scholarly journals Erythropoiesis-Stimulating Agents in Elderly Patients with Anemia of Unknown Etiology: Treatment Response and Cardiovascular Outcomes

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1267-1267
Author(s):  
Zachary Gowanlock ◽  
Swetha Sriram ◽  
Alison Martin ◽  
Anargyros Xenocostas ◽  
Alejandro Lazo-Langner

Abstract Background: Anemia of unknown etiology (AUE) is a common category of anemia in the elderly where investigations cannot identify a specific cause. We have previously shown that AUE patients exhibit lower erythropoietin (EPO) levels which may be associated with either decreased EPO production or a blunted EPO response to anemia. Erythropoiesis-stimulating agents (ESAs) mimic the effect of endogenous EPO and may play a role in treating AUE. In this study, we investigated the response to ESA treatment in patients with AUE compared to other causes of anemia. We also examined the effect of ESAs on cardiovascular outcomes in our cohort. To our knowledge, no previous study has specifically assessed ESAs in AUE. Patients and methods: We conducted a retrospective cohort study including all consecutive hematology patients referred to our centre and who had EPO levels determined between 2005 and 2013. We included patients 60 years or older who met the World Health Organization criteria for anemia (hemoglobin [Hb] <130 g/L in men, <120 g/L in women) excluding patients with insufficient electronic medical records. The cohort was subdivided into a group treated with ESAs and an untreated group. Three reviewers independently adjudicated each patient's anemia to one of four diagnostic groups: chronic kidney disease (CKD), myelodysplastic syndrome (MDS), AUE, or other miscellaneous etiologies. The etiology reported by at least two of the three reviewers was used in the analysis, with differences resolved by consensus. Inter-observer agreement was assessed using Fleiss' Kappa statistic. Treatment response was defined by at least a 15 g/L increase in the Hb level from baseline, or a decrease of at least 4 transfusions over 8 weeks, compared to pretreatment. We performed logistic regression to measure the association between the anemia etiology and treatment response while controlling for the following potential confounders: sex, age, weight, Charlson's comorbidity index, Hb, EPO level, estimated glomerular filtration rate (eGFR), and the presence of additional cytopenias. To evaluate safety we identified each documented cardiovascular event in the cohort including ischemic stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis or portal vein thrombosis. We generated Kaplan-Meier curves comparing cardiovascular events and cardiovascular event-free survival between the treated and untreated groups. Hazard ratios were calculated using Cox regression analysis. Results: The inclusion criteria were met by 570 of 1511 potentially eligible patients. Of the 113 patients treated with an ESA, data was adequate to assess treatment response in 101 patients. Of the patients treated with an ESA, the mean age was 75.1 years and 60% were male. The mean pretreatment hemoglobin was 88.5 g/L. Inter-observer agreement for diagnostic categories was adequate. Eighty-two patients were treated with epoetin alfa and 19 patients received darbepoetin alfa. Treatment response was better in the CKD and AUE groups (54% and 47%, respectively) compared to the other groups. Compared to the group of other etiologies logistic regression analysis showed a 3.6 and 3.3 adjusted odds ratio (OR) for response for CKD and AUE respectively, although this was not statistically significant (Table 1). A baseline EPO level <200 IU/L was associated with a response to ESAs (OR 9.3; 95% CI 1.1-75.4). There was no significant difference in cardiovascular events or cardiovascular event-free survival between the treated and untreated groups, even after adjusting for confounders (Table 2). Conclusion: Our results suggest that ESAs can be used to treat anemia of unknown etiology, and responses may be similar to those in chronic kidney disease. This supports the notion that a relative EPO deficiency is probably related to the pathogenesis of AUE. Although treatment may be associated with increased cardiovascular events, this was not found to be significant in our cohort. Limitations of this study include its retrospective nature and a relatively small sample size. Further studies exploring the safety and efficacy of ESAs in the treatment of AUE are warranted. Table 1 Odds ratio of treatment response in unadjusted and adjusted logistic regression models Table 1. Odds ratio of treatment response in unadjusted and adjusted logistic regression models Table 2 Hazard ratios for cardiovascular outcomes in patients receiving ESAs in unadjusted and adjusted Cox regression models Table 2. Hazard ratios for cardiovascular outcomes in patients receiving ESAs in unadjusted and adjusted Cox regression models Disclosures Xenocostas: Janssen Inc.: Research Funding. Lazo-Langner:Daiichi Sankyo: Research Funding; Pfizer: Honoraria; Bayer: Honoraria.

