Original research| Volume 101, ISSUE 9, P1515-1522.e1, September 2020

Differential Effects of Time to Initiation of Therapy on Disability and Quality of Life in Patients With Mild and Moderate to Severe Ischemic Stroke



      To assess the effect of time to acute therapy on health-related quality of life (HRQoL) and disability after ischemic stroke.


      Prospective cohort study.


      Comprehensive stroke care center in a large metropolitan city.


      Patients (N=553; mean age, 67 y; 51.9% male; 64.4% white; 88.8% ischemic stroke) with ischemic stroke or transient ischemic attack (TIA) enrolled in a longitudinal observational study between August 2012 to January 2014 who received rehabilitation services.


      Not applicable.

      Main Outcome Measures

      Disability status was assessed with the modified Rankin Scale (mRS) and Barthel Index (BI). HRQoL was assessed using the Quality of Life in Neurological Disorders measures of executive function, general cognitive concerns, upper extremity dexterity, and lower extremity mobility. Time to therapy consult and treatment were defined as the number of days from hospital admission to initial consult by a therapist and number of days from hospital admission to initial treatment, respectively.


      Among the participants, the median number of days from hospital admission to acute therapy consult was 2 days (interquartile range, 1-3d). Multivariable linear and logistic regression models indicated that for those with the National Institutes of Health Stroke Scale (NIHSS) score<5, longer time to therapy consult was associated with worse BI scores (BI=100; odds ratio [OR], 0.818; P=.008), executive function T scores (b=–0.865; P=.001), and general cognitive concerns T scores (b=–0.609; P=.009) at 1-month in adjusted analyses. In those with NIHSS score≥5, longer time to therapy treatment led to increased disability (ie, mRS≥ 2; OR, 1.15; P=.039) and lower extremity mobility T scores (b=–0.591; P=.046) at 1 month in adjusted analyses.


      Longer time to initiation of acute therapy has differential effects on poststroke disability and HRQoL up to 1-month after ischemic stroke and TIA. The effect of acute therapy consult is more notable for those with mild deficits, while the effect of acute therapy treatment is more notable for those with moderate to severe deficits. Minimizing time to therapy consults and treatments in the acute hospital period might improve outcomes after ischemic stroke and TIA.


      List of abbreviations:

