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Poststroke Fatigue at Admission is Associated With Independence Levels of Activities of Daily Living at Discharge From Subacute Rehabilitation Wards

Open AccessPublished:November 05, 2020DOI:https://doi.org/10.1016/j.apmr.2020.10.117

      Abstract

      Objective

      To determine whether poststroke fatigue at admission is associated with the degree of independence in activities of daily living in patients with stroke at discharge from subacute rehabilitation wards.

      Design

      Retrospective cohort study.

      Setting

      Subacute rehabilitation hospital.

      Participants

      A consecutive sample of patients (N=156) with stroke who were admitted to a subacute rehabilitation ward between December 2012 and November 2013 were enrolled in the study.

      Interventions

      Not applicable.

      Main Outcome Measures

      Poststroke fatigue was assessed using the Fatigue Severity Scale within 2 weeks of admission. Poststroke fatigue was defined as the mean score of 4 points or more from among 9 items in the Fatigue Severity Scale. Functional outcome was assessed by using FIM motor items.

      Results

      Fifty-six (35.9%) of the 156 participants had poststroke fatigue at admission. The scores of the FIM motor items at admission and discharge were significantly lower in the fatigue group than in the nonfatigue group (P<.05). Multiple regression analysis with potentially confounding variables revealed that poststroke fatigue was a significant independent factor for discharge FIM motor items score (P<.05).

      Conclusion

      Poststroke fatigue at admission was significantly associated with functional outcome at discharge from subacute rehabilitation wards. Our findings emphasize that rehabilitation professionals need to manage poststroke fatigue in addition to providing the interventions to improve daily activities in patients with subacute stroke.

      Keywords

      List of abbreviations:

