This study is fully supported by the Division of Intramural Research of the National Institute of Nursing Research of the NIH, Bethesda, Maryland.

The current study (NCT00852111) was approved by the Institutional Review Board (IRB) of the National Institutes of Health (NIH). Participants enrolled in this study were 18 years of age or older, diagnosed with non-metastatic prostate cancer with or without prior prostatectomy, and scheduled to receive external beam radiation therapy at the Radiation Oncology Clinic of the NIH Clinical Center. Potential participants were excluded if they had a progressive disease that could cause significant fatigue, had psychiatric disease within the past five years, had uncorrected hypothyroidism or anemia, or had a second malignancy. Individuals who used sedatives, steroids, or non-steroidal anti-inflammatory agents were also excluded. All participants were recruited at the Magnuson Clinical Research Center at the NIH. Signed written informed consents were obtained prior to study participation.
1. Handgrip preparation and testing position
<ol>
	<li>In a quiet room, set up a chair with armrests.</li>
	<li>Turn on the handheld dynamometer.
	<ol>
		<li>The software will prompt calibration of the dynamometer. Ensure the device is resting on a flat surface during calibration.</li>
	</ol>
	</li>
	<li>Seat the subject in an upright position with their feet in full contact with the floor and hips as far back as the chair supports.
	<ol>
		<li>Ensure the subject&#39;s hip and knee angles are close to 90&#176; and shoulders are in neutral abduction/adduction and neutrally rotated. Ensure the subject&#39;s elbow is flexed at 90&#176; and the wrist is unsupported, as recommended by the American Society of Hand Therapists handbook17.</li>
	</ol>
	</li>
	<li>After calibrating the dynamometer, instruct the subject to grasp the dynamometer, with the dorsal intermediate phalanges facing forward.
	<ol>
		<li>Adjust the grip position to the subject&#39;s hand size and record it7.</li>
		<li>Maintain the same handgrip testing position for all subsequent tests.</li>
		<li>Prior to each test, provide standardized scripts and ask subjects to perform a mock attempt to demonstrate understanding of the instructions.</li>
		<li>Inform the subjects that discomfort is normal, but the tests can be discontinued in the presence of unexpectedly severe strain/pain.</li>
		<li>Stop the test if severe discomfort is reported by the patient or in the event of unexpected circumstances.</li>
		<li>Ensure a 2 min rest period between trials to allow the muscle to recover18.</li>
	</ol>
	</li>
</ol>
2. Maximal voluntary isometric contraction (MVIC) test
<ol>
	<li>Provide subjects with standardized instructions. For example, &#34;in the test, you will squeeze as hard as you can for 5 s, starting with your non-dominant hand. This test will be done three times for each hand. For each test, I will count down 3, 2, 1...GO. Squeeze the device on GO as hard as you can.&#34;</li>
	<li>On &#34;Go&#34;, start the program by clicking on the GO button.</li>
	<li>Repeat the MVIC test for a total of three times with a 30 s rest between trials.</li>
	<li>The average for each hand from the three trials maximum force is the MVIC19.</li>
</ol>
3. Maximum force static fatigue test
<ol>
	<li>Instruct subjects to exert full effort to achieve maximal contraction during the static fatigue test.</li>
	<li>On &#34;Go&#34;, start the program by clicking on the GO button. Use standardized encouragement script such as squeeze hard repeatedly until the test ends.</li>
	<li>Continue the static fatigue test for 35 s, so as to provide up to 5 s to achieve Fmax (maximal handgrip strength).</li>
	<li>Static fatigue index (SFI)12,20,21
	<ol>
		<li>Calculate SFI using the following equation: 
		<img alt="Equation 1" src="/files/ftp_upload/60814/60814equ01.jpg" /></li>
		<li>Calculate AUCexpt by computing the experimental area under the curve from the time that Fmax was achieved (Tmax) to 30 s after Tmax.</li>
		<li>Calculate the hypothetical AUC (AUChypothetical) in the absence of fatigue by multiplying the Fmax by 30 s. 
		NOTE: Higher SFI values indicate increased divergence from the expected value, hence higher fatigue.</li>
		<li>Calculate SFI version 2 as the ratio of the maximal force during the last 5 s (Fmax 25-30s) to the maximal force in the first 5 seconds (Fmax 0-5s) using the equation: 
		<img alt="Equation 2" src="/files/ftp_upload/60814/60814equ02.jpg" /> 
		NOTE: Higher values of SFI indicate higher fatigue.</li>
	</ol>
	</li>
</ol>
4. Sub-maximum force static fatigue test
<ol>
	<li>Indicate the value of 50% of the MVIC of the participant&#39;s non-dominant hand by drawing a horizontal line on a transparency overlay of the screen.</li>
	<li>Draw a second line on the overlay in a different color to indicate a 10% decline of the target value.</li>
	<li>Ensure the participant can easily see the screen and 50% MVIC line.</li>
	<li>Instruct the subject to maintain a target value of 50% of MVIC for as long as possible.</li>
	<li>Count down. On &#34;Go&#34;, start the program by clicking on the GO button.</li>
	<li>Stop the test when the strength declines by 10% of the target value for more than 5 s as indicated by the second line on the transparency.</li>
	<li>Calculate total work performed7 as the force-versus-time area under the curve over the period of time during which the target force (T50% MVIC) is sustained: 
	Total work = AUC during T50% MVIC 
	 NOTE: Endurance can be measured as time to task completion22. Higher values of total work indicate lower fatigue.</li>
</ol>
5. Dynamic fatigue test
<ol>
	<li>Instruct subjects to perform a maximal squeeze every second for a duration of 30 s. Use a metronome to provide rhythm guidance20.</li>
	<li>Start the metronome which is set at 1 beep per second.</li>
	<li>Start the countdown. On &#34;Go&#34;, start the test by clicking on the GO button. Ensure the countdown matches the rate of the metronome.</li>
	<li>Inform the participant when passing the halfway point and when 5 s are remaining.</li>
	<li>Stop test after the 30 s are completed.</li>
	<li>Dynamic Fatigue Index
	<ol>
		<li>Calculate the Dynamic Fatigue Index20 using the maximal force (Fmax) of the last 5 s and the Fmax of the first 5 s. 
		<img alt="Equation 4" src="/files/ftp_upload/60814/60814equ04.jpg" /> 
		NOTE: Higher values of the dynamic fatigue index (DFI) indicate higher fatigue.</li>
	</ol>
	</li>
</ol>

