Symptomatic presentation of cervical cancer in emergency departments in California

Abstract Purpose Through screening and HPV vaccination, cervical cancer can mostly be prevented or detected very early, before symptoms develop. However, cervical cancer persists, and many women are diagnosed at advanced stages. Little is known about the degree to which U.S. women may begin their diagnostic workup for cervical cancer in Emergency Departments (ED). We sought to quantify the proportion of women presenting symptomatically in the ED prior to their diagnosis with cervical cancer and to describe their characteristics and outcomes. Methods We identified women diagnosed from 2006 to 2017 with cervical cancer in the California Cancer Registry. We linked this cohort to statewide ED discharge records to determine ED use and symptoms present at the encounter. Multivariable logistic regression models examined associations with ED use and multivariable Cox proportional hazards regression models examined associations with survival. Results Of the more than 16,000 women with cervical cancer in the study cohort, 28% presented symptomatically in the ED prior to diagnosis. Those presenting symptomatically were more likely to have public (odds ratio [OR] 1.16; 95% confidence interval [CI] 1.06–1.27) or no insurance (OR 4.81; CI 4.06–5.71) (vs. private), low socioeconomic status (SES) (OR 1.76; CI 1.52–2.04), late-stage disease (OR 5.29; CI 4.70–5.96), and had a 37% increased risk of death (CI 1.28–1.46). Conclusion Nearly a third of women with cervical cancer presented symptomatically, outside of a primary care setting, suggesting that many women, especially those with low SES, may not be benefiting from screening or healthcare following abnormal results.

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Accelerated aging and mortality in long-term survivors of childhood cancer: A report from the St. Jude Lifetime Cohort (SJLIFE).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10045 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10045-10045

Author(s):

AnnaLynn M. Williams ◽

Jeanne S. Mandelblatt ◽

Mingjuan Wang ◽

Kirsten K. Ness ◽

Gregory T. Armstrong ◽

...

Keyword(s):

Childhood Cancer ◽

Proportional Hazards ◽

Accelerated Aging ◽

Cox Proportional Hazards ◽

Premature Aging ◽

Self Report ◽

Deficit Accumulation ◽

Risk Of Death ◽

Increased Risk ◽

Survivors Of Childhood Cancer

10045 Background: Survivors of childhood cancer have functional limitations and health-related morbidity consistent with an accelerated aging phenotype. We characterized aging using a Deficit Accumulation Index (DAI) which examines the accumulation of multiple aging-related deficits readily available from medical records and self-report. DAI’s are used as surrogates of biologic aging and are validated to predict mortality in adult cancer patients. Methods: We included childhood cancer survivors (N = 3,758, mean age 30 [SD 8], 22 [9] years post diagnosis, 52% male) and community controls (N = 575, mean age 34 [10] 44% male) who completed clinical assessments and questionnaires and who were followed for mortality through December 31st, 2018 (mean follow-up 6.1 [3.1] years). Using the initial SJLIFE clinical assessment, a DAI score was generated as the proportion of deficits out of 44 items related to aging, including chronic conditions (e.g. hearing loss, hypertension), psychosocial and physical function, and activities of daily living. The total score ranged 0 to 1; scores > 0.20 are robust, while moderate and large clinically meaningful differences are 0.02 and 0.06, respectively. Linear regression compared the DAI in survivors and controls with an age*survivor/control interaction and examined treatment associations in survivors. Cox-proportional hazards models estimated risk of death associated with DAI. All models were adjusted for age, sex, and race. Results: Mean [SD] of DAI was 0.17 [0.11] for survivors and 0.10 [0.08] for controls. 32% of survivors had a DAI above the 90th percentile of the control distribution (p < 0.001). After adjustment for covariates, survivors had a statistically and clinically meaningfully higher DAI score than controls (β = 0.072 95%CI 0.062, 0.081; p < 0.001). When plotted against age, the adjusted DAI at the average age of survivors (30 years) was 0.166 (95% CI 0.160,0.171), which corresponded to 60 years of age in controls, suggesting premature aging of 30 years. The mean difference in DAI between survivors and controls increased with age from 0.06 (95% CI 0.04, 0.07) at age 20 to 0.11 (95% CI 0.08, 0.13) at age 60, consistent with an accelerated aging phenotype (p = 0.014). Cranial radiation, abdominal radiation, cyclophosphamide, platinum agents, neurosurgery, and amputation were each associated with a higher DAI (all p≤0.001). Among survivors, a 0.06 increase in DAI was associated with a 41% increased risk of all-cause mortality (HR 1.41 95%CI 1.32, 1.50; p < 0.001). Conclusions: Survivors of childhood cancer experience significant age acceleration that is associated with an increased risk of mortality; longitudinal analyses are underway to validate these findings. Given the ease of estimating a DAI, this may be a feasible method to quickly identify survivors for novel and tailored interventions that can improve health and prevent premature mortality.

