scholarly journals Absence of Obesity Paradox in All-Cause Mortality Among Chinese Patients With an Implantable Cardioverter Defibrillator: A Multicenter Cohort Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Bin Zhou ◽  
Xuerong Sun ◽  
Na Yu ◽  
Shuang Zhao ◽  
Keping Chen ◽  
...  
Keyword(s):  
Implantable Cardioverter Defibrillator ◽  
Proportional Hazards ◽  
Obesity Paradox ◽  
Cox Proportional Hazards ◽  
Chinese Patients ◽  
Proportional Hazards Models ◽  
Cardioverter Defibrillator ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
All Cause Mortality

Background: The results of studies on the obesity paradox in all-cause mortality are inconsistent in patients equipped with an implantable cardioverter-defibrillator (ICD). There is a lack of relevant studies on Chinese populations with large sample size. This study aimed to investigate whether the obesity paradox in all-cause mortality is present among the Chinese population with an ICD.Methods: We conducted a retrospective analysis of multicenter data from the Study of Home Monitoring System Safety and Efficacy in Cardiac Implantable Electronic Device–implanted Patients (SUMMIT) registry in China. The outcome was all-cause mortality. The Kaplan–Meier curves, Cox proportional hazards models, and smooth curve fitting were used to investigate the association between body mass index (BMI) and all-cause mortality.Results: After inclusion and exclusion criteria, 970 patients with an ICD were enrolled. After a median follow-up of 5 years (interquartile, 4.1–6.0 years), in 213 (22.0%) patients occurred all-cause mortality. According to the Kaplan–Meier curves and multivariate Cox proportional hazards models, BMI had no significant impact on all-cause mortality, whether as a continuous variable or a categorical variable classified by various BMI categorization criteria. The fully adjusted smoothed curve fit showed a linear relationship between BMI and all-cause mortality (p-value of 0.14 for the non-linearity test), with the curve showing no statistically significant association between BMI and all-cause mortality [per 1 kg/m2 increase in BMI, hazard ratio (HR) 0.97, 95% CI 0.93–1.02, p = 0.2644].Conclusions: The obesity paradox in all-cause mortality was absent in the Chinese patients with an ICD. Prospective studies are needed to further explore this phenomenon.

scholarly journals Fitting Marginal Structural and G-Estimation Models Under Complex Treatment Patterns: Investigating the Association Between De Novo Vitamin D Supplement Use After Breast Cancer Diagnosis and All-Cause Mortality Using Linked Pharmacy Claim and Registry Data

2019 ◽  
Vol 189 (3) ◽  
pp. 224-234
Author(s):  
Jamie M Madden ◽  
Finbarr P Leacy ◽  
Lina Zgaga ◽  
Kathleen Bennett
Keyword(s):  
Vitamin D ◽  
Cancer Diagnosis ◽  
Proportional Hazards ◽  
De Novo ◽  
Breast Cancer Diagnosis ◽  
Cox Proportional Hazards ◽  
Time Varying ◽  
Proportional Hazards Models ◽  
Cox Proportional Hazards Models ◽  
All Cause Mortality

Abstract Studies have shown that accounting for time-varying confounding through time-dependent Cox proportional hazards models may provide biased estimates of the causal effect of treatment when the confounder is also a mediator. We explore 2 alternative approaches to addressing this problem while examining the association between vitamin D supplementation initiated after breast cancer diagnosis and all-cause mortality. Women aged 50–80 years were identified in the National Cancer Registry Ireland (n = 5,417) between 2001 and 2011. Vitamin D use was identified from linked prescription data (n = 2,570). We sought to account for the time-varying nature of vitamin D use and time-varying confounding by bisphosphonate use using 1) marginal structural models (MSMs) and 2) G-estimation of structural nested accelerated failure-time models (SNAFTMs). Using standard adjusted Cox proportional hazards models, we found a reduction in all-cause mortality in de novo vitamin D users compared with nonusers (hazard ratio (HR) = 0.84, 95% confidence interval (CI): 0.73, 0.99). Additional adjustment for vitamin D and bisphosphonate use in the previous month reduced the hazard ratio (HR = 0.45, 95% CI: 0.33, 0.63). Results derived from MSMs (HR = 0.44, 95% CI: 0.32, 0.61) and SNAFTMs (HR = 0.45, 95% CI: 0.34, 0.52) were similar. Utilizing MSMs and SNAFTMs to account for time-varying bisphosphonate use did not alter conclusions in this example.

