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Association of frailty with clinical outcomes in myelofibrosis: a retrospective cohort study.

ABSTRACT: There is limited understanding of the impact of frailty on clinical outcomes in patients with myelofibrosis (MF). In this retrospective cohort study on 439 chronic phase MF patients [mean age: 68·7 ± 12 years; median follow-up: 3·4 years (IQR 0·4-8·6)] from 2004 till 2018, we used a 35-variable frailty index (FI) to categorise patient's frailty status as fit (FI < 0·2, reference), prefrail (FI 0·2-0·29) or frail (FI ≥ 0·3). The association of frailty with overall survival (OS) and cumulative JAK inhibitor (JAKi) therapy failure was measured using hazard ratio (HR, 95% CI). In multivariable analysis, prefrail (HR 1·7, 1·1-2·5) and frail patients (HR 2·9, 1·6-5·5), those with higher DIPSS score (HR 2·5, 1·6-3·9) and transfusion dependency (HR 1·9, 1·3-2·9) had shorter OS. In a subset analysis of patients on JAKi treatment (n = 222), frail patients (HR 2·5, 1·1-5·7), patients with higher DIPSS score (HR 1·7, 1·0-3·1) and transfusion dependence (HR 1·7, 1·1-2·7) had higher cumulative incidence of JAKi failure. Age, comorbidities, ECOG performance status, and MPN driver mutations did not impact outcomes. Thus, higher frailty scores are associated with worse OS and increased JAKi failure in MF, and is a superior indicator of fitness in comparison to age, comorbidities, and performance status.

SUBMITTER: Bankar A

PROVIDER: S-EPMC8361997 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Association of frailty with clinical outcomes in myelofibrosis: a retrospective cohort study.

Bankar Aniket A Alibhai Shabbir S Smith Elliot E Yang Dongyang D Malik Sarah S Cheung Verna V Siddiq Nancy N Claudio Jaime J Arruda Andrea A Tsui Hubert H Capo-Chichi Jose-Mario JM Kennedy James A JA McNamara Caroline C Sibai Hassan H Maze Dawn D Xu Wei W Gupta Vikas V

British journal of haematology 20210615 3

There is limited understanding of the impact of frailty on clinical outcomes in patients with myelofibrosis (MF). In this retrospective cohort study on 439 chronic phase MF patients [mean age: 68·7 ± 12 years; median follow-up: 3·4 years (IQR 0·4-8·6)] from 2004 till 2018, we used a 35-variable frailty index (FI) to categorise patient's frailty status as fit (FI < 0·2, reference), prefrail (FI 0·2-0·29) or frail (FI ≥ 0·3). The association of frailty with overall survival (OS) and cumulative JAK ...[more]

PMID: 34131896

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Project description:Rationale and objectiveFrailty is common among people with kidney failure treated with hemodialysis (HD). The objective was to describe how frailty evolves over time in people treated by HD, how improvements in frailty and frailty markers are associate with clinical outcomes, and the characteristics that are associated with improvement in frailty.Study designProspective cohort study.Setting and participantsAdults initiating thrice weekly in-center HD in Canada.ExposureWe classified frailty using a 5-point score (3 or more indicates frailty) based on physical inactivity, slowness or weakness, poor endurance or exhaustion, and malnutrition. We categorized the frailty trajectory as never present, improving, deteriorating, and always present.OutcomesAll-cause death, hospitalizations, and placement into long-term care.Analytical approachWe examined the association between time-varying frailty measures and these outcomes using Cox and negative binomial models, after adjustment for potential confounders.Results985 participants were included and followed up for a median of 33 months; 507 (51%) died, 761 (77%) experienced ≥1 hospitalization and 115 (12%) entered long-term care. Overall, 760 (77%) reported frailty during follow-up. Three-quarters (78%) of those with frailty at baseline remained frail throughout the follow-up, 46% without baseline frailty became frail, and 23% with baseline frailty became nonfrail. Higher frailty scores were associated with an increased risk of mortality (fully adjusted HR, 1.58 per unit; 95% CI, 1.39-1.80) and an increased rate of hospitalization (RR, 1.16 per unit; 95% CI, 1.09-1.23). Compared with those who were frail throughout the follow-up, participants with frailty at baseline but improving during follow-up showed a lower mortality (HR, 0.59; 95% CI, 0.42-0.81), and a lower rate of hospitalization (RR, 0.70; 95% CI, 0.56-0.87).LimitationsThere was missing data on frailty at baseline and during follow-up.ConclusionsFrailty was associated with a higher risk of poor outcomes compared with those without frailty, and participants whose status improved from frail to nonfrail showed better clinical outcomes than those who remained frail. These findings emphasize the importance of identifying and implementing effective treatments for frailty in patients receiving maintenance HD.

