scholarly journals Erythropoietin Dose and Mortality in Hemodialysis Patients: Marginal Structural Model to Examine Causality

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Elani Streja ◽  
Jongha Park ◽  
Ting-Yan Chan ◽  
Janet Lee ◽  
Melissa Soohoo ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Structural Model ◽  
Positive Association ◽  
Hemodialysis Patients ◽  
Adverse Outcomes ◽  
Time Varying ◽  
Marginal Structural Model ◽  
Time Varying Covariates ◽  
Dose Dependent

It has been previously reported that a higher erythropoiesis stimulating agent (ESA) dose in hemodialysis patients is associated with adverse outcomes including mortality; however the causal relationship between ESA and mortality is still hotly debated. We hypothesize ESA dose indeed exhibits a direct linear relationship with mortality in models of association implementing the use of a marginal structural model (MSM), which controls for time-varying confounding and examines causality in the ESA dose-mortality relationship. We conducted a retrospective cohort study of 128 598 adult hemodialysis patients over a 5-year follow-up period to evaluate the association between weekly ESA (epoetin-α) dose and mortality risk. A MSM was used to account for baseline and time-varying covariates especially laboratory measures including hemoglobin level and markers of malnutrition-inflammation status. There was a dose-dependent positive association between weekly epoetin-αdoses ≥18 000 U/week and mortality risk. Compared to ESA dose of <6 000 U/week, adjusted odds ratios (95% confidence interval) were 1.02 (0.94–1.10), 1.08 (1.00–1.18), 1.17 (1.06–1.28), 1.27 (1.15–1.41), and 1.52 (1.37–1.69) for ESA dose of 6 000 to <12 000, 12 000 to <18 000, 18 000 to <24 000, 24 000 to <30 000, and ≥30 000 U/week, respectively. High ESA dose may be causally associated with excessive mortality, which is supportive of guidelines which advocate for conservative management of ESA dosing regimen in hemodialysis patients.

scholarly journals Mild anemia and 11- to 15-year mortality risk in young-old and old-old: Results from two population-based cohort studies

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261899
Author(s):  
Alessia A. Galbussera ◽  
Sara Mandelli ◽  
Stefano Rosso ◽  
Roberto Zanetti ◽  
Marianna Rossi ◽  
...  
Keyword(s):  
Sex Education ◽  
Mortality Risk ◽  
Age Groups ◽  
Population Based ◽  
Adverse Outcomes ◽  
Smoking History ◽  
Time Varying ◽  
Mild Anemia ◽  
Time Varying Covariates ◽  
Young Old

Background Mild anemia is a frequent although often overlooked finding in old age. Nevertheless, in recent years anemia has been linked to several adverse outcomes in the elderly population. Objective of the study was to investigate the association of mild anemia (hemoglobin concentrations: 10.0–11.9/12.9 g/dL in women/men) with all-cause mortality over 11–15 years and the effect of change in anemia status on mortality in young-old (65–84 years) and old-old (80+ years). Methods The Health and Anemia and Monzino 80-plus are two door-to-door, prospective population-based studies that included residents aged 65-plus years in Biella municipality and 80-plus years in Varese province, Italy. No exclusion criteria were used. Results Among 4,494 young-old and 1,842 old-old, mortality risk over 15/11 years was significantly higher in individuals with mild anemia compared with those without (young-old: fully-adjusted HR: 1.35, 95%CI, 1.15–1.58; old-old: fully-adjusted HR: 1.28, 95%CI, 1.14–1.44). Results were similar in the disease-free subpopulation (age, sex, education, smoking history, and alcohol consumption adjusted HR: 1.54, 95%CI, 1.02–2.34). Both age groups showed a dose-response relationship between anemia severity and mortality (P for trend <0.0001). Mortality risk was significantly associated with chronic disease and chronic kidney disease mild anemia in both age groups, and with vitamin B12/folate deficiency and unexplained mild anemia in young-old. In participants with two hemoglobin determinations, seven-year mortality risk was significantly higher in incident and persistent anemic cases compared to constant non-anemic individuals in both age groups. In participants without anemia at baseline also hemoglobin decline was significantly associated with an increased mortality risk over seven years in both young-old and old-old. Limited to the Monzino 80-plus study, the association remained significant also when the risk was further adjusted also for time-varying covariates and time-varying anemia status over time. Conclusions Findings from these two large prospective population-based studies consistently suggest an independent, long-term impact of mild anemia on survival at older ages.

