scholarly journals Evaluating signals generated in a large-scale sequence symmetry analyses: macrolides and heart failure; and NSAIDs and pneumonia

2020 ◽  
Author(s):  
SJ Sinnott ◽  
KJ Lin ◽  
S Wang ◽  
J Hallas ◽  
R Desai ◽  
...  
Keyword(s):  
Heart Failure ◽  
Propensity Score ◽  
Large Scale ◽  
Proportional Hazards ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
Oral Nsaid ◽  
Hazard Ratios ◽  
Amoxicillin Clavulanate ◽  
Topical Diclofenac

AbstractObjectiveUsing US claims data and the most up-to-date pharmacoepidemiological study design tools we aimed to investigate two safety signals for (1) macrolides and heart failure; and (2) non-steroidal anti-inflammatory drugs (NSAIDs) and pneumonia generated from a large-scale screening analysis using a self-controlled sequence symmetry design in Danish data.MethodsWe used IBM Marketscan data to conduct two new-user, active-comparator cohort studies. In the macrolides example, the exposure was clarithromycin or azithromycin and the comparator was amoxicillin/clavulanate, in patients with sinusitis. In the NSAIDs example, the exposure was oral NSAIDs and the comparator was topical diclofenac, in patients with osteoarthritis. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) to adjust for approximately 50 investigator-specified confounders in a propensity score (PS) matched analysis. In a secondary analysis, we used high-dimensional PS (hd-PS) to adjust for 200 additional proxy confounders.ResultsWe had 1,012,364 propensity score matched patients exposed to clarithromycin or azithromycin versus amoxicillin/clavulanate. With 162 outcomes among clarithromycin or azithromycin exposed patients and 134 among amoxicillin/clavulanate, the HR for overall heart failure was 1.14 (95% CI 0.90 – 1.43). In the NSAIDs example, we included 94,490 patients after propensity score matching. With 794 pneumonia outcomes among oral NSAID patients and 700 among topical diclofenac, we found HR 0.98 (95% CI 0.89 – 1.09). Some upward bias was suspected as larger HRs were observed in the days immediately following exposure for both the macrolides and NSAIDs examples. We found similar results in the hd-PS matched analyses for both examples.ConclusionOur findings for NSAIDs and pneumonia suggest the original signal may have been due to protopathic or detection bias. Our analyses for macrolides and heart failure with short-term follow-up also suggest bias, although we encourage further research.

P1666Do beta-blockers increase the risk for hospitalizations in heart failure with preserved ejection fraction? A secondary analysis of beta-blocker use in the TOPCAT trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D N Silverman ◽  
T B Plante ◽  
M I Infeld ◽  
S P Juraschek ◽  
G Dougherty ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Beta Blocker ◽  
Proportional Hazards ◽  
Beta Blockers ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Reduced Ejection Fraction

Abstract Background The use of beta-blockers for treatment of heart failure (HF) with a reduced ejection fraction (EF) is unequivocally beneficial, but their role in the treatment of preserved EF (HFpEF) remains unclear. Purpose In a contemporary HFpEF cohort, we sought to assess the association of HF hospitalizations and the use of beta-blockers in patients with an EF above and below 50%. Methods The TOPCAT trial tested spironolactone vs. placebo among patients with HFpEF, including some with mild reductions in EF between 45–50%. The primary outcome was a composite of cardiovascular (CV) mortality, aborted cardiac arrest, or HF hospitalizations. Medication use, including beta-blockers, was reported at each visit and hospitalization. In the 1,761 participants from the Americas, we compared the association of beta-blocker use (vs. no use) and HF hospitalization or CV mortality using Cox proportional hazards models adjusted for baseline demographics, history of myocardial infarction, atrial fibrillation, chronic obstructive pulmonary disease, asthma, and hypertension. The analyses were repeated in the EF strata ≥50% and <50%. Results Among patients included in the current analysis (mean age 72 years, 50% female, 78% white), 1,496/1,761 (85%) received beta-blockers and 1,566/1,761 (89%) had an EF ≥50%. HF hospitalizations and CV mortality occurred in 399/1,761 (23%) and 223/1,761 (13%) of participants, respectively. Beta-blocker use was associated with an increase in risk of HF hospitalization among patients with preserved EF ≥50% [HR 1.56, (95% CI 1.09–2.24), p=0.01] and was associated with a reduction in risk of hospitalization in patients with an EF <50% [HR 0.42, (95% CI 0.18- 0.99), p<0.05]. We found a significant interaction for EF threshold and beta-blocker use on incident HF hospitalizations (p=0.01). There were no differences in CV mortality. Figure 1. Kaplan Meier incidence plots Conclusions Beta-blocker use was associated with an increase in HF hospitalizations in patients with HFpEF (EF≥50%) but did not affect CV mortality. Further research is needed to confirm these findings and elucidate causality.