2013 ◽  
Vol 31 (3) ◽  
pp. 306-314 ◽  
Author(s):  
Edson Theodoro dos S. Neto ◽  
Eliana Zandonade ◽  
Adauto Oliveira Emmerich

OBJECTIVE To analyze the factors associated with breastfeeding duration by two statistical models. METHODS A population-based cohort study was conducted with 86 mothers and newborns from two areas primary covered by the National Health System, with high rates of infant mortality in Vitória, Espírito Santo, Brazil. During 30 months, 67 (78%) children and mothers were visited seven times at home by trained interviewers, who filled out survey forms. Data on food and sucking habits, socioeconomic and maternal characteristics were collected. Variables were analyzed by Cox regression models, considering duration of breastfeeding as the dependent variable, and logistic regression (dependent variables, was the presence of a breastfeeding child in different post-natal ages). RESULTS In the logistic regression model, the pacifier sucking (adjusted Odds Ratio: 3.4; 95%CI 1.2-9.55) and bottle feeding (adjusted Odds Ratio: 4.4; 95%CI 1.6-12.1) increased the chance of weaning a child before one year of age. Variables associated to breastfeeding duration in the Cox regression model were: pacifier sucking (adjusted Hazard Ratio 2.0; 95%CI 1.2-3.3) and bottle feeding (adjusted Hazard Ratio 2.0; 95%CI 1.2-3.5). However, protective factors (maternal age and family income) differed between both models. CONCLUSIONS Risk and protective factors associated with cessation of breastfeeding may be analyzed by different models of statistical regression. Cox Regression Models are adequate to analyze such factors in longitudinal studies.


2015 ◽  
Vol 40 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Camiel L.M. de Roij van Zuijdewijn ◽  
Menso J. Nubé ◽  
Piet M. ter Wee ◽  
Peter J. Blankestijn ◽  
Renée Lévesque ◽  
...  

Background/Aims: Treatment time is associated with survival in hemodialysis (HD) patients and with convection volume in hemodiafiltration (HDF) patients. High-volume HDF is associated with improved survival. Therefore, we investigated whether this survival benefit is explained by treatment time. Methods: Participants were subdivided into four groups: HD and tertiles of convection volume in HDF. Three Cox regression models were fitted to calculate hazard ratios (HRs) for mortality of HDF subgroups versus HD: (1) crude, (2) adjusted for confounders, (3) model 2 plus mean treatment time. As the only difference between the latter models is treatment time, any change in HRs is due to this variable. Results: 114/700 analyzed individuals were treated with high-volume HDF. HRs of high-volume HDF are 0.61, 0.62 and 0.64 in the three models, respectively (p values <0.05). Confidence intervals of models 2 and 3 overlap. Conclusion: The survival benefit of high-volume HDF over HD is independent of treatment time.


2015 ◽  
Vol 41 (4-5) ◽  
pp. 409-417 ◽  
Author(s):  
Nadine Alexander ◽  
Kunihiro Matsushita ◽  
Yingying Sang ◽  
Shoshana Ballew ◽  
Bakhtawar K. Mahmoodi ◽  
...  

