scholarly journals Lack of Survival Advantage among Re-Resected Elderly Glioblastoma Patients: A SEER-Medicare Study

2020 ◽  
Author(s):  
Debra A Goldman ◽  
Anne S Reiner ◽  
Eli L Diamond ◽  
Lisa M DeAngelis ◽  
Viviane Tabar ◽  
...  
Keyword(s):  
Older Adults ◽  
Survival Benefit ◽  
Cox Regression ◽  
Geographic Region ◽  
Survival Advantage ◽  
Time Dependent ◽  
Poverty Level ◽  
Risk Of Death ◽  
Immortal Time Bias ◽  
Initial Resection

Abstract Background The survival benefit of re-resection for glioblastoma (GBM) remains controversial, owing to the immortal time bias inadequately considered in many studies where re-resection was treated as a fixed, rather than time-dependent factor. Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we assessed treatment patterns for older adults and evaluated the association between re-resection and overall survival (OS), accounting for timing of re-resection. Methods This retrospective cohort study included elderly patients (age≥66) in the SEER-Medicare linked database diagnosed with GBM between 2006 and 2015 who underwent initial resection. Time-dependent Cox regression was used to assess the association between re-resection and OS, controlling for age, gender, race, poverty level, geographic region, marital status, comorbidities, receipt of radiation+temozolomide, and surgical complications. Results Our analysis included 3,604 patients with median age 74 (range: 66-96); 54% were men and 94% were white. After initial resection, 44% received radiation+temozolomide and these patients had a lower hazard of death (HR: 0.28, 95%CI: 0.26-0.31, p<0.001). In total, 9.5% (n=343) underwent re-resection. In multivariable analyses, no survival benefit was seen for patients who underwent re-resection (HR: 1.12, 95%CI: 0.99-1.27, p=0.07). Conclusions Re-resection rates were low among elderly GBM patients and no survival advantage was observed for patients who underwent re-resection. However, patients who received standard of care at initial diagnosis had a lower risk of death. Older adults benefit from receiving radiation+temozolomide after initial resection, and future studies should assess the relationship between re-resection and OS taking time of re-resection into account.

scholarly journals Beta-Blocker Treatment in Ventilated COVID-19 patients – A Cox Regression with Time Dependent Covariate Analysis

2021 ◽  
Author(s):  
Dipesh Mistry ◽  
Anower Hossain ◽  
Jianxia Sun ◽  
Tonny Veenith ◽  
Ranjit Lall ◽  
...  
Keyword(s):  
Heart Rate ◽  
Critically Ill ◽  
Beta Blocker ◽  
Cox Regression ◽  
Prospective Trial ◽  
Time Dependent ◽  
Beta Blockade ◽  
Covariate Analysis ◽  
Risk Of Death ◽  
Immortal Time Bias

Abstract Background: Patients with co-morbidities are particularly vulnerable to severe COVID-19 disease. Critically ill patients with COVID-19 frequently experience severe tachycardias and avoidance of these is important in some co-morbidities, for instance cardiovascular disease. There is growing interest in beta blockade in critical illness as their use been associated with improved outcomes in a variety of conditions. We report the real-world use of heart rate management in patients during the first wave of the COVID-19 pandemic. As retrospective data are prone to an Immortal Time Bias, we created a Cohort Trial such as might be used for a future prospective trial and used Time Dependent Covariate Analysis for its analysis. Methods: Data for all PCR-proven COVID-19 patients ventilated in the Intensive Care Unit (ICU) were extracted from the hospital databases. To compensate for the risk of immortal time bias, we restricted analysis to 144 patients who achieved a heart rate (HR) of 90 beats per minute for more than 12 hours and were treated with norepinephrine. We recorded time from these ‘entry criteria’ to first beta blocker dose. Those patients who did not receive a beta blocker were given a nominal time to beta blocker beyond the censor day. Outcome was mortality censored at 28 days.Results: In the study group, 83/144 patients (57.6%) received a beta blocker. The median interval from entry criteria to beta blocker was 7.91 days (IQR 3.89, 13.15) and median duration of treatment was 7.00 days (IQR 4.00, 14.00). Twenty-four beta blocker patients (28.9%) died within 28 days compared with 29 (47.5%) who did not (adjusted OR 0.43; 95% CI 0.20-0.95, P=0.036). Cox Regression with time-dependent covariate analysis revealed there was an increased, but not significant, risk of death with beta blocker delay (Hazard Ratio 1.42 p=0.264). Mortality was also reduced for each day treated with beta blockade (adjusted Odds Ratio 0.76, 95% CI 0.64-0.91; P=0.002).Conclusions: In a retrospective analysis of critically ill ventilated patients with COVID-19 who developed a tachycardia >90 beats per minute and were treated with norepinephrine, beta blockade was associated with reduced mortality.