scholarly journals Routinely reported ejection fraction and mortality in clinical practice: where does the nadir of risk lie?

2019 ◽  
Author(s):  
Gregory J Wehner ◽  
Linyuan Jing ◽  
Christopher M Haggerty ◽  
Jonathan D Suever ◽  
Joseph B Leader ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Proportional Hazards ◽  
Patient Characteristics ◽  
Left Ventricular ◽  
Cox Proportional Hazards ◽  
Left Ventricular Ejection ◽  
Validation Dataset ◽  
Ventricular Ejection Fraction ◽  
Hazard Ratios

Abstract Aims We investigated the relationship between clinically assessed left ventricular ejection fraction (LVEF) and survival in a large, heterogeneous clinical cohort. Methods and results Physician-reported LVEF on 403 977 echocardiograms from 203 135 patients were linked to all-cause mortality using electronic health records (1998–2018) from US regional healthcare system. Cox proportional hazards regression was used for analyses while adjusting for many patient characteristics including age, sex, and relevant comorbidities. A dataset including 45 531 echocardiograms and 35 976 patients from New Zealand was used to provide independent validation of analyses. During follow-up of the US cohort, 46 258 (23%) patients who had undergone 108 578 (27%) echocardiograms died. Overall, adjusted hazard ratios (HR) for mortality showed a u-shaped relationship for LVEF with a nadir of risk at an LVEF of 60–65%, a HR of 1.71 [95% confidence interval (CI) 1.64–1.77] when ≥70% and a HR of 1.73 (95% CI 1.66–1.80) at LVEF of 35–40%. Similar relationships with a nadir at 60–65% were observed in the validation dataset as well as for each age group and both sexes. The results were similar after further adjustments for conditions associated with an elevated LVEF, including mitral regurgitation, increased wall thickness, and anaemia and when restricted to patients reported to have heart failure at the time of the echocardiogram. Conclusion Deviation of LVEF from 60% to 65% is associated with poorer survival regardless of age, sex, or other relevant comorbidities such as heart failure. These results may herald the recognition of a new phenotype characterized by supra-normal LVEF.

scholarly journals Plasma Volume and Renal Function Predict Six-Month Survival after Hospitalization for Acute Decompensated Heart Failure

2017 ◽  
Vol 8 (1) ◽  
pp. 61-70 ◽  
Author(s):  
Kenneth C. Bilchick ◽  
Nathaniel Chishinga ◽  
Alex M. Parker ◽  
David X. Zhuo ◽  
Mitchell H. Rosner ◽  
...  
Keyword(s):  
Heart Failure ◽  
Plasma Volume ◽  
Proportional Hazards ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure ◽  
Evaluation Study ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Patients With Heart Failure

