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/Title (The 6-Minute Walk Test and Person-Reported Outcomes in Boys with Duchenne Muscular Dystrophy and Typically Developing Controls: Longitudinal Comparisons and Clinically-Meaningful Changes Over One Year � PLOS Currents Muscular Dystrophy)
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BT 15.000 718.042 Td /F2 21.0 Tf  [(The 6-Minute Walk Test and Person-Reported Outcomes in )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(Boys with Duchenne Muscular Dystrophy and Typically )] TJ ET
BT 15.000 668.146 Td /F2 21.0 Tf  [(Developing Controls: Longitudinal Comparisons and Clinically-)] TJ ET
BT 15.000 643.198 Td /F2 21.0 Tf  [(Meaningful Changes Over One Year)] TJ ET
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BT 15.000 625.192 Td /F3 9.8 Tf  [(July 8, 2013)] TJ ET
BT 67.806 625.192 Td /F3 9.8 Tf  [(�)] TJ ET
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BT 72.681 625.192 Td /F3 9.8 Tf  [(Natural History and Outcome Measures)] TJ ET
BT 26.250 613.351 Td /F1 9.8 Tf  [(Erik Henricson)] TJ ET
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BT 89.635 613.351 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 95.056 613.351 Td /F1 9.8 Tf  [(Richard Abresch)] TJ ET
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BT 172.539 613.351 Td /F1 9.8 Tf  [(Jay J. Han)] TJ ET
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BT 224.019 613.351 Td /F1 9.8 Tf  [(Alina Nicorici)] TJ ET
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BT 26.250 601.446 Td /F1 9.8 Tf  [(Henricson E, Abresch R, Han JJ, Nicorici A, Goude Keller E, de Bie E, McDonald CM. The 6-Minute Walk Test and Person-)] TJ ET
BT 26.250 589.542 Td /F1 9.8 Tf  [(Reported Outcomes in Boys with Duchenne Muscular Dystrophy and Typically Developing Controls: Longitudinal Comparisons )] TJ ET
BT 26.250 577.637 Td /F1 9.8 Tf  [(and Clinically-Meaningful Changes Over One Year. PLOS Currents Muscular Dystrophy. 2013 Jul 8 . Edition 1. doi: )] TJ ET
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BT 26.250 536.630 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 516.675 Td /F1 9.8 Tf  [(INTRODUCTION:)] TJ ET
BT 26.250 497.271 Td /F1 9.8 Tf  [(Data is currently lacking anchoring a 30-meter longitudinal change in walking ability by 6-minute walk test \(6MWT\) in Duchenne )] TJ ET
BT 26.250 485.366 Td /F1 9.8 Tf  [(muscular dystrophy as a minimal clinically important difference and �clinically meaningful� person-reported outcomes \(PROs\) at )] TJ ET
BT 26.250 473.461 Td /F1 9.8 Tf  [(differing levels of ambulatory ability.)] TJ ET
BT 26.250 454.056 Td /F1 9.8 Tf  [(METHODS:)] TJ ET
BT 26.250 434.652 Td /F1 9.8 Tf  [(We describe correlation between measures, 1-year change in measures, and correlation of 1-year changes between measures )] TJ ET
BT 26.250 422.747 Td /F1 9.8 Tf  [(for the six-minute walk test \(6MWT\), 10-meter run/walk velocity, PedsQL and POSNA Pediatric Outcomes Data Collection )] TJ ET
BT 26.250 410.842 Td /F1 9.8 Tf  [(Instrument \(PODCI\) in 24 4-12 year old. ambulatory DMD and 36 typical controls, and determine if minimal clinically important )] TJ ET
BT 26.250 398.937 Td /F1 9.8 Tf  [(differences \(MCID\) of PROs contribute to different estimates of 6-minute walk distance \(6MWD\) change at differing levels of )] TJ ET
BT 26.250 387.033 Td /F1 9.8 Tf  [(ability.)] TJ ET
BT 26.250 367.628 Td /F1 9.8 Tf  [(RESULTS:)] TJ ET
BT 26.250 348.223 Td /F1 9.8 Tf  [(PedsQL total and physical function and PODCI global, transfer/mobility and sports/physical function PROs demonstrated )] TJ ET
