The effect on knee-joint load of instruction in analgesic use compared with neuromuscular exercise in patients with knee osteoarthritis: study protocol for a randomized, single-blind, controlled trial (the EXERPHARMA trial)

Brian Clausen, Anders Holsgaard-Larsen, Jens Søndergaard, Robin Christensen, Thomas P Andriacchi, Ewa M Roos, Brian Clausen, Anders Holsgaard-Larsen, Jens Søndergaard, Robin Christensen, Thomas P Andriacchi, Ewa M Roos

Abstract

Background: Knee osteoarthritis (OA) is a mechanically driven disease, and it is suggested that medial tibiofemoral knee-joint load increases with pharmacologic pain relief, indicating that pharmacologic pain relief may be positively associated with disease progression. Treatment modalities that can both relieve pain and reduce knee-joint load would be preferable. The knee-joint load is influenced by functional alignment of the trunk, pelvis, and lower-limb segments with respect to the knee, as well as the ground-reaction force generated during movement. Neuromuscular exercise can influence knee load and decrease knee pain. It includes exercises to improve balance, muscle activation, functional alignment, and functional knee stability. The primary objective of this randomized controlled trial (RCT) is to investigate the efficacy of a NEuroMuscular EXercise (NEMEX) therapy program, compared with optimized analgesics and antiinflammatory drug use, on the measures of knee-joint load in people with mild to moderate medial tibiofemoral knee osteoarthritis.

Method/design: One hundred men and women with mild to moderate medial knee osteoarthritis will be recruited from general medical practices and randomly allocated (1:1) to one of two 8-week treatments, either (a) NEMEX therapy twice a week or (b) information on the recommended use of analgesics and antiinflammatory drugs (acetaminophen and oral NSAIDs) via a pamphlet and video materials. The primary outcome is change in knee load during walking (the Knee Index, a composite score of the first external peak total reaction moment on the knee joint from all three planes based on 3D movement analysis) after 8 weeks of intervention. Secondary outcomes include changes in the external peak knee-adduction moment and impulse and functional performance measures, in addition to changes in self-reported pain, function, health status, and quality of life.

Discussion: These findings will help determine whether 8 weeks of neuromuscular exercise is superior to optimized use of analgesics and antiinflammatory drugs regarding knee-joint load, pain and physical function in people with mild to moderate knee osteoarthritis.

Trial registration: ClinicalTrials.gov Identifier: NCT01638962 (July 3, 2012).

Figures

Figure 1
Figure 1
Flow diagram.
Figure 2
Figure 2
Knee alignment. (A) “Knee-over-toe-position”, that is, lower extremity well aligned with appropriate position of knee over foot. (B) “Knee-medial to-foot-position”, that is, lower extremity not well aligned; the medial placement of the knee relative to the foot is inappropriate.
Figure 3
Figure 3
Equation for calculating the Knee Index.