Background: Plasma volume (PV) is contracted in stable patients with heart failure (HF) due to decongestion strategies. On the other hand, increased PV can adversely affect the trajectory of HF. We therefore examined the effects of increased percentage change in PV (%ΔPV), blood urea nitrogen (BUN), and %ΔPV stratified by BUN and glomerular filtration rate (GFR) on survival after discharge in patients hospitalized for acute decompensated HF (ADHF). Methods: We used the Strauss-Davis-Rosenbaum formula to calculate the %ΔPV between baseline and hospital discharge in a cohort from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial (ESCAPE). Kaplan-Meier curves were constructed for survival over 6 months. Cox proportional hazards regression was used to obtain adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between survival after discharge and %ΔPV, BUN, and %ΔPV stratified by BUN and GFR. Results: Of the 324 patients included in our study (age 56.1 ± 13.6 years, 26.5% female), those with increased or no %ΔPV at discharge were less likely to survive at 6 months compared with those having reduced %ΔPV (log rank, p = 0.0093). Increased %ΔPV (HR 1.08 per 10% increase; 95% CI: 1.02-1.14) and increased BUN at discharge (HR 1.02 per mg/dL; 95% CI: 1.01-1.03) were independently associated with worse survival. Decreasing %ΔPV had a greater association with improved survival in patients with discharge BUN <31 mg/dL (p = 0.02) and discharge GFR >40 mL/min/1.73 m2 (p = 0.047). Conclusions: Increased %ΔPV and BUN at discharge predicted worse 6-month survival in patients with ADHF. Decreased %ΔPV with low BUN or high GFR at discharge was associated with improved survival.

scholarly journals Racial Disparities in Delivery Gestational Age among Twin Pregnancies

2017 ◽  
Vol 34 (11) ◽  
pp. 1065-1071
Author(s):  
Catherine Vladutiu ◽  
Tracy Manuck ◽  
Jacqueline Grant
Keyword(s):  
Gestational Age ◽  
Proportional Hazards ◽  
Secondary Analysis ◽  
Neonatal Morbidity ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Hydroxyprogesterone Caproate

Objective This study aims to estimate the association between maternal race and delivery gestational age among women with twin gestations. Study Design Secondary analysis of a prospective, randomized control trial of 17-α hydroxyprogesterone caproate versus placebo for preterm birth (PTB) prevention in twin gestations. Non-Hispanic (NH) black and whites were included. Demographic and antenatal characteristics were compared. The primary outcome was delivery gestational age. Secondary outcomes included a composite of major neonatal morbidity. Kaplan–Meier curves estimated survival probabilities for delivery gestational age by race. Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI). Results A total of 535 women with twin gestations were included; 150 were NH black. NH blacks delivered earlier than NH whites (33.6 ± 4.8 weeks vs. 35.1 ± 3.5 weeks, p < 0.001). Differences in delivery gestational age between NH blacks and whites were consistent across gestation. In adjusted analyses, NH black race (HR: 1.24, 95% CI: 1.02–1.51), prior PTB (HR: 1.59, 95% CI: 1.15–2.19), and cerclage (HR: 3.90, 95% CI: 2.00–7.60) were associated with an increased risk of earlier delivery. Major neonatal morbidity was higher for NH blacks compared with NH whites (12.7 vs. 7.0%, p = 0.036). Conclusion NH blacks with twin gestations have an increased risk of early delivery and neonatal morbidity compared with NH whites.

scholarly journals Large‐Scale Plasma Protein Profiling of Incident Myocardial Infarction, Ischemic Stroke, and Heart Failure

2021 ◽  
Author(s):  
Lars Lind ◽  
Daniela Zanetti ◽  
Martin Ingelsson ◽  
Stefan Gustafsson ◽  
Johan Ärnlöv ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Ischemic Stroke ◽  
Large Scale ◽  
Proportional Hazards ◽  
Kidney Injury ◽  
Cox Proportional Hazards ◽  
Protein Profiling ◽  
Risk Markers ◽  
Cox Proportional Hazards Models