Higher sRAGE Levels Predict Mortality in Frail Older Adults with Cardiovascular Disease

Gerontology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Lee Butcher ◽  
Jose Antonio Carnicero ◽  
Karine Pérès ◽  
Marco Colpo ◽  
David Gomez Cabrero ◽  
...  
Keyword(s):  
Older Adults ◽  
Cox Regression ◽  
Population Based ◽  
Blood Levels ◽  
Roc Curve Analysis ◽  
Baseline Serum ◽  
Frailty Status ◽  
Risk Of Death ◽  
Survival Difference ◽  
Increased Risk

<b><i>Introduction:</i></b> The evidence that blood levels of the soluble receptor for advanced glycation end products (sRAGE) predict mortality in people with cardiovascular diseases (CVD) is inconsistent. To clarify this matter, we investigated if frailty status influences this association. <b><i>Methods:</i></b> We analysed data of 1,016 individuals (median age, 75 years) from 3 population-based European cohorts, enrolled in the FRAILOMIC project. Participants were stratified by history of CVD and frailty status. Mortality was recorded during 8 years of follow-up. <b><i>Results:</i></b> In adjusted Cox regression models, baseline serum sRAGE was positively associated with an increased risk of mortality in participants with CVD (HR 1.64, 95% CI 1.09–2.49, <i>p</i> = 0.019) but not in non-CVD. Within the CVD group, the risk of death was markedly enhanced in the frail subgroup (CVD-F, HR 1.97, 95% CI 1.18–3.29, <i>p</i> = 0.009), compared to the non-frail subgroup (CVD-NF, HR 1.50, 95% CI 0.71–3.15, <i>p</i> = 0.287). Kaplan-Meier analysis showed that the median survival time of CVD-F with high sRAGE (&#x3e;1,554 pg/mL) was 2.9 years shorter than that of CVD-F with low sRAGE, whereas no survival difference was seen for CVD-NF. Area under the ROC curve analysis demonstrated that for CVD-F, addition of sRAGE to the prediction model increased its prognostic value. <b><i>Conclusions:</i></b> Frailty status influences the relationship between sRAGE and mortality in older adults with CVD. sRAGE could be used as a prognostic marker of mortality for these individuals, particularly if they are also frail.

scholarly journals Immortal Time Bias in Observational Studies of Time-to-Event Outcomes

2018 ◽  
Vol 25 (1) ◽  
pp. 107327481878935 ◽  
Author(s):  
Parul Agarwal ◽  
Erin Moshier ◽  
Meng Ru ◽  
Nisha Ohri ◽  
Ronald Ennis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Effect ◽  
Cox Regression ◽  
Analytical Techniques ◽  
Time Dependent ◽  
Simulation Studies ◽  
Significant Treatment ◽  
Immortal Time Bias ◽  
Postmastectomy Radiation Therapy ◽  
Landmark Model

The objectives of this study are to illustrate the effects of immortal time bias (ITB) using an oncology outcomes database and quantify through simulations the magnitude and direction of ITB when different analytical techniques are used. A cohort of 11 626 women who received neoadjuvant chemotherapy and underwent mastectomy with pathologically positive lymph nodes were accrued from the National Cancer Database (2004-2008). Standard Cox regression, time-dependent (TD), and landmark models were used to compare overall survival in patients who did or did not receive postmastectomy radiation therapy (PMRT). Simulation studies showing ways to reduce the effect of ITB indicate that TD exposures should be included as variables in hazard-based analyses. Standard Cox regression models comparing overall survival in patients who did and did not receive PMRT showed a significant treatment effect (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.88-0.99). Time-dependent and landmark methods estimated no treatment effect with HR: 0.97, 95% CI: 0.92 to 1.03 and HR: 0.98, 95% CI, 0.92 to 1.04, respectively. In our simulation studies, the standard Cox regression model significantly overestimated treatment effects when no effect was present. Estimates of TD models were closest to the true treatment effect. Landmark model results were highly dependent on landmark timing. Appropriate statistical approaches that account for ITB are critical to minimize bias when examining relationships between receipt of PMRT and survival.

