- Email: [email protected]
Maximum Tolerated Dose of Walking for Community-Dwelling People Recovering From Hip Fracture: A Dose-Response Trial
Accepted Manuscript The maximum tolerated dose of walking for community-dwelling people recovering from hip fracture: a dose-response trial Casey Peiris, PhD, Nora Shields, PhD, Michael Kingsley, PhD, Jack Yeung, BPO, Raphael Hau, MBBS, Nicholas Taylor, PhD PII:
S0003-9993(17)30261-7
DOI:
10.1016/j.apmr.2017.03.027
Reference:
YAPMR 56871
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 16 March 2017 Accepted Date: 29 March 2017
Please cite this article as: Peiris C, Shields N, Kingsley M, Yeung J, Hau R, Taylor N, The maximum tolerated dose of walking for community-dwelling people recovering from hip fracture: a doseresponse trial, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2017), doi: 10.1016/ j.apmr.2017.03.027. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Running head: Walking after hip fracture Title: The maximum tolerated dose of walking for community-dwelling people recovering from hip fracture: a dose-response trial
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Authors: Casey Peiris PhD1,2, Nora Shields PhD1,2, Michael Kingsley PhD1, Jack Yeung BPO2, Raphael Hau MBBS2,3 and Nicholas Taylor PhD1,4
Service, Community Therapy Service, Allied Health.
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Affiliations:
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Institution: Northern Health, Bundoora Extended Care Centre and Broadmeadows Health
La Trobe University, College of Science, Health and Engineering, Department of
Rehabilitation, Nutrition and Sport, Allied Health, Physiotherapy.
Northern Health, Northern Centre for Health Education and Research
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Northern Clinical School, University of Melbourne
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Eastern Health, Eastern Health Clinical Research Office
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Financial support: this research was supported by a Northern Health Foundation research
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grant.
Conflicts of interest: The authors have no conflicts of interest to declare. Corresponding author: Casey Peiris Address: Level 5, HS3, La Trobe University, Melbourne, Australia, 3086 Phone: +613 9479 5931
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Email: [email protected]
Clinical Trial Registration Number: Australian and New Zealand Clinical Trials Registry
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The maximum tolerated dose of walking for community-dwelling people recovering from
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hip fracture: a dose-response trial
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Abstract
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Objective: To determine how much moderate-intensity physical activity, in the form of
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walking, could be prescribed for people living in the community after hip fracture in terms
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of safety, tolerability and feasibility.
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Design: Phase I dose-response design.
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Setting: Participants were recruited from two public community rehabilitation centres in
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Melbourne, Australia.
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Participants: Community-dwelling adults (n=21, 16 women, mean age ± SD, 75 ± 9 years)
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who were cognitively alert, attending community rehabilitation after a hip fracture (mean ±
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SD days post fracture, 110 ± 47 days), able to walk with or without a gait aid and for whom it
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was safe to participate in physical activity.
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Intervention: Individually supervised doses of moderate intensity walking completed in one
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week in addition to their usual levels of physical activity. Three participants were required to
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complete a dose of walking prior to dose escalation for the next cohort of three
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participants. Dose escalation ceased when more than one participant in a cohort had an
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adverse event or was unable to tolerate the dose or if the maximum dose of 150 minutes
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per week was achieved.
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Main Outcome Measures: Maximum tolerated dose of walking per week (minutes), adverse
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events, mobility and walking confidence.
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ACCEPTED MANUSCRIPT Results: The maximum tolerated dose of walking for adults after hip fracture before
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significant discomfort was experienced (e.g. breathlessness, pain, fatigue) by any participant
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was 100 minutes per week. No adverse events occurred but participants began to be unable
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to tolerate higher doses beyond 100 minutes per week.
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Conclusions: This provides preliminary evidence that community-dwelling older adults
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recovering from hip fracture can complete a sufficient amount of moderate intensity
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physical activity to maintain and improve their health.
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Introduction
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Regular physical activity is associated with positive health outcomes (1). These positive
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health outcomes have led to guidelines advocating adults should accumulate at least 30
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minutes of moderate-intensity aerobic activity in bouts of 10 minutes on at least 5 days of
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the week (2). Further, it is recommended that older adults who are limited by health
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conditions be “as physically active as their abilities and conditions allow” (3). As little as 92
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minutes of moderate-intensity physical activity a week can have long-term health benefits
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for community-dwelling adults and older adults (4).
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Resuming physical activity can be difficult after hip fracture. Following a hip fracture, more
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than 66% of people experience a catastrophic decline in their ability to walk in the
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community (5) and only 40% eventually return to their pre-injury level of walking (6, 7).
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Compared to their pre-fracture activity, people after hip fracture have much reduced levels
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of physical and leisure time activity (8-10). Two months after a hip fracture, people spend as
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ACCEPTED MANUSCRIPT little as 1.8 minutes a day in moderate-intensity physical activity (9). Three to 12 months
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after hip fracture physical activity levels remain low at 2 minutes a day in at least moderate-
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intensity physical activity (11). In addition, poor ambulatory status and sustained lack of
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physical activity after hip fracture can increase the risk of sustaining a second hip fracture
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(12, 13).
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The pattern of inactivity begins immediately after hip fracture. People after hip fracture
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spend 99% of their time sitting or lying down in acute hospital (14) and 23 out of 24 hours
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per day sitting or lying down in inpatient rehabilitation (15). This lack of activity leads to
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deconditioning, muscle loss and reduced aerobic capacity. However, a recent systematic
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review of 19 trials including 1589 older adults after hip fracture found rehabilitation
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programs that included more intensive exercise were most likely to enhance mobility after
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hip fracture (16). People with hip fracture who are more active during rehabilitation have
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better recovery and longer term functional ability (17); and older adults after hip fractures
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are able to safely perform moderate to high intensity exercise at home (18) at sufficent
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intensity to enable them to achieve long-term health benefits (1, 4). This suggests that
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people after hip fracture may be capable of, and benefit from, being more physically active
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than they currently are.
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While there is strong evidence that physical activity is beneficial for health, and there is a
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rationale to promote physical activity for patients following hip fracture, it is not known how
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much physical activity is appropriate and safe for people after hip fracture. Application of
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public health physical activity guidelines may not be appropriate for patients recovering
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from injury and surgery due to factors such as reduced mobility, function and lack of
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confidence. During early inpatient rehabilitation people with hip fracture (mean 15 days
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ACCEPTED MANUSCRIPT post-surgery) were only able to tolerate 6 minutes of additional walking per day in a dose-
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response trial (19). In early inpatient rehabilitation, patients may have difficulty in meeting
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recommended physical activity levels due to reduced mobility, and other factors such as
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fatigue, pain, co-morbidities and psychological factors. Rehabilitation aims to increase
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people’s function to prepare them for living independently in the community. Therefore
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when people with hip fracture are living independently in the community after discharge
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from inpatient rehabilitation they may be more likely to achieve or approach physical
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activity guidelines. However, no previous studies have assessed the maximum tolerated
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dose of walking for people recovering from hip fracture in the community.
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As there are no specific guidelines on how much walking people can do after hip fracture,
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rather than estimate how much walking they can do when they are discharged from hospital
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or base it on individual clinical judgement, this trial applied dose-response design methods
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to determine the maximum tolerated dose of walking. This design is commonly used to
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determine the maximum tolerated dose for medications and has been used to determine
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the maximum tolerated dose of walking for inpatients with hip fracture during rehabilitation
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(19) and community-dwelling people with severe knee osteoarthritis (20). Knowledge of the
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maximum tolerated dose of walking could inform clinicians prescribing exercise programs
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for people recovering from hip fracture.
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The primary aim of this dose-response trial was to find out how much moderate-intensity
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physical activity, in the form of walking, could be prescribed for people living in the
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community after hip fracture in terms of safety, tolerability and feasibility.