      BI (Barthel Index), HRQoL (health-related quality of life), ICU (intensive care unit), IQR (interquartile range), LOS (length of stay), MCID (minimal clinically important difference), mRS (modified Rankin Scale), Neuro-QoL (Quality of Life in Neurological Disorders), NIHSS (National Institutes of Health Stroke Scale), PRO (patient-reported outcome), TIA (transient ischemic attack), TOAST (Trial of Org 10172 in Acute Stroke Treatment)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Archives of Physical Medicine and Rehabilitation
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Pollock A.
        • Baer G.
        • Campbell P.
        • et al.
        Physical rehabilitation approaches for the recovery of function and mobility following stroke.
        Cochrane Database Syst Rev. 2014; 4: CD001920
        • Teasell R.
        • Foley N.
        • Salter K.
        • Bhogal S.
        • Jutai J.
        • Speechley M.
        Evidence-based review of stroke rehabilitation: executive summary, 12th edition.
        Top Stroke Rehabil. 2009; 16: 463-488
        • Peiris C.L.
        • Shields N.
        • Brusco N.K.
        • Watts J.J.
        • Taylor N.F.
        Additional physical therapy services reduce length of stay and improve health outcomes in people with acute and subacute conditions: an updated dystematic review and meta-analysis.
        Arch Phys Med Rehabil. 2018; 99: 2299-2312
        • Gittler M.
        • Davis A.M.
        Guidelines for adult stroke rehabilitation and recovery.
        JAMA. 2018; 319: 820-821
        • Winstein C.J.
        • Stein J.
        • Arena R.
        • et al.
        Guidelines for adult stroke rehabilitation and recovery: a guideline for healthcare pofessionals from the American Heart Association/American Stroke Association.
        Stroke. 2016; 47: e98-e169
        • Langhorne P.
        • Collier J.M.
        • Bate P.J.
        • Thuy M.N.
        • Bernhardt J.
        Very early versus delayed mobilisation after stroke.
        Cochrane Database Syst Rev. 2018; 10: CD006187
        • Lynch E.A.
        • Cumming T.
        • Janssen H.
        • Bernhardt J.
        Early mobilization after stroke: Changes in clinical opinion despite an unchanging evidence base.
        J Stroke Cerebrovasc Dis. 2017; 26: 1-6
        • Lynch E.
        • Hillier S.
        • Cadilhac D.
        When should physical rehabilitation commence after stroke: a systematic review.
        Int J Stroke. 2014; 9: 468-478
        • Bernhardt J.
        • Godecke E.
        • Johnson L.
        • Langhorne P.
        Early rehabilitation after stroke.
        Curr Opin Neurol. 2017; 30: 48-54
        • Ganesh A.
        • Luengo-Fernandez R.
        • Wharton R.M.
        • et al.
        Abstract 166: one-month modified Rankin scale (mRS) score predicts five-year disability, death, quality-of-life, and healthcare costs in ischaemic stroke: a prospective cohort study.
        Stroke. 2017; 48: A166
        • Kasner S.E.
        Clinical interpretation and use of stroke scales.
        Lancet Neurol. 2006; 5: 603-612
        • Katzan Irene L.
        • Thompson Nicolas R.
        • Lapin B.
        • Uchino K.
        Added value of patient-reported outcome measures in stroke clinical practice.
        J Am Heart Assoc. 2017; 6e005356
        • Joint Commission
        Specifications manual for joint commission national quality measures (v2018B1).
        (Available at:)
        • Cella D.
        • Yount S.
        • Rothrock N.
        • et al.
        The patient-reported outcomes measurement information system (PROMIS): progress of an NIH roadmap cooperative group during its first two years.
        Med Care. 2007; 45: S3-S11
        • Cella D.
        • Lai J.S.
        • Nowinski C.J.
        • et al.
        Neuro-QOL: brief measures of health-related quality of life for clinical research in neurology.
        Neurology. 2012; 78: 1860-1867
        • Katzan I.L.
        • Fan Y.
        • Uchino K.
        • Griffith S.D.
        The PROMIS physical function scale: a promising scale for use in patients with ischemic stroke.
        Neurology. 2016; 86: 1801-1807
        • Lin C.
        • Katkar M.
        • Lee J.
        • Roth E.
        • Harvey R.L.
        • Prabhakaran S.
        Functional measures upon admission to acute inpatient rehabilitation predict quality of life after ischemic stroke.
        Arch Phys Med Rehab. 2019; 100: 481-487
        • Sangha R.S.
        • Caprio F.Z.
        • Askew R.
        • et al.
        Quality of life in patients with TIA and minor ischemic stroke.
        Neurology. 2015; 85: 1957-1963
        • Reeves M.
        • Lisabeth L.
        • Williams L.
        • et al.
        Patient-reported outcome measures (PROMs) for acute stroke: rationale, methods and future directions.
        Stroke. 2018; 49: 1549-1556
        • Price-Haywood E.G.
        • Harden-Barrios J.
        • Carr C.
        • Reddy L.
        • Bazzano L.A.
        • van Driel M.L.
        Patient-reported outcomes in stroke clinical trials 2002–2016: a systematic review.
        Qual Life Res. 2019; 28: 1119-1128
        • Moran G.M.
        • Fletcher B.
        • Feltham M.G.
        • Calvert M.
        • Sackley C.
        • Marshall T.
        Fatigue, psychological and cognitive impairment following transient ischaemic attack and minor stroke: a systematic review.
        Eur J Neurol. 2014; 21: 1258-1267
        • Fens M.
        • van Heugten C.M.
        • Beusmans G.H.
        • et al.
        Not as transient: patients with transient ischaemic attack or minor stroke experience cognitive and communication problems; an exploratory study.
        Eur J Gen Pract. 2013; 19: 11-16
        • McHutchison C.A.
        • Cvoro V.
        • Makin S.
        • Chappell F.M.
        • Shuler K.
        • Wardlaw J.M.
        Functional, cognitive and physical outcomes 3 years after minor lacunar or cortical ischaemic stroke.
        J Neurol Neurosurg Psychiatry. 2019; 90: 436-443
        • Josephson S.A.
        • Hills N.K.
        • Johnston S.C.
