Response to Comment on Suissa. Lower Risk of Death With SGLT2 Inhibitors in Observational Studies: Real or Bias? Diabetes Care 2018;41:6–10

Abstract Peritonitis is a critical complication of peritoneal dialysis (PD). Investigators have reported the risk of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) versus automated peritoneal dialysis (APD), but the available evidence is predominantly based on observational studies which failed to report on the connection type. Our understanding of the relationship between peritonitis risk and PD modality thus remained insufficient. We studied 285 participants who began PD treatment between 1997 and 2014 at three hospitals in Nara Prefecture in Japan. We matched 106 APD patients with 106 CAPD patients based on their propensity scores. The primary outcome was time to first episode of peritonitis within 3 years after PD commencement. In total, PD peritonitis occurred in 64 patients during the study period. Patients initiated on APD had a lower risk of peritonitis than did those initiated on CAPD in both the unadjusted and adjusted models. The hazard ratio (HR) and 95% confidence interval (CI) for the primary endpoint were 0.30 (0.17–0.53) in the fully adjusted model including connection type. In the matched cohort, APD patients had a significantly lower risk of peritonitis than did CAPD patients (log-rank: p < 0.001, HR 0.32, 95% CI 0.16–0.59). The weighting-adjusted analysis of the inverse probability of treatment yielded a similar result (HR 0.35, 95% CI 0.18–0.67). In conclusion, patients initiated on APD at PD commencement had a reduced risk of peritonitis compared with those initiated on CAPD, suggesting APD may be preferable for prevention of peritonitis among PD patients.

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Comparative effectiveness of bisoprolol and carvedilol among patients receiving maintenance hemodialysis

Clinical Kidney Journal ◽

10.1093/ckj/sfaa248 ◽

2021 ◽

Author(s):

Ping-Hsun Wu ◽

Yi-Ting Lin ◽

Jia-Sin Liu ◽

Yi-Chun Tsai ◽

Mei-Chuan Kuo ◽

...

Keyword(s):

Heart Failure ◽

Ischemic Stroke ◽

Lower Risk ◽

Cox Model ◽

Major Adverse Cardiovascular Events ◽

Maintenance Hemodialysis ◽

Risk Of Death ◽

Relative Safety ◽

Dialysis Vintage ◽

All Cause Mortality

Abstract Background Despite widespread use, there is no trial evidence to inform β-blocker’s (BB) relative safety and efficacy among patients undergoing hemodialysis (HD). We herein compare health outcomes associated with carvedilol or bisoprolol use, the most commonly prescribed BBs in these patients. Methods We created a cohort study of 9305 HD patients who initiated bisoprolol and 11 171 HD patients who initiated carvedilol treatment between 2004 and 2011. We compared the risk of all-cause mortality and major adverse cardiovascular events (MACEs) between carvedilol and bisoprolol users during a 2-year follow-up. Results Bisoprolol initiators were younger, had shorter dialysis vintage, were women, had common comorbidities of hypertension and hyperlipidemia and were receiving statins and antiplatelets, but they had less heart failure and digoxin prescriptions than carvedilol initiators. During our observations, 1555 deaths and 5167 MACEs were recorded. In the multivariable-adjusted Cox model, bisoprolol initiation was associated with a lower all-cause mortality {hazard ratio [HR] 0.66 [95% confidence interval (CI) 0.60–0.73]} compared with carvedilol initiation. After accounting for the competing risk of death, bisoprolol use (versus carvedilol) was associated with a lower risk of MACEs [HR 0.85 (95% CI 0.80–0.91)] and attributed to a lower risk of heart failure [HR 0.83 (95% CI 0.77–0.91)] and ischemic stroke [HR 0.84 (95% CI 0.72–0.97)], but not to differences in the risk of acute myocardial infarction [HR 1.03 (95% CI 0.93–1.15)]. Results were confirmed in propensity score matching analyses, stratified analyses and analyses that considered prescribed dosages or censored patients discontinuing or switching BBs. Conclusions Relative to carvedilol, bisoprolol initiation by HD patients was associated with a lower 2-year risk of death and MACEs, mainly attributed to lower heart failure and ischemic stroke risk.

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Survival in elderly glioblastoma patients treated with bevacizumab-based regimens in the United States

Neuro-Oncology Practice ◽

10.1093/nop/npy001 ◽

2018 ◽

Vol 5 (4) ◽

pp. 251-261 ◽

Cited By ~ 2

Author(s):

Jessica Davies ◽

Irmarie Reyes-Rivera ◽

Thirupathi Pattipaka ◽

Stephen Skirboll ◽

Beatrice Ugiliweneza ◽

...