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The secondary aims were to describe participants’ physical activity levels, mobility and
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walking confidence.
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Method
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Design
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This study was a phase I dose-response design using an algorithm-based A+B design; the 3+3
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design (21, 22). The study was prospectively registered with the Australian and New Zealand
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Clinical Trials Registry (ACTRN12614001101673). The trial received ethics approval from the
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relevant ethics committees and all participants provided written informed consent.
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Setting
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Participants were recruited from two publicly funded community rehabilitation centres in
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northern metropolitan Melbourne, Australia. Community rehabilitation provides outpatient,
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multidisciplinary services to people living in the community after a recent acute illness or
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injury. Participants were recruited between November 2014 and March 2016.
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Participants
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Community-dwelling adults were eligible to participate if they attended community
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rehabilitation following surgical management of a hip fracture, could walk independently
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with or without a gait aid and if it was safe for them to participate in moderate intensity
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physical activity as assessed by the Physical Activity Readiness Questionnaire (PAR-Q) (23).
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Adults with moderate or severe cognitive impairment, as assessed by the Short Portable
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Mental Status Questionnaire (24) were not eligible to participate because they may not
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have been able to respond to self-report questionnaires. Community rehabilitation
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ACCEPTED MANUSCRIPT therapists referred potential participants to researchers for eligibility screening and to
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obtain written informed consent.
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Intervention
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Participants were individually supervised by an allied health professional to walk at a
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prescribed dose over one week.
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The dose of prescribed physical activity followed a modified Fibonacci scheme starting with
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an initial dose of 10 minutes of supervised walking per week for the first 3 participants, with
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dose increments until the value of 150 minutes of walking per week, as specified in physical
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activity recommendations, was reached (table 1). Dose escalation depended on the
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presence or absence of adverse events and tolerability.
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Participants accumulated the required physical activity during walking bouts of 10 minutes
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or more. Participants walked with their usual assistive device and were instructed to walk at
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a moderate level of intensity (determined by the Borg CR-10 rating of perceived exertion
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scale, where 3 = moderate “I am still comfortable but am breathing a little harder”).
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Participants were advised to continue their usual daily activities and prescribed
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rehabilitation exercises (e.g. hip strengthening exercises) but not to do any additional
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walking.
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Dose escalation
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[INSERT FIGURE 1 ABOUT HERE]
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ACCEPTED MANUSCRIPT The first cohort of three participants received the same initial dose (dose x) (figure 1). If no
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participant stopped due to an adverse event and all participants tolerated the dose, the next
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cohort of three participants received the next dose (dose x + 1). If one participant per cohort
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stopped due to an adverse event or was not able to tolerate the dose, a second cohort of
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three participants were prescribed the same dose (dose x). If one out of six participants had
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an adverse event or was unable to tolerate the dose, then the study continued as planned at
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the next higher dose (dose x + 1). If two or more participants out of the six had an adverse
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event or were not able to tolerate the dose, the dose escalation stopped at that level and
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the previous dose was considered the maximum tolerated dose (dose x – 1).
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Safety and feasibility considerations
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A dose was considered ‘not tolerated’ and stopped if a participant felt physically unable to
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continue walking but did not have an adverse event. Tolerability issues included pain,
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fatigue and shortness of breath that were not considered severe and that resolved within an
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hour of resting.
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An adverse event was defined as any incident that occurred during or immediately after the
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walking intervention that prevented a participant from completing the prescribed dose of
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walking for safety reasons. These included significant, unrelenting pain during or after
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walking, difficulty breathing, new or unrelenting chest pain, or acute change in conscious
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level.
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Feasibility related to problems preventing participation but not resulting from participation.
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For example, not feeling like walking due to lack of motivation or poor weather conditions
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as opposed to having to stop walking due to increased pain as a result of the walking. If a
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ACCEPTED MANUSCRIPT feasibility issue occurred more than once during the week, the participant was excluded
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from walking. In this case a replacement participant was included before the dose could be
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escalated.
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Outcomes
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The primary outcomes were: maximum tolerated dose of prescribed walking; and feasibility
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of completing the prescribed dose of walking.
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Secondary outcomes were mobility, walking confidence and baseline physical activity.
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Mobility was assessed by the De Morton Mobility Index (DEMMI; scores range from 0 to 100
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with low scores indicating poor mobility) (25) at baseline and on completion of the walking
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dose. Walking confidence was evaluated by the Ambulatory Self Confidence Questionnaire
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(scores range from 0 to 10 with 0 indicating low levels of confidence) (26). Baseline physical
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activity over the previous 3 months was assessed using the International Physical Activity
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Questionnaire (IPAQ-WA). The IPAQ-WA is a valid and reliable self-report questionnaire for
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assessing planned and incidental physical activity levels in older adults (27). The IPAQ-WA
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takes into account all physical activity, including low intensity physical activity required to
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complete usual activities of living. Considering a basal level of activity of one hour per day is
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required to complete usual activities of daily living, individuals are considered to be inactive
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if they complete less than 1.5 hours of total activity per day (28).
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To monitor compliance with the trial protocol cadence (used as an indicator of walking
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intensity was averaged from three 30-second timed step counts over each session), self-
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reported walking intensity (Borg CR-10) and pain (0-10 VAS) were monitored during
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prescribed walking sessions. Walking cadence >100 steps/minute is generally accepted as
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moderate intensity (29) but a cadence of > 60 is more often achieved in the community and
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may be beneficial to health (30) and therefore may be considered moderate intensity for
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people with mobility impairment.
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Data analysis
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Based on the traditional algorithm based design and dose escalation (22), it was estimated
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the maximum number of participants would be 48 (eight dose levels with a maximum of six
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participants at each dose).
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The primary analysis was based on decision rules described by Lin and Shih (22) to
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determine the maximum tolerated dose (minutes of walking) in relation to adverse events
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and tolerability (figure 1). Feasibility was described by reporting the number of occasions
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that a feasibility issue prevented walking. IBM SPSS version 22.0 was used for statistical
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analyses. Mean ± SD were used for descriptive statistics, pre-post comparisons were made
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using paired t-tests for continuous outcomes, and associations between walking dose and
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secondary outcomes were explored using Pearson’s r correlation coefficient (r). A p-value of
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.05 was considered statistically significant.
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Results
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Recruitment
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Thirty-four potential participants were referred over the recruitment period. Of these, six
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were ineligible and seven declined to participate) (figure 2). Outcome data were obtained
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for all participants. [INSERT FIGURE 2 ABOUT HERE]
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Participant characteristics
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Twenty-one community-dwelling adults (16 women) with hip fracture participated in the
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trial. Participants had a mean age of 75 ± 9 years and were a mean of 110 ± 47 days post-
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surgery (table 2). Participants mean baseline hip pain was 1.5 ± 1.9 out of 10. Nine
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participants walked with a wheeled frame, six used elbow crutches, four used a single-point
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stick and two walked without a gait aid. Participants had mobility limitations (mean baseline
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DEMMI score 63 ± 14 out of 100) and reduced walking confidence (mean baseline ASCQ
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score 6.5 ± 1.7 out of 10). Anecdotally, almost all of the participants reported they had not
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been for a walk outside of their own garden since their hip fracture. Using the IPAQ-WA
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participants reported doing a mean of 1.0 ± 0.8 hours of planned and incidental physical
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activities per day. Eight participants (38%) reported completing no planned walking activity
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over the previous 3 months.
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Maximum tolerated dose
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The maximum tolerated dose of walking was 100 minutes per week. All participants were
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able to tolerate all doses up to and including 100 minutes per week. There were no
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tolerability or safety issues at any of these doses. One supervised walk was cancelled (dose
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7) due to the feasibility issue of very hot weather. Two of three participants recruited to 10
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issues. Participant 20 could not tolerate the dose due to shortness of breath on exertion.
