceptive use. This is the first study of contraceptive continuation in a humanitarian setting. The high percentages of women continuing contraceptive use found here demonstrates that women will choose to initiate and continue use of their desired contraceptive method, even in a difficult, unstable and low contraceptive prevalence setting like North Kivu.

Ethnic Differences in Incidence and Outcomes of Childhood Nephrotic Syndrome.

PubMed

Banh, Tonny H M; Hussain-Shamsy, Neesha; Patel, Viral; Vasilevska-Ristovska, Jovanka; Borges, Karlota; Sibbald, Cathryn; Lipszyc, Deborah; Brooke, Josefina; Geary, Denis; Langlois, Valerie; Reddon, Michele; Pearl, Rachel; Levin, Leo; Piekut, Monica; Licht, Christoph P B; Radhakrishnan, Seetha; Aitken-Menezes, Kimberly; Harvey, Elizabeth; Hebert, Diane; Piscione, Tino D; Parekh, Rulan S

2016-10-07

Ethnic differences in outcomes among children with nephrotic syndrome are unknown. We conducted a longitudinal study at a single regional pediatric center comparing ethnic differences in incidence from 2001 to 2011 census data and longitudinal outcomes, including relapse rates, time to first relapse, frequently relapsing disease, and use of cyclophosphamide. Among 711 children, 24% were European, 33% were South Asian, 10% were East/Southeast Asian, and 33% were of other origins. Over 10 years, the overall incidence increased from 1.99/100,000 to 4.71/100,000 among children ages 1-18 years old. In 2011, South Asians had a higher incidence rate ratio of 6.61 (95% confidence interval, 3.16 to 15.1) compared with Europeans. East/Southeast Asians had a similar incidence rate ratio (0.76; 95% confidence interval, 0.13 to 2.94) to Europeans. We determined outcomes in 455 children from the three largest ethnic groups with steroid-sensitive disease over a median of 4 years. South Asian and East/Southeast Asian children had significantly lower odds of frequently relapsing disease at 12 months (South Asian: adjusted odds ratio; 0.55; 95% confidence interval, 0.39 to 0.77; East/Southeast Asian: adjusted odds ratio; 0.42; 95% confidence interval, 0.34 to 0.51), fewer subsequent relapses (South Asian: adjusted odds ratio; 0.64; 95% confidence interval, 0.50 to 0.81; East/Southeast Asian: adjusted odds ratio; 0.47; 95% confidence interval, 0.24 to 0.91), lower risk of a first relapse (South Asian: adjusted hazard ratio, 0.74; 95% confidence interval, 0.67 to 0.83; East/Southeast Asian: adjusted hazard ratio, 0.65; 95% CI, 0.63 to 0.68), and lower use of cyclophosphamide (South Asian: adjusted hazard ratio, 0.82; 95% confidence interval, 0.53 to 1.28; East/Southeast Asian: adjusted hazard ratio, 0.54; 95% confidence interval, 0.41 to 0.71) compared with European children. Despite the higher incidence among South Asians, South and East/Southeast Asian children have significantly less complicated clinical outcomes compared with Europeans. Copyright © 2016 by the American Society of Nephrology.

Augmenting the Deliberative Method for Ranking Risks.

PubMed

Susel, Irving; Lasley, Trace; Montezemolo, Mark; Piper, Joel

2016-01-01

The Department of Homeland Security (DHS) characterized and prioritized the physical cross-border threats and hazards to the nation stemming from terrorism, market-driven illicit flows of people and goods (illegal immigration, narcotics, funds, counterfeits, and weaponry), and other nonmarket concerns (movement of diseases, pests, and invasive species). These threats and hazards pose a wide diversity of consequences with very different combinations of magnitudes and likelihoods, making it very challenging to prioritize them. This article presents the approach that was used at DHS to arrive at a consensus regarding the threats and hazards that stand out from the rest based on the overall risk they pose. Due to time constraints for the decision analysis, it was not feasible to apply multiattribute methodologies like multiattribute utility theory or the analytic hierarchy process. Using a holistic approach was considered, such as the deliberative method for ranking risks first published in this journal. However, an ordinal ranking alone does not indicate relative or absolute magnitude differences among the risks. Therefore, the use of the deliberative method for ranking risks is not sufficient for deciding whether there is a material difference between the top-ranked and bottom-ranked risks, let alone deciding what the stand-out risks are. To address this limitation of ordinal rankings, the deliberative method for ranking risks was augmented by adding an additional step to transform the ordinal ranking into a ratio scale ranking. This additional step enabled the selection of stand-out risks to help prioritize further analysis. © 2015 Society for Risk Analysis.

Study of Site Response in the Seattle and Tacoma Basins, Washington, Using Spectral Ratio Methods

NASA Astrophysics Data System (ADS)

Keshvardoost, R.; Wolf, L. W.

2014-12-01

Sedimentary basins are known to have a pronounced influence on earthquake-generated ground motions, affecting both predominant frequencies and wave amplification. These site characteristics are important elements in estimating ground shaking and seismic hazard. In this study, we use three-component broadband and strong motion seismic data from three recent earthquakes to determine site response characteristics in the Seattle and Tacoma basins, Washington. Resonant frequencies and relative amplification of ground motions were determined using Fourier spectral ratios of velocity and acceleration records from the 2012 Mw 6.1 Vancouver Island earthquake, the 2012 Mw 7.8 Queen Charlotte Island earthquake, and the 2014 Mw 6.6 Vancouver Island earthquake. Recordings from sites within and adjacent to the Seattle and Tacoma basins were selected for the study based on their signal to noise ratios. Both the Standard Spectral Ratio (SSR) and the Horizontal-to-Vertical Spectral Ratio (HVSR) methods were used in the analysis, and results from each were compared to examine their agreement and their relation to local geology. Although 57% of the sites (27 out of 48) exhibited consistent results between the two methods, other sites varied considerably. In addition, we use data from the Seattle Liquefaction Array (SLA) to evaluate the site response at 4 different depths. Results indicate that resonant frequencies remain the same at different depths but amplification decreases significantly over the top 50 m.

Survival of cancer patients treated with mistletoe extract (Iscador): a systematic literature review

PubMed Central

2009-01-01

Background In Europe, extracts from Viscum album (VA-E), the European white-berry mistletoe, are widely used to treat patients with cancer. Methods We searched several databases such as Cochrane, EMBASE, NCCAM, NLM, DIMDI, CAMbase, and Medline. Inclusion criteria were controlled clinical studies on parameters associated with survival in cancer patients treated with Iscador. Outcome data were extracted as they were given in the publication, and expressed as hazard ratios (HR), their logarithm, and the respective standard errors using standard formulas. Results We found 49 publications on the clinical effects of Iscador usage on survival of cancer patients which met our criteria. Among them, 41 studies and strata provided enough data to extract hazard ratios (HR) and their standard errors (Iscador versus no extra treatment). The majority of studies reported positive effects in favour of the Iscador application. Heterogeneity of study results was moderate (I2 = 38.3%, p < 0.0001). The funnel plots were considerably skewed, indicating a publication bias, a notion which is corroborated by statistical means (AC = -1.3, CI: -1.9 to -0.6, p <= 0.0001). A random effect meta-analysis estimated the overall hazard ratio at HR = 0.59 (CI: 0.53 to 0.66, p < 0.0001). Randomized studies showed less effects than non-randomized studies (ratio of HRs: 1.24, CI: 0.79 to 1.92, p = 0.35), and matched-pair studies gave significantly better results than others (ratio of HRs: 0.33; CI: 0.17 to 0.65, p = 0.0012). Conclusions Pooled analysis of clinical studies suggests that adjuvant treatment of cancer patients with the mistletoe extract Iscador is associated with a better survival. Despite obvious limitations, and strong hints for a publication bias which limits the evidence found in this meta-analysis, one can not ignore the fact that studies with positive effects of VA-E on survival of cancer patients are accumulating. Future studies evaluating the effects of Iscador should focus on a transparent design and description of endpoints in order to provide greater insight into a treatment often being depreciated as ineffective, but highly valued by cancer patients. PMID:20021637

Study designs appropriate for the workplace.

PubMed

Hogue, C J

1986-01-01

Carlo and Hearn have called for "refinement of old [epidemiologic] methods and an ongoing evaluation of where methods fit in the overall scheme as we address the multiple complexities of reproductive hazard assessment." This review is an attempt to bring together the current state-of-the-art methods for problem definition and hypothesis testing available to the occupational epidemiologist. For problem definition, meta analysis can be utilized to narrow the field of potential causal hypotheses. Passive active surveillance may further refine issues for analytic research. Within analytic epidemiology, several methods may be appropriate for the workplace setting. Those discussed here may be used to estimate the risk ratio in either a fixed or dynamic population.

Effect of Long Working Hours on Self-reported Hypertension among Middle-aged and Older Wage Workers.

PubMed

Yoo, Dong Hyun; Kang, Mo-Yeol; Paek, Domyung; Min, Bokki; Cho, Sung-Il

2014-01-01

Many studies have reported an association between overwork and hypertension. However, research on the health effects of long working hours has yielded inconclusive results. The objective of this study was to identify an association between overtime work and hypertension in wage workers 45 years and over of age using prospective data. Wage workers in Korea aged 45 years and over were selected for inclusion in this study from among 10,254 subjects from the Korean Longitudinal Study of Ageing. Workers with baseline hypertension and those with other major diseases were excluded. In the end, a total of 1,079 subjects were included. A Cox proportional hazards model was used to calculate hazard ratios and adjust for baseline characteristics such as sex, age, education, income, occupation, form of employment, body mass index, alcohol habit, smoking habit, regular exercise, and number of working days per week. Additional models were used to calculate hazard ratios after gender stratification. Among the 1,079 subjects, 85 workers were diagnosed with hypertension during 3974.2 person-months. The average number of working hours per week for all subjects was 47.68. The proportion of overtime workers was 61.0% (cutoff, 40 h per week). Compared with those working 40 h and less per week, the hazard ratio of subjects in the final model, which adjusted for all selected variables, working 41-50 h per week was 2.20 (95% confidence interval [CI], 1.19-4.06), that of subjects working 51-60 h per week was 2.40 (95% CI, 1.07-5.39), and that of subjects working 61 h and over per week was 2.87 (95% CI, 1.33-6.20). In gender stratification models, the hazard ratio of the females tended to be higher than that of the males. As the number of working hours per week increased, the hazard ratio for diagnosis of hypertension significantly increased. This result suggests a positive association between overtime work and the risk of hypertension.

Relative effectiveness of adjuvant chemotherapy for invasive lobular compared with invasive ductal carcinoma of the breast.

PubMed

Marmor, Schelomo; Hui, Jane Yuet Ching; Huang, Jing Li; Kizy, Scott; Beckwith, Heather; Blaes, Anne H; Rueth, Natasha M; Tuttle, Todd M

2017-08-15

Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have distinct clinical, pathologic, and genomic characteristics. The objective of the current study was to compare the relative impact of adjuvant chemotherapy on the survival of patients with ILC versus those with IDC. Women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 1 (HER2) -negative, stage I/II IDC and ILC who received endocrine therapy were identified from the 2000 to 2014 California Cancer Registry. Patient, tumor, and treatment characteristics were collected. Ten-year overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional-hazards modeling. In total, 32,997 women with IDC and 4638 with ILC were identified. The receipt of chemotherapy significantly decreased during the study for both subtypes. For patients with IDC, the 10-year OS rate was 95% among those who received endocrine therapy alone versus 93% (P < .01) among those who received endocrine therapy plus chemotherapy. For patients with ILC, the 10-year OS rate was 94% among those who received endocrine therapy alone versus 92% (P < .01) among those who received endocrine therapy plus chemotherapy. After adjusting for patient and treatment factors, adjuvant chemotherapy was significantly associated with a decreased 10-year hazard of death for patients with IDC (hazard ratio, 0.83; 95% confidence interval, 0.74-0.92). In contrast, adjuvant chemotherapy was not independently associated with the adjusted 10-year hazard of death for patients with ILC (hazard ratio, 1.14; 95% confidence interval, 0.90-1.46). Adjuvant chemotherapy was not associated with improved OS for patients with ER-positive, HER2-negative, stage I/II ILC. Avoidance of ineffective chemotherapy will markedly reduce the adverse effects and economic burden of breast cancer treatment for a large proportion of patients with breast cancer. Cancer 2017;123:3015-21. © 2017 American Cancer Society. © 2017 American Cancer Society.

Induced abortion and breast cancer among parous women: a Danish cohort study.

PubMed

Braüner, Christina Marie; Overvad, Kim; Tjønneland, Anne; Attermann, Jørn

2013-06-01

We investigated whether induced abortion is associated with breast cancer when lifestyle confounders, including smoking and alcohol consumption, are adjusted for. Design. Prospective cohort study. Danish women from the Diet, Cancer and Health study. A total of 25,576 women. We obtained exposure data from baseline questionnaires filled in by the women between 1993 and 1997. Information on breast cancer and emigration was retrieved from Danish national registries. The study power was approximately 85% when applying a minimum detection hazard ratio of 1.2. Long-term effects of induced abortion on the risk of breast cancer among women above 50 years of age. During a follow up of approximately 12 years, 1215 women were diagnosed with breast cancer. When comparing parous women who had an abortion with parous women who never had an abortion, there was no association between breast cancer risk and induced abortion (ever vs. never), with a hazard ratio 0.95 (95% confidence interval 0.83-1.09), regardless of whether the abortion occurred before the first birth (hazard ratio 0.86; 95% confidence interval 0.65-1.14), or after the first birth (hazard ratio 0.97; 95% confidence interval 0.84-1.13). Our study did not show evidence of an association between induced abortion and breast cancer risk. © 2013 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2013 Nordic Federation of Societies of Obstetrics and Gynecology.

Gender related Long-term Differences after Open Infrainguinal Surgery for Critical Limb Ischemia.

PubMed

Lejay, A; Schaeffer, M; Georg, Y; Lucereau, B; Roussin, M; Girsowicz, E; Delay, C; Schwein, A; Thaveau, F; Geny, B; Chakfe, N

2015-10-01

The role of gender on long-term infrainguinal open surgery outcomes still remains uncertain in critical limb ischemia patients. The aim of this study is to evaluate the gender-specific differences in patient characteristics and long-term clinical outcomes in terms of survival, primary patency and limb salvage among patients undergoing infrainguinal open surgery for CLI. All consecutive patients undergoing infrainguinal open surgery for critical limb ischemia between 2003 and 2012 were included. Survival, limb salvage and primary patency rates were assessed. Independent outcome determinants were identified by the Cox proportional hazard ratio using age and gender as adjustment factors. 584 patients (269 women and 315 men, mean age 76 and 71 years respectively) underwent 658 infrainguinal open surgery (313 in women and 345 in men). Survival rate at 6 years was lower among women compared to men with 53.5% vs 70.9% (p < 0.001). The same applied to primary patency (35.9% vs 52.4%, p < 0.001) and limb salvage (54.3% vs 81.1%, p < 0.001) at 6 years. Female-gender was an independent factor predicting death (hazard ratio 1.50), thrombosis (hazard ratio 2.37) and limb loss (hazard ratio 7.05) in age and gender-adjusted analysis. Gender-related disparity in critical limb ischemia open surgical revascularization outcomes still remains. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Optimized breast MRI functional tumor volume as a biomarker of recurrence-free survival following neoadjuvant chemotherapy.

PubMed

Jafri, Nazia F; Newitt, David C; Kornak, John; Esserman, Laura J; Joe, Bonnie N; Hylton, Nola M

2014-08-01

To evaluate optimal contrast kinetics thresholds for measuring functional tumor volume (FTV) by breast magnetic resonance imaging (MRI) for assessment of recurrence-free survival (RFS). In this Institutional Review Board (IRB)-approved retrospective study of 64 patients (ages 29-72, median age of 48.6) undergoing neoadjuvant chemotherapy (NACT) for breast cancer, all patients underwent pre-MRI1 and postchemotherapy MRI4 of the breast. Tumor was defined as voxels meeting thresholds for early percent enhancement (PEthresh) and early-to-late signal enhancement ratio (SERthresh); and FTV (PEthresh, SERthresh) by summing all voxels meeting threshold criteria and minimum connectivity requirements. Ranges of PEthresh from 50% to 220% and SERthresh from 0.0 to 2.0 were evaluated. A Cox proportional hazard model determined associations between change in FTV over treatment and RFS at different PE and SER thresholds. The plot of hazard ratios for change in FTV from MRI1 to MRI4 showed a broad peak with the maximum hazard ratio and highest significance occurring at PE threshold of 70% and SER threshold of 1.0 (hazard ratio = 8.71, 95% confidence interval 2.86-25.5, P < 0.00015), indicating optimal model fit. Enhancement thresholds affect the ability of MRI tumor volume to predict RFS. The value is robust over a wide range of thresholds, supporting the use of FTV as a biomarker. © 2013 Wiley Periodicals, Inc.

Risk of Incident Coronary Heart Disease Events in Men Compared to Women by Menopause Type and Race

PubMed Central

Kim, Catherine; Cushman, Mary; Khodneva, Yulia; Lisabeth, Lynda D; Judd, Suzanne; Kleindorfer, Dawn O; Howard, Virginia J; Safford, Monika M

2015-01-01

Background We examined whether type of menopause affects sex differences in coronary heart disease (CHD) events and whether the impact is similar in blacks and whites. Methods and Results Participants were enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort between 2003 and 2007 without CHD at baseline (n=23 086). Cox regression models were used to calculate the hazard of incident nonfatal CHD (definite or probable myocardial infarction) and acute CHD death, adjusting for age, age at last menstrual period <45 years, region, education level, income, diabetes, smoking, systolic blood pressure, lipid levels, albumin-creatinine ratio, physical activity, C-reactive protein, body mass index, waist circumference, and medication use. White women in natural menopause (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.31, 0.66) and surgical menopause (HR, 0.65; 95% CI, 0.42, 0.99) had a reduced hazard of nonfatal events, compared to white men. Black women in natural menopause (HR, 0.69; 95% CI, 0.47, 1.03), but not surgical menopause (HR, 0.81; 95% CI, 0.51, 1.29), had a marginally reduced hazard of nonfatal events, compared to black men. Women had lower risk of acute CHD death than men regardless of their menopause type and race. Conclusions Sex differences in the risk of incident CHD events were larger among whites than blacks and varied by type of menopause. Women consistently had a lower risk of incident CHD death than men, but the magnitude of sex differences was greater in whites than blacks for nonfatal events, regardless of menopause type. PMID:26133958

Comparing the 12-month patency of low- versus high-pressure dilation in failing arteriovenous fistulae: A prospective multicenter trial (YOROI study).

PubMed

Wakamoto, Koki; Doi, Shigehiro; Nakashima, Ayumu; Kawai, Toru; Kyuden, Yasufumi; Naito, Takayuki; Asai, Mariko; Takahashi, Shunsuke; Murakami, Masaaki; Masaki, Takao

2018-03-01

This study was performed to investigate the effect of the balloon dilation pressure on the 12-month patency rate in patients with failed arteriovenous fistulas undergoing hemodialysis. In this multicenter, prospective, randomized trial, the 4-mm-diameter YOROI balloon was used for dilation of stenotic lesions. The balloons were inflated to a pressure of 8 atm (low-pressure group) or 30 atm to achieve complete expansion (high-pressure group). The 12-month patency rate after balloon angioplasty was analyzed by the Kaplan-Meier method and log-rank test and/or a Cox proportional hazard model. We also investigated the dilation pressure required to achieve complete expansion in the high-pressure group. In total, 71 patients were enrolled and allocated to either the low-pressure group (n = 34) or the high-pressure group (n = 37). The 12-month patency rates showed no significant difference between the low- and high-pressure groups (47% and 49%, respectively; p = 0.87). In the low-pressure group, the patency rate was not different between patients with complete dilation and residual stenosis (44% and 50%, respectively; p = 0.87). The Cox proportional hazard model revealed that the 12-month patency rate was associated with the stenosis diameter (hazard ratio 0.36; p = 0.001) and the presence of diabetes (hazard ratio 0.33; p = 0.018). Finally, the pressure required to achieve complete dilation was ≤20 atm in 76% of patients and ≤30 atm in 97% of patients. One patient required a dilation pressure of >30 atm. The patency rate does not differ between low-pressure dilation and high-pressure dilation.

Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes.

PubMed

Neal, Bruce; Perkovic, Vlado; Mahaffey, Kenneth W; de Zeeuw, Dick; Fulcher, Greg; Erondu, Ngozi; Shaw, Wayne; Law, Gordon; Desai, Mehul; Matthews, David R

2017-08-17

Background Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results The mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by Janssen Research and Development; CANVAS and CANVAS-R ClinicalTrials.gov numbers, NCT01032629 and NCT01989754 , respectively.).

Tumor-adjacent tissue co-expression profile analysis reveals pro-oncogenic ribosomal gene signature for prognosis of resectable hepatocellular carcinoma.

PubMed

Grinchuk, Oleg V; Yenamandra, Surya P; Iyer, Ramakrishnan; Singh, Malay; Lee, Hwee Kuan; Lim, Kiat Hon; Chow, Pierce Kah-Hoe; Kuznetsov, Vladamir A

2018-01-01

Currently, molecular markers are not used when determining the prognosis and treatment strategy for patients with hepatocellular carcinoma (HCC). In the present study, we proposed that the identification of common pro-oncogenic pathways in primary tumors (PT) and adjacent non-malignant tissues (AT) typically used to predict HCC patient risks may result in HCC biomarker discovery. We examined the genome-wide mRNA expression profiles of paired PT and AT samples from 321 HCC patients. The workflow integrated differentially expressed gene selection, gene ontology enrichment, computational classification, survival predictions, image analysis and experimental validation methods. We developed a 24-ribosomal gene-based HCC classifier (RGC), which is prognostically significant in both PT and AT. The RGC gene overexpression in PT was associated with a poor prognosis in the training (hazard ratio = 8.2, P = 9.4 × 10 -6 ) and cross-cohort validation (hazard ratio = 2.63, P = 0.004) datasets. The multivariate survival analysis demonstrated the significant and independent prognostic value of the RGC. The RGC displayed a significant prognostic value in AT of the training (hazard ratio = 5.0, P = 0.03) and cross-validation (hazard ratio = 1.9, P = 0.03) HCC groups, confirming the accuracy and robustness of the RGC. Our experimental and bioinformatics analyses suggested a key role for c-MYC in the pro-oncogenic pattern of ribosomal biogenesis co-regulation in PT and AT. Microarray, quantitative RT-PCR and quantitative immunohistochemical studies of the PT showed that DKK1 in PT is the perspective biomarker for poor HCC outcomes. The common co-transcriptional pattern of ribosome biogenesis genes in PT and AT from HCC patients suggests a new scalable prognostic system, as supported by the model of tumor-like metabolic redirection/assimilation in non-malignant AT. The RGC, comprising 24 ribosomal genes, is introduced as a robust and reproducible prognostic model for stratifying HCC patient risks. The adjacent non-malignant liver tissue alone, or in combination with HCC tissue biopsy, could be an important target for developing predictive and monitoring strategies, as well as evidence-based therapeutic interventions, that aim to reduce the risk of post-surgery relapse in HCC patients. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

An Ensemble Approach for Improved Short-to-Intermediate-Term Seismic Potential Evaluation

NASA Astrophysics Data System (ADS)

Yu, Huaizhong; Zhu, Qingyong; Zhou, Faren; Tian, Lei; Zhang, Yongxian

2017-06-01

Pattern informatics (PI), load/unload response ratio (LURR), state vector (SV), and accelerating moment release (AMR) are four previously unrelated subjects, which are sensitive, in varying ways, to the earthquake's source. Previous studies have indicated that the spatial extent of the stress perturbation caused by an earthquake scales with the moment of the event, allowing us to combine these methods for seismic hazard evaluation. The long-range earthquake forecasting method PI is applied to search for the seismic hotspots and identify the areas where large earthquake could be expected. And the LURR and SV methods are adopted to assess short-to-intermediate-term seismic potential in each of the critical regions derived from the PI hotspots, while the AMR method is used to provide us with asymptotic estimates of time and magnitude of the potential earthquakes. This new approach, by combining the LURR, SV and AMR methods with the choice of identified area of PI hotspots, is devised to augment current techniques for seismic hazard estimation. Using the approach, we tested the strong earthquakes occurred in Yunnan-Sichuan region, China between January 1, 2013 and December 31, 2014. We found that most of the large earthquakes, especially the earthquakes with magnitude greater than 6.0 occurred in the seismic hazard regions predicted. Similar results have been obtained in the prediction of annual earthquake tendency in Chinese mainland in 2014 and 2015. The studies evidenced that the ensemble approach could be a useful tool to detect short-to-intermediate-term precursory information of future large earthquakes.

Emergency Department–Based Brief Intervention to Reduce Risky Driving and Hazardous/Harmful Drinking in Young Adults: A Randomized Controlled Trial

PubMed Central

Sommers, Marilyn S.; Lyons, Michael S.; Fargo, Jamison D.; Sommers, Benjamin D.; McDonald, Catherine C.; Shope, Jean T.; Fleming, Michael F.

2014-01-01

Background Risky driving and hazardous drinking are associated with significant human and economic costs. Brief interventions for more than one risky behavior have the potential to reduce health-compromising behaviors in populations with multiple risk-taking behaviors such as young adults. Emergency department (ED) visits provide a window of opportunity for interventions meant to reduce both risky driving and hazardous drinking. Methods We determined the efficacy of a Screening, Brief Intervention, and Referral to Treatment (SBIRT) protocol addressing risky driving and hazardous drinking. We used a randomized controlled trial design with follow-ups through 12 months. ED patients aged 18 to 44 who screened positive for both behaviors (n = 476) were randomized to brief intervention (BIG), contact control (CCG), or no-contact control (NCG) groups. The BIG (n = 150) received a 20-minute assessment and two 20-minute interventions. The CCG (n = 162) received a 20-minute assessment at baseline and no intervention. The NCG (n = 164) were asked for contact information at baseline and had no assessment or intervention. Outcomes at 3, 6, 9, and 12 months were self-reported driving behaviors and alcohol consumption. Results Outcomes were significantly lower in BIG compared with CCG through 6 or 9 months, but not at 12 months: Safety belt use at 3 months (adjusted odds ratio [AOR], 0.22; 95% confidence interval [CI], 0.08 to 0.65); 6 months (AOR, 0.13; 95% CI, 0.04 to 0.42); and 9 months (AOR, 0.18; 95% CI, 0.06 to 0.56); binge drinking at 3 months (adjusted rate ratio [ARR] 0.84; 95% CI, 0.74 to 0.97) and 6 months (ARR, 0.81; 95% CI, 0.67 to 0.97); and ≥ 5 standard drinks/d at 3 months (AOR, 0.43; 95% CI, 0.20 to 0.91) and 6 months (AOR, 0.41; 95% CI, 0.17 to 0.98). No substantial differences were observed between BIG and NCG at 12 months. Conclusions Our findings indicate that SBIRT reduced risky driving and hazardous drinking in young adults, but its effects did not persist after 9 months. Future research should explore methods for extending the intervention effect. PMID:23802878

Risk of Revision Was Not Reduced by a Double-bundle ACL Reconstruction Technique: Results From the Scandinavian Registers.

PubMed

Aga, Cathrine; Kartus, Jüri-Tomas; Lind, Martin; Lygre, Stein Håkon Låstad; Granan, Lars-Petter; Engebretsen, Lars

2017-10-01

Double-bundle anterior cruciate ligament (ACL) reconstruction has demonstrated improved biomechanical properties and moderately better objective outcomes compared with single-bundle reconstructions. This could make an impact on the rerupture rate and reduce the risk of revisions in patients undergoing double-bundle ACL reconstruction compared with patients reconstructed with a traditional single-bundle technique. The National Knee Ligament Registers in Scandinavia provide information that can be used to evaluate the revision outcome after ACL reconstructions. The purposes of the study were (1) to compare the risk of revision between double-bundle and single-bundle reconstructions, reconstructed with autologous hamstring tendon grafts; (2) to compare the risk of revision between double-bundle hamstring tendon and single-bundle bone-patellar tendon-bone autografts; and (3) to compare the hazard ratios for the same two research questions after Cox regression analysis was performed. Data collection of primary ACL reconstructions from the National Knee Ligament Registers in Denmark, Norway, and Sweden from July 1, 2005, to December 31, 2014, was retrospectively analyzed. A total of 60,775 patients were included in the study; 994 patients were reconstructed with double-bundle hamstring tendon grafts, 51,991 with single-bundle hamstring tendon grafts, and 7790 with single-bundle bone-patellar tendon-bone grafts. The double-bundle ACL-reconstructed patients were compared with the two other groups. The risk of revision for each research question was detected by the risk ratio, hazard ratio, and the corresponding 95% confidence intervals. Kaplan-Meier analysis was used to estimate survival at 1, 2, and 5 years for the three different groups. Furthermore, a Cox proportional hazard regression model was applied and the hazard ratios were adjusted for country, age, sex, meniscal or chondral injury, and utilized fixation devices on the femoral and tibial sides. There were no differences in the crude risk of revision between the patients undergoing the double-bundle technique and the two other groups. A total of 3.7% patients were revised in the double-bundle group (37 of 994 patients) versus 3.8% in the single-bundle hamstring tendon group (1952 of 51,991; risk ratio, 1.01; 95% confidence interval (CI), 0.73-1.39; p = 0.96), and 2.8% of the patients were revised in the bone-patellar tendon-bone group (219 of the 7790 bone-patellar tendon-bone patients; risk ratio, 0.76; 95% CI, 0.54-1.06; p = 0.11). Cox regression analysis with adjustment for country, age, sex, menisci or cartilage injury, and utilized fixation device on the femoral and tibial sides, did not reveal any further difference in the risk of revision between the single-bundle hamstring tendon and double-bundle hamstring tendon groups (hazard ratio, 1.18; 95% CI, 0.85-1.62; p = 0.33), but the adjusted hazard ratio showed a lower risk of revision in the single-bundle bone-patellar tendon-bone group compared with the double-bundle group (hazard ratio, 0.62; 95% CI, 0.43-0.90; p = 0.01). Comparisons of the graft revision rates reported separately for each country revealed that double-bundle hamstring tendon reconstructions in Sweden had a lower hazard ratio compared with the single-bundle hamstring tendon reconstructions (hazard ratio, 1.00 versus 1.89; 95% CI, 1.09-3.29; p = 0.02). Survival at 5 years after index surgery was 96.0% for the double-bundle group, 95.4% for the single-bundle hamstring tendon group, and 97.0% for the single-bundle bone-patellar tendon-bone group. Based on the data from all three national registers, the risk of revision was not influenced by the reconstruction technique in terms of using single- or double-bundle hamstring tendons, although national differences in survival existed. Using bone-patellar tendon-bone grafts lowered the risk of revision compared with double-bundle hamstring tendon grafts. These findings should be considered when deciding what reconstruction technique to use in ACL-deficient knees. Future studies identifying the reasons for graft rerupture in single- and double-bundle reconstructions would be of interest to understand the findings of the present study. Level III, therapeutic study.

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

PubMed Central

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

2015-01-01

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

Total Laryngectomy Versus Larynx Preservation for T4a Larynx Cancer: Patterns of Care and Survival Outcomes

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

Grover, Surbhi; Swisher-McClure, Samuel; Mitra, Nandita

2015-07-01

Purpose: To examine practice patterns and compare survival outcomes between total laryngectomy (TL) and larynx preservation chemoradiation (LP-CRT) in the setting of T4a larynx cancer, using a large national cancer registry. Methods and Materials: Using the National Cancer Database, we identified 969 patients from 2003 to 2006 with T4a squamous cell larynx cancer receiving definitive treatment with either initial TL plus adjuvant therapy or LP-CRT. Univariate and multivariable logistic regression were used to assess predictors of undergoing surgery. Survival outcomes were compared using Kaplan-Meier and propensity score–adjusted and inverse probability of treatment–weighted Cox proportional hazards methods. Sensitivity analyses were performed tomore » account for unmeasured confounders. Results: A total of 616 patients (64%) received LP-CRT, and 353 (36%) received TL. On multivariable logistic regression, patients with advanced nodal disease were less likely to receive TL (N2 vs N0, 26.6% vs 43.4%, odds ratio [OR] 0.52, 95% confidence interval [CI] 0.37-0.73; N3 vs N0, 19.1% vs 43.4%, OR 0.23, 95% CI 0.07-0.77), whereas patients treated in high case-volume facilities were more likely to receive TL (46.1% vs 31.5%, OR 1.78, 95% CI 1.27-2.48). Median survival for TL versus LP was 61 versus 39 months (P<.001). After controlling for potential confounders, LP-CRT had inferior overall survival compared with TL (hazard ratio 1.31, 95% CI 1.10-1.57), and with the inverse probability of treatment–weighted model (hazard ratio 1.25, 95% CI 1.05-1.49). This survival difference was shown to be robust on additional sensitivity analyses. Conclusions: Most patients with T4a larynx cancer receive LP-CRT, despite guidelines suggesting TL as the preferred initial approach. Patients receiving LP-CRT had more advanced nodal disease and worse overall survival. Previous studies of (non-T4a) locally advanced larynx cancer showing no difference in survival between LP-CRT and TL may not apply to T4a disease, and patients should be counseled accordingly.« less

Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds

PubMed Central

Jarvis, J; Seed, M; Elton, R; Sawyer, L; Agius, R

2005-01-01

Aims: To investigate quantitatively, relationships between chemical structure and reported occupational asthma hazard for low molecular weight (LMW) organic compounds; to develop and validate a model linking asthma hazard with chemical substructure; and to generate mechanistic hypotheses that might explain the relationships. Methods: A learning dataset used 78 LMW chemical asthmagens reported in the literature before 1995, and 301 control compounds with recognised occupational exposures and hazards other than respiratory sensitisation. The chemical structures of the asthmagens and control compounds were characterised by the presence of chemical substructure fragments. Odds ratios were calculated for these fragments to determine which were associated with a likelihood of being reported as an occupational asthmagen. Logistic regression modelling was used to identify the independent contribution of these substructures. A post-1995 set of 21 asthmagens and 77 controls were selected to externally validate the model. Results: Nitrogen or oxygen containing functional groups such as isocyanate, amine, acid anhydride, and carbonyl were associated with an occupational asthma hazard, particularly when the functional group was present twice or more in the same molecule. A logistic regression model using only statistically significant independent variables for occupational asthma hazard correctly assigned 90% of the model development set. The external validation showed a sensitivity of 86% and specificity of 99%. Conclusions: Although a wide variety of chemical structures are associated with occupational asthma, bifunctional reactivity is strongly associated with occupational asthma hazard across a range of chemical substructures. This suggests that chemical cross-linking is an important molecular mechanism leading to the development of occupational asthma. The logistic regression model is freely available on the internet and may offer a useful but inexpensive adjunct to the prediction of occupational asthma hazard. PMID:15778257

Warfarin Use in Patients With Atrial Fibrillation Undergoing Hemodialysis: A Nationwide Population-Based Study.

PubMed

Yoon, Chang-Yun; Noh, Juhwan; Jhee, Jong Hyun; Chang, Tae Ik; Kang, Ea Wha; Kee, Youn Kyung; Kim, Hyoungnae; Park, Seohyun; Yun, Hae-Ryong; Jung, Su-Young; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Kang, Shin-Wook; Kim, Changsoo; Yoo, Tae-Hyun

2017-09-01

The aim of this study is to elucidate the effects of warfarin use in patients with atrial fibrillation undergoing dialysis using a population-based Korean registry. Data were extracted from the Health Insurance Review and Assessment Service, which is a nationwide, mandatory social insurance database of all Korean citizens enrolled in the National Health Information Service between 2009 and 2013. Thromboembolic and hemorrhagic outcomes were analyzed according to warfarin use. Overall and propensity score-matched cohorts were analyzed by Cox proportional hazards models. Among 9974 hemodialysis patients with atrial fibrillation, the mean age was 66.6±12.2 years, 5806 (58.2%) were men, and 2921 (29.3%) used warfarin. After propensity score matching to adjust for all described baseline differences, 5548 subjects remained, and differences in baseline variables were distributed equally between warfarin users and nonusers. During a mean follow-up duration of 15.9±11.1 months, ischemic and hemorrhagic stroke occurred in 678 (6.8%) and 227 (2.3%) patients, respectively. In a multiple Cox model, warfarin use was significantly associated with an increased risk of hemorrhagic stroke (hazard ratio, 1.44; 95% confidence interval, 1.09-1.91; P =0.010) in the overall cohort. Furthermore, a significant relationship between warfarin use and hemorrhagic stroke was found in propensity-matched subjects (hazard ratio, 1.56; 95% confidence interval, 1.10-2.22; P =0.013). However, the ratios for ischemic stroke were not significantly different in either the propensity-matched (hazard ratio, 0.95; 95% confidence interval, 0.78-1.15; P =0.569) or overall cohort (hazard ratio, 1.06; 95% confidence interval, 0.90-1.26; P =0.470). Our findings suggest that warfarin should be used carefully in hemodialysis patients, given the higher risk of hemorrhagic events and the lack of ability to prevent thromboembolic complications. © 2017 American Heart Association, Inc.

The combined influence of hypertension and common mental disorder on all-cause and cardiovascular disease mortality.

PubMed

Hamer, Mark; Batty, G David; Stamatakis, Emmanuel; Kivimaki, Mika

2010-12-01

Common mental disorders, such as anxiety and depression, are risk factors for mortality among cardiac patients, although this topic has gained little attention in individuals with hypertension. We examined the combined effects of hypertension and common mental disorder on mortality in participants with both treated and untreated hypertension. In a representative, prospective study of 31 495 adults (aged 52.5 ± 12.5 years, 45.7% men) we measured baseline levels of common mental disorder using the 12-item General Health Questionnaire (GHQ-12) and collected data on blood pressure, history of hypertension diagnosis, and medication use. High blood pressure (systolic/diastolic >140/90 mmHg) in study members with an existing diagnosis of hypertension indicated uncontrolled hypertension and, in undiagnosed individuals, untreated hypertension. There were 3200 deaths from all causes [943 cardiovascular disease (CVD)] over 8.4 years follow-up. As expected, the risk of CVD was elevated in participants with controlled [multivariate hazard ratio = 1.63, 95% confidence interval (CI) 1.26-2.12] and uncontrolled (multivariate hazard ratio = 1.57, 95% CI 1.08-2.27) hypertension compared with normotensive participants. Common mental disorder (GHQ-12 score of ≥4) was also associated with CVD death (multivariate hazard ratio = 1.60, 95% CI 1.35-1.90). The risk of CVD death was highest in participants with both diagnosed hypertension and common mental disorder, especially in study members with controlled (multivariate hazard ratio = 2.32, 95% CI 1.70-3.17) hypertension but also in uncontrolled hypertension (multivariate hazard ratio = 1.90, 95% CI 1.18-3.05). The combined effect of common mental disorder was also apparent in participants with undiagnosed (untreated) hypertension, especially for all-cause mortality. These findings suggest that the association of hypertension with total and CVD mortality is stronger when combined with common mental disorder.

Counterclockwise and Clockwise Rotation of QRS Transitional Zone: Prospective Correlates of Change and Time-Varying Associations With Cardiovascular Outcomes.

PubMed

Patel, Siddharth; Kwak, Lucia; Agarwal, Sunil K; Tereshchenko, Larisa G; Coresh, Josef; Soliman, Elsayed Z; Matsushita, Kunihiro

2017-11-03

A few studies have recently reported clockwise and counterclockwise rotations of QRS transition zone as predictors of mortality. However, their prospective correlates and associations with individual cardiovascular disease (CVD) outcomes are yet to be investigated. Among 13 567 ARIC (Atherosclerosis Risk in Communities) study participants aged 45 to 64 years, we studied key correlates of changes in the status of clockwise and counterclockwise rotation over time as well as the association of rotation status with incidence of coronary heart disease (2408 events), heart failure (2196 events), stroke (991 events), composite CVD (4124 events), 898 CVD deaths, and 3469 non-CVD deaths over 23 years of follow-up. At baseline, counterclockwise rotation was most prevalent (52.9%), followed by no (40.5%) and clockwise (6.6%) rotation. Of patients with no rotation, 57.9% experienced counterclockwise or clockwise rotation during follow-up, with diabetes mellitus and black race significantly predicting clockwise and counterclockwise conversion, respectively. Clockwise rotation was significantly associated with higher risk of heart failure (hazard ratio, 1.20; 95% confidence interval [CI], 1.02-1.41) and non-CVD death (hazard ratio, 1.28; 95% CI, 1.12-1.46) after adjusting for potential confounders including other ECG parameters. On the contrary, counterclockwise rotation was significantly related to lower risk of composite CVD (hazard ratio, 0.93; 95% CI, 0.87-0.99]), CVD mortality (hazard ratio, 0.76; 95% CI, 0.65-0.88), and non-CVD deaths (hazard ratio, 0.92; 95% CI, 0.85-0.99 [borderline significance with heart failure]). Counterclockwise rotation, the most prevalent QRS transition zone pattern, demonstrated the lowest risk of CVD and mortality, whereas clockwise rotation was associated with the highest risk of heart failure and non-CVD mortality. These results have implications on how to interpret QRS transition zone rotation when ECG was recorded. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke.

