scholarly journals DOP59 Evaluation of the efficacy of tofacitinib as maintenance therapy in patients with Ulcerative Colitis stratified by OCTAVE Sustain baseline endoscopic subscore

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S094-S095
Author(s):  
S D Lee ◽  
J R Allegretti ◽  
F Steinwurz ◽  
S B Connelly ◽  
N Lawendy ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Logistic Regression ◽  
Treatment Effect ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Phase 3 ◽  
Loss Of Response ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
The Difference

Abstract Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib in patients (pts) with UC were evaluated in two 8-week, Phase 3 induction studies (OCTAVE Induction 1&2), a 52-week, Phase 3 maintenance study (OCTAVE Sustain), and an open-label, long-term extension study. Here, we evaluate tofacitinib efficacy in OCTAVE Sustain (NCT01458574) by baseline Mayo endoscopic subscore (ES). Methods Pts with an OCTAVE Sustain baseline ES of 0 or 1 were included. Proportion of pts achieving efficacy endpoints at Week 52 of OCTAVE Sustain (responders from OCTAVE Induction 1&2; tofacitinib 5 or 10 mg twice daily [BID] or placebo [PBO]) was evaluated in relation to OCTAVE Sustain baseline ES. Using logistic regression, the difference in treatment effect (tofacitinib vs PBO) between baseline ES (0 vs 1) for each efficacy endpoint was assessed. Cox proportional hazards regression was used to model the difference in treatment effect between baseline ES (0 vs 1) for time to treatment failure and loss of response. Results At Week 52 of OCTAVE Sustain, a numerically higher proportion of pts with a baseline ES of 0 achieved remission and endoscopic improvement vs pts with a baseline ES of 1, regardless of tofacitinib dose (Table). Logistic regression analyses showed a larger treatment effect of tofacitinib 5 mg BID at Week 52 in pts with a baseline ES of 0 vs 1 (p=0.0306) for clinical response (Table). Treatment effect of tofacitinib 10 mg BID was not significantly different between baseline ES 0 vs 1 for any endpoint (Table). In tofacitinib 5 mg BID-treated pts, Cox proportional hazards regression showed difference in risk vs PBO to be larger in pts with a baseline ES of 0 vs 1 for treatment failure (p=0.0231) and loss of response (p=0.0209); corresponding differences for 10 mg BID-treated pts were not significant (p=0.9239 and p=0.9613, respectively). Conclusion In general, at Week 52 of OCTAVE Sustain, a higher proportion of tofacitinib-treated pts achieved endpoints with a baseline ES of 0 vs 1. Based on proportions, the treatment effect of tofacitinib 5 mg BID was more evident in pts with a baseline ES of 0 vs 1. This difference in treatment effect related to baseline ES was not observed with tofacitinib 10 mg BID. Baseline ES may be an important factor in predicting outcomes, and suggests that aiming for a deeper remission after induction may allow successful maintenance with tofacitinib 5 mg BID. These analyses were post hoc and limited by the small sample sizes.

PETCO2 gradient: a novel prognostic parameter in cardiopulmonary exercise testing

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I.D Poveda Pinedo ◽  
I Marco Clement ◽  
O Gonzalez ◽  
I Ponz ◽  
A.M Iniesta ◽  
...  
Keyword(s):  
Exercise Testing ◽  
Proportional Hazards ◽  
Cardiopulmonary Exercise Testing ◽  
Cox Proportional Hazards ◽  
Prognostic Parameter ◽  
Cardiopulmonary Exercise ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Baseline Characteristics ◽  
The Difference

Abstract Background Previous parameters such as peak VO2, VE/VCO2 slope and OUES have been described to be prognostic in heart failure (HF). The aim of this study was to identify further prognostic factors of cardiopulmonary exercise testing (CPET) in HF patients. Methods A retrospective analysis of HF patients who underwent CPET from January to November 2019 in a single centre was performed. PETCO2 gradient was defined by the difference between final PETCO2 and baseline PETCO2. HF events were defined as decompensated HF requiring hospital admission or IV diuretics, or decompensated HF resulting in death. Results A total of 64 HF patients were assessed by CPET, HF events occurred in 8 (12.5%) patients. Baseline characteristics are shown in table 1. Patients having HF events had a negative PETCO2 gradient while patients not having events showed a positive PETCO2 gradient (−1.5 [IQR −4.8, 2.3] vs 3 [IQR 1, 5] mmHg; p=0.004). A multivariate Cox proportional-hazards regression analysis revealed that PETCO2 gradient was an independent predictor of HF events (HR 0.74, 95% CI [0.61–0.89]; p=0.002). Kaplan-Meier curves showed a significantly higher incidence of HF events in patients having negative gradients, p=0.002 (figure 1). Conclusion PETCO2 gradient was demonstrated to be a prognostic parameter of CPET in HF patients in our study. Patients having negative gradients had worse outcomes by having more HF events. Time to first event, decompensated heart Funding Acknowledgement Type of funding source: None

scholarly journals Replacement of potatoes with other vegetables and risk of myocardial infarction in the Danish Diet, Cancer and Health cohort