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Participant 21 could not tolerate the dose due to fatigue and knee pain. No adverse events
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occurred and participants recovered quickly with rest.
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Secondary outcomes
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After 1 week (post-walking) participants had improved mobility (DEMMI mean difference
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5.3, 95%CI 1.7 to 8.9, p=.006). No changes were detected for walking confidence (ASCQ
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mean difference 0.4, 95%CI -0.1 to 0.9).
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Walking dose had a moderate positive correlation to Borg rating of perceived exertion (r =
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.48, p = .028). There were no other significant associations between dose and measured
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outcomes (table 3).
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Compliance with trial protocol
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The mean Borg rating of perceived exertion during supervised walking was 3.9 ± 0.9 units.
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The mean cadence of participants during supervised walking was 86 ± 12 steps/minute.
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Fifteen participants reported some pain during walking with a mean VAS pain rating of 1.5 ±
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1.3 (not significantly different from baseline, p=.93).
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Discussion
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ACCEPTED MANUSCRIPT In addition to usual baseline activity, the maximum tolerated dose of prescribed moderate-
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intensity walking for community-dwelling older adults who were an average of 3.6 months
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after surgery for hip fracture was 100 minutes per week. Participants walked at moderate
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intensity with a mean cadence of 86 steps per minute. One week of supervised walking did
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not appear to improve participants’ walking confidence. Mobility improved statistically,
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although the amount of improvement was likely less than the amount considered to be
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clinically significant (25). The current trial showed that compared to their ability during
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inpatient rehabilitation (19), adults with hip fracture have an increased capacity to complete
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moderate-intensity walking 3 months after surgery. This should give clinicians confidence to
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educate and prescribe graduated walking and exercise programs for their patients on
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discharge.
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Completing 100 minutes of moderate intensity walking per week would incur positive health
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benefits. Compared to inactive individuals, those who exercised for 92 minutes a week had
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a 14% reduced risk of all-cause mortality and 3 year longer life expectancy (4). Another large
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population study (31) also supports the idea that participating in physical activity, even
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below the recommended levels, can lead to positive health outcomes compared to being
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inactive. For adults in Sweden and the USA, 75 minutes of moderate-intensity physical
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activity a week was associated with 1.8 years gain in life expectancy compared to being
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inactive (31).
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Despite appearing to have the physical capacity to participate in a sufficient amount of
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moderate intensity physical activity (18), people with hip fracture remain relatively inactive.
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Participants in our trial lacked confidence in walking outdoors (as indicated by the ASCQ)
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and required encouragement and reassurance during their individually supervised walking
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ACCEPTED MANUSCRIPT sessions. The participants were also inactive prior to participating in the research as
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indicated by the IPAQ-WA. Participants completed an average of one hour of physical
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activity per day which is considered inactive (28), and is only a third of the levels completed
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by healthy older adults (27). These findings support previous research that people are
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relatively inactive after hip fracture (9, 11) and have reduced confidence (10, 32) and ability
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to walk outdoors and in the community (10, 33).
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A major barrier preventing older adults with mobility limitations from participating in
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regular physical activity is fear and a major motivator is health maintenance (34).
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Considering this fear, people with hip fracture need education and support to facilitate their
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participation in physical activity. Rehabilitation clinicians need to educate their patients with
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hip fracture on the importance of commencing or resuming regular physical activity for
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health. Facilitation to participate in physical activity may be achieved through outdoor
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mobility practice during inpatient rehabilitation, referral to community rehabilitation
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services to increase outdoor walking or other exercise options, and involving family and
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community groups for supervision and encouragement.
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Study limitations
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The maximum tolerated dose of walking could not fall outside of the pre-specified doses
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because of the trial design. However, the strength of the trial design was that it gave clear
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guidance to dose escalation and safety. Another limitation was all of the walking was
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supervised. This meant that participants did not have complete autonomy and flexibility to
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fit in extra bouts of walking at any time in order to achieve their prescribed doses. This may
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have limited the maximum dose achieved. While supervision ensured adherence to the
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protocol, this additional support provided by the supervising allied health professional may
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ACCEPTED MANUSCRIPT not be sustainable for practice. We did not control for background levels of physical activity
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and all participants were also participating in community rehabilitation which may have
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impacted on their ability to complete a dose but overall levels of baseline activity were low.
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Promisingly, this shows that older adults after hip fracture are able to complete both
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rehabilitation and walking concurrently. Our sample size was relatively small but there was a
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clear increase in difficulty when trying to achieve the 125 minute dose. Our participants’
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characteristics were similar to previous research on people with hip fracture (5, 11, 16, 18)
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suggesting our results may be generalizable. However, the heterogeneity within the sample
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in relation to fracture type, surgery, comorbidity (e.g. poor cardiovascular fitness) and gait
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aids used may have affected results, although there is evidence of similar outcomes
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regardless of fracture type and surgery type (35). The results from this phase I trial can
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inform larger trials to investigate whether medium to long term maintenance of the
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prescribed maximum tolerated dose of walking leads to health benefits.
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Conclusion
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The maximum tolerated dose of walking for adults after hip fracture before significant
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discomfort was experienced (e.g. breathlessness, pain, fatigue) by any participant was 100
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minutes per week. No adverse events occurred but participants began to be unable to
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tolerate higher doses beyond 100 minutes per week. This provides preliminary evidence
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that it is safe and feasible for community-dwelling older adults to complete moderate-
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intensity walking 3 months after hip fracture. This should give rehabilitation clinicians and
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of physical activity to maintain and improve health.
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16. Handoll HH, Sherrington C, Mak JC. Interventions for improving mobility after hip fracture surgery in adults. Cochrane Database of Systematic Reviews. 2011
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17. Talkowski JB, Lenze EJ, Munin MC, Harrison C, Brach JS. Patient participation and
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18. Mangione KK, Craik RL, Tomlinson SS, Palombaro KM. Can elderly patients who have
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had a hip fracture perform moderate- to high-intensity exercise at home? Physical
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Therapy. 2005;85(8):727-39. PubMed PMID: 16048421.
19. Taylor NF, Peiris CL, Kennedy G, Shields N. Walking tolerance of patients recovering
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from hip fracture: a phase I trial. Disability and Rehabilitation. 2016; DOI:
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20. Wallis JA, Webster KE, Levinger P, Singh PJ, Fong C, Taylor NF. The maximum tolerated dose of walking for people with severe osteoarthritis of the knee: a phase I
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21. Gao F, Trinkaus K, Maher JP. Early phase clinical trials: phase I and II. Handbook of Statistics. 27. Amsterdam: Elsevier; 2008.
22. Lin Y, Shih WJ. Statistical properties of the traditional algorithm-based designs for phase I cancer clinical trials. Biostatistics. 2001;2:203 - 15.
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23. Thomas S, Reading J, Shephard RJ. Revision of the Physical Activity Readiness
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Questionnaire (PAR-Q). Canadian Journal of Sport Sciences. 1992;17(4):338-45.
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PubMed PMID: 1330274.
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24. Pfieffer E. A short portable mental status questionnaire for the assessment of organic brain deficit in elderly patients. Journal of the American Geriatric Society.
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1975;23:9.
25. de Morton NA, Davidson M, Keating JL. The de Morton Mobility Index (DEMMI): an
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essential health index for an ageing world. Health & Quality of Life Outcomes.
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2008;6:63. PubMed PMID: 18713451. Pubmed Central PMCID: PMC2551589.
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26. Asano M, Miller WC, Eng JJ. Development and psychometric properties of the
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ambulatory self-confidence questionnaire. Gerontology. 2007;53(6):373-81. PubMed
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PMID: 17622732.
27. Delbaere K, Hauer K, Lord SR. Evaluation of the Incidental and Planned Physical
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Activity Questionnaire (IPAQ) for older people. British Journal of Sports Medicine.