PubMed

Sacco, Ralph L; Diener, Hans-Christoph; Yusuf, Salim; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A; Palesch, Yuko; Martin, Reneé H; Albers, Gregory W; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; Vandermaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

2008-09-18

Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.) 2008 Massachusetts Medical Society

Low-Risk Lifestyle, Coronary Calcium, Cardiovascular Events, and Mortality: Results From MESA

PubMed Central

Ahmed, Haitham M.; Blaha, Michael J.; Nasir, Khurram; Jones, Steven R.; Rivera, Juan J.; Agatston, Arthur; Blankstein, Ron; Wong, Nathan D.; Lakoski, Susan; Budoff, Matthew J.; Burke, Gregory L.; Sibley, Christopher T.; Ouyang, Pamela; Blumenthal, Roger S.

2013-01-01

Unhealthy lifestyle habits are a major contributor to coronary artery disease. The purpose of the present study was to investigate the associations of smoking, weight maintenance, physical activity, and diet with coronary calcium, cardiovascular events, and mortality. US participants who were 44–84 years of age (n = 6,229) were followed in the Multi-Ethnic Study of Atherosclerosis from 2000 to 2010. A lifestyle score ranging from 0 to 4 was created using diet, exercise, body mass index, and smoking status. Coronary calcium was measured at baseline and a mean of 3.1 (standard deviation, 1.3) years later to assess calcium progression. Participants who experienced coronary events or died were followed for a median of 7.6 (standard deviation, 1.5) years. Participants with lifestyle scores of 1, 2, 3, and 4 were found to have mean adjusted annual calcium progressions that were 3.5 (95% confidence interval (CI): 0.0, 7.0), 4.2 (95% CI: 0.6, 7.9), 6.8 (95% CI: 2.0, 11.5), and 11.1 (95% CI: 2.2, 20.1) points per year slower, respectively, relative to the reference group (P = 0.003). Unadjusted hazard ratios for death by lifestyle score were as follows: for a score of 1, the hazard ratio was 0.79 (95% CI: 0.61, 1.03); for a score of 2, the hazard ratio was 0.61 (95% CI: 0.46, 0.81); for a score of 3, the hazard ratio was 0.49 (95% CI: 0.32, 0.75); and for a score of 4, the hazard ratio was 0.19 (95% CI: 0.05, 0.75) (P < 0.001 by log-rank test). In conclusion, a combination of regular exercise, healthy diet, smoking avoidance, and weight maintenance was associated with lower coronary calcium incidence, slower calcium progression, and lower all-cause mortality over 7.6 years. PMID:23733562

Use of the quality management system “JACIE” and outcome after hematopoietic stem cell transplantation

PubMed Central

Gratwohl, Alois; Brand, Ronald; McGrath, Eoin; van Biezen, Anja; Sureda, Anna; Ljungman, Per; Baldomero, Helen; Chabannon, Christian; Apperley, Jane

2014-01-01

Competent authorities, healthcare payers and hospitals devote increasing resources to quality management systems but scientific analyses searching for an impact of these systems on clinical outcome remain scarce. Earlier data indicated a stepwise improvement in outcome after allogeneic hematopoietic stem cell transplantation with each phase of the accreditation process for the quality management system “JACIE”. We therefore tested the hypothesis that working towards and achieving “JACIE” accreditation would accelerate improvement in outcome over calendar time. Overall mortality of the entire cohort of 107,904 patients who had a transplant (41,623 allogeneic, 39%; 66,281 autologous, 61%) between 1999 and 2006 decreased over the 14-year observation period by a factor of 0.63 per 10 years (hazard ratio: 0.63; 0.58–0.69). Considering “JACIE“-accredited centers as those with programs having achieved accreditation by November 2012, at the latest, this improvement was significantly faster in “JACIE”-accredited centers than in non-accredited centers (approximately 5.3% per year for 49,459 patients versus approximately 3.5% per year for 58,445 patients, respectively; hazard ratio: 0.83; 0.71–0.97). As a result, relapse-free survival (hazard ratio 0.85; 0.75–0.95) and overall survival (hazard ratio 0.86; 0.76–0.98) were significantly higher at 72 months for those patients transplanted in the 162 “JACIE“-accredited centers. No significant effects were observed after autologous transplants (hazard ratio 1.06; 0.99–1.13). Hence, working towards implementation of a quality management system triggers a dynamic process associated with a steeper reduction in mortality over the years and a significantly improved survival after allogeneic stem cell transplantation. Our data support the use of a quality management system for complex medical procedures. PMID:24488562

Dronedarone in high-risk permanent atrial fibrillation.

PubMed

Connolly, Stuart J; Camm, A John; Halperin, Jonathan L; Joyner, Campbell; Alings, Marco; Amerena, John; Atar, Dan; Avezum, Álvaro; Blomström, Per; Borggrefe, Martin; Budaj, Andrzej; Chen, Shih-Ann; Ching, Chi Keong; Commerford, Patrick; Dans, Antonio; Davy, Jean-Marc; Delacrétaz, Etienne; Di Pasquale, Giuseppe; Diaz, Rafael; Dorian, Paul; Flaker, Greg; Golitsyn, Sergey; Gonzalez-Hermosillo, Antonio; Granger, Christopher B; Heidbüchel, Hein; Kautzner, Josef; Kim, June Soo; Lanas, Fernando; Lewis, Basil S; Merino, Jose L; Morillo, Carlos; Murin, Jan; Narasimhan, Calambur; Paolasso, Ernesto; Parkhomenko, Alexander; Peters, Nicholas S; Sim, Kui-Hian; Stiles, Martin K; Tanomsup, Supachai; Toivonen, Lauri; Tomcsányi, János; Torp-Pedersen, Christian; Tse, Hung-Fat; Vardas, Panos; Vinereanu, Dragos; Xavier, Denis; Zhu, Jun; Zhu, Jun-Ren; Baret-Cormel, Lydie; Weinling, Estelle; Staiger, Christoph; Yusuf, Salim; Chrolavicius, Susan; Afzal, Rizwan; Hohnloser, Stefan H

2011-12-15

Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02). Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.).

The prognostic utility of baseline alpha-fetoprotein for hepatocellular carcinoma patients.

PubMed

Silva, Jack P; Gorman, Richard A; Berger, Nicholas G; Tsai, Susan; Christians, Kathleen K; Clarke, Callisia N; Mogal, Harveshp; Gamblin, T Clark

2017-12-01

Alpha-fetoprotein (AFP) has a valuable role in postoperative surveillance for hepatocellular carcinoma (HCC) recurrence. The utility of pretreatment or baseline AFP remains controversial. The present study hypothesized that elevated baseline AFP levels are associated with worse overall survival in HCC patients. Adult HCC patients were identified using the National Cancer Database (2004-2013). Patients were stratified according to baseline AFP measurements into the following groups: Negative (<20), Borderline (20-199), Elevated (200-1999), and Highly Elevated (>2000). The primary outcome was overall survival (OS), which was analyzed by log-rank test and graphed using Kaplan-Meier method. Multivariate regression modeling was used to determine hazard ratios (HR) for OS. Of 41 107 patients identified, 15 809 (33.6%) were Negative. Median overall survival was highest in the Negative group, followed by Borderline, Elevated, and Highly Elevated (28.7 vs 18.9 vs 8.8 vs 3.2 months; P < 0.001). On multivariate analysis, overall survival hazard ratios for the Borderline, Elevated, and Highly Elevated groups were 1.18 (P = 0.267), 1.94 (P < 0.001), and 1.77 (P = 0.007), respectively (reference Negative). Baseline AFP independently predicted overall survival in HCC patients regardless of treatment plan. A baseline AFP value is a simple and effective method to assist in expected survival for HCC patients. © 2017 Wiley Periodicals, Inc.

Incidence of opioid-managed pelvic pain after hysteroscopic sterilization versus laparoscopic sterilization, U.S. 2005-2012

PubMed Central

Conover, Mitchell M.; Howell, Jennifer O.; Wu, Jennifer M.; Kinlaw, Alan C.; Dasgupta, Nabarun; Funk, Michele Jonsson

2015-01-01

Objective Compare incidence of opioid-managed pelvic pain within 12-months after hysteroscopic and laparoscopic sterilization. Methods Using administrative claims, we identified women age 18-49 without recent history of childbirth who underwent hysteroscopic or laparoscopic sterilization between 2005-2012. We defined the outcome as ≥2 diagnoses for pelvic pain and ≥2 prescription fills for opioids. We calculated adjusted hazard ratios (HR) using Cox models and propensity score methods (matching and inverse-probability-of-treatment-weighting [IPTW]). Results We identified 71,875 eligible women (hysteroscopic n=26,927 [37.5%], laparoscopic n=44,948 [62.5%]). Of those, 236 (0.88%) hysteroscopic patients and 420 (0.93%) laparoscopic patients experienced the outcome (crude HR=0.97, [95%CI: 0.83, 1.14]). Adjusted analyses also yielded near-null results (matched HR=1.08 [95%CI: 0.90, 1.31]; IPTW HR=0.97 [95%CI: 0.80, 1.18]). While most sensitivity analyses generated results close to the null, hazard ratios estimated using propensity score matching ranged from 0.65 to 1.53. Conclusions Among women without recent history of childbirth, we did not find compelling evidence of a clinically meaningful increase in the incidence of pelvic pain requiring opioids during the year after hysteroscopic sterilization. However, effects observed in sensitivity analyses may merit further investigation. PMID:25832014

Issues regarding 'immortal time' in the analysis of the treatment effects in observational studies.

PubMed

Liu, Jiannong; Weinhandl, Eric D; Gilbertson, David T; Collins, Allan J; St Peter, Wendy L

2012-02-01

In observational studies, treatment is often time dependent. Mishandling the time from the beginning of follow-up to treatment initiation can result in bias known as immortal time bias. Nephrology researchers who conduct observational research must be aware of how immortal time bias can be introduced into analyses. We review immortal time bias issues in time-to-event analyses in the biomedical literature and give examples from the nephrology literature. We also use simulations to quantify the bias in different methods of mishandling immortal time; intuitively explain how bias is introduced when immortal time is mishandled; raise issues regarding unadjusted treatment comparison, patient characteristics comparison, and confounder adjustment; and, using data from DaVita Inc., linked with the Centers for Medicare & Medicaid Services end-stage renal disease database, show that the severity of bias and the issues described can occur in actual data analyses of patients with end-stage renal disease. In the simulation examples, mishandling immortal time led to an underestimated hazard ratio (treatment vs. control), thus an overestimated treatment effect, by as much as 96%, and an overestimated hazard ratio by as much as 138%, depending on the distribution of 'survival' time and the method used. Results from the DaVita data were consistent with the simulation. Careful consideration of methodology is needed in observational analyses with time-dependent treatment.

Motivation, effort and life circumstances as predictors of foot ulcers and amputations in people with Type 2 diabetes mellitus.

PubMed

Bruun, C; Guassora, A D; Nielsen, A B S; Siersma, V; Holstein, P E; de Fine Olivarius, N

2014-11-01

To investigate the predictive value of both patients' motivation and effort in their management of Type 2 diabetes and their life circumstances for the development of foot ulcers and amputations. This study was based on the Diabetes Care in General Practice study and Danish population and health registers. The associations between patient motivation, effort and life circumstances and foot ulcer prevalence 6 years after diabetes diagnosis and the incidence of amputation in the following 13 years were analysed using odds ratios from logistic regression and hazard ratios from Cox regression models, respectively. Foot ulcer prevalence 6 years after diabetes diagnosis was 2.93% (95% CI 1.86-4.00) among 956 patients. General practitioners' indication of 'poor' vs 'very good' patient motivation for diabetes management was associated with higher foot ulcer prevalence (odds ratio 6.11, 95% CI 1.22-30.61). The same trend was seen for 'poor' vs 'good' influence of the patient's own effort in diabetes treatment (odds ratio 7.06, 95% CI 2.65-18.84). Of 1058 patients examined at 6-year follow-up, 45 experienced amputation during the following 13 years. 'Poor' vs 'good' influence of the patients' own effort was associated with amputation (hazard ratio 7.12, 95% CI 3.40-14.92). When general practitioners assessed the influence of patients' life circumstances as 'poor' vs 'good', the amputation incidence increased (hazard ratio 2.97, 95% CI 1.22-7.24). 'Poor' vs 'very good' patient motivation was also associated with a higher amputation incidence (hazard ratio 7.57, 95% CI 2.43-23.57), although not in fully adjusted models. General practitioners' existing knowledge of patients' life circumstances, motivation and effort in diabetes management should be included in treatment strategies to prevent foot complications. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Faster Blood Flow Rate Does Not Improve Circuit Life in Continuous Renal Replacement Therapy: A Randomized Controlled Trial.

PubMed

Fealy, Nigel; Aitken, Leanne; du Toit, Eugene; Lo, Serigne; Baldwin, Ian

2017-10-01

To determine whether blood flow rate influences circuit life in continuous renal replacement therapy. Prospective randomized controlled trial. Single center tertiary level ICU. Critically ill adults requiring continuous renal replacement therapy. Patients were randomized to receive one of two blood flow rates: 150 or 250 mL/min. The primary outcome was circuit life measured in hours. Circuit and patient data were collected until each circuit clotted or was ceased electively for nonclotting reasons. Data for clotted circuits are presented as median (interquartile range) and compared using the Mann-Whitney U test. Survival probability for clotted circuits was compared using log-rank test. Circuit clotting data were analyzed for repeated events using hazards ratio. One hundred patients were randomized with 96 completing the study (150 mL/min, n = 49; 250 mL/min, n = 47) using 462 circuits (245 run at 150 mL/min and 217 run at 250 mL/min). Median circuit life for first circuit (clotted) was similar for both groups (150 mL/min: 9.1 hr [5.5-26 hr] vs 10 hr [4.2-17 hr]; p = 0.37). Continuous renal replacement therapy using blood flow rate set at 250 mL/min was not more likely to cause clotting compared with 150 mL/min (hazards ratio, 1.00 [0.60-1.69]; p = 0.68). Gender, body mass index, weight, vascular access type, length, site, and mode of continuous renal replacement therapy or international normalized ratio had no effect on clotting risk. Continuous renal replacement therapy without anticoagulation was more likely to cause clotting compared with use of heparin strategies (hazards ratio, 1.62; p = 0.003). Longer activated partial thromboplastin time (hazards ratio, 0.98; p = 0.002) and decreased platelet count (hazards ratio, 1.19; p = 0.03) were associated with a reduced likelihood of circuit clotting. There was no difference in circuit life whether using blood flow rates of 250 or 150 mL/min during continuous renal replacement therapy.

The synergistic effect of breastfeeding discontinuation and cesarean section delivery on postpartum depression: A nationwide population-based cohort study in Korea.

PubMed

Nam, Jin Young; Choi, Young; Kim, Juyeong; Cho, Kyoung Hee; Park, Eun-Cheol

2017-08-15

The relationships between breastfeeding discontinuation and cesarean section delivery, and the occurrence of postpartum depression (PPD) remain unclear. Therefore, we aimed to investigate the association of breastfeeding discontinuation and cesarean section delivery with PPD during the first 6 months after delivery. Data were extracted from the Korean National Health Insurance Service-National Sample Cohort for 81,447 women who delivered during 2004-2013. PPD status was determined using the diagnosis code at outpatient or inpatient visit during the 6-month postpartum period. Breastfeeding discontinuation and cesarean section delivery were identified from prescription of lactation suppression drugs and diagnosis, respectively. Cox proportional hazards models were used to calculate adjusted hazard ratios. Of the 81,447 women, 666 (0.82%) had PPD. PPD risk was higher in women who discontinued breastfeeding than in those who continued breastfeeding (hazard ratio=3.23, P<0.0001), in women with cesarean section delivery than in those with vaginal delivery (hazard ratio=1.26, P=0.0040), and in women with cesarean section delivery who discontinued breastfeeding than in those with vaginal delivery who continued breastfeeding (hazard ratio=4.92, P<0.0001). Study limitations include low PPD incidence; use of indirect indicators for PPD, breastfeeding discontinuation, and working status, which could introduce selection bias and errors due to miscoding; and potential lack of adjustment for important confounders. Breastfeeding discontinuation and cesarean section delivery were associated with PPD during the 6-month postpartum period. Our results support the implementation of breastfeeding promoting policies, and PPD screening and treatment programs during the early postpartum period. Copyright © 2017 Elsevier B.V. All rights reserved.

Association of Modality with Mortality among Canadian Aboriginals

PubMed Central

Hemmelgarn, Brenda; Rigatto, Claudio; Komenda, Paul; Yeates, Karen; Promislow, Steven; Mojica, Julie; Tangri, Navdeep

2012-01-01

Summary Background and objectives Previous studies have shown that Aboriginals and Caucasians experience similar outcome on dialysis in Canada. Using the Canadian Organ Replacement Registry, this study examined whether dialysis modality (peritoneal or hemodialysis) impacted mortality in Aboriginal patients. Design, setting, participants, & measurements This study identified 31,576 adult patients (hemodialysis: Aboriginal=1839, Caucasian=21,430; peritoneal dialysis: Aboriginal=554, Caucasian=6769) who initiated dialysis between January of 2000 and December of 2009. Aboriginal status was identified by self-report. Dialysis modality was determined 90 days after dialysis initiation. Multivariate Cox proportional hazards and competing risk models were constructed to determine the association between race and mortality by dialysis modality. Results During the study period, 939 (51.1%) Aboriginals and 12,798 (53.3%) Caucasians initiating hemodialysis died, whereas 166 (30.0%) and 2037 (30.1%), respectively, initiating peritoneal dialysis died. Compared with Caucasians, Aboriginals on hemodialysis had a comparable risk of mortality (adjusted hazards ratio=1.04, 95% confidence interval=0.96–1.11, P=0.37). However, on peritoneal dialysis, Aboriginals experienced a higher risk of mortality (adjusted hazards ratio=1.36, 95% confidence interval=1.13–1.62, P=0.001) and technique failure (adjusted hazards ratio=1.29, 95% confidence interval=1.03–1.60, P=0.03) than Caucasians. The risk of technique failure varied by patient age, with younger Aboriginals (<50 years old) more likely to develop technique failure than Caucasians (adjusted hazards ratio=1.76, 95% confidence interval=1.23–2.52, P=0.002). Conclusions Aboriginals on peritoneal dialysis experience higher mortality and technique failure relative to Caucasians. Reasons for this race disparity in peritoneal dialysis outcomes are unclear. PMID:22997343

Long-term cardiovascular risk of nonsteroidal anti-inflammatory drug use according to time passed after first-time myocardial infarction: a nationwide cohort study.

PubMed

Olsen, Anne-Marie Schjerning; Fosbøl, Emil L; Lindhardsen, Jesper; Folke, Fredrik; Charlot, Mette; Selmer, Christian; Bjerring Olesen, Jonas; Lamberts, Morten; Ruwald, Martin H; Køber, Lars; Hansen, Peter R; Torp-Pedersen, Christian; Gislason, Gunnar H

2012-10-16

The cardiovascular risk after the first myocardial infarction (MI) declines rapidly during the first year. We analyzed whether the cardiovascular risk associated with using nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with the time elapsed following first-time MI. We identified patients aged 30 years or older admitted with first-time MI in 1997 to 2009 and subsequent NSAID use by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. We calculated the incidence rates of death and a composite end point of coronary death or nonfatal recurrent MIs associated with NSAID use in 1-year time intervals up to 5 years after inclusion and analyzed risk by using multivariable adjusted time-dependent Cox proportional hazards models. Of the 99 187 patients included, 43 608 (44%) were prescribed NSAIDs after the index MI. There were 36 747 deaths and 28 693 coronary deaths or nonfatal recurrent MIs during the 5 years of follow-up. Relative to noncurrent treatment with NSAIDs, the use of any NSAID in the years following MI was persistently associated with an increased risk of death (hazard ratio 1.59 [95% confidence interval, 1.49-1.69]) after 1 year and hazard ratio 1.63 [95% confidence interval, 1.52-1.74] after 5 years) and coronary death or nonfatal recurrent MI (hazard ratio, 1.30 [95% confidence interval,l 1.22-1.39] and hazard ratio, 1.41 [95% confidence interval, 1.28-1.55]). The use of NSAIDs is associated with persistently increased coronary risk regardless of time elapsed after first-time MI. We advise long-term caution in the use of NSAIDs for patients after MI.

Impact of Time to Treatment Initiation in Patients with Human Papillomavirus-positive and -negative Oropharyngeal Squamous Cell Carcinoma.

PubMed

Grønhøj, C; Jensen, D; Dehlendorff, C; Nørregaard, C; Andersen, E; Specht, L; Charabi, B; von Buchwald, C

2018-06-01

The distinct difference in disease phenotype of human papillomavirus-positive (HPV+) and -negative (HPV-) oropharyngeal squamous cell cancer (OPSCC) patients might also be apparent when assessing the effect of time to treatment initiation (TTI). We assessed the overall survival and progression-free survival (PFS) effect from increasing TTI for HPV+ and HPV- OPSCC patients. We examined patients who received curative-intended therapy for OPSCC in eastern Denmark between 2000 and 2014. TTI was the number of days from diagnosis to the initiation of curative treatment. Overall survival and PFS were measured from the start of treatment and estimated with the Kaplan-Meier estimator. Hazard ratios and 95% confidence intervals were estimated with Cox proportional hazard regression. At a median follow-up of 3.6 years (interquartile range 1.86-6.07 years), 1177 patients were included (59% HPV+). In the adjusted analysis for the HPV+ and HPV- patient population, TTI influenced overall survival and PFS, most evident in the HPV- group, where TTI >60 days statistically significantly influenced overall survival but not PFS (overall survival: hazard ratio 1.60; 95% confidence interval 1.04-2.45; PFS: hazard ratio 1.46; 95% confidence interval 0.96-2.22). For patients with a TTI >60 days in the HPV+ group, TTI affected overall survival and PFS similarly, with slightly lower hazard ratio estimates of 1.44 (95% confidence interval 0.83-2.51) and 1.15 (95% confidence interval 0.70-1.88), respectively. For patients treated for a HPV+ or HPV- OPSCC, TTI affects outcome, with the strongest effect for overall survival among HPV- patients. Reducing TTI is an important tool to improve the prognosis. Copyright © 2018. Published by Elsevier Ltd.

Association of neighbourhood unemployment rate with incident Type 2 diabetes mellitus in five German regions.

PubMed

Müller, G; Wellmann, J; Hartwig, S; Greiser, K H; Moebus, S; Jöckel, K-H; Schipf, S; Völzke, H; Maier, W; Meisinger, C; Tamayo, T; Rathmann, W; Berger, K

2015-08-01

To analyse the association of neighbourhood unemployment with incident self-reported physician-diagnosed Type 2 diabetes in a population aged 45-74 years from five German regions. Study participants were linked via their addresses at baseline to particular neighbourhoods. Individual-level data from five population-based studies were pooled and combined with contextual data on neighbourhood unemployment. Type 2 diabetes was assessed according to a self-reported physician diagnosis of diabetes. We estimated proportional hazard models (Weibull distribution) in order to obtain hazard ratios and 95% CIs of Type 2 diabetes mellitus, taking into account interval-censoring and clustering. We included 7250 participants residing in 228 inner city neighbourhoods in five German regions in our analysis. The incidence rate was 12.6 per 1000 person-years (95% CI 11.4-13.8). The risk of Type 2 diabetes mellitus was higher in men [hazard ratio 1.79 (95% CI 1.47-2.18)] than in women and higher in people with a low education level [hazard ratio 1.55 (95% CI 1.18-2.02)] than in those with a high education level. Independently of individual-level characteristics, we found a higher risk of Type 2 diabetes mellitus in neighbourhoods with high levels of unemployment [quintile 5; hazard ratio 1.72 (95% CI 1.23-2.42)] than in neighbourhoods with low unemployment (quintile 1). Low education level and high neighbourhood unemployment were independently associated with an elevated risk of Type 2 diabetes mellitus. Studies examining the impact of the residential environment on Type 2 diabetes mellitus will provide knowledge that is essential for the identification of high-risk populations. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Relations of Arterial Stiffness and Brachial Flow-Mediated Dilation With New-Onset Atrial Fibrillation: The Framingham Heart Study.

PubMed

Shaikh, Amir Y; Wang, Na; Yin, Xiaoyan; Larson, Martin G; Vasan, Ramachandran S; Hamburg, Naomi M; Magnani, Jared W; Ellinor, Patrick T; Lubitz, Steven A; Mitchell, Gary F; Benjamin, Emelia J; McManus, David D

2016-09-01

The relations of measures of arterial stiffness, pulsatile hemodynamic load, and endothelial dysfunction to atrial fibrillation (AF) remain poorly understood. To better understand the pathophysiology of AF, we examined associations between noninvasive measures of vascular function and new-onset AF. The study sample included participants aged ≥45 years from the Framingham Heart Study offspring and third-generation cohorts. Using Cox proportional hazards regression models, we examined relations between incident AF and tonometry measures of arterial stiffness (carotid-femoral pulse wave velocity), wave reflection (augmentation index), pressure pulsatility (central pulse pressure), endothelial function (flow-mediated dilation), resting brachial arterial diameter, and hyperemic flow. AF developed in 407/5797 participants in the tonometry sample and 270/3921 participants in the endothelial function sample during follow-up (median 7.1 years, maximum 10 years). Higher augmentation index (hazard ratio, 1.16; 95% confidence interval, 1.02-1.32; P=0.02), baseline brachial artery diameter (hazard ratio, 1.20; 95% confidence interval, 1.01-1.43; P=0.04), and lower flow-mediated dilation (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99; P=0.04) were associated with increased risk of incident AF. Central pulse pressure, when adjusted for age, sex, and hypertension (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28; P=0.02) was associated with incident AF. Higher pulsatile load assessed by central pulse pressure and greater apparent wave reflection measured by augmentation index were associated with increased risk of incident AF. Vascular endothelial dysfunction may precede development of AF. These measures may be additional risk factors or markers of subclinical cardiovascular disease associated with increased risk of incident AF. © 2016 American Heart Association, Inc.

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

PubMed

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

2015-02-15

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

Male circumcision and risk of male-to-female HIV-1 transmission: a multinational prospective study in African HIV-1-serodiscordant couples.

PubMed

Baeten, Jared M; Donnell, Deborah; Kapiga, Saidi H; Ronald, Allan; John-Stewart, Grace; Inambao, Mubiana; Manongi, Rachel; Vwalika, Bellington; Celum, Connie

2010-03-13

Male circumcision reduces female-to-male HIV-1 transmission risk by approximately 60%. Data assessing the effect of circumcision on male-to-female HIV-1 transmission are conflicting, with one observational study among HIV-1-serodiscordant couples showing reduced transmission but a randomized trial suggesting no short-term benefit of circumcision. Data collected as part of a prospective study among African HIV-1-serodiscordant couples were analyzed for the relationship between circumcision status of HIV-1-seropositive men and risk of HIV-1 acquisition among their female partners. Circumcision status was determined by physical examination. Cox proportional hazards analysis was used. A total of 1096 HIV-1-serodiscordant couples in which the male partner was HIV-1-infected were followed for a median of 18 months; 374 (34%) male partners were circumcised. Sixty-four female partners seroconverted to HIV-1 (incidence 3.8 per 100 person-years). Circumcision of the male partner was associated with a nonstatistically significant approximately 40% lower risk of HIV-1 acquisition by the female partner (hazard ratio 0.62, 95% confidence interval 0.35-1.10, P = 0.10). The magnitude of this effect was similar when restricted to the subset of HIV-1 transmission events confirmed by viral sequencing to have occurred within the partnership (n = 50, hazard ratio 0.57, P = 0.11), after adjustment for male partner plasma HIV-1 concentrations (hazard ratio 0.60, P = 0.13), and when excluding follow-up time for male partners who initiated antiretroviral therapy (hazard ratio 0.53, P = 0.07). Among HIV-1-serodiscordant couples in which the HIV-1-seropositive partner was male, we observed no increased risk and potentially decreased risk from circumcision on male-to-female transmission of HIV-1.

Combined effect of blood pressure and total cholesterol levels on long-term risks of subtypes of cardiovascular death: Evidence for Cardiovascular Prevention from Observational Cohorts in Japan.

PubMed

Satoh, Michihiro; Ohkubo, Takayoshi; Asayama, Kei; Murakami, Yoshitaka; Sakurai, Masaru; Nakagawa, Hideaki; Iso, Hiroyasu; Okayama, Akira; Miura, Katsuyuki; Imai, Yutaka; Ueshima, Hirotsugu; Okamura, Tomonori

2015-03-01

No large-scale, longitudinal studies have examined the combined effects of blood pressure (BP) and total cholesterol levels on long-term risks for subtypes of cardiovascular death in an Asian population. To investigate these relationships, a meta-analysis of individual participant data, which included 73 916 Japanese subjects (age, 57.7 years; men, 41.1%) from 11 cohorts, was conducted. During a mean follow-up of 15.0 years, deaths from coronary heart disease, ischemic stroke, and intraparenchymal hemorrhage occurred in 770, 724, and 345 cases, respectively. Cohort-stratified Cox proportional hazard models were used. After stratifying the participants by 4 systolic BP ×4 total cholesterol categories, the group with systolic BP ≥160 mm Hg with total cholesterol ≥5.7 mmol/L had the greatest risk for coronary heart disease death (adjusted hazard ratio, 4.39; P<0.0001 versus group with systolic BP <120 mm Hg and total cholesterol <4.7 mmol/L). The adjusted hazard ratios of systolic BP (per 20 mm Hg) increased with increases in total cholesterol categories (hazard ratio, 1.52; P<0.0001 in group with total cholesterol ≥5.7 mmol/L). Similarly, the adjusted hazard ratios of total cholesterol increased with increases in systolic BP categories (P for interaction ≤0.04). Systolic BP was positively associated with ischemic stroke and intraparenchymal hemorrhage death, and total cholesterol was inversely associated with intraparenchymal hemorrhage, but no significant interactions between BP and total cholesterol were observed for stroke. High BP and high total cholesterol can synergistically increase the risk for coronary heart disease death but not for stroke in the Asian population. © 2015 American Heart Association, Inc.

Association between divorce and risks for acute myocardial infarction.

PubMed

Dupre, Matthew E; George, Linda K; Liu, Guangya; Peterson, Eric D

2015-05-01

Divorce is a major life stressor that can have economic, emotional, and physical health consequences. However, the cumulative association between divorce and risks for acute myocardial infarction (AMI) is unknown. This study investigated the association between lifetime exposure to divorce and the incidence of AMI in US adults. We used nationally representative data from a prospective cohort of ever-married adults aged 45 to 80 years (n=15,827) who were followed biennially from 1992 to 2010. Approximately 14% of men and 19% of women were divorced at baseline and more than one third of the cohort had ≥1 divorce in their lifetime. In 200,524 person-years of follow-up, 8% (n=1211) of the cohort had an AMI and age-specific rates of AMI were consistently higher in those who were divorced compared with those who were continuously married (P<0.05). Results from competing-risk hazard models showed that AMI risks were significantly higher in women who had 1 divorce (hazard ratio, 1.24; 95% confidence interval, 1.01-1.55), ≥2 divorces (hazard ratio, 1.77; 95% confidence interval, 1.30-2.41), and among the remarried (hazard ratio, 1.35; 95% confidence interval, 1.07-1.70) compared with continuously married women after adjusting for multiple risk factors. Multivariable-adjusted risks were elevated only in men with a history of ≥2 divorces (hazard ratio, 1.30; 95% confidence interval, 1.02-1.66) compared with continuously married men. Men who remarried had no significant risk for AMI. Interaction terms for sex were not statistically significant. Divorce is a significant risk factor for AMI. The risks associated with multiple divorces are especially high in women and are not reduced with remarriage. © 2015 American Heart Association, Inc.

Increased risk of pernicious anemia following scabies: a nationwide population-based matched-cohort study.

PubMed

Liu, Jui-Ming; Hsu, Ren-Jun; Chang, Fung-Wei; Chiu, Feng-Hsiang; Yeh, Chia-Lun; Huang, Chun-Fa; Chang, Shu-Ting; Lee, Hung-Chang; Chi, Hsin; Lin, Chien-Yu

2017-01-01

Scabies is a common and annoying disorder. Pernicious anemia (PA) is a serious disease which, when untreated, leads to death. Mounting evidence suggests that immune-mediated inflammatory processes play a role in the pathophysiology of both diseases. The relationship between these two diseases has not been investigated. We conducted this study to explore the potential relationship between scabies and PA. This nationwide, population-based study was conducted using the National Health Insurance Research Database of Taiwan. In total, 5,407 patients with scabies were identified as a study group and 20,089 matched patients were randomly selected as a control group. We tracked patients in both groups for a 7-year period to identify the incidence of PA. The demographic characteristics and comorbidities of the patients were analyzed, and Cox proportional hazards regression was used to calculate the hazard ratios for PA. Of the 25,496 patients in this study, 183 (0.7%) patients with newly diagnosed PA were identified during the 7-year follow-up period; 71 of 5,407 (1.3%) from the scabies group and 112 of 20,089 (0.6%) from the control group. Patients with scabies had a higher risk of subsequent PA, with a crude hazard ratio of 2.368. After adjusting for covariates, the adjusted hazard ratio was 1.51 (95% confidence interval: 1.09-2.08). This study demonstrated an increased risk of PA (adjusted hazard ratio 1.51) among patients with scabies. Immune-mediated inflammatory processes may contribute to this association. Further studies are warranted to investigate the entire pathological mechanisms between these two diseases. Physicians should pay attention to patients with history of scabies presented with anemia. Further confirmative tests of PA may contribute to correct diagnosis and initiation of vitamin B12 supplement.

An Estimation of Mortality Risks among People Living with HIV in Karnataka State, India: Learnings from an Intensive HIV/AIDS Care and Support Programme

PubMed Central

Prakash, Ravi; Isac, Shajy; Washington, Reynold; Halli, Shiva S.

2016-01-01

Background In Indian context, limited attempts have been made to estimate the mortality risks among people living with HIV (PLHIV). We estimated the rates of mortality among PLHIV covered under an integrated HIV-prevention cum care and support programme implemented in Karnataka state, India, and attempted to identify the key programme components associated with the higher likelihood of their survival. Methods Retrospective programme data of 55,801 PLHIV registered with the Samastha programme implemented in Karnataka state during 2006–11 was used. Kaplan-Meier survival methods were used to estimate the ten years expected survival probabilities and Cox-proportional hazard model was used to examine the factors associated with risk of mortality among PLHIV. We also calculated mortality rates (per 1000 person-year) across selected demographic and clinical parameters. Results Of the total PLHIV registered with the programme, about nine percent died within the 5-years of programme period with an overall death rate of 38 per 1000 person-years. The mortality rate was higher among males, aged 18 and above, among illiterates, and those residing in rural areas. While the presence of co-infections such as Tuberculosis leads to higher mortality rate, adherence to ART was significantly associated with reduction in overall death rate. Cox proportional hazard model revealed that increase in CD4 cell counts and exposure to intensive care and support programme for at least two years can bring significant reduction in risk of death among PLHIV [(hazard ratio: 0.234; CI: 0.211–0.260) & (hazard ratio: 0.062; CI: 0.054–0.071), respectively] even after adjusting the effect of other socio-demographic, economic and health related confounders. Conclusion Study confirms that while residing in rural areas and presence of co-infection significantly increases the mortality risk among PLHIV, adherence to ART and improvement in CD4 counts led to significant reduction in their mortality risk. Longer exposure to the intervention contributed significantly to reduce mortality among PLHIV. PMID:27253974

All-Cause Mortality After Fertility-Sparing Surgery for Stage I Epithelial Ovarian Cancer.

PubMed

Melamed, Alexander; Rizzo, Anthony E; Nitecki, Roni; Gockley, Allison A; Bregar, Amy J; Schorge, John O; Del Carmen, Marcela G; Rauh-Hain, J Alejandro

2017-07-01

To compare all-cause mortality between women who underwent fertility-sparing surgery with those who underwent conventional surgery for stage I ovarian cancer. In a cohort study using the National Cancer Database, we identified women younger than 40 years diagnosed with stage IA and unilateral IC epithelial ovarian cancer between 2004 and 2012. Fertility-sparing surgery was defined as conservation of one ovary and the uterus. The primary outcome was time from diagnosis to death. We used propensity score methods to assemble a cohort of women who underwent fertility-sparing or conventional surgery but were otherwise similar on observed covariates and conducted survival analyses using the Kaplan-Meier method and Cox proportional hazard models. We identified 1,726 women with stage IA and unilateral IC epithelial ovarian cancer of whom 825 (47.8%) underwent fertility-sparing surgery. Fertility-sparing surgery was associated with younger age, residence in the northeastern and western United States, and serous or mucinous histology (P<.05 for all). Propensity score matching yielded a cohort of 904 women who were balanced on observed covariates. We observed 30 deaths among women who underwent fertility-sparing surgery and 37 deaths among propensity-matched women who underwent conventional surgery after a median follow-up of 63 months. Fertility-sparing surgery was not associated with hazard of death (hazard ratio 0.80, 95% confidence interval [CI] 0.49-1.29, P=.36). The probability of survival 10 years after diagnosis was 88.5% (95% CI 82.4-92.6) in the fertility-sparing group and 88.9% (95% CI 84.9-92.0) in the conventional surgery group. In patients with high-risk features such as clear cell histology, grade 3, or stage IC, 10-year survival was 80.5% (95% CI 68.5-88.3) among women who underwent fertility-sparing surgery and 83.4% (95% 76.0-88.7) among those who had conventional surgery (hazard ratio 0.86, 95% CI 0.49-1.53, P=.61). Compared with conventional surgery, fertility-sparing surgery was not associated with increased risk of death in young women with stage I epithelial ovarian cancer.

Influence of the Extent and Dose of Radiation on Complications After Neoadjuvant Chemoradiation and Subsequent Esophagectomy With Gastric Tube Reconstruction With a Cervical Anastomosis

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

Koëter, M.; Kathiravetpillai, N.; Gooszen, J.A.

Purpose: To determine, in a large series, the influence of the extent and dose of radiation to the fundus of the stomach and mediastinum on the development and severity of anastomotic complications in patients with esophageal cancer treated with neoadjuvant chemoradiation followed by esophagectomy with cervical anastomosis. Methods and Materials: Between 2005 and 2012, 364 consecutive patients with esophageal cancer treated with neoadjuvant chemoradiation (41.4 Gy combined with chemotherapy) followed by esophagectomy were included. The future anastomotic region in the fundus was determined, and the mean dose, V20-V40, and upper planning target volume border in relation to mediastinal length, expressed as themore » mediastinal ratio, were calculated. Results: Anastomotic leakage occurred in 22% and anastomotic stenosis in 41%. Logistic regression analysis revealed no influence of age, comorbidity, mean fundus dose, V20-V40, or the mediastinal ratio on the incidence of anastomotic leakage or anastomotic stenosis. In 28% of the patients severe complications (Clavien-Dindo score of ≥IIIB) occurred. The presence of multiple comorbidities (hazard ratio 2.4 [95% confidence interval 1.3-4.5], P=.006) and a mediastinal ratio of 0.5 to 1.0 (hazard ratio 1.9 [95% confidence interval 1.0-3.5], P=.036) were both independent predictors of severe complications. Conclusion: With a mean radiation dose of 24.2 Gy to the future anastomotic region of the gastric fundus, the radiation dose was not associated with the incidence of anastomotic leakage or anastomotic stenosis. The incidence of severe complications was associated with a high superior mediastinal planning target volume border.« less

Blood Urea Nitrogen/Creatinine Ratio Identifies a High-Risk but Potentially Reversible Form of Renal Dysfunction in Patients With Decompensated Heart Failure

PubMed Central

Brisco, Meredith A.; Coca, Steven G.; Chen, Jennifer; Owens, Anjali Tiku; McCauley, Brian D.; Kimmel, Stephen E.; Testani, Jeffrey M.

2014-01-01

Background Identifying reversible renal dysfunction (RD) in the setting of heart failure is challenging. The goal of this study was to evaluate whether elevated admission blood urea nitrogen/creatinine ratio (BUN/Cr) could identify decompensated heart failure patients likely to experience improvement in renal function (IRF) with treatment. Methods and Results Consecutive hospitalizations with a discharge diagnosis of heart failure were reviewed. IRF was defined as ≥20% increase and worsening renal function as ≥20% decrease in estimated glomerular filtration rate. IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with inhospital IRF (odds ratio, 1.5 per 10 increase; 95% confidence interval [CI], 1.3–1.8; P<0.001), an association persisting after adjustment for baseline characteristics (odds ratio, 1.4; 95% CI, 1.1–1.8; P=0.004). However, higher admission BUN/Cr was also associated with post-discharge worsening renal function (odds ratio, 1.4; 95% CI, 1.1–1.8; P=0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (estimated glomerular filtration rate <45) was substantial (hazard ratio, 2.2; 95% CI, 1.6–3.1; P<0.001). However, in patients with a normal admission BUN/Cr, RD was not associated with increased mortality (hazard ratio, 1.2; 95% CI, 0.67–2.0; P=0.59; p interaction=0.03). Conclusions An elevated admission BUN/Cr identifies decompensated patients with heart failure likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement seems to be largely transient, and RD, in the setting of an elevated BUN/Cr, remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients. PMID:23325460

Diagnosis and mortality in 47,XYY persons: a registry study

PubMed Central

2010-01-01

Background Sex chromosomal abnormalities are relatively common, yet many aspects of these syndromes remain unexplored. For instance epidemiological data in 47,XYY persons are still limited. Methods Using a national Danish registry, we identified 208 persons with 47,XYY or a compatible karyotype, whereof 36 were deceased; all were diagnosed from 1968 to 2008. For further analyses, we identified age matched controls from the male background population (n = 20,078) in Statistics Denmark. We report nationwide prevalence data, data regarding age at diagnosis, as well as total and cause specific mortality data in these persons. Results The average prevalence was 14.2 47,XYY persons per 100,000, which is reduced compared to the expected 98 per 100,000. Their median age at diagnosis was 17.1 years. We found a significantly decreased lifespan from 77.9 years (controls) to 67.5 years (47,XYY persons). Total mortality was significantly increased compared to controls, with a hazard ratio of 3.6 (2.6-5.1). Dividing the causes of deaths according to the International Classification of Diseases, we identified an increased hazard ratio in all informative chapters, with a significantly increased ratio in cancer, pulmonary, neurological and unspecified diseases, and trauma. Conclusion We here present national epidemiological data regarding 47,XYY syndrome, including prevalence and mortality data, showing a significantly delay to diagnosis, reduced life expectancy and an increased total and cause specific mortality. PMID:20509956

Outcomes of Kidney Transplantation in HIV-Infected Recipients

PubMed Central

Stock, Peter G.; Barin, Burc; Murphy, Barbara; Hanto, Douglas; Diego, Jorge M.; Light, Jimmy; Davis, Charles; Blumberg, Emily; Simon, David; Subramanian, Aruna; Millis, J. Michael; Lyon, G. Marshall; Brayman, Kenneth; Slakey, Doug; Shapiro, Ron; Melancon, Joseph; Jacobson, Jeffrey M.; Stosor, Valentina; Olson, Jean L.; Stablein, Donald M.; Roland, Michelle E.