      ADL (activities of daily living), CI (confidence interval), MCID (minimal clinically important difference), SIAS (Stroke Impairment Assessment Set)
      Poststroke fatigue has been described as a feeling of early exhaustion with weariness, lack of energy, and aversion to effort that develops during physical or mental activity and is usually not ameliorated by rest.
      • Staub F.
      • Bogousslavsky J.
      Fatigue after stroke: a major but neglected issue.
      Estimates of the prevalence of poststroke fatigue range from 25% to 85%.
      • Cumming T.B.
      • Packer M.
      • Kramer S.F.
      • English C.
      The prevalence of fatigue after stroke: a systematic review and meta-analysis.
      Poststroke fatigue predicts a lower rate of returning to work, poorer quality of life outcome, and a higher risk of death in individuals with stroke.
      • Wu S.
      • Mead G.
      • Macleod M.
      • Chalder T.
      Model of understanding fatigue after stroke.
      • Hinkle J.L.
      • Becker K.J.
      • Kim J.S.
      • et al.
      Poststroke fatigue: emerging evidence and approaches to management: a scientific statement for healthcare professionals from the American Heart Association.
      • Andersen G.
      • Christensen D.
      • Kirkevold M.
      • Johnsen S.P.
      Post-stroke fatigue and return to work: a 2-year follow-up.
      • Pihlaja R.
      • Uimonen J.
      • Mustanoja S.
      • Tatlisumak T.
      • Poutiainen E.
      Post-stroke fatigue is associated with impaired processing speed and memory functions in first-ever stroke patients.
      • Lerdal A.
      • Gay C.L.
      Fatigue in the acute phase after first stroke predicts poorer physical health 18 months later.
      • van de Port I.G.
      • Kwakkel G.
      • Schepers V.P.
      • Heinemans C.T.
      • Lindeman E.
      Is fatigue an independent factor associated with activities of daily living, instrumental activities of daily living and health-related quality of life in chronic stroke?.
      • Glader E.L.
      • Stegmayr B.
      • Asplund K.
      Poststroke fatigue: a 2-year follow-up study of stroke patients in Sweden.
      • Naess H.
      • Nyland H.
      Poststroke fatigue and depression are related to mortality in young adults: a cohort study.
      However, poststroke fatigue remains a neglected symptom after stroke in clinical practice.
      • Zedlitz A.M.E.E.
      • van Eijk M.
      • Kessels R.P.C.
      • Geurts A.C.H.
      • Fasotti L.
      Poststroke fatigue is still a neglected issue: findings from an internet-based study on the need for information and treatment in the Netherlands.
      Evidence-based interventions for poststroke fatigue have not been established.
      • Hinkle J.L.
      • Becker K.J.
      • Kim J.S.
      • et al.
      Poststroke fatigue: emerging evidence and approaches to management: a scientific statement for healthcare professionals from the American Heart Association.
      ,
      • Wu S.
      • Kutlubaev M.A.
      • Chun H.Y.
      • et al.
      Interventions for post-stroke fatigue.
      The relationship between poststroke fatigue and activities of daily living (ADL) remains controversial.
      • Glader E.L.
      • Stegmayr B.
      • Asplund K.
      Poststroke fatigue: a 2-year follow-up study of stroke patients in Sweden.
      ,
      • Chen Y.K.
      • Qu J.F.
      • Xiao W.M.
      • et al.
      Poststroke fatigue: risk factors and its effect on functional status and health-related quality of life.
      • Mandliya A.
      • Das A.
      • Unnikrishnan J.P.
      • Amal M.G.
      • Sarma P.S.
      • Sylaja P.N.
      Post-stroke fatigue is an independent predictor of post-stroke disability and burden of care: a path analysis study.
      • Badaru U.M.
      • Ogwumike O.O.
      • Adeniyi A.F.
      • Olowe O.O.
      Variation in functional independence among stroke survivors having fatigue and depression.
      • Crosby G.A.
      • Munshi S.
      • Karat A.S.
      • Worthington E.
      • Lincoln N.B.
      Fatigue after stroke: frequency and effect on daily life.
      Poststroke fatigue has been reported to be longitudinally associated with instrumental ADL and health-related quality of life, but not with basic ADL, between 6 and 36 months after stroke.
      • van de Port I.G.
      • Kwakkel G.
      • Schepers V.P.
      • Heinemans C.T.
      • Lindeman E.
      Is fatigue an independent factor associated with activities of daily living, instrumental activities of daily living and health-related quality of life in chronic stroke?.
      One longitudinal study demonstrated that acute-phase fatigue within 2 weeks after the onset of stroke was associated with the inability of patients to be completely independent in ADL measures at 18 months after stroke, even when controlling for potentially confounding variables such as age and baseline ADL.
      • Lerdal A.
      • Gay C.L.
      Acute-phase fatigue predicts limitations with activities of daily living 18 months after first-ever stroke.
      However, information on whether poststroke fatigue at baseline is associated with the degree of independence in future ADL is lacking. Additionally, more than half of the participants in the previously mentioned study
      • Lerdal A.
      • Gay C.L.
      Acute-phase fatigue predicts limitations with activities of daily living 18 months after first-ever stroke.
      discontinued their rehabilitation program before the end of the study. Therefore, it remains unclear whether poststroke fatigue at baseline is associated with functional outcomes when all patients continue rehabilitation, which has been shown to be a strong confounder for outcomes.
      In subacute rehabilitation wards, intensive rehabilitation programs are provided during hospitalization to improve the ability of patients with subacute stroke to perform ADL.
      • Miyai I.
      • Sonoda S.
      • Nagai S.
      • et al.
      Results of new policies for inpatient rehabilitation coverage in Japan.
      We hypothesized that poststroke fatigue would be associated with greater dependence in ADL at discharge from subacute rehabilitation wards, because fatigue may cause stroke patients to avoid or reduce physical activity.
      • Saunders D.H.
      • Greig C.A.
      • Mead G.E.
      Physical activity and exercise after stroke: review of multiple meaningful benefits.
      ,
      • Thilarajah S.
      • Mentiplay B.F.
      • Bower K.J.
      • et al.
      Factors associated with post-stroke physical activity: a systematic review and meta-analysis.
      Evidence supporting this hypothesis would provide a rationale for treating poststroke fatigue in subacute rehabilitation wards. Thus, this study aimed to determine whether poststroke fatigue at admission was associated with levels of independence in ADL at discharge from a subacute rehabilitation ward, even when controlling for potentially confounding variables.

      Methods

      Study design

      This study used a retrospective cohort study design. The study protocol was approved by the appropriate ethics committee (approval no.: 168). The study was conducted based on the Declaration of Helsinki of 1964 guidelines, as revised in 2013. The need for participant consent was waived owing to the retrospective nature of the study.

      Participants

      We retrospectively analyzed 340 consecutive patients with subacute stroke who were admitted to a subacute rehabilitation ward between December 2012 and November 2013. Each patient was examined with computed tomography or magnetic resonance imaging to confirm the diagnosis of stroke. Patients were included in the analyses if poststroke fatigue assessment was performed within 2 weeks of admission to the subacute rehabilitation hospital.

      Data collection

      Poststroke fatigue

      Poststroke fatigue was assessed using the 9-item Fatigue Severity Scale
      • Krupp L.B.
      • LaRocca N.G.
      • Muir-Nash J.
      • Steinberg A.D.
      The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus.
      ,
      • Nadarajah M.
      • Mazlan M.
      • Abdul-Latif L.
      • Goh H.T.
      Test-retest reliability, internal consistency and concurrent validity of Fatigue Severity Scale in measuring post-stroke fatigue.
      within 2 weeks of admission to the subacute rehabilitation ward. Participants rated their level of agreement with 9 statements about fatigue interference on a 7-point Likert scale with scores ranging from 1 to 7 in which “1” indicated strong disagreement and “7” indicated strong agreement. A mean score of 4 points or more on the Fatigue Severity Scale was indicative of poststroke fatigue.
      • Cumming T.B.
      • Packer M.
      • Kramer S.F.
      • English C.
      The prevalence of fatigue after stroke: a systematic review and meta-analysis.