References

    1. Bitton R. The economic burden of osteoarthritis. Am J Managed Care. 2009;15:S230–S235.
    1. Lachance L, Sowers MF, Jamadar D, Hochberg M. The natural history of emergent osteoarthritis of the knee in women. Osteoarthritis Cartilage. 2002;10:849–854. doi: 10.1053/joca.2002.0840.
    1. Bentley G. European Instructional Lectures. Heidelberg New York Dordrecht London: Springer; 2011.
    1. Sundhedsstyrelsen . Referenceprogram for knæartrose. København: Sundhedsstyrelsen; 2007. Edited by Sundhedssyrelsen.
    1. Jordan KM. EULAR recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a task force of the standing committee for international clinical studies including therapeutic trials (ESCISIT) Ann Rheum Dis. 2003;62:1145–1155. doi: 10.1136/ard.2003.011742.
    1. Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, Bierma-Zeinstra S, Brandt KD, Croft P, Doherty M, Dougados M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008;16:137–162. doi: 10.1016/j.joca.2007.12.013.
    1. Brand CA, Harrison C, Tropea J, Hinman RS, Britt H, Bennell K. Management of osteoarthritis in general practice in Australia. Arthritis Care Res (Hoboken) 2014;66:551–558. doi: 10.1002/acr.22197.
    1. Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, Towheed T, Welch V, Wells G, Tugwell P. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken) 2012;64:465–474. doi: 10.1002/acr.21596.
    1. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. 2011;8:e1001098. doi: 10.1371/journal.pmed.1001098.
    1. Fosbol EL, Folke F, Jacobsen S, Rasmussen JN, Sorensen R, Schramm TK, Andersen SS, Rasmussen S, Poulsen HE, Kober L, Torp-Pedersen C, Gislason GH. Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals. Circ Cardiovasc Qual Outcomes. 2010;3:395–405. doi: 10.1161/CIRCOUTCOMES.109.861104.
    1. Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, Egger M, Juni P. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:c7086. doi: 10.1136/bmj.c7086.
    1. Lane NE, Schnitzer TJ, Birbara CA, Mokhtarani M, Shelton DL, Smith MD, Brown MT. Tanezumab for the treatment of pain from osteoarthritis of the knee. N Engl J Med. 2010;363:1521–1531. doi: 10.1056/NEJMoa0901510.
    1. Wood JN. Nerve growth factor and pain. N Engl J Med. 2010;363:1572–1573. doi: 10.1056/NEJMe1004416.
    1. Andriacchi TP, Mundermann A, Smith RL, Alexander EJ, Dyrby CO, Koo S. A framework for the in vivo pathomechanics of osteoarthritis at the knee. Ann Biomed Eng. 2004;32:447–457. doi: 10.1023/B:ABME.0000017541.82498.37.
    1. Zhao D, Banks SA, Mitchell KH, D'Lima DD, Colwell CW, Jr, Fregly BJ. Correlation between the knee adduction torque and medial contact force for a variety of gait patterns. J Orthop Res. 2007;25:789–797. doi: 10.1002/jor.20379.
    1. Sharma L, Hurwitz DE, Thonar EJ-MA, Sum JA, Lenz ME, Dunlop DD, Schnitzer TJ, Kirwan-Mellis G, Andriacchi TP. Knee adduction moment, serum hyaluronan level, and disease severity in medial tibiofemoral osteoarthritis. Arthritis Rheum. 1998;41:1233–1240. doi: 10.1002/1529-0131(199807)41:7<1233::AID-ART14>;2-L.
    1. Schnitzer TJ, Popovich JM, Andersson GBJ, Andriacchi TP. Effect of piroxicam on gait in patients with osteoarthritis of the knee. Arthritis Rheum. 1993;36:1207–1213. doi: 10.1002/art.1780360905.
    1. Kean CO, Hinman RS, Bowles KA, Cicuttini F, Davies-Tuck M, Bennell KL. Comparison of peak knee adduction moment and knee adduction moment impulse in distinguishing between severities of knee osteoarthritis. Clin Biomech (Bristol, Avon) 2012;27:520–523. doi: 10.1016/j.clinbiomech.2011.12.007.