2010-01-01

BACKGROUND The outcomes of kidney transplantation and immunosuppression in people infected with human immunodeficiency virus (HIV) are incompletely understood. METHODS We undertook a prospective, nonrandomized trial of kidney transplantation in HIV-infected candidates who had CD4+ T-cell counts of at least 200 per cubic millimeter and undetectable plasma HIV type 1 (HIV-1) RNA levels while being treated with a stable antiretroviral regimen. Post-transplantation management was provided in accordance with study protocols that defined prophylaxis against opportunistic infection, indications for biopsy, and acceptable approaches to immunosuppression, management of rejection, and antiretroviral therapy. RESULTS Between November 2003 and June 2009, a total of 150 patients underwent kidney transplantation; survivors were followed for a median period of 1.7 years. Patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90.4% and 73.7%. In general, these rates fall somewhere between those reported in the national database for older kidney-transplant recipients (≥65 years) and those reported for all kidney-transplant recipients. A multivariate proportional-hazards analysis showed that the risk of graft loss was increased among patients treated for rejection (hazard ratio, 2.8; 95% confidence interval [CI], 1.2 to 6.6; P = 0.02) and those receiving antithymocyte globulin induction therapy (hazard ratio, 2.5; 95% CI, 1.1 to 5.6; P = 0.03); living-donor transplants were protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.8; P = 0.02). A higher-than-expected rejection rate was observed, with 1-year and 3-year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52), respectively. HIV infection remained well controlled, with stable CD4+ T-cell counts and few HIV-associated complications. CONCLUSIONS In this cohort of carefully selected HIV-infected patients, both patient- and graft-survival rates were high at 1 and 3 years, with no increases in complications associated with HIV infection. The unexpectedly high rejection rates are of serious concern and indicate the need for better immunotherapy. PMID:21083386

Sleep-Disordered Breathing and Mortality: A Prospective Cohort Study

PubMed Central

Punjabi, Naresh M.; Caffo, Brian S.; Goodwin, James L.; Gottlieb, Daniel J.; Newman, Anne B.; O'Connor, George T.; Rapoport, David M.; Redline, Susan; Resnick, Helaine E.; Robbins, John A.; Shahar, Eyal; Unruh, Mark L.; Samet, Jonathan M.

2009-01-01

Background Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older. Methods and Findings We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea–hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: <5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0–14.9 events/h), moderate (AHI: 15.0–29.9 events/h), and severe (AHI: ≥30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80–1.08), 1.17 (95% CI: 0.97–1.42), and 1.46 (95% CI: 1.14–1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40–70 y (hazard ratio: 2.09; 95% CI: 1.31–3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease–related mortality associated with sleep-disordered breathing showed a pattern of association similar to all-cause mortality. Conclusions Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40–70 y with severe sleep-disordered breathing. Please see later in the article for the Editors' Summary PMID:19688045

Survival After MI in a Community Cohort Study Contribution of Comorbidities in NSTEMI

PubMed Central

Foraker, Randi E.; Guha, Avirup; Chang, Henry; O’Brien, Emily C.; Bower, Julie K.; Crouser, Elliott D.; Rosamond, Wayne D.; Raman, Subha V.

2018-01-01

Background Non–ST-segment elevation myocardial infarction (NSTEMI) comprises the majority of MI worldwide, yet mortality remains high. Management of NSTEMI is relatively delayed and heterogeneous compared with the “time is muscle” approach to ST-segment elevation MI, though it is unknown to what extent comorbid conditions drive NSTEMI mortality. Objectives We sought to quantify mortality due to MI versus comorbid conditions in patients with NSTEMI. Methods Participants of the ARIC (Atherosclerosis Risk in Communities) study cohort ages 45 to 64 years, who developed incident NSTEMI were identified and incidence-density matched to participants who did not experience an MI by age group, sex, race, and study community. We estimated hazard ratios for all-cause mortality, comparing those who developed NSTEMI to those who did not experience an MI. Results ARIC participants with incident NSTEMI were more likely at baseline to be smokers, have diabetes and renal dysfunction, and take blood pressure or cholesterol-lowering medications than were participants who did not have an MI. Over one-half of participants experiencing NSTEMI died over a median follow-up of 8.4 years; incident NSTEMI was associated with 30% higher risk of mortality after adjusting for comorbid conditions (hazard ratio: 1.30; 95% confidence interval: 1.11 to 1.53). Conclusions NSTEMI confers a significantly higher mortality hazard beyond what can be attributed to comorbid conditions. More consistent and effective strategies are needed to reduce mortality in NSTEMI amid comorbid conditions. PMID:29409724

Genome-wide Association Study Implicates PARD3B-based AIDS Restriction

PubMed Central

Nelson, George W.; Lautenberger, James A.; Chinn, Leslie; McIntosh, Carl; Johnson, Randall C.; Sezgin, Efe; Kessing, Bailey; Malasky, Michael; Hendrickson, Sher L.; Pontius, Joan; Tang, Minzhong; An, Ping; Winkler, Cheryl A.; Limou, Sophie; Le Clerc, Sigrid; Delaneau, Olivier; Zagury, Jean-François; Schuitemaker, Hanneke; van Manen, Daniëlle; Bream, Jay H.; Gomperts, Edward D.; Buchbinder, Susan; Goedert, James J.; Kirk, Gregory D.; O'Brien, Stephen J.

2011-01-01

Background. Host genetic variation influences human immunodeficiency virus (HIV) infection and progression to AIDS. Here we used clinically well-characterized subjects from 5 pretreatment HIV/AIDS cohorts for a genome-wide association study to identify gene associations with rate of AIDS progression. Methods.  European American HIV seroconverters (n = 755) were interrogated for single-nucleotide polymorphisms (SNPs) (n = 700,022) associated with progression to AIDS 1987 (Cox proportional hazards regression analysis, co-dominant model). Results.  Association with slower progression was observed for SNPs in the gene PARD3B. One of these, rs11884476, reached genome-wide significance (relative hazard = 0.3; P =3. 370 × 10−9) after statistical correction for 700,022 SNPs and contributes 4.52% of the overall variance in AIDS progression in this study. Nine of the top-ranked SNPs define a PARD3B haplotype that also displays significant association with progression to AIDS (hazard ratio, 0.3; P = 3.220 × 10−8). One of these SNPs, rs10185378, is a predicted exonic splicing enhancer; significant alteration in the expression profile of PARD3B splicing transcripts was observed in B cell lines with alternate rs10185378 genotypes. This SNP was typed in European cohorts of rapid progressors and was found to be protective for AIDS 1993 definition (odds ratio, 0.43, P = .025). Conclusions. These observations suggest a potential unsuspected pathway of host genetic influence on the dynamics of AIDS progression. PMID:21502085

Prognosis of Parkinson disease: risk of dementia and mortality: the Rotterdam Study.

PubMed

de Lau, Lonneke M L; Schipper, C Maarten A; Hofman, Albert; Koudstaal, Peter J; Breteler, Monique M B

2005-08-01

Most prognostic studies on Parkinson disease have been hospital based or have applied register-based case-finding methods. Potential under-representation of mild cases may have given biased results. To evaluate whether Parkinson disease is associated with an increased risk of dementia and death. Population-based cohort study. Parkinson disease and dementia were assessed through in-person examination at baseline (1990-1993) and 2 follow-up visits (1993-1994 and 1997-1999). Computerized linkage to medical and municipality records provided additional information on disease outcomes and mortality. General population. A total of 6969 participants, including 99 prevalent and 67 incident cases of Parkinson disease. Incident dementia and death. Adjusted hazard ratios were calculated through Cox proportional hazards regression analysis. Patients with Parkinson disease had an increased risk of dementia (hazard ratio, 2.8; 95% confidence interval, 1.8-4.4), which was especially pronounced in participants carrying at least 1 apolipoprotein E gene (APOE) epsilon2 allele (13.5; 4.5-40.6). Parkinson disease was associated with an increased mortality risk (1.8; 1.5-2.3). The association consistently diminished when analyses were sequentially restricted to patients with shorter disease duration and after adjustment for the occurrence of dementia. Especially patients with Parkinson disease who carry an APOE epsilon2 allele have an increased risk of developing dementia. Increased mortality risk in Parkinson disease is dependent on disease duration and is only modest in the absence of dementia.

The Effect of Cotrimoxazole Prophylactic Treatment on Malaria, Birth Outcomes, and Postpartum CD4 Count in HIV-Infected Women

PubMed Central

Dow, Anna; Hudgens, Michael G.; Van Rie, Annelies; King, Caroline C.; Ellington, Sascha; Chome, Nelecy; Turner, Abigail Norris; Kacheche, Zebrone; Jamieson, Denise J.; Chasela, Charles; van der Horst, Charles

2013-01-01

Background. Limited data exist on cotrimoxazole prophylactic treatment (CPT) in pregnant women, including protection against malaria versus standard intermittent preventive therapy with sulfadoxine-pyrimethamine (IPTp). Methods. Using observational data we examined the effect of CPT in HIV-infected pregnant women on malaria during pregnancy, low birth weight and preterm birth using proportional hazards, logistic, and log binomial regression, respectively. We used linear regression to assess effect of CPT on CD4 count. Results. Data from 468 CPT-exposed and 768 CPT-unexposed women were analyzed. CPT was associated with protection against malaria versus IPTp (hazard ratio: 0.35, 95% Confidence Interval (CI): 0.20, 0.60). After adjustment for time period this effect was not statistically significant (adjusted hazard ratio: 0.66, 95% CI: 0.28, 1.52). Among women receiving and not receiving CPT, rates of low birth weight (7.1% versus 7.6%) and preterm birth (23.5% versus 23.6%) were similar. CPT was associated with lower CD4 counts 24 weeks postpartum in women receiving (−77.6 cells/μL, 95% CI: −125.2, −30.1) and not receiving antiretrovirals (−33.7 cells/μL, 95% CI: −58.6, −8.8). Conclusions. Compared to IPTp, CPT provided comparable protection against malaria in HIV-infected pregnant women and against preterm birth or low birth weight. Possible implications of CPT-associated lower CD4 postpartum warrant further examination. PMID:24363547

Characterization of airborne float coal dust emitted during continuous mining, longwall mining and belt transport

PubMed Central

Shahan, M.R.; Seaman, C.E.; Beck, T.W.; Colinet, J.F.; Mischler, S.E.

2017-01-01

Float coal dust is produced by various mining methods, carried by ventilating air and deposited on the floor, roof and ribs of mine airways. If deposited, float dust is re-entrained during a methane explosion. Without sufficient inert rock dust quantities, this float coal dust can propagate an explosion throughout mining entries. Consequently, controlling float coal dust is of critical interest to mining operations. Rock dusting, which is the adding of inert material to airway surfaces, is the main control technique currently used by the coal mining industry to reduce the float coal dust explosion hazard. To assist the industry in reducing this hazard, the Pittsburgh Mining Research Division of the U.S. National Institute for Occupational Safety and Health initiated a project to investigate methods and technologies to reduce float coal dust in underground coal mines through prevention, capture and suppression prior to deposition. Field characterization studies were performed to determine quantitatively the sources, types and amounts of dust produced during various coal mining processes. The operations chosen for study were a continuous miner section, a longwall section and a coal-handling facility. For each of these operations, the primary dust sources were confirmed to be the continuous mining machine, longwall shearer and conveyor belt transfer points, respectively. Respirable and total airborne float dust samples were collected and analyzed for each operation, and the ratio of total airborne float coal dust to respirable dust was calculated. During the continuous mining process, the ratio of total airborne float coal dust to respirable dust ranged from 10.3 to 13.8. The ratios measured on the longwall face were between 18.5 and 21.5. The total airborne float coal dust to respirable dust ratio observed during belt transport ranged between 7.5 and 21.8. PMID:28936001

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

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

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

2011-12-01

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

Impact of lymph node ratio on survival in stage III ovarian high-grade serous cancer: a Turkish Gynecologic Oncology Group study

PubMed Central

2018-01-01

Objective The purpose of this study was to investigate the prognostic value of lymph node ratio (LNR) in patients with stage III ovarian high-grade serous carcinoma (HGSC). Methods A multicenter, retrospective department database review was performed to identify patients with ovarian HGSC at 6 gynecologic oncology centers in Turkey. A total of 229 node-positive women with stage III ovarian HGSC who had undergone maximal or optimal cytoreductive surgery plus systematic lymphadenectomy followed by paclitaxel plus carboplatin combination chemotherapy were included. LNR, defined as the percentage of positive lymph nodes (LNs) to total nodes recovered, was stratified into 3 groups: LNR1 (<10%), LNR2 (10%≤LNR<50%), and LNR3 (≥50%). Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analyzed using Cox proportional hazards models. Results Thirty-one women (13.6%) were classified as stage IIIA1, 15 (6.6%) as stage IIIB, and 183 (79.9%) as stage IIIC. The median age at diagnosis was 56 (range, 18–87), and the median duration of follow-up was 36 months (range, 1–120 months). For the entire cohort, the 5-year overall survival (OS) was 52.8%. An increased LNR was associated with a decrease in 5-year OS from 65.1% for LNR1, 42.5% for LNR2, and 25.6% for LNR3, respectively (p<0.001). In multivariate analysis, women with LNR≥0.50 were 2.7 times more likely to die of their tumors (hazard ratio [HR]=2.7; 95% confidence interval [CI]=1.42–5.18; p<0.001). Conclusion LNR seems to be an independent prognostic factor for decreased OS in stage III ovarian HGSC patients. PMID:29185270

Prognostic impact of the pretreatment aspartate transaminase/alanine transaminase ratio in patients treated with first-line systemic tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma.

PubMed

Kang, Minyong; Yu, Jiwoong; Sung, Hyun Hwan; Jeon, Hwang Gyun; Jeong, Byong Chang; Park, Se Hoon; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han Yong; Seo, Seong Il

2018-05-13

To examine the prognostic role of the pretreatment aspartate transaminase/alanine transaminase or De Ritis ratio in patients with metastatic renal cell carcinoma receiving first-line systemic tyrosine kinase inhibitor therapy. We retrospectively searched the medical records of 579 patients with metastatic renal cell carcinoma who visited Samsung Medical Center, Seoul, Korea, from January 2001 through August 2016. After excluding 210 patients, we analyzed 360 patients who received first-line tyrosine kinase inhibitor therapy. Cancer-specific survival and overall survival were defined as the primary and secondary end-points, respectively. A multivariate Cox proportional hazards regression model was used to identify independent prognosticators of survival outcomes. The overall population was divided into two groups according to the pretreatment De Ritis ratio as an optimal cut-off value of 1.2, which was determined by a time-dependent receiver operating characteristic curve analysis. Patients with a higher pretreatment De Ritis ratio (≥1.2) had worse cancer-specific survival and overall survival outcomes, compared with those with a lower De Ritis ratio (<1.2). Notably, a higher De Ritis ratio (≥1.2) was found to be an independent predictor of both cancer-specific survival (hazard ratio 1.61, 95% confidence interval 1.13-2.30) and overall survival outcomes (hazard ratio 1.69, 95% confidence interval 1.19-2.39), along with male sex, multiple metastasis (≥2), non-clear cell histology, advanced pT stage (≥3), previous metastasectomy and the Memorial Sloan Kettering Cancer Center risk classification. Our findings show that the pretreatment De Ritis ratio can provide valuable information about the survival outcomes of metastatic renal cell carcinoma patients receiving first-line tyrosine kinase inhibitor therapy. © 2018 The Japanese Urological Association.

Aluminum phosphate ceramics for waste storage

DOEpatents

Wagh, Arun; Maloney, Martin D

2014-06-03

The present disclosure describes solid waste forms and methods of processing waste. In one particular implementation, the invention provides a method of processing waste that may be particularly suitable for processing hazardous waste. In this method, a waste component is combined with an aluminum oxide and an acidic phosphate component in a slurry. A molar ratio of aluminum to phosphorus in the slurry is greater than one. Water in the slurry may be evaporated while mixing the slurry at a temperature of about 140-200.degree. C. The mixed slurry may be allowed to cure into a solid waste form. This solid waste form includes an anhydrous aluminum phosphate with at least a residual portion of the waste component bound therein.

Impact of breast cancer subtypes on 3-year survival among adolescent and young adult women

PubMed Central

2013-01-01

Introduction Young women have poorer survival after breast cancer than do older women. It is unclear whether this survival difference relates to the unique distribution of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2)-defined molecular breast cancer subtypes among adolescent and young adult (AYA) women aged 15 to 39 years. The purpose of our study was to examine associations between breast cancer subtypes and short-term survival in AYA women, as well as to determine whether the distinct molecular subtype distribution among AYA women explains the unfavorable overall breast cancer survival statistics reported for AYA women compared with older women. Methods Data for 5,331 AYA breast cancers diagnosed between 2005 and 2009 were obtained from the California Cancer Registry. Survival by subtype (triple-negative; HR+/HER2-; HR+/HER2+; HR-/HER2+) and age-group (AYA versus 40- to 64-year-olds) was analyzed with Cox proportional hazards regression with follow-up through 2010. Results With up to 6 years of follow-up and a mean survival time of 3.1 years (SD = 1.5 years), AYA women diagnosed with HR-/HER + and triple-negative breast cancer experienced a 1.6-fold and 2.7-fold increased risk of death, respectively, from all causes (HR-/HER + hazard ratio: 1.55; 95% confidence interval (CI): 1.10 to 2.18; triple-negative HR: 2.75; 95% CI, 2.06 to 3.66) and breast cancer (HR-/HER + hazard ratio: 1.63; 95% CI, 1.12 to 2.36; triple-negative hazard ratio: 2.71; 95% CI, 1.98 to 3.71) than AYA women with HR+/HER2- breast cancer. AYA women who resided in lower socioeconomic status neighborhoods, had public health insurance, and were of Black, compared with White, race/ethnicity experienced worse survival. This race/ethnicity association was attenuated somewhat after adjusting for breast cancer subtypes (hazard ratio, 1.33; 95% CI, 0.98 to 1.82). AYA women had similar all-cause and breast cancer-specific short-term survival as older women for all breast cancer subtypes and across all stages of disease. Conclusions Among AYA women with breast cancer, short-term survival varied by breast cancer subtypes, with the distribution of breast cancer subtypes explaining some of the poorer survival observed among Black, compared with White, AYA women. Future studies should consider whether distribution of breast cancer subtypes and other factors, including differential receipt of treatment regimens, influences long-term survival in young compared with older women. PMID:24131591

Effects of Antiretroviral Therapy and Depressive Symptoms on All-Cause Mortality Among HIV-Infected Women

PubMed Central

Todd, Jonathan V.; Cole, Stephen R.; Pence, Brian W.; Lesko, Catherine R.; Bacchetti, Peter; Cohen, Mardge H.; Feaster, Daniel J.; Gange, Stephen; Griswold, Michael E.; Mack, Wendy; Rubtsova, Anna; Wang, Cuiwei; Weedon, Jeremy; Anastos, Kathryn; Adimora, Adaora A.

2017-01-01

Abstract Depression affects up to 30% of human immunodeficiency virus (HIV)-infected individuals. We estimated joint effects of antiretroviral therapy (ART) initiation and depressive symptoms on time to death using a joint marginal structural model and data from a cohort of HIV-infected women from the Women's Interagency HIV Study (conducted in the United States) from 1998–2011. Among 848 women contributing 6,721 years of follow-up, 194 participants died during follow-up, resulting in a crude mortality rate of 2.9 per 100 women-years. Cumulative mortality curves indicated greatest mortality for women who reported depressive symptoms and had not initiated ART. The hazard ratio for depressive symptoms was 3.38 (95% confidence interval (CI): 2.15, 5.33) and for ART was 0.47 (95% CI: 0.31, 0.70). Using a reference category of women without depressive symptoms who had initiated ART, the hazard ratio for women with depressive symptoms who had initiated ART was 3.60 (95% CI: 2.02, 6.43). For women without depressive symptoms who had not started ART, the hazard ratio was 2.36 (95% CI: 1.16, 4.81). Among women reporting depressive symptoms who had not started ART, the hazard ratio was 7.47 (95% CI: 3.91, 14.3). We found a protective effect of ART initiation on mortality, as well as a harmful effect of depressive symptoms, in a cohort of HIV-infected women. PMID:28430844

Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation.

PubMed

Kim, Sung-Yong; Le Rademacher, Jennifer; Antin, Joseph H; Anderlini, Paolo; Ayas, Mouhab; Battiwalla, Minoo; Carreras, Jeanette; Kurtzberg, Joanne; Nakamura, Ryotaro; Eapen, Mary; Deeg, H Joachim

2014-12-01

A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patients with de novo myelodysplastic syndrome. There was no difference in overall survival. There were no significant differences with regard to 5-year probabilities of relapse, non-relapse mortality, relapse-free survival and overall survival; these were 14%, 40%, 46% and 49% for post-aplastic anemia myelodysplastic syndrome, and 20%, 33%, 47% and 49% for de novo myelodysplastic syndrome, respectively. In multivariate analysis, relapse (hazard ratio 0.71; P=0.18), non-relapse mortality (hazard ratio 1.28; P=0.18), relapse-free survival (hazard ratio 0.97; P=0.80) and overall survival (hazard ratio 1.02; P=0.88) of post-aplastic anemia myelodysplastic syndrome were similar to those of patients with de novo myelodysplastic syndrome. Cytogenetic risk was independently associated with overall survival in both groups. Thus, transplant success in patients with post-aplastic anemia myelodysplastic syndrome was similar to that in patients with de novo myelodysplastic syndrome, and cytogenetics was the only significant prognostic factor for post-aplastic anemia myelodysplastic syndrome patients. Copyright© Ferrata Storti Foundation.

Tea, coffee, carbonated soft drinks and upper gastrointestinal tract cancer risk in a large United States prospective cohort study.

PubMed

Ren, J S; Freedman, N D; Kamangar, F; Dawsey, S M; Hollenbeck, A R; Schatzkin, A; Abnet, C C

2010-07-01

The authors investigated the relationship between hot tea, iced tea, coffee and carbonated soft drinks consumption and upper gastrointestinal tract cancers risk in the NIH-AARP Study. During 2,584,953 person-years of follow-up on 481,563 subjects, 392 oral cavity, 178 pharynx, 307 larynx, 231 gastric cardia, 224 gastric non-cardia cancer, 123 Oesophageal Squamous Cell Carcinoma (ESCC) and 305 Oesophageal Adenocarcinoma (EADC) cases were accrued. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated by multivariate-adjusted Cox regression. Compared to non-drinking, the hazard ratio for hot tea intake of > or =1 cup/day was 0.37 (95% CI: 0.20, 0.70) for pharyngeal cancer. The authors also observed a significant association between coffee drinking and risk of gastric cardia cancer (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 1.57 (95% CI: 1.03, 2.39)), and an inverse association between coffee drinking and EADC for the cases occurring in the last 3 years of follow-up (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 0.54 (95% CI: 0.31, 0.92)), but no association in earlier follow-up. In summary, hot tea intake was inversely associated with pharyngeal cancer, and coffee was directly associated with gastric cardia cancer, but was inversely associated with EADC during some follow-up periods. Published by Elsevier Ltd.

Tea, coffee, carbonated soft drinks and upper gastrointestinal tract cancer risk in a large United States prospective cohort study

PubMed Central

Ren, JS; Freedman, ND; Kamangar, F; Dawsey, SM; Hollenbeck, AR; Schatzkin, A; Abnet, CC

2010-01-01

The authors investigated the relationship between hot tea, iced tea, coffee and carbonated soft drinks consumption and upper gastrointestinal tract cancers risk in the NIH-AARP Study. During 2,584,953 person-years of follow-up on 481,563 subjects, 392 oral cavity, 178 pharynx, 307 larynx, 231 gastric cardia, 224 gastric noncardia cancer, 123 esophageal squamous cell carcinoma (ESCC) and 305 esophageal adenocarcinoma (EADC) cases were accrued. Hazard ratios (HRs) and 95% Confidence Intervals (95%CIs) were calculated by multivariate-adjusted Cox regression. Compared to non-drinking, the hazard ratio for hot tea intake of ≥1 cup/day was 0.37 (95%CI: 0.20, 0.70) for pharyngeal cancer. The authors also observed a significant association between coffee drinking and risk of gastric cardia cancer (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 1.57 (95%CI: 1.03, 2.39)), and an inverse association between coffee drinking and EADC for the cases occurring in the last three years of follow-up (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 0.54 (95%CI: 0.31, 0.92)), but no association in earlier follow-up. In summary, hot tea intake was inversely associated with pharyngeal cancer, and coffee was directly associated with gastric cardia cancer, but was inversely associated with EADC during some follow-up periods. PMID:20395127

Anthropometry and the Risk of Lung Cancer in EPIC.

PubMed

Dewi, Nikmah Utami; Boshuizen, Hendriek C; Johansson, Mattias; Vineis, Paolo; Kampman, Ellen; Steffen, Annika; Tjønneland, Anne; Halkjær, Jytte; Overvad, Kim; Severi, Gianluca; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Kaaks, Rudolf; Li, Kuanrong; Boeing, Heiner; Trichopoulou, Antonia; Bamia, Christina; Klinaki, Eleni; Tumino, Rosario; Palli, Domenico; Mattiello, Amalia; Tagliabue, Giovanna; Peeters, Petra H; Vermeulen, Roel; Weiderpass, Elisabete; Torhild Gram, Inger; Huerta, José María; Agudo, Antonio; Sánchez, María-José; Ardanaz, Eva; Dorronsoro, Miren; Quirós, José Ramón; Sonestedt, Emily; Johansson, Mikael; Grankvist, Kjell; Key, Tim; Khaw, Kay-Tee; Wareham, Nick; Cross, Amanda J; Norat, Teresa; Riboli, Elio; Fanidi, Anouar; Muller, David; Bueno-de-Mesquita, H Bas

2016-07-15

The associations of body mass index (BMI) and other anthropometric measurements with lung cancer were examined in 348,108 participants in the European Investigation Into Cancer and Nutrition (EPIC) between 1992 and 2010. The study population included 2,400 case patients with incident lung cancer, and the average length of follow-up was 11 years. Hazard ratios were calculated using Cox proportional hazard models in which we modeled smoking variables with cubic splines. Overall, there was a significant inverse association between BMI (weight (kg)/height (m)(2)) and the risk of lung cancer after adjustment for smoking and other confounders (for BMI of 30.0-34.9 versus 18.5-25.0, hazard ratio = 0.72, 95% confidence interval: 0.62, 0.84). The strength of the association declined with increasing follow-up time. Conversely, after adjustment for BMI, waist circumference and waist-to-height ratio were significantly positively associated with lung cancer risk (for the highest category of waist circumference vs. the lowest, hazard ratio = 1.25, 95% confidence interval: 1.05, 1.50). Given the decline of the inverse association between BMI and lung cancer over time, the association is likely at least partly due to weight loss resulting from preclinical lung cancer that was present at baseline. Residual confounding by smoking could also have influenced our findings. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios together with age assemble a significant Cox's proportional-hazards regression model for prediction of survival in high-grade gliomas.

PubMed

Roldan-Valadez, Ernesto; Rios, Camilo; Motola-Kuba, Daniel; Matus-Santos, Juan; Villa, Antonio R; Moreno-Jimenez, Sergio

2016-11-01

A long-lasting concern has prevailed for the identification of predictive biomarkers for high-grade gliomas (HGGs) using MRI. However, a consensus of which imaging parameters assemble a significant survival model is still missing in the literature; we investigated the significant positive or negative contribution of several MR biomarkers in this tumour prognosis. A retrospective cohort of supratentorial HGGs [11 glioblastoma multiforme (GBM) and 17 anaplastic astrocytomas] included 28 patients (9 females and 19 males, respectively, with a mean age of 50.4 years, standard deviation: 16.28 years; range: 13-85 years). Oedema and viable tumour measurements were acquired using regions of interest in T 1 weighted, T 2 weighted, fluid-attenuated inversion recovery, apparent diffusion coefficient (ADC) and MR spectroscopy (MRS). We calculated Kaplan-Meier curves and obtained Cox's proportional hazards. During the follow-up period (3-98 months), 17 deaths were recorded. The median survival time was 1.73 years (range, 0.287-8.947 years). Only 3 out of 20 covariates (choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios and age) showed significance in explaining the variability in the survival hazards model; score test: χ 2 (3) = 9.098, p = 0.028. MRS metabolites overcome volumetric parameters of peritumoral oedema and viable tumour, as well as tumour region ADC measurements. Specific MRS ratios (Cho/Naa, L-L/Cr) might be considered in a regular follow-up for these tumours. Advances in knowledge: Cho/Naa ratio is the strongest survival predictor with a log-hazard function of 2.672 in GBM. Low levels of lipids-lactate/Cr ratio represent up to a 41.6% reduction in the risk of death in GBM.

Predictive value of night-time heart rate for cardiovascular events in hypertension. The ABP-International study.

PubMed

Palatini, Paolo; Reboldi, Gianpaolo; Beilin, Lawrence J; Eguchi, Kazuo; Imai, Yutaka; Kario, Kazuomi; Ohkubo, Takayoshi; Pierdomenico, Sante D; Saladini, Francesca; Schwartz, Joseph E; Wing, Lindon; Verdecchia, Paolo

2013-09-30

Data from prospective cohort studies regarding the association between ambulatory heart rate (HR) and cardiovascular events (CVE) are conflicting. To investigate whether ambulatory HR predicts CVE in hypertension, we performed 24-hour ambulatory blood pressure and HR monitoring in 7600 hypertensive patients aged 52 ± 16 years from Italy, U.S.A., Japan, and Australia, included in the 'ABP-International' registry. All were untreated at baseline examination. Standardized hazard ratios for ambulatory HRs were computed, stratifying for cohort, and adjusting for age, gender, blood pressure, smoking, diabetes, serum total cholesterol and serum creatinine. During a median follow-up of 5.0 years there were 639 fatal and nonfatal CVE. In a multivariable Cox model, night-time HR predicted fatal combined with nonfatal CVE more closely than 24h HR (p=0.007 and =0.03, respectively). Daytime HR and the night:day HR ratio were not associated with CVE (p=0.07 and =0.18, respectively). The hazard ratio of the fatal combined with nonfatal CVE for a 10-beats/min increment of the night-time HR was 1.13 (95% CI, 1.04-1.22). This relationship remained significant when subjects taking beta-blockers during the follow-up (hazard ratio, 1.15; 95% CI, 1.05-1.25) or subjects who had an event within 5 years after enrollment (hazard ratio, 1.23; 95% CI, 1.05-1.45) were excluded from analysis. At variance with previous data obtained from general populations, ambulatory HR added to the risk stratification for fatal combined with nonfatal CVE in the hypertensive patients from the ABP-International study. Night-time HR was a better predictor of CVE than daytime HR. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Comparison of five-year outcomes of coronary artery bypass grafting versus percutaneous coronary intervention in patients with left ventricular ejection fractions≤50% versus >50% (from the CREDO-Kyoto PCI/CABG Registry Cohort-2).

PubMed

Marui, Akira; Kimura, Takeshi; Nishiwaki, Noboru; Mitsudo, Kazuaki; Komiya, Tatsuhiko; Hanyu, Michiya; Shiomi, Hiroki; Tanaka, Shiro; Sakata, Ryuzo

2014-10-01

Coronary heart disease is a major risk factor for left ventricular (LV) systolic dysfunction. However, limited data are available regarding long-term benefits of percutaneous coronary intervention (PCI) in the era of drug-eluting stent or coronary artery bypass grafting (CABG) in patients with LV systolic dysfunction with severe coronary artery disease. We identified 3,584 patients with 3-vessel and/or left main disease of 15,939 patients undergoing first myocardial revascularization enrolled in the CREDO-Kyoto PCI/CABG Registry Cohort-2. Of them, 2,676 patients had preserved LV systolic function, defined as an LV ejection fraction (LVEF) of >50% and 908 had impaired LV systolic function (LVEF≤50%). In patients with preserved LV function, 5-year outcomes were not different between PCI and CABG regarding propensity score-adjusted risk of all-cause and cardiac deaths. In contrast, in patients with impaired LV systolic function, the risks of all-cause and cardiac deaths after PCI were significantly greater than those after CABG (hazard ratio 1.49, 95% confidence interval 1.04 to 2.14, p=0.03 and hazard ratio 2.39, 95% confidence interval 1.43 to 3.98, p<0.01). In both patients with moderate (35%

Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.

PubMed

Ridker, Paul M; Danielson, Eleanor; Fonseca, Francisco A H; Genest, Jacques; Gotto, Antonio M; Kastelein, John J P; Koenig, Wolfgang; Libby, Peter; Lorenzatti, Alberto J; MacFadyen, Jean G; Nordestgaard, Børge G; Shepherd, James; Willerson, James T; Glynn, Robert J

2008-11-20

Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment. We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P=0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P=0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P=0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes. In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events. (ClinicalTrials.gov number, NCT00239681.) 2008 Massachusetts Medical Society

Utilization of Zn-containing electric arc furnace dust for multi-metal doped ferrite with enhanced magnetic property: From hazardous solid waste to green product.

PubMed

Wang, Hui-Gang; Zhang, Mei; Guo, Min

2017-10-05

One-step solid state reaction method was proposed for the first time to realize the transformation of the Zn-containing EAFD from hazardous solid waste to multi-metal doped ferrite with enhanced magnetic property. The effect of Zn-containing EAFD to NiCl 2 ·6H 2 O mass ratio (R ZE/N , g·g -1 ) on the phases transformation was investigated by X-ray diffraction (XRD), Scanning electron microscopy (SEM) and Raman spectroscopy. The as-synthesized samples were treated by toxicity characteristic leaching procedure (TCLP). It is shown that the TCPL played a key role in determining both the purity and toxicity of the obtained ferrites. The pure metal doped Ni-Zn ferrite with higher saturation magnetization (Ms, 56.8 emu·g -1 ) and lower coercivity (Hc, 58.5Oe) was gained under the optimum conditions. And the pure ferrite was a green product according to the TCLP and EN12457 standards. Moreover, the evaluation of environmental impact and the recovery ratio of the dust were also discussed. Copyright © 2017. Published by Elsevier B.V.

Decision support for mitigating the risk of tree induced transmission line failure in utility rights-of-way.

PubMed

Poulos, H M; Camp, A E

2010-02-01

Vegetation management is a critical component of rights-of-way (ROW) maintenance for preventing electrical outages and safety hazards resulting from tree contact with conductors during storms. Northeast Utility's (NU) transmission lines are a critical element of the nation's power grid; NU is therefore under scrutiny from federal agencies charged with protecting the electrical transmission infrastructure of the United States. We developed a decision support system to focus right-of-way maintenance and minimize the potential for a tree fall episode that disables transmission capacity across the state of Connecticut. We used field data on tree characteristics to develop a system for identifying hazard trees (HTs) in the field using limited equipment to manage Connecticut power line ROW. Results from this study indicated that the tree height-to-diameter ratio, total tree height, and live crown ratio were the key characteristics that differentiated potential risk trees (danger trees) from trees with a high probability of tree fall (HTs). Products from this research can be transferred to adaptive right-of-way management, and the methods we used have great potential for future application to other regions of the United States and elsewhere where tree failure can disrupt electrical power.

The impact of anxiety on the progression of mild cognitive impairment to dementia in Chinese and English data bases: a systematic review and meta-analysis.

PubMed

Li, Xiao-Xue; Li, Zheng

2018-01-01

It remains unclear whether or not anxiety increases the risk of dementia in people with mild cognitive impairment (MCI). The aim of this systematic review and meta-analysis was to investigate the risk of dementia among people with MCI and anxiety compared with those with MCI and no anxiety. The hazard ratio of conversion to dementia in people with anxiety and MCI was compared with those without anxiety and was calculated using a generic inverse variance method with fixed effect models. Eleven studies from the English and Chinese databases were included, seven of which were included in the meta-analysis. The pooled hazard ratio of conversion to dementia was 1.18 95% CI [1.07, 1.31] (p = 0.002) in the group of MCI plus anxiety compared with those without anxiety. The results suggest that anxiety increases the risk of progression to dementia in people with MCI. Future interventions targeting anxiety management in vulnerable people with MCI may reduce the risk of dementia. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Anticholinergic Drugs and Their Effects on Delirium and Mortality in the Elderly

PubMed Central

Luukkanen, M.J.; Uusvaara, J.; Laurila, J.V.; Strandberg, T.E; Raivio, M.M.; Tilvis, R.S.; Pitkälä, K.H.

2011-01-01

Aim To investigate the use of drugs with anticholinergic properties (DAPs) and their associations with delirium and mortality among elderly patients with comorbidities. Methods 425 patients (≥70 years of age) in geriatric wards and nursing homes were assessed. The use of DAPs was retrieved from their medical records. Delirium was diagnosed according to the DSM-IV criteria. Results Of the 341 patients (80.2%) treated with multiple DAPs (≥2), 92 patients (27.0%) suffered from delirium, whereas 14 of 84 patients (16.7%) without DAP treatment had delirium (p = 0.050). In a logistic regression analysis with age, gender, and Charlson Comorbidity Index as covariates, DAP treatment did not predict delirium (odds ratio 1.67, 95% confidence interval 0.87–3.21). The 2-year mortality was 49.3% (n = 168) in DAP users and 35.7% (n = 30) in non-users, respectively (p = 0.026). In the Cox proportional hazard model adjusted for age, gender, and comorbidity, DAPs did not predict mortality (hazard ratio 1.12, 95% confidence interval 0.75–1.68). Conclusion The use of DAPs is very frequent among frail inpatients with comorbidities, but their use has no independent prognostic significance. PMID:22163232

[Self-employed and small business owners diagnosed with cancer: effect on entrepreneurial survival].

PubMed

Ha-Vinh, Philippe; Régnard, Pierre; Huiart, Laetitia; Sauze, Laurent; Eisinger, François

2015-01-01

When self-employed andsmall business owners are diagnosed with cancer what is the effect on their small-firm survival duration? Data Sources: secondary data for 3,587 subjects, 18-65 years, working when diagnosed with cancer in 1995-2009 and a comparison group of 27,688 subjects matched for gender, age and occupation. Study design: a comprehensive population-based longitudinal study. A Cox model described time to failures of small businesses and terminations ofself-employment. Data Collection Methods: extraction from the statutory mandatory self-employed social security scheme database. Findings were that age, cancer prognosis and very intense physical workload occupation were independent predictors of enterprise failure for cancer-exposed subjects. Compared with unexposed subjects, their global hazard ratio was 1.59 (95% CI = 1.50 - 1.70). However, the difference atfiveyears after cancer diagnosis became non-significant: hazard ratio 1.11 (95% CI = 0.95 - 1.30). These findings demonstrate that beyond 5 years of maintenance of activity, the economic cost of cancer supported by very small businesses and self-employed is not important. However, support is required to pass through these first 5 years. The authors describe the various possible aids that could be implemented.

Occupational Exposure to Magnetic Fields and Breast Cancer Among Women Textile Workers in Shanghai, China

PubMed Central

Li, Wenjin; Ray, Roberta M.; Thomas, David B.; Yost, Michael; Davis, Scott; Breslow, Norman; Gao, Dao Li; Fitzgibbons, E. Dawn; Camp, Janice E.; Wong, Eva; Wernli, Karen J.; Checkoway, Harvey

2013-01-01

Exposure to magnetic fields (MFs) is hypothesized to increase the risk of breast cancer by reducing production of melatonin by the pineal gland. A nested case-cohort study was conducted to investigate the association between occupational exposure to MFs and the risk of breast cancer within a cohort of 267,400 female textile workers in Shanghai, China. The study included 1,687 incident breast cancer cases diagnosed from 1989 to 2000 and 4,702 noncases selected from the cohort. Subjects’ complete work histories were linked to a job–exposure matrix developed specifically for the present study to estimate cumulative MF exposure. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards modeling that was adapted for the case-cohort design. Hazard ratios were estimated in relation to cumulative exposure during a woman's entire working years. No association was observed between cumulative exposure to MFs and overall risk of breast cancer. The hazard ratio for the highest compared with the lowest quartile of cumulative exposure was 1.03 (95% confidence interval: 0.87, 1.21). Similar null findings were observed when exposures were lagged and stratified by age at breast cancer diagnosis. The findings do not support the hypothesis that MF exposure increases the risk of breast cancer. PMID:24043439

Antenatal Steroid Therapy for Fetal Lung Maturation and the Subsequent Risk of Childhood Asthma: A Longitudinal Analysis

PubMed Central

Pole, Jason D.; Mustard, Cameron A.; To, Teresa; Beyene, Joseph; Allen, Alexander C.