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2009;doi: 10.1136/bjsm.2009.060350
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28. Guidelines for data processing and analysis of the International Physical Activity Questionnaire (IPAQ) – short form. Version 2.2. April 2004. Accessed 10 November
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2016. http://www.institutferran.org/documentos/scoring_short_ipaq_april04.pdf
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29. Rowe DA, Welk GJ, Heil DP, Mahar MT, Kemble CD, Calabra MA, Camenisch K. Stride
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rate recommendations for moderate-intensity walking. Medicine and Science in
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Sports and Exercise. 2011;43:312-18 30. Tudor-Locke C, Camhi SM, Leonardi C, Johnson WD, Katzmarzyk PT, Earnest CP,
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Church TS. Patterns of adult stepping cadence in the 2005-2006 NHANES.
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Preventative Medicine 2011;53:178-81 19
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31. Moore SC, Patel AV, Matthews CE, Berrington de Gonzalez A, Park Y, Katki HA, Linet
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MS, Weiderpass E, VisvanathanK, Helzlsouer KJ, Thun M, Gapstur SM, Hartge P, Lee I-
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M. Leisure time physical activity of moderate to vigorous intensity and mortality: A
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large pooled cohort analysis. PLOS Medicine. 2010;9(11):e1001335 32. Dennett AM, Taylor NF, Mulrain K. Community ambulation after hip fracture:
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completing tasks to enable access to common community venues. Disability &
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Rehabilitation. 2012;34(9):707-14. PubMed PMID: 22010644.
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33. Nevalainen TH, Hiltunen LA, Jalovaara P. Functional ability after hip fracture among patients home-dwelling at the time of fracture. Central European Journal of Public
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Health. 2004 Dec;12(4):211-6. PubMed PMID: 15666460.
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34. Rasinaho M, Hirvensalo M, Leinonen R, Lintunen T, Rantanen T. Motives for and barriers to physical activity among older adults with mobility limitations. Journal of
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Ageing and Physical Activity. 2006;15:90-102
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35. Butler M, Forte ML, Joglekar SB, Swiontkowski MF, Kane RL. Evidence summary:
Systematic review of surgical treatments for geriatric hip fractures. The Journal of
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Bone and Joint Surgery American Volume. 2011;93:1104-05
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Figure legends
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Figure 1. Study design. Phase I, 3+3 design
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Figure 2. Flow of participants through the trial
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21
ACCEPTED MANUSCRIPT Table 1: Prescribed doses of moderate intensity walking.
1
10
2
20
100%
3
35
75%
4
55
57%
5
75
36%
6
100
33%
7
125
8
150
25% 20%
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Increment
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Minutes per week
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Age, mean (SD) Gender (Male:Female)
Dose 1
Dose 2
Dose 3
Dose 4
(n=3)
(n=3)
(n=3)
(n=3)
73 (10)
76 (10)
65 (16)
84 (4)
0:3
0:3
1:2
1:2
Surgery type Hemiarthroplasty
-
THR
-
ORIF
1
Dose 5
Dose 6
Dose 7
TOTAL
(n=3)
(n=3)
(n=3)
(n=21)
79 (4)
78 (4)
70 (7)
75 (9)
1:2
0:3
2:1
5:16
1
3
1
2
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Characteristic
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1
1
4
2
1
3
3
2
14
1
Days post-surgery, mean (SD)
71 (24)
68 (16)
176 (18)
129 (62)
124 (42)
127 (12)
78 (35)
110 (47)
DEMMI baseline , mean (SD)
53 (11)
56 (3)
54 (9)
72 (4)
74 (12)
53 (9)
80 (17)
63 (14)
ASCQ baseline, mean (SD)
5.5 (3.2)
6.9 (1.0)
5.2 (2.9)
7.2 (0.7)
7.0 (2.3)
4.9 (1.7)
7.4 (0.7)
6.3 (2.0)
IPAQ-WA total activity (hours
7.6 (8.6)
7.1 (7.6)
9.5 (7.0)
10.7 (3.8)
7.9 (2.9)
1.8 (1.3)
6.0 (4.2)
7.2 (5.5)
2.1 (3.4)
0.6 (1.1)
2.7 (1.7)
3.4 (3.4)
3.1 (0.9)
0.3 (0.5)
0.5 (0.6)
1.8 (2.1)
1.3 (1.2)
.7 (1.2)
.7 (1.2)
2.7 (2.3)
0 (0)
1.5 (1.9)
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per week), mean (SD) Baseline pain, mean (SD) (0-10)
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IPAQ-WA walking activity (hours
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per week), mean (SD)
4 (3)
1.3 (1.2)
Table 2. Participant characteristics and baseline measures
Note: SD=standard deviation; DEMMI = de Morten Mobility Index; ASCQ = Ambulatory self-confidence questionnaire; IPAQ-WA = Incidental and Planned Physical Activity Questionnaire THR = total hip replacement; ORIF = open reduction and internal fixation
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Dose 2
Dose 3
Dose 4
Dose 5
Dose 6
Dose 7
TOTAL
Correlation with dose,
(n=3)
(n=3)
(n=3)
(n=3)
(n=3)
(n=3)
(n=3)
(n=21)
Pearson’s r (significance)
68.0 (8.5)
67.7 (6.0)
68.3 (16)
69.3 (4.0)
77.3 (13.3)
56 (10.4)
80.3 (17.4)
69.7 (12.5)
.31 (p=.57)
7.2 (1)
6.7 (0.5)
5.6 (2.5)
7.9 (1.2)
8.5 (.4)
5.1 (1.4)
7.4 (1.8)
6.9 (1.7)
.02 (p=.94)
Hip pain, mean (SD) (0-10)
1.7 (2.1)
1.5 (1.3)
1.8 (.8)
2.7 (1.2)
0.4 (.8)
1.0 (1.2)
1.3 (1.6)
1.5 (1.3)
-.21 (p=.36)
Borg, mean (SD) (0-10)
3.3 (.6)
3.7 (.6)
3.7 (.6)
4.0 (1.0)
3.3 (.6)
4.0 (1.0)
5.0 (1.0)
3.9 (.9)
.48 ( p = .028*)
Post DEMMI, mean (SD) Post ASCQ, mean (SD)
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Outcome
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Note: DEMMI = de Morten Mobility Index; SD=standard deviation; ASCQ = Ambulatory self-confidence questionnaire; *denotes statistically significant
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3 participants
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0 adverse events or tolerability issues
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Figure 1. Study design. Phase I, 3+3 design
>1 adverse events or tolerability issues
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1 adverse event or tolerability issue
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0 adverse events or tolerability issues
≥1 adverse events or tolerability issues
Maximum tolerated dose reached
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Ineligible (n = 6)
No longer receiving community therapy, n = 2 Not recent hip fracture, n = 1 Not cognitively intact, n = 1 Medically unwell, n = 2
Declined (n = 7)
Not interested, n = 5 Anxious about walking, n = 2
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Figure 2. Flow of participants through the trial
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Potentially eligible participants identified by physiotherapists, n= 34
S0003-9993(17)30261-7
DOI:
10.1016/j.apmr.2017.03.027
Reference:
YAPMR 56871
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 16 March 2017 Accepted Date: 29 March 2017
Please cite this article as: Peiris C, Shields N, Kingsley M, Yeung J, Hau R, Taylor N, The maximum tolerated dose of walking for community-dwelling people recovering from hip fracture: a doseresponse trial, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2017), doi: 10.1016/ j.apmr.2017.03.027. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Running head: Walking after hip fracture Title: The maximum tolerated dose of walking for community-dwelling people recovering from hip fracture: a dose-response trial
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Authors: Casey Peiris PhD1,2, Nora Shields PhD1,2, Michael Kingsley PhD1, Jack Yeung BPO2, Raphael Hau MBBS2,3 and Nicholas Taylor PhD1,4
Service, Community Therapy Service, Allied Health.