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Abstract 2646: Aortic Arch Plaques and Risk of Vascular Events in Subjects Without Prior Stroke

Circulation ◽

10.1161/circ.118.suppl_18.s_760 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Cesare Russo ◽

Zhezhen Jin ◽

Ralph L Sacco ◽

Shunichi Homma ◽

Tatjana Rundek ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Aortic Arch ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Study Cohort ◽

Vascular Events ◽

Increased Risk ◽

Prior Stroke

BACKGROUND: Aortic arch plaques (AAP) are a risk factor for cardiovascular embolic events. However, the risk of vascular events associated with AAP in the general population is unclear. AIM: To assess whether AAP detected by transesophageal echocardiography (TEE) are associated with an increased risk of vascular events in a stroke-free cohort. METHODS: The study cohort consisted of stroke-free subjects over age 50 from the Aortic Plaques and Risk of Ischemic Stroke (APRIS) study. AAP were assessed by multiplane TEE, and considered large if ≥ 4 mm in thickness. Vascular events including myocardial infarction, ischemic stroke and vascular death were recorded during the follow-up. The association between AAP and outcomes was assessed by univariate and multivariate Cox proportional hazards models. RESULTS: A group of 209 subjects was studied (mean age 67±9 years; 45% women; 14% whites, 30% blacks, 56% Hispanics). AAP of any size were present in 130 subjects (62%); large AAP in 50 (24%). Subjects with AAP were older (69±8 vs. 63±7 years), had higher systolic BP (146±21 vs.139±20 mmHg), were more often white (19% vs. 8%), smokers (20% vs. 9%) and more frequently had a history of coronary artery disease (26% vs. 14%) than those without AAP (all p<0.05). Lipid parameters, prevalence of atrial fibrillation and diabetes mellitus were not significantly different between the two groups. During the follow up (94±29 months) 30 events occurred (13 myocardial infarctions, 11 ischemic strokes, 6 vascular deaths). After adjustment for other risk factors, AAP of any size were not associated with an increased risk of combined vascular events (HR 1.07, 95% CI 0.44 to 2.56). The same result was observed for large AAP (HR 0.94, CI 0.34 to 2.64). Age (HR 1.05, CI 1.01 to 1.10), body mass index (HR 1.08, CI 1.01 to 1.15) and atrial fibrillation (HR 3.52, CI 1.07 to 11.61) showed independent association with vascular events. In a sub-analysis with ischemic stroke as outcome, neither AAP of any size nor large AAP were associated with an increased risk. CONCLUSIONS: In this cohort without prior stroke, the incidental detection of AAP was not associated with an increased risk of future vascular events. Associated co-factors may affect the AAP-related risk of vascular events reported in previous studies.

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Risk of Appendicitis among Children with Different Piped Water Supply: A Nationwide Population-Based Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph15081601 ◽

2018 ◽

Vol 15 (8) ◽

pp. 1601

Author(s):

Hao-Ming Li ◽

Shi-Zuo Liu ◽

Ying-Kai Huang ◽

Yuan-Chih Su ◽

Chia-Hung Kao

Keyword(s):