Effectiveness of Sofosbuvir and Velpatasvir Combination in Chronic Hepatitis C with Hemodialysis Patients

2021 ◽  
Vol 15 (5) ◽  
pp. 1205-1207
Author(s):  
R. A. Khan ◽  
A. Ali ◽  
S. Munib ◽  
I. Muhammad ◽  
NOSHER WAN ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Prospective Observational Study ◽  
Hemodialysis Patients ◽  
Hemoglobin Level ◽  
Adverse Outcomes ◽  
Keywords Hemodialysis

Objective: The aim of this study is to determine the response of sofosbuvir and velpatasvir combination in chronic hepatitis C with hemodialysis patients. Study Design: Prospective/observational study Place and Duration: The study was conducted at department of Nephrology Nawaz Sharif Kidney Hospital, Swat for duration of six months from 1st July to 31st December, 2020. Methods: Total 27 patients of both genders were presented in this study. Patients were aged between 18-85 years. Patients details demographics age, sex and body mass index were recorded after taking written consent. Patients diagnosis hepatitis C with recognized genotypes were presented. Enrolled patients received combination of sofosbuvir and velpatasvir regime (SOF/VLP) for 14 weeks and follow up was taken. Effectiveness and safety among HCV patients on hemodialysis were observed. Complete data was analyzed by SPSS 22.0 version. Results: Out of 27 patients 17 (62.96%) were males 10 (37.04%) were females. Mean age of the patients was 35.14±5.18 years with mean BMI 24.41±6.25 kg/m2. Hypertension was the most common comorbidity found in 15 (55.55%) patients followed by obesity 8 (29.63%) and diabetes found in 3 (14.81%). Among 27 cases 20 (74.04%) were naïve and 7 (25.96%) were treatment experienced. Sustained virological response was found in 26 (96.3%) and 1(3.7%) patients were lost at follow up. Significantly improvement was found in hemoglobin level 12.11 ± 5.24, alanine aminotransferase (ALT) 28.51 ± 9.62 and aspartate aminotransferase (AST) 35.24 ± 7.08 after treatment. Headache, fatigue and nausea were the most common adverse outcomes. Conclusion: We concluded in this study that the use of sofosbuvir and velpatasvir was effective safe and well tolerated in the treatment of hepatitis C patients with hemodialysis. Keywords: Hemodialysis, Hepatitis C, Sofosbuvir, Velpatasvir, Complications

Dealing with Treatment-confounder Feedback and Sparse Follow-up in Longitudinal studies - Application of a Marginal Structural Model in a Multiple Sclerosis Cohort

2020 ◽  
Author(s):  
Mohammad Ehsanul Karim ◽  
Helen Tremlett ◽  
Feng Zhu ◽  
John Petkau ◽  
Elaine Kingwell
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Multiple Imputation ◽  
Structural Model ◽  
Potential Effect ◽  
Hazard Ratio ◽  
Survival Advantage ◽  
Marginal Structural Model ◽  
Beta Interferon

Abstract The beta-interferons are widely prescribed platform therapies for patients with multiple sclerosis (MS). We accessed a cohort of patients with relapsing onset MS from British Columbia, Canada (1995-2013) to examine the potential survival advantage associated with beta-interferon exposure using a marginal structural model. Accounting for potential treatment-confounder feedback between comorbidity, MS disease progression and beta-interferon exposure, we found an association between beta-interferon exposure of at least 6 contiguous months and improved survival (hazard ratio (HR) = 0.63, 95% confidence interval 0.47-0.86). We also assessed potential effect modifications by sex, baseline age or baseline disease duration, and found these factors to be important effect modifiers. Sparse follow-up due to variability in patient contact with the health system is one of the biggest challenges in longitudinal analyses. We considered several single-level and multi-level multiple imputation approaches to deal with sparse follow-up and disease progression information; both types of approach produced similar estimates. Compared to ad hoc imputation approaches, such as linear interpolation (HR: 0.63), and last observation carried forward (HR: 0.65), all multiple imputation approaches produced a smaller hazard ratio (HR: 0.53), although the direction of effect and conclusions drawn concerning the survival advantage remained the same.