1
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Affiliations:
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Institution: Northern Health, Bundoora Extended Care Centre and Broadmeadows Health
La Trobe University, College of Science, Health and Engineering, Department of
Rehabilitation, Nutrition and Sport, Allied Health, Physiotherapy.
Northern Health, Northern Centre for Health Education and Research
3
Northern Clinical School, University of Melbourne
4
Eastern Health, Eastern Health Clinical Research Office
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Financial support: this research was supported by a Northern Health Foundation research
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grant.
Conflicts of interest: The authors have no conflicts of interest to declare. Corresponding author: Casey Peiris Address: Level 5, HS3, La Trobe University, Melbourne, Australia, 3086 Phone: +613 9479 5931
ACCEPTED MANUSCRIPT Fax: +613 9495 3254
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Email: [email protected]
Clinical Trial Registration Number: Australian and New Zealand Clinical Trials Registry
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(ACTRN12614001101673)
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The maximum tolerated dose of walking for community-dwelling people recovering from
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hip fracture: a dose-response trial
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Abstract
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Objective: To determine how much moderate-intensity physical activity, in the form of
6
walking, could be prescribed for people living in the community after hip fracture in terms
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of safety, tolerability and feasibility.
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Design: Phase I dose-response design.
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Setting: Participants were recruited from two public community rehabilitation centres in
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Melbourne, Australia.
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Participants: Community-dwelling adults (n=21, 16 women, mean age ± SD, 75 ± 9 years)
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who were cognitively alert, attending community rehabilitation after a hip fracture (mean ±
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SD days post fracture, 110 ± 47 days), able to walk with or without a gait aid and for whom it
14
was safe to participate in physical activity.
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Intervention: Individually supervised doses of moderate intensity walking completed in one
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week in addition to their usual levels of physical activity. Three participants were required to
17
complete a dose of walking prior to dose escalation for the next cohort of three
18
participants. Dose escalation ceased when more than one participant in a cohort had an
19
adverse event or was unable to tolerate the dose or if the maximum dose of 150 minutes
20
per week was achieved.
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Main Outcome Measures: Maximum tolerated dose of walking per week (minutes), adverse
22
events, mobility and walking confidence.
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ACCEPTED MANUSCRIPT Results: The maximum tolerated dose of walking for adults after hip fracture before
24
significant discomfort was experienced (e.g. breathlessness, pain, fatigue) by any participant
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was 100 minutes per week. No adverse events occurred but participants began to be unable
26
to tolerate higher doses beyond 100 minutes per week.
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Conclusions: This provides preliminary evidence that community-dwelling older adults
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recovering from hip fracture can complete a sufficient amount of moderate intensity
29
physical activity to maintain and improve their health.
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Introduction
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Regular physical activity is associated with positive health outcomes (1). These positive
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health outcomes have led to guidelines advocating adults should accumulate at least 30
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minutes of moderate-intensity aerobic activity in bouts of 10 minutes on at least 5 days of
36
the week (2). Further, it is recommended that older adults who are limited by health
37
conditions be “as physically active as their abilities and conditions allow” (3). As little as 92
38
minutes of moderate-intensity physical activity a week can have long-term health benefits
39
for community-dwelling adults and older adults (4).
40
Resuming physical activity can be difficult after hip fracture. Following a hip fracture, more
41
than 66% of people experience a catastrophic decline in their ability to walk in the
42
community (5) and only 40% eventually return to their pre-injury level of walking (6, 7).
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Compared to their pre-fracture activity, people after hip fracture have much reduced levels
44
of physical and leisure time activity (8-10). Two months after a hip fracture, people spend as
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ACCEPTED MANUSCRIPT little as 1.8 minutes a day in moderate-intensity physical activity (9). Three to 12 months
46
after hip fracture physical activity levels remain low at 2 minutes a day in at least moderate-
47
intensity physical activity (11). In addition, poor ambulatory status and sustained lack of
48
physical activity after hip fracture can increase the risk of sustaining a second hip fracture
49
(12, 13).
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The pattern of inactivity begins immediately after hip fracture. People after hip fracture
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spend 99% of their time sitting or lying down in acute hospital (14) and 23 out of 24 hours
52
per day sitting or lying down in inpatient rehabilitation (15). This lack of activity leads to
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deconditioning, muscle loss and reduced aerobic capacity. However, a recent systematic
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review of 19 trials including 1589 older adults after hip fracture found rehabilitation
55
programs that included more intensive exercise were most likely to enhance mobility after
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hip fracture (16). People with hip fracture who are more active during rehabilitation have
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better recovery and longer term functional ability (17); and older adults after hip fractures
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are able to safely perform moderate to high intensity exercise at home (18) at sufficent
59
intensity to enable them to achieve long-term health benefits (1, 4). This suggests that
60
people after hip fracture may be capable of, and benefit from, being more physically active
61
than they currently are.
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While there is strong evidence that physical activity is beneficial for health, and there is a
63
rationale to promote physical activity for patients following hip fracture, it is not known how
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much physical activity is appropriate and safe for people after hip fracture. Application of
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public health physical activity guidelines may not be appropriate for patients recovering
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from injury and surgery due to factors such as reduced mobility, function and lack of
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confidence. During early inpatient rehabilitation people with hip fracture (mean 15 days
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ACCEPTED MANUSCRIPT post-surgery) were only able to tolerate 6 minutes of additional walking per day in a dose-
69
response trial (19). In early inpatient rehabilitation, patients may have difficulty in meeting
70
recommended physical activity levels due to reduced mobility, and other factors such as
71
fatigue, pain, co-morbidities and psychological factors. Rehabilitation aims to increase
72
people’s function to prepare them for living independently in the community. Therefore
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when people with hip fracture are living independently in the community after discharge
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from inpatient rehabilitation they may be more likely to achieve or approach physical
75
activity guidelines. However, no previous studies have assessed the maximum tolerated
76
dose of walking for people recovering from hip fracture in the community.
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As there are no specific guidelines on how much walking people can do after hip fracture,
78
rather than estimate how much walking they can do when they are discharged from hospital
79
or base it on individual clinical judgement, this trial applied dose-response design methods
80
to determine the maximum tolerated dose of walking. This design is commonly used to
81
determine the maximum tolerated dose for medications and has been used to determine
82
the maximum tolerated dose of walking for inpatients with hip fracture during rehabilitation
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(19) and community-dwelling people with severe knee osteoarthritis (20). Knowledge of the
84
maximum tolerated dose of walking could inform clinicians prescribing exercise programs
85
for people recovering from hip fracture.
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The primary aim of this dose-response trial was to find out how much moderate-intensity
87
physical activity, in the form of walking, could be prescribed for people living in the
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community after hip fracture in terms of safety, tolerability and feasibility.
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The secondary aims were to describe participants’ physical activity levels, mobility and
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walking confidence.
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Method
93
Design
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This study was a phase I dose-response design using an algorithm-based A+B design; the 3+3
96
design (21, 22). The study was prospectively registered with the Australian and New Zealand
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Clinical Trials Registry (ACTRN12614001101673). The trial received ethics approval from the
98
relevant ethics committees and all participants provided written informed consent.
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Setting
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Participants were recruited from two publicly funded community rehabilitation centres in
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northern metropolitan Melbourne, Australia. Community rehabilitation provides outpatient,
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multidisciplinary services to people living in the community after a recent acute illness or
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injury. Participants were recruited between November 2014 and March 2016.
104
Participants
105
Community-dwelling adults were eligible to participate if they attended community
106
rehabilitation following surgical management of a hip fracture, could walk independently
107
with or without a gait aid and if it was safe for them to participate in moderate intensity
108
physical activity as assessed by the Physical Activity Readiness Questionnaire (PAR-Q) (23).