      Functional outcome

      The FIM,
      • Granger C.V.
      • Hamilton B.B.
      • Linacre J.M.
      • Heinemann A.W.
      • Wright B.D.
      Performance profiles of the functional independence measure.
      which was assessed within 2 weeks of admission and within 1 week before discharge from the subacute rehabilitation ward, was collected for functional outcome. Possible scores of the FIM motor items ranged from 13 to 91 points, whereas those of the FIM cognitive items ranged from 5 to 35 points. Additionally, the FIM gain and FIM efficiency scores in the motor and cognition items were calculated to assess the amount of improvement in ADL during hospitalization. The FIM gain was calculated as the difference between the discharge and admission FIM scores.
      • Koh G.C.
      • Chen C.H.
      • Petrella R.
      • Thind A.
      Rehabilitation impact indices and their independent predictors: a systematic review.
      The FIM efficiency score was defined as the FIM gain score divided by the total length of hospital stay.
      • Koh G.C.
      • Chen C.H.
      • Petrella R.
      • Thind A.
      Rehabilitation impact indices and their independent predictors: a systematic review.

      Participants’ demographic and clinical characteristics

      Data on age, sex, body mass index, type of stroke, history of stroke, side of motor paresis, days from stroke onset to admission, length of hospital stay, and comorbidities, including hypertension, diabetes mellitus, hyperlipidemia, and heart diseases, were collected from the participant’s medical records. The type of stroke was categorized as ischemic or hemorrhagic stroke based on computed tomography or magnetic resonance imaging findings.
      Motor impairments, aphasia, and unilateral spatial neglect were assessed using the Stroke Impairment Assessment Set (SIAS)
      • Chino N.
      • Sonoda S.
      • Domen K.
      • Saitoh E.
      • Kimura A.
      Stroke Impairment Assessment Set (SIAS) A new evaluation instrument for stroke patients.
      within 2 weeks of admission to the subacute rehabilitation hospital. The severity of motor impairments was assessed using the motor items of the SIAS. The SIAS motor items consist of 5 items (knee-mouth, finger function, hip-flexion, knee-extension, and foot-pat). The score of each item ranges from 0 to 5 points, with 0 and 5 points indicating complete paralysis and normal movement (ie, same as that of the nonparetic limb), respectively. The total possible score of the SIAS motor items ranges from 0 to 25 points. If motor paresis was bilateral, we used scores from the weaker extremity. Aphasia was assessed using the aphasia item of the SIAS. The presence of aphasia was defined as a score of less than 3 points for an SIAS aphasia item. Unilateral spatial neglect was assessed using the visuospatial perception item of the SIAS. The presence of unilateral spatial neglect was defined as a score of less than 3 points on the SIAS visuospatial perception item.

      Analysis

      The participants were divided into “fatigue” and “nonfatigue” groups based on the Fatigue Severity Scale (≥4 points and <4 points, respectively) scores. Demographic and clinical characteristics were compared between participants with and without poststroke fatigue by using an unpaired t test for continuous variables and a Fisher’s exact test for dichotomous variables, respectively. For the statistical analysis, body mass index was categorized according to World Health Organization cut points
      World Health Organization Regional Office for Europe
      Body mass index – BMI.
      : underweight (<18.5 kg/m2), normal weight (18.5-25.0 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30.0 kg/m2). The scores of the FIM motor and cognition items were compared between the fatigue and nonfatigue groups by using the unpaired t test to examine the association of poststroke fatigue with the ADL. We determined relationships between the FIM score at discharge and other variables at baseline with bivariate analyses using the Pearson’s product-moment correlation coefficient, the unpaired t test, and analysis of variance based on variable types. To determine associations between admission poststroke fatigue and the discharge FIM motor score, we performed a multiple regression analysis for discharge FIM motor score with poststroke fatigue and variables that showed significant association with the discharge FIM motor score in the bivariate analyses. Statistical analyses were conducted by using the Statistical Package for the Social Sciences software, version 24.0.a A P value less than .05 was statistically significant.

      Results

      Participants

      Of the 340 patients who were admitted to the subacute rehabilitation wards, 156 were excluded because they failed to receive the poststroke fatigue assessment within 2 weeks of admission. Another 28 patients were excluded because of missing FIM data at admission or discharge. Thus, 156 patients were included in this analysis. All participants included in this study underwent approximately 120 minutes of a subacute rehabilitation program every day during hospitalization.