scholarly journals High N-Terminal proB-Type Natriuretic Peptide Indicates Elevated Risk of Death after Percutaneous Coronary Intervention Compared to Coronary Artery Bypass Surgery in Patients with Left Ventricular Dysfunction

2019 ◽  
Vol 8 (6) ◽  
pp. 898 ◽  
Author(s):  
Christian Roth ◽  
Matthias Schneider ◽  
Daniel Dalos ◽  
Clemens Gangl ◽  
Christian Toth ◽  
...  
Keyword(s):  
Heart Failure ◽  
Percutaneous Coronary Intervention ◽  
Survival Benefit ◽  
Cox Regression ◽  
Artery Bypass ◽  
Coronary Intervention ◽  
Left Ventricular ◽  
Revascularization Procedure ◽  
Risk Of Death ◽  
Percutaneous Coronary

Background: Reduced left ventricular function (LVF) is a predictor for stent-thrombosis. In advanced heart failure (characterized by high NT-proBNP) with an activated coagulation system, coronary events clinically perceived as sudden death or death from heart failure may be more common in patients treated by percutaneous coronary intervention (PCI) than in patients treated by coronary artery bypass grafting (CABG). Our study analyses (1) if patients with reduced LVF who require coronary revascularization will have a better survival benefit with CABG or PCI, and (2) if the survival benefit is predicted by NT-proBNP. Methods: This observational retrospective study included patients from the coronary catheter laboratory database of the Medical University of Vienna (CCLD-MUW). Multivariate Cox regression analyses were performed to test the hypothesis that there is an interaction in the risk of death between those with lower or elevated NT-proBNP levels and the revascularization procedure (PCI or CABG). The relative risk of PCI compared to CABG as reference was calculated for patients with low and elevated NT-proBNP levels. Results: In the entire study population with 398 patients (340 PCI and 58 CABG) the revascularization procedure had no predictive value. When the revascularization procedure*NTproBNP interaction was forced into the Cox regression model, this term was an independent predictor of death. The relative risk of PCI compared to CABG was similar in patients with lower NT-proBNP—1.01 (95% confidence interval (CI), 0.45–2.24), but was significantly increased in patients with elevated NT-proBNP—1.58 (95% CI, 1.07–2.33). Conclusion: Death is associated to the revascularization procedure, but only in those patients with elevated NT-proBNP levels. NT-proBNP is a predicting factor for the revascularization procedure: elevated levels showed an increased risk of death after PCI compared to CABG, whereas lower levels were associated with a similar risk after both revascularization procedures.

scholarly journals Dental Health Behaviors, Dentition, and Mortality in the Elderly: The Leisure World Cohort Study

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Annlia Paganini-Hill ◽  
Stuart C. White ◽  
Kathryn A. Atchison
Keyword(s):  
Older Adults ◽  
Oral Health ◽  
Health Behaviors ◽  
Cox Regression ◽  
Dental Health ◽  
Significant Risk ◽  
Dental Floss ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Increased Risk

In the last decade the effect of oral health on the general health and mortality of elderly people has attracted attention. We explored the association of dental health behaviors and dentition on all-cause mortality in 5611 older adults followed from 1992 to 2009 (median=9years) and calculated risk estimates using Cox regression analysis in men and women separately. Toothbrushing at night before bed, using dental floss everyday, and visiting the dentist were significant risk factors for longevity. Never brushing at night increased risk 20–35% compared with brushing everyday. Never flossing increased risk 30% compared with flossing everyday. Not seeing a dentist within the last 12 months increased risk 30–50% compared with seeing a dentist two or more times. Mortality also increased with increasing number of missing teeth. Edentulous individuals (even with dentures) had a 30% higher risk of death compared with those with 20+ teeth. Oral health behaviors help maintain natural, healthy and functional teeth but also appear to promote survival in older adults.