    1. Boyer KA, Angst MS, Asay J, Giori NJ, Andriacchi TP. Sensitivity of gait parameters to the effects of anti-inflammatory and opioid treatments in knee osteoarthritis patients. J Orthop Res. 2012;30:1118–1124. doi: 10.1002/jor.22037.
    1. Lim BW, Hinman RS, Wrigley TV, Sharma L, Bennell KL. Does knee malalignment mediate the effects of quadriceps strengthening on knee adduction moment, pain, and function in medial knee osteoarthritis? A randomized controlled trial. Arthritis Rheum. 2008;59:943–951. doi: 10.1002/art.23823.
    1. Miyazaki T, Wada M, Kawahara H, Sato M, Bada S, Shimada S. Dynamic load at baseline can predict radiographic disease progression in medial compartment knee osteoarthritis. Ann Rheum Dis. 2002;61:617–622. doi: 10.1136/ard.61.7.617.
    1. Bennell KL, Hinman RS. A review of the clinical evidence for exercise in osteoarthritis of the hip and knee. J Sci Med Sport. 2011;14:4–9. doi: 10.1016/j.jsams.2010.08.002.
    1. Block JA, Shakoor N. Lower limb osteoarthritis: biomechanical alterations and implications for therapy. Curr Opin Rheumatol. 2010;22:544–550. doi: 10.1097/BOR.0b013e32833bd81f.
    1. Simic M, Hinman RS, Wrigley TV, Bennell KL, Hunt MA. Gait modification strategies for altering medial knee joint load: a systematic review. Arthritis Care Res (Hoboken) 2011;63:405–426.
    1. Fitzgerald GK, Childs JD, Ridge TM, Irrgang JJ. Agility and perturbation training for a physically active individual with knee osteoarthritis. Phys Ther. 2002;82:372–382.
    1. Risberg MA, Holm I, Mykleburst G, Engebretsen L. Neuromuscular training versus strength training during first 6 months after anterior cruciate ligament reconstruction: a randomized clinical trial. Physical Ther. 2007;87:737–750. doi: 10.2522/ptj.20060041.
    1. Thorstensson CA, Henriksson M, von Porat A, Sjodahl C, Roos EM. The effect of eight weeks of exercise on knee adduction moment in early knee osteoarthritis: a pilot study. Osteoarthritis Cartilage. 2007;15:1163–1170. doi: 10.1016/j.joca.2007.03.012.
    1. Thorp LE, Wimmer MA, Foucher KC, Sumner DR, Shakoor N, Block JA. The biomechanical effects of focused muscle training on medial knee loads in OA of the knee: a pilot, proof of concept study. J Musculoskel Neuronal Interact. 2010;10:166–173.
    1. Roos EM, Dahlberg L. Positive effects of moderate exercise on glycosaminoglycan content in knee cartilage: a four-month, randomized, controlled trial in patients at risk of osteoarthritis. Arthritis Rheum. 2005;52:3507–3514. doi: 10.1002/art.21415.
    1. Bennell K, Wrigley T, Kyriakides M, Metcalf B, Roos E, Egerton T, Hunt M, Hodges P, Forbes A, Ageberg E, Hinman R. Comparison of neuromuscular and quadriceps strengthening exercise in people with medial knee osteoarthritis and varus malalignment: randomised controlled trial. Osteoarthritis Cartilage. 2013;21:S273–S274. doi: 10.1016/j.joca.2013.02.573.
    1. Mandelbaum BR, Silvers HJ, Watanabe DS, Knarr JF, Thomas SD, Griffin LY, Kirkendall DT, Garrett W., Jr Effectiveness of a neuromuscular and proprioceptive training program in preventing anterior cruciate ligament injuries in female athletes: 2-year follow-up. Am J Sports Med. 2005;33:1003–1010. doi: 10.1177/0363546504272261.
    1. Henriksen M, Simonsen EB, Alkjaer T, Lund H, Graven-Nielsen T, Danneskiold-Samsoe B, Bliddal H. Increased joint loads during walking: a consequence of pain relief in knee osteoarthritis. Knee. 2006;13:445–450. doi: 10.1016/j.knee.2006.08.005.
    1. Alentorn-Geli E, Myer GD, Silvers HJ, Samitier G, Romero D, Lazaro-Haro C, Cugat R. Prevention of non-contact anterior cruciate ligament injuries in soccer players. Part 2: a review of prevention programs aimed to modify risk factors and to reduce injury rates. Knee Surg Sports Traumatol Arthrosc. 2009;17:859–879. doi: 10.1007/s00167-009-0823-z.