Background: Whether the association of chronic kidney disease (CKD) with cardiovascular risk differs based on diabetes mellitus (DM) and hypertension (HTN) status remains unanswered. Methods: We investigated 11,050 participants from the Atherosclerosis Risk in Communities Study (fourth examination (1996-1998)) with follow-up for cardiovascular outcomes (coronary disease, heart failure and stroke) through 2009. Using the Cox regression models, we quantified cardiovascular risk associated with estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) in individuals with and without DM and/or HTN and assessed their interactions. Results: Individuals with DM and HTN generally had higher cardiovascular risk relative to those without at all the levels of eGFR and ACR. Cardiovascular risk increased with lower eGFR and higher ACR regardless of DM and HTN status (e.g. adjusted hazards ratio (HR) for eGFR 30-44 vs. 90-104 ml/min/1.73 m2, 2.32 (95% CI, 1.66-3.26) in non-diabetics vs. 1.83 (1.25-2.67) in diabetics and 2.45 (2.20-5.01) in non-hypertensives vs. 1.51 (1.27-1.81) in hypertensives and corresponding adjusted HR for ACR 30-299 vs. <10 mg/g, 1.70 (1.45-2.00) vs. 1.34 (1.10-1.64) and 1.42 (1.10-1.85) vs. 1.57 (1.36-1.81), respectively). Only the ACR-DM interaction reached significance, with a shallower relative risk gradient among diabetics than among non-diabetics (p = 0.02). Analysis of individual cardiovascular outcomes showed similar results. Conclusion: Although individuals with DM and HTN generally had higher cardiovascular risk relative to those without these complications, both low eGFR and high ACR were associated with cardiovascular diseases regardless of the presence or absence of DM and HTN. These findings reinforce the importance of CKD in cardiovascular outcomes.


2018 ◽  
Vol 48 (6) ◽  
pp. 425-433 ◽  
Author(s):  
Solène Guilloteau ◽  
Thierry Lobbedez ◽  
Sonia Guillouët ◽  
Christian Verger ◽  
Maxence Ficheux ◽  
...  

Background: Patients on peritoneal dialysis (PD) can be assisted by a nurse or a family member and treated either by automated PD (APD) or continuous ambulatory PD (CAPD). The aim of this study was to evaluate the effect of PD modality and type of assistance on the risk of transfer to haemodialysis (HD) and on the peritonitis risk in assisted PD patients. Method: This was a retrospective study based on data from the French Language PD Registry. All adults starting assisted PD in France between 2006 and 2015 were included. Events of interest were transfer to HD, peritonitis and death. Cox regression models were used for statistical analysis. Results: Among the 12,144 incident patients who started PD in France during the study period, 6,167 were assisted. There were 5,060 nurse-assisted and 1,095 family-assisted PD patients. Overall, 5,171 were treated by CAPD and 996 by APD. In multivariate analysis, CAPD, compared to APD, was not associated with the risk of transfer to HD (cause specific hazard ratios [cs-HR] 0.96 [95% CI 0.84–1.09]). Patients on nurse-assisted PD had a lower risk of transfer to HD than family assisted PD patients (cs-HR 0.85 [95% CI 0.75–0.97]). Neither PD modality nor type of assistance were associated with peritonitis risk. Conclusions: In assisted PD, technique survival was not associated with PD modality. Nurse-assisted patients had a lower risk of transfer to HD than family assisted patients. Peritonitis risk was not influenced either by PD modality, or by type of assistance. Both APD and CAPD should be offered to assisted-PD patients.


Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Daniel M Huck ◽  
Michael A Rosenberg ◽  
Michael R Bristow ◽  
Brian L Stauffer