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Adults with moderate or severe cognitive impairment, as assessed by the Short Portable
110
Mental Status Questionnaire (24) were not eligible to participate because they may not
111
have been able to respond to self-report questionnaires. Community rehabilitation
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ACCEPTED MANUSCRIPT therapists referred potential participants to researchers for eligibility screening and to
113
obtain written informed consent.
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Intervention
115
Participants were individually supervised by an allied health professional to walk at a
116
prescribed dose over one week.
117
The dose of prescribed physical activity followed a modified Fibonacci scheme starting with
118
an initial dose of 10 minutes of supervised walking per week for the first 3 participants, with
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dose increments until the value of 150 minutes of walking per week, as specified in physical
120
activity recommendations, was reached (table 1). Dose escalation depended on the
121
presence or absence of adverse events and tolerability.
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[INSERT TABLE 1 ABOUT HERE]
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Participants accumulated the required physical activity during walking bouts of 10 minutes
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or more. Participants walked with their usual assistive device and were instructed to walk at
125
a moderate level of intensity (determined by the Borg CR-10 rating of perceived exertion
126
scale, where 3 = moderate “I am still comfortable but am breathing a little harder”).
127
Participants were advised to continue their usual daily activities and prescribed
128
rehabilitation exercises (e.g. hip strengthening exercises) but not to do any additional
129
walking.
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Dose escalation
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[INSERT FIGURE 1 ABOUT HERE]
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ACCEPTED MANUSCRIPT The first cohort of three participants received the same initial dose (dose x) (figure 1). If no
133
participant stopped due to an adverse event and all participants tolerated the dose, the next
134
cohort of three participants received the next dose (dose x + 1). If one participant per cohort
135
stopped due to an adverse event or was not able to tolerate the dose, a second cohort of
136
three participants were prescribed the same dose (dose x). If one out of six participants had
137
an adverse event or was unable to tolerate the dose, then the study continued as planned at
138
the next higher dose (dose x + 1). If two or more participants out of the six had an adverse
139
event or were not able to tolerate the dose, the dose escalation stopped at that level and
140
the previous dose was considered the maximum tolerated dose (dose x – 1).
141
Safety and feasibility considerations
142
A dose was considered ‘not tolerated’ and stopped if a participant felt physically unable to
143
continue walking but did not have an adverse event. Tolerability issues included pain,
144
fatigue and shortness of breath that were not considered severe and that resolved within an
145
hour of resting.
146
An adverse event was defined as any incident that occurred during or immediately after the
147
walking intervention that prevented a participant from completing the prescribed dose of
148
walking for safety reasons. These included significant, unrelenting pain during or after
149
walking, difficulty breathing, new or unrelenting chest pain, or acute change in conscious
150
level.
151
Feasibility related to problems preventing participation but not resulting from participation.
152
For example, not feeling like walking due to lack of motivation or poor weather conditions
153
as opposed to having to stop walking due to increased pain as a result of the walking. If a
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ACCEPTED MANUSCRIPT feasibility issue occurred more than once during the week, the participant was excluded
155
from walking. In this case a replacement participant was included before the dose could be
156
escalated.
157
Outcomes
158
The primary outcomes were: maximum tolerated dose of prescribed walking; and feasibility
159
of completing the prescribed dose of walking.
160
Secondary outcomes were mobility, walking confidence and baseline physical activity.
161
Mobility was assessed by the De Morton Mobility Index (DEMMI; scores range from 0 to 100
162
with low scores indicating poor mobility) (25) at baseline and on completion of the walking
163
dose. Walking confidence was evaluated by the Ambulatory Self Confidence Questionnaire
164
(scores range from 0 to 10 with 0 indicating low levels of confidence) (26). Baseline physical
165
activity over the previous 3 months was assessed using the International Physical Activity
166
Questionnaire (IPAQ-WA). The IPAQ-WA is a valid and reliable self-report questionnaire for
167
assessing planned and incidental physical activity levels in older adults (27). The IPAQ-WA
168
takes into account all physical activity, including low intensity physical activity required to
169
complete usual activities of living. Considering a basal level of activity of one hour per day is
170
required to complete usual activities of daily living, individuals are considered to be inactive
171
if they complete less than 1.5 hours of total activity per day (28).
172
To monitor compliance with the trial protocol cadence (used as an indicator of walking
173
intensity was averaged from three 30-second timed step counts over each session), self-
174
reported walking intensity (Borg CR-10) and pain (0-10 VAS) were monitored during
175
prescribed walking sessions. Walking cadence >100 steps/minute is generally accepted as
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moderate intensity (29) but a cadence of > 60 is more often achieved in the community and
177
may be beneficial to health (30) and therefore may be considered moderate intensity for
178
people with mobility impairment.
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Data analysis
181
Based on the traditional algorithm based design and dose escalation (22), it was estimated
182
the maximum number of participants would be 48 (eight dose levels with a maximum of six
183
participants at each dose).
184
The primary analysis was based on decision rules described by Lin and Shih (22) to
185
determine the maximum tolerated dose (minutes of walking) in relation to adverse events
186
and tolerability (figure 1). Feasibility was described by reporting the number of occasions
187
that a feasibility issue prevented walking. IBM SPSS version 22.0 was used for statistical
188
analyses. Mean ± SD were used for descriptive statistics, pre-post comparisons were made
189
using paired t-tests for continuous outcomes, and associations between walking dose and
190
secondary outcomes were explored using Pearson’s r correlation coefficient (r). A p-value of
191
.05 was considered statistically significant.
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Results
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Recruitment
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Thirty-four potential participants were referred over the recruitment period. Of these, six
197
were ineligible and seven declined to participate) (figure 2). Outcome data were obtained
198
for all participants. [INSERT FIGURE 2 ABOUT HERE]
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Participant characteristics
201
Twenty-one community-dwelling adults (16 women) with hip fracture participated in the
202
trial. Participants had a mean age of 75 ± 9 years and were a mean of 110 ± 47 days post-
203
surgery (table 2). Participants mean baseline hip pain was 1.5 ± 1.9 out of 10. Nine
204
participants walked with a wheeled frame, six used elbow crutches, four used a single-point
205
stick and two walked without a gait aid. Participants had mobility limitations (mean baseline
206
DEMMI score 63 ± 14 out of 100) and reduced walking confidence (mean baseline ASCQ
207
score 6.5 ± 1.7 out of 10). Anecdotally, almost all of the participants reported they had not
208
been for a walk outside of their own garden since their hip fracture. Using the IPAQ-WA
209
participants reported doing a mean of 1.0 ± 0.8 hours of planned and incidental physical
210
activities per day. Eight participants (38%) reported completing no planned walking activity
211
over the previous 3 months.
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[INSERT TABLE 2 ABOUT HERE]
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Maximum tolerated dose
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The maximum tolerated dose of walking was 100 minutes per week. All participants were
215
able to tolerate all doses up to and including 100 minutes per week. There were no
216
tolerability or safety issues at any of these doses. One supervised walk was cancelled (dose
217
7) due to the feasibility issue of very hot weather. Two of three participants recruited to 10
ACCEPTED MANUSCRIPT dose 7 (125 minutes per week) were unable to complete their doses due to tolerability
219
issues. Participant 20 could not tolerate the dose due to shortness of breath on exertion.
220
Participant 21 could not tolerate the dose due to fatigue and knee pain. No adverse events
221
occurred and participants recovered quickly with rest.
222
Secondary outcomes
223
After 1 week (post-walking) participants had improved mobility (DEMMI mean difference
224
5.3, 95%CI 1.7 to 8.9, p=.006). No changes were detected for walking confidence (ASCQ
225
mean difference 0.4, 95%CI -0.1 to 0.9).
226
Walking dose had a moderate positive correlation to Borg rating of perceived exertion (r =
227
.48, p = .028). There were no other significant associations between dose and measured
228
outcomes (table 3).
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[INSERT TABLE 3 ABOUT HERE]
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Compliance with trial protocol
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The mean Borg rating of perceived exertion during supervised walking was 3.9 ± 0.9 units.