BT 26.250 336.318 Td /F1 9.8 Tf  [(significant differences between DMD and controls \(p<0.00001\). In DMD, 6MWD and 10-meter run/walk velocity were correlated )] TJ ET
BT 26.250 324.414 Td /F1 9.8 Tf  [(with PODCI domain scores, with the transfer/mobility scale showing the strongest relationship \(r=0.79 and r=0.76\). In DMD, )] TJ ET
BT 26.250 312.509 Td /F1 9.8 Tf  [(6MWD distance and 10-meter run/walk velocity weakly correlated with PedsQL domain scores. In DMD, 6MWD, 10-meter )] TJ ET
BT 26.250 300.604 Td /F1 9.8 Tf  [(run/walk velocity, and PODCI global and transfer and basic mobility demonstrated significant one-year change and exceeded )] TJ ET
BT 26.250 288.699 Td /F1 9.8 Tf  [(the amount of change representing MCID. In DMD, 6MWD change highly correlated with change in PODCI global and PODCI )] TJ ET
BT 26.250 276.795 Td /F1 9.8 Tf  [(transfer/mobility scores \(r=0.76 and r=0.93\). PODCI global and PODCI transfer/mobility scales provided the best estimates of )] TJ ET
BT 26.250 264.890 Td /F1 9.8 Tf  [(6MWT performance. A �meaningful� 4.5 point change in a low PODCI transfer / basic mobility score of 30 to 34.5 was )] TJ ET
BT 26.250 252.985 Td /F1 9.8 Tf  [(associated with a 5.6m 6MWD change from 150.3 to 155.9m. At PODCI levels closer to normative levels for healthy controls, )] TJ ET
BT 26.250 241.080 Td /F1 9.8 Tf  [(the change in 6MWD distance associated with a �meaningful� change in PODCI scores was almost 46m.)] TJ ET
BT 26.250 221.676 Td /F1 9.8 Tf  [(DISCUSSION:)] TJ ET
BT 26.250 202.271 Td /F1 9.8 Tf  [(At lower levels of function, smaller increases in 6MWD result in meaningful change in quality of life \(QoL\) instrument scores. At )] TJ ET
BT 26.250 190.366 Td /F1 9.8 Tf  [(higher levels of function, larger increases may be necessary to achieve the same QoL change score.)] TJ ET
BT 26.250 153.764 Td /F4 12.0 Tf  [(Funding Statement)] TJ ET
BT 26.250 133.809 Td /F1 9.8 Tf  [(This project was funded through grants from the U.S. Department of Education/NIDRR \(#H133B031118, #H133B090001\), the )] TJ ET
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BT 26.250 110.000 Td /F1 9.8 Tf  [(research grant from PTC Therapeutics.)] TJ ET
BT 26.250 80.897 Td /F4 12.0 Tf  [(Background)] TJ ET
BT 26.250 60.943 Td /F1 9.8 Tf  [(Duchenne muscular dystrophy \(DMD\) is an X-linked developmental disorder caused by mutations of the dystrophin gene)] TJ ET
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BT 26.250 49.038 Td /F1 9.8 Tf  [(subsequent alteration or loss of production of dystrophin protein isoforms in muscle, central nervous system \(CNS\), and other )] TJ ET
BT 26.250 37.134 Td /F1 9.8 Tf  [(tissues. Affecting approximately 1/3500 males)] TJ ET
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BT 15.000 718.042 Td /F2 21.0 Tf  [(The 6-Minute Walk Test and Person-Reported Outcomes in )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(Boys with Duchenne Muscular Dystrophy and Typically )] TJ ET
BT 15.000 668.146 Td /F2 21.0 Tf  [(Developing Controls: Longitudinal Comparisons and Clinically-)] TJ ET
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BT 72.681 625.192 Td /F3 9.8 Tf  [(Natural History and Outcome Measures)] TJ ET
BT 26.250 613.351 Td /F1 9.8 Tf  [(Erik Henricson)] TJ ET
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BT 89.635 613.351 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 95.056 613.351 Td /F1 9.8 Tf  [(Richard Abresch)] TJ ET
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BT 167.118 613.351 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 172.539 613.351 Td /F1 9.8 Tf  [(Jay J. Han)] TJ ET
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BT 218.598 613.351 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 224.019 613.351 Td /F1 9.8 Tf  [(Alina Nicorici)] TJ ET
