Abstract WP79: Choice Of Treatment And Effect On Hemorrhage Rates Of Unruptured Intracranial Aneurysms

INTRODUCTION: The decision regarding whether to perform an interventional procedure as a strategy to prevent hemorrhage of an unruptured intracranial aneurysm (UIA) requires careful consideration of procedural risk and the UIA natural history. No randomized trial data are available. The International Study of Unruptured Intracranial Aneurysms (ISUIA) included a prospective cohort, examining hemorrhage risk and treatment risk. Hypothesis: The purpose of this analysis was to compare the factors related to treatment selection and determination of the number of hemorrhages prevented. Methods: Patients were allocated into the initial treatment and untreated cohorts based upon observation or treatment practices in 61 centers from 1991-1998. 1691 patients were in the observational cohort, 471 were in the endovascular cohort and 1917 patients were in the surgical cohort. The cohorts were followed for a median follow-up of 9.2 years. Outcomes were determined prospectively and with central review. The data were grouped together and analyzed to determine treatment decisions. A Cox proportional hazards model predicting hemorrhage developed in the observation cohort and was applied to the surgery and endovascular cohorts across the follow-up period. Results: Significant baseline variable differences between treated and observed patients were aneurysm size, symptoms, age, prior SAH group, geographical region, treatment percentage, aneurysm daughter sacs or multiple lobes, and history of hypertension, smoking and myocardial infarction. Aneurysm site and family history were not significant. Site, size, and aspirin use were significant predictors of hemorrhage. Long-term the predicted hemorrhage rates were 6.7% at 5 years and 8.0% at 10 years in the surgery group and 8.1% and 9.6% for the endovascular group, respectively. For comparison the rates in the observed cohort were 4.1% and 4.8%, respectively. Conclusions: Decisions for treatment are influenced by patient characteristics such as age and medical history, aneurysm characteristics such as size and morphology and center and regional practices. Patients in the treated cohorts were at moderately increased risk for hemorrhage compared to those in the observed cohort.

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Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa324 ◽

2020 ◽

Author(s):

Yuko Yamaguchi ◽

Marta Zampino ◽

Toshiko Tanaka ◽

Stefania Bandinelli ◽

Yusuke Osawa ◽

...

Keyword(s):

Older Adults ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Differentiation Factor ◽

Hazards Model ◽

Increased Risk ◽

The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P<.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

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Survival of Captive Chimpanzees: Impact of Location and Transfers

10.1101/068858 ◽

2016 ◽

Author(s):

Michael S. Lauer

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Premature Mortality ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Increased Risk ◽

Random Survival Forests ◽

Survival Forests

AbstractTo inform the retirement of NIH-owned chimpanzees, we analyzed the outcomes of 764 NIH-owned chimpanzees that were located at various points in time in at least one of 4 specific locations. All chimpanzees considered were alive and at least 10 years of age on January 1, 2005; transfers to a federal sanctuary began a few months later. During a median follow-up of just over 7 years, there were 314 deaths. In a Cox proportional hazards model that accounted for age, sex, and location (which was treated as a time-dependent covariate), age and sex were strong predictors of mortality, but location was only marginally predictive. Among 273 chimpanzees who were transferred to the federal sanctuary, we found no material increased risk in mortality in the first 30 days after arrival. During a median follow-up at the sanctuary of 3.5 years, age was strongly predictive of mortality, but other variables – sex, season of arrival, and ambient temperature on the day of arrival – were not predictive. We confirmed our regression findings using random survival forests. In summary, in a large cohort of captive chimpanzees, we find no evidence of materially important associations of location of residence or recent transfer with premature mortality.