scholarly journals HOUT-10. TREATMENT OUTCOME IN ADOLESCENTS AND YOUNG ADULTS (AYAS) WITH GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi114-vi114
Author(s):  
Josiah An ◽  
Adithya Chennamadhavuni ◽  
Sarah Mott ◽  
Rohan Garje
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Private Insurance ◽  
Multivariable Analysis ◽  
Treatment Modalities ◽  
Study Objective ◽  
Risk Of Death ◽  
Immortal Time Bias ◽  
Survival Difference ◽  
Increased Risk

Abstract BACKGROUND Glioblastoma is one of the most aggressive and commonly encountered brain tumors. Standard of care includes surgical resection with adjuvant or concurrent chemoradiation which is predominantly based on adult clinical trials. Our study objective was to assess whether survival differed in AYA compared to older adults. METHODS The National Cancer Database was used to identify patients with at least surgically resected glioblastoma from 2004 to 2016. Cox regression models were utilized to estimate the effect of treatment on overall survival (OS) while accounting for immortal time bias (3-months) and clustering within facility. RESULTS Among 51,718 patients with glioblastoma identified, 2,930 patients were AYA. Multivariable analysis (MVA) shows OS was significantly higher in AYA, female, non-white, high income, unilateral cancer patients with private insurance receiving treatments in high volume facilities. OS among AYA patients was significantly lower in surgery + (radiation or chemotherapy: S+(RT or CT) group compared to surgery only (S) (HR=1.33, 95% CI 1.06–1.65), but no significant survival difference between surgery + chemoradiation (S+C+RT) groups and surgery only (HR=0.97, 95% CI 0.83–1.14). Median survival is ~28 months in AYA among S and S+C+RT groups whereas significantly lower survival (median OS ~18 months) is seen in S+RT or CT. Non-AYA patients were at 2 times increased risk of death compared to AYA patients who received the same type of treatment. CONCLUSIONS In conclusion, AYA population has more than twice the median OS in comparison to non-AYA patients. Worse overall survival was seen among S+RT or CT in comparison to S and S+RT+CT in AYA group. For patients needing either chemotherapy or radiation with surgery, possibly a trimodal approach might provide better survival advantage. Prospective studies are needed to further explore optimal treatment modalities in this unique population.

scholarly journals Importance of previous hospital stays on the risk of hospital re-admission in older adults: a real-life analysis of the PAERPA study population

2020 ◽  
Author(s):  
Fabien Visade ◽  
Genia Babykina ◽  
Antoine Lamer ◽  
Marguerite-Marie Defebvre ◽  
David Verloop ◽  
...  
Keyword(s):  
Older Adults ◽  
Relative Risk ◽  
Hospital Stay ◽  
Cox Regression ◽  
Real Life ◽  
Frailty Model ◽  
Health Insurance Data ◽  
Risk Of Death ◽  
Hospital Stays ◽  
The Impact

Abstract Background consideration of the first hospital re-admission only and failure to take account of previous hospital stays, which are the two significant limitations when studying risk factors for hospital re-admission. The objective of the study was to use appropriate statistical models to analyse the impact of previous hospital stays on the risk of hospital re-admission among older patients. Methods an exhaustive analysis of hospital discharge and health insurance data for a cohort of patients participating in the PAERPA (‘Care Pathways for Elderly People at Risk of Loss of Personal Independence’) project in the Hauts de France region of France. All patients aged 75 or over were included. All data on hospital re-admissions via the emergency department were extracted. The risk of unplanned hospital re-admission was estimated by applying a semiparametric frailty model, the risk of death by applying a time-dependent semiparametric Cox regression model. Results a total of 24,500 patients (median [interquartile range] age: 81 [77–85]) were included between 1 January 2015 and 31 December 2017. In a multivariate analysis, the relative risk (95% confidence interval [CI]) of hospital re-admission rose progressively from 1.8 (1.7–1.9) after one previous hospital stay to 3.0 (2.6–3.5) after five previous hospital stays. The relative risk [95%CI] of death rose slowly from 1.1 (1.07–1.11) after one previous hospital stay to 1.3 (1.1–1.5) after five previous hospital stays. Conclusion analyses of the risk of hospital re-admission in older adults must take account of the number of previous hospital stays. The risk of death should also be analysed.