Project description:BackgroundUnderstanding potentially modifiable factors that influence the risk of frailty is a key concern for the management of this urgent contemporary public health challenge. This study evaluates the association between the use of various medications or alcohol and the incidence of frailty among older adults.MethodsThis study was a retrospective cohort study on older adults (≥ 65 years) using data from the longitudinal Survey of Health, Ageing and Retirement in Europe (SHARE survey, 28 countries). Medication use was measured as taking several different groups of medications. Alcohol use was assessed with SHARE questions corresponding to AUDIT-C. The outcome measure was the incidence of frailty after two years, defined by frailty index (FI) and frailty phenotype (FP). A multiple logistic regression model was used to evaluate the association with adjustment for several potential confounding factors.ResultsOf the 14,665 FI-population participants, 1800 (12.3%) developed frailty within two years. Of the 8133 FP-population participants, 2798 (34.4%) developed pre-frailty and 247 (3.0%) developed frailty within two years of baseline. After adjustment for potential confounding variables, non-hazardous alcohol use (adjusted OR; 95% CI for the FI-population: 0.68; 0.60-0.77) and hazardous alcohol use (0.80; 0.68-0.93) are associated with lower incidence of frailty compared to no alcohol use. The odds of frailty are increased when taking medications; the largest effect size was observed in older adults taking medication for chronic bronchitis (adjusted OR; 95% CI for the FI-population: 2.45; 1.87-3.22), joint pain and other pain medication (2.26; 2.00-2.54), medication for coronary and other heart disease (1.72; 1.52-1.96), medication for diabetes (1.69; 1.46-1.96), and medication for anxiety, depression and sleep problems (1.56; 1.33-1.84). Additionally, the risk of frailty was increased with stroke, Parkinson's disease and dementia.ConclusionsTaking certain groups of medication was associated with increased incidence of frailty and pre-frailty, which might be due to either medication use or the underlying disease. Alcohol use was associated with a lower risk of pre-frailty and frailty compared to no alcohol use, which might be due to reverse causality or residual confounding. There was no significant interaction effect between medication groups and alcohol use on frailty incidence.

Project description:Background & aimsThe intensity and duration of the catabolic phase in COVID-19 patients can differ between survivors and non-survivors. The purpose of the study was to assess the determinants of, and association between, nitrogen balance trajectories and outcome in critically ill COVID-19 patients.MethodsThis retrospective monocentric observational study involved patients admitted to the intensive care unit (ICU) of the University Hospital of Clermont Ferrand, France, from January 2020 to May 2021 for COVID-19 pneumonia. Patients were excluded if referred from another ICU, if their ICU length of stay was <72 h, or if they were treated with renal replacement therapy during the first seven days after ICU admission. Data were collected prospectively at admission and during ICU stay. Death was recorded at the end of ICU stay. Comparisons of the time course of nitrogen balance according to outcome were analyzed using two-way ANOVA. At days 3, 5, 7, 10 and 14, uni- and multivariate logistic regression analyses were performed to assess the impact of a non-negative nitrogen-balance on ICU death. To investigate the relationships between nitrogen balance, inflammatory markers and protein intake, linear and non-nonlinear models were run at days 3, 5 and 7, and the amount of protein intake necessary to reach a neutral nitrogen balance was calculated. Subgroup analyses were carried out according to BMI, age, and sex.Results99 patients were included. At day 3, a similar negative nitrogen balance was observed in survivors and non-survivors: -16.4 g/d [-26.5, -3.3] and -17.3 g/d [-22.2, -3.8] (p = 0.54). The trajectories of nitrogen balance over time thus differed between survivors and non-survivors (p = 0.01). In survivors, nitrogen balance increased over time, but decreased from day 2 to day 6 in non-survivors, and thereafter increased slowly up to day 14. At days 5 and 7, a non-negative nitrogen-balance was protective from death. Administering higher protein amounts was associated with higher nitrogen balance.ConclusionWe report a prolonged catabolic state in COVID patients that seemed more pronounced in non-survivors than in survivors. Our study underlines the need for monitoring urinary nitrogen excretion to guide the amount of protein intake required by COVID-19 patients.