2010-01-01

This study was designed to test the hypothesis that fetal exposure to corticosteroids in the antenatal period is an independent risk factor for the development of asthma in early childhood with little or no effect in later childhood. A population-based cohort study of all pregnant women who resided in Nova Scotia, Canada, and gave birth to a singleton fetus between 1989 and 1998 was undertaken. After a priori specified exclusions, 80,448 infants were available for analysis. Using linked health care utilization records, incident asthma cases developed after 36 months of age were identified. Extended Cox proportional hazards models were used to estimate hazard ratios while controlling for confounders. Exposure to corticosteroids during pregnancy was associated with a risk of asthma in childhood between 3–5 years of age: adjusted hazard ratio of 1.19 (95% confidence interval: 1.03, 1.39), with no association noted after 5 years of age: adjusted hazard ratio for 5–7 years was 1.06 (95% confidence interval: 0.86, 1.30) and for 8 or greater years was 0.74 (95% confidence interval: 0.54, 1.03). Antenatal steroid therapy appears to be an independent risk factor for the development of asthma between 3 and 5 years of age. PMID:21490744

Optimal Scaling of Aftershock Zones using Ground Motion Forecasts

NASA Astrophysics Data System (ADS)

Wilson, John Max; Yoder, Mark R.; Rundle, John B.

2018-02-01

The spatial distribution of aftershocks following major earthquakes has received significant attention due to the shaking hazard these events pose for structures and populations in the affected region. Forecasting the spatial distribution of aftershock events is an important part of the estimation of future seismic hazard. A simple spatial shape for the zone of activity has often been assumed in the form of an ellipse having semimajor axis to semiminor axis ratio of 2.0. However, since an important application of these calculations is the estimation of ground shaking hazard, an effective criterion for forecasting future aftershock impacts is to use ground motion prediction equations (GMPEs) in addition to the more usual approach of using epicentral or hypocentral locations. Based on these ideas, we present an aftershock model that uses self-similarity and scaling relations to constrain parameters as an option for such hazard assessment. We fit the spatial aspect ratio to previous earthquake sequences in the studied regions, and demonstrate the effect of the fitting on the likelihood of post-disaster ground motion forecasts for eighteen recent large earthquakes. We find that the forecasts in most geographic regions studied benefit from this optimization technique, while some are better suited to the use of the a priori aspect ratio.

The Risk of Occupational Injury Increased According to Severity of Noise Exposure After Controlling for Occupational Environment Status in Korea

PubMed Central

Yoon, Jin-Ha; Roh, Jaehoon; Kim, Chi-Nyon; Won, Jong-Uk

2016-01-01

Objectives: The aim of this study was to examine the relationship between noise exposure and risk of occupational injury. Materials and Methods: Korean National Health and Nutrition Examination Survey was used for the current study. Self-report questionnaires were used to investigate occupational injury and exposure to noise, chemicals, and machines and equipments. Results: In separate analyses for occupation and occupational hazard, the proportion of occupational injuries increased according to severity of noise exposure (all P < 0.05). Compared to the non-exposure group, the respective odds ratio (95% confidence intervals) for occupational injury was 1.39 (1.07–1.80) and 1.67 (1.13–2.46) in the mild and severe noise exposure groups, after controlling for age, gender, sleep hours, work schedule (shift work), and exposure status to hazardous chemicals and hazardous machines and equipments. Conclusions: The current study highlights the association between noise exposure and risk of occupational injury. Furthermore, risk of occupational injury increased according to severity of noise exposure. PMID:27991467

Losses Assessment of Crops due to Typhoon Disaster in China Coastal Areas —— A Case Study of Zhanjiang City, Guangdong Province

NASA Astrophysics Data System (ADS)

Mo, W.; Fang, W.

2015-12-01

Vulnerability which quantifies the loss ratio under different hazard intensity is an important feature of the natural disaster system and has important significance to natural disaster risk assessment. Agriculture is an outdoor industry with high risk of meteorological disasters. The strong winds, heavy rain and storm surge are main typhoon hazard factors to crops. To provide a quantitative research method for the loss evaluation of crops due to typhoon disaster we first revised two vulnerability curves for crops under comprehensive intensity of typhoon based on the simulated hazard data and loss data related to historical typhoon events landing on China from 1949 to 2014；and then established a storm surge vulnerability matrix of crops regarding Zhanjiang City of Guangdong Province as the study area ; finally, we put forward three storm surge fragility curves for crops representing different states of loss. The results can effectively describe the typhoon vulnerability for crops in China coastal areas so as to provide the input to post-disaster loss assessments and catastrophe modeling applications.

Quantification of Treatment Effect Modification on Both an Additive and Multiplicative Scale

PubMed Central

Girerd, Nicolas; Rabilloud, Muriel; Pibarot, Philippe; Mathieu, Patrick; Roy, Pascal

2016-01-01

Background In both observational and randomized studies, associations with overall survival are by and large assessed on a multiplicative scale using the Cox model. However, clinicians and clinical researchers have an ardent interest in assessing absolute benefit associated with treatments. In older patients, some studies have reported lower relative treatment effect, which might translate into similar or even greater absolute treatment effect given their high baseline hazard for clinical events. Methods The effect of treatment and the effect modification of treatment were respectively assessed using a multiplicative and an additive hazard model in an analysis adjusted for propensity score in the context of coronary surgery. Results The multiplicative model yielded a lower relative hazard reduction with bilateral internal thoracic artery grafting in older patients (Hazard ratio for interaction/year = 1.03, 95%CI: 1.00 to 1.06, p = 0.05) whereas the additive model reported a similar absolute hazard reduction with increasing age (Delta for interaction/year = 0.10, 95%CI: -0.27 to 0.46, p = 0.61). The number needed to treat derived from the propensity score-adjusted multiplicative model was remarkably similar at the end of the follow-up in patients aged < = 60 and in patients >70. Conclusions The present example demonstrates that a lower treatment effect in older patients on a relative scale can conversely translate into a similar treatment effect on an additive scale due to large baseline hazard differences. Importantly, absolute risk reduction, either crude or adjusted, can be calculated from multiplicative survival models. We advocate for a wider use of the absolute scale, especially using additive hazard models, to assess treatment effect and treatment effect modification. PMID:27045168

Considering the ranges of uncertainties in the New Probabilistic Seismic Hazard Assessment of Germany - Version 2016

NASA Astrophysics Data System (ADS)

Grunthal, Gottfried; Stromeyer, Dietrich; Bosse, Christian; Cotton, Fabrice; Bindi, Dino

2017-04-01

The seismic load parameters for the upcoming National Annex to the Eurocode 8 result from the reassessment of the seismic hazard supported by the German Institution for Civil Engineering . This 2016 version of hazard assessment for Germany as target area was based on a comprehensive involvement of all accessible uncertainties in models and parameters into the approach and the provision of a rational framework for facilitating the uncertainties in a transparent way. The developed seismic hazard model represents significant improvements; i.e. it is based on updated and extended databases, comprehensive ranges of models, robust methods and a selection of a set of ground motion prediction equations of their latest generation. The output specifications were designed according to the user oriented needs as suggested by two review teams supervising the entire project. In particular, seismic load parameters were calculated for rock conditions with a vS30 of 800 ms-1 for three hazard levels (10%, 5% and 2% probability of occurrence or exceedance within 50 years) in form of, e.g., uniform hazard spectra (UHS) based on 19 sprectral periods in the range of 0.01 - 3s, seismic hazard maps for spectral response accelerations for different spectral periods or for macroseismic intensities. The developed hazard model consists of a logic tree with 4040 end branches and essential innovations employed to capture epistemic uncertainties and aleatory variabilities. The computation scheme enables the sound calculation of the mean and any quantile of required seismic load parameters. Mean, median and 84th percentiles of load parameters were provided together with the full calculation model to clearly illustrate the uncertainties of such a probabilistic assessment for a region of a low-to-moderate level of seismicity. The regional variations of these uncertainties (e.g. ratios between the mean and median hazard estimations) were analyzed and discussed.

Rates of Atrial Fibrillation in Black Versus White Patients With Pacemakers.

PubMed

Kamel, Hooman; Kleindorfer, Dawn O; Bhave, Prashant D; Cushman, Mary; Levitan, Emily B; Howard, George; Soliman, Elsayed Z

2016-02-12

Black US residents experience higher rates of ischemic stroke than white residents but have lower rates of clinically apparent atrial fibrillation (AF), a strong risk factor for stroke. It is unclear whether black persons truly have less AF or simply more undiagnosed AF. We obtained administrative claims data from state health agencies regarding all emergency department visits and hospitalizations in California, Florida, and New York. We identified a cohort of patients with pacemakers, the regular interrogation of which reduces the likelihood of undiagnosed AF. We compared rates of documented AF or atrial flutter at follow-up visits using Kaplan-Meier survival statistics and Cox proportional hazards models adjusted for demographic characteristics and vascular risk factors. We identified 10 393 black and 91 380 white patients without documented AF or atrial flutter before or at the index visit for pacemaker implantation. During 3.7 (±1.8) years of follow-up, black patients had a significantly lower rate of AF (21.4%; 95% CI 19.8-23.2) than white patients (25.5%; 95% CI 24.9-26.0). After adjustment for demographic characteristics and comorbidities, black patients had a lower hazard of AF (hazard ratio 0.91; 95% CI 0.86-0.96), a higher hazard of atrial flutter (hazard ratio 1.29; 95% CI 1.11-1.49), and a lower hazard of the composite of AF or atrial flutter (hazard ratio 0.94; 95% CI 0.88-99). In a population-based sample of patients with pacemakers, black patients had a lower rate of AF compared with white patients. These findings indicate that the persistent racial disparities in rates of ischemic stroke are likely to be related to factors other than undiagnosed AF. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Ethnic variations in morbidity and mortality from lower respiratory tract infections: a retrospective cohort study.

PubMed

Simpson, Colin R; Steiner, Markus Fc; Cezard, Genevieve; Bansal, Narinder; Fischbacher, Colin; Douglas, Anne; Bhopal, Raj; Sheikh, Aziz

2015-10-01

There is evidence of substantial ethnic variations in asthma morbidity and the risk of hospitalisation, but the picture in relation to lower respiratory tract infections is unclear. We carried out an observational study to identify ethnic group differences for lower respiratory tract infections. A retrospective, cohort study. Scotland. 4.65 million people on whom information was available from the 2001 census, followed from May 2001 to April 2010. Hospitalisations and deaths (any time following first hospitalisation) from lower respiratory tract infections, adjusted risk ratios and hazard ratios by ethnicity and sex were calculated. We multiplied ratios and confidence intervals by 100, so the reference Scottish White population's risk ratio and hazard ratio was 100. Among men, adjusted risk ratios for lower respiratory tract infection hospitalisation were lower in Other White British (80, 95% confidence interval 73-86) and Chinese (69, 95% confidence interval 56-84) populations and higher in Pakistani groups (152, 95% confidence interval 136-169). In women, results were mostly similar to those in men (e.g. Chinese 68, 95% confidence interval 56-82), although higher adjusted risk ratios were found among women of the Other South Asians group (145, 95% confidence interval 120-175). Survival (adjusted hazard ratio) following lower respiratory tract infection for Pakistani men (54, 95% confidence interval 39-74) and women (31, 95% confidence interval 18-53) was better than the reference population. Substantial differences in the rates of lower respiratory tract infections amongst different ethnic groups in Scotland were found. Pakistani men and women had particularly high rates of lower respiratory tract infection hospitalisation. The reasons behind the high rates of lower respiratory tract infection in the Pakistani community are now required. © The Royal Society of Medicine.

Strongly Iridescent Hybrid Photonic Sensors Based on Self-Assembled Nanoparticles for Hazardous Solvent Detection.

PubMed

Sato, Ayaka; Ikeda, Yuya; Yamaguchi, Koichi; Vohra, Varun

2018-03-16

Facile detection and the identification of hazardous organic solvents are essential for ensuring global safety and avoiding harm to the environment caused by industrial wastes. Here, we present a simple method for the fabrication of silver-coated monodisperse polystyrene nanoparticle photonic structures that are embedded into a polydimethylsiloxane (PDMS) matrix. These hybrid materials exhibit a strong green iridescence with a reflectance peak at 550 nm that originates from the close-packed arrangement of the nanoparticles. This reflectance peak measured under Wulff-Bragg conditions displays a 20 to 50 nm red shift when the photonic sensors are exposed to five commonly employed and highly hazardous organic solvents. These red-shifts correlate well with PDMS swelling ratios using the various solvents, which suggests that the observable color variations result from an increase in the photonic crystal lattice parameter with a similar mechanism to the color modulation of the chameleon skin. Dynamic reflectance measurements enable the possibility of clearly identifying each of the tested solvents. Furthermore, as small amounts of hazardous solvents such as tetrahydrofuran can be detected even when mixed with water, the nanostructured solvent sensors we introduce here could have a major impact on global safety measures as innovative photonic technology for easily visualizing and identifying the presence of contaminants in water.

TRENDS IN MORTALITY FROM OCCUPATIONAL HAZARDS AMONG MEN IN ENGLAND AND WALES DURING 1979-2010

PubMed Central

Harris, E Clare; Palmer, Keith T; Cox, Vanessa; Darnton, Andrew; Osman, John; Coggon, David

2016-01-01

Objectives To monitor the impact of health and safety provisions and inform future preventive strategies, we investigated trends in mortality from established occupational hazards in England and Wales. Methods We analysed data from death certificates on underlying cause of death and last full-time occupation for 3,688,916 deaths among men aged 20-74 years in England and Wales during 1979-2010 (excluding 1981 when records were incomplete). Proportional mortality ratios (PMRs), standardised for age and social class, were calculated for occupations at risk of specified hazards. Observed and expected numbers of deaths for each hazard were summed across occupations, and the differences summarised as average annual excesses. Results Excess mortality declined substantially for most hazards. For example, the annual excess of deaths from chronic bronchitis and emphysema fell from 170.7 during 1979-90 to 36.0 in 2001-10, and that for deaths from injury and poisoning from 237.0 to 87.5. In many cases the improvements were associated with falling PMRs (suggesting safer working practices), but they also reflected reductions in the numbers of men employed in more hazardous jobs, and declining mortality from some diseases across the whole population. Notable exceptions to the general improvement were diseases caused by asbestos, especially in some construction trades and sinonasal cancer in woodworkers. Conclusions The highest priority for future prevention of work-related fatalities is the minority of occupational disorders for which excess mortality remains static or is increasing, in particular asbestos-related disease among certain occupations in the construction industry and sinonasal cancer in woodworkers. PMID:26976946

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.

Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3.

PubMed

Slamon, Dennis J; Neven, Patrick; Chia, Stephen; Fasching, Peter A; De Laurentiis, Michelino; Im, Seock-Ah; Petrakova, Katarina; Bianchi, Giulia Val; Esteva, Francisco J; Martín, Miguel; Nusch, Arnd; Sonke, Gabe S; De la Cruz-Merino, Luis; Beck, J Thaddeus; Pivot, Xavier; Vidam, Gena; Wang, Yingbo; Rodriguez Lorenc, Karen; Miller, Michelle; Taran, Tetiana; Jerusalem, Guy

2018-06-03

Purpose This phase III study evaluated ribociclib plus fulvestrant in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer who were treatment naïve or had received up to one line of prior endocrine therapy in the advanced setting. Patients and Methods Patients were randomly assigned at a two-to-one ratio to ribociclib plus fulvestrant or placebo plus fulvestrant. The primary end point was locally assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. Results A total of 484 postmenopausal women were randomly assigned to ribociclib plus fulvestrant, and 242 were assigned to placebo plus fulvestrant. Median progression-free survival was significantly improved with ribociclib plus fulvestrant versus placebo plus fulvestrant: 20.5 months (95% CI, 18.5 to 23.5 months) versus 12.8 months (95% CI, 10.9 to 16.3 months), respectively (hazard ratio, 0.593; 95% CI, 0.480 to 0.732; P < .001). Consistent treatment effects were observed in patients who were treatment naïve in the advanced setting (hazard ratio, 0.577; 95% CI, 0.415 to 0.802), as well as in patients who had received up to one line of prior endocrine therapy for advanced disease (hazard ratio, 0.565; 95% CI, 0.428 to 0.744). Among patients with measurable disease, the overall response rate was 40.9% for the ribociclib plus fulvestrant arm and 28.7% for placebo plus fulvestrant. Grade 3 adverse events reported in ≥ 10% of patients in either arm (ribociclib plus fulvestrant v placebo plus fulvestrant) were neutropenia (46.6% v 0%) and leukopenia (13.5% v 0%); the only grade 4 event reported in ≥ 5% of patients was neutropenia (6.8% v 0%). Conclusion Ribociclib plus fulvestrant might represent a new first- or second-line treatment option in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer.

Regional danger assessment of Debris flow and its engineering mitigation practice in Sichuan-Tibet highway

NASA Astrophysics Data System (ADS)

Su, Pengcheng; Sun, Zhengchao; li, Yong

2017-04-01

Luding-Kangding highway cross the eastern edge of Qinghai-Tibet Plateau where belong to the most deep canyon area of plateau and mountains in western Sichuan with high mountain and steep slope. This area belongs to the intersection among Xianshuihe, Longmenshan and Anninghe fault zones which are best known in Sichuan province. In the region, seismic intensity is with high frequency and strength, new tectonic movement is strong, rock is cracked, there are much loose solid materials. Debris flow disaster is well developed under the multiple effects of the earthquake, strong rainfall and human activity which poses a great threat to the local people's life and property security. So this paper chooses Kangding and LuDing as the study area to do the debris flow hazard assessment through the in-depth analysis of development characteristics and formation mechanism of debris flow. Which can provide important evidence for local disaster assessment and early warning forecast. It also has the important scientific significance and practical value to safeguard the people's life and property safety and the security implementation of the national major project. In this article, occurrence mechanism of debris flow disasters in the study area is explored, factor of evaluation with high impact to debris flow hazards is identified, the database of initial evaluation factors is made by the evaluation unit of basin. The factors with high impact to hazards occurrence are selected by using the stepwise regression method of logistic regression model, at the same time the factors with low impact are eliminated, then the hazard evaluation factor system of debris flow is determined in the study area. Then every factors of evaluation factor system are quantified, and the weights of all evaluation factors are determined by using the analysis of stepwise regression. The debris flows hazard assessment and regionalization of all the whole study area are achieved eventually after establishing the hazard assessment model. In this paper, regional debris flows hazard assessment method with strong universality and reliable evaluation result is presented. The whole study area is divided into 1674 units by automatically extracting and artificial identification, and then 11 factors are selected as the initial assessment factors of debris flow hazard assessment in the study area. The factors of the evaluation index system are quantified using the method of standardized watershed unit amount ratio. The relationship between debris flow occurrence and each evaluation factor is simulated using logistic regression model. The weights of evaluation factors are determined, and the model of debris flows hazard assessment is established in the study area. Danger assessment result of debris flow was applied in line optimization and engineering disaster reduction of Sichuan-Tibet highway (section of Luding-Kangding).

The ratio of hemoglobin to red cell distribution width as a novel prognostic parameter in esophageal squamous cell carcinoma: a retrospective study from southern China

PubMed Central

Bi, Xiwen; Yang, Hang; An, Xin; Wang, Fenghua; Jiang, Wenqi

2016-01-01

Background We propose a novel prognostic parameter for esophageal squamous cell carcinoma (ESCC)—hemoglobin/red cell distribution width (HB/RDW) ratio. Its clinical prognostic value and relationship with other clinicopathological characteristics were investigated in ESCC patients. Results The optimal cut-off value was 0.989 for the HB/RDW ratio. The HB/RDW ratio (P= 0.035), tumor depth (P = 0.020) and lymph node status (P<0.001) were identified to be an independent prognostic factors of OS by multivariate analysis, which was validated by bootstrap resampling. Patients with a low HB/RDW ratio had a 1.416 times greater risk of dying during follow-up compared with those with a high HB/RDW (95% CI = 1.024–1.958, P = 0.035). Materials and Methods We retrospectively analyzed 362 patients who underwent curative treatment at a single institution between January 2007 and December 2008. The chi-square test was used to evaluate relationships between the HB/RDW ratio and other clinicopathological variables; the Kaplan–Meier method was used to analyze the 5-year overall survival (OS); and the Cox proportional hazards models were used for univariate and multivariate analyses of variables related to OS. Conclusion A significant association was found between the HB/RDW ratio and clinical characteristics and survival outcomes in ESCC patients. Based on these findings, we believe that the HB/RDW ratio is a novel and promising prognostic parameter for ESCC patients. PMID:27223088

The influence of maximum magnitude on seismic-hazard estimates in the Central and Eastern United States

USGS Publications Warehouse

Mueller, C.S.

2010-01-01

I analyze the sensitivity of seismic-hazard estimates in the central and eastern United States (CEUS) to maximum magnitude (mmax) by exercising the U.S. Geological Survey (USGS) probabilistic hazard model with several mmax alternatives. Seismicity-based sources control the hazard in most of the CEUS, but data seldom provide an objective basis for estimating mmax. The USGS uses preferred mmax values of moment magnitude 7.0 and 7.5 for the CEUS craton and extended margin, respectively, derived from data in stable continental regions worldwide. Other approaches, for example analysis of local seismicity or judgment about a source's seismogenic potential, often lead to much smaller mmax. Alternative models span the mmax ranges from the 1980s Electric Power Research Institute/Seismicity Owners Group (EPRI/SOG) analysis. Results are presented as haz-ard ratios relative to the USGS national seismic hazard maps. One alternative model specifies mmax equal to moment magnitude 5.0 and 5.5 for the craton and margin, respectively, similar to EPRI/SOG for some sources. For 2% probability of exceedance in 50 years (about 0.0004 annual probability), the strong mmax truncation produces hazard ratios equal to 0.35-0.60 for 0.2-sec spectral acceleration, and 0.15-0.35 for 1.0-sec spectral acceleration. Hazard-controlling earthquakes interact with mmax in complex ways. There is a relatively weak dependence on probability level: hazardratios increase 0-15% for 0.002 annual exceedance probability and decrease 5-25% for 0.00001 annual exceedance probability. Although differences at some sites are tempered when faults are added, mmax clearly accounts for some of the discrepancies that are seen in comparisons between USGS-based and EPRI/SOG-based hazard results.

Enzalutamide in metastatic prostate cancer before chemotherapy.

PubMed

Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana E; Loriot, Yohann; Sternberg, Cora N; Higano, Celestia S; Iversen, Peter; Bhattacharya, Suman; Carles, Joan; Chowdhury, Simon; Davis, Ian D; de Bono, Johann S; Evans, Christopher P; Fizazi, Karim; Joshua, Anthony M; Kim, Choung-Soo; Kimura, Go; Mainwaring, Paul; Mansbach, Harry; Miller, Kurt; Noonberg, Sarah B; Perabo, Frank; Phung, De; Saad, Fred; Scher, Howard I; Taplin, Mary-Ellen; Venner, Peter M; Tombal, Bertrand

2014-07-31

Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy. In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression-free survival and overall survival. The study was stopped after a planned interim analysis, conducted when 540 deaths had been reported, showed a benefit of the active treatment. The rate of radiographic progression-free survival at 12 months was 65% among patients treated with enzalutamide, as compared with 14% among patients receiving placebo (81% risk reduction; hazard ratio in the enzalutamide group, 0.19; 95% confidence interval [CI], 0.15 to 0.23; P<0.001). A total of 626 patients (72%) in the enzalutamide group, as compared with 532 patients (63%) in the placebo group, were alive at the data-cutoff date (29% reduction in the risk of death; hazard ratio, 0.71; 95% CI, 0.60 to 0.84; P<0.001). The benefit of enzalutamide was shown with respect to all secondary end points, including the time until the initiation of cytotoxic chemotherapy (hazard ratio, 0.35), the time until the first skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P<0.001 for all comparisons). Fatigue and hypertension were the most common clinically relevant adverse events associated with enzalutamide treatment. Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas Pharma; PREVAIL ClinicalTrials.gov number, NCT01212991.).

Peritoneal dialysis in rural Australia.

PubMed

Gray, Nicholas A; Grace, Blair S; McDonald, Stephen P

2013-12-20

Australians living in rural areas have lower incidence rates of renal replacement therapy and poorer dialysis survival compared with urban dwellers. This study compares peritoneal dialysis (PD) patient characteristics and outcomes in rural and urban Australia. Non-indigenous Australian adults who commenced chronic dialysis between 1 January 2000 and 31 December 2010 according to the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) were investigated. Each patient's residence was classified according to the Australian Bureau of Statistics remote area index as major city (MC), inner regional (IR), outer regional (OR), or remote/very remote (REM). A total of 7657 patients underwent PD treatment during the study period. Patient distribution was 69.0% MC, 19.6% IR, 9.5% OR, and 1.8% REM. PD uptake increased with increasing remoteness. Compared with MC, sub-hazard ratios [95% confidence intervals] for commencing PD were 1.70 [1.61-1.79] IR, 2.01 [1.87-2.16] OR, and 2.60 [2.21-3.06] REM. During the first 6 months of PD, technique failure was less likely outside MC (sub-hazard ratio 0.47 [95% CI: 0.35-0.62], P < 0.001), but no difference was seen after 6 months (sub-hazard ratio 1.05 [95% CI: 0.84-1.32], P = 0.6). Technique failure due to technical (sub-hazard ratio 0.57 [95% CI: 0.38-0.84], P = 0.005) and non-medical causes (sub-hazard ratio 0.52 [95% CI: 0.31-0.87], P = 0.01) was less likely outside MC. Time to first peritonitis episode was not associated with remoteness (P = 0.8). Patient survival while on PD or within 90 days of stopping PD did not differ by region (P = 0.2). PD uptake increases with increasing remoteness. In rural areas, PD technique failure is less likely during the first 6 months and time to first peritonitis is comparable to urban areas. Mortality while on PD does not differ by region. PD is therefore a good dialysis modality choice for rural patients in Australia.

Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia.

PubMed

Fitzhugh, Courtney D; Hsieh, Matthew M; Allen, Darlene; Coles, Wynona A; Seamon, Cassie; Ring, Michael; Zhao, Xiongce; Minniti, Caterina P; Rodgers, Griffin P; Schechter, Alan N; Tisdale, John F; Taylor, James G

2015-01-01

Adults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea. We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010. An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648. Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003-1.006, p<0.0.0001), kidney dysfunction (elevated creatinine, Hazard Ratio = 1.13, 95% CI 1.00-1.27, p = 0.043), and cardiopulmonary dysfunction (elevated tricuspid jet velocity on echocardiogram, Hazard Ratio = 2.22, 1.23-4.02, p = 0.0082). Sixty-six percent of subjects were treated with hydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34-0.97, p = 0.040). This effect was most pronounced in those taking the recommended dose of 15-35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17-0.73, p = 0.0050). Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004). While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively), other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels. Our data suggest that adults should be treated with the maximum tolerated hydroxyurea dose, ideally before organ damage occurs. Prospective studies are indicated to validate these findings.

Effects of clopidogrel added to aspirin in patients with recent lacunar stroke.

PubMed

Benavente, Oscar R; Hart, Robert G; McClure, Leslie A; Szychowski, Jeffrey M; Coffey, Christopher S; Pearce, Lesly A

2012-08-30

Lacunar infarcts are a frequent type of stroke caused mainly by cerebral small-vessel disease. The effectiveness of antiplatelet therapy for secondary prevention has not been defined. We conducted a double-blind, multicenter trial involving 3020 patients with recent symptomatic lacunar infarcts identified by magnetic resonance imaging. Patients were randomly assigned to receive 75 mg of clopidogrel or placebo daily; patients in both groups received 325 mg of aspirin daily. The primary outcome was any recurrent stroke, including ischemic stroke and intracranial hemorrhage. The participants had a mean age of 63 years, and 63% were men. After a mean follow-up of 3.4 years, the risk of recurrent stroke was not significantly reduced with aspirin and clopidogrel (dual antiplatelet therapy) (125 strokes; rate, 2.5% per year) as compared with aspirin alone (138 strokes, 2.7% per year) (hazard ratio, 0.92; 95% confidence interval [CI], 0.72 to 1.16), nor was the risk of recurrent ischemic stroke (hazard ratio, 0.82; 95% CI, 0.63 to 1.09) or disabling or fatal stroke (hazard ratio, 1.06; 95% CI, 0.69 to 1.64). The risk of major hemorrhage was almost doubled with dual antiplatelet therapy (105 hemorrhages, 2.1% per year) as compared with aspirin alone (56, 1.1% per year) (hazard ratio, 1.97; 95% CI, 1.41 to 2.71; P<0.001). Among classifiable recurrent ischemic strokes, 71% (133 of 187) were lacunar strokes. All-cause mortality was increased among patients assigned to receive dual antiplatelet therapy (77 deaths in the group receiving aspirin alone vs. 113 in the group receiving dual antiplatelet therapy) (hazard ratio, 1.52; 95% CI, 1.14 to 2.04; P=0.004); this difference was not accounted for by fatal hemorrhages (9 in the group receiving dual antiplatelet therapy vs. 4 in the group receiving aspirin alone). Among patients with recent lacunar strokes, the addition of clopidogrel to aspirin did not significantly reduce the risk of recurrent stroke and did significantly increase the risk of bleeding and death. (Funded by the National Institute of Neurological Disorders and Stroke and others; SPS3 ClinicalTrials.gov number, NCT00059306.).

Additive survival least square support vector machines: A simulation study and its application to cervical cancer prediction

NASA Astrophysics Data System (ADS)

Khotimah, Chusnul; Purnami, Santi Wulan; Prastyo, Dedy Dwi; Chosuvivatwong, Virasakdi; Sriplung, Hutcha

2017-11-01

Support Vector Machines (SVMs) has been widely applied for prediction in many fields. Recently, SVM is also developed for survival analysis. In this study, Additive Survival Least Square SVM (A-SURLSSVM) approach is used to analyze cervical cancer dataset and its performance is compared with the Cox model as a benchmark. The comparison is evaluated based on the prognostic index produced: concordance index (c-index), log rank, and hazard ratio. The higher prognostic index represents the better performance of the corresponding methods. This work also applied feature selection to choose important features using backward elimination technique based on the c-index criterion. The cervical cancer dataset consists of 172 patients. The empirical results show that nine out of the twelve features: age at marriage, age of first getting menstruation, age, parity, type of treatment, history of family planning, stadium, long-time of menstruation, and anemia status are selected as relevant features that affect the survival time of cervical cancer patients. In addition, the performance of the proposed method is evaluated through a simulation study with the different number of features and censoring percentages. Two out of three performance measures (c-index and hazard ratio) obtained from A-SURLSSVM consistently yield better results than the ones obtained from Cox model when it is applied on both simulated and cervical cancer data. Moreover, the simulation study showed that A-SURLSSVM performs better when the percentage of censoring data is small.

Apixaban versus warfarin in patients with atrial fibrillation.

PubMed

Granger, Christopher B; Alexander, John H; McMurray, John J V; Lopes, Renato D; Hylek, Elaine M; Hanna, Michael; Al-Khalidi, Hussein R; Ansell, Jack; Atar, Dan; Avezum, Alvaro; Bahit, M Cecilia; Diaz, Rafael; Easton, J Donald; Ezekowitz, Justin A; Flaker, Greg; Garcia, David; Geraldes, Margarida; Gersh, Bernard J; Golitsyn, Sergey; Goto, Shinya; Hermosillo, Antonio G; Hohnloser, Stefan H; Horowitz, John; Mohan, Puneet; Jansky, Petr; Lewis, Basil S; Lopez-Sendon, Jose Luis; Pais, Prem; Parkhomenko, Alexander; Verheugt, Freek W A; Zhu, Jun; Wallentin, Lars

2011-09-15

Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42). In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.).

C-reactive protein and serum creatinine, but not haemoglobin A1c, are independent predictors of coronary heart disease risk in non-diabetic Chinese.

PubMed

Salim, Agus; Tai, E Shyong; Tan, Vincent Y; Welsh, Alan H; Liew, Reginald; Naidoo, Nasheen; Wu, Yi; Yuan, Jian-Min; Koh, Woon P; van Dam, Rob M

2016-08-01

In western populations, high-sensitivity C-reactive protein (hsCRP), and to a lesser degree serum creatinine and haemoglobin A1c, predict risk of coronary heart disease (CHD). However, data on Asian populations that are increasingly affected by CHD are sparse and it is not clear whether these biomarkers can be used to improve CHD risk classification. We conducted a nested case-control study within the Singapore Chinese Health Study cohort, with incident 'hard' CHD (myocardial infarction or CHD death) as an outcome. We used data from 965 men (298 cases, 667 controls) and 528 women (143 cases, 385 controls) to examine the utility of hsCRP, serum creatinine and haemoglobin A1c in improving the prediction of CHD risk over and above traditional risk factors for CHD included in the ATP III model. For each sex, the performance of models with only traditional risk factors used in the ATP III model was compared with models with the biomarkers added using weighted Cox proportional hazards analysis. The impact of adding these biomarkers was assessed using the net reclassification improvement index. For men, loge hsCRP (hazard ratio 1.25, 95% confidence interval: 1.05; 1.49) and loge serum creatinine (hazard ratio 4.82, 95% confidence interval: 2.10; 11.04) showed statistically significantly associations with CHD risk when added to the ATP III model. We did not observe a significant association between loge haemoglobin A1c and CHD risk (hazard ratio 1.83, 95% confidence interval: 0.21; 16.06). Adding hsCRP and serum creatinine to the ATP III model improved risk classification in men with a net gain of 6.3% of cases (p-value = 0.001) being reclassified to a higher risk category, while it did not significantly reduce the accuracy of classification for non-cases. For women, squared hsCRP was borderline significantly (hazard ratio 1.01, 95% confidence interval: 1.00; 1.03) and squared serum creatinine was significantly (hazard ratio 1.81, 95% confidence interval: 1.49; 2.21) associated with CHD risk. However, the association between squared haemoglobin A1c and CHD risk was not significant (hazard ratio 1.05, 95% confidence interval: 0.99; 1.12). The addition of hsCRP and serum creatinine to the ATP III model resulted in 3.7% of future cases being reclassified to a higher risk category (p-value = 0.025), while it did not significantly reduce the accuracy of classification for non-cases. Adding hsCRP and serum creatinine, but not haemoglobin A1c, to traditional risk factors improved CHD risk prediction among non-diabetic Singaporean Chinese. The improved risk estimates will allow better identification of individuals at high risk of CHD than existing risk calculators such as the ATP III model. © The European Society of Cardiology 2016.

TU-CD-BRB-08: Radiomic Analysis of FDG-PET Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated with SBRT

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

Cui, Y; Shirato, H; Song, J

2015-06-15

Purpose: This study aims to identify novel prognostic imaging biomarkers in locally advanced pancreatic cancer (LAPC) using quantitative, high-throughput image analysis. Methods: 86 patients with LAPC receiving chemotherapy followed by SBRT were retrospectively studied. All patients had a baseline FDG-PET scan prior to SBRT. For each patient, we extracted 435 PET imaging features of five types: statistical, morphological, textural, histogram, and wavelet. These features went through redundancy checks, robustness analysis, as well as a prescreening process based on their concordance indices with respect to the relevant outcomes. We then performed principle component analysis on the remaining features (number ranged frommore » 10 to 16), and fitted a Cox proportional hazard regression model using the first 3 principle components. Kaplan-Meier analysis was used to assess the ability to distinguish high versus low-risk patients separated by median predicted survival. To avoid overfitting, all evaluations were based on leave-one-out cross validation (LOOCV), in which each holdout patient was assigned to a risk group according to the model obtained from a separate training set. Results: For predicting overall survival (OS), the most dominant imaging features were wavelet coefficients. There was a statistically significant difference in OS between patients with predicted high and low-risk based on LOOCV (hazard ratio: 2.26, p<0.001). Similar imaging features were also strongly associated with local progression-free survival (LPFS) (hazard ratio: 1.53, p=0.026) on LOOCV. In comparison, neither SUVmax nor TLG was associated with LPFS (p=0.103, p=0.433) (Table 1). Results for progression-free survival and distant progression-free survival showed similar trends. Conclusion: Radiomic analysis identified novel imaging features that showed improved prognostic value over conventional methods. These features characterize the degree of intra-tumor heterogeneity reflected on FDG-PET images, and their biological underpinnings warrant further investigation. If validated in large, prospective cohorts, this method could be used to stratify patients based on individualized risk.« less

Idiopathic Pulmonary Fibrosis: The Association between the Adaptive Multiple Features Method and Fibrosis Outcomes.

PubMed

Salisbury, Margaret L; Lynch, David A; van Beek, Edwin J R; Kazerooni, Ella A; Guo, Junfeng; Xia, Meng; Murray, Susan; Anstrom, Kevin J; Yow, Eric; Martinez, Fernando J; Hoffman, Eric A; Flaherty, Kevin R

2017-04-01

Adaptive multiple features method (AMFM) lung texture analysis software recognizes high-resolution computed tomography (HRCT) patterns. To evaluate AMFM and visual quantification of HRCT patterns and their relationship with disease progression in idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis in a clinical trial of prednisone, azathioprine, and N-acetylcysteine underwent HRCT at study start and finish. Proportion of lung occupied by ground glass, ground glass-reticular (GGR), honeycombing, emphysema, and normal lung densities were measured by AMFM and three radiologists, documenting baseline disease extent and postbaseline change. Disease progression includes composite mortality, hospitalization, and 10% FVC decline. Agreement between visual and AMFM measurements was moderate for GGR (Pearson's correlation r = 0.60, P < 0.0001; mean difference = -0.03 with 95% limits of agreement of -0.19 to 0.14). Baseline extent of GGR was independently associated with disease progression when adjusting for baseline Gender-Age-Physiology stage and smoking status (hazard ratio per 10% visual GGR increase = 1.98, 95% confidence interval [CI] = 1.20-3.28, P = 0.008; and hazard ratio per 10% AMFM GGR increase = 1.36, 95% CI = 1.01-1.84, P = 0.04). Postbaseline visual and AMFM GGR trajectories were correlated with postbaseline FVC trajectory (r = -0.30, 95% CI = -0.46 to -0.11, P = 0.002; and r = -0.25, 95% CI = -0.42 to -0.06, P = 0.01, respectively). More extensive baseline visual and AMFM fibrosis (as measured by GGR densities) is independently associated with elevated hazard for disease progression. Postbaseline change in AMFM-measured and visually measured GGR densities are modestly correlated with change in FVC. AMFM-measured fibrosis is an automated adjunct to existing prognostic markers and may allow for study enrichment with subjects at increased disease progression risk.

Phenotype at diagnosis predicts recurrence rates in Crohn's disease.

PubMed

Wolters, F L; Russel, M G; Sijbrandij, J; Ambergen, T; Odes, S; Riis, L; Langholz, E; Politi, P; Qasim, A; Koutroubakis, I; Tsianos, E; Vermeire, S; Freitas, J; van Zeijl, G; Hoie, O; Bernklev, T; Beltrami, M; Rodriguez, D; Stockbrügger, R W; Moum, B

2006-08-01

In Crohn's disease (CD), studies associating phenotype at diagnosis and subsequent disease activity are important for patient counselling and health care planning. To calculate disease recurrence rates and to correlate these with phenotypic traits at diagnosis. A prospectively assembled uniformly diagnosed European population based inception cohort of CD patients was classified according to the Vienna classification for disease phenotype at diagnosis. Surgical and non-surgical recurrence rates throughout a 10 year follow up period were calculated. Multivariate analysis was performed to classify risk factors present at diagnosis for recurrent disease. A total of 358 were classified for phenotype at diagnosis, of whom 262 (73.2%) had a first recurrence and 113 patients (31.6%) a first surgical recurrence during the first 10 years after diagnosis. Patients with upper gastrointestinal disease at diagnosis had an excess risk of recurrence (hazard ratio 1.54 (95% confidence interval (CI) 1.13-2.10)) whereas age >/=40 years at diagnosis was protective (hazard ratio 0.82 (95% CI 0.70-0.97)). Colonic disease was a protective characteristic for resective surgery (hazard ratio 0.38 (95% CI 0.21-0.69)). More frequent resective surgical recurrences were reported from Copenhagen (hazard ratio 3.23 (95% CI 1.32-7.89)). A mild course of disease in terms of disease recurrence was observed in this European cohort. Phenotype at diagnosis had predictive value for disease recurrence with upper gastrointestinal disease being the most important positive predictor. A phenotypic North-South gradient in CD may be present, illustrated by higher surgery risks in some of the Northern European centres.

Intracoronary injection of CD34-cells in chronic ischemic heart failure: 7 years follow-up of the DanCell study.