2021 ◽  
pp. 1-21
Author(s):  
Anne Mette L. Würtz ◽  
Mette D. Hansen ◽  
Anne Tjønneland ◽  
Eric B. Rimm ◽  
Erik B. Schmidt ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Similar Pattern ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Heterogeneous Group ◽  
Dietary Guidelines ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Root Vegetables

ABSTRACT Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29,142 women and 26,029 men aged 50-64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazards ratios (HR) with 95% CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13.6 years of follow-up, 656 female and 1,694 male cases were identified. Among women, the adjusted HR for MI was 1.02 (95% CI: 0.93, 1.13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0.93 (95% CI: 0.77, 1.13) for replacement of potatoes with fruiting vegetables and 0.91 (95% CI: 0.77, 1.07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups.

Development and Validation of a Prognostic Nomogram Model for Recurrence of Non-Muscle Invasive Bladder Cancer

2021 ◽  
Author(s):  
Sanhe Liu ◽  
Yongzhi Li ◽  
Diansheng Cui ◽  
Yuexia Jiao ◽  
Liqun Duan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Risk Stratification ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Muscle Invasive Bladder Cancer ◽  
Clinicopathologic Characteristics ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Muscle Invasive

Abstract BackgroundDifferent recurrence probability of non-muscle invasive bladder cancer (NMIBC) requests different adjuvant treatments and follow-up strategies. However, there is no simple, intuitive, and generally accepted clinical recurrence predictive model available for NMIBC. This study aims to construct a predictive model for the recurrence of NMIBC based on demographics and clinicopathologic characteristics from two independent centers. MethodsDemographics and clinicopathologic characteristics of 511 patients with NMIBC were retrospectively collected. Recurrence free survival (RFS) was estimated using the Kaplan-Meier method and log-rank tests. Univariate Cox proportional hazards regression analysis was used to screen variables associated with RFS, and a multivariate Cox proportional hazards regression model with a stepwise procedure was used to identify those factors of significance. A final nomogram model was built using the multivariable Cox method. The performance of the nomogram model was evaluated with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed with bootstrap resampling. X-tile software was used for risk stratification calculated by the nomogram model. ResultsIndependent prognostic factors including tumor stage, recurrence status, and European Association of Urology (EAU) risk stratification group were introduced to the nomogram model. The model showed acceptable calibration and discrimination (area under the receiver operating characteristic [ROC] curve was 0.85; the consistency index [C-index] was 0.79 [95% CI: 0.76 to 0.82]), which was superior to the EAU risk stratification group alone. The decision curve also proved well clinical usefulness. Moreover, all populations could be stratified into three distinct risk groups by the nomogram model. ConclusionsWe established and validated a novel nomogram model that can provide individual prediction of RFS for patients with NMIBC. This intuitively prognostic nomogram model may help clinicians in postoperative treatment and follow-up decision-making.

Antibiotic and acid-suppression medications during early childhood are associated with obesity

Gut ◽  
2018 ◽  
Vol 68 (1) ◽  
pp. 62-69 ◽  
Author(s):  
Christopher M Stark ◽  
Apryl Susi ◽  
Jill Emerick ◽  
Cade M Nylund
Keyword(s):  
Early Childhood ◽  
Department Of Defense ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Event Analysis ◽  
Early Exposure ◽  
Single Event ◽  
Inclusion Criteria ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

ObjectiveGut microbiota alterations are associated with obesity. Early exposure to medications, including acid suppressants and antibiotics, can alter gut biota and may increase the likelihood of developing obesity. We investigated the association of antibiotic, histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) prescriptions during early childhood with a diagnosis of obesity.DesignWe performed a cohort study of US Department of Defense TRICARE beneficiaries born from October 2006 to September 2013. Exposures were defined as having any dispensed prescription for antibiotic, H2RA or PPI medications in the first 2 years of life. A single event analysis of obesity was performed using Cox proportional hazards regression.Results333 353 children met inclusion criteria, with 241 502 (72.4%) children prescribed an antibiotic, 39 488 (11.8%) an H2RA and 11 089 (3.3%) a PPI. Antibiotic prescriptions were associated with obesity (HR 1.26; 95% CI 1.23 to 1.28). This association persisted regardless of antibiotic class and strengthened with each additional class of antibiotic prescribed. H2RA and PPI prescriptions were also associated with obesity, with a stronger association for each 30-day supply prescribed. The HR increased commensurately with exposure to each additional medication group prescribed.ConclusionsAntibiotics, acid suppressants and the combination of multiple medications in the first 2 years of life are associated with a diagnosis of childhood obesity. Microbiota-altering medications administered in early childhood may influence weight gain.