Project description:BackgroundDuring the COVID-19 pandemic, the scarcity of resources has necessitated triage of critical care for patients with the disease. In patients aged 65 years and older, triage decisions are regularly based on degree of frailty measured by the Clinical Frailty Scale (CFS). However, the CFS could also be useful in patients younger than 65 years. We aimed to examine the association between CFS score and hospital mortality and between CFS score and admission to intensive care in adult patients of all ages with COVID-19 across Europe.MethodsThis analysis was part of the COVID Medication (COMET) study, an international, multicentre, retrospective observational cohort study in 63 hospitals in 11 countries in Europe. Eligible patients were aged 18 years and older, had been admitted to hospital, and either tested positive by PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or were judged to have a high clinical likelihood of having SARS-CoV-2 infection by the local COVID-19 expert team. CFS was used to assess level of frailty: fit (CFS1-3), mildly frail (CFS4-5), or frail (CFS6-9). The primary outcome was hospital mortality. The secondary outcome was admission to intensive care. Data were analysed using a multivariable binary logistic regression model adjusted for covariates (age, sex, number of drugs prescribed, and type of drug class as a proxy for comorbidities).FindingsBetween March 30 and July 15, 2020, 2434 patients (median age 68 years [IQR 55-77]; 1480 [61%] men, 954 [30%] women) had CFS scores available and were included in the analyses. In the total sample and in patients aged 65 years and older, frail patients and mildly frail patients had a significantly higher risk of hospital mortality than fit patients (total sample: CFS6-9 vs CFS1-3 odds ratio [OR] 2·71 [95% CI 2·04-3·60], p<0·0001 and CFS4-5 vs CFS1-3 OR 1·54 [1·16-2·06], p=0·0030; age ≥65 years: CFS6-9 vs CFS1-3 OR 2·90 [2·12-3·97], p<0·0001 and CFS4-5 vs CFS1-3 OR 1·64 [1·20-2·25], p=0·0020). In patients younger than 65 years, an increased hospital mortality risk was only observed in frail patients (CFS6-9 vs CFS1-3 OR 2·22 [1·08-4·57], p=0·030; CFS4-5 vs CFS1-3 OR 1·08 [0·48-2·39], p=0·86). Frail patients had a higher incidence of admission to intensive care than fit patients (CFS6-9 vs CFS1-3 OR 1·54 [1·21-1·97], p=0·0010), whereas mildly frail patients had a lower incidence than fit patients (CFS4-5 vs CFS1-3 OR 0·71 [0·55-0·92], p=0·0090). Among patients younger than 65 years, frail patients had an increased incidence of admission to intensive care (CFS6-9 vs CFS1-3 OR 2·96 [1·98-4·43], p<0·0001), whereas mildly frail patients had no significant difference in incidence compared with fit patients (CFS4-5 vs CFS1-3 OR 0·93 [0·63-1·38], p=0·72). Among patients aged 65 years and older, frail patients had no significant difference in the incidence of admission to intensive care compared with fit patients (CFS6-9 vs CFS1-3 OR 1·27 [0·92-1·75], p=0·14), whereas mildly frail patients had a lower incidence than fit patients (CFS4-5 vs CFS1-3 OR 0·66 [0·47-0·93], p=0·018).InterpretationThe results of this study suggest that CFS score is a suitable risk marker for hospital mortality in adult patients with COVID-19. However, treatment decisions based on the CFS in patients younger than 65 years should be made with caution.FundingLOEY Foundation.

Dataset Information

Association of frailty with clinical outcomes in myelofibrosis: a retrospective cohort study.

Publications

Association of frailty with clinical outcomes in myelofibrosis: a retrospective cohort study.

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