Water Supply ◽

Proportional Hazards ◽

Population Based ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

Study Cohort ◽

Research Database ◽

Piped Water ◽

Increased Risk

Appendicitis is a common surgical condition for children. However, environmental effects, such as piped water supply, on pediatric appendicitis risk remain unclear. This longitudinal, nationwide, cohort study aimed to compare the risk of appendicitis among children with different levels of piped water supply. Using data from Taiwan Water Resource Agency and National Health Insurance Research Database, we identified 119,128 children born in 1996–2010 from areas of the lowest piped water supply (prevalence 51.21% to 63.06%) as the study cohort; additional 119,128 children of the same period in areas of the highest piped water supply (prevalence 98.97% to 99.63%) were selected as the controls. Both cohorts were propensity-score matched by baseline variables. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of appendicitis in the study cohort compared to the controls by Cox proportional hazards regression. The study cohort had a raised overall incidence rates of appendicitis compared to the control cohort (12.8 vs. 8.7 per 10,000 person-years). After covariate adjustment, the risk of appendicitis was significantly increased in the study cohort (adjusted HR = 1.46, 95% CI: 1.35, 1.58, p < 0.001). Subgroup and sensitivity analyses showed consistent results that children with low piped water supply had a higher risk of appendicitis than those with high piped water supply. This study demonstrated that children with low piped water supply were at an increased risk of appendicitis. Enhancement of piped water availability in areas lacking adequate, secure, and sanitized water supply may protect children against appendicitis.

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Repeat Self-Harm Following Hospital-Presenting Intentional Drug Overdose among Young People—A National Registry Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17176159 ◽

2020 ◽

Vol 17 (17) ◽

pp. 6159

Author(s):

Caroline Daly ◽

Eve Griffin ◽

Elaine McMahon ◽

Paul Corcoran ◽

Roger T. Webb ◽

...

Keyword(s):

Young People ◽

Drug Overdose ◽

Regression Models ◽

Proportional Hazards ◽

Cumulative Risk ◽

National Registry ◽

Cox Proportional Hazards ◽

Young Males ◽

Increased Risk ◽

Self Harm

Background: The incidence of hospital-presenting self-harm peaks among young people, who most often engage in intentional drug overdose (IDO). The risk of self-harm repetition is high among young people and switching methods between self-harm episodes is common. However, little is known about their patterns of repetition and switching following IDO. This study aimed to investigate repeat self-harm and method-switching following hospital-presenting IDO among young people. Methods: Data from the National Self-Harm Registry Ireland on hospital-presenting self-harm by individuals aged 10–24 years during 2009–2018 were examined. Cox proportional hazards regression models with associated hazard ratios (HRs), survival curves and Poisson regression models with risk ratios (RRs), were used to examine risk factors for repetition and method-switching. Results: During 2009–2018, 16,800 young people presented following IDO. Within 12 months, 2136 young people repeated self-harm. Factors associated with repetition included being male (HR = 1.13, 95% CI: 1.03–1.24), aged 10–17 years (HR = 1.29, 95% CI: 1.18–1.41), consuming ≥ 50 tablets (HR = 1.27, 95% CI: 1.07–1.49) and taking benzodiazepines (HR = 1.67, 95% CI: 1.40–1.98) or antidepressants (HR = 1.36, 95% CI: 1.18–1.56). The cumulative risk for switching method was 2.4% (95% CI: 2.2–2.7). Method-switching was most likely to occur for males (RR = 1.36; 95% CI: 1.09–1.69) and for those who took illegal drugs (RR = 1.63; 95% CI: 1.19–2.25). Conclusion: Young males are at increased risk of repeat self-harm and method-switching following IDO and the type and quantity of drugs taken are further indicators of risk. Interventions targeting IDO among young people are needed that ensure that mental health assessments are undertaken and which address access to drugs.

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Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis

Viruses ◽

10.3390/v10110658 ◽

2018 ◽

Vol 10 (11) ◽

pp. 658 ◽

Cited By ~ 2

Author(s):

Paul Blair ◽

Maryam Keshtkar-Jahromi ◽

Kevin Psoter ◽

Ronald Reisler ◽

Travis Warren ◽

...