scholarly journals Identification of Arp2/3 Complex Subunits as Prognostic Biomarkers for Hepatocellular Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Shenglan Huang ◽  
Dan Li ◽  
LingLing Zhuang ◽  
Liying Sun ◽  
Jianbing Wu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Expression ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Gene Set Enrichment Analysis ◽  
Prognostic Biomarkers ◽  
Migration And Invasion ◽  
Regression Analyses ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

The actin-related protein 2/3 complex (Arp2/3) is a major actin nucleator that has been widely reported and plays an important role in promoting the migration and invasion of various cancers. However, the expression patterns and prognostic values of Arp2/3 subunits in hepatocellular carcinoma (HCC) remain unclear. In this study, The Cancer Genome Atlas (TCGA) and UCSC Xena databases were used to obtain mRNA expression and the corresponding clinical information, respectively. The differential expression and Arp2/3 subunits in HCC were analyzed using the “limma” package of R 4.0.4 software. The prognostic value of each subunit was evaluated using Kaplan–Meier survival analysis and Cox proportional hazards regression analyses. The results revealed that mRNA expression of Arp2/3 members (ACTR2, ACTR3, ARPC1A, APRC1B, ARPC2, ARPC3, ARPC4, ARPC5, and ARPC5L) was upregulated in HCC. Higher expression of Arp2/3 members was significantly correlated with worse overall survival (OS) and shorter progression-free survival (PFS) in HCC patients. Cox proportional hazards regression analyses demonstrated that ACTR3, ARPC2, and ARPC5 were independent prognostic biomarkers of survival in patients with HCC. The relation between tumor immunocyte infiltration and the prognostic subunits was determined using the TIMER 2.0 platform and the GEPIA database. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms of prognostic subunits in the carcinogenesis of HCC. The results revealed that ACTR3, ARPC2, and ARPC5 were significantly positively correlated with the infiltration of immune cells in HCC. The GSEA results indicated that ACTR3, ARPC2, and ARPC5 are involved in multiple cancer-related pathways that promote the development of HCC. In brief, various analyses indicated that Arp2/3 complex subunits were significantly upregulated and predicted worse survival in HCC, and they found that ACTR3, ARPC2, and ARPC5 could be used as independent predictors of survival and might be applied as promising molecular targets for diagnosis and therapy of HCC in the future.

Serum FGF21 Is Associated with Future Cardiovascular Events in Patients with Coronary Artery Disease

Cardiology ◽  
2018 ◽  
Vol 139 (4) ◽  
pp. 212-218 ◽  
Author(s):  
Yun Shen ◽  
Xueli Zhang ◽  
Yiting Xu ◽  
Qin Xiong ◽  
Zhigang Lu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Regression Analysis ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Artery Disease

Objectives: To investigate whether serum fibroblast growth factor 21 (FGF21) levels can be used to predict the future development of major adverse cardiovascular events (MACEs). Methods: This study included 253 patients who received subsequent follow-up, and complete data were collected for 234 patients. Independent predictors of MACEs were identified by using the Cox proportional-hazards regression analysis. The prognostic value of FGF21 levels for MACEs was evaluated by Kaplan-Meier survival analysis. Results: Of 229 patients finally enrolled in the analysis, 27/60 without coronary artery disease (CAD) at baseline experienced a MACE, and 132/169 patients with CAD at baseline experienced a MACE. Among patients with CAD at baseline, serum FGF21 levels were significantly higher in patients with MACEs (p < 0.05) than in patients without MACEs. Kaplan-Meier survival analysis showed patients with a higher serum FGF21 had a significantly lower event-free survival (p = 0.001) than those with a lower level. Further Cox proportional-hazards regression analysis, including the traditional risk factors for cardiovascular disease, showed that serum FGF21 was an independent predictor of MACE occurrence. Conclusions: In patients with CAD at baseline, an elevated serum FGF21 level was associated with the development of a MACE in the future.