      Comparisons of the participants’ characteristics and functional outcome between the fatigue and nonfatigue groups

      Fifty-six (35.9%) participants had poststroke fatigue. The median score of the Fatigue Severity Scale in the fatigue group was 4.56 (interquartile range, 4.11-5.11) points, whereas that of the nonfatigue group was 2.33 (interquartile range, 1.44-3.11) points. Demographic and clinical characteristics in each group are shown in table 1. The length of hospital stay was significantly longer in the fatigue group than in the nonfatigue group (mean difference, 18.2; 95% confidence interval [CI], 5.0-31.6; P=.007). The other demographic and clinical characteristics were not significantly different between the groups (P>.05).
      Table 1Comparisons between the fatigue and nonfatigue group demographic and clinical characteristics
      VariableFatigue Group (n=56)Nonfatigue Group (n=100)Age- and Sex- MatchedNonfatigue Group (n=56)Fatigue Group vs Nonfatigue GroupFatigue Group vs

      56 Matched Nonfatigue Group
      95% CIP Value95% CIP Value
      Age, y64.9±12.667.0±12.165.2±12.3−6.1 to 2.0.310−4.9 to 4.4.922
      SexNA.999NA.999
       Male356335
       Female213721
      Body mass index, kg/m223.0±3.823.9±18.621.6±3.4−5.9 to 4.1.723−0.0 to 2.7.052
      Body mass index categoriesNA.868NA.570
       Underweight51210
       Normal396834
       Overweight101811
       Obese221
      Type of strokeNA.133NA.999
       Ischemic255821
       Hemorrhagic314225
      Previous stroke8 (14.3)13 (13.0)8 (14.3)NA.811NA.999
      Side of motor paresis
       Right263622NA.283NA.295
       Left224118
       Bilateral222
       None62114
      No. of days from stroke onset to admission37.1±12.935.1±12.335.0±11.6−2.2 to 6.1.346−2.5 to 6.7.366
      Length of hospital stay, days93.3±45.675.1±37.175.8±39.15.0-31.6.0071.6-33.4.031
      Total score of the SIAS motor items, points14.8±9.417.2±7.817.0±7.9−5.2 to 0.3.083−5.5 to 1.0.173
      Aphasia12 (21.4)24 (24.0)14 (25.0)NA.843NA.654
      Unilateral spatial neglect11 (19.6)13 (13.0)7 (12.5)NA.355NA.441
      Comorbidities
       Hypertension46 (82.1)84 (84.0)45 (80.4)NA.795NA.809
       Diabetes mellitus18 (32.1)22 (22.0)11 (19.6)NA.144NA.117
       Hyperlipidemia20 (35.7)49 (49.0)21 (37.5)NA.109NA.844
       Heart diseases11 (19.6)24 (24.0)13 (23.2)NA.569NA.681
      NOTE. Values are presented as mean ± SD or as number (%), unless otherwise indicated.
      Abbreviation: NA, not applicable.
      The FIM motor and cognition scores for each group at admission and discharge are shown in table 2. The admission FIM scores were significantly lower in the fatigue group than in the nonfatigue group. The mean differences in the motor and cognition items between groups were –8.4 (95% CI, –15.0 to –1.8; P=.013) and –3.4 (95% CI, –5.7 to –1.1; P=.004), respectively. The discharge FIM scores were also significantly lower in the fatigue group than in the nonfatigue group. The mean differences in the motor and cognition items between groups were –7.9 (95% CI, –12.6 to –3.3; P<.001) and –2.7 (95% CI, –4.5 to –0.9; P=.004), respectively. However, the FIM gain and FIM efficiency scores in the motor and cognition items were not significantly different between the groups (P>.05).
      Table 2Comparison of the FIM scores between the fatigue and nonfatigue groups
      VariableFatigue Group (n=56)Nonfatigue Group (n=100)Age- and Sex-MatchedNonfatigue Group (n=56)Fatigue Group vs Nonfatigue GroupFatigue Group vs

      56 Matched Nonfatigue Group
      95% CIP Value95% CIP Value
      FIM motor score, points
       Admission50.7±21.259.1±19.559.3±20.0−15.0 to −1.8.013−16.3 to −8.8.029
       Discharge73.3±19.281.2±10.281.6±9.4−12.6 to −3.3<.001−13.9 to −2.6.004
       Gain22.6±14.422.1±14.122.3±14.4−4.2 to 5.2.843−5.1 to 5.7.906
       Efficiency, points per day0.29±0.210.30±0.160.31±0.17−0.07 to 0.04.605−0.10 to 0.05.505
      FIM cognition score, points
       Admission24.4±8.627.8±6.127.6±5.7−5.7 to −1.1.004−6.0 to −0.6.019
       Discharge28.4±6.531.1±5.030.9±5.2−4.5 to −0.9.004−4.7 to −0.3.024
       Gain4.02±5.173.31±3.613.27±3.60−0.69 to 2.10.318−0.92 to 2.42.375
       Efficiency, points per day0.05±0.070.05±0.060.05±0.07−0.03 to 0.02.775−0.03 to 0.02.827
      NOTE. Values are presented as mean ± SD.
      To make precise comparisons between participants with and without poststroke fatigue, we compared 56 fatigue participants with 56 age- and sex-matched participants without fatigue. The results were similar to those obtained when comparing the participants with fatigue and all participants without fatigue (see tables 1 and 2).