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Hemorrhage From Arteriovenous Malformations During Pregnancy

Neurosurgery ◽

10.1227/neu.0b013e318256c34b ◽

2012 ◽

Vol 71 (2) ◽

pp. 349-356 ◽

Cited By ~ 59

Author(s):

Bradley A. Gross ◽

Rose Du

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Venous Drainage ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Cox Proportional Hazards Model ◽

Relative Paucity ◽

Increased Risk ◽

Risk Of Hemorrhage

Abstract BACKGROUND: Previous hemorrhage, deep venous drainage, and deep location are established risk factors for arteriovenous malformation (AVM) hemorrhage. Although pregnancy is an assumed risk factor, there is a relative paucity of data to support this neurosurgical tenet. OBJECTIVE: To elucidate the hemorrhage rate of AVMs during pregnancy. METHODS: We reviewed the records of 54 women with an angiographic diagnosis of an AVM at our institution. Annual hemorrhage rates were calculated as the ratio of the number of bleeds to total number of patient-years of follow-up. Patient-years of follow-up were tallied assuming lesion presence from birth until AVM obliteration. The Cox proportional hazards model for hemorrhage with pregnancy as the time-dependent variable was used to calculate the hazard ratio. RESULTS: Five hemorrhages in 4 patients occurred over 62 pregnancies, yielding a hemorrhage rate of 8.1% per pregnancy or 10.8% per year. Over the remaining 2461.3 patient-years of follow-up, only 28 hemorrhages occurred, yielding an annual hemorrhage rate of 1.1%. The hazard ratio for hemorrhage during pregnancy was 7.91 (P = 2.23 × 10−4), increasing to 18.12 (P = 7.31 × 10−5) when limiting the analysis to patient follow-up up to age 40. CONCLUSION: Because of the increased risk of hemorrhage from AVMs during pregnancy, we recommend intervention in women who desire to bear children, particularly if the AVM has bled. If the AVM is discovered during pregnancy, we recommend early intervention if it has ruptured; if it is unruptured, we recommend comprehensive counseling, weighing risks of intervention against continuation of pregnancy without intervention.

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Risk of Blindness Among Patients With Diabetes and Newly Diagnosed Diabetic Retinopathy

10.2337/figshare.13477362.v1 ◽

2021 ◽

Author(s):

Charles C. Wykoff ◽

Rahul N. Khurana ◽

Quan Dong Nguyen ◽

Scott P. Kelly ◽

Flora Lum ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Significant Risk ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Newly Diagnosed ◽

Increased Risk ◽

Good Vision

OBJECTIVE To evaluate association between initial diabetic retinopathy (DR) severity/risk of blindness in patients with newly diagnosed DR/good vision in the U.S. RESEARCH DESIGN AND METHODS Retrospective cohort study of adult patients with good vision (20/40 or better)/newly diagnosed DR between 1 January 2013 and 31 December 2017 (index date) in the American Academy of Ophthalmology’s IRIS® Registry. Primary exposure of interest, DR severity at index: mild nonproliferative DR (NPDR), moderate NPDR, severe NPDR, proliferative DR (PDR). Main outcome measure: development of sustained blindness (SB), defined as study eyes with Snellen visual acuity readings of 20/200 or worse at two separate visits ≥3 months apart that did not improve beyond 20/100. RESULTS Among 53,535 eligible eyes (mean follow-up, 662.5 days), 678 (1.3%) eyes developed SB. Eyes with PDR at index represented 10.5% (5,629/53,535) of the analysis population but made up 26.5% (180/678) of eyes that developed SB. Kaplan-Meier analysis revealed that eyes with moderate NPDR, severe NPDR, and PDR at index were 2.6, 3.6, and 4.0 times more likely, respectively, to develop SB after 2 years of DR diagnosis versus eyes with mild DR at index. In a Cox proportional hazards model adjusted for index characteristics/development of ocular conditions during follow-up, eyes with PDR had an increased risk of developing SB versus eyes with mild NPDR at index (hazard ratio, 2.26; 95% CI, 2.09−2.45). CONCLUSIONS In this longitudinal ophthalmologic registry population involving eyes with good vision, more advanced DR at first diagnosis was a significant risk factor for developing SB.