<ol>
	<li>Berger, A. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cancer-Related+Fatigue,+Version+2.2015.">Cancer-Related Fatigue, Version 2.2015.</a> Journal of the National Comprehensive Cancer Network : JNCCN. 13 (8), 1012-1039 (2015).</li><li>Campos, M. P. O., Hassan, B. J., Riechelmann, R., Del Giglio, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cancer-related+fatigue:+a+practical+review.">Cancer-related fatigue: a practical review.</a> Annals of Oncology. 22 (6), 1273-1279 (2011).</li><li>Feng, L. R., Dickinson, K., Kline, N., Saligan, L. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Different+phenotyping+approaches+lead+to+dissimilar+biologic+profiles+in+men+with+chronic+fatigue+following+radiation+therapy.">Different phenotyping approaches lead to dissimilar biologic profiles in men with chronic fatigue following radiation therapy.</a> Journal of Pain and Symptom Management. 52 (6), 832-840 (2016).</li><li>Minton, O., Stone, P. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+comparison+of+cognitive+function,+sleep+and+activity+levels+in+disease-free+breast+cancer+patients+with+or+without+cancer-related+fatigue+syndrome.">A comparison of cognitive function, sleep and activity levels in disease-free breast cancer patients with or without cancer-related fatigue syndrome.</a> BMJ Supportive &amp; Palliative Care. 2, 231-238 (2012).</li><li>Wan, J. J., Qin, Z., Wang, P. Y., Sun, Y., Liu, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Muscle+fatigue:+general+understanding+and+treatment.">Muscle fatigue: general understanding and treatment.</a> Experimental &amp; Molecular Medicine. 49 (10), 384 (2017).</li><li>Bautmans, I., Gorus, E., Njemini, R., Mets, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Handgrip+performance+in+relation+to+self-perceived+fatigue,+physical+functioning+and+circulating+IL-6+in+elderly+persons+without+inflammation.">Handgrip performance in relation to self-perceived fatigue, physical functioning and circulating IL-6 in elderly persons without inflammation.</a> BMC geriatrics. 7, 5-5 (2007).</li><li>Gerodimos, V., Karatrantou, K., Psychou, D., Vasilopoulou, T., Zafeiridis, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Static+and+Dynamic+Handgrip+Strength+Endurance:+Test-Retest+Reproducibility.">Static and Dynamic Handgrip Strength Endurance: Test-Retest Reproducibility.</a> The Journal of Hand Surgery. 42 (3), 175-184 (2017).</li><li>van der Werf, S. P., Prins, J. B., Vercoulen, J. H. M. M., van der Meer, J. W. M., Bleijenberg, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identifying+physical+activity+patterns+in+chronic+fatigue+syndrome+using+actigraphic+assessment.">Identifying physical activity patterns in chronic fatigue syndrome using actigraphic assessment.</a> Journal of Psychosomatic Research. 49 (5), 373-379 (2000).</li><li>Connaughton, J., Patman, S., Pardoe, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Are+there+associations+among+physical+activity,+fatigue,+sleep+quality+and+pain+in+people+with+mental+illness?+A+pilot+study.">Are there associations among physical activity, fatigue, sleep quality and pain in people with mental illness? A pilot study.</a> Journal of Psychiatric and Mental Health Nursing. 21 (8), 738-745 (2014).</li><li>Gurses, H. N., Zeren, M., Denizoglu Kulli, H., Durgut, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+relationship+of+sit-to-stand+tests+with+6-minute+walk+test+in+healthy+young+adults.">The relationship of sit-to-stand tests with 6-minute walk test in healthy young adults.</a> Medicine. 97 (1), 9489 (2018).</li><li>Beg, M. S., Gupta, A., Stewart, T., Rethorst, C. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Promise+of+Wearable+Physical+Activity+Monitors+in+Oncology+Practice.">Promise of Wearable Physical Activity Monitors in Oncology Practice.</a> Journal of Oncology Practice. 13 (2), 82-89 (2017).</li><li>Severijns, D., Lamers, I., Kerkhofs, L., Feys, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hand+grip+fatigability+in+persons+with+multiple+sclerosis+according+to+hand+dominance+and+disease+progression.">Hand grip fatigability in persons with multiple sclerosis according to hand dominance and disease progression.</a> Journal of Rehabilitation Medicine. 47 (2), 154-160 (2015).</li><li>Feng, L. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+and+motor+aspects+of+cancer-related+fatigue.">Cognitive and motor aspects of cancer-related fatigue.</a> Cancer Medicine. 8 (13), 5840-5849 (2019).</li><li>Bohannon, R. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hand-Grip+Dynamometry+Predicts+Future+Outcomes+in+Aging+Adults.">Hand-Grip Dynamometry Predicts Future Outcomes in Aging Adults.</a> Journal of Geriatric Physical Therapy. 31 (1), 3-10 (2008).</li><li>Reuter, S. E., Massy-Westropp, N., Evans, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reliability+and+validity+of+indices+of+hand-grip+strength+and+endurance.">Reliability and validity of indices of hand-grip strength and endurance.</a> Australian Occupational Therapy Journal. 58 (2), 82-87 (2011).</li><li>Roberts, H. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+review+of+the+measurement+of+grip+strength+in+clinical+and+epidemiological+studies:+towards+a+standardised+approach.">A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach.</a> Age and Ageing. 40 (4), 423-429 (2011).</li><li>American Society of Hand Therapists. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Clinical Assessment Recommendations. 2nd edn. , (1992).</li><li>Bhuanantanondh, P., Nanta, P., Mekhora, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Determining+Sincerity+of+Effort+Based+on+Grip+Strength+Test+in+Three+Wrist+Positions.">Determining Sincerity of Effort Based on Grip Strength Test in Three Wrist Positions.</a> Safety and Health at Work. 9 (1), 59-62 (2018).</li><li>van Meeteren, J., van Rijn, R. M., Selles, R. W., Roebroeck, M. E., Stam, H. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Grip+strength+parameters+and+functional+activities+in+young+adults+with+unilateral+cerebral+palsy+compared+with+healthy+subjects.">Grip strength parameters and functional activities in young adults with unilateral cerebral palsy compared with healthy subjects.</a> Journal of Rehabilitation Medicine. 39 (8), 598-604 (2007).</li><li>Meldrum, D., Cahalane, E., Conroy, R., Guthrie, R., Hardiman, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+assessment+of+motor+fatigue:+normative+values+and+comparison+with+prior-polio+patients.">Quantitative assessment of motor fatigue: normative values and comparison with prior-polio patients.</a> Amyotrophic Lateral Sclerosis. 8 (3), 170-176 (2007).</li><li>Schwid, S. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+assessment+of+motor+fatigue+and+strength+in+MS.">Quantitative assessment of motor fatigue and strength in MS.</a> Neurology. 53, 743-743 (1999).</li><li>Hunter, S. K., Critchlow, A., Shin, I. S., Enoka, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Men+are+more+fatigable+than+strength-matched+women+when+performing+intermittent+submaximal+contractions.">Men are more fatigable than strength-matched women when performing intermittent submaximal contractions.</a> Journal of Applied Physiology. 96 (6), 2125-2132 (2004).</li><li>Karatrantou, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dynamic+Handgrip+Strength+Endurance:+A+Reliable+Measurement+in+Older+Women.">Dynamic Handgrip Strength Endurance: A Reliable Measurement in Older Women.</a> Journal of Geriatric Physical Therapy. 42 (3), 51-56 (2019).</li><li>The National Isometric Muscle Strength Database. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Muscular+weakness+assessment:+Use+of+normal+isometric+strength+data.">Muscular weakness assessment: Use of normal isometric strength data.</a> Archives of Physical Medicine and Rehabilitation. 77 (12), 1251-1255 (1996).</li><li>Desrosiers, J., Bravo, G., H&#233;bert, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Isometric+grip+endurance+of+healthy+elderly+men+and+women.">Isometric grip endurance of healthy elderly men and women.</a> Archives of Gerontology and Geriatrics. 24 (1), 75-85 (1997).</li><li>White, C., Dixon, K., Samuel, D., Stokes, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Handgrip+and+quadriceps+muscle+endurance+testing+in+young+adults.">Handgrip and quadriceps muscle endurance testing in young adults.</a> SpringerPlus. 2 (1), 451 (2013).</li><li>Trajano, G., Pinho, C., Costa, P., Oliveira, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Static+stretching+increases+muscle+fatigue+during+submaximal+sustained+isometric+contractions.">Static stretching increases muscle fatigue during submaximal sustained isometric contractions.