Keyword(s):

Elderly Patients ◽

Lower Risk ◽

Karnofsky Performance Status ◽

The United States ◽

Cox Proportional Hazards Model ◽

Sensitivity Analyses ◽

Primary Analysis ◽

Risk Of Death ◽

Initial Surgery ◽

The Impact

AbstractBackgroundThe efficacy of bevacizumab (BEV) in elderly patients with glioblastoma remains unclear. We evaluated the effect of BEV on survival in this patient population using the Survival, Epidemiology, and End Results (SEER)-Medicare database.MethodsThis retrospective, cohort study analyzed SEER-Medicare data for patients (aged ≥66 years) diagnosed with glioblastoma from 2006 to 2011. Two cohorts were constructed: one comprised patients who had received BEV (BEV cohort); the other comprised patients who had received any anticancer treatment other than BEV (NBEV cohort). The primary analysis used a multivariate Cox proportional hazards model to compare overall survival in the BEV and NBEV cohorts with initiation of BEV as a time-dependent variable, adjusting for potential confounders (age, gender, Charlson comorbidity index, region, race, radiotherapy after initial surgery, and diagnosis of coronary artery disease). Sensitivity analyses were conducted using landmark survival, propensity score modeling, and the impact of poor Karnofsky Performance Status.ResultsWe identified 2603 patients (BEV, n = 597; NBEV, n = 2006). In the BEV cohort, most patients were Caucasian males and were younger with fewer comorbidities and more initial resections. In the primary analysis, the BEV cohort showed a lower risk of death compared with the NBEV cohort (hazard ratio, 0.80; 95% confidence interval, 0.72–0.89; P < .01). The survival benefit of BEV appeared independent of the number of temozolomide cycles or frontline treatment with radiotherapy and temozolomide.ConclusionBEV exposure was associated with a lower risk of death, providing evidence that there might be a potential benefit of BEV in elderly patients with glioblastoma.

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Response to Comment on Rosenstock and Ferrannini. Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, and Preventable Safety Concern With SGLT2 Inhibitors. Diabetes Care 2015;38:1638–1642

Diabetes Care ◽

10.2337/dci16-0005 ◽

2016 ◽

Vol 39 (8) ◽

pp. e139-e140

Author(s):

Julio Rosenstock ◽

Ele Ferrannini

Keyword(s):

Diabetic Ketoacidosis ◽

Diabetes Care ◽

Safety Concern ◽

Sglt2 Inhibitors ◽

Euglycemic Diabetic Ketoacidosis

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308 Indirect treatment comparison of nivolumab versus placebo as adjuvant treatment for melanoma

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0308 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A335-A335

Author(s):

Jeffrey Weber ◽

Paolo Ascierto ◽

Mark Middleton ◽

Delphine Hennicken ◽

Roberto Zoffoli ◽

...

Keyword(s):

Sensitivity Analysis ◽

Lower Risk ◽

Phase 3 ◽

Free Survival ◽

Intention To Treat ◽

Risk Of Death ◽

Link Type ◽

Indirect Treatment ◽

Resected Stage

BackgroundWe have previously performed indirect treatment comparisons (ITCs) to demonstrate improvements in recurrence-free survival (RFS) and distant metastasis-free survival with nivolumab versus placebo as adjuvant treatment for resected melanoma; however, overall survival (OS) data were not available at the time. Recently, results of the phase 3 CheckMate 238 trial in patients with resected stage IIIB–IIIC/IV melanoma (American Joint Committee on Cancer [AJCC], 7th edition) showed no statistically significant difference in OS between nivolumab and ipilimumab; however, OS events were fewer than expected. In the phase 3 EORTC 18071 trial in patients with resected stage IIIA–IIIC melanoma (AJCC, 6th edition), OS was improved with ipilimumab versus placebo. Here, we provide an update on RFS and an analysis of OS in ITCs of nivolumab and placebo using data from these 2 trials with a common comparator arm: ipilimumab 10 mg/kg.MethodsITCs of nivolumab versus placebo were conducted using 4-year minimum follow-up data from CheckMate 238 (NCT02388906) and 5.3-year median follow-up data from EORTC 18071 (NCT00636168). Bucher ITCs were performed to estimate RFS and OS in the intention-to-treat populations. A sensitivity analysis of OS adjusting for subsequent therapy options was conducted in 2 steps: (1) after controlling for possible confounders and assuming that the only difference was the effect of different subsequent therapies, postrecurrence survival was compared between the 2 ipilimumab arms in each study, and (2) after adjusting for differences in postrecurrence survival, ITCs of nivolumab versus adjusted placebo were performed.ResultsIn these ITC analyses, RFS and OS results with nivolumab suggested an improvement compared with placebo. In the intention-to-treat population, nivolumab was associated with a lower risk of recurrence or death (RFS HR, 0.55; 95% CI, 0.43–0.70) and a lower risk of death (OS HR, 0.62; 95% CI, 0.44–0.88) than placebo. In the sensitivity analysis, a 63% average increase in postrecurrence survival benefit was estimated with ipilimumab in CheckMate 238 compared with ipilimumab in EORTC 18071. After adjusting for this increase in both the ipilimumab and placebo arms in EORTC 18071, nivolumab was associated with a lower risk of death than placebo (OS HR, 0.65; 95% CI, 0.45–0.91), similar to the unadjusted analysis.ConclusionsDespite the changing treatment landscape and the increased number of therapeutic options for metastatic melanoma, these ITCs suggested clinically meaningful improvement in RFS and OS with adjuvant nivolumab compared with a wait-and-watch strategy in high-risk patients with resected melanoma.AcknowledgementsWriting and editorial assistance were provided by Kakoli Parai, PhD, and Andrea Lockett of Ashfield Healthcare Communications, funded by Bristol-Myers Squibb Company.Trial RegistrationNCT02388906 (CheckMate 238), NCT00636168 (EORTC 18071)

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Abstract 11324: Immediate Percutaneous Coronary Intervention in Patients with Refractory Out of Hospital Cardiac Arrest

Circulation ◽

10.1161/circ.144.suppl_2.11324 ◽

2021 ◽

Vol 144 (Suppl_2) ◽

Author(s):

Daniel Rob ◽

Jana Smalcova ◽

Tomas Kovarnik ◽

David Zemanek ◽

Ales Kral ◽

...