Introduction: Beta blockers are not guideline-recommended first-line agents for hypertension, based on evidence that older generation beta blockers such as atenolol are associated with inferior reduction of some cardiovascular events compared to other antihypertensive classes. Vasodilatory beta blockers such as nebivolol have been found to have beneficial effects on peripheral vasculature through nitric oxide, endothelin-1, and tissue plasminogen activator pathways. The objective of this study is to compare longitudinal cardiovascular outcomes of hypertensive patients taking the vasodilatory beta blocker nebivolol with hypertensive patients taking the non-vasodilatory beta blockers atenolol and metoprolol. Hypothesis: Nebivolol will be associated with a reduction in odds of adverse cardiovascular outcomes compared with non-vasodilatory beta blockers. Methods: The study is a retrospective cohort analysis of de-identified data from adults in the University of Colorado health system with hypertension and on the vasodilatory beta blocker nebivolol or the non-vasodilatory beta blockers atenolol or metoprolol, without preceding diagnosis of cardiovascular or cerebrovascular disease. The primary outcome is incident cardiovascular hospitalization or diagnosis of cardiovascular event including heart failure, stroke, myocardial infarction, angina pectoris, or coronary revascularization based on diagnosis or procedure codes. Nearest-available propensity matching logistic regression was used, with each patient taking nebivolol matched to two control patients taking a non-vasodilatory beta blocker. Propensity matching variables included baseline demographics, cardiovascular risk factors, Charlson comorbidity index, other cardiovascular medications, and duration of follow-up. Results: There were 1395 patients taking nebivolol, and 20208 patients taking atenolol or metoprolol. Patients were predominantly female (54%, 11681 of 21603) and non-Hispanic white (75%, 16185 of 21603), with mean age of 60. The primary outcome occurred in 19% (259 of 1395) of those taking nebivolol, 29% (1891 of 6527) of those taking atenolol, and 40% (5500 of 13681) of those taking metoprolol. In propensity matched logistic regression, nebivolol is associated with reduced odds of incident cardiovascular events when compared to the non-vasodilatory beta blockers atenolol and metoprolol (OR 0.33, 95% CI 0.28 to 0.40). This association was also found with individual comparison with atenolol (OR 0.47, 95% CI 0.39 to 0.57) and metoprolol (OR 0.26, 95% CI 0.21 to 0.32). Conclusions: The vasodilatory beta blocker nebivolol is associated with reduced odds of incident cardiovascular events compared to non-vasodilatory beta blockers. Additional study of other beta blockers is necessary to determine if this is a vasodilatory beta blocker class effect, or is specific to nebivolol.


2015 ◽  
Vol 46 (1) ◽  
pp. 63-72 ◽  
Author(s):  
K. S. Kendler ◽  
S. L. Lönn ◽  
P. Lichtenstein ◽  
J. Sundquist ◽  
K. Sundquist

Background.Certain personality traits predispose to criminal behavior (CB). We further clarify this relationship in a Swedish national sample.Method.Psychological strength (PS) was assessed on a nine-point scale at personal interview in 1 653 721 Swedish men aged 18–20 years. We examined the association between PS and total, violent and recurrent CB over the lifetime (logistic regression), prospectively (Cox regression) and by bivariate Cholesky decomposition in 2507 monozygotic and 2244 dizygotic twin pairs (OpenMx).Results.Examining linear effects by logistic regression, PS was robustly associated with lifetime risk of total CB (per point, odds ratio = 0.74) and even more strongly associated with risk for violent (0.69) and recurrent CB (0.52). Prospective predictions of these three forms of CB by PS were similar, with hazard ratios of 0.80, 0.73 and 0.54, respectively. Twin modeling demonstrated that, for all three CB types, the association with PS arose almost entirely from familial effects. Common shared environment accounted for 72, 56 and 43% of the phenotypic correlation between PS and, respectively, total, violent and recurrent CB. Parallel figures for common genetic effects were for 24, 37 and 54%, respectively.Conclusions.PS is strongly related to risk for total CB, and even more strongly for violent and, especially, recurrent CB. This association is probably not causal but rather results from shared familial risk factors that make an impact both on PS and risk for CB. PS has a stronger overall correlation with more severe criminal outcomes and a higher proportion of that correlation results from common genetic factors.


2019 ◽  
Vol 75 (10) ◽  
pp. 2263-2267
Author(s):  
Kendra L Ratnapradipa ◽  
Jing Wang ◽  
Marla Berg-Weger ◽  
and Mario Schootman

Abstract Objectives Driving cessation is associated with adverse social and health outcomes including increased mortality risk. Some former drivers resume driving. Do resumed drivers have a different mortality risk compared to former drivers or continued drivers? Method We analyzed National Health and Aging Trends Study (2011–2015) data of community-dwelling self-responding ever drivers (n = 6,189) with weighted stratified life tables and discrete time logistic regression models to characterize mortality risk by driving status (continued, resumed, former), adjusting for relevant sociodemographic and health variables. Results Overall, 14% (n = 844) of participants died and 52% (n = 3,209) completed Round 5. Former drivers had the highest mortality (25%), followed by resumed (9%) and continued (6%) drivers. Former drivers had 2.4 times the adjusted odds of mortality compared with resumed drivers (adjusted odds ratio [aOR] = 2.41; 95% confidence interval [CI] = 1.51, 3.83), with no difference between continued and resumed drivers (aOR = 1.22; 95% CI = 0.74, 1.99). Discussion Those who resumed driving had better survival than those who did not. Practice implications include driver rehabilitation and retraining to safely promote and prolong driving.