</a> Journal of Sports Medicine and Physical Fitness. 55 (1-2), 43-50 (2015).</li><li>Liu, J. Z., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+Brain+Activation+During+Sustained+and+Intermittent+Submaximal+Fatigue+Muscle+Contractions:+An+fMRI+Study.">Human Brain Activation During Sustained and Intermittent Submaximal Fatigue Muscle Contractions: An fMRI Study.</a> Journal of Neurophysiology. 90 (1), 300-312 (2003).</li><li>Demura, S., Yamaji, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+grip+types+and+intensities+on+force-decreasing+curves+and+physiological+responses+during+sustained+muscle+contractions.">Influence of grip types and intensities on force-decreasing curves and physiological responses during sustained muscle contractions.</a> Sport Sciences for Health. 3 (1), 33-40 (2008).</li><li>Matuszczak, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+N-acetylcysteine+on+glutathione+oxidation+and+fatigue+during+handgrip+exercise.">Effects of N-acetylcysteine on glutathione oxidation and fatigue during handgrip exercise.</a> Muscle &amp; Nerve. 32 (5), 633-638 (2005).</li><li>Medved, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=N-acetylcysteine+infusion+alters+blood+redox+status+but+not+time+to+fatigue+during+intense+exercise+in+humans.">N-acetylcysteine infusion alters blood redox status but not time to fatigue during intense exercise in humans.</a> Journal of Applied Physiology. 94 (4), 1572-1582 (2003).</li><li>L&#246;scher, W. N., Cresswell, A. G., Thorstensson, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Excitatory+drive+to+the+alpha-motoneuron+pool+during+a+fatiguing+submaximal+contraction+in+man.">Excitatory drive to the alpha-motoneuron pool during a fatiguing submaximal contraction in man.</a> The Journal of Physiology. 491 (1), 271-280 (1996).</li><li>Taylor, J. L., Allen, G. M., Butler, J. E., Gandevia, S. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Supraspinal+fatigue+during+intermittent+maximal+voluntary+contractions+of+the+human+elbow+flexors.">Supraspinal fatigue during intermittent maximal voluntary contractions of the human elbow flexors.</a> Journal of Applied Physiology. 89 (1), 305-313 (2000).</li><li>Fulco, C. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Slower+fatigue+and+faster+recovery+of+the+adductor+pollicis+muscle+in+women+matched+for+strength+with+men.">Slower fatigue and faster recovery of the adductor pollicis muscle in women matched for strength with men.</a> Acta Physiologica Scandinavica. 167 (3), 233-239 (1999).</li><li>Gonzales, J. U., Scheuermann, B. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Absence+of+gender+differences+in+the+fatigability+of+the+forearm+muscles+during+intermittent+isometric+handgrip+exercise.">Absence of gender differences in the fatigability of the forearm muscles during intermittent isometric handgrip exercise.</a> Journal of Sports Science &amp; Medicine. 6 (1), 98-105 (2007).</li><li>Liepert, J., Mingers, D., Heesen, C., B&#228;umer, T., Weiller, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+cortex+excitability+and+fatigue+in+multiple+sclerosis:+a+transcranial+magnetic+stimulation+study.">Motor cortex excitability and fatigue in multiple sclerosis: a transcranial magnetic stimulation study.</a> Multiple Sclerosis Journal. 11 (3), 316-321 (2005).</li><li>Kim, J., Yim, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+an+Exercise+Protocol+for+Improving+Handgrip+Strength+and+Walking+Speed+on+Cognitive+Function+in+Patients+with+Chronic+Stroke.">Effects of an Exercise Protocol for Improving Handgrip Strength and Walking Speed on Cognitive Function in Patients with Chronic Stroke.</a> Medical science monitor : international medical journal of experimental and clinical research. 23, 5402-5409 (2017).</li><li>Schnelle, J. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=et+al+Evaluation+of+Two+Fatigability+Severity+Measures+in+Elderly+Adults.">et al Evaluation of Two Fatigability Severity Measures in Elderly Adults.</a> Journal of the American Geriatrics Society. 60 (8), 1527-1533 (2012).</li><li>Enoka, R. M., Duchateau, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Translating+Fatigue+to+Human+Performance.">Translating Fatigue to Human Performance.</a> Medicine and science in sports and exercise. 48 (11), 2228-2238 (2016).</li></ol>