PubMed

Hansen, Morten; Nyby, Sebastian; Eifer Møller, Jacob; Videbæk, Lars; Kassem, Moustapha; Barington, Torben; Thayssen, Per; Diederichsen, Axel Cosmus Pyndt

2014-01-01

Seven years ago, the DanCell study was carried out to test the hypothesis of improvement in left ventricular ejection fraction (LVEF) following repeated intracoronary injections of autologous bone marrow-derived stem cells (BMSCs) in patients suffering from chronic ischemic heart failure. In this post hoc analysis, the long-term effect of therapy is assessed. 32 patients [mean age 61 (SD ± 9), 81% males] with systolic dysfunction (LVEF 33 ± 9%) received two repeated intracoronary infusions (4 months apart) of autologous BMSCs (1,533 ± 765 × 10(6) BMSCs including 23 ± 11 × 10(6) CD34(+) cells and 14 ± 7 × 10(6) CD133(+) cells). Patients were followed for 7 years and deaths were recorded. During follow-up, 10 patients died (31%). In univariate regression analysis, the total number of BMSCs, CD34(+) cell count and CD133(+) cell count did not significantly correlate with survival (hazard ratio: 0.999, 95% CI: 0.998-1.000, p = 0.24; hazard ratio: 0.94, 95% CI: 0.88-1.01, p = 0.10, and hazard ratio: 0.96, 95% CI: 0.87-1.07, p = 0.47, respectively). After adjustment for baseline variables in multivariate regression analysis, the CD34(+) cell count was significantly associated with survival (hazard ratio: 0.90, 95% CI: 0.82-1.00, p = 0.04). Intracoronary injections of a high number of CD34(+) cells may have a beneficial effect on chronic ischemic heart failure in terms of long-term survival.

Cardiac rehabilitation attendance and outcomes in coronary artery disease patients.

PubMed

Martin, Billie-Jean; Hauer, Trina; Arena, Ross; Austford, Leslie D; Galbraith, P Diane; Lewin, Adriane M; Knudtson, Merril L; Ghali, William A; Stone, James A; Aggarwal, Sandeep G

2012-08-07

Cardiac rehabilitation (CR) is an efficacious yet underused treatment for patients with coronary artery disease. The objective of this study was to determine the association between CR completion and mortality and resource use. We conducted a prospective cohort study of 5886 subjects (20.8% female; mean age, 60.6 years) who had undergone angiography and were referred for CR in Calgary, AB, Canada, between 1996 and 2009. Outcomes of interest included freedom from emergency room visits, hospitalization, and survival in CR completers versus noncompleters, adjusted for clinical covariates, treatment strategy, and coronary anatomy. Hazard ratios for events for CR completers versus noncompleters were also constructed. A propensity model was used to match completers to noncompleters on baseline characteristics, and each outcome was compared between propensity-matched groups. Of the subjects referred for CR, 2900 (49.3%) completed the program, and an additional 554 subjects started but did not complete CR. CR completion was associated with a lower risk of death, with an adjusted hazard ratio of 0.59 (95% confidence interval, 0.49-0.70). CR completion was also associated with a decreased risk of all-cause hospitalization (adjusted hazard ratio, 0.77; 95% confidence interval, 0.71-0.84) and cardiac hospitalization (adjusted hazard ratio, 0.68; 95% confidence interval, 0.55-0.83) but not with emergency room visits. Propensity-matched analysis demonstrated a persistent association between CR completion and reduced mortality. Among those coronary artery disease patients referred, CR completion is associated with improved survival and decreased hospitalization. There is a need to explore reasons for nonattendance and to test interventions to improve attendance after referral.

Sleeping difficulty, disease and mortality in older women: a latent class analysis and distal survival analysis.

PubMed

Leigh, Lucy; Hudson, Irene L; Byles, Julie E

2015-12-01

The aim of this study is to identify patterns of sleep difficulty in older women, to investigate whether sleep difficulty is an indicator for poorer survival, and to determine whether sleep difficulty modifies the association between disease and death. Data were from the Australian Longitudinal Study on Women's Health, a 15-year longitudinal cohort study, with 10 721 women aged 70-75 years at baseline. Repeated-measures latent class analysis identified four classes of persistent sleep difficulty: troubled sleepers (N = 2429, 22.7%); early wakers (N = 3083, 28.8%); trouble falling asleep (N = 1767, 16.5%); and untroubled sleepers (N = 3442, 32.1%). Sleep difficulty was an indicator for mortality. Compared with untroubled sleepers, hazard ratios and 95% confidence intervals for troubled sleepers, early wakers, and troubled falling asleep were 1.12 (1.03, 1.23), 0.81 (0.75, 0.91) and 0.89 (0.79, 1.00), respectively. Sleep difficulty may modify the prognosis of women with chronic diseases. Hazard ratios (and 95% confidence intervals) for having three or more diseases (compared with 0 diseases) were enhanced for untroubled sleepers, early wakers and trouble falling asleep [hazard ratio = 1.86 (1.55, 2.22), 1.91 (1.56, 2.35) and 1.98 (1.47, 2.66), respectively], and reduced for troubled sleepers [hazard ratio = 1.57 (1.24, 1.98)]. Sleep difficulty in older women is more complex than the presence or absence of sleep difficulty, and should be considered when assessing the risk of death associated with disease. © 2015 European Sleep Research Society.

Combination Antifungal Therapy for Cryptococcal Meningitis

PubMed Central

Day, Jeremy N.; Chau, Tran T.H.; Wolbers, Marcel; Mai, Pham P.; Dung, Nguyen T.; Mai, Nguyen H.; Phu, Nguyen H.; Nghia, Ho D.; Phong, Nguyen D.; Thai, Cao Q.; Thai, Le H.; Chuong, Ly V.; Sinh, Dinh X.; Duong, Van A.; Hoang, Thu N.; Diep, Pham T.; Campbell, James I.; Sieu, Tran P.M.; Baker, Stephen G.; Chau, Nguyen V.V.; Hien, Tran T.

2014-01-01

BACKGROUND Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days. METHODS We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks. RESULTS A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval [CI], 0.30 to 1.08; unadjusted P = 0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P = 0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P = 0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P = 0.13). amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (−0.42 log10 colony-forming units [CFU] per milliliter per day vs. −0.31 and −0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although neutropenia was more frequent in patients receiving a combination therapy. CONCLUSIONS Amphotericin B plus flucytosine, as compared with amphotericin B alone, is associated with improved survival among patients with cryptococcal meningitis. A survival benefit of amphotericin B plus fluconazole was not found. (Funded by the Wellcome Trust and the British Infection Society; Controlled-Trials.com number, ISRCTN95123928.) PMID:23550668

A comparison of robust principal component analysis techniques for buried object detection in downward looking GPR sensor data

NASA Astrophysics Data System (ADS)

Pinar, Anthony; Havens, Timothy C.; Rice, Joseph; Masarik, Matthew; Burns, Joseph; Thelen, Brian

2016-05-01

Explosive hazards are a deadly threat in modern conflicts; hence, detecting them before they cause injury or death is of paramount importance. One method of buried explosive hazard discovery relies on data collected from ground penetrating radar (GPR) sensors. Threat detection with downward looking GPR is challenging due to large returns from non-target objects and clutter. This leads to a large number of false alarms (FAs), and since the responses of clutter and targets can form very similar signatures, classifier design is not trivial. One approach to combat these issues uses robust principal component analysis (RPCA) to enhance target signatures while suppressing clutter and background responses, though there are many versions of RPCA. This work applies some of these RPCA techniques to GPR sensor data and evaluates their merit using the peak signal-to-clutter ratio (SCR) of the RPCA-processed B-scans. Experimental results on government furnished data show that while some of the RPCA methods yield similar results, there are indeed some methods that outperform others. Furthermore, we show that the computation time required by the different RPCA methods varies widely, and the selection of tuning parameters in the RPCA algorithms has a major effect on the peak SCR.

Joint association between body fat and its distribution with all-cause mortality: A data linkage cohort study based on NHANES (1988-2011)

PubMed Central

Peng, Yang; Wang, Zhiqiang; Adegbija, Odewumi; Hu, Jie; Ma, Jun; Ma, Ying-Hua

2018-01-01

Objective Although obesity is recognized as an important risk of mortality, how the amount and distribution of body fat affect mortality risk is unclear. Furthermore, whether fat distribution confers any additional risk of mortality in addition to fat amount is not understood. Methods This data linkage cohort study included 16415 participants (8554 females) aged 18 to 89 years from National Health and Nutrition Examination Survey III (1988–1994) and its linked mortality data (31 December 2011). Cox proportional hazard models and parametric survival models were used to estimate the association between body fat percentage (BF%), based on bioelectrical impedance analysis, and waist-hip ratio (WHR) with mortality. Results A total of 4999 deaths occurred during 19-year follow-up. A U-shaped association between BF% and mortality was found in both sexes, with the adjusted hazard ratios for other groups between 1.02 (95% confidence interval: 0.89, 1.18) and 2.10 (1.47, 3.01) when BF% groups of 25–30% in males and 30–35% in females were used as references. A non-linear relationship between WHR and mortality was detected in males, with the adjusted hazard ratios among other groups ranging from 1.05 (0.94, 1.18) to 1.52 (1.15, 2.00) compared with the WHR category of 0.95–1.0. However in females, the death risk constantly increased across the WHR spectrum. Joint impact of BF% and WHR suggested males with BF% of 25–30% and WHR of 0.95–1.0 and females with BF% of 30–35% and WHR <0.9 were associated with the lowest mortality risk and longest survival age compared with their counterparts in other categories. Conclusions This study supported the use of body fat distribution in addition to fat amount in assessing the risk of all-cause mortality. PMID:29474498

A Gender-Stratified Comparative Analysis of Various Definitions of Metabolic Syndrome and Cardiovascular Risk in a Multiethnic U.S. Population

PubMed Central

Hari, Pawan; Nerusu, Kamalakar; Veeranna, Vikas; Sudhakar, Rajeev; Zalawadiya, Sandip; Ramesh, Krithi

2012-01-01

Abstract Introduction We sought to evaluate the ability of various metabolic syndrome definitions in predicting primary cardiovascular disease (CVD) outcomes in a vast multiethnic U.S. cohort. Methods This study included 6,814 self-identified men and women aged 45–84 years enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) study. Gender-stratified analyses were performed to calculate hazard ratios of CVD, stroke, and mortality associated with various metabolic syndrome definitions and their individual constructs. Results The hazard ratios [95% confidence interval (CI)] for all-cause CVD in men were 2.90 (2.18–3.85), 2.64 (1.98–3.51), 2.16 (1.62–2.88), 2.56 (1.91–3.44), 1.82 (1.35–2.46), and 2.92 (2.15–3.95) for the National Cholesterol Education Program (NCEP), American Heart Association (AHA), World Health Organization (WHO), International Diabetes Federation (IDF), European Group for the Study of Insulin Resistance (EGIR), and the newly defined consensus criteria. Hazard ratios in women were 2.11 (1.41–3.15), 2.17 (1.45–3.27), 2.04 (1.37–3.06), 1.91 (1.27–2.88), 1.85 (1.23–2.79), and 2.08 (1.37–3.14), respectively. Metabolic syndrome was strongly associated with stroke risk only in males. In men, all constitutive metabolic syndrome components were continuously and strongly associated with CVD. In women, high-density lipoprotein and triglycerides did not appear to be associated with short term CVD risk. Conclusion We found the newly defined consensus criteria for metabolic syndrome to be similarly predictive of cardiovascular events when compared to existing definitions. Significant gender differences exist in the association between metabolic syndrome, its individual components, and CVD. PMID:21999397

Diabetes mellitus with obesity is a predictor of recurrence in patients with non-metastatic renal cell carcinoma.

PubMed

Fukushima, Hiroshi; Masuda, Hitoshi; Yokoyama, Minato; Tatokoro, Manabu; Yoshida, Soichiro; Ishioka, Junichiro; Matsuoka, Yoh; Numao, Noboru; Koga, Fumitaka; Saito, Kazutaka; Fujii, Yasuhisa; Kihara, Kazunori

2013-07-01

To investigate the associations of diabetes mellitus with recurrence and prognosis after surgery for non-metastatic renal cell carcinoma and the effect modification of obesity on the above relationships. We retrospectively evaluated 543 patients with non-metastatic renal cell carcinoma (pT1-4N0M0) who underwent radical or partial nephrectomy. The association of diabetes mellitus with recurrence was analyzed using the Kaplan-Meier method and the Cox regression model. We also examined whether the above relationships were modified by obesity using subgroup analysis and tests of interaction. For subgroup analysis, the body mass index was categorized as non-obese (<25 kg/m(2)) and obese (≥25 kg/m(2)). Eighty-two patients (15.1%) had a history of diabetes mellitus. During the mean follow-up of 66.7 months, 68 patients (12.5%) developed recurrence. Although the body mass index was not associated with recurrence, diabetes mellitus was an independent predictor of recurrence in multivariate analysis (hazard ratio 2.43, P = 0.003), along with tumor diameter, grade and pathological T stage. In further subgroup analysis, the same relationship between diabetes mellitus and recurrence was clearly shown in the obese group (hazard ratio 4.07, P = 0.010), but not in the non-obese group (hazard ratio 1.95, P = 0.125). At the same time, obesity modified the effect of diabetes mellitus on recurrence with a trend (P-interaction = 0.086). In the obese group, 5-year recurrence-free survival rates were 75.3 and 91.9% for diabetes mellitus and non-diabetes mellitus patients, respectively (P < 0.001). Restricting analyses to patients with clear cell type histology did not materially change these results. Diabetes mellitus is a predictor of recurrence following surgery for non-metastatic renal cell carcinoma, especially in obese patients.

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

Metabolic syndrome and risk of incident diabetes: findings from the European Prospective Investigation into Cancer and Nutrition-Potsdam Study

PubMed Central

Ford, Earl S; Schulze, Matthias B; Pischon, Tobias; Bergmann, Manuela M; Joost, Hans-Georg; Boeing, Heiner

2008-01-01

Background Several aspects concerning the relationship between the metabolic syndrome and incident diabetes are incompletely understood including the magnitude of the risk estimate, potential gender differences in the associations between the metabolic syndrome and incident diabetes, the associations between the components of the metabolic syndrome and incident diabetes, and whether the metabolic syndrome provides additional prediction beyond its components. To shed light on these issues, we examined the prospective association between the metabolic syndrome defined by the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) and diabetes. Methods We used data for 2796 men and women aged 35–65 years from the European Prospective Investigation into Cancer and Nutrition-Potsdam Study followed for an average of 6.9 years. This analysis employed a case-cohort design that included 697 participants who developed diabetes and 2099 participants who did not. Incident diabetes was identified on the basis of self-reports and verified by contacting the patient's attending physician. Results The adjusted hazard ratio for the NCEP definition was 4.62 (95% confidence interval [CI]: 3.90–5.48) and that for the IDF definition was 4.59 (95% CI: 3.84–5.50). The adjusted hazard ratios for the NCEP but not IDF definition were higher for women than men. When participants who had no cardiometabolic abnormalities were used as the reference group for the NCEP definition, the adjusted hazard ratio for having 3 or more abnormalities increased to 22.50 (95% CI: 11.21–45.19). Of the five components, abdominal obesity and hyperglycemia were most strongly associated with incident diabetes. Conclusion In this study population, both definitions of the metabolic syndrome provided similar estimates of relative risk for incident diabetes. The increase in risk for participants with the metabolic syndrome according to the NCEP definition was very large when contrasted with the risk among those who had no cardiometabolic abnormalities. PMID:19077281

Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy.

PubMed

Lee, Yi-Ying; Wei, Yu-Ching; Tian, Yu-Feng; Sun, Ding-Ping; Sheu, Ming-Jen; Yang, Ching-Chieh; Lin, Li-Ching; Lin, Chen-Yi; Hsing, Chung-Hsi; Li, Wan-Shan; Li, Chien-Feng; Hsieh, Pei-Ling; Lin, Ching-Yih

2017-01-01

Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an increasingly common therapeutic strategy for locally advanced rectal cancer, but stratification of risk and final outcomes remain a major challenge. Transcobalamin 1 (TCN1), a vitamin B12 (cobalamin)-binding protein, regulates cobalamin homeostasis. High expression of TCN1 have been reported in neoplasms such as breast cancer and hepatocellular carcinoma. However, little is known about the relevance of TCN1 to rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of TCN1 expression in patients with rectal cancer following neoadjuvant CCRT. Methods: Through data mining from a published transcriptome of rectal cancers (GSE35452), we identified upregulation of TCN1 gene as the most significantly predicted poor response to CCRT among ion transport-related genes (GO:0006811). We evaluated TCN1 immunohistochemistry and performed an H-score analysis on endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery. Expression levels of TCN1 were further correlated with clinicopathologic features, therapeutic response, tumor regression grade (TRG) and survivals including metastasis-free survival (MeFS), disease-specific survival (DSS) and recurrent-free survival (LRFS). Results: TCN1 overexpression was significantly related to advanced post-treatment tumor (T3, T4; p <0.001) and nodal status (N1, N2; p <0.001), vascular invasion ( p =0.003) and inferior tumor regression grade ( p < 0.001). In survival analyses, TCN1 overexpression was significantly associated with shorter DSS ( p <0.0001), MeFS ( p =0.0002) and LRFS ( p =0.0001). Furthermore, it remained an independent prognosticator of worse DSS ( p =0.002, hazard ratio=3.344), MeFS ( p =0.021, hazard ratio=3.015) and LRFS ( p =0.037, hazard ratio=3.037) in the multivariate comparison. Conclusion: Overexpression of TCN1 is associated with poor therapeutic response and adverse outcomes in rectal cancer patients receiving CCRT, justifying the potential prognostic value of TCN1 in rectal cancer receiving CCRT.

Adjuvant Exemestane with Ovarian Suppression in Premenopausal Breast Cancer

PubMed Central

Pagani, Olivia; Regan, Meredith M.; Walley, Barbara A.; Fleming, Gini F.; Colleoni, Marco; Láng, István; Gomez, Henry L.; Tondini, Carlo; Burstein, Harold J.; Perez, Edith A.; Ciruelos, Eva; Stearns, Vered; Bonnefoi, Hervé R.; Martino, Silvana; Geyer, Charles E.; Pinotti, Graziella; Puglisi, Fabio; Crivellari, Diana; Ruhstaller, Thomas; Winer, Eric P.; Rabaglio-Poretti, Manuela; Maibach, Rudolf; Ruepp, Barbara; Giobbie-Hurder, Anita; Price, Karen N.; Bernhard, Jürg; Luo, Weixiu; Ribi, Karin; Viale, Giuseppe; Coates, Alan S.; Gelber, Richard D.; Goldhirsch, Aron; Francis, Prudence A.

2014-01-01

BACKGROUND Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor–positive breast cancer. METHODS In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor–positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials. RESULTS After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane–ovarian suppression group and 87.3% in the tamoxifen–ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane–ovarian suppression group, as compared with 88.8% in the tamoxifen–ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane–ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P = 0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane–ovarian suppression group and 29.4% of those in the tamoxifen–ovarian suppression group, with profiles similar to those for postmenopausal women. CONCLUSIONS In premenopausal women with hormone-receptor–positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence. (Funded by Pfizer and others; TEXT and SOFT ClinicalTrials.gov numbers, NCT00066703 and NCT00066690, respectively.) PMID:24881463

Serum Albumin and High-Sensitivity C-reactive Protein are Independent Risk Factors of Chronic Kidney Disease in Middle-Aged Japanese Individuals: the Circulatory Risk in Communities Study

PubMed Central

Kubo, Sachimi; Kitamura, Akihiko; Imano, Hironori; Cui, Renzhe; Yamagishi, Kazumasa; Umesawa, Mitsumasa; Muraki, Isao; Kiyama, Masahiko; Okada, Takeo

2016-01-01

Aim: It is important to explore predictive markers other than conventional cardiovascular risk factors for early detection and treatment of chronic kidney disease (CKD), a major risk factor for end-stage renal failure. We hypothesized that serum albumin and high-sensitivity C-reactive protein (hs-CRP) to be independent markers, and examined their associations with the risk of CKD. Methods: We examined the associations of serum albumin and hs-CRP levels with the risk of incident CKD, in 2535 Japanese adults aged 40–69 years without CKD at baseline during a median 9.0-year follow-up after adjustment for known cardiovascular risk factors. Results: During the follow-up period, 367 cases of CKD developed. In multivariable analyses adjusted for known risk factors, the CKD hazard ratios (95% confidence intervals) for the highest versus lowest quartiles of serum albumin levels were 0.69 (0.40–1.17) for men and 0.42 (0.28–0.64) for women. Corresponding values for hs-CRP were 0.95 (0.54–1.67) for men and 1.85 (1.25 -2.75) for women. The association of combined serum albumin and hs-CRP with the risk of CKD was examined for women. The hazard ratio was 1.72 (1.17–2.54) for low versus higher albumin levels at lower hs-CRP levels, but such an association was not observed at high hs-CRP level. The hazard ratio was 1.96 (1.44–2.66) for high versus lower hs-CRP levels at higher serum albumin levels, but such association was not observed at low serum albumin level. Conclusion: Both low serum albumin and high hs-CRP levels were predictive of CKD for women. PMID:26911856

Alleviation of mandibular anterior crowding with copper-nickel-titanium vs nickel-titanium wires: a double-blind randomized control trial.

PubMed

Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2009-08-01

The purpose of this study was to investigate the efficiency of copper-nickel-titanium (CuNiTi) vs nickel-titanium (NiTi) archwires in resolving crowding of the anterior mandibular dentition. Sixty patients were included in this single-center, single-operator, double-blind randomized trial. All patients were bonded with the In Ovation-R self-ligating bracket (GAC, Central Islip, NY) with a 0.022-in slot, and the amount of crowding of the mandibular anterior dentition was assessed by using the irregularity index. The patients were randomly allocated into 2 groups of 30 patients, each receiving a 0.016-in CuNiTi 35 degrees C (Ormco, Glendora, Calif) or a 0.016-in NiTi (ModernArch, Wyomissing, Pa) wire. The type of wire selected for each patient was not disclosed to the provider or the patient. The date that each patient received a wire was recorded, and all patients were followed monthly for a maximum of 6 months. Demographic and clinical characteristics between the 2 wire groups were compared with the t test or the chi-square test and the Fisher exact test. Time to resolve crowding was explored with statistical methods for survival analysis, and alignment rate ratios for wire type and crowding level were calculated with Cox proportional hazards multivariate modeling. The type of wire (CuNiTi vs NiTi) had no significant effect on crowding alleviation (129.4 vs 121.4 days; hazard ratio, 1.3; P >0.05). Severe crowding (>5 on the irregularity index) showed a significantly higher probability of crowding alleviation duration relative to dental arches with a score of <5 (138.5 vs 113.1 days; hazard ratio, 2.2; P=0.02). The difference of the loading pattern of wires in laboratory and clinical conditions might effectively eliminate the laboratory-derived advantage of CuNiTi wires.

Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement

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

Bingham, Brian; Orton, Andrew; Boothe, Dustin

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

Drug-eluting stents versus bare-metal stents for off-label indications: a propensity score-matched outcome study.

PubMed

Austin, David; Oldroyd, Keith G; McConnachie, Alex; Slack, Rachel; Eteiba, Hany; Flapan, Andrew D; Jennings, Kevin P; Northcote, Robin J; Pell, Alastair C H; Starkey, Ian R; Pell, Jill P

2008-08-01

The US Food and Drug Administration recently concluded that data on off-label drug-eluting stent (DES) safety are limited. However, in actual clinical practice, DES are often used for off-label indications, and observational studies demonstrate that complications are higher when compared with on-label use. We aimed to determine whether clinical outcomes differ after DES and bare-metal stent implantation in a patient cohort defined by DES off-label indications. We used the national revascularization registry in Scotland to identify patients who underwent coronary stenting for an off-label indication between January 2003 and September 2005. Individual-level linkage to comprehensive national admission and death databases was used to ascertain the end points of death, myocardial infarction, and target-vessel revascularization. We calculated propensity scores on the basis of clinical, demographic, and angiographic variables and matched DES to bare-metal stents on a 1:1 basis. The final study population consisted of 1642 patients, well matched for important covariables at baseline. Event-free survival was calculated over 24 months with the Kaplan-Meier method. All-cause death was more common after bare-metal stent implantation during follow-up (7.7% versus 6.6%; hazard ratio 0.63; 95% confidence interval, 0.40 to 0.99; P=0.04). No difference in the rates of myocardial infarction were noted (7.3% versus 7.5%; hazard ratio 1.02; 95% confidence interval, 0.69 to 1.54; P=0.92). Target-vessel revascularization was reduced in patients treated with DES (13.9% versus 10.7%; hazard ratio 0.67; 95% confidence interval, 0.49 to 0.93; P=0.02). At 24 months, patients treated with DES for off-label indications had lower rates of death and target-vessel revascularization and similar rates of myocardial infarction, as compared with patients treated with bare-metal stents.

Identifying an optimal cutpoint value for the diagnosis of hypertriglyceridemia in the nonfasting state

PubMed Central

White, Khendi T.; Moorthy, M.V.; Akinkuolie, Akintunde O.; Demler, Olga; Ridker, Paul M; Cook, Nancy R.; Mora, Samia

2015-01-01

Background Nonfasting triglycerides are similar to or superior to fasting triglycerides at predicting cardiovascular events. However, diagnostic cutpoints are based on fasting triglycerides. We examined the optimal cutpoint for increased nonfasting triglycerides. Methods Baseline nonfasting (<8 hours since last meal) samples were obtained from 6,391 participants in the Women’s Health Study, followed prospectively for up to 17 years. The optimal diagnostic threshold for nonfasting triglycerides, determined by logistic regression models using c-statistics and Youden index (sum of sensitivity and specificity minus one), was used to calculate hazard ratios for incident cardiovascular events. Performance was compared to thresholds recommended by the American Heart Association (AHA) and European guidelines. Results The optimal threshold was 175 mg/dL (1.98 mmol/L), corresponding to a c-statistic of 0.656 that was statistically better than the AHA cutpoint of 200 mg/dL (c-statistic of 0.628). For nonfasting triglycerides above and below 175 mg/dL, adjusting for age, hypertension, smoking, hormone use, and menopausal status, the hazard ratio for cardiovascular events was 1.88 (95% CI, 1.52–2.33, P<0.001), and for triglycerides measured at 0–4 and 4–8 hours since last meal, hazard ratios (95%CIs) were 2.05 (1.54– 2.74) and 1.68 (1.21–2.32), respectively. Performance of this optimal cutpoint was validated using ten-fold cross-validation and bootstrapping of multivariable models that included standard risk factors plus total and HDL cholesterol, diabetes, body-mass index, and C-reactive protein. Conclusions In this study of middle aged and older apparently healthy women, we identified a diagnostic threshold for nonfasting hypertriglyceridemia of 175 mg/dL (1.98 mmol/L), with the potential to more accurately identify cases than the currently recommended AHA cutpoint. PMID:26071491

Early Mortality and Primary Causes of Death in Mothers of Children with Intellectual Disability or Autism Spectrum Disorder: A Retrospective Cohort Study

PubMed Central

Fairthorne, Jenny; Hammond, Geoff; Bourke, Jenny; Jacoby, Peter; Leonard, Helen

2014-01-01

Introduction Mothers of children with intellectual disability or autism spectrum disorder (ASD) have poorer health than other mothers. Yet no research has explored whether this poorer health is reflected in mortality rates or whether certain causes of death are more likely. We aimed to calculate the hazard ratios for death and for the primary causes of death in mothers of children with intellectual disability or ASD compared to other mothers. Methods The study population comprised all mothers of live-born children in Western Australia from 1983–2005. We accessed state-wide databases which enabled us to link socio-demographic details, birth dates, diagnoses of intellectual disability or ASD in the children and dates and causes of death for all mothers who had died prior to 2011. Using Cox Regression with death by any cause and death by each of the three primary causes as the event of interest, we calculated hazard ratios for death for mothers of children intellectual disability or ASD compared to other mothers. Results and Discussion During the study period, mothers of children with intellectual disability or ASD had more than twice the risk of death. Mothers of children with intellectual disability were 40% more likely to die of cancer; 150% more likely to die of cardiovascular disease and nearly 200% more likely to die from misadventure than other mothers. Due to small numbers, only hazard ratios for cancer were calculated for mothers of children with ASD. These mothers were about 50% more likely to die from cancer than other mothers. Possible causes and implications of our results are discussed. Conclusion Similar studies, pooling data from registries elsewhere, would improve our understanding of factors increasing the mortality of mothers of children with intellectual disability or ASD. This would allow the implementation of informed services and interventions to improve these mothers' longevity. PMID:25535971

Detection of a negative correlation between prescription of Chinese herbal products containing coumestrol, genistein or daidzein and risk of subsequent endometrial cancer among tamoxifen-treated female breast cancer survivors in Taiwan between 1998 and 2008: A population-based study.

PubMed

Hu, Yi-Cheng; Wu, Chien-Tung; Lai, Jung-Nien; Tsai, Yueh-Ting

2015-07-01

Tamoxifen users sometimes seek complementary and alternative medicine advice for treatment of a variety of illness and co-administer with phytoestrogen-containing herbs, resulting in an increasing concern of its influence in subsequent endometrial cancer risk. Our study aims to determine the prevalence of Chinese herbal products containing coumestrol, genistein, or daidzein and their association with subsequent endometrial cancer risk among tamoxifen-treated breast cancer survivors in Taiwan. We selected all patients who were newly diagnosed with invasive breast cancer and received tamoxifen treatment between January 1, 1998, and December 31, 2008, from the National Health Insurance Research Database. Among the 26,656 tamoxifen-treated breast cancer survivors, we evaluated the usage, frequency of service, and prescription of Chinese herbal products containing coumestrol, genistein, or daidzein. The logistic regression method was employed to calculate the odds ratios for utilization of those herbal products. Cox proportional hazard regression was set to calculate the hazard ratios of endometrial cancer associated with such usage. Of the patients surveyed, 36.2% (n=9652) of the tamoxifen-treated breast cancer survivors examined in the study had consumed Chinese herbal products containing coumestrol, genistein, or daidzein during the study period. Exposure to Ge Gen(Puerariae Radix) specifically was the most extensive. For it, the population consumed an average cumulative dose of above 180g. Compared to those who had never used Chinese herbal products, breast cancer survivors who had taken Chinese herbal products containing coumestrol, genistein, or daidzein concurrently with tamoxifen treatment did not have a higher hazard ratio for subsequent development of endometrial cancer. Among those tamoxifen-treated female breast cancer survivors in Taiwan, consumption of Chinese herbal products containing coumestrol, genistein, or daidzein is negatively correlated with subsequent endometrial cancer risk. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

Dinshaw, Ketayun A.; Budrukkar, Ashwini N.; Chinoy, Roshan F.

Purpose: The outcome of breast cancer treatment can vary in different geographic and ethnic groups. A multivariate analysis was performed for various prognostic factors in 1022 Indian women with pathologic Stage I-II breast cancer treated between 1980 and 2000 with standard breast-conserving therapy with or without systemic adjuvant therapy. Methods and Materials: At a mean follow-up of 53 months, the outcomes studied were local failure, locoregional failure, and distant failure, overall survival (OS), and disease-free survival (DFS). Results: The median pathologic tumor size was 3 cm (range, 1-5 cm), and axillary lymph node metastasis was present in 39% of women.more » The actuarial 5- and 10-year OS and DFS rate was 87% and 77% and 76% and 68%, respectively. Lymphovascular emboli or invasion (LVI) was the strongest independent adverse factor for all failure and survival (local failure, hazard ratio 2.85; 95% confidence interval, 1.68-4.83; OS; hazard ratio, 2.01, 95% confidence interval, 1.35-2.99). Lymph node metastasis was also an independent adverse factor for local failure, locoregional failure, distant failure, DFS, and OS (hazard ratio, 1.55, 95% confidence interval, 1.04-2.30). Age {<=}40 years increased the incidence of local recurrence, and patients with inner quadrant tumors had inferior DFS. The incidence of LVI was significantly greater in women with lymph node metastases than in node-negative women (p < 0.001) and in women with Grade 3 tumors than in those with Grade 1 or 2 tumors (p = 0.001). Conclusion: In Indian women, LVI was the strongest independent prognostic factor for OS, DFS, and local recurrence, irrespective of nodal status and systemic adjuvant treatment. Although LVI may not be a contraindication for BCT, as has been proposed by certain groups, it is necessary to define its role in prospective studies in determining local and systemic treatment.« less

Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

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

Freedland, Stephen J., E-mail: steve.freedland@duke.edu; Department of Surgery; Department of Pathology, Duke University School of Medicine, Durham, North Carolina

Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-upmore » for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.« less

Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

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

Tan, Terence, E-mail: trdtwk@nccs.com.sg; Lim, Wan-Teck; Fong, Kam-Weng

Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m{sup 2}, carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m{sup 2} given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m{sup 2}), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5%more » significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.« less

Stress cardiac magnetic resonance imaging provides effective cardiac risk reclassification in patients with known or suspected stable coronary artery disease.

PubMed

Shah, Ravi; Heydari, Bobak; Coelho-Filho, Otavio; Murthy, Venkatesh L; Abbasi, Siddique; Feng, Jiazhuo H; Pencina, Michael; Neilan, Tomas G; Meadows, Judith L; Francis, Sanjeev; Blankstein, Ron; Steigner, Michael; di Carli, Marcelo; Jerosch-Herold, Michael; Kwong, Raymond Y

2013-08-06

A recent large-scale clinical trial found that an initial invasive strategy does not improve cardiac outcomes beyond optimized medical therapy in patients with stable coronary artery disease. Novel methods to stratify at-risk patients may refine therapeutic decisions to improve outcomes. In a cohort of 815 consecutive patients referred for evaluation of myocardial ischemia, we determined the net reclassification improvement of the risk of cardiac death or nonfatal myocardial infarction (major adverse cardiac events) incremental to clinical risk models, using guideline-based low (<1%), moderate (1% to 3%), and high (>3%) annual risk categories. In the whole cohort, inducible ischemia demonstrated a strong association with major adverse cardiac events (hazard ratio=14.66; P<0.0001) with low negative event rates of major adverse cardiac events and cardiac death (0.6% and 0.4%, respectively). This prognostic robustness was maintained in patients with previous coronary artery disease (hazard ratio=8.17; P<0.0001; 1.3% and 0.6%, respectively). Adding inducible ischemia to the multivariable clinical risk model (adjusted for age and previous coronary artery disease) improved discrimination of major adverse cardiac events (C statistic, 0.81-0.86; P=0.04; adjusted hazard ratio=7.37; P<0.0001) and reclassified 91.5% of patients at moderate pretest risk (65.7% to low risk; 25.8% to high risk) with corresponding changes in the observed event rates (0.3%/y and 4.9%/y for low and high risk posttest, respectively). Categorical net reclassification index was 0.229 (95% confidence interval, 0.063-0.391). Continuous net reclassification improvement was 1.11 (95% confidence interval, 0.81-1.39). Stress cardiac magnetic resonance imaging effectively reclassifies patient risk beyond standard clinical variables, specifically in patients at moderate to high pretest clinical risk and in patients with previous coronary artery disease. http://www.clinicaltrials.gov. Unique identifier: NCT01821924.

Glutamate Decarboxylase 1 Overexpression as a Poor Prognostic Factor in Patients with Nasopharyngeal Carcinoma.

PubMed

Lee, Yi-Ying; Chao, Tung-Bo; Sheu, Ming-Jen; Tian, Yu-Feng; Chen, Tzu-Ju; Lee, Sung-Wei; He, Hong-Lin; Chang, I-Wei; Hsing, Chung-Hsi; Lin, Ching-Yih; Li, Chien-Feng

2016-01-01

Background : Glutamate decarboxylase 1 (GAD1) which serves as a rate-limiting enzyme involving in the production of γ-aminobutyric acid (GABA), exists in the GABAergic neurons in the central nervous system (CNS). Little is known about the relevance of GAD1 to nasopharyngeal carcinoma (NPC). Through data mining on a data set derived from a published transcriptome database, this study first identified GAD1 as a differentially upregulated gene in NPC. We aimed to evaluate GAD1 expression and its prognostic effect on patients with early and locoregionally advanced NPC. Methods : We evaluated GAD1 immunohistochemistry and performed an H-score analysis on biopsy specimens from 124 patients with nonmetastasized NPC receiving treatment. GAD1 overexpression was defined as an H score higher than the median value. The findings of such an analysis are correlated with clinicopathological behaviors and survival rates, namely disease-specific survival (DSS), distant-metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) rates. Results : GAD1 overexpression was significantly associated with an increase in the primary tumor status ( p < 0.001) and American Joint Committee on Cancer (AJCC) stages III-IV ( p = 0.002) and was a univariate predictor of adverse outcomes of DSS ( p = 0.002), DMeFS ( p < 0.0001), and LRFS ( p = 0.001). In the multivariate comparison, in addition to advanced AJCC stages III-IV, GAD1 overexpression remained an independent prognosticator of short DSS ( p = 0.004, hazard ratio = 2.234), DMeFS ( p < 0.001, hazard ratio = 4.218), and LRFS ( p = 0.013, hazard ratio = 2.441) rates. Conclusions : Our data reveal that GAD1 overexpression was correlated with advanced disease status and may thus be a critical prognostic indicator of poor outcomes in NPC and a potential therapeutic target to facilitate the development of effective treatment modalities.

Frequent methamphetamine injection predicts emergency department utilization among street-involved youth

PubMed Central

Marshall, B.D.L.; Grafstein, E.; Buxton, J.A.; Qi, J.; Wood, E.; Shoveller, J.A.; Kerr, T.

2011-01-01

SUMMARY Objectives Methamphetamine (MA) use has been associated with health problems that commonly present in the emergency department (ED). This study sought to determine whether frequent MA injection was a risk factor for ED utilization among street-involved youth. Study design Prospective cohort study. Methods Data were derived from a street-involved youth cohort known as the ‘At Risk Youth Study’. Behavioural data including MA use were linked to ED records at a major inner-city hospital. Kaplan-Meier and Cox proportional hazards methods were used to determine the risk factors for ED utilization. Results Between September 2005 and January 2007, 427 eligible participants were enrolled, among whom the median age was 21 (interquartile range 19–23) years and 154 (36.1%) were female. Within 1 year, 163 (38.2%) visited the ED, resulting in an incidence density of 53.7 per 100 person-years. ED utilization was significantly higher among frequent (i.e. ≥daily) MA injectors (log-rank P=0.004). In multivariate analysis, frequent MA injection was associated with an increased hazard of ED utilization (adjusted hazard ratio=1.84, 95% confidence interval 1.04–3.25; P=0.036). Conclusions Street-involved youth who frequently inject MA appear to be at increased risk of ED utilization. The integration of MA-specific addiction treatment services within emergency care settings for high-risk youth is recommended. PMID:22133669

Meat intake and meat preparation in relation to risk of postmenopausal breast cancer in the NIH-AARP diet and health study.

PubMed

Kabat, Geoffrey C; Cross, Amanda J; Park, Yikyung; Schatzkin, Arthur; Hollenbeck, Albert R; Rohan, Thomas E; Sinha, Rashmi

2009-05-15

A number of studies have reported that intake of red meat or meat cooked at high temperatures is associated with increased risk of breast cancer, but other studies have shown no association. We assessed the association between meat, meat-cooking methods, and meat-mutagen intake and postmenopausal breast cancer in the NIH-AARP Diet and Health Study cohort of 120,755 postmenopausal women who completed a food frequency questionnaire at baseline (1995-1996) as well as a detailed meat-cooking module within 6 months following baseline. During 8 years of follow-up, 3,818 cases of invasive breast cancer were identified in this cohort. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). After adjusting for covariates, intake of total meat, red meat, meat cooked at high temperatures, and meat mutagens showed no association with breast cancer risk. This large prospective study with detailed information on meat preparation methods provides no support for a role of meat mutagens in the development of postmenopausal breast cancer. (c) 2008 Wiley-Liss, Inc.

How much does a reminder letter increase cervical screening among under-screened women in NSW?

PubMed

Morrell, Stephen; Taylor, Richard; Zeckendorf, Sue; Niciak, Amanda; Wain, Gerard; Ross, Jayne

2005-02-01

To evaluate a direct mail-out campaign to increase Pap screening rates in women who have not had a test in 48 months. Ninety thousand under-screened women were randomised to be mailed a 48-month reminder letter to have a Pap test (n=60,000), or not to be mailed a letter (n=30,000). Differences in Pap test rates were assessed by Kaplan-Meier survival analysis, by chi2 tests of significance between Pap test rates in letter versus no-letter groups, and by proportional hazards regression modelling of predictors of a Pap test with letter versus no-letter as the main study variable. T-tests were conducted on mean time to Pap test to assess whether time to Pap test was significantly different between the intervention and control groups. After 90 days following each mail-out, Pap test rates in the letter group were significantly higher than in the non-letter group, by approximately two percentage points. After controlling for potential confounders, the hazard ratio of a Pap test within 90 days of a mail-out in the letter group was 1.5 compared with 1.0 in the no-letter group. Hazard ratios of having a Pap test within 90 days decreased significantly with time since last Pap test (p<0.0001); were significantly higher than 1.0 for most non-metropolitan areas of NSW compared with metropolitan areas; and increased significantly with age (p<0.0001). Pap test hazard ratios were not associated with socio-economic status of area of residence, but the hazard ratio was significantly higher than 1.0 if the reminder letter was sent after the Christmas/New Year break. No significant differences in mean time to Pap test were found between the letter and no-letter groups. Being sent a reminder letter is associated with higher Pap testing rates in under-screened women.

Association of Osteopontin, Neopterin, and Myeloperoxidase With Stroke Risk in Patients With Prior Stroke or Transient Ischemic Attacks: Results of an Analysis of 13 Biomarkers From the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trial.