MODELLING THE DETERMINANTS OF UNDER-FIVE CHILD MORTALITY RATES USING COX PROPORTIONAL HAZARDS REGRESSION MODEL

2021 ◽  
Vol 4 (4) ◽  
pp. 401-408
Author(s):  
M. C. Musa ◽  
O. E. Asiribo ◽  
H. G. Dikko ◽  
M. Usman ◽  
S. S. Sani
Keyword(s):  
Regression Model ◽  
Child Mortality ◽  
Proportional Hazards ◽  
Mortality Rates ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Predictor Variables ◽  
Under Five ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

An under-five childhood mortality rates in Nigeria is still high, despite efforts of government at all levels to combat the menace. This study examined some factors that significantly affect under-five child mortality. A sample of mothers with children under the age of five from Nigeria Demographic and Health Survey data (NDHS, 2013 & 2018) was used to assess the effect of some selected predictor variables (or covariates) on childhood survival. Cox proportional hazards model is essentially a regression model popularly used for investigating the association between the survival time and one or more predictor variables. The results from final fitted Cox proportional hazards regression model that the covariates, contraceptive used by the mother, state of residence, birth weight of child and type of toilet facility used by the h-ousehold were found to be significantly associated with under-five survival in the North Central Region of Nigeria. All the calculations are performed using the R software for statistical analysis.

scholarly journals Prognostic Significance of Serum Free Amino Acids in Head and Neck Cancers

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 428 ◽  
Author(s):  
Vit Vsiansky ◽  
Marketa Svobodova ◽  
Jaromir Gumulec ◽  
Natalia Cernei ◽  
Dagmar Sterbova ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Regression Model ◽  
Head And Neck ◽  
Cell Lines ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Transformed Cells ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

Despite distinctive advances in the field of head and neck squamous cell cancer (HNSCC) biomarker discovery, the spectrum of clinically useful prognostic serum biomarkers is limited. As metabolic activities in highly proliferative transformed cells are fundamentally different from those in non-transformed cells, specific shifts in concentration of different metabolites may serve as diagnostic or prognostic markers. Blood amino acids have been identified as promising biomarkers in different cancers before, but little is known about this field in HNSCC. Blood amino acid profiles of 140 HNSCC patients were examined using high-performance liquid chromatography. Cox proportional hazards regression model was used to assess the prognostic value of amino acid concentrations in serum. Colony forming assay was used to identify the effect of amino acids that were significant in Cox proportional hazards regression models on colony forming ability of FaDu and Detroit 562 cell lines. In the multivariable Cox regression model for overall survival (OS), palliative treatment was associated with an unfavourable prognosis while high serum levels of methionine have had a positive prognostic impact. In the relapse-free survival (RFS) multivariable model, methionine was similarly identified as a positive prognostic factor, along with tumor localization in the oropharynx. Oral cavity localization and primary radio(chemo)therapy treatment strategy have been linked to poorer RFS. 1mM serine was shown to support the forming of colonies in both tested HNSCC cell lines. Effect of methionine was exactly the opposite.

scholarly journals The prognostic value of B7-H6 in esophageal squamous cell carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Huan Zhou ◽  
Jun Dong ◽  
Liyi Guo ◽  
Xicheng Wang ◽  
Kailin Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lymphatic Metastasis ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Tissue Samples ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

AbstractB7-H6, a member of the B7 family molecules, participates in the clearance of tumor cells by binding to NKp30 on NK cells. B7-H6 expression level in esophageal squamous cell carcinoma (ESCC) and the clinical value remain unknown. The goal of this study was to determine the expression of B7-H6 in ESCC and further explore its clinical significance. We retrospectively collected the clinical data of 145 patients diagnosed with ESCC between January 2007 and December 2008. The expression of B7-H6 of the pathological tissue samples was detected by immunohistochemistry. The chi-square (χ2) test was used to analyse the relationships of B7-H6 and clinicopathological characteristics. Survival and hazard functions were estimated using the Kaplan-Meier method, and survival between groups was compared using the two-sided log-rank test. The Cox proportional hazards regression model was used to adjust for the risk factors related to overall survival (OS). 133/145 (91.72%) of the ESCC tissue samples exhibited B7-H6 expression. The expression level of B7-H6 was correlated with T stage (P = 0.036) and lymphatic metastasis status (P = 0.044). High B7-H6 expression (P = 0.003) was associated with a significantly worse OS than low B7-H6 expression. Multivariate Cox proportional hazards regression analysis demonstrated that tumour size (P = 0.021), B7-H6 expression (P = 0.025) and lymphatic metastasis status (P = 0.049) were independent prognostic factors of OS for ESCC. Collectively, our findings suggest that B7-H6 is widely expressed in ESCC samples. And B7-H6 may represent a predictor of poor prognosis for ESCC.

Sign in / Sign up

Export Citation Format

Share Document