Background We recently reported a link between plasma levels of 2 of 84 cardiovascular disease (CVD)–related proteins and the 3 major CVDs, myocardial infarction, ischemic stroke, and heart failure. The present study investigated whether measurement of almost 10 times the number of proteins could lead to discovery of additional risk markers for CVD. Methods and Results We measured 742 proteins using the proximity extension assay in 826 male participants of ULSAM (Uppsala Longitudinal Study of Adult Men) who were free from CVD at the age of 70 years. Cox proportional hazards models were adjusted for age only, as well as all traditional risk factors. During a 12.5‐year median follow‐up (maximal, 22.0 years), 283 incident CVDs occurred. Forty‐one proteins were significantly (false discovery rate <0.05) related to the combined end point of incident CVD, with N‐terminal pro–brain natriuretic peptide as the top finding, while 53 proteins were related to incident myocardial infarction. A total of 13 and 16 proteins were significantly related to incident ischemic stroke and heart failure, respectively. Growth differentiation factor 15, 4‐disulfide core domain protein 2, and kidney injury molecule were related to all of the 3 major CVD outcomes. A lasso selection of 11 proteins improved discrimination of incident CVD by 5.0% ( P =0.0038). Conclusions Large‐scale proteomics seem useful for the discovery of new risk markers for CVD and to improve risk prediction in an elderly population of men. Further studies are needed to replicate the findings in independent samples of both men and women of different ages.

scholarly journals Goal‐Striving Stress and Incident Cardiovascular Disease in Blacks: The Jackson Heart Study

2020 ◽  
Vol 9 (9) ◽  
Author(s):  
LáShauntá M. Glover ◽  
Loretta R. Cain‐Shields ◽  
Tanya M. Spruill ◽  
Emily C. O'Brien ◽  
Sharrelle Barber ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Jackson Heart Study ◽  
Goal Striving ◽  
Hazard Ratios ◽  
Heart Study ◽  
Increased Risk ◽  
Unit Increase

Background Goal‐striving stress (GSS), the stress from striving for goals, is associated with poor health. Less is known about its association with cardiovascular disease (CVD). Methods and Results We used data from the JHS (Jackson Heart Study), a study of CVD among blacks (21–95 years old) from 2000 to 2015. Participants free of CVD at baseline (2000–2004) were included in this analysis (n=4648). GSS was examined in categories (low, moderate, high) and in SD units. Incident CVD was defined as fatal or nonfatal stroke, coronary heart disease (CHD), and/or heart failure. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident CVD by levels of GSS, adjusting for demographics, socioeconomic status, health behaviors, risk factors, and perceived stress. The distribution of GSS categories was as follows: 40.77% low, 33.97% moderate, and 25.26% high. Over an average of 12 years, there were 140 incident stroke events, 164 CHD events, and 194 heart failure events. After full adjustment, high (versus low) GSS was associated with a lower risk of stroke (HR, 0.38; 95% CI, 0.17–0.83) and a higher risk of CHD (HR, 1.91; 95% CI, 1.10–3.33) among women. A 1‐standard deviation unit increase in GSS was associated with a 31% increased risk of CHD (HR, 1.31; 95% CI, 1.10–1.56) among women. Conclusions Higher GSS may be a risk factor for developing CHD among women; however, it appears to be protective of stroke among women. These analyses should be replicated in other samples of black individuals.

scholarly journals Predictors of hospitalizations for heart failure decompensation in patients with comorbid occupational chronic obstructive pulmonary disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L.A Shpagina ◽  
O.S Kotova ◽  
I.S Shpagin ◽  
G.V Kuznetsova ◽  
N.V Kamneva ◽  
...  
Keyword(s):  
Heart Failure ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Chronic Obstructive ◽  
Length Of Service ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Patients With Heart Failure ◽  
Occupational Copd ◽  
Heart Failure Decompensation