      Association of fatigue at admission with the discharge FIM motor score after adjusting by confounding variables

      The relationships between the FIM motor score at discharge and other variables are shown in table 3. Older age, female sex, longer length of hospital stay, lower total SIAS motor item score, and lower FIM motor and cognition score at admission were significantly associated with a lower discharge FIM motor score (P<.05). The results of multiple regression analysis are presented in table 4. The analysis (adjusted R2=0.558; P<.001) revealed that that poststroke fatigue (β=–0.122; P=.032) was a significant independent variable for the discharge FIM motor score after adjusting confounding variables.
      Table 3Relationships between the FIM motor items score at discharge and potentially confounding variables
      VariableCorrelation CoefficientP Valuet ValueP ValueF ValueP Value
      Age−0.242<.001NANANANA
      SexNANA2.53.013NANA
      Body mass index categoriesNANANANA0.683.564
      Type of strokeNANA1.22.224NANA
      Previous strokeNANA1.01.314NANA
      Side of motor paresis, right vs leftNANA0.85.397NANA
      No. of days from stroke onset to admission−0.146.069NANANANA
      Length of hospital stay−0.580<.001NANANANA
      Total score of the SIAS motor items0.604<.001NANANANA
      AphasiaNANA1.88.061NANA
      Unilateral spatial neglectNANA1.40.163NANA
      HypertensionNANA1.44.151NANA
      Diabetes mellitusNANA0.146.884NANA
      HyperlipidemiaNANA0.509.612NANA
      Heart diseasesNANA0.821.413NANA
      FIM motor score at admission0.721<.001NANANANA
      FIM cognition score at admission0.479<.001NANANANA
      Abbreviation: NA, not applicable.
      Table 4Multiple regression analysis to determine the FIM motor items score at discharge from the subacute rehabilitation ward
      VariableβCoefficientSEt ValueP Value
      FIM motor score at admission0.4120.2940.0743.965<.001
      Total score of SIAS motor items0.1830.3160.1591.989.049
      FIM cognition score at admission0.1540.3100.1292.406.017
      Poststroke fatigue (present=1, absent=0)−0.122−3.6801.697−2.169.032
      Sex (male=1, female=0)0.1073.2001.6421.947.053
      Age−0.105−0.1240.068−1.811.072
      Length of hospital stay−0.029−0.0100.030−0.343.732
      Constant56.8667.7907.300<.001
      NOTE. F7,147=28.9, P<.001, R2=0.578, adjusted R2=0.558.
      Abbreviations: β, standard coefficient; SE, standard error.