PubMed

Ganz, Peter; Amarenco, Pierre; Goldstein, Larry B; Sillesen, Henrik; Bao, Weihang; Preston, Gregory M; Welch, K Michael A

2017-12-01

Established risk factors do not fully identify patients at risk for recurrent stroke. The SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) evaluated the effect of atorvastatin on stroke risk in patients with a recent stroke or transient ischemic attack and no known coronary heart disease. This analysis explored the relationships between 13 plasma biomarkers assessed at trial enrollment and the occurrence of outcome strokes. We conducted a case-cohort study of 2176 participants; 562 had outcome strokes and 1614 were selected randomly from those without outcome strokes. Time to stroke was evaluated by Cox proportional hazards models. There was no association between time to stroke and lipoprotein-associated phospholipase A 2 , monocyte chemoattractant protein-1, resistin, matrix metalloproteinase-9, N-terminal fragment of pro-B-type natriuretic peptide, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, or soluble CD40 ligand. In adjusted analyses, osteopontin (hazard ratio per SD change, 1.362; P <0.0001), neopterin (hazard ratio, 1.137; P =0.0107), myeloperoxidase (hazard ratio, 1.177; P =0.0022), and adiponectin (hazard ratio, 1.207; P =0.0013) were independently associated with outcome strokes. After adjustment for the Stroke Prognostic Instrument-II and treatment, osteopontin, neopterin, and myeloperoxidase remained independently associated with outcome strokes. The addition of these 3 biomarkers to Stroke Prognostic Instrument-II increased the area under the receiver operating characteristic curve by 0.023 ( P =0.015) and yielded a continuous net reclassification improvement (29.1%; P <0.0001) and an integrated discrimination improvement (42.3%; P <0.0001). Osteopontin, neopterin, and myeloperoxidase were independently associated with the risk of recurrent stroke and improved risk classification when added to a clinical risk algorithm. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00147602. © 2017 American Heart Association, Inc.

Invasive adenocarcinoma with bronchoalveolar features: a population-based evaluation of the extent of resection in bronchoalveolar cell carcinoma.

PubMed

Whitson, Bryan A; Groth, Shawn S; Andrade, Rafael S; Mitiek, Mohi O; Maddaus, Michael A; D'Cunha, Jonathan

2012-03-01

We used a population-based data set to assess the association between the extent of pulmonary resection for bronchoalveolar carcinoma and survival. The reports thus far have been limited to small, institutional series. Using the Surveillance, Epidemiology, and End Results database (1988-2007), we identified patients with bronchoalveolar carcinoma who had undergone wedge resection, segmentectomy, or lobectomy. The bronchoalveolar carcinoma histologic findings were mucinous, nonmucinous, mixed, not otherwise specified, and alveolar carcinoma. To adjust for potential confounders, we used a Cox proportional hazards regression model. A total of 6810 patients met the inclusion criteria. Compared with the sublobar resections (wedge resections and segmentectomies), lobectomy conferred superior 5-year overall (59.5% vs 43.9%) and cancer-specific (67.1% vs 53.1%) survival (P < .0001). After adjusting for potential confounding patient and tumor characteristics, we found that patients who underwent an anatomic resection had significantly better overall (segmentectomy: hazard ratio, 0.59; 95% confidence interval, 0.43-0.81; lobectomy: hazard ratio, 0.50; 95% confidence interval, 0.44-0.57) and cancer-specific (segmentectomy: hazard ratio, 0.51; 95% confidence interval, 0.34-0.75; lobectomy: hazard ratio, 0.46; 95% confidence interval, 0.40-0.53) survival compared with patients who underwent wedge resection. Additionally, gender, race, tumor size, and degree of tumor de-differentiation were negative prognostic factors. Our results were unchanged when we limited our analysis to early-stage disease. Using a population-based data set, we found that anatomic resections for bronchoalveolar carcinoma conferred superior overall and cancer-specific survival rates compared with wedge resection. Bronchoalveolar carcinoma's propensity for intraparenchymal spread might be the underlying biologic basis of our observation of improved survival after anatomic resection. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

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

PubMed Central

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

2018-01-01

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

Association between low-dose acetylsalicylic acid reinitiation and the risk of myocardial infarction or coronary heart disease death.

PubMed

Sáez, María E; González-Pérez, Antonio; Johansson, Saga; Himmelmann, Anders; García Rodríguez, Luis A

2016-07-01

In secondary cardiovascular prevention, discontinuation of acetylsalicylic acid (ASA) is associated with an increased risk of cardiovascular events. This study assessed the impact of ASA reinitiation on the risk of myocardial infarction and coronary heart disease death. Patients prescribed ASA for secondary cardiovascular prevention and who had had a period of ASA discontinuation of ≥90 days in 2000-2007 were identified from The Health Improvement Network (N = 10,453). Incidence of myocardial infarction/coronary heart disease death was calculated. Survival analyses using adjusted Cox proportional hazard models were performed to calculate hazard ratios and 95% confidence intervals for the risk of myocardial infarction/coronary heart disease death associated with ASA use patterns after the initial period of discontinuation. Individuals who were prescribed ASA during follow-up were considered reinitiators. The incidence of myocardial infarction/coronary heart disease death was 8.90 cases per 1000 person-years. Risk of myocardial infarction/coronary heart disease death was similar for current ASA users, who had been continuously exposed since reinitiation, and patients who had not reinitiated ASA (hazard ratio 1.27, 95% confidence interval 0.93-1.73). Among reinitiators, an additional period of ASA discontinuation was associated with increased risk of myocardial infarction/coronary heart disease death compared with no reinitiation (current users: hazard ratio 1.46, 95% confidence interval 1.13-1.90; noncurrent users: hazard ratio 1.70, 95% confidence interval 1.31-2.21). ASA reinitiation was not associated with a decreased risk of myocardial infarction/coronary heart disease death. This may be explained by confounding by indication/comorbidity, whereby higher-risk patients are more likely to reinitiate therapy. An additional period of ASA discontinuation among reinitiators was associated with an increased risk of myocardial infarction/coronary heart disease death. © The European Society of Cardiology 2015.

History of Childhood Kidney Disease and Risk of Adult End-Stage Renal Disease.

PubMed

Calderon-Margalit, Ronit; Golan, Eliezer; Twig, Gilad; Leiba, Adi; Tzur, Dorit; Afek, Arnon; Skorecki, Karl; Vivante, Asaf

2018-02-01

The long-term risk associated with childhood kidney disease that had not progressed to chronic kidney disease in childhood is unclear. We aimed to estimate the risk of future end-stage renal disease (ESRD) among adolescents who had normal renal function and a history of childhood kidney disease. We conducted a nationwide, population-based, historical cohort study of 1,521,501 Israeli adolescents who were examined before compulsory military service in 1967 through 1997; data were linked to the Israeli ESRD registry. Kidney diseases in childhood included congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease; all participants included in the primary analysis had normal renal function and no hypertension in adolescence. Cox proportional-hazards models were used to estimate the hazard ratio for ESRD associated with a history of childhood kidney disease. During 30 years of follow-up, ESRD developed in 2490 persons. A history of any childhood kidney disease was associated with a hazard ratio for ESRD of 4.19 (95% confidence interval [CI], 3.52 to 4.99). The associations between each diagnosis of kidney disease in childhood (congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease) and the risk of ESRD in adulthood were similar in magnitude (multivariable-adjusted hazard ratios of 5.19 [95% CI, 3.41 to 7.90], 4.03 [95% CI, 3.16 to 5.14], and 3.85 [95% CI, 2.77 to 5.36], respectively). A history of kidney disease in childhood was associated with younger age at the onset of ESRD (hazard ratio for ESRD among adults <40 years of age, 10.40 [95% CI, 7.96 to 13.59]). A history of clinically evident kidney disease in childhood, even if renal function was apparently normal in adolescence, was associated with a significantly increased risk of ESRD, which suggests that kidney injury or structural abnormality in childhood has long-term consequences.

Longer Duration and Earlier Age of Onset of Paternal Betel Chewing and Smoking Increase Metabolic Syndrome Risk in Human Offspring, Independently, in a Community-Based Screening Program in Taiwan.

PubMed

Yen, Amy Ming-Fang; Boucher, Barbara J; Chiu, Sherry Yueh-Hsia; Fann, Jean Ching-Yuan; Chen, Sam Li-Sheng; Huang, Kuo-Chin; Chen, Hsiu-Hsi

2016-08-02

Transgenerational effects of paternal Areca catechu nut chewing on offspring metabolic syndrome (MetS) risk in humans, on obesity and diabetes mellitus experimentally, and of paternal smoking on offspring obesity, are reported, likely attributable to genetic and epigenetic effects previously reported in betel-associated disease. We aimed to determine the effects of paternal smoking, and betel chewing, on the risks of early MetS in human offspring. The 13 179 parent-child trios identified from 238 364 Taiwanese aged ≥20 years screened at 2 community-based integrated screening sessions were tested for the effects of paternal smoking, areca nut chewing, and their duration prefatherhood on age of detecting offspring MetS at screen by using a Cox proportional hazards regression model. Offspring MetS risks increased with prefatherhood paternal areca nutusage (adjusted hazard ratio, 1.77; 95% confidence interval [CI], 1.23-2.53) versus nonchewing fathers (adjusted hazard ratio, 3.28; 95% CI, 1.67-6.43) with >10 years paternal betel chewing, 1.62 (95% CI, 0.88-2.96) for 5 to 9 years, and 1.42 (95% CI, 0.80-2.54) for <5 years betel usage prefatherhood (Ptrend=0.0002), with increased risk (adjusted hazard ratio, 1.95; 95% CI, 1.26-3.04) for paternal areca nut usage from 20 to 29 years of age, versus from >30 years of age (adjusted hazard ratio,1.61; 95% CI, 0.22-11.69). MetS offspring risk for paternal smoking increased dosewise (Ptrend<0.0001) with earlier age of onset (Ptrend=0.0009), independently. Longer duration of paternal betel quid chewing and smoking, prefatherhood, independently predicted early occurrence of incident MetS in offspring, corroborating previously reported transgenerational effects of these habits, and supporting the need for habit-cessation program provision. © 2016 American Heart Association, Inc.

Prognostic value of the post-training oxygen uptake efficiency slope in patients with coronary artery disease.

PubMed

Buys, Roselien; Coeckelberghs, Ellen; Cornelissen, Véronique A; Goetschalckx, Kaatje; Vanhees, Luc

2016-09-01

Peak oxygen uptake is an independent predictor of mortality in patients with coronary artery disease (CAD). However, patients with CAD are not always capable of reaching peak effort, and therefore submaximal gas exchange variables such as the oxygen uptake efficiency slope (OUES) have been introduced. Baseline exercise capacity as expressed by OUES provides prognostic information and this parameter responds to training. Therefore, we aimed to assess the prognostic value of post-training OUES in patients with CAD. We included 960 patients with CAD (age 60.6 ± 9.5 years; 853 males) who completed a cardiac rehabilitation program between 2000 and 2011. The OUES was calculated before and after cardiac rehabilitation and information on mortality was obtained. The relationships of post-training OUES with all-cause and cardiovascular (CV) mortality was assessed by Cox proportional hazards regression analyses. Receiver operator characteristic curve analysis was performed in order to obtain the optimal cut-off value. During 7.37 ± 3.20 years of follow-up (range: 0.45-13.75 years), 108 patients died, among whom 47 died due to CV reasons. The post-training OUES was related to all-cause (hazard ratio: 0.50, p < 0.001) and CV (hazard ratio: 0.40, p < 0.001) mortality. When significant covariates, including baseline OUES, were entered into the Cox regression analysis, post-training OUES remained related to all-cause and CV mortality (hazard ratio: 0.40, p < 0.01 and 0.26, p < 0.01, respectively). In addition, the change in OUES due to exercise training was positively related to mortality (hazard ratio: 0.49, p < 0.01). Post-training OUES has stronger prognostic value compared to baseline OUES. The lack of improvement in exercise capacity expressed by OUES after an exercise training program relates to a worse prognosis and can help distinguish patients with favorable and unfavorable prognoses. © The European Society of Cardiology 2016.

The effect of sibutramine prescribing in routine clinical practice on cardiovascular outcomes: a cohort study in the United Kingdom.

PubMed

Hayes, J F; Bhaskaran, K; Batterham, R; Smeeth, L; Douglas, I

2015-09-01

The marketing authorization for the weight loss drug sibutramine was suspended in 2010 following a major trial that showed increased rates of non-fatal myocardial infarction and cerebrovascular events in patients with pre-existing cardiovascular disease. In routine clinical practice, sibutramine was already contraindicated in patients with cardiovascular disease and so the relevance of these influential clinical trial findings to the 'real World' population of patients receiving or eligible for the drug is questionable. We assessed rates of myocardial infarction and cerebrovascular events in a cohort of patients prescribed sibutramine or orlistat in the United Kingdom. A cohort of patients prescribed weight loss medication was identified within the Clinical Practice Research Datalink. Rates of myocardial infarction or cerebrovascular event, and all-cause mortality were compared between patients prescribed sibutramine and similar patients prescribed orlistat, using both a multivariable Cox proportional hazard model, and propensity score-adjusted model. Possible effect modification by pre-existing cardiovascular disease and cardiovascular risk factors was assessed. Patients prescribed sibutramine (N=23,927) appeared to have an elevated rate of myocardial infarction or cerebrovascular events compared with those taking orlistat (N=77,047; hazard ratio 1.69, 95% confidence interval 1.12-2.56). However, subgroup analysis showed the elevated rate was larger in those with pre-existing cardiovascular disease (hazard ratio 4.37, 95% confidence interval 2.21-8.64), compared with those with no cardiovascular disease (hazard ratio 1.52, 95% confidence interval 0.92-2.48, P-interaction=0.0076). All-cause mortality was not increased in those prescribed sibutramine (hazard ratio 0.67, 95% confidence interval 0.34-1.32). Sibutramine was associated with increased rates of acute cardiovascular events in people with pre-existing cardiovascular disease, but there was a low absolute risk in those without. Sibutramine's marketing authorization may have, therefore, been inappropriately withdrawn for people without cardiovascular disease.

Do Self-Management Interventions Work in Patients With Heart Failure? An Individual Patient Data Meta-Analysis.

PubMed

Jonkman, Nini H; Westland, Heleen; Groenwold, Rolf H H; Ågren, Susanna; Atienza, Felipe; Blue, Lynda; Bruggink-André de la Porte, Pieta W F; DeWalt, Darren A; Hebert, Paul L; Heisler, Michele; Jaarsma, Tiny; Kempen, Gertrudis I J M; Leventhal, Marcia E; Lok, Dirk J A; Mårtensson, Jan; Muñiz, Javier; Otsu, Haruka; Peters-Klimm, Frank; Rich, Michael W; Riegel, Barbara; Strömberg, Anna; Tsuyuki, Ross T; van Veldhuisen, Dirk J; Trappenburg, Jaap C A; Schuurmans, Marieke J; Hoes, Arno W

2016-03-22

Self-management interventions are widely implemented in the care for patients with heart failure (HF). However, trials show inconsistent results, and whether specific patient groups respond differently is unknown. This individual patient data meta-analysis assessed the effectiveness of self-management interventions in patients with HF and whether subgroups of patients respond differently. A systematic literature search identified randomized trials of self-management interventions. Data from 20 studies, representing 5624 patients, were included and analyzed with the use of mixed-effects models and Cox proportional-hazard models, including interaction terms. Self-management interventions reduced the risk of time to the combined end point of HF-related hospitalization or all-cause death (hazard ratio, 0.80; 95% confidence interval [CI], 0.71-0.89), time to HF-related hospitalization (hazard ratio, 0.80; 95% CI, 0.69-0.92), and improved 12-month HF-related quality of life (standardized mean difference, 0.15; 95% CI, 0.00-0.30). Subgroup analysis revealed a protective effect of self-management on the number of HF-related hospital days in patients <65 years of age (mean, 0.70 versus 5.35 days; interaction P=0.03). Patients without depression did not show an effect of self-management on survival (hazard ratio for all-cause mortality, 0.86; 95% CI, 0.69-1.06), whereas in patients with moderate/severe depression, self-management reduced survival (hazard ratio, 1.39; 95% CI, 1.06-1.83, interaction P=0.01). This study shows that self-management interventions had a beneficial effect on time to HF-related hospitalization or all-cause death and HF-related hospitalization alone and elicited a small increase in HF-related quality of life. The findings do not endorse limiting self-management interventions to subgroups of patients with HF, but increased mortality in depressed patients warrants caution in applying self-management strategies in these patients. © 2016 American Heart Association, Inc.

Comparison of Transplant Waitlist Outcomes for Pediatric Candidates Supported by Ventricular Assist Devices Versus Medical Therapy.

PubMed

Law, Sabrina P; Oron, Assaf P; Kemna, Mariska S; Albers, Erin L; McMullan, D Michael; Chen, Jonathan M; Law, Yuk M

2018-05-01

Ventricular assist devices have gained popularity in the management of refractory heart failure in children listed for heart transplantation. Our primary aim was to compare the composite endpoint of all-cause pretransplant mortality and loss of transplant eligibility in children who were treated with a ventricular assist device versus a medically managed cohort. This was a retrospective cohort analysis. Data were obtained from the Scientific Registry of Transplant Recipients. The at-risk population (n = 1,380) was less than 18 years old, either on a ventricular assist device (605 cases) or an equivalent-severity, intensively medically treated group (referred to as MED, 775 cases). None. The impact of ventricular assist devices was estimated via Cox proportional hazards regression (hazard ratio), dichotomizing 1-year outcomes to "poor" (22%: 193 deaths, 114 too sick) versus all others (940 successful transplants, 41 too healthy, 90 censored), while adjusting for conventional risk factors. Among children 0-12 months old, ventricular assist device was associated with a higher risk of poor outcomes (hazard ratio, 2.1; 95% CI, 1.5-3.0; p < 0.001). By contrast, ventricular assist device was associated with improved outcomes for ages 12-18 (hazard ratio, 0.3; 95% CI, 0.1-0.7; p = 0.003). For candidates 1-5 and 6-11 years old, there were no differences in outcomes between the ventricular assist device and MED groups (hazard ratio, 0.8 and 1.0, p = 0.43 and 0.9). The interaction between ventricular assist devices and age group was strongly significant (p < 0.001). This is a comparative study of ventricular assist devices versus medical therapy in children. Age is a significant modulator of waitlist outcomes for children with end-stage heart failure supported by ventricular assist device, with the impact of ventricular assist devices being more beneficial in adolescents.

The Relationship Between Caregiving and Mortality After Accounting for Time-Varying Caregiver Status and Addressing the Healthy Caregiver Hypothesis.

PubMed

Fredman, Lisa; Lyons, Jennifer G; Cauley, Jane A; Hochberg, Marc; Applebaum, Katie M

2015-09-01

Previous studies have shown inconsistent associations between caregiving and mortality. This may be due to analyzing caregiver status at baseline only, and that better health is probably related to taking on caregiving responsibilities and continuing in that role. The latter is termed The Healthy Caregiver Hypothesis, similar to the Healthy Worker Effect in occupational epidemiology. We applied common approaches from occupational epidemiology to evaluate the association between caregiving and mortality, including treating caregiving as time-varying and lagging exposure up to 5 years. Caregiving status among 1,068 women (baseline mean age = 81.0 years; 35% caregivers) participating in the Caregiver-Study of Osteoporotic Fractures study was assessed at five interviews conducted between 1999 and 2009. Mortality was determined through January 2012. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals adjusted for sociodemographics, perceived stress, and functional limitations. A total of 483 participants died during follow-up (38.8% and 48.7% of baseline caregivers and noncaregivers, respectively). Using baseline caregiving status, the association with mortality was 0.77, 0.62-0.95. Models of time-varying caregiving status showed a more pronounced reduction in mortality in current caregivers (hazard ratios = 0.54, 0.38-0.75), which diminished with longer lag periods (3-year lag hazard ratio = 0.68, 0.52-0.88, 5-year lag hazard ratios = 0.76, 0.60-0.95). Overall, caregivers had lower mortality rates than noncaregivers in all analyses. These associations were sensitive to the lagged period, indicating that the timing of leaving caregiving does influence this relationship and should be considered in future investigations. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mortality risk attributable to smoking, hypertension and diabetes among English and Brazilian older adults (The ELSA and Bambui cohort ageing studies)

PubMed Central

Marmot, Michael G.; Demakakos, Panayotes; Vaz de Melo Mambrini, Juliana; Peixoto, Sérgio Viana; Lima-Costa, Maria Fernanda

2016-01-01

Background: The main aim of this study was to quantify and compare 6-year mortality risk attributable to smoking, hypertension and diabetes among English and Brazilian older adults. This study represents a rare opportunity to approach the subject in two different social and economic contexts. Methods: Data from the data from the English Longitudinal Study of Ageing (ELSA) and the Bambuí Cohort Study of Ageing (Brazil) were used. Deaths in both cohorts were identified through mortality registers. Risk factors considered in this study were baseline smoking, hypertension and diabetes mellitus. Both age–sex adjusted hazard ratios and population attributable risks (PAR) of all-cause mortality and their 95% confidence intervals for the association between risk factors and mortality were estimated using Cox proportional hazards models. Results: Participants were 3205 English and 1382 Brazilians aged 60 years and over. First, Brazilians showed much higher absolute risk of mortality than English and this finding was consistent in all age, independently of sex. Second, as a rule, hazard ratios for mortality to smoking, hypertension and diabetes showed more similarities than differences between these two populations. Third, there was strong difference among English and Brazilians on attributable deaths to hypertension. Conclusions: The findings indicate that, despite of being in more recent transitions, the attributable deaths to one or more risk factors was twofold among Brazilians relative to the English. These findings call attention for the challenge imposed to health systems to prevent and treat non-communicable diseases, particularly in populations with low socioeconomic level. PMID:26666869

Periodontitis and early mortality among adults treated with hemodialysis: a multinational propensity-matched cohort study.

PubMed

Ruospo, Marinella; Palmer, Suetonia C; 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; Del Castillo, Domingo; Schon, Staffan; Bernat, Amparo G; Hegbrant, Jorgen; Wollheim, Charlotta; Gargano, Letizia; Bots, Casper P; Strippoli, Giovanni Fm

2017-05-22

Periodontitis is associated with cardiovascular mortality in the general population and adults with chronic diseases. However, it is unclear whether periodontitis predicts survival in the setting of kidney failure. ORAL-D was a propensity matched analysis in 3338 dentate adults with end-stage kidney disease treated in a hemodialysis network in Europe and South America designed to examine the association between periodontitis and all-cause and cardiovascular-related mortality in people on long-term hemodialysis. Participants were matched 1:1 on their propensity score for moderate to severe periodontitis assessed using the World Health Organization Community Periodontal Index. A random-effects Cox proportional hazards model was fitted with shared frailty to account for clustering of mortality risk within countries. Among the 3338 dentate participants, 1355 (40.6%) had moderate to severe periodontitis at baseline. After using propensity score methods to generate a matched cohort of participants with periodontitis similar to those with none or mild periodontal disease, moderate to severe periodontitis was associated with a lower risk of all-cause (9.1 versus 13.0 per 100 person years, hazard ratio 0.74, 95% confidence interval 0.61 to 0.90) and cardiovascular (4.3 versus 6.9 per 100 person years, hazard ratio 0.67, 0.51 to 0.88) mortality. These associations were not changed substantially when participants were limited to those with 12 or more natural teeth and when accounting for competing causes of cardiovascular death. In contrast to the general population, periodontitis does not appear to be associated with an increased risk of early death in adults treated with hemodialysis.

Statins Are Associated With Reduced Mortality in Multiple Myeloma

PubMed Central

Keller, Jesse; Gage, Brian F.; Luo, Suhong; Wang, Tzu-Fei; Moskowitz, Gerald; Gumbel, Jason; Blue, Brandon; O’Brian, Katiuscia; Carson, Kenneth R.

2016-01-01

Purpose The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have activity in one of the pathways influenced by nitrogen-containing bisphosphonates, which are associated with improved survival in multiple myeloma (MM). To understand the benefit of statins in MM, we evaluated the association between statin use and mortality in a large cohort of patients with MM. Patients and Methods From the Veterans Administration Central Cancer Registry, we identified patients diagnosed with MM between 1999 and 2013. We defined statin use as the presence of any prescription for a statin within 3 months before or any time after MM diagnosis. Cox proportional hazards regression assessed the association of statin use with mortality, while controlling for known MM prognostic factors. Results We identified a cohort of 4,957 patients, of whom 2,294 received statin therapy. Statin use was associated with a 21% decrease in all-cause mortality (adjusted hazard ratio, 0.79; 95% CI, 0.73 to 0.86; P < .001) as well as a 24% decrease in MM-specific mortality (adjusted hazard ratio, 0.76; 95% CI, 0.67 to 0.86; P < .001). This association remained significant across all sensitivity analyses. In addition to reductions in mortality, statin use was associated with a 31% decreased risk of developing a skeletal-related event. Conclusion In this cohort study of US veterans with MM, statin therapy was associated with a reduced risk of both all-cause and MM-specific mortality. Our findings suggest a potential role for statin therapy in patients with MM. The putative benefit of statin therapy in MM should be corroborated in prospective studies. PMID:27646948

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

PubMed Central

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

2015-01-01

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

Coffee consumption and the incidence of type 2 diabetes in men and women with normal glucose tolerance: The Strong Heart Study

PubMed Central

Zhang, Ying; Lee, Elisa T.; Cowan, Linda D.; Fabsitz, Richard R.; Howard, Barbara V.

2009-01-01

Background and aims It was reported that high coffee consumption was related to decreased diabetes risk. The aim of this study is to examine the association between coffee consumption and the incidence of type 2 diabetes in persons with normal glucose tolerance in a population with a high incidence and prevalence of diabetes. Methods and results In a prospective cohort study, information about daily coffee consumption was collected at the baseline examination (1989-1992) in a population-based sample of American Indian men and women 45-74 years of age. Participants with normal glucose tolerance (N=1141) at the baseline examination were followed for an average of 7.6 years. The incidence of diabetes was compared across the categories of daily coffee consumption. The hazard ratios of diabetes related to coffee consumption were calculated using Cox proportional hazards models, adjusted for potential confounders. Levels of coffee consumption were positively related to levels of current smoking and inversely related to body mass index, waist circumference, female gender, and hypertension. Compared to those who did not drink coffee, participants who drank 12 or more cups of coffee daily had 67% less risk of developing diabetes during the follow-up (hazard ratio: 0.33, 95% confidence interval: 0.13, 0.81). Conclusion In this population, a high level of coffee consumption was associated with a reduced risk of deterioration of glucose metabolism over an average 7.6 years of follow-up. More work is needed to understand whether there is a plausible biological mechanism for this observation. PMID:20171062

Post-Inhaled Corticosteroid Pulmonary Tuberculosis Increases Lung Cancer in Patients with Asthma

PubMed Central

Lin, Frank Cheau-Feng; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Wu, Min-Chen; Wu, Ming-Fang; Liaw, Yung-Po

2016-01-01

Purpose To evaluate the association between post-inhaled corticosteroid (ICS) pulmonary tuberculosis (TB), pneumonia and lung cancer in patients with asthma. Methods The study samples were collected from the National Health Insurance Database. Asthmatic patients who were first-time users of ICS between 2003 and 2005 were identified as cases. For each case, 4 control individuals were randomly matched for sex, age and date of ICS use. Cases and matched controls were followed up until the end of 2010. Cox proportional hazard regression was used to determine the hazard ratio for pulmonary infections and lung cancer risk in the ICS users and non-users. Results A total of 10,904 first-time users of ICS were matched with 43,616 controls. The hazard ratios for lung cancer were: 2.52 (95% confidence interval [CI], 1.22–5.22; p = 0.012) for individuals with post-ICS TB, 1.28 (95%CI, 0.73–2.26; p = 0.389) for post-ICS pneumonia, 2.31(95%CI, 0.84–6.38; p = 0.105) for post-ICS pneumonia+TB, 1.08 (95%CI, 0.57–2.03; p = 0.815) for TB, 0.99 (95%CI, 0.63–1.55; p = 0.970) for pneumonia, and 0.32 (95%CI, 0.05–2.32; p = 0.261) for pneumonia+ TB, respectively. Conclusions Post-ICS TB increased lung cancer risk in patients with asthma. Because of the high mortality associated with lung cancer, screening tests are recommended for patients with post-ICS TB. PMID:27448321

Measuring the Association Between Body Mass Index and All-Cause Mortality in the Presence of Missing Data: Analyses From the Scottish National Diabetes Register.

PubMed

Read, Stephanie H; Lewis, Steff C; Halbesma, Nynke; Wild, Sarah H

2017-04-15

Incorrectly handling missing data can lead to imprecise and biased estimates. We describe the effect of applying different approaches to handling missing data in an analysis of the association between body mass index and all-cause mortality among people with type 2 diabetes. We used data from the Scottish diabetes register that were linked to hospital admissions data and death registrations. The analysis was based on people diagnosed with type 2 diabetes between 2004 and 2011, with follow-up until May 31, 2014. The association between body mass index and mortality was investigated using Cox proportional hazards models. Findings were compared using 4 different missing-data methods: complete-case analysis, 2 multiple-imputation models, and nearest-neighbor imputation. There were 124,451 cases of type 2 diabetes, among which there were 17,085 deaths during 787,275 person-years of follow-up. Patients with missing data (24.8%) had higher mortality than those without missing data (adjusted hazard ratio = 1.36, 95% confidence interval: 1.31, 1.41). A U-shaped relationship between body mass index and mortality was observed, with the lowest hazard ratios occurring among moderately obese people, regardless of the chosen approach for handling missing data. Missing data may affect absolute and relative risk estimates differently and should be considered in analyses of routinely collected data. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Association of QRS duration and survival in dogs with dilated cardiomyopathy: a retrospective study of 266 clinical cases.

PubMed

Pedro, Brigite M; Alves, Joana V; Cripps, Peter J; Stafford Johnson, Mike J; Martin, Mike W S

2011-12-01

The purpose of this study was to investigate the prognostic value of QRS duration in dogs with dilated cardiomyopathy (DCM) by studying its relationship with survival time. The medical records of dogs diagnosed with DCM were retrospectively searched for good quality ECG tracings. The QRS duration was measured from the ECG tracing and two different models were used: binary variable (dogs were divided into 2 groups based on a QRS duration of <60 ms or ≥60 ms) and continuous variable. The survival times were analysed by the Kaplan-Meier method and Cox's proportional hazard model. 266 dogs met the inclusion and exclusion criteria. A QRS duration ≥60 ms was associated with a reduced survival time compared to those with a QRS duration <60 ms (Hazard Ratio of 1.34, 95% CI 1.05-1.71, P = 0.02). When considered as a continuous variable the Hazard Ratio was 1.015 for each increase in QRS duration of 1 ms (95% CI 1.006-1.024, p = 0.001).Dogs with a QRS duration < 60 ms had a median survival time (IQ range) of 25 weeks (97-65) and dogs with a QRS duration ≥60 ms had a median survival time (IQ range) of 13 weeks (3-34). The measurement of QRS duration is relatively simple to perform from a surface ECG recording. A duration ≥60 ms is associated with shorter survival times in dogs with DCM, which may provide practitioners with additional prognostic information. Copyright © 2011 Elsevier B.V. All rights reserved.

Plasma FGF23 and the risk of stroke

PubMed Central

Dong, Chuanhui; Stark, Matthew; Silverberg, Shonni; Rundek, Tatjana; Elkind, Mitchell S.V.; Sacco, Ralph L.; Mendez, Armando; Wolf, Myles

2014-01-01

Objective: To examine fibroblast growth factor 23 (FGF23) as a risk factor for incident stroke in a racially/ethnically diverse population-based urban cohort. Methods: Stroke-free Northern Manhattan Study participants with FGF23 measurements (n = 2,525) were followed for a mean of 12 (±5) years to detect incident strokes. We used Cox proportional hazards models to estimate the association of baseline FGF23 with incident total, ischemic, and hemorrhagic stroke. Results: Median FGF23 was 57 relative units (RU)/mL (interquartile range = 44–81 RU/mL). Each unit increase of natural log-transformed FGF23 conferred a 40% greater overall stroke risk after adjusting for estimated glomerular filtration rate and sociodemographic and vascular risk factors (hazard ratio = 1.4, 95% confidence interval 1.1–1.6, p = 0.004). Penalized spline analysis revealed a linear association with overall stroke risk at ≥90 RU/mL FGF23, compared with <90 RU/mL (hazard ratio = 1.5, 95% confidence interval = 1.2–2.1, p = 0.004). Greater FGF23 conferred a doubling of intracerebral hemorrhage (ICH) risk but no significant increased risk of ischemic stroke. The associations of elevated FGF23 levels with greater risks of overall stroke and ICH events were independent of phosphate and parathyroid hormone levels and were similar among participants without chronic kidney disease. Conclusions: Elevated FGF23 was a risk factor for overall stroke and ICH events, in particular in a racially and ethnically diverse urban community, independent of chronic kidney disease. PMID:24706015

Assessment of Canine Mast Cell Tumor Mortality Risk Based on Clinical, Histologic, Immunohistochemical, and Molecular Features.

PubMed

Horta, Rodrigo S; Lavalle, Gleidice E; Monteiro, Lidianne N; Souza, Mayara C C; Cassali, Geovanni D; Araújo, Roberto B

2018-03-01

Mast cell tumor (MCT) is a frequent cutaneous neoplasm in dogs that is heterogeneous in clinical presentation and biological behavior, with a variable potential for recurrence and metastasis. Accurate prediction of clinical outcomes has been challenging. The study objective was to develop a system for classification of canine MCT according to the mortality risk based on individual assessment of clinical, histologic, immunohistochemical, and molecular features. The study included 149 dogs with a histologic diagnosis of cutaneous or subcutaneous MCT. By univariate analysis, MCT metastasis and related death was significantly associated with clinical stage ( P < .0001, r P = -0.610), history of tumor recurrence ( P < .0001, r P = -0.550), Patnaik ( P < .0001, r P = -0.380) and Kiupel grades ( P < .0001, r P = -0.500), predominant organization of neoplastic cells ( P < .0001, r P = -0.452), mitotic count ( P < .0001, r P = -0.325), Ki-67 labeling index ( P < .0001, r P = -0.414), KITr pattern ( P = .02, r P = 0.207), and c-KIT mutational status ( P < .0001, r P = -0.356). By multivariate analysis with Cox proportional hazard model, only 2 features were independent predictors of overall survival: an amendment of the World Health Organization clinical staging system (hazard ratio [95% CI]: 1.824 [1.210-4.481]; P = .01) and a history of tumor recurrence (hazard ratio [95% CI]: 9.250 [2.158-23.268]; P < .001]. From these results, we propose an amendment of the WHO staging system, a method of risk analysis, and a suggested approach to clinical and laboratory evaluation of dogs with cutaneous MCT.

Preclinical Alzheimer disease and risk of falls

PubMed Central

Roe, Catherine M.; Grant, Elizabeth A.; Hollingsworth, Holly; Benzinger, Tammie L.; Fagan, Anne M.; Buckles, Virginia D.; Morris, John C.

2013-01-01

Objective: We determined the rate of falls among cognitively normal, community-dwelling older adults, some of whom had presumptive preclinical Alzheimer disease (AD) as detected by in vivo imaging of fibrillar amyloid plaques using Pittsburgh compound B (PiB) and PET and/or by assays of CSF to identify Aβ42, tau, and phosphorylated tau. Methods: We conducted a 12-month prospective cohort study to examine the cumulative incidence of falls. Participants were evaluated clinically and underwent PiB PET imaging and lumbar puncture. Falls were reported monthly using an individualized calendar journal returned by mail. A Cox proportional hazards model was used to test whether time to first fall was associated with each biomarker and the ratio of CSF tau/Aβ42 and CSF phosphorylated tau/Aβ42, after adjustment for common fall risk factors. Results: The sample (n = 125) was predominately female (62.4%) and white (96%) with a mean age of 74.4 years. When controlled for ability to perform activities of daily living, higher levels of PiB retention (hazard ratio = 2.95 [95% confidence interval 1.01–6.45], p = 0.05) and of CSF biomarker ratios (p < 0.001) were associated with a faster time to first fall. Conclusions: Presumptive preclinical AD is a risk factor for falls in older adults. This study suggests that subtle noncognitive changes that predispose older adults to falls are associated with AD and may precede detectable cognitive changes. PMID:23803314

Home safety measures and the risk of unintentional injury among young children: a multicentre case–control study

PubMed Central

LeBlanc, John C.; Pless, I. Barry; King, W. James; Bawden, Harry; Bernard-Bonnin, Anne-Claude; Klassen, Terry; Tenenbein, Milton

2006-01-01

Background Young children may sustain injuries when exposed to certain hazards in the home. To better understand the relation between several childproofing strategies and the risk of injuries to children in the home, we undertook a multicentre case–control study in which we compared hazards in the homes of children with and without injuries. Methods We conducted this case-control study using records from 5 pediatric hospital emergency departments for the 2-year period 1995–1996. The 351 case subjects were children aged 7 years and less who presented with injuries from falls, burns or scalds, ingestions or choking. The matched control subjects were children who presented during the same period with acute non-injury-related conditions. A home visitor, blinded to case-control status, assessed 19 injury hazards at the children's homes. Results Hazards found in the homes included baby walkers (21% of homes with infants), no functioning smoke alarm (17% of homes) and no fire extinguisher (51% of homes). Cases did not differ from controls in the mean proportion of home hazards. After controlling for siblings, maternal education and employment, we found that cases differed from controls for 5 hazards: the presence of a baby walker (odds ratio [OR] 9.0, 95% confidence interval [CI] 1.1–71.0), the presence of choking hazards within a child's reach (OR 2.0, 95% CI 1.0–3.7), no child-resistant lids in bathroom (OR 1.6, 95% CI 1.0–2.5), no smoke alarm (OR 3.2, 95% CI 1.4–7.7) and no functioning smoke alarm (OR 1.7, 95% CI 1.0–2.8). Interpretation Homes of children with injuries differed from those of children without injuries in the proportions of specific hazards for falls, choking, poisoning and burns, with a striking difference noted for the presence of a baby walker. In addition to counselling parents about specific hazards, clinicians should consider that the presence of some hazards may indicate an increased risk for home injuries beyond those directly related to the hazard found. Families with any home hazard may be candidates for interventions to childproof against other types of home hazards. PMID:16998079

230Th/U ages Supporting Hanford Site-Wide Probabilistic Seismic Hazard Analysis

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

Paces, James B.

This product represents a USGS Administrative Report that discusses samples and methods used to conduct uranium-series isotope analyses and resulting ages and initial 234U/238U activity ratios of pedogenic cements developed in several different surfaces in the Hanford area middle to late Pleistocene. Samples were collected and dated to provide calibration of soil development in surface deposits that are being used in the Hanford Site-Wide probabilistic seismic hazard analysis conducted by AMEC. The report includes description of sample locations and physical characteristics, sample preparation, chemical processing and mass spectrometry, analytical results, and calculated ages for individual sites. Ages of innermost rindsmore » on a number of samples from five sites in eastern Washington are consistent with a range of minimum depositional ages from 17 ka for cataclysmic flood deposits to greater than 500 ka for alluvium at several sites.« less

230Th/U ages Supporting Hanford Site‐Wide Probabilistic Seismic Hazard Analysis

USGS Publications Warehouse

Paces, James B.

2014-01-01

This product represents a USGS Administrative Report that discusses samples and methods used to conduct uranium-series isotope analyses and resulting ages and initial 234U/238U activity ratios of pedogenic cements developed in several different surfaces in the Hanford area middle to late Pleistocene. Samples were collected and dated to provide calibration of soil development in surface deposits that are being used in the Hanford Site-Wide probabilistic seismic hazard analysis conducted by AMEC. The report includes description of sample locations and physical characteristics, sample preparation, chemical processing and mass spectrometry, analytical results, and calculated ages for individual sites. Ages of innermost rinds on a number of samples from five sites in eastern Washington are consistent with a range of minimum depositional ages from 17 ka for cataclysmic flood deposits to greater than 500 ka for alluvium at several sites.

Additive mixed effect model for recurrent gap time data.

PubMed

Ding, Jieli; Sun, Liuquan

2017-04-01

Gap times between recurrent events are often of primary interest in medical and observational studies. The additive hazards model, focusing on risk differences rather than risk ratios, has been widely used in practice. However, the marginal additive hazards model does not take the dependence among gap times into account. In this paper, we propose an additive mixed effect model to analyze gap time data, and the proposed model includes a subject-specific random effect to account for the dependence among the gap times. Estimating equation approaches are developed for parameter estimation, and the asymptotic properties of the resulting estimators are established. In addition, some graphical and numerical procedures are presented for model checking. The finite sample behavior of the proposed methods is evaluated through simulation studies, and an application to a data set from a clinic study on chronic granulomatous disease is provided.

Clinical and Serological Predictors of Suicide in Schizophrenia and Major Mood Disorders.

PubMed

Dickerson, Faith; Origoni, Andrea; Schweinfurth, Lucy A B; Stallings, Cassie; Savage, Christina L G; Sweeney, Kevin; Katsafanas, Emily; Wilcox, Holly C; Khushalani, Sunil; Yolken, Robert

2018-03-01

Persons with serious mental illness are at high risk for suicide, but this outcome is difficult to predict. Serological markers may help to identify suicide risk. We prospectively assessed 733 persons with a schizophrenia spectrum disorder, 483 with bipolar disorder, and 76 with major depressive disorder for an average of 8.15 years. The initial evaluation consisted of clinical and demographic data as well as a blood samples from which immunoglobulin G antibodies to herpes viruses and Toxoplasma gondii were measured. Suicide was determined using data from the National Death Index. Cox proportional hazard regression models examined the role of baseline variables on suicide outcomes. Suicide was associated with male sex, divorced/separated status, Caucasian race, and elevated levels of antibodies to Cytomegalovirus (CMV). Increasing levels of CMV antibodies were associated with increasing hazard ratios for suicide. The identification of serological variables associated with suicide might provide more personalized methods for suicide prevention.