scholarly journals The U-Shape Relationship Between Glycated Hemoglobin Level and Long-Term All-Cause Mortality Among Patients With Coronary Artery Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Liwei Liu ◽  
Jianfeng Ye ◽  
Ming Ying ◽  
Qiang Li ◽  
Shiqun Chen ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Proportional Hazards ◽  
Glycated Hemoglobin ◽  
Cox Proportional Hazards ◽  
Proportional Hazards Models ◽  
Cox Proportional Hazards Models ◽  
Risk Of Mortality ◽  
All Cause Mortality ◽  
Artery Disease

Background: Although glycated hemoglobin (HbA1c) was considered as a prognostic factor in some subgroup of coronary artery disease (CAD), the specific relationship between HbA1c and the long-term all-cause death remains controversial in patients with CAD.Methods: The study enrolled 37,596 CAD patients and measured HbAlc at admission in Guangdong Provincial People's Hospital. The patients were divided into 4 groups according to HbAlc level (Quartile 1: HbA1c ≤ 5.7%; Quartile 2: 5.7% < HbA1c ≤ 6.1%; Quartile 3: 6.1% < HbA1c ≤ 6.7%; Quartile 4: HbA1c > 6.7%). The study endpoint was all-cause death. The restricted cubic splines and cox proportional hazards models were used to investigate the association between baseline HbAlc levels and long-term all-cause mortality.Results: The median follow-up was 4 years. The cox proportional hazards models revealed that HbAlc is an independent risk factor in the long-term all-cause mortality. We also found an approximate U-shape association between HbA1c and the risk of mortality, including increased risk of mortality when HbA1c ≤ 5.7% and HbA1c > 6.7% [Compared with Quartile 2, Quartile 1 (HbA1c ≤ 5.7), aHR = 1.13, 95% CI:1.01–1.26, P < 0.05; Quartile 3 (6.1% < HbA1c ≤ 6.7%), aHR = 1.04, 95% CI:0.93–1.17, P =0.49; Quartile 4 (HbA1c > 6.7%), aHR = 1.32, 95% CI:1.19–1.47, P < 0.05].Conclusions: Our study indicated a U-shape relationship between HbA1c and long-term all-cause mortality in CAD patients.

scholarly journals Identification of a Novel Prognostic Gene Signature From the Immune Cell Infiltration Landscape of Osteosarcoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Lei Fan ◽  
Jingtao Ru ◽  
Tao Liu ◽  
Chao Ma
Keyword(s):  
Proportional Hazards ◽  
Immune Cell ◽  
Roc Curves ◽  
Gene Signature ◽  
Cox Proportional Hazards ◽  
Immune Cell Infiltration ◽  
Training Cohort ◽  
Proportional Hazards Models ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models