Abstract Background Heart failure decompensation requiring hospitalization is an important event, associated with mortality and investigating its predictors is topical problem. Chronic obstructive pulmonary disease (COPD) is a common comorbidity for heart failure. Both conditions share common molecular mechanisms such as systemic inflammation. COPD is heterogeneous and subpopulations with different inflammation patterns may interact with heart failure in different manner. Airway inflammation in occupational COPD may differs from COPD in tobacco smokers. Additionally cardiotoxicity of industrial chemicals influence heart failure features. Despite this biological plausibility, heart failure and occupational COPD comorbidity is not studied enough. Purpose To reveal predictors of hospitalizations for heart failure decompensation in patients with heart failure and occupational COPD comorbidity. Methods Occupational COPD patients (n=115) were investigated in a prospective cohort observational study. Comparison group – 115 tobacco smokers with COPD. Control group – 115 healthy persons. Controls were selected by propensity score matching, covariates were COPD duration, age and gender. Then COPD groups were stratified according to heart failure. Working conditions, echocardiography, spirometry, pulsoxymetry, 6-mitute walking test were done. Molecular markers of tissue damage – chemokine ligand 18 (CCL 18), lactate dehydrogenase, cardiac troponin T, N-terminal pro-B-type natriuretic peptide (NT pro-BNP), protein S100 beta, von Willebrand factor were measured in serum by ELISA. Follow up after initial assessment was 12 month. Predictors were determined by Cox proportional hazards regression with ROC analysis. Results Heart failure rate in occupational COPD patients were higher – 54.8% versus 36.5% in tobacco smokers with COPD, p&lt;0.05. Heart failure with preserved ejection fraction was predominant – 40.9%. Prevalence of biventricular heart failure was 38.3%, isolated right heart failure – 13%, left heart failure – 2.6%. Cumulative hospitalization rate in occupational COPD with heart failure group was higher than in comparison group, 17.5% and 9.5% respectively, p=0.01. In Cox proportional hazards regression model predictors of hospitalizations for heart failure decompensation during 12 months in this group were length of service (HR 1.22, 95% CI: 1.03–2.5), aromatic hydrocarbons concentration at workplaces air (HR 1.4, 95% CI: 1.15–1.96), serum protein S100 beta (HR 1.10, 95% CI: 1.02–1.87), SaO2 (HR 1.2, 95% CI: 1.06–2.13). Area under the ROC curve was 0.82. Conclusion Length of service, aromatic hydrocarbons concentration at workplaces air, serum protein S100 beta, SaO2 are considered to be independent risk factors of heart failure decompensation required hospitalization in patients with heart failure and occupational COPD comorbidity. Funding Acknowledgement Type of funding source: None

scholarly journals Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

2021 ◽  
Vol 10 (7) ◽  
pp. 1514
Author(s):  
Hilde Espnes ◽  
Jocasta Ball ◽  
Maja-Lisa Løchen ◽  
Tom Wilsgaard ◽  
Inger Njølstad ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Pressure Management ◽  
Reference Models ◽  
Proportional Hazards Regression ◽  
Hazard Ratios ◽  
Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

scholarly journals Changes in Metabolic Syndrome Status and Breast Cancer Risk: A Nationwide Cohort Study

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1177
Author(s):  
In Young Choi ◽  
Sohyun Chun ◽  
Dong Wook Shin ◽  
Kyungdo Han ◽  
Keun Hye Jeon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metabolic Syndrome ◽  
Proportional Hazards ◽  
Screening Program ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Health Screening Program ◽  
Design And Methods

Objective: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. Research Design and Methods: We enrolled 930,055 postmenopausal women aged 40–74 years who participated in a biennial National Health Screening Program in 2009–2010 and 2011–2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. Results: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06–1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26–1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04–1.19) in the transition to MetS group, 1.05 (0.96–1.14) in the transition to non-MetS group, and 1.18 (1.12–1.25) in the sustained MetS group. Conclusions: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC.

The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Significant Difference ◽  
The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

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