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Risk of Blindness Among Patients With Diabetes and Newly Diagnosed Diabetic Retinopathy

10.2337/figshare.13477362 ◽

2021 ◽

Author(s):

Charles C. Wykoff ◽

Rahul N. Khurana ◽

Quan Dong Nguyen ◽

Scott P. Kelly ◽

Flora Lum ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Significant Risk ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Newly Diagnosed ◽

Increased Risk ◽

Good Vision

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Apolipoprotein Eɛ2 Is Associated with New Hemorrhage Risk in Brain Arteriovenous Malformations

Neurosurgery ◽

10.1227/01.neu.0000209605.18358.e5 ◽

2006 ◽

Vol 58 (5) ◽

pp. 838-843 ◽

Cited By ~ 33

Author(s):

Ludmila Pawlikowska ◽

K.Y. Trudy Poon ◽

Achal S. Achrol ◽

Charles E. McCulloch ◽

Connie Ha ◽

...

Keyword(s):

Confidence Interval ◽

Proportional Hazards ◽

Clinical Presentation ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Increased Risk ◽

Brain Avm

Abstract OBJECTIVE: Patients with brain arteriovenous malformation (AVM) are at life-threatening risk of intracranial hemorrhage (ICH). Identification of genetic variants associated with increased new ICH risk would facilitate risk stratification and guide therapeutic intervention. METHODS: Brain AVM patients evaluated at University of California, San Francisco or Kaiser Permanente Northern California were followed longitudinally. Primary outcome was new ICH after diagnosis; censoring events were any AVM treatment or last follow-up examination. The association of ApoE ɛ2 and ɛ4 genotype with new ICH was evaluated by Kaplan-Meier survival analysis and further characterized via a Cox proportional hazards model. RESULTS: We genotyped 284 brain AVM patients (50% women; 57% Caucasian; median follow-up time, 0.3 yr) including 18 patients with a history of new ICH). ApoE ɛ2, but not ApoE ɛ4 genotype, was associated with new ICH (P = 0.0052). ApoE ɛ2 carriers had fivefold increased risk of new ICH (hazard ratio, 5.09; 95% confidence interval, 1.46–17.7; P = 0.010; Cox proportional hazards model adjusting for race/ethnicity and clinical presentation). Subset analysis in the largest homogenous ethnic subcohort (Caucasians) confirmed the increased risk of new ICH in ApoE ɛ2 carriers (hazard ratio, 8.71; 95% confidence interval, 1.4–53.9; P = 0.020; multivariate model adjusting for clinical presentation). CONCLUSION: ApoE genotype may influence the risk of ICH in the natural course of brain AVM. The identification of genetic predictors of ICH risk may facilitate estimation of AVM natural history risk and individualize clinical decision-making and therapeutic recommendations.

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Risk factors associated with major adverse cardiac and cerebrovascular events following percutaneous coronary intervention: a 10-year follow-up comparing random survival forest and Cox proportional-hazards model

BMC Cardiovascular Disorders ◽

10.1186/s12872-020-01834-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Maryam Farhadian ◽

Sahar Dehdar Karsidani ◽

Azadeh Mozayanimonfared ◽

Hossein Mahjub

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Coronary Intervention ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Cerebrovascular Events ◽

Long Term Follow Up ◽

Stent Length

Abstract Background Due to the limited number of studies with long term follow-up of patients undergoing Percutaneous Coronary Intervention (PCI), we investigated the occurrence of Major Adverse Cardiac and Cerebrovascular Events (MACCE) during 10 years of follow-up after coronary angioplasty using Random Survival Forest (RSF) and Cox proportional hazards models. Methods The current retrospective cohort study was performed on 220 patients (69 women and 151 men) undergoing coronary angioplasty from March 2009 to March 2012 in Farchshian Medical Center in Hamadan city, Iran. Survival time (month) as the response variable was considered from the date of angioplasty to the main endpoint or the end of the follow-up period (September 2019). To identify the factors influencing the occurrence of MACCE, the performance of Cox and RSF models were investigated in terms of C index, Integrated Brier Score (IBS) and prediction error criteria. Results Ninety-six patients (43.7%) experienced MACCE by the end of the follow-up period, and the median survival time was estimated to be 98 months. Survival decreased from 99% during the first year to 39% at 10 years' follow-up. By applying the Cox model, the predictors were identified as follows: age (HR = 1.03, 95% CI 1.01–1.05), diabetes (HR = 2.17, 95% CI 1.29–3.66), smoking (HR = 2.41, 95% CI 1.46–3.98), and stent length (HR = 1.74, 95% CI 1.11–2.75). The predictive performance was slightly better by the RSF model (IBS of 0.124 vs. 0.135, C index of 0.648 vs. 0.626 and out-of-bag error rate of 0.352 vs. 0.374 for RSF). In addition to age, diabetes, smoking, and stent length, RSF also included coronary artery disease (acute or chronic) and hyperlipidemia as the most important variables. Conclusion Machine-learning prediction models such as RSF showed better performance than the Cox proportional hazards model for the prediction of MACCE during long-term follow-up after PCI.