The authors have nothing to disclose.

Here, we provide three different methods for measuring the physical dimension of CRF. Motor fatigue tests using handheld dynamometers are simple and easily adaptable for clinical use. Since many variations of the test exist in the literature, our goal was to provide standardized methods to administer these tests and decrease the need for extensive in-person trainings for clinicians.
Although the fatigue tests outlined in this study demonstrate good test-retest reliability7</s...

Cancer-related fatigue (CRF) is an prevalent and debilitating symptom that is reported by up to 80% of cancer patients1. The National Comprehensive Cancer Network (NCCN) defines CRF as a persistent sense of physical, emotional, and cognitive exhaustion1. The main differentiating characteristics of CRF are the disproportionality to recent activity and the inability of CRF to be relieved by rest1. As a result, CRF severely impacts patients&#39; participation in daily activities and their health-related quality of life1.
The current assessment of CRF relies primarily on self-report questionnaires2. As a result, symptom severity which is measured using self-reports is subject to recall and reporting biases and can be influenced by the specific questionnaire and cutoff scores used to assess CRF3. As a multidimensional construct, the physical dimension of CRF has been shown to correlate with daily activity changes and a need for daytime naps4, whereas the influence of CRF on physical functioning is less explored. To this date, CRF remains an underdiagnosed and undertreated symptom with no well-defined underlying mechanism or treatment option1. To better understand this debilitating condition, there is an increasing need to measure CRF and its dimensions objectively and quantitatively.
Physical fatigue refers to an inability to maintain the required force during sustained contractile activity5. The subsequent compromised daily functioning as a result of not being able to carry out daily tasks (e.g., carrying grocery bags, lifting and holding an object) greatly affects the health-related quality of life, especially in older adults, and contributes to future injuries6,7. Various tools have been developed to quantify physical impairment including physical performance tests, such as the 6 min walk test (6MWT) and sit-to-stand test (STS), as well as wearable physical activity monitors, such as actigraphy devices and fitness trackers8,9,10. Physical performance tests such as 6MWT and STS are easy to administer and do not require special equipment10. However, the reliability and success of such tests require clinician training and logistical requirements such as a 30 m corridor10. Wearable activity monitors allow for automated data collection and longitudinal symptom monitoring11. However, these activity monitors often need to be worn for multiple days, and patient compliance can be an issue11. In addition, the large amount of data collected using activity monitors can be challenging to process, making it difficult to derive clinically meaningful information11.
The handheld dynamometer, or instrumented handgrip device with computer-assisted data acquisition, is a portable apparatus that measures grip strength. Handheld dynamometry has been used to test motor fatigue and impairment in disease conditions that typically involve the motor system including motor neurons and muscular problems12. Recent work has demonstrated an association between self-reported subjective CRF scores and motor fatigue measured using a handgrip static fatigue test13. Handgrip fatigue tests are particularly suitable for clinical use due to their reliability and time efficiency, requiring a few minutes to complete14,15. Furthermore, handgrip fatigue tests can be pre-programed, ensuring data reproducibility7. Administering the handgrip test requires minimal training on the part of the test administrator and can be easily implemented in a clinical setting given a standardized protocol. Using self-reported fatigue questionnaires in conjunction with the handgrip fatigue test should provide additional tools for clinicians to screen, monitor, and manage fatigue symptoms in cancer patients.
The lack of standardized consensus methods has limited the adoption of the handgrip fatigue test in the clinics16. In this current work, we outline three different methods to use the handheld dynamometer to quantify motor fatigue objectively. The utility of each method should be tested in each cancer population to ensure it accurately distinguishes between fatigued and non-fatigued subjects. We also outline methods to calculate the fatigue index for each handgrip fatigue test. The goal of this work is to provide a comprehensive toolkit to supplement self-reported questionnaires and to standardize CRF physical performance measurement accurately and objectively.

<table><tbody><tr><td>Quantitative Muscle Assessment application (QMA)</td><td>Aeverl Medical</td><td>QMA 4.6</td><td>Data acquisition software. NOTE: other brands/models can be used as long as the software records force over time.</td></tr><tr><td>QMA distribution box</td><td>Aeverl Medical</td><td>DSTBX</td><td>Software distribution box which connects the handgrip to the software.</td></tr><tr><td>Baseline hand dynamometer with analog output</td><td>Aeverl Medical</td><td>BHG</td><td>Instrumented handgrip device with computer assisted data acquisition. NOTE: other brands/models can be used as long as the instrument measures force over time</td></tr></tbody></table>

measuring the motor aspect of cancer-related fatigue using a handheld dynamometer

Cancer-related fatigue (CRF) is commonly reported by patients both during and after receiving treatment for cancer. Current CRF diagnoses rely on self-report questionnaires which are subject to report and recall biases. Objective measurements using a handheld dynamometer, or handgrip device, have been shown in recent studies to correlate significantly with subjective self-reported fatigue scores. However, variations of both the handgrip fatigue test and fatigue index calculations exist in the literature. The lack of standardized methods limits the utilization of the handgrip fatigue test in the clinical and research settings. In this study, we provide detailed methods for administering the physical fatigue test and calculating the fatigue index. These methods should supplement existing self-reported fatigue questionnaires and help clinicians assess fatigue symptom severity in an objective and quantitative manner.

Representative force (kg) versus time (s) traces are shown in Figure 1. During the static fatigue test, subjects typically reach maximal strength (Fmax) within 2&#8211;3 s23. Self-reported fatigue in subjects was measured based on previous studies3. The absence of Fmax (&#177;10% MVIC) within 3 s indicates insufficient effort23. To prevent this issue, verbal encouragement should be provided. Both su...

Watch this Scientific Journal Video about Measuring the Motor Aspect of Cancer-Related Fatigue using a Handheld Dynamometer at JoVE.com

Measuring the Motor Aspect of Cancer-Related Fatigue using a Handheld Dynamometer

Simple and accessible methods were developed to measure the motor aspect of cancer-related fatigue objectively and quantitatively. We describe, in detail, ways to administer the physical fatigue test using a simple handgrip device as well as methods to calculate fatigue indices.

Cancer-related fatigue (CRF) is commonly reported by patients both during and after receiving treatment for cancer. Current CRF diagnoses rely on ...

measuring-motor-aspect-cancer-related-fatigue-using-handheld

Research

JoVE Journal

Cancer Research

5.8K Views.  National Institutes of Health. Simple and accessible methods were developed to measure the motor aspect of cancer-related fatigue objectively and quantitatively. We describe, in detail, ways to administer the physical fatigue test using a simple handgrip device as well as methods to calculate fatigue indices.