Background: The tumor microenvironment (TME) mainly comprises tumor cells and tumor-infiltrating immune cells mixed with stromal components. Latestresearch hasdisplayed that tumor immune cell infiltration (ICI) is associated with the clinical outcome of patients with osteosarcoma (OS). This work aimed to build a gene signature according to ICI in OS for predicting patient outcomes.Methods: The TARGET-OS dataset was used for model training, while the GSE21257 dataset was taken forvalidation. Unsupervised clustering was performed on the training cohort based on the ICI profiles. The Kaplan–Meier estimator and univariate Cox proportional hazards models were used to identify the differentially expressed genes between clusters to preliminarily screen for potential prognostic genes. We incorporated these potential prognostic genes into a LASSO regression analysis and produced a gene signature, which was next assessed with the Kaplan–Meier estimator, Cox proportional hazards models, ROC curves, IAUC, and IBS in the training and validation cohorts. In addition, we compared our signature to previous models. GSEAswere deployed to further study the functional mechanism of the signature. We conducted an analysis of 22 TICsfor identifying the role of TICs in the gene signature’s prognosis ability.Results: Data from the training cohort were used to generate a nine-gene signature. The Kaplan–Meier estimator, Cox proportional hazards models, ROC curves, IAUC, and IBS validated the signature’s capacity and independence in predicting the outcomes of OS patients in the validation cohort. A comparison with previous studies confirmed the superiority of our signature regarding its prognostic ability. Annotation analysis revealed the mechanism related to the gene signature specifically. The immune-infiltration analysis uncoveredkey roles for activated mast cells in the prognosis of OS.Conclusion: We identified a robust nine-gene signature (ZFP90, UHRF2, SELPLG, PLD3, PLCB4, IFNGR1, DLEU2, ATP6V1E1, and ANXA5) that can predict OS outcome precisely and is strongly linked to activated mast cells.

scholarly journals Lower values of a novel index of Vagal-Neuroimmunomodulation are associated to higher all-cause mortality in two large general population samples with 18 year follow up

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marc N. Jarczok ◽  
Julian Koenig ◽  
Julian F. Thayer
Keyword(s):  
General Population ◽  
Proportional Hazards ◽  
Population Studies ◽  
Large Population ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Proportional Hazards Models ◽  
Cox Proportional Hazards Models ◽  
All Cause Mortality

AbstractIn recent clinical practice, a biomarker of vagal neuroimmunomodulation (NIM), namely the ratio of vagally-mediated heart rate variability (vmHRV) and CRP, was proposed to index the functionality of the cholinergic anti-inflammatory pathway. This study aims to transfer and extend the previous findings to two general population-based samples to explore the hypothesis that NIM-ratio is associated with all-cause mortality. Two large population studies (MIDUS 2: N = 1255 and Whitehall II wave 5: N = 7870) with complete data from a total of N = 3860 participants (36.1% females; average age = 56.3 years; 11.1% deaths, last exit 18.1 years post inclusion) were available. NIM indices were calculated using the vagally-mediated HRV measure RMSSD divided by measures of CRP (NIMCRP) or IL-6 (NIMIL6). The NIM-ratios were quartiled and entered into age, ethnicity and body mass index adjusted Cox proportional hazards models. For NIMIL6 the lowest quartile was 45% more likely to die during the observed period (max. 18 years follow-up) compared to the highest quartile (HR = 0.55 CI 0.41–0.73; p < .0001). NIMCRP parallel these results. Here we show that an easily computable index of IL-6 inhibition is associated with all-cause mortality in two large general population samples. These results suggest that this index might be useful for risk stratification and warrant further examination.

scholarly journals Decreased Mortality with Beta-Blocker Therapy in HFpEF Patients Associated with Atrial Fibrillation

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yanhua Yang ◽  
Suxia Guo ◽  
Ziyao Huang ◽  
Chunhua Deng ◽  
Lihua Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Beta Blocker ◽  
Proportional Hazards ◽  
Heart Diseases ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Significant Difference ◽  
All Cause Mortality