scholarly journals Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study

2019 ◽  
Vol 70 (9) ◽  
pp. 1837-1844 ◽  
Author(s):  
Yaseen M Arabi ◽  
Sarah Shalhoub ◽  
Yasser Mandourah ◽  
Fahad Al-Hameed ◽  
Awad Al-Omari ◽  
...  
Keyword(s):  
Middle East ◽  
Observational Study ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Structural Model ◽  
Middle East Respiratory Syndrome ◽  
Time Varying ◽  
Marginal Structural Model ◽  
Recombinant Interferon ◽  
Multicenter Observational Study

Abstract Background The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders. Methods This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders. Results Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73–1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30–1.44]; P = .29). Conclusions In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.

scholarly journals An assessment of the potential miscalibration of cardiovascular disease risk predictions caused by a secular trend in cardiovascular disease in England

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Alexander Pate ◽  
Tjeerd van Staa ◽  
Richard Emsley
Keyword(s):  
Cardiovascular Disease ◽  
Risk Prediction ◽  
Structural Model ◽  
Validation Cohort ◽  
Secular Trend ◽  
Marginal Structural Model ◽  
Cvd Risk ◽  
Model Framework ◽  
Statin Use

Abstract Background A downwards secular trend in the incidence of cardiovascular disease (CVD) in England was identified through previous work and the literature. Risk prediction models for primary prevention of CVD do not model this secular trend, this could result in over prediction of risk for individuals in the present day. We evaluate the effects of modelling this secular trend, and also assess whether it is driven by an increase in statin use during follow up. Methods We derived a cohort of patients (1998–2015) eligible for cardiovascular risk prediction from the Clinical Practice Research Datalink with linked hospitalisation and mortality records (N = 3,855,660). Patients were split into development and validation cohort based on their cohort entry date (before/after 2010). The calibration of a CVD risk prediction model developed in the development cohort was tested in the validation cohort. The calibration was also assessed after modelling the secular trend. Finally, the presence of the secular trend was evaluated under a marginal structural model framework, where the effect of statin treatment during follow up is adjusted for. Results Substantial over prediction of risks in the validation cohort was found when not modelling the secular trend. This miscalibration could be minimised if one was to explicitly model the secular trend. The reduction in risk in the validation cohort when introducing the secular trend was 35.68 and 33.24% in the female and male cohorts respectively. Under the marginal structural model framework, the reductions were 33.31 and 32.67% respectively, indicating increasing statin use during follow up is not the only the cause of the secular trend. Conclusions Inclusion of the secular trend into the model substantially changed the CVD risk predictions. Models that are being used in clinical practice in the UK do not model secular trend and may thus overestimate the risks, possibly leading to patients being treated unnecessarily. Wider discussion around the modelling of secular trends in a risk prediction framework is needed.

An analysis of the impact of fluid overload and fluid depletion for all-cause and cardiovascular mortality