Video: Measuring the Motor Aspect of Cancer-Related Fatigue using a Handheld Dynamometer

Methods to Quantify Pharmacologically Induced Alterations in Motor Function in Human Incomplete SCI

Spinal cord injury (SCI) is a debilitating disorder, which produces profound deficits in volitional motor control. Following medical stabilization, recovery from SCI typically involves long term rehabilitation. While recovery of walking ability is a primary goal in many patients early after injury, those with a motor incomplete SCI, indicating partial preservation of volitional control, may have the sufficient residual descending pathways necessary to attain this goal. However, despite physical interventions, motor impairments including weakness, and the manifestation of abnormal involuntary reflex activity, called spasticity or spasms, are thought to contribute to reduced walking recovery. Doctrinaire thought suggests that remediation of this abnormal motor reflexes associated with SCI will produce functional benefits to the patient. For example, physicians and therapists will provide specific pharmacological or physical interventions directed towards reducing spasticity or spasms, although there continues to be little empirical data suggesting that these strategies improve walking ability.
In the past few decades, accumulating data has suggested that specific neuromodulatory agents, including agents which mimic or facilitate the actions of the monoamines, including serotonin (5HT) and norepinephrine (NE), can initiate or augment walking behaviors in animal models of SCI. Interestingly, many of these agents, particularly 5HTergic agonists, can markedly increase spinal excitability, which in turn also increases reflex activity in these animals. Counterintuitive to traditional theories of recovery following human SCI, the empirical evidence from basic science experiments suggest that this reflex hyper excitability and generation of locomotor behaviors are driven in parallel by neuromodulatory inputs (5HT) and may be necessary for functional recovery following SCI. 
The application of this novel concept derived from basic scientific studies to promote recovery following human SCI would appear to be seamless, although the direct translation of the findings can be extremely challenging. Specifically, in the animal models, an implanted catheter facilitates delivery of very specific 5HT agonist compounds directly onto the spinal circuitry. The translation of this technique to humans is hindered by the lack of specific surgical techniques or available pharmacological agents directed towards 5HT receptor subtypes that are safe and effective for human clinical trials. However, oral administration of commonly available 5HTergic agents, such as selective serotonin reuptake inhibitors (SSRIs), may be a viable option to increase central 5HT concentrations in order to facilitate walking recovery in humans. Systematic quantification of how these SSRIs modulate human motor behaviors following SCI, with a specific focus on strength, reflexes, and the recovery of walking ability, are missing.
This video demonstration is a progressive attempt to systematically and quantitatively assess the modulation of reflex activity, volitional strength and ambulation following the acute oral administration of an SSRI in human SCI. Agents are applied on single days to assess the immediate effects on motor function in this patient population, with long-term studies involving repeated drug administration combined with intensive physical interventions.

This video demonstrates modulation of reflex activity, volitional strength and ambulation through clinical and quantitative assessments in individuals with motor incomplete SCI as a result of acute oral administration of a serotonin reuptake inhibitor (SSRI).

Spinal cord injury (SCI) is a debilitating disorder, which produces profound deficits in volitional motor control. Following medical stabilization, ...

Medicine

A Mouse Model of Fatigue Induced by Peripheral Irradiation

Cancer-related fatigue (CRF) is a distressing and costly condition that often affects patients receiving cancer treatments, including radiation therapy. Here we describe a method using targeted peripheral irradiation to induce fatigue-like behavior in mice. With appropriate shielding, the irradiation targets the lower abdominal/pelvic region of the mouse, sparing the brain, in an effort to model radiation treatment received by individuals with pelvic cancers. We deliver an irradiation dose that is sufficient to induce fatigue-like behavior in mice, measured by voluntary wheel-running activity (VWRA), without causing obvious morbidity. Since wheel running is a normal, voluntary behavior in mice, its use should have little confounding effect on other behavioral tests or biological measures. Hence, wheel running can be used as a feasible outcome measure in understanding the behavioral and biological correlates of fatigue. CRF is a complex condition with frequent comorbidities, and likely has causes related both to cancer and its various treatments. The methods described in this paper are useful for investigating radiation-induced changes that contribute to the development of CRF and, more generally, to explore the biological networks that can explain the development and persistence of a peripherally-triggered but centrally-driven behavior like fatigue.

We describe a method using targeted peripheral irradiation to induce fatigue-like behavior in mice. The selected non-lethal irradiation dose leads to a week-long reduction in voluntary wheel-running activity.

Cancer-related fatigue (CRF) is a distressing and costly condition that often affects patients receiving cancer treatments, including radiation therapy. ...

Manual Muscle Testing:  A Method of Measuring Extremity Muscle Strength Applied to Critically Ill Patients 

Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, and persistent nerve and muscle impairments after hospital discharge.1-6 Using an explicit protocol with a structured approach to training and quality assurance of research staff, manual muscle testing (MMT) is a highly reliable method for assessing strength, using a standardized clinical examination, for patients following ARDS, and can be completed with mechanically ventilated patients who can tolerate sitting upright in bed and are able to follow two-step commands. 7, 8 
This video demonstrates a protocol for MMT, which has been taught to &ge;43 research staff who have performed &gt;800 assessments on &gt;280 ARDS survivors. Modifications for the bedridden patient are included. Each muscle is tested with specific techniques for positioning, stabilization, resistance, and palpation for each score of the 6-point ordinal Medical Research Council scale.7,9-11 Three upper and three lower extremity muscles are graded in this protocol: shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion. These muscles were chosen based on the standard approach for evaluating patients for ICU-acquired weakness used in prior publications. 1,2.