Author(s):  
Andrew Stickley ◽  
Tetsuya Matsubayashi ◽  
Michiko Ueda

Abstract Background There is some evidence that loneliness may be linked to poorer health behaviours. Despite this, there has been little research to date on the relationship between loneliness and COVID-19 preventive behaviours. We studied these associations in a sample of the Japanese population. Methods Data were analysed from an online survey of 2000 adults undertaken in April and May 2020. Loneliness was assessed with the Three-Item Loneliness Scale. Information was also collected on 13 COVID-19 preventive behaviours. Regression analyses were used to examine associations. Results In linear regression models adjusted for demographic and mental health variables, both dichotomous and continuous loneliness measures were negatively associated with engaging in COVID-19 preventive behaviours. Logistic regression analyses further showed that loneliness was also associated with reduced odds for a variety of individual preventive behaviours including wearing a mask (odds ratio [OR]: 0.77, 95% confidence interval [CI]: 0.62–0.95), disinfecting hands (OR: 0.80, 95% CI: 0.67–0.94) and social distancing when outdoors (OR: 0.75, 95% CI: 0.61–0.92). Conclusions Loneliness is associated with lower engagement in COVID-19 preventive behaviours. Interventions to prevent or ameliorate loneliness during the ongoing pandemic may be important in combating the spread of the coronavirus.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 720-720
Author(s):  
Amanda Rose Townsend ◽  
Rebecca Asher ◽  
Timothy Jay Price ◽  
Chee Khoon Lee ◽  
Hilary Dorward ◽  
...  

720 Background: Our previous study has identified COL4A2, PPP1R17 and ARHGAP44 SNPs using whole exome sequencing with potential prognostic significance (Townsend et al. ASCO GI 2017). COL4A2 encodes a subunit of type IV collagen, the C-terminal of which is an inhibitor of angiogenesis. We assessed prognostic impact of these variants in patients from the phase III MAX study (capecitabine +/- bevacizumab (+/- mitomycin C)). An analysis of predictive effect on bevacizumab was also undertaken. Methods: DNA was extracted from archival macrodissected formalin fixed paraffin embedded tumor tissue and genotyped using Agena Bioscience MassARRAY system (AGRF). Univariate association of variant group (WT versus mutation (MT)) with progression free survival (PFS) and overall survival (OS) was assessed using Kaplan-Meier curves and Cox regression models. Logistic regression models were used to assess association with response rate (RR). A cox regression model with treatment, variant status and their interaction investigated if variants were predictive of bevacizumab effect. Results: Of the available 145 of 471 (31%) patients in the MAX study, 25 (17%) had COL4A2 MT, 29 (20%) PPP1R17 MT, 14 (10%) ARHGAP44 MT. Patient demographics were comparable across treatment groups and outcomes similar to whole study population. On univariate analysis median PFS was numerically longer for WT vs MT in all 3 variants, but these differences were not significant (COL4A2 WT 8.4m v MT 6.0m, p=0.09; PPP1R17 WT 7.8m v MT 7.5m, p=0.76; ARHGAP44 WT 8.2m v MT 6.5m, p=0.86). There was also no significant association between variant type and OS. Multivariate analysis for COL4A2 MT v WT showed no significant difference in PFS or OS (HR 1.42; 95% CI 0.91-2.22, p=0.13 and HR 1.33; 95% CI 0.85-2.1, p=0.21). There was no association between treatment response and variant status. Variant status was not predictive of bevazicumab efficacy for treatment response, PFS or OS. Conclusions: There was no significant prognostic or predictive impact of novel gene variants in patients treated with bevacizumab. This may be due to small numbers of MT variants in this study and further studies in larger populations may be useful.


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