        NIH Stroke scale reliability in ratings from a large sample of clinicians.
        Cerebrovasc Dis. 2006; 22: 389-395
        • Adams Jr., H.P.
        • Davis P.H.
        • Leira E.C.
        • et al.
        Baseline NIH stroke scale score strongly predicts outcome after stroke: a report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST).
        Neurology. 1999; 53: 126-131
        • Adams Jr., H.P.
        • Bendixen B.H.
        • Kappelle L.J.
        • et al.
        Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment.
        Stroke. 1993; 24: 35-41
        • Bruno A.
        • Akinwuntan A.E.
        • Lin C.
        • et al.
        Simplified modified rankin scale questionnaire: reproducibility over the telephone and validation with quality of life.
        Stroke. 2011; 42: 2276-2279
        • Banks J.L.
        • Marotta C.A.
        Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis.
        Stroke. 2007; 38: 1091-1096
        • Collin C.
        • Wade D.T.
        • Davies S.
        • Horne V.
        The Barthel ADL Index: a reliability study.
        Int Disabil Stud. 1988; 10: 61-63
        • de Morton N.A.
        • Keating J.L.
        • Davidson M.
        Rasch analysis of the barthel index in the assessment of hospitalized older patients after admission for an acute medical condition.
        Arch Phys Med Rehabil. 2008; 89: 641-647
        • Gershon R.C.
        • Lai J.S.
        • Bode R.
        • et al.
        Neuro-QOL: quality of life item banks for adults with neurological disorders: item development and calibrations based upon clinical and general population testing.
        Qual Life Res. 2012; 21: 475-486
        • Katzan I.L.
        • Thompson N.
        • Uchino K.
        Innovations in stroke: the use of PROMIS and NeuroQoL scales in clinical stroke trials.
        Stroke. 2016; 47: e27-e30
        • Kozlowski A.J.
        • Singh R.
        • Victorson D.
        • et al.
        Agreement between responses from community-dwelling persons with stroke and their proxies on the NIH neurological quality of life (Neuro-QoL) short forms.
        Arch Phys Med Rehabil. 2015; 96: 1986-1992
        • Bode R.K.
        • Heinemann A.W.
        • Butt Z.
        • et al.
        Development and validation of participation and positive psychologic function measures for stroke survivors.
        Arch Phys Med Rehabil. 2010; 91: 1347-1356
        • Victorson D.
        • Peterman A.
        • Bode R.
        • et al.
        Development and clinical validation of a new item bank and short form of emotional and behavioral dyscontrol for major neurological disorders: results from the Neuro-QOL study.
        J Neurol Disord Stroke. 2015; 3: 1098
        • Rundek T.
        • Mast H.
        • Hartmann A.
        • et al.
        Predictors of resource use after acute hospitalization: the Northern Manhattan Stroke Study.
        Neurology. 2000; 55: 1180-1187
        • Schlegel D.
        • Kolb S.J.
        • Luciano J.M.
        • et al.
        Utility of the NIH stroke scale as a predictor of hospital disposition.
        Stroke. 2003; 34: 134-137
        • Sato S.
        • Toyoda K.
        • Uehara T.
        • et al.
        Baseline NIH stroke scale score predicting outcome in anterior and posterior circulation strokes.
        Neurology. 2008; 70: 2371-2377
        • Prvu Bettger J.A.
        • Kaltenbach L.
        • Reeves M.J.
        • et al.
        Assessing stroke patients for rehabilitation during the acute hospitalization: findings from the get with the guidelines-stroke program.
        Arch Phys Med Rehabil. 2013; 94: 38-45
        • Freburger J.K.
        • Holmes G.M.
        • Ku L.J.
        • Cutchin M.P.
        • Heatwole-Shank K.
        • Edwards L.J.
        Disparities in postacute rehabilitation care for stroke: an analysis of the state inpatient databases.
        Arch Phys Med Rehabil. 2011; 92: 1220-1229
        • Yost K.J.
        • Eton D.T.
        • Garcia S.F.
        • Cella D.
        Minimally important differences were estimated for six patient-reported outcomes measurement information system-cancer scales in advanced-stage cancer patients.
        J Clin Epidemiol. 2011; 64: 507-516
        • Kozlowski A.J.
        • Cella D.
        • Nitsch K.P.
        • Heinemann A.W.
        Evaluating individual change with the Quality of Life in Neurological Disorders (Neuro-QoL) short forms.
        Arch Phys Med Rehabil. 2016; 97: 650-654
        • Revicki D.A.
        • Cella D.
        • Hays R.D.
        • Sloan J.A.
        • Lenderking W.R.
        • Aaronson N.K.
        Responsiveness and minimal important differences for patient reported outcomes.
        Health Qual Life Outcomes. 2006; 4: 70
        • Norman G.R.
        • Sloan J.A.
        • Wyrwich K.W.
        The truly remarkable universality of half a standard deviation: confirmation through another look.
        Expert Rev Pharmacoecon Outcomes Res. 2004; 4: 581-585
        • Tong Y.
        • Cheng Z.
        • Rajah G.B.
        • et al.
        High intensity physical rehabilitation later than 24 h post stroke is beneficial in patients: a pilot randomized controlled trial (RCT) study in mild to moderate ischemic stroke.
        Front Neurol. 2019; 10: 113
        • Avert Trial Collaboration Group
        Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial.
        Lancet. 2015; 386: 46-55
        • Awad A.J.
        • Kellner C.P.
        • Mascitelli J.R.
        • Bederson J.B.
        • Mocco J.
        No early mobilization after stroke: lessons learned from the AVERT trial.
        World Neurosurg. 2016; 87: 474
        • Maulden S.A.
        • Gassaway J.
        • Horn S.D.
        • Smout R.J.
        • DeJong G.
        Timing of initiation of rehabilitation after stroke.
        Arch Phys Med Rehabil. 2005; 86: S34-S40
        • Wang H.
        • Camicia M.
        • DiVita M.
        • Mix J.
        • Niewczyk P.
        Early inpatient rehabilitation admission and stroke patient outcomes.
        Am J Phys Med Rehabil. 2015; 94: 85-96