    1. Stensrud S, Roos EM, Risberg MA. A 12-week exercise therapy program in middle-aged patients with degenerative meniscus tears: a case series with 1 year follow up. JOSPT. 2012;42:919–931. doi: 10.2519/jospt.2012.4165.
    1. Ericsson YB, Dahlberg LE, Roos EM. Effects of functional exercise training on performance and muscle strength after meniscectomy: a randomized trial. Scand J Med Sci Sports. 2009;19:156–165. doi: 10.1111/j.1600-0838.2008.00794.x.
    1. Ageberg E, Nilsdottir A, Kosek E, Roos E. Effects of neuromuscular training (NEMEX-TJR) on patient-reported outcomes and physical function in severe primary hip or knee osteoarthritis: a controlled before-and-after study. BMC Musculoskel Disord. 2013;14:232–245. doi: 10.1186/1471-2474-14-232.
    1. Villadsen A, Roos EM, Overgaard S, Holsgaard-Larsen A. Agreement and reliability of functional performance and muscle power in patients with advanced osteoarthritis of the hip or knee. Am J Phys Med Rehabil. 2012;91:401–410. doi: 10.1097/PHM.0b013e3182465ed0.
    1. Henriksen M, Graven-Nielsen T, Aaboe J, Andriacchi TP, Bliddal H. Gait changes in patients with knee osteoarthritis are replicated by experimental knee pain. Arthritis Care Res (Hoboken) 2010;62:501–509. doi: 10.1002/acr.20033.
    1. Briem K, Axe MJ, Snyder-Mackler L. Medial knee joint loading increases in those who respond to hyaluronan injection for medial knee osteoarthritis. J Orthop Res. 2009;27:1420–1425. doi: 10.1002/jor.20899.
    1. Hurwitz DE, Ryals AB, Block JA, Sharma L, Schnitzer TJ, Andriacchi TP. Knee pain and joint loading in subjects with osteoarthritis of the knee. J Orthop Res. 2000;18:572–579. doi: 10.1002/jor.1100180409.
    1. Doi T, Akai M, Fujino K, Hoshino Y, Iwaya T, Sunami Y. Effect of nonsteroidal anti-inflammatory drug plasters for knee osteoarthritis in Japanese: a randomized controlled trial. Mod Rheumatol. 2010;20:24–33. doi: 10.3109/s10165-009-0227-4.
    1. Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK, Bierma-Zeinstra S, Brandt KD, Croft P, Doherty M, Dougadol M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P. OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage. 2010;18:476–499. doi: 10.1016/j.joca.2010.01.013.
    1. Chan AW, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hrobjartsson A, Schulz KF, Parulekar WR, Krleža-Jeric K, Laupacis A, Moher D. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586–e7586. doi: 10.1136/bmj.e7586.
    1. Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, Elbourne D, Egger M, Altman DG. CONSORT, 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c869–c869. doi: 10.1136/bmj.c869.
    1. Pedersen KM, Andersen JS, Sondergaard J. General practice and primary health care in Denmark. J Am Board Family Med. 2012;25(Suppl 1):S34–S38. doi: 10.3122/jabfm.2012.02.110216.
    1. Zwarenstein M, Treweek S, Gagnier JJ, Altman DG, Tunis S, Haynes B, Oxman AD, Moher D. Improving the reporting of pragmatic trials: an extension of the CONSORT statement. BMJ. 2008;337:a2390–a2390. doi: 10.1136/bmj.a2390.
    1. Altman RD, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, Howell D, Kaplan D, Koopman W, Longley S, Mankin H, McShane DJ, Medsger T, Meenan R, Mikkelsen W, Moskowitz W, Murphy W, Rothschild B, Segal M, Sokoloff L, Wolfe F. Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthritis Rheum. 1986;29:1039–1049. doi: 10.1002/art.1780290816.
    1. Zhang W, Doherty M, Peat G, Bierma-Zeinstra MA, Arden NK, Bresnihan B, Herrero-Beaumont G, Kirschner S, Leeb BF, Lohmander LS, Mezières B, Pavelka K, Punzi L, So AK, Tuncer T, Watt I, Bijlsma JW. EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis. Ann Rheum Dis. 2010;69:483–489. doi: 10.1136/ard.2009.113100.