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BT 280.354 613.351 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 285.775 613.351 Td /F1 9.8 Tf  [(Erica Goude Keller)] TJ ET
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BT 373.018 613.351 Td /F1 9.8 Tf  [(Evan de Bie)] TJ ET
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BT 431.011 613.351 Td /F1 9.8 Tf  [(Craig M. McDonald)] TJ ET
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BT 26.250 589.542 Td /F1 9.8 Tf  [(Reported Outcomes in Boys with Duchenne Muscular Dystrophy and Typically Developing Controls: Longitudinal Comparisons )] TJ ET
BT 26.250 577.637 Td /F1 9.8 Tf  [(and Clinically-Meaningful Changes Over One Year. PLOS Currents Muscular Dystrophy. 2013 Jul 8 . Edition 1. doi: )] TJ ET
BT 26.250 565.732 Td /F1 9.8 Tf  [(10.1371/currents.md.9e17658b007eb79fcd6f723089f79e06.)] TJ ET
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BT 26.250 536.630 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 516.675 Td /F1 9.8 Tf  [(INTRODUCTION:)] TJ ET
BT 26.250 497.271 Td /F1 9.8 Tf  [(Data is currently lacking anchoring a 30-meter longitudinal change in walking ability by 6-minute walk test \(6MWT\) in Duchenne )] TJ ET
BT 26.250 485.366 Td /F1 9.8 Tf  [(muscular dystrophy as a minimal clinically important difference and �clinically meaningful� person-reported outcomes \(PROs\) at )] TJ ET
BT 26.250 473.461 Td /F1 9.8 Tf  [(differing levels of ambulatory ability.)] TJ ET
BT 26.250 454.056 Td /F1 9.8 Tf  [(METHODS:)] TJ ET
BT 26.250 434.652 Td /F1 9.8 Tf  [(We describe correlation between measures, 1-year change in measures, and correlation of 1-year changes between measures )] TJ ET
BT 26.250 422.747 Td /F1 9.8 Tf  [(for the six-minute walk test \(6MWT\), 10-meter run/walk velocity, PedsQL and POSNA Pediatric Outcomes Data Collection )] TJ ET
BT 26.250 410.842 Td /F1 9.8 Tf  [(Instrument \(PODCI\) in 24 4-12 year old. ambulatory DMD and 36 typical controls, and determine if minimal clinically important )] TJ ET
BT 26.250 398.937 Td /F1 9.8 Tf  [(differences \(MCID\) of PROs contribute to different estimates of 6-minute walk distance \(6MWD\) change at differing levels of )] TJ ET
BT 26.250 387.033 Td /F1 9.8 Tf  [(ability.)] TJ ET
BT 26.250 367.628 Td /F1 9.8 Tf  [(RESULTS:)] TJ ET
BT 26.250 348.223 Td /F1 9.8 Tf  [(PedsQL total and physical function and PODCI global, transfer/mobility and sports/physical function PROs demonstrated )] TJ ET
BT 26.250 336.318 Td /F1 9.8 Tf  [(significant differences between DMD and controls \(p<0.00001\). In DMD, 6MWD and 10-meter run/walk velocity were correlated )] TJ ET
BT 26.250 324.414 Td /F1 9.8 Tf  [(with PODCI domain scores, with the transfer/mobility scale showing the strongest relationship \(r=0.79 and r=0.76\). In DMD, )] TJ ET
BT 26.250 312.509 Td /F1 9.8 Tf  [(6MWD distance and 10-meter run/walk velocity weakly correlated with PedsQL domain scores. In DMD, 6MWD, 10-meter )] TJ ET
BT 26.250 300.604 Td /F1 9.8 Tf  [(run/walk velocity, and PODCI global and transfer and basic mobility demonstrated significant one-year change and exceeded )] TJ ET
BT 26.250 288.699 Td /F1 9.8 Tf  [(the amount of change representing MCID. In DMD, 6MWD change highly correlated with change in PODCI global and PODCI )] TJ ET
BT 26.250 276.795 Td /F1 9.8 Tf  [(transfer/mobility scores \(r=0.76 and r=0.93\). PODCI global and PODCI transfer/mobility scales provided the best estimates of )] TJ ET
BT 26.250 264.890 Td /F1 9.8 Tf  [(6MWT performance. A �meaningful� 4.5 point change in a low PODCI transfer / basic mobility score of 30 to 34.5 was )] TJ ET