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Clinical impact of regression from sustained to paroxysmal atrial fibrillation: the Fushimi AF registry

European Heart Journal ◽

10.1093/ehjci/ehaa946.0678 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Fujino ◽

H Ogawa ◽

S Ikeda ◽

K Doi ◽

Y Hamatani ◽

...

Keyword(s):

Cardiac Death ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Clinical Impact ◽

Cox Proportional Hazards Model ◽

Cardiac Events ◽

Hazards Model ◽

Adverse Cardiac Events

Abstract Background Atrial fibrillation (AF) commonly progresses from paroxysmal type to sustained type in the natural course of the disease, and we previously demonstrated that the progression of AF was associated with increased risk of clinical adverse events. There are some patients, though less frequently, who regress from sustained to paroxysmal AF, but the clinical impact of the regression of AF remains unknown. Purpose We sought to investigate whether regression from sustained to paroxysmal AF is associated with better clinical outcomes. Methods Using the dataset of the Fushimi AF Registry, patients who were diagnosed as sustained (persistent or permanent) AF at baseline were studied. Conversion of sustained AF to paroxysmal AF during follow-up was defined as regression of AF. Major adverse cardiac events (MACE) were defined as the composite of cardiac death, stroke, and hospitalization for heart failure (HF). Event rates were compared between the patients with and without regression of AF. In patients with sustained AF at baseline, predictors of MACE were identified using Cox proportional hazards model. Results Among 2,253 patients who were diagnosed as sustained AF at baseline, regression of AF was observed in 9.0% (202/2,253, 2.0 per 100 patient-years) during a median follow-up of 4.0 years. Of these, 24.3% (49/202, 4.6 per 100 patient-years) of the patients finally recurred to sustained AF during follow-up. The proportion of asymptomatic patients was lower in patients with regression of AF than those without (with vs without regression; 49.0% vs 69.5%, p<0.01). The percentage of beta-blocker use at baseline was similar between the two groups (37.2% vs 33.8%, p=0.34). The prevalence of patients who underwent catheter ablation or electrical cardioversion during follow-up was higher in patients with regression of AF (catheter ablation: 15.8% vs 5.5%; p<0.01, cardioversion: 4.0% vs 1.4%; p<0.01, respectively). The rate of MACE was significantly lower in patients with regression of AF as compared with patients who maintained sustained AF (3.7 vs 6.2 per 100 patient-years, log-rank p<0.01). Figure shows the Kaplan-Meier curves for MACE, cardiac death, hospitalization for heart failure, and stroke. In patients with sustained AF at baseline, multivariable Cox proportional hazards model demonstrated that regression of AF was an independent predictor of lower MACE (adjusted hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.28 to 0.88, p=0.02), stroke (HR: 0.51, 95% CI: 0.30 to 0.88, p=0.02), and hospitalization for HF (HR: 0.50, 95% CI: 0.29 to 0.85, p=0.01). Conclusion Regression from sustained to paroxysmal AF was associated with a lower incidence of adverse cardiac events. Funding Acknowledgement Type of funding source: None

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CTIM-10. REPRODUCIBILITY OF CLINICAL TRIALS USING CMV-TARGETED DENDRITIC CELL VACCINES IN PATIENTS WITH GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noab196.202 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi51-vi51

Author(s):

Kristen Batich ◽

Duane Mitchell ◽

Patrick Healy ◽

James Herndon ◽

Gloria Broadwater ◽

...