Keyword(s):

Proportional Hazards ◽

Clinical Laboratory ◽

Cynomolgus Macaque ◽

The United States ◽

Cox Proportional Hazards ◽

Marburg Virus ◽

Time To Death ◽

Risk Of Death ◽

Published Evidence ◽

Increased Risk

Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the higher virulence of MARV/Ang. In this retrospective study, we used data pooled from eight separate studies in nonhuman primates experimentally exposed with either 1000 pfu intramuscular (IM) MARV/Ang or MARV/MtE-Mus between 2012 and 2017 at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Multivariable Cox proportional hazards regression was used to evaluate the association of variant type with time to death, the development of anorexia, rash, viremia, and 10 select clinical laboratory values. A total of 47 cynomolgus monkeys were included, of which 18 were exposed to MARV/Ang in three separate studies and 29 to MARV/MtE-Mus in five studies. Following universally fatal Marburg virus exposure, compared to MARV/MtE-Mus, MARV/Ang was associated with an increased risk of death (HR = 22.10; 95% CI: 7.08, 68.93), rash (HR = 5.87; 95% CI: 2.76, 12.51) and loss of appetite (HR = 35.10; 95% CI: 7.60, 162.18). Our data demonstrate an increased virulence of MARV/Ang compared to MARV/MtE-Mus variant in the 1000 pfu IM cynomolgus macaque model.

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Doxorubicin, cardiac risk factors and cardiac toxicity in elderly patients with diffuse b-cell non-Hodgkin's lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.9050 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 9050-9050

Author(s):

D. L. Hershman ◽

A. Eisenberger ◽

J. Wang ◽

J. Jacobson ◽

V. Grann ◽

...

Keyword(s):

Elderly Patients ◽

B Cell ◽

Regression Models ◽

Proportional Hazards ◽

Cardiac Toxicity ◽

B Cell Lymphoma ◽

Female Gender ◽

Cox Proportional Hazards ◽

Black Race ◽

Increased Risk

9050 Background: Anthracyclines are known to cause acute and chronic cardiotoxicity. In a population-based sample of elderly patients with diffuse large B-cell lymphoma (DLBCL), we studied the cardiac effects of doxorubicin (DOX)-containing regimens and of pre-existing diabetes (DM), hypertension (HTN), and heart disease (HD). Methods: Patients aged =65 years diagnosed with DLBCL 1/1/1992–12/31/2000 in the SEER/Medicare database were grouped by treatment: no chemotherapy, doxorubicin-based chemotherapy, or other chemotherapy. We developed multivariable logistic regression models of the associations of DOX-based chemotherapy with demographic and clinical variables and pre-diagnosis DM, HTN, and HD. We then developed Cox proportional hazards regression models of the association between treatment and subsequent congestive heart failure (CHF) taking the predictors of treatment into account. Results: Of 6,413 patients with DLBCL, 2,536 (39%) received doxorubicin-based chemotherapy. DOX use was associated with later year of diagnosis, female gender, younger age, and being married. Black race (HR 0.50, 95% CI 0.33–0.75), comorbidities, preexisting CHF, HD, and DM (HR 0.73, 95% CI 0.62–0.86) were associated with decreased DOX use. The post-treatment HR for CHF following DOX treatment vs. no chemotherapy was 1.39 (95% CI 1.15–1.67); CHF risk increased with duration of DOX use. It was also associated with increasing age, comorbidities, black race, DM, HTN, and HD. There was a significant interaction between race and DOX (P=0.01); For black patients treated with DOX the HR for CHF was 3.4, as compared to a HR of 1.3 for white patients. Conclusions: Among patients with DLBCL, black race, CRFs and pre-existing HD are all associated with both a reduced likelihood of receiving anthracyclines, and an increased risk of CHF. We have previously found a powerful effect of DOX on survival in this patient population; thus, for most patients, the benefits of treatment would appear to outweigh the risks of cardiac toxicity. However, as the number of long-term survivors grows, the need for research on the side effects of treatment, on host factors that may increase the risk of adverse effects, and on ways to minimize such risks will also grow. No significant financial relationships to disclose.