Manual Muscle Testing:  A Method of Measuring Extremity Muscle Strength Applied to Critically Ill Patients

Survivors of acute respiratory distress syndrome (ARDS) and critical illness frequently develop long-lasting muscle weakness. Manual muscle testing (MMT) is a standardized clinical examination commonly used to measure strength of peripheral skeletal muscle groups. This video demonstrates MMT using the 6-point Medical Research Council scale.

Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, ...

Evaluating the Role of Mitochondrial Function in Cancer-related Fatigue

Fatigue is a common and debilitating condition that affects most cancer patients. To date, fatigue remains poorly characterized with no diagnostic test to objectively measure the severity of this condition. Here we describe an optimized method for assessing mitochondrial function of PBMCs collected from fatigued cancer patients. Using a compact extracellular flux system and sequential injection of respiratory inhibitors, we examined PBMC mitochondrial functional status by measuring basal mitochondrial respiration, spare respiratory capacity, and energy phenotype, which describes the preferred energy pathway to respond to stress. Fresh PBMCs are readily available in the clinical setting using standard phlebotomy. The entire assay described in this protocol can be completed in less than 4 hours without the involvement of complex biochemical techniques. Additionally, we describe a normalization method that is necessary for obtaining reproducible data. The simple procedure and normalization methods presented allow for repeated sample collection from the same patient and generation of reproducible data that can be compared between time points to evaluate potential treatment effects.

Our goal was to develop a practical protocol to evaluate mitochondrial dysfunction associated with fatigue in cancer patients. This innovative protocol is optimized for clinical use involving only standard phlebotomy and basic laboratory procedures.

Fatigue is a common and debilitating condition that affects most cancer patients. To date, fatigue remains poorly characterized with no diagnostic test to ...

The Treadmill Fatigue Test: A Simple, High-throughput Assay of Fatigue-like Behavior for the Mouse

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of current interventions to adequately treat fatigue in all patients leaves a need for new treatment options. Despite the therapeutic need and importance of preclinical research in helping identify promising novel treatments, few preclinical assays of fatigue are available. Moreover, the most common preclinical assay used to assess fatigue-like behavior, voluntary wheel running, is not suitable for use with some strains of mice, may not be sensitive to drugs that reduce fatigue, and has relatively low throughput. The current protocol describes a novel, non-voluntary preclinical assay of fatigue-like behavior, the treadmill fatigue test, and provides evidence of its efficacy in detecting fatigue-like behavior in mice treated with a chemotherapy drug known to cause fatigue in humans and fatigue-like behavior in animals. This assay may be a beneficial alternative to wheel running, as fatigue-like behavior and potential interventions can be assessed in a greater number of mice over a shorter time frame, thus permitting faster discovery of new therapeutic options.

Fatigue is a common, undertreated and frequently poorly-understood symptom in many diseases and disorders. New preclinical assays of fatigue may help to improve current understanding and future treatment of fatigue. To that end, the current protocol provides a novel means of measuring fatigue-like behavior in the mouse.

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of ...

Behavior

Whole Body Vibration Methods with Survivors of Polio

The purpose of the original study was to examine the use of whole body vibration (WBV) on polio survivors with and without post-polio syndrome as a form of weight bearing exercise. The goal of this article is to highlight the strengths, limitations, and applications of the method used. Fifteen participants completed two intervention blocks with a wash-out period in between the blocks. Each block consisted of twice a week (four weeks) WBV interventions, progressing from 10 to 20 min per session. Low intensity (peak to peak displacement 4.53 mm, frequency 24 Hz, g force 2.21) and higher intensity (peak to peak displacement 8.82 mm, frequency 35 Hz, g force 2.76) WBV blocks were used. Pain severity significantly improved in both groups following higher intensity vibration. Walking speed significantly improved in the group who participated in higher intensity intervention first. No study-related adverse events occurred. Even though this population can be at risk of developing overuse-related muscle weakness, fatigue, or pain from excessive physical activity or exercise, the vibration intensity levels utilized did not cause significant muscle weakness, pain, fatigue, or sleep disturbances. Therefore, WBV appears to provide a safe method of weight bearing exercise for this population. Limitations included the lack of measurement of reflexes, muscular activity, or circulation, the difficulty in participant recruitment, and insufficient strength of some participants to stand in recommended position. Strengths included a standard, safe protocol with intentional monitoring of symptoms and the heterogeneity of the participants in their physical abilities. An application of the methods is the home use of WBV to reduce the barriers associated with going to a facility for weight bearing exercise for longer term interventions, and benefits for conditions such as osteoporosis, particularly for aging adults with mobility difficulties due to paralysis or weakness. Presented method may serve as a starting point in future studies.

The goal of this article is to highlight the strengths, limitations, and applications of the method used with whole body vibration on polio survivors with and without post-polio syndrome as a feasible and safe form of weight bearing exercise.

The purpose of the original study was to examine the use of whole body vibration (WBV) on polio survivors with and without post-polio syndrome as a form ...

A Standardized Method for Measurement of Elbow Kinesthesia

Proprioception is an important component of controlled movement. The threshold to detection of passive movement (TDPM) is a commonly used method for quantifying the proprioceptive submodality of kinesthesia in research settings. The TDPM paradigm has been found to be valid and reliable; however, the equipment and methods used for TDPM vary between studies. In particular, the research laboratory apparatuses for producing passive movement of an extremity are often custom designed by individual laboratories or inaccessible due to high cost. There is a need for a standardized, valid, and reliable method for measuring TDPM using readily available equipment. The purpose of this protocol is to provide a standardized method for measurement of TDPM at the elbow that is economical, easy to administer, and that produces quantitative results for measurement purposes in research-based settings. This method was tested on 20 healthy adults without neurological impairment, and eight adults with chronic stroke. The results obtained suggest this method is a reliable way to quantify elbow TDPM in healthy adults, and provides initial support for validity. Researchers seeking a balance between equipment affordability and measurement precision are most likely to find this protocol of benefit.