      Discussion

      This study appears to be the first to determine whether poststroke fatigue is associated with levels of independence in ADL at discharge from a subacute rehabilitation ward. Upon admission to the subacute rehabilitation ward, 35.9% of participants with stroke had fatigue. This finding is consistent with those of previous studies reporting that more than one-third of patients have fatigue within the first 3 months after the onset of stroke.
      • Wu S.
      • Mead G.
      • Macleod M.
      • Chalder T.
      Model of understanding fatigue after stroke.
      ,
      • Schepers V.P.
      • Visser-Meily A.M.
      • Ketelaar M.
      • Lindeman E.
      Poststroke fatigue: course and its relation to personal and stroke-related factors.
      • Duncan F.
      • Greig C.
      • Lewis S.
      • et al.
      Clinically significant fatigue after stroke: a longitudinal cohort study.
      • Egerton T.
      • Hokstad A.
      • Askim T.
      • Bernhardt J.
      • Indredavik B.
      Prevalence of fatigue in patients 3 months after stroke and association with early motor activity: a prospective study comparing stroke patients with a matched general population cohort.
      In addition to neurophysiological factors, comorbidities have also been associated with poststroke fatigue.
      • Hinkle J.L.
      • Becker K.J.
      • Kim J.S.
      • et al.
      Poststroke fatigue: emerging evidence and approaches to management: a scientific statement for healthcare professionals from the American Heart Association.
      ,
      • Ponchel A.
      • Bombois S.
      • Bordet R.
      • Hénon H.
      Factors associated with poststroke fatigue: a systematic review.
      Comorbidities such as hypertension and diabetes mellitus may produce fatigue by themselves.
      • Hinkle J.L.
      • Becker K.J.
      • Kim J.S.
      • et al.
      Poststroke fatigue: emerging evidence and approaches to management: a scientific statement for healthcare professionals from the American Heart Association.
      However, we found no significant differences in the proportions of participants with a given comorbidity when comparing between the fatigue and nonfatigue groups. Therefore, the fatigue that participants experienced in this study may not be attributed solely to these comorbidities. The scores of the FIM motor items at admission and discharge were significantly lower in the fatigue group than in the nonfatigue group, even when comparing between 56 matched pairs based on age and sex. Moreover, our results indicated that poststroke fatigue at admission was a significant independent variable for the score of FIM motor items at discharge from a subacute rehabilitation ward, even when controlling for potential confounding variables.
      The lower FIM motor scores in participants with poststroke fatigue at admission support the findings of previous cross-sectional studies indicating that poststroke fatigue was significantly associated with ADL limitations in individuals with stroke.
      • Glader E.L.
      • Stegmayr B.
      • Asplund K.
      Poststroke fatigue: a 2-year follow-up study of stroke patients in Sweden.
      ,
      • Chen Y.K.
      • Qu J.F.
      • Xiao W.M.
      • et al.
      Poststroke fatigue: risk factors and its effect on functional status and health-related quality of life.
      ,
      • Mandliya A.
      • Das A.
      • Unnikrishnan J.P.
      • Amal M.G.
      • Sarma P.S.
      • Sylaja P.N.
      Post-stroke fatigue is an independent predictor of post-stroke disability and burden of care: a path analysis study.
      The level of baseline ADL function in addition to age, stroke type, motor impairment, neurologic status, and comorbidities have been reported as factors associated with the outcome of ADL.
      • Kwakkel G.
      • Wagenaar R.C.
      • Kollen B.J.
      • Lankhorst G.J.
      Predicting disability in stroke--a critical review of the literature.
      • Jeong S.
      • Inoue Y.
      • Kondo K.
      • Matsumoto D.
      • Shiraishi N.
      Formula for predicting FIM for stroke patients at discharge from an acute ward or convalescent rehabilitation ward.
      • Mutai H.
      • Furukawa T.
      • Araki K.
      • Misawa K.
      • Hanihara T.
      Factors associated with functional recovery and home discharge in stroke patients admitted to a convalescent rehabilitation ward.
      • Gialanella B.
      • Santoro R.
      • Ferlucci C.
      Predicting outcome after stroke: the role of basic activities of daily living predicting outcome after stroke.
      • Veerbeek J.M.
      • Kwakkel G.
      • van Wegen E.E.
      • Ket J.C.
      • Heymans M.W.
      Early prediction of outcome of activities of daily living after stroke: a systematic review.
      Therefore, we conducted multiple regression analysis, while controlling for these potentially confounding variables, to examine the relationship between poststroke fatigue at admission and the FIM motor score at discharge. We consequently revealed that poststroke fatigue was a significant independent variable for lower FIM motor score at discharge. A previous longitudinal study also reported that ADL function and fatigue in the acute phase were independent factors for activity limitations at 18 months after stroke onset,
      • Lerdal A.
      • Gay C.L.
      Acute-phase fatigue predicts limitations with activities of daily living 18 months after first-ever stroke.
      which was similar to our results. However, there were 2 major differences between the previous study
      • Lerdal A.
      • Gay C.L.
      Acute-phase fatigue predicts limitations with activities of daily living 18 months after first-ever stroke.
      and the current study. First, the dependent variable used in the multiple regression analysis was different. In the previous study,
      • Lerdal A.
      • Gay C.L.
      Acute-phase fatigue predicts limitations with activities of daily living 18 months after first-ever stroke.
      the dependent variable was defined as whether participants could be completely independent in ADL at 18 months after stroke, whereas our study focused on examining whether poststroke fatigue was related to the degree of dependence in ADL. Another difference was whether participants continued rehabilitation programs until the end of the study. In the previous study,
      • Lerdal A.
      • Gay C.L.
      Acute-phase fatigue predicts limitations with activities of daily living 18 months after first-ever stroke.