Background. There are no proven effective treatments that can reduce the mortality in heart failure with preserved ejection fraction (HFpEF), probably due to its heterogeneous nature which will weaken the effect of therapy in clinical studies. We evaluated the effect of beta-blocker treatment in HFpEF patients associated with atrial fibrillation (AF), which is a homogeneous syndrome and has seldom been discussed. Methods. This retrospective cohort study screened 955 patients diagnosed with AF and HFpEF. Patients with a range of underlying heart diseases or severe comorbidities were excluded; 191 patients were included and classified as with or without beta-blocker treatment at baseline. The primary outcome was all-cause mortality and rehospitalization due to heart failure. Kaplan-Meier curves and multivariable Cox proportional-hazards models were used to evaluate the differences in outcomes. Results. The mean follow-up was 49 months. After adjustment for multiple clinical risk factors and biomarkers for prognosis in heart failure, patients with beta-blocker treatment were associated with significantly lower all-cause mortality (hazard ratio (HR) = 0.405, 95% confidence interval (CI) = 0.233–0.701, p=0.001) compared with those without beta-blocker treatment. However, the risk of rehospitalization due to heart failure was increased in the beta-blocker treatment group (HR = 1.740, 95% CI = 1.085–2.789, p=0.022). There was no significant difference in all-cause rehospitalization between the two groups (HR = 1.137, 95% CI = 0.803–1.610, p=0.470). Conclusions. In HFpEF patients associated with AF, beta-blocker treatment is associated with significantly lower all-cause mortality, but it increased the risk of rehospitalization due to heart failure.

Multicenter study on prognostic factors in 692 patients with brain metastases of malignant melanoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9081-9081
Author(s):  
T. K. Eigentler ◽  
A. Figl ◽  
D. Krex ◽  
P. Mohr ◽  
P. Kurschat ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Malignant Melanoma ◽  
Stereotactic Radiotherapy ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Proportional Hazards Models ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Pre Treatment

9081 Background: This multicenter study aimed to identify prognostic factors in patients with brain metastases from malignant melanoma (BM-MM). Methods: In a retrospective survey in nine cancer centres of the German Cancer Society 692 patients were identified with BM-MM during the period 1986–2007. Overall survival was analysed using Kaplan-Meier estimator and compared by log-rank analysis. Cox proportional hazards models were used to identify prognostic factors significant for survival. Results: The median overall survival of the entire cohort was 5.0 months (95%CI: 4–5). Prognostic factors in the univariate Kaplan- Meier analysis were: Karnofsky Performance Status (≥ 70 vs. <70; p<0.001), number of BM-MM (single vs. multiple; p<0.001), pre-treatment levels of serum LDH (normal vs. elevated; p<0.001), pre-treatment levels of S100 (normal vs. elevated; p<0.001), Prognostic groups according to Radiation Therapy Oncology Group (Class I vs. Class II vs. Class III; p=0.0485), kind of applied treatment (for the cohort with single BM-MM, only) (stereotactic radiotherapy or neurosurgical metastasectomy vs. others; p=0.036). Cox proportional hazards models revealed pre-treatment elevated level of serum LDH (HR: 1.6, 95%CI: 1.3–2.0; p=0.00013) and number of BM-MM (HR: 1.6, 95%CI: 1.3–2.0; p=0.00011) in the whole cohort of patients as independent prognostic variables, whereas in patients with single BM-MM the kind of applied treatment (stereotactic radiotherapy or neurosurgical metastasectomy vs. others; HR: 1.5, 95%CI: 1.1–1.9; p=0.0061) was identified as unique prognostic factor. Conclusions: Overall survival of patients with BM-MM mainly depends on the number of metastases and pre-treatment levels of LDH. In case of a single brain metastasis the application of stereotactic radiotherapy or neurosurgical metastasectomy is by far the most important factor for improving survival. No significant financial relationships to disclose.

Effects of antiarrhythmic drugs on atrioventricular conduction in patients with preexisting bundle branch block

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Kochav ◽  
R.C Chen ◽  
J.M.D Dizon ◽  
J.A.R Reiffel
Keyword(s):  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Class I ◽  
Class Iii ◽  
Bundle Branch Block ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Hazard Ratios ◽  
History Of ◽  
Propensity Score Stratification