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Brain metastases in breast cancer: Different survival by biological subtype and Ki67 expression

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.1069 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 1069-1069

Author(s):

D. Sartori ◽

M. Bari ◽

G. L. Pappagallo ◽

F. Rosetti ◽

S. Olsen ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Proportional Hazards ◽

Fold Increase ◽

Cox Proportional Hazards ◽

Her2 Overexpression ◽

Cns Metastases ◽

Risk Of Death ◽

Pathologic Features ◽

Increased Risk

1069 Background: Ten to 15% of patients (pts) with breast cancer will be diagnosed with central nervous system (CNS) metastases, and autopsy series suggest that up to 30% of pts have evidence of CNS disease at the time of death. The idenfication of factors that may predispose to CNS metastasis may help lead to earlier detection and possibly to improvement in disease management. Methods: Breast cancer pts with CNS metastases were identified within a database of 1300 breast cancer diganoses from 1995 to 2007 at the Department of Oncology, Azienda ULSS 13 VE. Pathologic features of tumor samples were examined using standard immunohistochemical assays. Results: Fifty-one pts with CNS metastases were identified. Median age at primary breast cancer diagnosis was 49 years (range, 28–78); median time to CNS metastases was 45 months (range, 3–244). HER2 overexpression was found in tumors from 25 pts (49.0%); 23 pts had tumors lacking overexpression of HER2, estrogen receptors (ER), and progesterone receptors (PgR) (ie, “triple negative” disease). Overexpression of p53 (at least 20% tumor cells positive), Ki67 (at least 20%), and BCL2 (at least 30%) were detected in tumors from 16 pts (31.4%), 32 pts (62.7%), and 14 pts (27.5%), respectively. Median survival from CNS involvement was 3.67 months (95% CI 2.05–5.28), with 24.4% and 15.3% of patients estimated to be alive at 12 and 24 months, respectively (Kaplan-Meier product limit method). A Cox proportional hazards analysis found that Ki67 overexpression was the only factor independently associated with a significantly increased risk of death (2.7-fold increase, p=0.028), while triple negative status was associated with a 1.8-fold increase in the risk of death (P=0.08) (Table). Conclusions: In our series of breast cancer pts with CNS metastases, nearly all had either HER2 overexpression or triple-negative disease. Pts whose tumors had higher proliferative indices, assessed by Ki67, had the poorest prognosis. [Table: see text] [Table: see text]

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Increased risk of prostate cancer following sexually transmitted infection in an Asian population

Epidemiology and Infection ◽

10.1017/s0950268813000459 ◽

2013 ◽

Vol 141 (12) ◽

pp. 2663-2670 ◽

Cited By ~ 6

Author(s):

S. D. CHUNG ◽

Y. K. LIN ◽

C. C. HUANG ◽

H. C. LIN

Keyword(s):

Prostate Cancer ◽

Proportional Hazards ◽

Asian Population ◽

Population Based ◽

Cox Proportional Hazards ◽

Study Cohort ◽

Transmitted Infection ◽

Sexually Transmitted ◽

Increased Risk ◽

History Of

SUMMARYThe relationship between sexually transmitted infections (STIs) and prostate cancer (PC) remains inconclusive. Moreover, all such studies to date have been conducted in Western populations. This study aimed to investigate the risk of PC following STI using a population-based matched-cohort design in Taiwan. The study cohort comprised 1055 patients with STIs, and 10 550 randomly selected subjects were used as a comparison cohort. Cox proportional hazards regression analysis revealed that the hazard ratio for PC during the 5-year follow-up period for patients with a STI was 1·95 (95% confidence interval 1·18–3·23), that of comparison subjects after adjusting for urbanization level, geographical region, monthly income, hypertension, diabetes, hyperlipidaemia, obesity, chronic prostatitis, history of vasectomy, tobacco use disorder, and alcohol abuse. We concluded that the risk of PC was higher for men who were diagnosed with a STI in an Asian population.

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Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study

BMJ Open ◽

10.1136/bmjopen-2021-050051 ◽

2021 ◽

Vol 11 (12) ◽

pp. e050051

Author(s):

Arthur W Wallace ◽

Piera M Cirillo ◽

James C Ryan ◽

Nickilou Y Krigbaum ◽

Anusha Badathala ◽

...