Keyword(s):

Percutaneous Coronary Intervention ◽

Cardiac Arrest ◽

Lower Risk ◽

Coronary Intervention ◽

Post Hoc Analysis ◽

Risk Of Death ◽

Coronary Syndrome ◽

Percutaneous Coronary ◽

Post Hoc ◽

Hospital Cardiac Arrest

Background: An increasing number of cardiac centres are using immediate percutaneous coronary intervention (PCI) and extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory out of hospital cardiac arrest (r-OHCA). Published evidence regarding PCI in OHCA has been mainly reporting to patients with early return of spontaneous circulation and the influence of PCI and ECPR on survival in the population of patients with r-OHCA and acute coronary syndrome (ACS) remains unclear. Methods: In this post hoc analysis of the randomized r-OHCA trial, all patients with ACS as a cause of r-OHCA were included. The effect of successful PCI and ECPR on 180-days survival was examined using Kaplan-Meier estimates and multivariable Cox regression. Results: In total, 256 patients were evaluated in Prague OHCA study and 127 (49.6 %) had ACS as the cause of r-OHCA constituting current study population. The mean age was 58 years (46.3-64) and duration of resuscitation was 52.5 minutes (36.5-68). ECPR was used in 51 (40.2 %) of patients. Immediate PCI was performed in 86 (67.7%) patients and TIMI flow 2 or 3 was achieved in 75 (87.2%) patients. The overall 180-days survival of patients with successful PCI was 40 % compared to 7.7 % with no or failed immediate PCI (log-rank p < 0.001). After adjustment for confounders, successful PCI was associated with a lower risk of death (HR 0.47, CI 0.24-0.93, p = 0.031). Likewise, ECPR was associated with a lower risk of death (HR 0.11, CI 0.05-0.24, p< 0.001). Conclusion: In this post hoc analysis of the randomized r-OHCA trial, successful immediate PCI as well as ECPR were associated with improved 180-days survival in patients with r-OHCA due to ACS.

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Abstract MP35: The American Heart Association’s Life’s Simple 7 and Mortality by Race and Sex in the U.S.: the REasons for Geographic And Racial Differences in Stroke (REGARDS) Cohort

Circulation ◽

10.1161/circ.129.suppl_1.mp35 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Mary Cushman ◽

Suzanne E Judd ◽

Virginia J Howard ◽

Neil A Zakai ◽

Brett Kissela ◽

...

Keyword(s):

Racial Differences ◽

Mortality Risk ◽

Lower Risk ◽

Population Sample ◽

White Men ◽

The United States ◽

Risk Of Death ◽

Life’S Simple 7 ◽

Life's Simple 7 ◽

The Impact

Background: The Life’s Simple 7 (LSS) metric is being used by AHA to track the cardiovascular health of the United States population and move toward a 2020 impact goal for improvement. Levels of LSS are associated with mortality risk but there are limited data on whether this association differs by race or sex. Hypothesis: There will be sex and race differences in the association of LSS with mortality in the REGARDS cohort study. Methods: We studied 29,692 REGARDS participants; a population sample of black and white men and women aged 45-98 from across the US, enrolled in 2003-7. Extensive baseline risk factor data were measured in participants’ homes. The 7 LSS components (blood pressure, cholesterol, glucose, body-mass index, smoking, physical activity, diet) were each scored in AHA-defined categories of poor (0 points), intermediate (1 point) and ideal (2 points), and were summed to yield scores ranging from poor for all (0) to ideal for all (14). With 6.4 years follow up there were 3709 deaths. Results: The LSS score was normally distributed with mean (SD) of 7.9 (2.0) in whites and 6.9 (2.0) in blacks. The age, region, income and education adjusted hazard ratio (HR) of death for a 1-unit worse LSS score, stratified by race and sex, are shown in the table. Race and sex interactions were tested individually in separate models. While better scores for LSS were strongly associated with lower mortality, associations differed by race and sex, being weaker in blacks than whites and in men than women. Conclusion: There were large associations of LSS with mortality risk in the REGARDS national sample; 1 point difference in score, corresponding to movement from poor to intermediate or intermediate to ideal for 1 of the 7 factors, was associated with a 16% lower risk of death in white women, 14% lower risk in white men or black women, but only an 11% lower risk in black men. Observed differences in the association of LSS with mortality by race and sex should be considered in efforts to gauge the impact of LSS interventions on health disparities.

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