BT 26.250 252.985 Td /F1 9.8 Tf  [(associated with a 5.6m 6MWD change from 150.3 to 155.9m. At PODCI levels closer to normative levels for healthy controls, )] TJ ET
BT 26.250 241.080 Td /F1 9.8 Tf  [(the change in 6MWD distance associated with a �meaningful� change in PODCI scores was almost 46m.)] TJ ET
BT 26.250 221.676 Td /F1 9.8 Tf  [(DISCUSSION:)] TJ ET
BT 26.250 202.271 Td /F1 9.8 Tf  [(At lower levels of function, smaller increases in 6MWD result in meaningful change in quality of life \(QoL\) instrument scores. At )] TJ ET
BT 26.250 190.366 Td /F1 9.8 Tf  [(higher levels of function, larger increases may be necessary to achieve the same QoL change score.)] TJ ET
BT 26.250 153.764 Td /F4 12.0 Tf  [(Funding Statement)] TJ ET
BT 26.250 133.809 Td /F1 9.8 Tf  [(This project was funded through grants from the U.S. Department of Education/NIDRR \(#H133B031118, #H133B090001\), the )] TJ ET
BT 26.250 121.905 Td /F1 9.8 Tf  [(U.S. Department of Defense \(W81XWH-09-1-0592\), the National Institutes of Health \(1R01AR061875, 1R01AR062380\) and a )] TJ ET
BT 26.250 110.000 Td /F1 9.8 Tf  [(research grant from PTC Therapeutics.)] TJ ET
BT 26.250 80.897 Td /F4 12.0 Tf  [(Background)] TJ ET
BT 26.250 60.943 Td /F1 9.8 Tf  [(Duchenne muscular dystrophy \(DMD\) is an X-linked developmental disorder caused by mutations of the dystrophin gene)] TJ ET
0.267 0.267 0.267 rg
BT 545.915 62.450 Td /F4 8.7 Tf  [(1)] TJ ET
0.271 0.267 0.267 rg
BT 550.734 60.943 Td /F1 9.8 Tf  [( and )] TJ ET
BT 26.250 49.038 Td /F1 9.8 Tf  [(subsequent alteration or loss of production of dystrophin protein isoforms in muscle, central nervous system \(CNS\), and other )] TJ ET
BT 26.250 37.134 Td /F1 9.8 Tf  [(tissues. Affecting approximately 1/3500 males)] TJ ET
0.267 0.267 0.267 rg
BT 224.584 38.641 Td /F4 8.7 Tf  [(2)] TJ ET
0.271 0.267 0.267 rg
BT 229.403 37.134 Td /F1 9.8 Tf  [( , the disease is characterized by progressive loss of muscle strength that is )] TJ ET
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0.267 0.267 0.267 rg
BT 15.000 718.042 Td /F2 21.0 Tf  [(The 6-Minute Walk Test and Person-Reported Outcomes in )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(Boys with Duchenne Muscular Dystrophy and Typically )] TJ ET
BT 15.000 668.146 Td /F2 21.0 Tf  [(Developing Controls: Longitudinal Comparisons and Clinically-)] TJ ET
BT 15.000 643.198 Td /F2 21.0 Tf  [(Meaningful Changes Over One Year)] TJ ET
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BT 15.000 625.192 Td /F3 9.8 Tf  [(July 8, 2013)] TJ ET
BT 67.806 625.192 Td /F3 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
BT 72.681 625.192 Td /F3 9.8 Tf  [(Natural History and Outcome Measures)] TJ ET
BT 26.250 613.351 Td /F1 9.8 Tf  [(Erik Henricson)] TJ ET
0.271 0.267 0.267 rg
BT 89.635 613.351 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 95.056 613.351 Td /F1 9.8 Tf  [(Richard Abresch)] TJ ET
0.271 0.267 0.267 rg
BT 167.118 613.351 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 172.539 613.351 Td /F1 9.8 Tf  [(Jay J. Han)] TJ ET
0.271 0.267 0.267 rg
BT 218.598 613.351 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 224.019 613.351 Td /F1 9.8 Tf  [(Alina Nicorici)] TJ ET
0.271 0.267 0.267 rg
BT 280.354 613.351 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 285.775 613.351 Td /F1 9.8 Tf  [(Erica Goude Keller)] TJ ET
0.271 0.267 0.267 rg
BT 367.597 613.351 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 373.018 613.351 Td /F1 9.8 Tf  [(Evan de Bie)] TJ ET
0.271 0.267 0.267 rg
BT 425.590 613.351 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 431.011 613.351 Td /F1 9.8 Tf  [(Craig M. McDonald)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 601.446 Td /F1 9.8 Tf  [(Henricson E, Abresch R, Han JJ, Nicorici A, Goude Keller E, de Bie E, McDonald CM. The 6-Minute Walk Test and Person-)] TJ ET