Evaluation of Occupational Exposure to Magnetic Fields and Motor Neuron Disease Mortality in a Population-Based Cohort

PubMed Central

Parlett, Lauren E.; Bowman, Joseph D.; van Wijngaarden, Edwin

2015-01-01

Objective Epidemiologic evidence for the association between electromagnetic fields and amyotrophic lateral sclerosis, the most common form of motor neuron disease (MND), has been inconclusive. We evaluated the association between electromagnetic fields and MND among workers in occupations potentially exposed to magnetic fields. Methods MND mortality (ICD-9 335.2) was examined in the National Longitudinal Mortality Study using multivariable proportional hazards models. Occupational exposure to magnetic fields was determined on the basis of a population-based job-exposure matrix. Age at entry, education, race, sex, and income were considered for inclusion as covariates. Results After adjusting for age, sex, and education, there were no increased risks of MND mortality in relation to potential magnetic field exposure, with hazard ratios around the null in all magnetic field exposure quartiles. Conclusions Our study does not provide evidence for an association between magnetic field exposure and MND mortality. PMID:22076040

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

PubMed

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

2017-03-01

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

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

Increased risk of bipolar disorder in patients with scabies: A nationwide population-based matched-cohort study.

PubMed

Lin, Chien-Yu; Chang, Fung-Wei; Yang, Jing-Jung; Chang, Chun-Hung; Yeh, Chia-Lun; Lei, Wei-Te; Huang, Chun-Fa; Liu, Jui-Ming; Hsu, Ren-Jun

2017-11-01

Both scabies and bipolar disorder (BD) are common and troublesome disorders. There are several similarities in both diseases: pruritus, a higher prevalence in crowded environments, and cytokine-mediated inflammatory processes in the pathophysiology. We conducted this nationwide population-based study to investigate the possible relationship between scabies and BD. Based on the National Health Insurance Research Database (NHIRD) of Taiwan, a total of 7096 patients with scabies were identified as a study group and 28,375 matched patients as a control. We tracked the patients in both groups for a 7-year period to identify those newly diagnosed with BD. The demographic characteristics and comorbidities of the patients were analyzed, and Cox proportional hazard regressions were performed to calculate the hazard ratio (HR) of BD. Of the 35,471 patients in this study, 183 (0.5%) patients with newly diagnosed BD were identified, with 58 (0.8%) from the scabies group and 125 (0.4%) from the control group. The patients with scabies had a higher risk of subsequent BD, with a crude hazard ratio of 1.86 and an adjusted hazard ratio of 1.55 (95% confidence interval: 1.12-2.09, P < 0.05). This study shows there is an increased risk for BD among patients with scabies. Immunopathology may contribute to this association. Copyright © 2017 Elsevier B.V. All rights reserved.

Relationship between Clinic and Ambulatory Blood-Pressure Measurements and Mortality.

PubMed

Banegas, José R; Ruilope, Luis M; de la Sierra, Alejandro; Vinyoles, Ernest; Gorostidi, Manuel; de la Cruz, Juan J; Ruiz-Hurtado, Gema; Segura, Julián; Rodríguez-Artalejo, Fernando; Williams, Bryan

2018-04-19

Evidence for the influence of ambulatory blood pressure on prognosis derives mainly from population-based studies and a few relatively small clinical investigations. This study examined the associations of blood pressure measured in the clinic (clinic blood pressure) and 24-hour ambulatory blood pressure with all-cause and cardiovascular mortality in a large cohort of patients in primary care. We analyzed data from a registry-based, multicenter, national cohort that included 63,910 adults recruited from 2004 through 2014 in Spain. Clinic and 24-hour ambulatory blood-pressure data were examined in the following categories: sustained hypertension (elevated clinic and elevated 24-hour ambulatory blood pressure), "white-coat" hypertension (elevated clinic and normal 24-hour ambulatory blood pressure), masked hypertension (normal clinic and elevated 24-hour ambulatory blood pressure), and normotension (normal clinic and normal 24-hour ambulatory blood pressure). Analyses were conducted with Cox regression models, adjusted for clinic and 24-hour ambulatory blood pressures and for confounders. During a median follow-up of 4.7 years, 3808 patients died from any cause, and 1295 of these patients died from cardiovascular causes. In a model that included both 24-hour and clinic measurements, 24-hour systolic pressure was more strongly associated with all-cause mortality (hazard ratio, 1.58 per 1-SD increase in pressure; 95% confidence interval [CI], 1.56 to 1.60, after adjustment for clinic blood pressure) than the clinic systolic pressure (hazard ratio, 1.02; 95% CI, 1.00 to 1.04, after adjustment for 24-hour blood pressure). Corresponding hazard ratios per 1-SD increase in pressure were 1.55 (95% CI, 1.53 to 1.57, after adjustment for clinic and daytime blood pressures) for nighttime ambulatory systolic pressure and 1.54 (95% CI, 1.52 to 1.56, after adjustment for clinic and nighttime blood pressures) for daytime ambulatory systolic pressure. These relationships were consistent across subgroups of age, sex, and status with respect to obesity, diabetes, cardiovascular disease, and antihypertensive treatment. Masked hypertension was more strongly associated with all-cause mortality (hazard ratio, 2.83; 95% CI, 2.12 to 3.79) than sustained hypertension (hazard ratio, 1.80; 95% CI, 1.41 to 2.31) or white-coat hypertension (hazard ratio, 1.79; 95% CI, 1.38 to 2.32). Results for cardiovascular mortality were similar to those for all-cause mortality. Ambulatory blood-pressure measurements were a stronger predictor of all-cause and cardiovascular mortality than clinic blood-pressure measurements. White-coat hypertension was not benign, and masked hypertension was associated with a greater risk of death than sustained hypertension. (Funded by the Spanish Society of Hypertension and others.).

Delayed seizures after intracerebral haemorrhage

PubMed Central

Rattani, Abbas; Anderson, Christopher D.; Ayres, Alison M.; Gurol, Edip M.; Greenberg, Steven M.; Rosand, Jonathan; Viswanathan, Anand

2016-01-01

Late seizures after intracerebral haemorrhage occur after the initial acute haemorrhagic insult subsides, and represent one of its most feared long-term sequelae. Both susceptibility to late seizures and their functional impact remain poorly characterized. We sought to: (i) compare patients with new-onset late seizures (i.e. delayed seizures), with those who experienced a recurrent late seizure following an immediately post-haemorrhagic seizure; and (ii) investigate the effect of late seizures on long-term functional performance after intracerebral haemorrhage. We performed prospective longitudinal follow-up of consecutive intracerebral haemorrhage survivors presenting to a single tertiary care centre. We tested for association with seizures the following neuroimaging and genetic markers of cerebral small vessel disease: APOE variants ε2/ε4, computer tomography-defined white matter disease, magnetic resonance imaging-defined white matter hyperintensities volume and cerebral microbleeds. Cognitive performance was measured using the Modified Telephone Interview for Cognitive Status, and functional performance using structured questionnaires obtained every 6 months. We performed time-to-event analysis using separate Cox models for risk to develop delayed and recurrent seizures, as well as for functional decline risk (mortality, incident dementia, and loss of functional independence) after intracerebral haemorrhage. A total of 872 survivors of intracerebral haemorrhage were enrolled and followed for a median of 3.9 years. Early seizure developed in 86 patients, 42 of whom went on to experience recurrent seizures. Admission Glasgow Coma Scale, increasing haematoma volume and cortical involvement were associated with recurrent seizure risk (all P < 0.01). Recurrent seizures were not associated with long-term functional outcome (P = 0.67). Delayed seizures occurred in 37 patients, corresponding to an estimated incidence of 0.8% per year (95% confidence interval 0.5–1.2%). Factors associated with delayed seizures included cortical involvement on index haemorrhage (hazard ratio 1.63, P = 0.036), pre-haemorrhage dementia (hazard ratio 1.36, P = 0.044), history of multiple prior lobar haemorrhages (hazard ratio 2.50, P = 0.038), exclusively lobar microbleeds (hazard ratio 2.22, P = 0.008) and presence of ≥ 1 APOE ε4 copies (hazard ratio 1.95, P = 0.020). Delayed seizures were associated with worse long-term functional outcome (hazard ratio 1.83, P = 0.005), but the association was removed by adjusting for neuroimaging and genetic markers of cerebral small vessel disease. Delayed seizures after intracerebral haemorrhage are associated with different risk factors, when compared to recurrent seizures. They are also associated with worse functional outcome, but this finding appears to be related to underlying small vessel disease. Further investigations into the connections between small vessel disease and delayed seizures are warranted. PMID:27497491

Method of making nanostructured glass-ceramic waste forms

DOEpatents

Gao, Huizhen; Wang, Yifeng; Rodriguez, Mark A.; Bencoe, Denise N.

2012-12-18

A method of rendering hazardous materials less dangerous comprising trapping the hazardous material in nanopores of a nanoporous composite material, reacting the trapped hazardous material to render it less volatile/soluble, sealing the trapped hazardous material, and vitrifying the nanoporous material containing the less volatile/soluble hazardous material.

Breast-feeding patterns of ethnic groups in rural western China.

PubMed

Qu, Pengfei; Wang, Ting; Liu, Fang; Dang, Shaonong; Zeng, Lengxia; Yan, Hong

2015-12-01

To determine the breast-feeding pattern of four main ethnic groups (the Han, Uygur, Tibetan and Zhuang) living in rural western China. The study utilized a cross-sectional design. Forty-five counties in ten provinces in western China in 2005. A sample of 11 783 children younger than 36 months old (8960 Han, 1281 Uygur, 792 Tibetan and 750 Zhuang) and their mothers were recruited using a stratified, multistage, cluster random sampling method. The rates of exclusive breast-feeding of children at 6 months of age in the Han, Uygur, Tibetan and Zhuang ethnic groups were 11.6 %, 0.8%, 4.4% and 13.8%, respectively. The rates of any breast-feeding for children at 24 months of age were 8.5%, 25.7%, 3.0% and 4.3% in the four ethnic groups, respectively. After adjusting for related factors, Zhuang children had a higher odds ratio of exclusive breast-feeding to 6 months compared with Han children, whereas Uygur and Tibetan children had lower odds ratio (Zhuang: OR=1.291; 95% CI 1.006, 1.657; Uugur: OR=0.062; 95% CI 0.032, 0.121; Tibetan: OR=0.323; 95% CI 0.220, 0.475). Uygur children had a lower hazard ratio of discontinued breast-feeding compared with Han children, whereas Tibetan children had a higher hazard ratio (Uygur: HR=0.368; 95% CI 0.333, 0.408; Tibetan: HR=1.366; 95% CI 1.244, 1.500). The breast-feeding pattern differed among the Han, Uygur, Tibetan and Zhuang ethnic groups. The results suggest that health education regarding the benefits of breast-feeding is needed in rural western China.

Optimal Utilization of Donor Grafts With Extended Criteria

PubMed Central

Cameron, Andrew M.; Ghobrial, R Mark; Yersiz, Hasan; Farmer, Douglas G.; Lipshutz, Gerald S.; Gordon, Sherilyn A.; Zimmerman, Michael; Hong, Johnny; Collins, Thomas E.; Gornbein, Jeffery; Amersi, Farin; Weaver, Michael; Cao, Carlos; Chen, Tony; Hiatt, Jonathan R.; Busuttil, Ronald W.

2006-01-01

Objective: Severely limited organ resources mandate maximum utilization of donor allografts for orthotopic liver transplantation (OLT). This work aimed to identify factors that impact survival outcomes for extended criteria donors (ECD) and developed an ECD scoring system to facilitate graft-recipient matching and optimize utilization of ECDs. Methods: Retrospective analysis of over 1000 primary adult OLTs at UCLA. Extended criteria (EC) considered included donor age (>55 years), donor hospital stay (>5 days), cold ischemia time (>10 hours), and warm ischemia time (>40 minutes). One point was assigned for each extended criterion. Cox proportional hazard regression model was used for multivariate analysis. Results: Of 1153 allografts considered in the study, 568 organs exhibited no extended criteria (0 score), while 429, 135 and 21 donor allografts exhibited an EC score of 1, 2 and 3, respectively. Overall 1-year patient survival rates were 88%, 82%, 77% and 48% for recipients with EC scores of 0, 1, 2 and 3 respectively (P < 0.001). Adjusting for recipient age and urgency at the time of transplantation, multivariate analysis identified an ascending mortality risk ratio of 1.4 and 1.8 compared to a score of 0 for an EC score of 1, and 2 (P < 0.01) respectively. In contrast, an EC score of 3 was associated with a mortality risk ratio of 4.5 (P < 0.001). Further, advanced recipient age linearly increased the death hazard ratio, while an urgent recipient status increased the risk ratio of death by 50%. Conclusions: Extended criteria donors can be scored using readily available parameters. Optimizing perioperative variables and matching ECD allografts to appropriately selected recipients are crucial to maintain acceptable outcomes and represent a preferable alternative to both high waiting list mortality and to a potentially futile transplant that utilizes an ECD for a critically ill recipient. PMID:16772778

Predictors of mortality in HIV-associated hospitalizations in Portugal: a hierarchical survival model

PubMed Central

Dias, Sara S; Andreozzi, Valeska; Martins, Maria O; Torgal, Jorge

2009-01-01

Background The beneficial effects of highly active antiretroviral therapy, increasing survival and the prevention of AIDS defining illness development are well established. However, the annual Portuguese hospital mortality is still higher than expected. It is crucial to understand the hospitalization behaviour to better allocate resources. This study investigates the predictors of mortality in HIV associated hospitalizations in Portugal through a hierarchical survival model. Methods The study population consists of 12,078 adult discharges from patients with HIV infection diagnosis attended at Portuguese hospitals from 2005–2007 that were registered on the diagnosis-related groups' database. We used discharge and hospital level variables to develop a hierarchical model. The discharge level variables were: age, gender, type of admission, type of diagnoses-related group, related HIV complication, the region of the patient's residence, the number of diagnoses and procedures, the Euclidean distance from hospital to the centroid of the patient's ward, and if patient lived in the hospital's catchment area. The hospital characteristics include size and hospital classification according to the National Health System. Kaplan-Meier plots were used to examine differences in survival curves. Cox proportional hazard models with frailty were applied to identify independent predictors of hospital mortality and to calculate hazard ratios (HR). Results The Cox proportional model with frailty showed that male gender, older patient, great number of diagnoses and pneumonia increased the hazard of HIV related hospital mortality. On the other hand tuberculosis was associated with a reduced risk of death. Central hospital discharge also presents less risk of mortality. The frailty variance was small but statistically significant, indicating hazard ratio heterogeneity among hospitals that varied between 0.67 and 1.34, and resulted in two hospitals with HR different from the average risk. Conclusion The frailty model suggests that there are unmeasured factors affecting mortality in HIV associated hospitalizations. Consequently, for healthcare policy purposes, hospitals should not all be treated in an equal manner. PMID:19627574

Impact of Preexisting Mental Illness on All-Cause and Breast Cancer-Specific Mortality in Elderly Patients With Breast Cancer.

PubMed

Iglay, Kristy; Santorelli, Melissa L; Hirshfield, Kim M; Williams, Jill M; Rhoads, George G; Lin, Yong; Demissie, Kitaw

2017-12-20

Purpose Limited data are available on the survival of patients with breast cancer with preexisting mental illness, and elderly women are of special interest because they experience the highest incidence of breast cancer. Therefore, we compared all-cause and breast cancer-specific mortality for elderly patients with breast cancer with and without mental illness. Methods A retrospective cohort study was conducted by using SEER-Medicare data, including 19,028 women ≥ 68 years of age who were diagnosed with stage I to IIIa breast cancer in the United States from 2005 to 2007. Patients were classified as having severe mental illness if an International Classification of Diseases, Ninth Edition, Clinical Modification code for bipolar disorder, schizophrenia, or other psychotic disorder was recorded on at least one inpatient or two outpatient claims during the 3 years before breast cancer diagnosis. Patients were followed for up to 5 years after breast cancer diagnosis to assess survival outcomes, which were then compared with those of patients without mental illness. Results Nearly 3% of patients had preexisting severe mental illness. We observed a two-fold increase in the all-cause mortality hazard between patients with severe mental illness compared with those without mental illness after adjusting for age, income, race, ethnicity, geographic location, and marital status (adjusted hazard ratio, 2.19; 95% CI, 1.84 to 2.60). A 20% increase in breast cancer-specific mortality hazard was observed, but the association was not significant (adjusted hazard ratio, 1.20; 95% CI, 0.82 to 1.74). Patients with severe mental illness were more likely to be diagnosed with advanced breast cancer and aggressive tumor characteristics. They also had increased tobacco use and more comorbidities. Conclusion Patients with severe mental illness may need assistance with coordinating medical services.

Women's Health Initiative estrogen plus progestin clinical trial: a study that does not allow establishing relevant clinical risks.

PubMed

Aedo, Sócrates; Cavada, Gabriel; Blümel, Juan E; Chedraui, Peter; Fica, Juan; Barriga, Patricio; Brantes, Sergio; Irribarra, Cristina; Vallejo, María; Campodónico, Ítalo

2015-12-01

This study aims to determine time differences (differences in restricted mean survival times [RMSTs]) in the onset of invasive breast cancer, coronary heart disease, stroke, pulmonary embolism, colorectal cancer, and hip fracture between the placebo group and the conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg group of the Women's Health Initiative (WHI) trial based on survival curves of the original report and to provide adequate interpretation of the clinical effects of a given intervention. Distribution of survival function was obtained from cumulative hazard plots of the WHI report; Monte Carlo simulation was performed to obtain censored observations for each outcome, in which assumptions of the Cox model were evaluated once corresponding hazard ratios had been estimated. Using estimation methods such as numerical integration, pseudovalues, and flexible parametric modeling, we determined differences in RMSTs for each outcome. Obtained cumulative hazard plots, hazard ratios, and outcome rates from the simulated model did not show differences in relation to the original WHI report. The differences in RMST between placebo and conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg (in flexible parametric modeling) were 1.17 days (95% CI, -2.25 to 4.59) for invasive breast cancer, 7.50 days (95% CI, 2.90 to 12.11) for coronary heart disease, 2.75 days (95% CI, -0.84 to 6.34) for stroke, 4.23 days (95% CI, 1.82 to 6.64) for pulmonary embolism, -2.73 days (95% CI, -5.32 to -0.13) for colorectal cancer, and -2.77 days (95% CI, -5.44 to -0.1) for hip fracture. The differences in RMST for the outcomes of the WHI study are too small to establish clinical risks related to hormone therapy use.

Signal Detection and Monitoring Based on Longitudinal Healthcare Data

PubMed Central

Suling, Marc; Pigeot, Iris

2012-01-01

Post-marketing detection and surveillance of potential safety hazards are crucial tasks in pharmacovigilance. To uncover such safety risks, a wide set of techniques has been developed for spontaneous reporting data and, more recently, for longitudinal data. This paper gives a broad overview of the signal detection process and introduces some types of data sources typically used. The most commonly applied signal detection algorithms are presented, covering simple frequentistic methods like the proportional reporting rate or the reporting odds ratio, more advanced Bayesian techniques for spontaneous and longitudinal data, e.g., the Bayesian Confidence Propagation Neural Network or the Multi-item Gamma-Poisson Shrinker and methods developed for longitudinal data only, like the IC temporal pattern detection. Additionally, the problem of adjustment for underlying confounding is discussed and the most common strategies to automatically identify false-positive signals are addressed. A drug monitoring technique based on Wald’s sequential probability ratio test is presented. For each method, a real-life application is given, and a wide set of literature for further reading is referenced. PMID:24300373

40 CFR 270.66 - Permits for boilers and industrial furnaces burning hazardous waste.

Code of Federal Regulations, 2011 CFR

2011-07-01

... blended, and blending ratios. (3) A detailed engineering description of the boiler or industrial furnace... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Permits for boilers and industrial... PROGRAM Special Forms of Permits § 270.66 Permits for boilers and industrial furnaces burning hazardous...

40 CFR 270.66 - Permits for boilers and industrial furnaces burning hazardous waste.

Code of Federal Regulations, 2013 CFR

2013-07-01

... blended, and blending ratios. (3) A detailed engineering description of the boiler or industrial furnace... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Permits for boilers and industrial... PROGRAM Special Forms of Permits § 270.66 Permits for boilers and industrial furnaces burning hazardous...

40 CFR 270.66 - Permits for boilers and industrial furnaces burning hazardous waste.

Code of Federal Regulations, 2012 CFR

2012-07-01

... blended, and blending ratios. (3) A detailed engineering description of the boiler or industrial furnace... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Permits for boilers and industrial... PROGRAM Special Forms of Permits § 270.66 Permits for boilers and industrial furnaces burning hazardous...

40 CFR 270.66 - Permits for boilers and industrial furnaces burning hazardous waste.

Code of Federal Regulations, 2014 CFR

2014-07-01

... blended, and blending ratios. (3) A detailed engineering description of the boiler or industrial furnace... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Permits for boilers and industrial... PROGRAM Special Forms of Permits § 270.66 Permits for boilers and industrial furnaces burning hazardous...

40 CFR 270.66 - Permits for boilers and industrial furnaces burning hazardous waste.

Code of Federal Regulations, 2010 CFR

2010-07-01

... blended, and blending ratios. (3) A detailed engineering description of the boiler or industrial furnace... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Permits for boilers and industrial... PROGRAM Special Forms of Permits § 270.66 Permits for boilers and industrial furnaces burning hazardous...

An overall strategy based on regression models to estimate relative survival and model the effects of prognostic factors in cancer survival studies.

PubMed

Remontet, L; Bossard, N; Belot, A; Estève, J

2007-05-10

Relative survival provides a measure of the proportion of patients dying from the disease under study without requiring the knowledge of the cause of death. We propose an overall strategy based on regression models to estimate the relative survival and model the effects of potential prognostic factors. The baseline hazard was modelled until 10 years follow-up using parametric continuous functions. Six models including cubic regression splines were considered and the Akaike Information Criterion was used to select the final model. This approach yielded smooth and reliable estimates of mortality hazard and allowed us to deal with sparse data taking into account all the available information. Splines were also used to model simultaneously non-linear effects of continuous covariates and time-dependent hazard ratios. This led to a graphical representation of the hazard ratio that can be useful for clinical interpretation. Estimates of these models were obtained by likelihood maximization. We showed that these estimates could be also obtained using standard algorithms for Poisson regression. Copyright 2006 John Wiley & Sons, Ltd.

Time to detection of circulating microbubbles as a risk factor for symptoms of altitude decompression sickness

NASA Technical Reports Server (NTRS)

Kumar, K. V.; Calkins, Dick S.; Waligora, James M.; Gilbert, John H., III; Powell, Michael R.

1992-01-01

This study investigated the association between time at onset of circulating microbubbles (CMB) and symptoms of altitude decompression sickness (DCS), using Cox proportional hazard regression models. The study population consisted of 125 individuals who participated in direct ascent, simulated extravehicular activities profiles. Using individual CMB status as a time-dependent variable, we found that the hazard for symptoms increased significantly (at the end of 180 min at altitude) in the presence of CMB (Hazard Ratio = 29.59; 95 percent confidence interval (95 percent CI) = 7.66-114.27), compared to no CMB. Further examination was conducted on the subgroup of individuals who developed microbubbles during the test (n = 49), by using Cox regression. Individuals with late onset of CMB (greater than 60 min at altitude) showed a significantly reduced risk of symptoms (hazard ratio = 0.92; 95 percent CI = 0.89-0.95), compared to those with early onset (equal to or less than 60 min), while controlling for other risk factors. We conclude that time to detection of circulating microbubbles is an independent determinant of symptoms of DCS.

Landslide and Land Subsidence Hazards to Pipelines

USGS Publications Warehouse

Baum, Rex L.; Galloway, Devin L.; Harp, Edwin L.

2008-01-01

Landslides and land subsidence pose serious hazards to pipelines throughout the world. Many existing pipeline corridors and more and more new pipelines cross terrain that is affected by either landslides, land subsidence, or both. Consequently the pipeline industry recognizes a need for increased awareness of methods for identifying and evaluating landslide and subsidence hazard for pipeline corridors. This report was prepared in cooperation with the U.S. Department of Transportation Pipeline and Hazardous Materials Safety Administration, and Pipeline Research Council International through a cooperative research and development agreement (CRADA) with DGH Consulting, Inc., to address the need for up-to-date information about current methods to identify and assess these hazards. Chapters in this report (1) describe methods for evaluating landslide hazard on a regional basis, (2) describe the various types of land subsidence hazard in the United States and available methods for identifying and quantifying subsidence, and (3) summarize current methods for investigating individual landslides. In addition to the descriptions, this report provides information about the relative costs, limitations and reliability of various methods.

Food insecurity and its association with co-occurring postnatal depression, hazardous drinking, and suicidality among women in peri-urban South Africa

PubMed Central

Dewing, Sarah; Tomlinson, Mark; le Roux, Ingrid M.; Chopra, Mickey; Tsai, Alexander C.

2013-01-01

Background Although the public health impacts of food insecurity and depression on both maternal and child health are extensive, no studies have investigated the associations between food insecurity and postnatal depression or suicidality. Methods We interviewed 249 women three months after they had given birth and assessed food insecurity, postnatal depression symptom severity, suicide risk, and hazardous drinking. Multivariable Poisson regression models with robust standard errors were used to estimate the impact of food insecurity on psychosocial outcomes. Results Food insecurity, probable depression, and hazardous drinking were highly prevalent and co-occurring. More than half of the women (149 [59.8%]) were severely food insecure, 79 (31.7%) women met screening criteria for probable depression, and 39 (15.7%) women met screening criteria for hazardous drinking. Nineteen (7.6%) women had significant suicidality, of whom 7 (2.8%) were classified as high risk. Each additional point on the food insecurity scale was associated with increased risks of probable depression (adjusted risk ratio [ARR], 1.05; 95% CI, 1.02–1.07), hazardous drinking (ARR, 1.04; 95% CI, 1.00–1.09), and suicidality (ARR, 1.12; 95% CI, 1.02–1.23). Evaluated at the means of the covariates, these estimated associations were large in magnitude. Limitations The study is limited by lack of data on formal DSM-IV diagnoses of major depressive disorder, potential sample selection bias, and inability to assess the causal impact of food insecurity. Conclusion Food insecurity is strongly associated with postnatal depression, hazardous drinking, and suicidality. Programmes promoting food security for new may enhance overall psychological well-being in addition to improving nutritional status. PMID:23707034

Association of Severity of Coronary Artery Aneurysms in Patients With Kawasaki Disease and Risk of Later Coronary Events.

PubMed

Miura, Masaru; Kobayashi, Tohru; Kaneko, Tetsuji; Ayusawa, Mamoru; Fukazawa, Ryuji; Fukushima, Naoya; Fuse, Shigeto; Hamaoka, Kenji; Hirono, Keiichi; Kato, Taichi; Mitani, Yoshihide; Sato, Seiichi; Shimoyama, Shinya; Shiono, Junko; Suda, Kenji; Suzuki, Hiroshi; Maeda, Jun; Waki, Kenji; Kato, Hitoshi; Saji, Tsutomu; Yamagishi, Hiroyuki; Ozeki, Aya; Tomotsune, Masako; Yoshida, Makiko; Akazawa, Yohei; Aso, Kentaro; Doi, Shouzaburoh; Fukasawa, Yoshi; Furuno, Kenji; Hayabuchi, Yasunobu; Hayashi, Miyuki; Honda, Takafumi; Horita, Norihisa; Ikeda, Kazuyuki; Ishii, Masahiro; Iwashima, Satoru; Kamada, Masahiro; Kaneko, Masahide; Katyama, Hiroshi; Kawamura, Yoichi; Kitagawa, Atushi; Komori, Akiko; Kuraishi, Kenji; Masuda, Hiroshi; Matsuda, Shinichi; Matsuzaki, Satoshi; Mii, Sayaka; Miyamoto, Tomoyuki; Moritou, Yuji; Motoki, Noriko; Nagumo, Kiyoshi; Nakamura, Tsuneyuki; Nishihara, Eiki; Nomura, Yuichi; Ogata, Shohei; Ohashi, Hiroyuki; Okumura, Kenichi; Omori, Daisuke; Sano, Tetsuya; Suganuma, Eisuke; Takahashi, Tsutomu; Takatsuki, Shinichi; Takeda, Atsuhito; Terai, Masaru; Toyono, Manatomo; Watanabe, Kenichi; Watanabe, Makoto; Yamamoto, Masaki; Yamamura, Kenichiro

2018-05-07

Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA). To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA. This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011. The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ≥5 to <10; actual internal diameter, <8 mm), and large (z score, ≥10 or ≥8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications. Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P < .001) and 100%, 100%, and 75% in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1-15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7-4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4-3.6) were significantly associated with CE. Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.

Blood Cadmium Levels and Incident Cardiovascular Events during Follow-up in a Population-Based Cohort of Swedish Adults: The Malmö Diet and Cancer Study

PubMed Central

Barregard, Lars; Sallsten, Gerd; Fagerberg, Björn; Borné, Yan; Persson, Margaretha; Hedblad, Bo; Engström, Gunnar

2015-01-01

Background: Cadmium exposure may increase the risk of cardiovascular disease. The only published longitudinal study on cadmium and incident cardiovascular disease was performed in American Indians with relatively high cadmium exposure. Objectives: Our aim was to examine the association between blood cadmium at baseline and incident cardiovascular events in a population-based study of Swedish men and women with cadmium levels similar to those of most European and U.S. populations. Methods: A Swedish population-based cohort (n = 6,103, age 46–67 years) was recruited between 1991 and 1994. After we excluded those with missing data on smoking, 4,819 participants remained. Acute coronary events, other major cardiac events, stroke, and cardiovascular mortality were followed until 2010. Associations with blood cadmium (estimated from cadmium in erythrocytes) were analyzed using Cox proportional hazards regression including potential confounders and important cardiovascular risk factors. Results: Hazard ratios for all cardiovascular end points were consistently increased for participants in the 4th blood cadmium quartile (median, 0.99 μg/L). In models that also included sex, smoking, waist circumference, education, physical activity, alcohol intake, serum triglycerides, HbA1c, and C-reactive protein, the hazard ratios comparing the highest and lowest quartiles of exposure were 1.8 (95% CI: 1.2, 2.7) for acute coronary events, and 1.9 (1.3, 2.9) for stroke. Hazard ratios in never-smokers were consistent with these estimates. Conclusions: Blood cadmium in the highest quartile was associated with incident cardiovascular disease and mortality in our population-based samples of Swedish adults. The consistent results among never-smokers are important because smoking is a strong confounder. Our findings suggest that measures to reduce cadmium exposures are warranted, even in populations without unusual sources of exposure. Citation: Barregard L, Sallsten G, Fagerberg B, Borné Y, Persson M, Hedblad B, Engström G. 2016. Blood cadmium levels and incident cardiovascular events during follow-up in a population-based cohort of Swedish adults: the Malmö Diet and Cancer Study. Environ Health Perspect 124:594–600; http://dx.doi.org/10.1289/ehp.1509735 PMID:26517380

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

PubMed

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

2012-01-01

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

Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL).

PubMed

Preston, Ioana R; Roberts, Kari E; Miller, Dave P; Sen, Ginny P; Selej, Mona; Benton, Wade W; Hill, Nicholas S; Farber, Harrison W

2015-12-22

Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH. Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients. No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214. © 2015 The Authors.

Hot wet spots of Swiss buildings - detecting clusters of flood exposure

NASA Astrophysics Data System (ADS)

Röthlisberger, Veronika; Zischg, Andreas; Keiler, Margreth

2016-04-01

Where are the hotspots of flood exposure in Switzerland? There is no single answer but rather a wide range of findings depending on the databases and methods used. In principle, the analysis of flood exposure is the overlay of two spatial datasets, one on flood hazard and one on assets, e.g. buildings. The presented study aims to test a new developed approach which is based on public available Swiss data. On the hazard side, these are two different types of flood hazard maps each representing a similar return period beyond the dimensioning of structural protection systems. When it comes to assets we use nationwide harmonized data on building, namely a complete dataset of building polygons to which we assign features as volume, residents and monetary value. For the latter we apply findings of multivariate analyses of insurance data. By overlaying building polygons with the flood hazard map we identify the exposed buildings. We analyse the resulting spatial distribution of flood exposure at different levels of scales (local to regional) using administrative units (e.g. municipalities) but also artificial grids with a corresponding size (e.g. 5 000 m). The presentation focuses on the identification of hotspots highlighting the influence of the applied data and methods, e.g. local scan statistics testing intensities within and without potential clusters or log relative exposure surfaces based on kernel intensity estimates. We find a major difference of identified hotspots between absolute values and normalized values of exposure. Whereas the hotspots of flood exposure in absolute figures mirrors the underlying distribution of buildings, the hotspots of flood exposure ratios show very different pictures. We conclude that findings on flood exposure vary depending on the data and moreover the methods used and therefore need to be communicated carefully and appropriate to different stakeholders who may use the information for decision making on flood risk management.

Neighborhood social and physical environments and type 2 diabetes mellitus in African Americans: The Jackson Heart Study.

PubMed

Gebreab, Samson Y; Hickson, DeMarc A; Sims, Mario; Wyatt, Sharon B; Davis, Sharon K; Correa, Adolfo; Diez-Roux, Ana V

2017-01-01

Using data from Jackson Heart Study, we investigated the associations of neighborhood social and physical environments with prevalence and incidence of type 2 diabetes mellitus (T2DM) in African Americans (AA). Among non-diabetic participants at baseline (n=3670), 521 (14.2%) developed T2DM during a median follow-up of 7.3 years. Measures of neighborhood social environments, and food and physical activity resources were derived using survey-and GIS-based methods. Prevalence ratios (PR) and Hazard ratios (HR) were estimated using generalized estimating equations and Cox proportional hazards models. Higher neighborhood social cohesion was associated with a 22% lower incidence of T2DM while higher density of unfavorable food stores was associated with a 34% higher incidence of T2DM after adjusting for individual-level risk factors (HR=0.78 [95% CI:0.62, 0.99] and HR=1.34 [1.12, 1.60], respectively). In addition, neighborhood problems was also associated with prevalence of T2DM (PR=1.12 [1.03, 1.21]) independent of individual-level risk factors. Our findings suggest that efforts to strengthen community ties or to attract healthy food retail outlets might be important strategies to consider for prevention of T2DM in AA. Published by Elsevier Ltd.

Serum Urate at Trial Entry and ALS Progression in EMPOWER

PubMed Central

O'Reilly, Éilis J.; Liu, Dawei; Johns, Donald R.; Cudkowicz, Merit E.; Paganoni, Sabrina; Schwarzschild, Michael A.; Leitner, Melanie; Ascherio, Alberto

2017-01-01

Objective Determine whether serum urate predicts ALS progression. Methods The study population comprised adult participants of EMPOWER (n=942), a phase III clinical trial to evaluate the efficacy of dexpramipexole to treat ALS. Urate was measured in blood samples collected during enrollment as part of the routine block chemistry. Outcomes Combined assessment of function and survival rank (CAFs), and time to death, by 12 months. Results In women there was not a significant relation between urate and outcomes. In men, outcomes improved with increasing urate (comparing highest to lowest urate quartile: CAFS was 53 points better with p for trend=0.04; and hazard ratio for death was 0.60 with p for trend=0.07), but with adjustment for body mass index (BMI) at baseline, a predictor of both urate levels and prognosis, associations were attenuated and no longer statistically significant. Overall, participants with urate levels equal to or above the median (5.1 mg/dL) appeared to have a survival advantage compared to those below (hazard ratio adjusted for BMI: 0.67; 95% confidence interval: 0.47 to 0.95). Conclusion These findings suggest that while the association between urate at baseline and ALS progression is partially explained by BMI, there may be an independent beneficial effect of urate. PMID:27677562

Workplace Social Capital and All-Cause Mortality: A Prospective Cohort Study of 28 043 Public-Sector Employees in Finland

PubMed Central

Kivimäki, Mika; Kawachi, Ichiro; Subramanian, S. V.; Takao, Soshi; Suzuki, Etsuji; Kouvonen, Anne; Pentti, Jaana; Salo, Paula; Virtanen, Marianna; Vahtera, Jussi

2011-01-01

Objectives. We examined the association between workplace social capital and all-cause mortality in a large occupational cohort from Finland. Methods. We linked responses of 28 043 participants to surveys in 2000 to 2002 and in 2004 to national mortality registers through 2009. We used repeated measurements of self- and coworker-assessed social capital. We carried out Cox proportional hazard and fixed-effects logistic regressions. Results. During the 5-year follow-up, 196 employees died. A 1-unit increase in the mean of repeat measurements of self-assessed workplace social capital (range 1–5) was associated with a 19% decrease in the risk of all-cause mortality (age- and gender-adjusted hazard ratio [HR] = 0.81; 95% confidence interval [CI] = 0.66, 0.99). The corresponding point estimate for the mean of coworker-assessed social capital was similar, although the association was less precisely estimated (age- and gender-adjusted HR = 0.77; 95% CI = 0.50, 1.20). In fixed-effects analysis, a 1-unit increase in self-assessed social capital across the 2 time points was associated with a lower mortality risk (odds ratio = 0.81; 95% CI = 0.55, 1.19). Conclusions. Workplace social capital appears to be associated with lowered mortality in the working-aged population. PMID:21778502

Effect of Pretreatment Anemia on Treatment Outcome of Concurrent Radiochemotherapy in Patients With Head and Neck Cancer

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

Fortin, Andre; Wang Changshu; Vigneault, Eric

2008-09-01

Purpose: To investigate the effect of anemia on outcome of treatment with radiochemotherapy in patients with head-and-neck cancer. Methods and Materials: The data of 196 patients with Stage II-IV head-and-neck cancer treated with concomitant cisplatin-based radiochemotherapy were retrospectively reviewed. Anemia was defined according to World Health Organization criteria as hemoglobin <130 g/L in men and <120 g/L in women. Results: Fifty-three patients were classified as anemic, 143 as nonanemic. The 3-year local control rate of anemic and nonanemic patients was 72% and 85%, respectively (p = 0.01). The 3-year overall survival rate of anemic and nonanemic patients was 52% andmore » 77%, respectively (p = 0.004). In multivariate analysis, anemia was the most significant predictor of local control (hazard ratio, 0.37, p = 0.009) and survival (hazard ratio, 0.47, p = 0.007). A dose-effect relationship was also found for local control (p = .04) and survival (0.04) when grouping by hemoglobin concentration: <120, 120-140, and >140 g/L. Conclusions: Anemia was strongly associated with local control and survival in this cohort of patients with head-and-neck cancer receiving radiochemotherapy.« less

Validation and Potential Mechanisms of Red Cell Distribution Width as a Prognostic Marker in Heart Failure

PubMed Central

ALLEN, LARRY A.; FELKER, G. MICHAEL; MEHRA, MANDEEP R.; CHIONG, JUN R.; DUNLAP, STEPHANIE H.; GHALI, JALAL K.; LENIHAN, DANIEL J.; OREN, RON M.; WAGONER, LYNNE E.; SCHWARTZ, TODD A.; ADAMS, KIRKWOOD F.

2014-01-01

Background: Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association. Methods and Results: Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization. Conclusions: Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system. PMID:20206898

Early-Life Origins of Adult Disease: National Longitudinal Population-Based Study of the United States

PubMed Central

Schoeni, Robert F.

2011-01-01

Objectives. We examined the relation between low birth weight and childhood family and neighborhood socioeconomic disadvantage and disease onset in adulthood. Methods. Using US nationally representative longitudinal data, we estimated hazard models of the onset of asthma, hypertension, diabetes, and stroke, heart attack, or heart disease. The sample contained 4387 children who were members of the Panel Study of Income Dynamics in 1968; they were followed up to 2007, when they were aged 39 to 56 years. Our research design included sibling comparisons of disease onset among siblings with different birth weights. Results. The odds ratios of having asthma, hypertension, diabetes, and stroke, heart attack, or heart disease by age 50 years for low–birth weight babies vs others were 1.64 (P < .01), 1.51 (P < .01), 2.09 (P < .01), and 2.16 (P < .01), respectively. Adult disease prevalence differed substantially by childhood socioeconomic status (SES). After accounting for childhood socioeconomic factors, we found a substantial hazard ratio of disease onset associated with low birth weight, which persisted for sibling comparisons. Conclusions. Childhood SES is strongly associated with the onset of chronic disease in adulthood. Low birth weight plays an important role in disease onset; this relation persists after an array of childhood socioeconomic factors is accounted for. PMID:22021306

Social vulnerability of rural households to flood hazards in western mountainous regions of Henan province, China

NASA Astrophysics Data System (ADS)

Liu, D. L.; Li, Y.