2019 ◽  
Vol 34 (8) ◽  
pp. 1385-1393 ◽  
Author(s):  
Dimitrie Siriopol ◽  
Mihaela Siriopol ◽  
Stefano Stuard ◽  
Luminita Voroneanu ◽  
Peter Wabel ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Fluid Overload ◽  
Reference Group ◽  
Volume Status ◽  
Time Varying ◽  
Dialysis Fluid ◽  
Fluid Status ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Background Both baseline fluid overload (FO) and fluid depletion are associated with increased mortality risk and cardiovascular complications in haemodialysis patients. Fluid status may vary substantially over time, and this variability could also be associated with poor outcomes. Methods In our retrospective cohort study, including 4114 haemodialysis patients from 34 Romanian dialysis units, we investigated both all-cause and cardiovascular mortality risk according to baseline pre- and post-dialysis volume status, changes in pre- and post-dialysis fluid status during follow-up (time-varying survival analysis), pre–post changes in volume status during dialysis and pre-dialysis fluid status variability during the first 6 months of evaluation. Results According to their pre-dialysis fluid status, patients were stratified in the following groups: normovolaemic with an absolute FO (AFO) compartment between −1.1 and 1.1 L, fluid depletion with an AFO below −1.1 L, moderate FO with an AFO compartment >1.1 but <2.5 L and severe FO with the AFO compartment >2.5 L. Baseline pre-dialysis FO and fluid depletion patients had a significantly elevated risk of all-cause mortality risk {hazard ratio [HR] 1.53 [95% confidence interval (CI) 1.22–1.93], HR 2.04 (95% CI 1.59–2.60) and HR 1.88 (95% CI 1.07–3.39) for moderate FO, severe FO and fluid depletion, respectively}. In contrast, post-dialysis fluid depletion was associated with better survival [HR 0.71 (95% CI 0.57–0.89)]. Similar results were found when using changes in pre- or post-dialysis fluid status during follow-up (time-varying values): FO patients had an increased risk of all-cause [moderate FO: HR 1.39 (95% CI 1.11–1.75); severe FO: HR 2.29 (95% CI 2.01–3.31] and cardiovascular (CV) mortality [moderate FO: HR 1.34 (95% CI 1.05–1.70); severe FO: HR 2.34 (95% CI 1.67–3.28)] as compared with normohydrated patients. Using pre–post changes in volume status during dialysis, we categorized the patients into six groups: Group 1, AFO <−1.1 L pre- and post-dialysis; Group 2, AFO between −1.1 and 1.1 L pre-dialysis and <−1.1 L post-dialysis (the reference group); Group 3, AFO between −1.1 and 1.1 L pre- and post-dialysis; Group 4, AFO >1.1 L pre-dialysis and <−1.1 L post-dialysis; Group 5, AFO >1.1 L pre-dialysis and between −1.1 and 1.1 L post-dialysis; Group 6, AFO >1.1 L pre- and post-dialysis. Using the baseline values, only patients in Groups 1, 5 and 6 maintained an increased risk for all-cause mortality as compared with the reference group. Additionally, CV mortality risk was significantly higher for patients in Groups 5 and 6. When we applied the time-varying analysis, patients in Groups 1, 5 and 6 had a significantly higher risk for both all-cause and CV mortality risk. In the last approach, the highest risk for the all-cause mortality outcome was observed for patients with high-amplitude fluctuation during the first 6 months of evaluation [HR 2.75 (95% CI 1.29–5.84)]. Conclusion We reconfirm the association between baseline pre- and post-dialysis volume status and mortality in dialysis patients; additionally, we showed that greater fluid status variability is independently associated with higher mortality.

scholarly journals Impact of depression on clinical outcomes following percutaneous coronary intervention: a systematic review and meta-analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e026445 ◽  
Author(s):  
Wen Yi Zhang ◽  
Nan Nan ◽  
Xian Tao Song ◽  
Jin Fan Tian ◽  
Xue Yao Yang
Keyword(s):  
Systematic Review ◽  
Percutaneous Coronary Intervention ◽  
Meta Analysis ◽  
Positive Association ◽  
Coronary Intervention ◽  
Adverse Outcomes ◽  
Increased Risk ◽  
Percutaneous Coronary ◽  
Assessment Time