Abstract Background Theoretical concern exists regarding AV block (AVB) with class I antiarrhythmics (AADs) when bundle branch block (BBB) is present. Whether this is substantiated in real-world populations is unknown. Purpose To determine the relationship between type of AAD and incidence of AVB in patients with preexisting BBB. Methods We retrospectively studied all patients with BBB who received class I and III AADs between 1997–2019 to compare incidence of AVB. We defined index time as first exposure to either drug class and excluded patients with prior AVB or exposed to both classes. Time-at-risk window ended at first outcome occurrence or when patients were no longer observed in the database. We estimated hazard ratios for incident AVB using Cox proportional hazards models with propensity score stratification, adjusting for over 32,000 covariates from the electronic health record. Kaplan-Meier methods were used to determine treatment effects over time. Results Of 40,120 individuals with BBB, 148 were exposed to a class I AAD and 2401 to a class III AAD. Over nearly 4,200 person-years of follow up, there were 22 and 620 outcome events in the class I and class III cohorts, respectively (Figure). In adjusted analyses, AVB risk was markedly lower in patients exposed to class I AADs compared with class III (HR 0.48 [95% CI 0.30–0.75]). Conclusion Among patients with BBB, exposure to class III AADs was strongly associated with greater risk of incident AVB. This likely reflects differences in natural history of patients receiving class I vs class III AADs rather than adverse class III effects, however, the lack of worse outcomes acutely with class I AADs suggests that they may be safer in BBB than suspected. Funding Acknowledgement Type of funding source: None

scholarly journals Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in “real-world” clinical practice

2017 ◽  
Vol 117 (06) ◽  
pp. 1072-1082 ◽  
Author(s):  
Xiaoyan Li ◽  
Steve Deitelzweig ◽  
Allison Keshishian ◽  
Melissa Hamilton ◽  
Ruslan Horblyuk ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Real World ◽  
Proportional Hazards ◽  
Significant Risk ◽  
Haemorrhagic Stroke ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Warfarin Treatment

SummaryThe ARISTOTLE trial showed a risk reduction of stroke/systemic embolism (SE) and major bleeding in non-valvular atrial fibrillation (NVAF) patients treated with apixaban compared to warfarin. This retrospective study used four large US claims databases (MarketScan, PharMetrics, Optum, and Humana) of NVAF patients newly initiating apixaban or warfarin from January 1, 2013 to September 30, 2015. After 1:1 warfarin-apixaban propensity score matching (PSM) within each database, the resulting patient records were pooled. Kaplan-Meier curves and Cox proportional hazards models were used to estimate the cumulative incidence and hazard ratios (HRs) of stroke/SE and major bleeding (identified using the first listed diagnosis of inpatient claims) within one year of therapy initiation. The study included a total of 76,940 (38,470 warfarin and 38,470 apixaban) patients. Among the 38,470 matched pairs, 14,563 were from MarketScan, 7,683 were from PharMetrics, 7,894 were from Optum, and 8,330 were from Humana. Baseline characteristics were balanced between the two cohorts with a mean (standard deviation [SD]) age of 71 (12) years and a mean (SD) CHA2DS2-VASc score of 3.2 (1.7). Apixaban initiators had a significantly lower risk of stroke/SE (HR: 0.67, 95 % CI: 0.59–0.76) and major bleeding (HR: 0.60, 95 % CI: 0.54–0.65) than warfarin initiators. Different types of stroke/SE and major bleeding – including ischaemic stroke, haemorrhagic stroke, SE, intracranial haemorrhage, gastrointestinal bleeding, and other major bleeding – were all significantly lower for apixaban compared to warfarin treatment. Subgroup analyses (apixaban dosage, age strata, CHA2DS2-VASc or HAS-BLED score strata, or dataset source) all show consistently lower risks of stroke/SE and major bleeding associated with apixaban as compared to warfarin treatment. This is the largest “real-world” study on apixaban effectiveness and safety to date, showing that apixaban initiation was associated with significant risk reductions in stroke/SE and major bleeding compared to warfarin initiation after PSM. These benefits were consistent across various high-risk subgroups and both the standard-and low-dose apixaban dose regimens.Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief.Supplementary Material to this article is available online at www.thrombosis-online.com.

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