      more than half of the participants discontinued rehabilitation services before the end of the study, whereas our study included participants with subacute stroke who were admitted to a rehabilitation hospital and underwent an intensive rehabilitation program to improve ADL throughout the study period. Thus, our study was well controlled with regards to rehabilitation, which has been shown to be a strong confounder for overall outcomes. The findings of the present study offer compelling evidence that poststroke fatigue at admission is associated with levels of independence in ADL at discharge, even after patients underwent intensive rehabilitation programs during the course of hospitalization. These 2 key differences from the previously mentioned study
      • Lerdal A.
      • Gay C.L.
      Acute-phase fatigue predicts limitations with activities of daily living 18 months after first-ever stroke.
      are considered to be the main strengths of this study.
      A systematic review
      • Thilarajah S.
      • Mentiplay B.F.
      • Bower K.J.
      • et al.
      Factors associated with post-stroke physical activity: a systematic review and meta-analysis.
      reported that poststroke fatigue was a factor associated with physical activity in individuals with stroke. Strong evidence indicates that physical activity such as cardiorespiratory endurance exercise improves the ability to perform ADL in individuals with stroke.
      • Saunders D.H.
      • Sanderson M.
      • Hayes S.
      • et al.
      Physical fitness training for stroke patients.
      Patients with poststroke fatigue have poor adherence to rehabilitative efforts because of the significant decrease in physical and mental energy, which may negatively affect improvement in ADL.
      • Chen Y.K.
      • Qu J.F.
      • Xiao W.M.
      • et al.
      Poststroke fatigue: risk factors and its effect on functional status and health-related quality of life.
      ,
      • Saunders D.H.
      • Greig C.A.
      • Mead G.E.
      Physical activity and exercise after stroke: review of multiple meaningful benefits.
      Further studies monitoring the amount of physical activity could explore whether poststroke fatigue at admission leads to the avoidance of physical activity during rehabilitation, which then contributes to ADL limitations at discharge.
      The minimal clinically important difference (MCID) for the FIM motor score in patients with stroke was reported to be 17 points.
      • Beninato M.
      • Gill-Body K.M.
      • Salles S.
      • Stark P.C.
      • Black-Schaffer R.M.
      • Stein J.
      Determination of the minimal clinically important difference in the FIM instrument in patients with stroke.
      The mean gain in the FIM motor score was higher than the MCID, even in the fatigue group. In addition, we found no significant differences in the overall FIM gain score in motor scores between the groups. The mean difference in the FIM motor score at discharge between the fatigue and nonfatigue groups was –8.4 points, which was less than the MCID. Furthermore, multiple regression analysis showed that 4 independent variables explained only 55.8% of the overall variability in the FIM motor score at discharge and the beta coefficient for fatigue was relatively small. Therefore, the influence of poststroke fatigue on improvements in ADL observed in this study was clinically vague, although poststroke fatigue at admission was a statistically significant independent variable for the FIM motor score at discharge. These results may be at least partly attributed to the degree of fatigue experienced in the fatigue group. The median Fatigue Severity Scale score in the fatigue group was 4.56 points, which is only slightly higher than 4 points. Thus, the participants in the fatigue group appeared to have only mild fatigue, which may have reduced the effect of fatigue on functional outcomes in this study. Nonetheless, poststroke fatigue is known to be related to lower levels of physical activity,
      • Thilarajah S.
      • Mentiplay B.F.
      • Bower K.J.
      • et al.
      Factors associated with post-stroke physical activity: a systematic review and meta-analysis.
      a lower rate of returning to work,
      • Andersen G.
      • Christensen D.
      • Kirkevold M.
      • Johnsen S.P.
      Post-stroke fatigue and return to work: a 2-year follow-up.
      ,
      • Pihlaja R.
      • Uimonen J.
      • Mustanoja S.
      • Tatlisumak T.
      • Poutiainen E.
      Post-stroke fatigue is associated with impaired processing speed and memory functions in first-ever stroke patients.
      and poor quality of life outcomes.
      • Lerdal A.
      • Gay C.L.
      Fatigue in the acute phase after first stroke predicts poorer physical health 18 months later.
      ,
      • van de Port I.G.
      • Kwakkel G.
      • Schepers V.P.
      • Heinemans C.T.
      • Lindeman E.
      Is fatigue an independent factor associated with activities of daily living, instrumental activities of daily living and health-related quality of life in chronic stroke?.
      Furthermore, patients with poststroke fatigue lack the energy necessary to perform activities, are more easily tired by activity, experience unpredictable and unexplainable feelings of fatigue, and have increased stress sensitivity and an increased need for longer sleep durations, naps, or rest.
      • Eilertsen G.
      • Ormstad H.
      • Kirkevold M.
      Experiences of poststroke fatigue: qualitative meta-synthesis.
      The main purposes of the subacute rehabilitation wards are not only to improve ADL, but also to avoid prolonged bed rest, to facilitate home discharge, and to improve quality of life. As poststroke fatigue is a modifiable variable,
      • Thilarajah S.
      • Mentiplay B.F.
      • Bower K.J.
      • et al.
      Factors associated with post-stroke physical activity: a systematic review and meta-analysis.
      rehabilitation professionals in subacute rehabilitation wards need to manage poststroke fatigue in addition to providing intensive rehabilitation programs. Education programs, mindfulness-based stress reduction therapy, and physical training have been reported as promising strategies for the treatment of poststroke fatigue.
      • Wu S.
      • Kutlubaev M.A.
      • Chun H.Y.
      • et al.
      Interventions for post-stroke fatigue.
      Psychological and exercise interventions are also recommended to reduce fatigue in other conditions such as multiple sclerosis,
      • Miller P.
      • Soundy A.
      The pharmacological and non-pharmacological interventions for the management of fatigue related multiple sclerosis.
      cancer,
      • Thong M.S.Y.
      • van Noorden C.J.F.
      • Steindorf K.
      • Arndt V.
      Cancer-related fatigue: causes and current treatment options.
      and chronic fatigue syndrome.
      • Kim D.Y.
      • Lee J.S.
      • Park S.Y.
      • Kim S.J.
      • Son C.G.
      Systematic review of randomized controlled trials for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).
      The efficacy of these interventions should be investigated in future randomized controlled trials with more robust study designs and adequate sample sizes.