ObjectivesThe objective of this meta-analysis was to assess whether depression in percutaneous coronary intervention (PCI) patients is associated with higher risk of adverse outcomes.DesignSystematic review and meta-analysis.MethodsEMBASE, PubMed, CINAHL and PsycINFO were searched as data sources. We selected prospective cohort studies evaluating the relationship between depression and any adverse medical outcome, including all-cause mortality, cardiac mortality and non-fatal events, from inception to 28 February 2019. Two reviewers independently extracted information and calculated the risk of cardiovascular events in patients with preoperative or postoperative depression compared with non-depressed patients.ResultsEight studies (n=3297) met our inclusion criteria. Most studies found a positive association between depression and adverse cardiovascular outcomes. Meta-analysis yielded an aggregate risk ratio of 1.57 (95% CI 1.28 to 1.92, p<0.0001) for the magnitude of the relation between depression and adverse outcomes.ConclusionsOur systematic review and meta-analysis suggests that depression is associated with an increased risk of worse clinical outcome or mortality in patients undergoing PCI. Assessment time and length of follow-up do not have a significant effect on this conclusion.

Association of Graft-Versus-Host Disease and Immunosuppressive Treatment with Risks of Recurrent Malignancy and Mortality After Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 218-218
Author(s):  
Yoshihiro Inamoto ◽  
Mary E.D. Flowers ◽  
Stephanie J. Lee ◽  
Paul A. Carpenter ◽  
Edus H. Warren ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Immunosuppressive Treatment ◽  
Time Varying ◽  
Graft Versus Host ◽  
Recurrent Malignancy ◽  
Time Varying Covariates

Abstract Abstract 218 Background: Graft-versus-leukemia (GVL) effects are closely associated with graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). In a reexamination of GVL effects, we evaluated acute and chronic GVHD defined by NIH consensus criteria and immunosuppressive treatment (IST) as risk factors for recurrent malignancy after HCT. Patients and methods: We analyzed a cohort of 2656 consecutive patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN) who received allogeneic HCT after high-intensity conditioning between 1992 and 2005. The onset of NIH chronic GVHD was ascertained by retrospective chart review using follow-up information obtained by our Long Term Follow Up clinic. Rates and hazards of recurrent malignancy and mortality were analyzed according to GVHD and IST as time-varying covariates. To illustrate the effect of time-varying covariates, we calculated the rate of recurrent malignancy per patient-year according to prior GVHD within sequential 90-day intervals after HCT. Cox proportional hazard models were adjusted for potential factors affecting outcomes. Results: The median patient age at HCT was 39 years (range, 0 to 71 years). Donors were HLA-identical relatives (n=1088), HLA-matched unrelated volunteers (n=912), HLA-mismatched relatives (n=243), and HLA-mismatched unrelated volunteers (n=413). GVHD prophylaxis was mostly cyclosporine and methotrexate (n=1885, 71%). Relapse rates per patient-year declined from 3 months until at least 36 months after HCT for patients with prior acute GVHD or NIH chronic GVHD (Figure). Patients without prior GVHD showed a much less pronounced decline between 12 and 30 months after HCT. Adjusted Cox analysis showed that acute GVHD and NIH chronic GVHD were associated with statistically similar reductions in risk of late recurrent malignancy beyond 18 months after HCT, with no incremental effect of chronic GVHD in patients with prior acute GVHD (Table 1). GVL effects were demonstrable in patients with CML or AML but not in those with ALL or MDS/MPN. Discontinuation of IST was associated with a decreased risk of recurrent malignancy among patients without prior GVHD but not among those with prior GVHD (Table 2). Grades III–IV acute GVHD and NIH chronic GVHD with prior acute GVHD were associated with a statistically significant increase in risk of early mortality between 3 and 18 months, but grade II acute GVHD and NIH chronic GVHD without prior acute GVHD were not. Conclusion: Both acute and NIH chronic GVHD are associated with potent GVL effects, but NIH chronic GVHD does not confer any incremental benefit after acute GVHD. Withdrawal of IST was associated with a reduction in risk of recurrent malignancy in patients without prior GVHD. Analyses of GVL effects should account for time from HCT, the history of GVHD, type of malignancy and IST. Immune manipulations such as prophylactic donor lymphocyte infusion or early withdrawal of IST may represent reasonable approaches to decrease the risk of recurrent malignancy in patients without prior GVHD, if the risk of GVHD could be minimized. Disclosures: No relevant conflicts of interest to declare.

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