Here, we present a standardized method for measurement of elbow passive kinesthesia using the threshold to detection of passive movement (TDPM) that is appropriate for a research setting.

Proprioception is an important component of controlled movement. The threshold to detection of passive movement (TDPM) is a commonly used method for ...

Measurement of the Hand Transmitted Vibration of the Human Hand Arm System During Operation of a Hand Tractor

Operators of hand tractors are exposed to high levels of hand transmitted vibration (HTV). This vibration, which can be both irksome and hazardous to human health, is imparted to the operator via his or her hands and arms. However, a standardized method for measuring HTV of hand tractors has yet to be defined. The aim of the study was to present an experimental method for the investigation of the biodynamic response and vibration transmissibility of the hand-arm system during the operation of a hand tractor in a stationary mode. Measurements were performed with ten subjects using three grip forces and three handle vibration levels to examine the influences of the hand pressure and frequency on hand transmitted vibration (HTV). The results indicate that the tightness of grip on the handle influences the vibration response of the hand-arm system, especially at frequencies between 20 and 100 Hz. The transmission of lower frequencies in the hand-arm system was relatively unattenuated. In comparison, attenuation was found to be quite marked for higher frequencies during the operation of the hand tractor. The vibration transmissibility to different parts of the hand-arm system decreased with the increase of the distance from the vibration source. The proposed methodology contributes to the collection of consistent data for the evaluation of operator vibration exposure and the ergonomics development of hand tractors.

Here, we present a standardized method for measurement of the hand transmitted vibration from handles of a single-axle tractor with special reference to changes in grip force and vibration frequency.

Operators of hand tractors are exposed to high levels of hand transmitted vibration (HTV). This vibration, which can be both irksome and hazardous to ...

Engineering

Measurements of Motor Function and Other Clinical Outcome Parameters in Ambulant Children with Duchenne Muscular Dystrophy

While the number of new treatment options tested in patients with Duchenne muscular dystrophy (DMD) is increasing, there is still no defining of the most reliable assessments regarding therapeutic efficacy. We present clinical and radiological outcome measures used in ambulatory patients participating in our trial &#34;Treatment with L-citrulline and metformin in Duchenne muscular dystrophy&#34;. The motor function measure is a validated test in patients with neuromuscular disorders that consists of 32 items and assesses all three dimensions of motor performance including standing and transfer (D1 subscore), axial and proximal motor function (D2 subscore), and distal motor function (D3 subscore). The test shows high intra- and inter-rater variability but only when strictly following guidelines of the materials, examination steps, and calculation of scores. The 6-minute walk test, timed 10-meter walk/run test, and supine-up time are commonly used timed functional tests that also sufficiently monitor changes in muscle function; however, they strongly depend on patient collaboration. Quantitative MRI is an objective and sensitive biomarker to detect subclinical changes, though the examination costs may be a reason for its limited use. In this study, a high correlation between all clinical assessments and quantitative MRI scans was found. The combinational use of these methods provides a better understanding about disease progression; however, longitudinal studies are needed to validate their reliability.

The aim of this study is to present the most reliable clinical outcome measures and their correlations with quantitative muscle MRI in ambulant patients with Duchenne muscular dystrophy.

While the number of new treatment options tested in patients with Duchenne muscular dystrophy (DMD) is increasing, there is still no defining of the most ...

Determining and Controlling External Power Output During Regular Handrim Wheelchair Propulsion

The use of a manual wheelchair is critical to 1% of the world&#39;s population. Human powered wheeled mobility research has considerably matured, which has led to improved research techniques becoming available over the last decades. To increase the understanding of wheeled mobility performance, monitoring, training, skill acquisition, and optimization of the wheelchair-user interface in rehabilitation, daily life, and sports, further standardization of measurement set-ups and analyses is required. A crucial stepping-stone is the accurate measurement and standardization of external power output (measured in Watts), which is pivotal for the interpretation and comparison of experiments aiming to improve rehabilitation practice, activities of daily living, and adaptive sports. The different methodologies and advantages of accurate power output determination during overground, treadmill, and ergometer-based testing are presented and discussed in detail. Overground propulsion provides the most externally valid mode for testing, but standardization can be troublesome. Treadmill propulsion is mechanically similar to overground propulsion, but turning and accelerating is not possible. An ergometer is the most constrained and standardization is relatively easy. The goal is to stimulate good practice and standardization to facilitate the further development of theory and its application among research facilities and applied clinical and sports sciences around the world.

Accurate and standardized assessment of external power output is crucial in the evaluation of physiological, biomechanical, and perceived stress, strain, and capacity in manual wheelchair propulsion. The current article presents various methods to determine and control power output during wheelchair propulsion studies in the laboratory and beyond.

The use of a manual wheelchair is critical to 1% of the world&#39;s population. Human powered wheeled mobility research has considerably matured, which ...