    1. Altman RD, Gold GE. Atlas of individual radiographic features in osteoarthritis, revised. Osteoarthritis Cartilage. 2007;15(Suppl A):A1–56. doi: 10.1016/j.joca.2006.11.009.
    1. Schiphof D, de Klerk BM, Kerkhof HJ, Hofman A, Koes BW, Boers M, Bierma-Zeinstra SM. Impact of different descriptions of the Kellgren and Lawrence classification criteria on the diagnosis of knee osteoarthritis. Ann Rheum Dis. 2011;70:1422–1427. doi: 10.1136/ard.2010.147520.
    1. Borg G, Ljunggren G, Ceci R. The increase of perceived exertion, aches and pain in the legs, heart-rate and blood lactate during exercise on a bicycle ergometer. Eur J Appl Physiol Occup Physiol. 1985;54:343–349. doi: 10.1007/BF02337176.
    1. Ageberg E, Link A, Roos EM. Feasibility of neuromuscular training in patients with severe hip or knee OA: the individualized goal-based NEMEX-TJR training program. BMC Musculoskel Disord. 2010;11:126. doi: 10.1186/1471-2474-11-126.
    1. Villadsen A, Overgaard S, Holsgaard-Larsen A, Christensen R, Roos EM. Postoperative effects of neuromuscular exercise prior to hip or knee arthroplasty: a randomised controlled trial. Ann Rheum Dis. 2013;73:1130–1137. doi: 10.1136/annrheumdis-2012-203135.
    1. Fransen M, McConnell S. Cochrane Database Syst Rev. 2008. Fransen - Exercise for osteoarthritis of the knee (review)
    1. Thomee R. A comprehensive treatment approach for patellofemoral pain syndrome in young women. Phys Ther. 1997;77:1690–1703.
    1. Jespersen T, Jorgensen MB, Hansen JV, Holtermann A, Sogaard K. The relationship between low back pain and leisure time physical activity in a working population of cleaners: a study with weekly follow-ups for 1 year. BMC Musculoskel Disord. 2012;13:28. doi: 10.1186/1471-2474-13-28.
    1. Kumar D, Manal KT, Rudolph KS. Knee joint loading during gait in healthy controls and individuals with knee osteoarthritis. Osteoarthritis Cartilage. 2013;21:298–305. doi: 10.1016/j.joca.2012.11.008.
    1. Boyer KA, Bertin J, Asay J, Giori NJ, Andriacchi TP. 56th Annual Meeting of the Orthopaedic Research Society (Poster) 2010. Gait adaptations in response to treatment of OA pain by NSAID or opioid.
    1. Kadaba MP, Ramakrishnan HK, Wootten ME. Measurement of lower extremity kinematics during level walking. J Orthop Res. 1990;8:383–392. doi: 10.1002/jor.1100080310.
    1. Davis RB, Õunpuu S, Tyburski D, Gage JR. A gait analysis data-collection and reduction technique. Hum Mov Sci. 1991;10:575–587. doi: 10.1016/0167-9457(91)90046-Z.
    1. Dobson F, Hinman RS, Hall M, Terwee CB, Roos EM, Bennell KL. Measurement properties of performance-based measures to assess physical function in hip and knee osteoarthritis: a systematic review. Osteoarthritis Cartilage. 2012;20:1548–1562. doi: 10.1016/j.joca.2012.08.015.
    1. Thorstensson CA. Reduced functional performance in the lower extremity predicted radiographic knee osteoarthritis five years later. Ann Rheum Dis. 2004;63:402–407. doi: 10.1136/ard.2003.007583.
    1. Bremander AB, Dahl LL, Roos EM. Validity and reliability of functional performance tests in meniscectomized patients with or without knee osteoarthritis. Scand J Med Sci Sports. 2007;17:120–127.
    1. Larsson A-C, Petersson I, Ekdahl C. Functional capacity and early radiographic osteoarthritis in middle-aged people with chronic knee pain. Physiother Res Int. 1998;3:153–163. doi: 10.1002/pri.137.