2015-11-01

Evaluating social vulnerability is a crucial issue in risk and disaster management. In this study, a household social vulnerability index (HSVI) to flood hazards was developed and used to assess the social vulnerability of rural households in western mountainous regions of Henan province, China. Eight key indicators were indentified through interactive discussions with multidisciplinary specialists and local farmers, and their weights were determined using principle component analysis (PCA). The results showed that (1) the ratio of perennial working in other places, hazard-related training and illiteracy ratio (15+) were the most dominant factors to social vulnerability. (2) The numbers of high, moderate and low vulnerable households were 14, 64 and 16, respectively, which accounted for 14.9, 68.1, and 17.0 % of the total interviewed rural households, respectively. (3) The correlation coefficient between household social vulnerability scores and casualties in a storm flood in July 2010 was significant at 0.05 significance level (r = 0.248), which indicated that the selected indicators and their weights were valid. (4) Some mitigation strategies to reduce the household social vulnerability to flood hazards were proposed based on the assessment results. The results provide useful information for rural households and local governments to prepare, mitigate and response to flood hazards.

Multivariate factorial analysis to design a robust batch leaching test to assess the volcanic ash geochemical hazard.

PubMed

Ruggieri, Flavia; Gil, Raúl A; Fernandez-Turiel, Jose-Luis; Saavedra, Julio; Gimeno, Domingo; Lobo, Agustin; Martinez, Luis D; Rodriguez-Gonzalez, Alejandro

2012-04-30

A method to obtain robust information on short term leaching behaviour of volcanic ashes has been developed independently on the sample age. A mixed factorial design (MFD) was employed as a multivariate strategy for the evaluation of the effects of selected control factors and their interactions (amount of sample (A), contact time (B), and liquid to solid ratio or L/S (C)) on the leaching process of selected metals (Na, K, Mg, Ca, Si, Al, V, Mn, Fe, and Co) and anions (Cl(-) and SO(4)(2-)). Box plots of the data acquired were used to evaluate the reproducibility achieved at different experimental conditions. Both the amount of sample (A) and leaching time (B) had a significant effect on the element stripping whereas the L/S ratio influenced only few elements. The lowest dispersion values have been observed when 1.0 g was leached with an L/S ratio equal to 10, shaking during 4 h. The entire method is completed within few hours, and it is simple, feasible and reliable in laboratory conditions. Copyright © 2012 Elsevier B.V. All rights reserved.

An evaluation of bias in propensity score-adjusted non-linear regression models.

PubMed

Wan, Fei; Mitra, Nandita

2018-03-01

Propensity score methods are commonly used to adjust for observed confounding when estimating the conditional treatment effect in observational studies. One popular method, covariate adjustment of the propensity score in a regression model, has been empirically shown to be biased in non-linear models. However, no compelling underlying theoretical reason has been presented. We propose a new framework to investigate bias and consistency of propensity score-adjusted treatment effects in non-linear models that uses a simple geometric approach to forge a link between the consistency of the propensity score estimator and the collapsibility of non-linear models. Under this framework, we demonstrate that adjustment of the propensity score in an outcome model results in the decomposition of observed covariates into the propensity score and a remainder term. Omission of this remainder term from a non-collapsible regression model leads to biased estimates of the conditional odds ratio and conditional hazard ratio, but not for the conditional rate ratio. We further show, via simulation studies, that the bias in these propensity score-adjusted estimators increases with larger treatment effect size, larger covariate effects, and increasing dissimilarity between the coefficients of the covariates in the treatment model versus the outcome model.

Reciprocal Risk of Acute Kidney Injury and Acute Respiratory Distress Syndrome in Critically Ill Burn Patients.

PubMed

Clemens, Michael S; Stewart, Ian J; Sosnov, Jonathan A; Howard, Jeffrey T; Belenkiy, Slava M; Sine, Christy R; Henderson, Jonathan L; Buel, Allison R; Batchinsky, Andriy I; Cancio, Leopoldo C; Chung, Kevin K

2016-10-01

To evaluate the association between acute respiratory distress syndrome and acute kidney injury with respect to their contributions to mortality in critically ill patients. Retrospective analysis of consecutive adult burn patients requiring mechanical ventilation. A 16-bed burn ICU at tertiary military teaching hospital. Adult patients more than 18 years old requiring mechanical ventilation during their initial admission to our burn ICU from January 1, 2003, to December 31, 2011. None. A total 830 patients were included, of whom 48.2% had acute kidney injury (n = 400). These patients had a 73% increased risk of developing acute respiratory distress syndrome after controlling for age, gender, total body surface area burned, and inhalation injury (hazard ratio, 1.73; 95% CI, 1.18-2.54; p = 0.005). In a reciprocal multivariate analysis, acute respiratory distress syndrome (n = 299; 36%) demonstrated a strong trend toward developing acute kidney injury (hazard ratio, 1.39; 95% CI, 0.99-1.95; p = 0.05). There was a 24% overall in-hospital mortality (n = 198). After adjusting for the aforementioned confounders, both acute kidney injury (hazard ratio, 3.73; 95% CI, 2.39-5.82; p < 0.001) and acute respiratory distress syndrome (hazard ratio, 2.16; 95% CI, 1.58-2.94; p < 0.001) significantly contributed to mortality. Age, total body surface area burned, and inhalation injury were also significantly associated with increased mortality. Acute kidney injury increases the risk of acute respiratory distress syndrome in mechanically ventilated burn patients, whereas acute respiratory distress syndrome similarly demonstrates a strong trend toward the development of acute kidney injury. Acute kidney injury and acute respiratory distress syndrome are both independent risks for subsequent death. Future research should look at this interplay for possible early interventions.

Gender Differences in Appropriate Shocks and Mortality among Patients with Primary Prophylactic Implantable Cardioverter-Defibrillators: Systematic Review and Meta-Analysis.

PubMed

Conen, David; Arendacká, Barbora; Röver, Christian; Bergau, Leonard; Munoz, Pascal; Wijers, Sofieke; Sticherling, Christian; Zabel, Markus; Friede, Tim

2016-01-01

Some but not all prior studies have shown that women receiving a primary prophylactic implantable cardioverter defibrillator (ICD) have a lower risk of death and appropriate shocks than men. To evaluate the effect of gender on the risk of appropriate shock, all-cause mortality and inappropriate shock in contemporary studies of patients receiving a primary prophylactic ICD. PubMed, LIVIVO, Cochrane CENTRAL between 2010 and 2016. Studies providing at least 1 gender-specific risk estimate for the outcomes of interest. Abstracts were screened independently for potentially eligible studies for inclusion. Thereby each abstract was reviewed by at least two authors. Out of 680 abstracts retained by our search strategy, 20 studies including 46'657 patients had gender-specific information on at least one of the relevant endpoints. Mean age across the individual studies varied between 58 and 69 years. The proportion of women enrolled ranged from 10% to 30%. Across 6 available studies, women had a significantly lower risk of first appropriate shock compared with men (pooled multivariable adjusted hazard ratio 0.62 (95% CI [0.44; 0.88]). Across 14 studies reporting multivariable adjusted gender-specific hazard ratio estimates for all-cause mortality, women had a lower risk of death than men (pooled hazard ratio 0.75 (95% CI [0.66; 0.86]). There was no statistically significant difference for the incidence of first inappropriate shocks (3 studies, pooled hazard ratio 0.99 (95% CI [0.56; 1.73]). Individual patient data were not available for most studies. In this large contemporary meta-analysis, women had a significantly lower risk of appropriate shocks and death than men, but a similar risk of inappropriate shocks. These data may help to select patients who benefit from primary prophylactic ICD implantation.

Red meat, chicken, and fish consumption and risk of colorectal cancer.

PubMed

English, Dallas R; MacInnis, Robert J; Hodge, Allison M; Hopper, John L; Haydon, Andrew M; Giles, Graham G

2004-09-01

Red meat and processed meat consumption have been associated with increased risk of colorectal cancer in some, but not all, relevant cohort studies. Evidence on the relationship between risk of colorectal cancer and poultry and fish consumption is inconsistent. We conducted a prospective cohort study of 37,112 residents of Melbourne, Australia recruited from 1990 to 1994. Diet was measured with a food frequency questionnaire. We categorized the frequency of fresh red meat, processed meat, chicken, and fish consumption into approximate quartiles. Adenocarcinomas of the colon or rectum were ascertained via the Victorian Cancer Registry. We identified 283 colon cancers and 169 rectal cancers in an average of 9 years of follow-up. For rectal cancer, the hazard ratios [95% confidence intervals (95% CI)] in the highest quartile of consumption of fresh red meat and processed meat were 2.3 (1.2-4.2; P for trend = 0.07) and 2.0 (1.1-3.4; P for trend = 0.09), respectively. The corresponding hazard ratios (95% CIs) for colon cancer were 1.1 (0.7-1.6; P for trend = 0.9) and 1.3 (0.9-1.9; P for trend = 0.06). However, for neither type of meat was the heterogeneity between subsites significant. Chicken consumption was weakly negatively associated with colorectal cancer (hazard ratio highest quartile, 0.7; 95% CI, 0.6-1.0; P for trend = 0.03), whereas hazard ratios for fish consumption were close to unity. Consumption of fresh red meat and processed meat seemed to be associated with an increased risk of rectal cancer. Consumption of chicken and fish did not increase risk.

Daytime Napping and the Risk of All-Cause and Cause-Specific Mortality: A 13-Year Follow-up of a British Population

PubMed Central

Leng, Yue; Wainwright, Nick W. J.; Cappuccio, Francesco P.; Surtees, Paul G.; Hayat, Shabina; Luben, Robert; Brayne, Carol; Khaw, Kay-Tee

2014-01-01

Epidemiologic studies have reported conflicting results on the relationship between daytime napping and mortality risk, and there are few data on the potential association in the British population. We investigated the associations between daytime napping and all-cause or cause-specific mortality in the European Prospective Investigation Into Cancer-Norfolk study, a British population-based cohort study. Among the 16,374 men and women who answered questions on napping habits between 1998 and 2000, a total of 3,251 died during the 13-year follow-up. Daytime napping was associated with an increased risk of all-cause mortality (for napping less than 1 hour per day on average, hazard ratio = 1.14, 95% confidence interval: 1.02, 1.27; for napping 1 hour or longer per day on average, hazard ratio = 1.32, 95% confidence interval: 1.04, 1.68), independent of age, sex, social class, educational level, marital status, employment status, body mass index, physical activity level, smoking status, alcohol intake, depression, self-reported general health, use of hypnotic drugs or other medications, time spent in bed at night, and presence of preexisting health conditions. This association was more pronounced for death from respiratory diseases (for napping less than 1 hour, hazard ratio = 1.40, 95% confidence interval: 0.95, 2.05; for napping 1 hour or more, hazard ratio = 2.56, 95% confidence interval: 1.34, 4.86) and in individuals 65 years of age or younger. Excessive daytime napping might be a useful marker of underlying health risk, particularly of respiratory problems, especially among those 65 years of age or younger. Further research is required to clarify the nature of the observed association. PMID:24685532

Daytime napping and the risk of all-cause and cause-specific mortality: a 13-year follow-up of a British population.

PubMed

Leng, Yue; Wainwright, Nick W J; Cappuccio, Francesco P; Surtees, Paul G; Hayat, Shabina; Luben, Robert; Brayne, Carol; Khaw, Kay-Tee

2014-05-01

Epidemiologic studies have reported conflicting results on the relationship between daytime napping and mortality risk, and there are few data on the potential association in the British population. We investigated the associations between daytime napping and all-cause or cause-specific mortality in the European Prospective Investigation Into Cancer-Norfolk study, a British population-based cohort study. Among the 16,374 men and women who answered questions on napping habits between 1998 and 2000, a total of 3,251 died during the 13-year follow-up. Daytime napping was associated with an increased risk of all-cause mortality (for napping less than 1 hour per day on average, hazard ratio = 1.14, 95% confidence interval: 1.02, 1.27; for napping 1 hour or longer per day on average, hazard ratio = 1.32, 95% confidence interval: 1.04, 1.68), independent of age, sex, social class, educational level, marital status, employment status, body mass index, physical activity level, smoking status, alcohol intake, depression, self-reported general health, use of hypnotic drugs or other medications, time spent in bed at night, and presence of preexisting health conditions. This association was more pronounced for death from respiratory diseases (for napping less than 1 hour, hazard ratio = 1.40, 95% confidence interval: 0.95, 2.05; for napping 1 hour or more, hazard ratio = 2.56, 95% confidence interval: 1.34, 4.86) and in individuals 65 years of age or younger. Excessive daytime napping might be a useful marker of underlying health risk, particularly of respiratory problems, especially among those 65 years of age or younger. Further research is required to clarify the nature of the observed association.

Right Ventricular Structure and Function Are Associated With Incident Atrial Fibrillation: MESA-RV Study (Multi-Ethnic Study of Atherosclerosis-Right Ventricle).

PubMed

Chatterjee, Neal A; Shah, Ravi V; Murthy, Venkatesh L; Praestgaard, Amy; Shah, Sanjiv J; Ventetuolo, Corey E; Barr, R Graham; Kronmal, Richard; Lima, Joao A C; Bluemke, David A; Jerosch-Herold, Michael; Alonso, Alvaro; Kawut, Steven M

2017-01-01

Right ventricular (RV) morphology has been associated with drivers of atrial fibrillation (AF) risk, including left ventricular and pulmonary pathology, systemic inflammation, and neurohormonal activation. The aim of this study was to investigate the association between RV morphology and risk of incident AF. We interpreted cardiac magnetic resonance imaging in 4204 participants free of clinical cardiovascular disease in the MESA (Multi-Ethnic Study of Atherosclerosis). Incident AF was determined using hospital discharge records, study electrocardiograms, and Medicare claims data. The study sample (n=3819) was 61±10 years old and 47% male with 47.2% current/former smokers. After adjustment for demographics and clinical factors, including incident heart failure, higher RV ejection fraction (hazard ratio, 1.16 per SD; 95% confidence interval, 1.03-1.32; P=0.02) and greater RV mass (hazard ratio, 1.25 per SD; 95% confidence interval, 1.08-1.44; P=0.002) were significantly associated with incident AF. After additional adjustment for the respective left ventricular parameter, higher RV ejection fraction remained significantly associated with incident AF (hazard ratio, 1.15 per SD; 95% confidence interval, 1.01-1.32; P=0.04), whereas the association was attenuated for RV mass (hazard ratio, 1.16 per SD; 95% confidence interval, 0.99-1.35; P=0.07). In a subset of patients with available spirometry (n=2540), higher RV ejection fraction and mass remained significantly associated with incident AF after additional adjustment for lung function (P=0.02 for both). Higher RV ejection fraction and greater RV mass were associated with an increased risk of AF in a multiethnic population free of clinical cardiovascular disease at baseline. © 2017 American Heart Association, Inc.

Pancreatic β-Cell Function and Prognosis of Nondiabetic Patients With Ischemic Stroke.

PubMed

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

2017-11-01

Pancreatic β-cell dysfunction is an important factor in the development of type 2 diabetes mellitus. This study aimed to estimate the association between β-cell dysfunction and prognosis of nondiabetic patients with ischemic stroke. Patients with ischemic stroke without a history of diabetes mellitus in the ACROSS-China (Abnormal Glucose Regulation in Patients with Acute Stroke across China) registry were included. Disposition index was estimated as computer-based model of homeostatic model assessment 2-β%/homeostatic model assessment 2-insulin resistance based on fasting C-peptide level. Outcomes included stroke recurrence, all-cause death, and dependency (modified Rankin Scale, 3-5) at 12 months after onset. Among 1171 patients, 37.2% were women with a mean age of 62.4 years. At 12 months, 167 (14.8%) patients had recurrent stroke, 110 (9.4%) died, and 184 (16.0%) had a dependency. The first quartile of the disposition index was associated with an increased risk of stroke recurrence (adjusted hazard ratio, 3.57; 95% confidence interval, 2.13-5.99) and dependency (adjusted hazard ratio, 2.30; 95% confidence interval, 1.21-4.38); both the first and second quartiles of the disposition index were associated with an increased risk of death (adjusted hazard ratio, 5.09; 95% confidence interval, 2.51-10.33; adjusted hazard ratio, 2.42; 95% confidence interval, 1.17-5.03) compared with the fourth quartile. Using a multivariable regression model with restricted cubic spline, we observed an L-shaped association between the disposition index and the risk of each end point. In this large-scale registry, β-cell dysfunction was associated with an increased risk of 12-month poor prognosis in nondiabetic patients with ischemic stroke. © 2017 American Heart Association, Inc.

Effect and clinical prediction of worsening renal function in acute decompensated heart failure.

PubMed

Breidthardt, Tobias; Socrates, Thenral; Noveanu, Markus; Klima, Theresia; Heinisch, Corinna; Reichlin, Tobias; Potocki, Mihael; Nowak, Albina; Tschung, Christopher; Arenja, Nisha; Bingisser, Roland; Mueller, Christian

2011-03-01

We aimed to establish the prevalence and effect of worsening renal function (WRF) on survival among patients with acute decompensated heart failure. Furthermore, we sought to establish a risk score for the prediction of WRF and externally validate the previously established Forman risk score. A total of 657 consecutive patients with acute decompensated heart failure presenting to the emergency department and undergoing serial creatinine measurements were enrolled. The potential of the clinical parameters at admission to predict WRF was assessed as the primary end point. The secondary end point was all-cause mortality at 360 days. Of the 657 patients, 136 (21%) developed WRF, and 220 patients had died during the first year. WRF was more common in the nonsurvivors (30% vs 41%, p = 0.03). Multivariate regression analysis found WRF to independently predict mortality (hazard ratio 1.92, p <0.01). In a single parameter model, previously diagnosed chronic kidney disease was the only independent predictor of WRF and achieved an area under the receiver operating characteristic curve of 0.60. After the inclusion of the blood gas analysis parameters into the model history of chronic kidney disease (hazard ratio 2.13, p = 0.03), outpatient diuretics (hazard ratio 5.75, p <0.01), and bicarbonate (hazard ratio 0.91, p <0.01) were all predictive of WRF. A risk score was developed using these predictors. On receiver operating characteristic curve analysis, the Forman and Basel prediction rules achieved an area under the curve of 0.65 and 0.71, respectively. In conclusion, WRF was common in patients with acute decompensated heart failure and was linked to significantly worse outcomes. However, the clinical parameters failed to adequately predict its occurrence, making a tailored therapy approach impossible. Copyright © 2011 Elsevier Inc. All rights reserved.

Dimensions of socioeconomic status and clinical outcome after primary percutaneous coronary intervention.

PubMed

Jakobsen, Lars; Niemann, Troels; Thorsgaard, Niels; Thuesen, Leif; Lassen, Jens F; Jensen, Lisette O; Thayssen, Per; Ravkilde, Jan; Tilsted, Hans H; Mehnert, Frank; Johnsen, Søren P

2012-10-01

The association between low socioeconomic status (SES) and high mortality from coronary heart disease is well-known. However, the role of SES in relation to the clinical outcome after primary percutaneous coronary intervention remains poorly understood. We studied 7385 patients treated with primary percutaneous coronary intervention. Participants were divided into high-SES and low-SES groups according to income, education, and employment status. The primary outcome was major adverse cardiac events (cardiac death, recurrent myocardial infarction, and target vessel revascularization) at maximum follow-up (mean, 3.7 years). Low-SES patients had more adverse baseline risk profiles than high-SES patients. The cumulative risk of major adverse cardiac events after maximum follow-up was higher among low-income patients and unemployed patients compared with their counterparts (income: hazard ratio, 1.68; 95% CI, 1.47-1.92; employment status: hazard ratio, 1.75; 95% CI, 1.46-2.10). After adjustment for patient characteristics, these differences were substantially attenuated (income: hazard ratio, 1.12; 95% CI, 0.93-1.33; employment status: hazard ratio, 1.27; 95% CI, 1.03-1.56). Further adjustment for admission findings, procedure-related data, and medical treatment during follow-up did not significantly affect the associations. With education as the SES indicator, no between-group differences were observed in the risk of the composite end point. Even in a tax-financed healthcare system, low-SES patients treated with primary percutaneous coronary intervention face a worse prognosis than high-SES patients. The poor outcome seems to be largely explained by differences in baseline patient characteristics. Employment status and income (but not education level) were associated with clinical outcomes.

Effects of Antiretroviral Therapy and Depressive Symptoms on All-Cause Mortality Among HIV-Infected Women.

PubMed

Todd, Jonathan V; Cole, Stephen R; Pence, Brian W; Lesko, Catherine R; Bacchetti, Peter; Cohen, Mardge H; Feaster, Daniel J; Gange, Stephen; Griswold, Michael E; Mack, Wendy; Rubtsova, Anna; Wang, Cuiwei; Weedon, Jeremy; Anastos, Kathryn; Adimora, Adaora A

2017-05-15

Depression affects up to 30% of human immunodeficiency virus (HIV)-infected individuals. We estimated joint effects of antiretroviral therapy (ART) initiation and depressive symptoms on time to death using a joint marginal structural model and data from a cohort of HIV-infected women from the Women's Interagency HIV Study (conducted in the United States) from 1998-2011. Among 848 women contributing 6,721 years of follow-up, 194 participants died during follow-up, resulting in a crude mortality rate of 2.9 per 100 women-years. Cumulative mortality curves indicated greatest mortality for women who reported depressive symptoms and had not initiated ART. The hazard ratio for depressive symptoms was 3.38 (95% confidence interval (CI): 2.15, 5.33) and for ART was 0.47 (95% CI: 0.31, 0.70). Using a reference category of women without depressive symptoms who had initiated ART, the hazard ratio for women with depressive symptoms who had initiated ART was 3.60 (95% CI: 2.02, 6.43). For women without depressive symptoms who had not started ART, the hazard ratio was 2.36 (95% CI: 1.16, 4.81). Among women reporting depressive symptoms who had not started ART, the hazard ratio was 7.47 (95% CI: 3.91, 14.3). We found a protective effect of ART initiation on mortality, as well as a harmful effect of depressive symptoms, in a cohort of HIV-infected women. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Very-high-risk localized prostate cancer: definition and outcomes.

PubMed

Sundi, D; Wang, V M; Pierorazio, P M; Han, M; Bivalacqua, T J; Ball, M W; Antonarakis, E S; Partin, A W; Schaeffer, E M; Ross, A E

2014-03-01

Outcomes in men with National Comprehensive Cancer Network (NCCN) high-risk prostate cancer (PCa) can vary substantially-some will have excellent cancer-specific survival, whereas others will experience early metastasis even after aggressive local treatments. Current nomograms, which yield continuous risk probabilities, do not separate high-risk PCa into distinct sub-strata. Here, we derive a binary definition of very-high-risk (VHR) localized PCa to aid in risk stratification at diagnosis and selection of therapy. We queried the Johns Hopkins radical prostatectomy database to identify 753 men with NCCN high-risk localized PCa (Gleason sum 8-10, PSA >20 ng ml(-1), or clinical stage ≥T3). Twenty-eight alternate permutations of adverse grade, stage and cancer volume were compared by their hazard ratios for metastasis and cancer-specific mortality. VHR criteria with top-ranking hazard ratios were further evaluated by multivariable analyses and inclusion of a clinically meaningful proportion of the high-risk cohort. The VHR cohort was best defined by primary pattern 5 present on biopsy, or ≥5 cores with Gleason sum 8-10, or multiple NCCN high-risk features. These criteria encompassed 15.1% of the NCCN high-risk cohort. Compared with other high-risk men, VHR men were at significantly higher risk for metastasis (hazard ratio 2.75) and cancer-specific mortality (hazard ratio 3.44) (P<0.001 for both). Among high-risk men, VHR men also had significantly worse 10-year metastasis-free survival (37% vs 78%) and cancer-specific survival (62% vs 90%). Men who meet VHR criteria form a subgroup within the current NCCN high-risk classification who have particularly poor oncological outcomes. Use of these characteristics to distinguish VHR localized PCa may help in counseling and selection optimal candidates for multimodal treatments or clinical trials.

Mortality after a diagnosis of dementia in a population aged 75 and over in Spain.

PubMed

Llinàs-Regla, Jordi; López-Pousa, Secundino; Vilalta-Franch, Joan; Garre-Olmo, Josep; Román, Gustavo C

2008-01-01

To examine the impact of incident dementia on the risk of death, taking into account other chronic illnesses potentially related to death. Six-year, prospective, two-phase, observational cohort study. 8 municipalities from a rural area in Girona (Spain). A representative community-based cohort of 1,153 adults aged over 70 living at home at study enrolment. Surviving participants underwent detailed clinical evaluation and were assessed by means of the Cambridge Examination for Mental Disorders of the Elderly. Relatives of deceased participants were interviewed using the Retrospective Collateral Dementia Interview. Mortality rates and relative risk of death for subjects with a diagnosis of dementia were calculated. The Cox proportional hazards regression model was used to assess the relationship between mortality and the diagnosis of dementia. In this cohort, 40.0% (n = 49) of the subjects with a diagnosis of dementia died. The mortality rate specific to dementia was 1.0 per 100 person-years. Mortality risk ratios for dementia were 1.79 in men [95% confidence interval (CI) = 1.06-3.02], and 3.14 in women (95% CI = 2.04-4.85). The population death risk attributable to the diagnosis of dementia in our cohort was 11.8%. The most important mortality risks were severe dementia (hazard ratio = 5.7, 95% CI = 3.7-8.6), cancer (hazard ratio = 3.2, 95% CI = 2.2-4.5), heart disease, and an age over 85 (hazard ratio = 1.4, 95% CI = 1.1-1.9). Dementia is a major risk factor for death in advanced age, with the highest mortality rates in women. Moderate and severe dementia was associated with an increased mortality risk even after appropriate control of comorbid conditions. Copyright 2008 S. Karger AG, Basel.

Mortality in former Olympic athletes: retrospective cohort analysis

PubMed Central

Zwiers, R; Zantvoord, F W A; van Bodegom, D; van der Ouderaa, F J G; Westendorp, R G J

2012-01-01

Objective To assess the mortality risk in subsequent years (adjusted for year of birth, nationality, and sex) of former Olympic athletes from disciplines with different levels of exercise intensity. Design Retrospective cohort study. Setting Former Olympic athletes. Participants 9889 athletes (with a known age at death) who participated in the Olympic Games between 1896 and 1936, representing 43 types of disciplines with different levels of cardiovascular, static, and dynamic intensity exercise; high or low risk of bodily collision; and different levels of physical contact. Main outcome measure All cause mortality. Results Hazard ratios for mortality among athletes from disciplines with moderate cardiovascular intensity (1.01, 95% confidence interval 0.96 to 1.07) or high cardiovascular intensity (0.98, 0.92 to 1.04) were similar to those in athletes from disciplines with low cardiovascular intensity. The underlying static and dynamic components in exercise intensity showed similar non-significant results. Increased mortality was seen among athletes from disciplines with a high risk of bodily collision (hazard ratio 1.11, 1.06 to 1.15) and with high levels of physical contact (1.16, 1.11 to 1.22). In a multivariate analysis, the effect of high cardiovascular intensity remained similar (hazard ratio 1.05, 0.89 to 1.25); the increased mortality associated with high physical contact persisted (hazard ratio 1.13, 1.06 to 1.21), but that for bodily collision became non-significant (1.03, 0.98 to 1.09) as a consequence of its close relation with physical contact. Conclusions Among former Olympic athletes, engagement in disciplines with high intensity exercise did not bring a survival benefit compared with disciplines with low intensity exercise. Those who engaged in disciplines with high levels of physical contact had higher mortality than other Olympians later in life. PMID:23241269

Pregnancy during breast cancer: does a mother's parity status modify an offspring's mortality risk?

PubMed

Simonella, Leonardo; Verkooijen, Helena M; Edgren, Gustaf; Liu, Jenny; Hui, Miao; Salim, Agus; Czene, Kamila; Hartman, Mikael

2014-07-01

To assess whether children born to primiparous women around the time of a breast cancer diagnosis have an increased mortality risk. From the merged Swedish Multi-Generation and Cancer Registers, we identified 49,750 eligible children whose mother was diagnosed with breast cancer between 1958 and 2010. Mortality rates in offspring were compared to the background population using standardized mortality ratios (SMR), adjusted for calendar year of birth, attained age, and sex, and calculated for each category of timing of delivery (before, around, or after mother's diagnosis) and mother's parity status. Hazard ratios were assessed using a Cox proportional hazards model and adjusted for socioeconomic status, year of birth and mother's age at birth. Children born to a primiparous woman around a breast cancer diagnosis had a mortality rate five times greater than the background population (SMR 5.26, 95 % CI 1.93-11.5), whereas children born to a multiparous woman had a twofold increase (SMR 2.40, 95 % CI 1.10-4.55). Children of primiparous women born around diagnosis had an adjusted hazard ratio fourfold to that of children of primiparous women born before their mother's diagnosis (HR 4.29, 95 % CI 1.68-8.91), whereas hazard ratios for children of primiparous or multiparous women born at other times were not statistically significant. Children born to primiparous women around a breast cancer diagnosis have an increased relative mortality risk. Although relative risk is increased, in absolute terms children born from a cancer complicated pregnancy do relatively well. Additional investigations are needed to elucidate the reason(s) underlying this observation before the information can be used to inform patient counseling and clinical care.

Association of Cognitive Function With Cause-Specific Mortality in Middle and Older Age: Follow-up of Participants in the English Longitudinal Study of Ageing.

PubMed

Batty, G David; Deary, Ian J; Zaninotto, Paola

2016-02-01

We examined the little-tested associations between general cognitive function in middle and older age and later risk of death from chronic diseases. In the English Longitudinal Study of Ageing (2002-2012), 11,391 study participants who were 50-100 years of age at study induction underwent a battery of cognitive tests and provided a range of collateral data. In an analytical sample of 9,204 people (4,982 women), there were 1,488 deaths during follow-up (mean duration, 9.0 years). When we combined scores from 4 cognition tests that represented 3 acknowledged key domains of cognitive functioning (memory, executive function, and processing speed), cognition was inversely associated with deaths from cancer (per each 1-standard-deviation decrease in general cognitive function score, hazard ratio = 1.21, 95% CI: 1.10, 1.33), cardiovascular disease (hazard ratio = 1.71, 95% CI: 1.55, 1.89), other causes (hazard ratio = 2.07, 95% CI: 1.79, 2.40), and respiratory illness (hazard ratio = 2.48, 95% CI: 2.12, 2.90). Controlling for a range of covariates, such as health behaviors and socioeconomic status, and left-censoring to explore reverse causality had very little impact on the strength of these relationships. These findings indicate that cognitive test scores can provide relatively simple indicators of the risk of death from an array of chronic diseases and that these associations appear to be independent of other commonly assessed risk factors. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Incidence Rate of Cardiovascular Disease End Points in the National Aeronautics and Space Administration Astronaut Corps.

PubMed

Ade, Carl J; Broxterman, Ryan M; Charvat, Jacqueline M; Barstow, Thomas J

2017-08-07

It is unknown whether the astronaut occupation or exposure to microgravity influences the risk of long-term cardiovascular disease (CVD). This study explored the effects of being a career National Aeronautics and Space Administration (NASA) astronaut on the risk for clinical CVD end points. During the Longitudinal Study of Astronaut Health, data were collected on 310 NASA astronauts and 981 nonastronaut NASA employees. The nonastronauts were matched to the astronauts on age, sex, and body mass index, to evaluate acute and chronic morbidity and mortality. The primary outcomes were composites of clinical CVD end points (myocardial infarction, congestive heart failure, stroke, and coronary artery bypass surgery) or coronary artery disease (CAD) end points (myocardial infarction and coronary artery bypass surgery). Of the astronauts, 5.2% had a clinical CVD end point and 2.9% had a CAD end point compared with the nonastronaut comparisons with 4.7% and 3.1% having CVD and CAD end points, respectively. In the multivariate models adjusted for traditional risk factors, astronauts had a similar risk of CVD compared with nonastronauts (adjusted hazard ratio, 1.08; 95% CI, 0.60-1.93; P =0.80). Risk of a CAD end point was similar between groups (hazard ratio, 0.97; CI, 0.45-2.08; P =0.93). In astronauts with early spaceflight experience, the risk of CVD (hazard ratio, 0.80; CI, 0.25-2.56; P =0.71) and CAD (hazard ratio, 1.23; CI: 0.27-5.61; P =0.79) compared with astronauts with no experience were not different. These findings suggest that being an astronaut is not associated with increased long-term risk of CVD development. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

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.

Biomarkers Investigation for In-Hospital Death in Patients With Stanford Type A Acute Aortic Dissection.

PubMed

Zhang, Ruoxi; Chen, Shuyuan; Zhang, Hui; Wang, Wei; Xing, Jianpang; Wang, Yu; Yu, Bo; Hou, Jingbo

2016-09-28

This retrospective study aimed to investigate the predictive value of biomarkers for in-hospital mortality of patients with Stanford type A acute aortic dissection (AAD).AAD is a life-threatening disease with an incidence of about 2.6-3.6 cases per 100,000/year.A total of 67 consecutive Stanford type A AAD patients admitted to hospital were divided into a deceased group and survival group. The baseline information of the patients between two groups was systematically compared, followed by examination of the electrocardiograms (ECG). Based on the follow-up during hospitalization, we investigated the simultaneous assessment of indexes like fragmented QRS complex (fQRS), admission systolic blood pressure (SBP), aortic diameter, surgical management, troponin I (TnI), white blood cell (WBC) count, N-terminal pro-brain natriuretic peptide (NT-proBNP), and D-dimer.The levels of TnI and NT-proBNP, WBC counts, and rate of fQRS (+) in patients of the deceased group were significantly higher than those in the survival group. The male sex (hazard ratio, 10.88; P = 0.001), admission SBP (hazard ratio, 0.98; P = 0.012), NT-proBNP (hazard ratio, 1.00; P = 0.001), and WBC count (hazard ratio, 1.10; P = 0.033) were independently related with in-hospital death. As a single marker, WBC count had the highest sensitivity at 84.6% (specificity 65.9%).Admission SBP, NT-proBNP, and WBC count were potential independent risk factors of in-hospital death in Stanford type A AAD patients. WBC count may be a more accurate predictor of type A AAD than either alone.

Assessing the risk of incident hypertension and chronic kidney disease after exposure to shockwave lithotripsy and ureteroscopy

PubMed Central

Denburg, Michelle R.; Jemielita, Thomas; Tasian, Gregory; Haynes, Kevin; Mucksavage, Phillip; Shults, Justine; Copelovitch, Lawrence

2015-01-01

In this study we sought to determine if among individuals with urolithiasis, extracorporeal shock wave lithotripsy (SWL) and ureteroscopy are associated with a higher risk of incident arterial hypertension (HTN) and/or chronic kidney disease (CKD). This was measured in a population-based retrospective study of 11,570 participants with incident urolithiasis and 127,464 without urolithiasis in The Health Improvement Network. Patients with pre-existing HTN and CKD were excluded. The study included 1319 and 919 urolithiasis patients with at least one SWL or URS procedure, respectively. Multivariable Cox regression was used to estimate the hazard ratio for incident CKD stage 3–5 and HTN in separate analyses. Over a median of 3.7 and 4.1 years, 1423 and 595 of urolithiasis participants developed HTN and CKD, respectively. Urolithiasis was associated with a significant hazard ratio each for HTN of 1.42 (95% CI: 1.35, 1.51) and for CKD of 1.82 (1.67, 1.98). SWL was associated with a significant increased risk of HTN 1.34 (1.15, 1.57), while ureteroscopy was not. When further stratified as SWL to the kidney or ureter, only SWL to the kidney was significantly and independently associated with HTN 1.40 (1.19, 1.66). Neither SWL nor ureteroscopy was associated with incident CKD. Since urolithiasis itself was associated with a hazard ratio of 1.42 for HTN, an individual who undergoes SWL to the kidney can be expected to have a significantly increased hazard ratio for HTN of 1.96 (1.67, 2.29) compared to an individual without urolithiasis. PMID:26509587

Liver Cirrhosis in Patients With Atrial Fibrillation: Would Oral Anticoagulation Have a Net Clinical Benefit for Stroke Prevention?

PubMed

Kuo, Ling; Chao, Tze-Fan; Liu, Chia-Jen; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Lip, Gregory Y H; Chen, Shih-Ann

2017-06-23

Patients with liver cirrhosis have been excluded from randomized clinical trials of oral anticoagulation therapy for stroke prevention in atrial fibrillation. We hypothesized that patients with liver cirrhosis would have a positive net clinical benefit for oral anticoagulation when used for stroke prevention in atrial fibrillation. This study used the National Health Insurance Research Database in Taiwan. Among 289 559 atrial fibrillation patients aged ≥20 years, there were 10 336 with liver cirrhosis, and 9056 of them having a CHA 2 DS 2 -VASc score ≥2 were divided into 3 groups, that is, no treatment, antiplatelet therapy, and warfarin. Patients with liver cirrhosis had a higher risk of ischemic stroke (hazard ratio=1.10, P =0.046) and intracranial hemorrhage (hazard ratio=1.20, P =0.043) compared with those without. Among patients with liver cirrhosis, patients taking antiplatelet therapy had a similar risk of ischemic stroke (hazard ratio=1.02, 95%CI=0.88-1.18) compared to those without antithrombotic therapies, but the risk was significantly lowered among warfarin users (hazard ratio=0.76, 95%CI=0.58-0.99). For intracranial hemorrhage, there were no significant differences between those untreated and those taking antiplatelet therapy or warfarin. The use of warfarin was associated with a positive net clinical benefit compared with being untreated or receiving only antiplatelet therapy. For atrial fibrillation patients with liver cirrhosis in the current analysis of an observational study, warfarin use was associated with a lower risk of ischemic stroke and a positive net clinical benefit compared with nontreatment, and thus, thromboprophylaxis should be considered for such patients. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Cardiac Magnetic Resonance-Measured Left Atrial Volume and Function and Incident Atrial Fibrillation: Results From MESA (Multi-Ethnic Study of Atherosclerosis).

PubMed

Habibi, Mohammadali; Samiei, Sanaz; Ambale Venkatesh, Bharath; Opdahl, Anders; Helle-Valle, Thomas M; Zareian, Mytra; Almeida, Andre L C; Choi, Eui-Young; Wu, Colin; Alonso, Alvaro; Heckbert, Susan R; Bluemke, David A; Lima, João A C

2016-08-01

Early detection of structural changes in left atrium (LA) before atrial fibrillation (AF) development could be helpful in identification of those at higher risk for AF. Using cardiac magnetic resonance imaging, we examined the association of LA volume and function, and incident AF in a multiethnic population free of clinical cardiovascular diseases. In a case-cohort study embedded in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA size and function assessed by cardiac magnetic resonance feature-tracking were compared between 197 participants with incident AF and 322 participants randomly selected from the whole MESA cohort. Participants were followed up for 8 years. Incident AF cases had a larger LA volume and decreased passive, active, and total LA emptying fractions and peak global LA longitudinal strain (peak LA strain) at baseline. In multivariable analysis, elevated LA maximum volume index (hazard ratio, 1.38 per SD; 95% confidence interval, 1.01-1.89) and decreased peak LA strain (hazard ratio, 0.68 per SD; 95% confidence interval, 0.48-0.96), and passive and total LA emptying fractions (hazard ratio for passive LA emptying fractions, 0.55 per SD; 95% confidence interval, 0.40-0.75 and hazard ratio for active LA emptying fractions, 0.70 per SD; 95% confidence interval, 0.52-0.95), but not active LA emptying fraction, were associated with incident AF. Elevated LA volumes and decreased passive and total LA emptying fractions were independently associated with incident AF in an asymptomatic multiethnic population. Including LA functional variables along with other risk factors of AF may help to better risk stratify individuals at risk of AF development. © 2016 American Heart Association, Inc.

Four ECG left ventricular hypertrophy criteria and the risk of cardiovascular events and mortality in patients with vascular disease.

PubMed

van Kleef, Monique E A M; Visseren, Frank L J; Vernooij, Joris W P; Nathoe, Hendrik M; Cramer, Maarten-Jan M; Bemelmans, Remy H H; van der Graaf, Yolanda; Spiering, Wilko

2018-06-06

The relation between different electrocardiographic left ventricular hypertrophy (ECG-LVH) criteria and cardiovascular risk in patients with clinical manifest arterial disease is unclear. Therefore, we determined the association between four ECG-LVH criteria: Sokolow-Lyon, Cornell product, Cornell/strain index and Framingham criterion; and risk of cardiovascular events and mortality in this population. Risk of cardiovascular events was estimated in 6913 adult patients with clinical manifest arterial disease originating from the Secondary Manifestations of ARTerial disease (SMART) cohort. Cox proportional regression analysis was used to estimate the risk of the four ECG-LVH criteria and the primary composite outcome: myocardial infarction (MI), stroke or cardiovascular death; and secondary outcomes: MI, stroke and all-cause mortality; adjusted for confounders. The highest prevalence of ECG-LVH was observed for Cornell product (10%) and Cornell/strain index (9%). All four ECG-LVH criteria were associated with an increased risk of the primary composite endpoint: Sokolow-Lyon (hazard ratio 1.37, 95% CI 1.13-1.66), Cornell product (hazard ratio 1.54, 95% CI 1.30-1.82), Cornell/strain index (hazard ratio 1.70, 95% CI 1.44-2.00) and Framingham criterion (hazard ratio 1.78, 95% CI 1.21-2.62). Cornell product, Cornell/strain index and Framingham criterion ECG-LVH were additionally associated with an elevated risk of secondary outcomes. Cardiovascular risk increased whenever two, or three or more ECG-LVH criteria were present concurrently. All four ECG-LVH criteria are associated with an increased risk of cardiovascular events. As Cornell/strain index is both highly prevalent and carries a high cardiovascular risk, this is likely the most relevant ECG-LVH criterion for clinical practice.