scholarly journals mRNA vaccines effectiveness against COVID-19 hospitalizations and deaths in older adults: a cohort study based on data-linkage of national health registries in Portugal

2021 ◽  
Author(s):  
Baltazar Nunes ◽  
Ana Rodrigues ◽  
Irina Kislaya ◽  
Camila Cruz ◽  
Andre Peralta-Santos ◽  
...  
Keyword(s):  
Older Adults ◽  
Cohort Study ◽  
National Health ◽  
Data Linkage ◽  
Cox Regression ◽  
Vaccine Effectiveness ◽  
Hazard Ratio ◽  
Time Dependent ◽  
Age Group ◽  
Vaccination Scheme

Background: We used electronic health registries to estimate the mRNA vaccine effectiveness (VE) against COVID-19 hospitalizations and deaths in older adults. Methods: We established a cohort of individuals aged 65 and more years, resident in Portugal mainland through data linkage of eight national health registries. For each outcome, VE was computed as one minus the confounder-adjusted hazard ratio, estimated by time-dependent Cox regression. Results: VE against COVID-19 hospitalization ≥14 days after the second dose was 94% (95%CI 88 to 97) for age-group 65-79 years old (yo) and 82% (95%CI 72 to 89) for ≥80 yo. VE against COVID-19 related deaths ≥ 14 days after second dose was 96% (95%CI 92 to 98) for age-group 65-79 yo and 81% (95%CI 74 to 87), for ≥80 yo individuals. No evidence of VE waning was observed after 98 days of second dose uptake. Conclusions: mRNA vaccine effectiveness was high for the prevention of hospitalizations and deaths in age-group 65-79 yo and ≥80 yo with a complete vaccination scheme, even after 98 days of second dose uptake.

Allogeneic stem cell transplantation (allo-SCT) in adult acute lymphoblastic leukemia (ALL)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17513-17513
Author(s):  
S. J. Wu ◽  
M. Yao ◽  
J. L. Tang ◽  
Y. C. Chen ◽  
A. L. Cheng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Benefit ◽  
Proportional Hazards Model ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Early Period ◽  
Population Based ◽  
Cox Proportional Hazards Model ◽  
Time Dependent ◽  
Immortal Time Bias

17513 Background: Although viewed as a potentially curable disease, the outcome of adult ALL is extremely poor. The role of allo-SCT, a possible curative modality, is of debate. Although the solid evidence is lacking, allo-SCT is viewed as a standard treatment in some institutions and some trials. The objective of the study is to clarify the effect of allo-SCT in the treatment of adult ALL patietns. Methods: From Jan. 1999 to Jun. 2006, we included 103 adult ALL patients whose age were between 15 and 55, the upper limit of age for allo-SCT in this institution. Their data, including clinical characteristics, cytogenetic results, treatment response and outcomes, were collected. To avoid the “immortal-time bias” in assessing the effect of transplant, the results from a time-independent and time-dependent Cox proportional hazards model were compared. We also conducted a population-based study to compare the outcomes of these patients with those diagnosed between Jan. 1986 and Dec.1993 in our institution. Results: There were 46 females and 57 males. The median age was 25.8, with 63 patients (61.2%) younger than 30. The median survival was 21.9 months and the 3-year overall survival was 34.2%. 48 patients(46.6%) received allo-SCT. The transplant conferred to marginally better survival in univariate analysis (p=0.049), but by time-dependent regression method, there was, after adjusting for other risk factors, no survival benefit for patients receiving transplant (HR 1.452, 95% CI 0.766∼2,751, p=0.253). The outcomes of these 103 patients were compared with another group of 69 patients diagnosed in the early period, among whom 13 patients(18.8%) received transplant. Although with higher proportion of patients undergoing allo- SCT, there was no advance in overall survival (p=0.157). Conclusions: In adult ALL, the outcome is still poor. Although there are new treatment protocols and modalities in chemotherapy and transplantation, these advances do not reflect to survival improvement. Transplantation provides limited survival benefit in population-based viewpoint. The candidates of allo-SCT should thus be carefully selected and allo-SCT should not be viewed as a standard in the treatment of adult ALL patients. No significant financial relationships to disclose.

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