    1. Roos EM, Ostenberg A, Roos H, Ekdahl C, Lohmander LS. Long-term outcome of meniscectomy: symptoms, function, and performance tests in patients with or without radiographic osteoarthritis compared to matched controls. Osteoarthritis Cartilage. 2001;9:316–324. doi: 10.1053/joca.2000.0391.
    1. Noyes FR, Barber SD, Mangine RE. Abnormal lower limb symmetry determined by function hop tests after anterior cruciate ligament rupture. Am J Sports Med. 1991;19:513–518. doi: 10.1177/036354659101900518.
    1. Roos EM, Bremander AB, Englund M, Lohmander LS. Change in self-reported outcomes and objective physical function over 7 years in middle-aged subjects with or at high risk of knee osteoarthritis. Ann Rheum Dis. 2008;67:505–510. doi: 10.1136/ard.2007.074088.
    1. Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee Injury and Osteoarthritis Outcome Score (KOOS)-development of a self-administered outcome measure kopi. J Orthop Sports Phys Ther. 1998;78:88–96. doi: 10.2519/jospt.1998.28.2.88.
    1. Roos EM, Lohmander LS. The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis. Health Qual Life Outcome. 2003;1:64. doi: 10.1186/1477-7525-1-64.
    1. Roos EM, Toksvig-Larsen Knee injury and Osteoarthritis Outcome Score (KOOS) - validation and comparison to the WOMAC in total knee replacement. Health Qual Life Outcome. 2003;1:17. doi: 10.1186/1477-7525-1-17.
    1. Terwee CB, Bouwmeester W, van Elsland SL, de Vet HC, Dekker J. Instruments to assess physical activity in patients with osteoarthritis of the hip or knee: a systematic review of measurement properties. Osteoarthritis Cartilage. 2011;19:620–633. doi: 10.1016/j.joca.2011.01.002.
    1. Peterfy C, Li J, Zaim S, Duryea J, Lynch J, Miaux Y, Yu W, Genant HK. Comparison of fixed-flexion positioning with fluoroscopic semi-flexed positioning for quantifying radiographic joint-space width in the knee: test-retest reproducibility. Skeletal Radiol. 2003;32:128–132. doi: 10.1007/s00256-002-0603-z.
    1. Yochum TR, Rowe LJ. Essentials of skeletal radiology. 3. Philadelphia: Lippincott Williams & Wilkins; 2004.
    1. Sorensen J, Davidsen M, Gudex C, Pedersen KM, Bronnum-Hansen H. Danish EQ-5D population norms. Scand J Public Health. 2009;37:467–474. doi: 10.1177/1403494809105286.
    1. Wittrup-Jensen KU, Lauridsen J, Gudex C, Pedersen KM. Generation of a Danish TTO value set for EQ-5D health states. Scand J Public Health. 2009;37:459–466. doi: 10.1177/1403494809105287.
    1. Bjørner JB, Damsgaard MT, Watt T, Bech P, Rasmussen NK, Kristensen TS, Modvig J, Thunedborg K. Dansk manual til SF-36. Et spørgeskema om helbredsstatus. Copenhagen: Lif Lægemiddelindustriforeningen; 1997.
    1. Riecke BF, Christensen R, Christensen P, Leeds AR, Boesen M, Lohmander LS, Astrup A, Bliddal H. Comparing two low-energy diets for the treatment of knee osteoarthritis symptoms in obese patients: a pragmatic randomized clinical trial. Osteoarthritis Cartilage. 2010;18:746–754. doi: 10.1016/j.joca.2010.02.012.
    1. De Vet HC, Terwee CB, Mokkink LB, Knol DL. Measurement in medicine: a practical guide. Cambridge: Cambridge University Press; 2011.
    1. Pocock SJ, Assmann SE, Enos LE, Kasten LE. Subgroup analysis, covariate adjustment and baseline comparisons in clinical trial reporting: current practice and problems. Stat Med. 2002;21:2917–2930. doi: 10.1002/sim.1296.
    1. Buckwalter JA, Stanish WD, Rosier RN, Schenck RC, Dennis DA, Coutts RD. The increasing need for nonoperative treatment of patients with osteoarthritis. Clin Orthop Relat Res. 2001;385:36–45. doi: 10.1097/00003086-200104000-00008.
    1. Lai PP, Leung AK, Li AN, Zhang M. Three-dimensional gait analysis of obese adults. Clin Biomech (Bristol, Avon) 2008;23(Suppl 1):S2–S6. doi: 10.1016/j.clinbiomech.2008.02.004.

Source: PubMed

3
订阅