      Study limitations

      This study had the following limitations. First, we did not include data for depressive symptoms, medications, and pain, which might be confounding factors. We cannot exclude the possibility that depression was a confounding factor between poststroke fatigue at admission and functional outcome in the present study, although poststroke fatigue has been distinguished from depressive symptoms.
      • Hinkle J.L.
      • Becker K.J.
      • Kim J.S.
      • et al.
      Poststroke fatigue: emerging evidence and approaches to management: a scientific statement for healthcare professionals from the American Heart Association.
      ,
      • Wu S.
      • Barugh A.
      • Macleod M.
      • Mead G.
      Psychological associations of poststroke fatigue: a systematic review and meta-analysis.
      • Winward C.
      • Sackley C.
      • Metha Z.
      • Rothwell P.M.
      A population-based study of the prevalence of fatigue after transient ischemic attack and minor stroke.
      • van der Werf S.P.
      • van den Broek H.L.
      • Anten H.W.
      • Bleijenberg G.
      Experience of severe fatigue long after stroke and its relation to depressive symptoms and disease characteristics.
      • Choi-Kwon S.
      • Choi J.
      • Kwon S.U.
      • Kang D.W.
      • Kim J.S.
      Fluoxetine is not effective in the treatment of post-stroke fatigue: a double-blind, placebo-controlled study.
      • Karaiskos D.
      • Tzavellas E.
      • Spengos K.
      • Vassilopoulou S.
      • Paparrigopoulos T.
      Duloxetine versus citalopram and sertraline in the treatment of poststroke depression, anxiety, and fatigue.
      Medications that are commonly prescribed in patients with stroke, including sedatives and antidepressants, may cause fatigue.
      • Hinkle J.L.
      • Becker K.J.
      • Kim J.S.
      • et al.
      Poststroke fatigue: emerging evidence and approaches to management: a scientific statement for healthcare professionals from the American Heart Association.
      ,
      • Ponchel A.
      • Bombois S.
      • Bordet R.
      • Hénon H.
      Factors associated with poststroke fatigue: a systematic review.
      Pain also impairs patient function and may contribute to poststroke fatigue.
      • Wu S.
      • Mead G.
      • Macleod M.
      • Chalder T.
      Model of understanding fatigue after stroke.
      ,
      • Hinkle J.L.
      • Becker K.J.
      • Kim J.S.
      • et al.
      Poststroke fatigue: emerging evidence and approaches to management: a scientific statement for healthcare professionals from the American Heart Association.
      ,
      • Ponchel A.
      • Bombois S.
      • Bordet R.
      • Hénon H.
      Factors associated with poststroke fatigue: a systematic review.
      Therefore, medications taken and pain experience can potentially act to confound the relationship between poststroke fatigue and ADL independence. Second, the persistence of poststroke fatigue over time is well known.
      • Wu S.
      • Mead G.
      • Macleod M.
      • Chalder T.
      Model of understanding fatigue after stroke.
      ,
      • Pihlaja R.
      • Uimonen J.
      • Mustanoja S.
      • Tatlisumak T.
      • Poutiainen E.
      Post-stroke fatigue is associated with impaired processing speed and memory functions in first-ever stroke patients.
      ,
      • Schepers V.P.
      • Visser-Meily A.M.
      • Ketelaar M.
      • Lindeman E.
      Poststroke fatigue: course and its relation to personal and stroke-related factors.
      ,
      • Duncan F.
      • Greig C.
      • Lewis S.
      • et al.
      Clinically significant fatigue after stroke: a longitudinal cohort study.
      The present study was designed to focus on associations between poststroke fatigue at admission and levels of independence in ADL at discharge. Therefore, poststroke fatigue at the time of discharge was not examined. However, future studies using multiple assessments of fatigue during the course of rehabilitation will reveal the effects of fatigue on the final ADL outcome more thoroughly. Finally, participants with stroke in this study were recruited from a single facility. Further multicenter studies are needed to increase the generalizability of our findings.

      Conclusions

      Poststroke fatigue at admission was associated with a lower FIM motor score at discharge, even when controlling for potentially confounding factors. The addition of interventions for poststroke fatigue to rehabilitation programs may be beneficial for patients who are hospitalized in subacute rehabilitation wards.

      Supplier

      • a.
        Statistical Package for the Social Sciences; IBM Corp.

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