Keyword(s):

Clinical Trials ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Recurrent Glioblastoma ◽

Cox Proportional Hazards Model ◽

Total N ◽

Dc Vaccine ◽

Dc Vaccines

Abstract INTRODUCTION Vaccination with dendritic cells (DCs) fares poorly in primary and recurrent glioblastoma (GBM). Moreover, GBM vaccine trials are often underpowered due to limited sample size. METHODS To address these limitations, we conducted three sequential clinical trials utilizing Cytomegalovirus (CMV)-specific DC vaccines in patients with primary GBM. Autologous DCs were generated and electroporated with mRNA encoding for the CMV protein pp65. Serial vaccination was given throughout adjuvant temozolomide cycles, and 111Indium radiolabeling was implemented to assess migration efficiency of DC vaccines. Patients were followed for median overall survival (mOS) and OS. RESULTS Our initial study was the phase II ATTAC study (NCT00639639; total n=12) with 6 patients randomized to vaccine site preconditioning with tetanus-diphtheria (Td) toxoid. This led to an expanded cohort trial (ATTAC-GM; NCT00639639) of 11 patients receiving CMV DC vaccines containing granulocyte-macrophage colony-stimulating factor (GM-CSF). Follow-up data from ATTAC and ATTAC-GM revealed 5-year OS rates of 33.3% (mOS 38.3 months; CI95 17.5-undefined) and 36.4% (mOS 37.7 months; CI95 18.2-109.1), respectively. ATTAC additionally revealed a significant increase in DC migration to draining lymph nodes following Td preconditioning (P=0.049). Increased DC migration was associated with OS (Cox proportional hazards model, HR=0.820, P=0.023). Td-mediated increased migration has been recapitulated in our larger confirmatory trial ELEVATE (NCT02366728) of 43 patients randomized to preconditioning (Wilcoxon rank sum, Td n=24, unpulsed DC n=19; 24h, P=0.031 and 48h, P=0.0195). In ELEVATE, median follow-up of 42.2 months revealed significantly longer OS in patients randomized to Td (P=0.026). The 3-year OS for Td-treated patients in ELEVATE was 34% (CI95 19-63%) compared to 6% given unpulsed DCs (CI95 1-42%). CONCLUSION We report reproducibility of our findings across three sequential clinical trials using CMV pp65 DCs. Despite their small numbers, these successive trials demonstrate consistent survival outcomes, thus supporting the efficacy of CMV DC vaccine therapy in GBM.

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Abstract 15567: Residual Cholesterol and Cardiovascular Events in Patients With Coronary Artery Disease Under Different Glucose Metabolism Status

Circulation ◽

10.1161/circ.142.suppl_3.15567 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Jian-jun Li ◽

Yexuan Cao ◽

Hui-Wen Zhang ◽

Jing-Lu Jin ◽

Yan Zhang ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Glucose Metabolism ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Significant Difference ◽

Artery Disease

Introduction: The atherogenicity of residual cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). Hypothesis: This study aimed to examine the prognostic value of plasma RC, clinically presented as triglyceride-rich lipoprotein-cholesterol (TRL-C) or remnant-like lipoprotein particles-cholesterol (RLP-C), in CAD patients with different glucose metabolism status. Methods: Fasting plasma TRL-C and RLP-C levels were directly calculated or measured in 4331 patients with CAD. Patients were followed for incident MACEs for up to 8.6 years and categorized according to both glucose metabolism status [DM, pre-DM, normal glycaemia regulation (NGR)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. Results: During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NGR groups (p>0.05). When stratified by status of glucose metabolism and RC levels, highest levels of RLP-C, calculated and measured TRL-C were significant and independent predictors of developing MACEs in pre-DM (HR: 2.10, 1.98, 1.92, respectively; all p<0.05) and DM (HR: 2.25, 2.00, 2.16, respectively; all p<0.05). Conclusions: In this large cohort study with long-term follow-up, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting RC might be a target for patients with impaired glucose metabolism.

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