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The mean cadence of participants during supervised walking was 86 ± 12 steps/minute.
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Fifteen participants reported some pain during walking with a mean VAS pain rating of 1.5 ±
234
1.3 (not significantly different from baseline, p=.93).
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Discussion
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ACCEPTED MANUSCRIPT In addition to usual baseline activity, the maximum tolerated dose of prescribed moderate-
239
intensity walking for community-dwelling older adults who were an average of 3.6 months
240
after surgery for hip fracture was 100 minutes per week. Participants walked at moderate
241
intensity with a mean cadence of 86 steps per minute. One week of supervised walking did
242
not appear to improve participants’ walking confidence. Mobility improved statistically,
243
although the amount of improvement was likely less than the amount considered to be
244
clinically significant (25). The current trial showed that compared to their ability during
245
inpatient rehabilitation (19), adults with hip fracture have an increased capacity to complete
246
moderate-intensity walking 3 months after surgery. This should give clinicians confidence to
247
educate and prescribe graduated walking and exercise programs for their patients on
248
discharge.
249
Completing 100 minutes of moderate intensity walking per week would incur positive health
250
benefits. Compared to inactive individuals, those who exercised for 92 minutes a week had
251
a 14% reduced risk of all-cause mortality and 3 year longer life expectancy (4). Another large
252
population study (31) also supports the idea that participating in physical activity, even
253
below the recommended levels, can lead to positive health outcomes compared to being
254
inactive. For adults in Sweden and the USA, 75 minutes of moderate-intensity physical
255
activity a week was associated with 1.8 years gain in life expectancy compared to being
256
inactive (31).
257
Despite appearing to have the physical capacity to participate in a sufficient amount of
258
moderate intensity physical activity (18), people with hip fracture remain relatively inactive.
259
Participants in our trial lacked confidence in walking outdoors (as indicated by the ASCQ)
260
and required encouragement and reassurance during their individually supervised walking
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ACCEPTED MANUSCRIPT sessions. The participants were also inactive prior to participating in the research as
262
indicated by the IPAQ-WA. Participants completed an average of one hour of physical
263
activity per day which is considered inactive (28), and is only a third of the levels completed
264
by healthy older adults (27). These findings support previous research that people are
265
relatively inactive after hip fracture (9, 11) and have reduced confidence (10, 32) and ability
266
to walk outdoors and in the community (10, 33).
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A major barrier preventing older adults with mobility limitations from participating in
268
regular physical activity is fear and a major motivator is health maintenance (34).
269
Considering this fear, people with hip fracture need education and support to facilitate their
270
participation in physical activity. Rehabilitation clinicians need to educate their patients with
271
hip fracture on the importance of commencing or resuming regular physical activity for
272
health. Facilitation to participate in physical activity may be achieved through outdoor
273
mobility practice during inpatient rehabilitation, referral to community rehabilitation
274
services to increase outdoor walking or other exercise options, and involving family and
275
community groups for supervision and encouragement.
276
Study limitations
277
The maximum tolerated dose of walking could not fall outside of the pre-specified doses
278
because of the trial design. However, the strength of the trial design was that it gave clear
279
guidance to dose escalation and safety. Another limitation was all of the walking was
280
supervised. This meant that participants did not have complete autonomy and flexibility to
281
fit in extra bouts of walking at any time in order to achieve their prescribed doses. This may
282
have limited the maximum dose achieved. While supervision ensured adherence to the
283
protocol, this additional support provided by the supervising allied health professional may
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ACCEPTED MANUSCRIPT not be sustainable for practice. We did not control for background levels of physical activity
285
and all participants were also participating in community rehabilitation which may have
286
impacted on their ability to complete a dose but overall levels of baseline activity were low.
287
Promisingly, this shows that older adults after hip fracture are able to complete both
288
rehabilitation and walking concurrently. Our sample size was relatively small but there was a
289
clear increase in difficulty when trying to achieve the 125 minute dose. Our participants’
290
characteristics were similar to previous research on people with hip fracture (5, 11, 16, 18)
291
suggesting our results may be generalizable. However, the heterogeneity within the sample
292
in relation to fracture type, surgery, comorbidity (e.g. poor cardiovascular fitness) and gait
293
aids used may have affected results, although there is evidence of similar outcomes
294
regardless of fracture type and surgery type (35). The results from this phase I trial can
295
inform larger trials to investigate whether medium to long term maintenance of the
296
prescribed maximum tolerated dose of walking leads to health benefits.
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Conclusion
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The maximum tolerated dose of walking for adults after hip fracture before significant
301
discomfort was experienced (e.g. breathlessness, pain, fatigue) by any participant was 100
302
minutes per week. No adverse events occurred but participants began to be unable to
303
tolerate higher doses beyond 100 minutes per week. This provides preliminary evidence
304
that it is safe and feasible for community-dwelling older adults to complete moderate-
305
intensity walking 3 months after hip fracture. This should give rehabilitation clinicians and
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ACCEPTED MANUSCRIPT people with hip fracture confidence that they will be able to complete a sufficient amount
307
of physical activity to maintain and improve health.
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References
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2. Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, et al. Physical activity and public health: updated recommendation for adults from the American College of
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3. WHO. World Health Organisation Global recommendations on physical activity for health: 65 years and above, 2011 [cited 2015 14 September]. Available from:
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7. Koval KJ, Zuckerman JD. Functional recovery after fracture of the hip. Journal of Bone
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8. Bernhardt J, Borschmann K, Crock D, Hill K, McGann A, DeGoori M (2005): Stand up and be counted: measuring time spent upright after hip fracture and comparison
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10. Taylor NF, Barelli C, Harding KE. Community ambulation before and after hip fracture: a qualitative analysis. Disability & Rehabilitation. 2010;32(15):1281-90.
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12. Chang JD, Yoo JH, Reddy P, Lee SS, Hwang JH, Kim TY. Risk factors for contra-lateral
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13. Rodaro E, Wade R, Woodward Y, Pendleton N, Baldwin R, Tarrier N, et al. Functional
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14. Davenport SJ, Arnold M, Hua C, Schenck A, Batten S, Taylor NF (2015): Physical
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activity levels during acute inpatient admission after hip fracture are very low.
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15. Peiris C, Taylor NF, Shields N. Patients receiving inpatient rehabilitation for lower
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limb orthopaedic conditions do much less physical activity than recommended in
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16. Handoll HH, Sherrington C, Mak JC. Interventions for improving mobility after hip fracture surgery in adults. Cochrane Database of Systematic Reviews. 2011
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17. Talkowski JB, Lenze EJ, Munin MC, Harrison C, Brach JS. Patient participation and
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physical activity during rehabilitation and future functional outcomes in patients
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18. Mangione KK, Craik RL, Tomlinson SS, Palombaro KM. Can elderly patients who have
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19. Taylor NF, Peiris CL, Kennedy G, Shields N. Walking tolerance of patients recovering
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from hip fracture: a phase I trial. Disability and Rehabilitation. 2016; DOI:
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20. Wallis JA, Webster KE, Levinger P, Singh PJ, Fong C, Taylor NF. The maximum tolerated dose of walking for people with severe osteoarthritis of the knee: a phase I
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21. Gao F, Trinkaus K, Maher JP. Early phase clinical trials: phase I and II. Handbook of Statistics. 27. Amsterdam: Elsevier; 2008.
22. Lin Y, Shih WJ. Statistical properties of the traditional algorithm-based designs for phase I cancer clinical trials. Biostatistics. 2001;2:203 - 15.
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23. Thomas S, Reading J, Shephard RJ. Revision of the Physical Activity Readiness
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Questionnaire (PAR-Q). Canadian Journal of Sport Sciences. 1992;17(4):338-45.
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PubMed PMID: 1330274.