Keyword(s):

Propensity Score ◽

Observational Study ◽

Ace Inhibitors ◽

Proportional Hazards ◽

Therapeutic Potential ◽

Angiotensin Receptor Blockers ◽

Cox Proportional Hazards ◽

Risk Of Death ◽

Hospitalised Patients ◽

Increased Risk

ObjectivesSARS-CoV-2 enters cells using the ACE2 receptor. Medications that affect ACE2 expression or function such as angiotensin receptor blockers (ARBs) and ACE inhibitors (ACE-I) and metformin have the potential to counter the dysregulation of ACE2 by the virus and protect against viral injury. Here, we describe COVID-19 survival associated with ACE-I, ARB and metformin use.DesignThis is a hospital-based observational study of patients with COVID-19 infection using logistic regression with correction for pre-existing conditions and propensity score weighted Cox proportional hazards models to estimate associations between medication use and mortality.SettingMedical record data from the US Veterans Affairs (VA) were used to identify patients with a reverse transcription PCR diagnosis of COVID-19 infection, to classify patterns of ACE inhibitors (ACE-I), ARB, beta blockers, metformin, famotidine and remdesivir use, and, to capture mortality.Participants9532 hospitalised patients with COVID-19 infection followed for 60 days were analysed.Outcome measureDeath from any cause within 60 days of COVID-19 diagnosis was examined.ResultsDiscontinuation of ACE-I was associated with increased risk of death (OR: 1.4; 95% CI 1.2–1.7). Initiating (OR: 0.3; 95% CI 0.2–0.5) or continuous (OR: 0.6; 95% CI 0.5–0.7) ACE-I was associated with reduced risk of death. ARB and metformin associations were similar in direction and magnitude and also statistically significant. Results were unchanged when accounting for pre-existing morbidity and propensity score adjustment.ConclusionsRecent randomised clinical trials support the safety of continuing ACE-I and ARB treatment in patients with COVID-19 where indicated. Our study extends these findings to suggest a possible COVID-19 survival benefit for continuing or initiating ACE-I, ARB and metformin medications. Randomised trials are appropriate to confirm or refute the therapeutic potential for ACE-I, ARBs and metformin.

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Early hemoglobin decline and survival prognosis in epoetin alfa studies

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.9625 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 9625-9625

Author(s):

J. A. Berlin ◽

P. J. Bowers ◽

S. Rao ◽

S. Sun ◽

K. Liu ◽

...

Keyword(s):

Proportional Hazards ◽

Cox Proportional Hazards ◽

Time Dependent ◽

Epoetin Alfa ◽

Survival Prognosis ◽

Proportional Hazards Models ◽

Risk Of Death ◽

Cox Proportional Hazards Models ◽

Level Data ◽

Increased Risk

9625 Background: When cancer patients (pts) with chemotherapy-induced anemia (CIA) respond to erythropoietic-stimulating agents (ESA), hemoglobin (Hb) typically increases within 4–8 weeks. This exploratory analysis examined whether mortality differs depending on Hb response after 4 or 8 weeks of epoetin alfa (EPO) treatment or depending on transfusion. Methods: Pt-level data were analyzed from 31 randomized studies (7,215 pts) of epoetin alfa vs non-EPO (15 studies) or placebo (16 studies) in pts with CIA. A landmark analysis was used; Hb change was set at a specific time (4 and 8 weeks) and subsequent survival was examined separately for EPO and placebo. Pts were categorized as “Hb increased” (>0.5 g/dL), “Hb decreased” (>0.5 g/dL), or “Hb stable” (within ±0.5 g/dL) compared to baseline. Hb stable was compared to other Hb change categories with Cox proportional hazards models, stratified by study and adjusted for potential confounders. Results: The hazard ratio (HR) for Hb decreased versus Hb stable at 4 weeks was 1.44 for EPO (95% CI: 1.04, 1.99), indicating worse survival for pts with a decline in Hb. This association was weaker for placebo (HR: 1.12; 95% CI: 0.74, 1.67). Increased risk with declining Hb in EPO-treated pts was most pronounced in studies that maintained Hb ≥12 g/dL or treated pts for >12–16 weeks (1,876 pts). Patterns were similar using the 8-week landmark. In both EPO-treated and placebo pts, transfusion increased the rate of on-study death ∼3.5 fold (treating transfusion as a time-dependent variable). Conclusions: These exploratory findings suggest that both decreased Hb after 4 or 8 weeks of EPO treatment and transfusion are associated with increased risk of death. In spite of adjustment for other prognostic factors, it is likely that this association reflects poorer underlying prognosis of pts whose Hb fails to respond. ESAs should be discontinued in the absence of a Hb response. [Table: see text]

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