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24. Pfieffer E. A short portable mental status questionnaire for the assessment of organic brain deficit in elderly patients. Journal of the American Geriatric Society.
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25. de Morton NA, Davidson M, Keating JL. The de Morton Mobility Index (DEMMI): an
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essential health index for an ageing world. Health & Quality of Life Outcomes.
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2008;6:63. PubMed PMID: 18713451. Pubmed Central PMCID: PMC2551589.
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26. Asano M, Miller WC, Eng JJ. Development and psychometric properties of the
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ambulatory self-confidence questionnaire. Gerontology. 2007;53(6):373-81. PubMed
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PMID: 17622732.
27. Delbaere K, Hauer K, Lord SR. Evaluation of the Incidental and Planned Physical
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Activity Questionnaire (IPAQ) for older people. British Journal of Sports Medicine.
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28. Guidelines for data processing and analysis of the International Physical Activity Questionnaire (IPAQ) – short form. Version 2.2. April 2004. Accessed 10 November
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2016. http://www.institutferran.org/documentos/scoring_short_ipaq_april04.pdf
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29. Rowe DA, Welk GJ, Heil DP, Mahar MT, Kemble CD, Calabra MA, Camenisch K. Stride
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rate recommendations for moderate-intensity walking. Medicine and Science in
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Sports and Exercise. 2011;43:312-18 30. Tudor-Locke C, Camhi SM, Leonardi C, Johnson WD, Katzmarzyk PT, Earnest CP,
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Church TS. Patterns of adult stepping cadence in the 2005-2006 NHANES.
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31. Moore SC, Patel AV, Matthews CE, Berrington de Gonzalez A, Park Y, Katki HA, Linet
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MS, Weiderpass E, VisvanathanK, Helzlsouer KJ, Thun M, Gapstur SM, Hartge P, Lee I-
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M. Leisure time physical activity of moderate to vigorous intensity and mortality: A
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large pooled cohort analysis. PLOS Medicine. 2010;9(11):e1001335 32. Dennett AM, Taylor NF, Mulrain K. Community ambulation after hip fracture:
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completing tasks to enable access to common community venues. Disability &
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Rehabilitation. 2012;34(9):707-14. PubMed PMID: 22010644.
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33. Nevalainen TH, Hiltunen LA, Jalovaara P. Functional ability after hip fracture among patients home-dwelling at the time of fracture. Central European Journal of Public
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Health. 2004 Dec;12(4):211-6. PubMed PMID: 15666460.
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34. Rasinaho M, Hirvensalo M, Leinonen R, Lintunen T, Rantanen T. Motives for and barriers to physical activity among older adults with mobility limitations. Journal of
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Ageing and Physical Activity. 2006;15:90-102
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35. Butler M, Forte ML, Joglekar SB, Swiontkowski MF, Kane RL. Evidence summary:
Systematic review of surgical treatments for geriatric hip fractures. The Journal of
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Bone and Joint Surgery American Volume. 2011;93:1104-05
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Figure legends
418
Figure 1. Study design. Phase I, 3+3 design
419
Figure 2. Flow of participants through the trial
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21
ACCEPTED MANUSCRIPT Table 1: Prescribed doses of moderate intensity walking.
1
10
2
20
100%
3
35
75%
4
55
57%
5
75
36%
6
100
33%
7
125
8
150
25% 20%
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Increment
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Minutes per week
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Dose
Age, mean (SD) Gender (Male:Female)
Dose 1
Dose 2
Dose 3
Dose 4
(n=3)
(n=3)
(n=3)
(n=3)
73 (10)
76 (10)
65 (16)
84 (4)
0:3
0:3
1:2
1:2
Surgery type Hemiarthroplasty
-
THR
-
ORIF
1
Dose 5
Dose 6
Dose 7
TOTAL
(n=3)
(n=3)
(n=3)
(n=21)
79 (4)
78 (4)
70 (7)
75 (9)
1:2
0:3
2:1
5:16
1
3
1
2
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Characteristic
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1
1
4
2
1
3
3
2
14
1
Days post-surgery, mean (SD)
71 (24)
68 (16)
176 (18)
129 (62)
124 (42)
127 (12)
78 (35)
110 (47)
DEMMI baseline , mean (SD)
53 (11)
56 (3)
54 (9)
72 (4)
74 (12)
53 (9)
80 (17)
63 (14)
ASCQ baseline, mean (SD)
5.5 (3.2)
6.9 (1.0)
5.2 (2.9)
7.2 (0.7)
7.0 (2.3)
4.9 (1.7)
7.4 (0.7)
6.3 (2.0)
IPAQ-WA total activity (hours
7.6 (8.6)
7.1 (7.6)
9.5 (7.0)
10.7 (3.8)
7.9 (2.9)
1.8 (1.3)
6.0 (4.2)
7.2 (5.5)
2.1 (3.4)
0.6 (1.1)
2.7 (1.7)
3.4 (3.4)
3.1 (0.9)
0.3 (0.5)
0.5 (0.6)
1.8 (2.1)
1.3 (1.2)
.7 (1.2)
.7 (1.2)
2.7 (2.3)
0 (0)
1.5 (1.9)
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per week), mean (SD) Baseline pain, mean (SD) (0-10)
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per week), mean (SD)
4 (3)
1.3 (1.2)
Table 2. Participant characteristics and baseline measures
Note: SD=standard deviation; DEMMI = de Morten Mobility Index; ASCQ = Ambulatory self-confidence questionnaire; IPAQ-WA = Incidental and Planned Physical Activity Questionnaire THR = total hip replacement; ORIF = open reduction and internal fixation
ACCEPTED MANUSCRIPT
Dose 2
Dose 3
Dose 4
Dose 5
Dose 6
Dose 7
TOTAL
Correlation with dose,
(n=3)
(n=3)
(n=3)
(n=3)
(n=3)
(n=3)
(n=3)
(n=21)
Pearson’s r (significance)
68.0 (8.5)
67.7 (6.0)
68.3 (16)
69.3 (4.0)
77.3 (13.3)
56 (10.4)
80.3 (17.4)
69.7 (12.5)
.31 (p=.57)
7.2 (1)
6.7 (0.5)
5.6 (2.5)
7.9 (1.2)
8.5 (.4)
5.1 (1.4)
7.4 (1.8)
6.9 (1.7)
.02 (p=.94)
Hip pain, mean (SD) (0-10)
1.7 (2.1)
1.5 (1.3)
1.8 (.8)
2.7 (1.2)
0.4 (.8)
1.0 (1.2)
1.3 (1.6)
1.5 (1.3)
-.21 (p=.36)
Borg, mean (SD) (0-10)
3.3 (.6)
3.7 (.6)
3.7 (.6)
4.0 (1.0)
3.3 (.6)
4.0 (1.0)
5.0 (1.0)
3.9 (.9)
.48 ( p = .028*)
Post DEMMI, mean (SD) Post ASCQ, mean (SD)
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Dose 1
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Outcome
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Note: DEMMI = de Morten Mobility Index; SD=standard deviation; ASCQ = Ambulatory self-confidence questionnaire; *denotes statistically significant
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3 participants
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0 adverse events or tolerability issues
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Escalate dose
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Figure 1. Study design. Phase I, 3+3 design
>1 adverse events or tolerability issues
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1 adverse event or tolerability issue
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0 adverse events or tolerability issues
≥1 adverse events or tolerability issues
Maximum tolerated dose reached
ACCEPTED MANUSCRIPT
Ineligible (n = 6)
No longer receiving community therapy, n = 2 Not recent hip fracture, n = 1 Not cognitively intact, n = 1 Medically unwell, n = 2
Declined (n = 7)
Not interested, n = 5 Anxious about walking, n = 2
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Total participants recruited, n= 21
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Figure 2. Flow of participants through the trial
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-
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Potentially eligible participants identified by physiotherapists, n= 34