BT 26.250 589.542 Td /F1 9.8 Tf  [(Reported Outcomes in Boys with Duchenne Muscular Dystrophy and Typically Developing Controls: Longitudinal Comparisons )] TJ ET
BT 26.250 577.637 Td /F1 9.8 Tf  [(and Clinically-Meaningful Changes Over One Year. PLOS Currents Muscular Dystrophy. 2013 Jul 8 . Edition 1. doi: )] TJ ET
BT 26.250 565.732 Td /F1 9.8 Tf  [(10.1371/currents.md.9e17658b007eb79fcd6f723089f79e06.)] TJ ET
q
15.000 22.848 577.500 540.503 re W n
0.271 0.267 0.267 rg
BT 26.250 536.630 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 516.675 Td /F1 9.8 Tf  [(INTRODUCTION:)] TJ ET
BT 26.250 497.271 Td /F1 9.8 Tf  [(Data is currently lacking anchoring a 30-meter longitudinal change in walking ability by 6-minute walk test \(6MWT\) in Duchenne )] TJ ET
BT 26.250 485.366 Td /F1 9.8 Tf  [(muscular dystrophy as a minimal clinically important difference and �clinically meaningful� person-reported outcomes \(PROs\) at )] TJ ET
BT 26.250 473.461 Td /F1 9.8 Tf  [(differing levels of ambulatory ability.)] TJ ET
BT 26.250 454.056 Td /F1 9.8 Tf  [(METHODS:)] TJ ET
BT 26.250 434.652 Td /F1 9.8 Tf  [(We describe correlation between measures, 1-year change in measures, and correlation of 1-year changes between measures )] TJ ET
BT 26.250 422.747 Td /F1 9.8 Tf  [(for the six-minute walk test \(6MWT\), 10-meter run/walk velocity, PedsQL and POSNA Pediatric Outcomes Data Collection )] TJ ET
BT 26.250 410.842 Td /F1 9.8 Tf  [(Instrument \(PODCI\) in 24 4-12 year old. ambulatory DMD and 36 typical controls, and determine if minimal clinically important )] TJ ET
BT 26.250 398.937 Td /F1 9.8 Tf  [(differences \(MCID\) of PROs contribute to different estimates of 6-minute walk distance \(6MWD\) change at differing levels of )] TJ ET
BT 26.250 387.033 Td /F1 9.8 Tf  [(ability.)] TJ ET
BT 26.250 367.628 Td /F1 9.8 Tf  [(RESULTS:)] TJ ET
BT 26.250 348.223 Td /F1 9.8 Tf  [(PedsQL total and physical function and PODCI global, transfer/mobility and sports/physical function PROs demonstrated )] TJ ET
BT 26.250 336.318 Td /F1 9.8 Tf  [(significant differences between DMD and controls \(p<0.00001\). In DMD, 6MWD and 10-meter run/walk velocity were correlated )] TJ ET
BT 26.250 324.414 Td /F1 9.8 Tf  [(with PODCI domain scores, with the transfer/mobility scale showing the strongest relationship \(r=0.79 and r=0.76\). In DMD, )] TJ ET
BT 26.250 312.509 Td /F1 9.8 Tf  [(6MWD distance and 10-meter run/walk velocity weakly correlated with PedsQL domain scores. In DMD, 6MWD, 10-meter )] TJ ET
BT 26.250 300.604 Td /F1 9.8 Tf  [(run/walk velocity, and PODCI global and transfer and basic mobility demonstrated significant one-year change and exceeded )] TJ ET
BT 26.250 288.699 Td /F1 9.8 Tf  [(the amount of change representing MCID. In DMD, 6MWD change highly correlated with change in PODCI global and PODCI )] TJ ET
BT 26.250 276.795 Td /F1 9.8 Tf  [(transfer/mobility scores \(r=0.76 and r=0.93\). PODCI global and PODCI transfer/mobility scales provided the best estimates of )] TJ ET
BT 26.250 264.890 Td /F1 9.8 Tf  [(6MWT performance. A �meaningful� 4.5 point change in a low PODCI transfer / basic mobility score of 30 to 34.5 was )] TJ ET
BT 26.250 252.985 Td /F1 9.8 Tf  [(associated with a 5.6m 6MWD change from 150.3 to 155.9m. At PODCI levels closer to normative levels for healthy controls, )] TJ ET
BT 26.250 241.080 Td /F1 9.8 Tf  [(the change in 6MWD distance associated with a �meaningful� change in PODCI scores was almost 46m.)] TJ ET
BT 26.250 221.676 Td /F1 9.8 Tf  [(DISCUSSION:)] TJ ET
BT 26.250 202.271 Td /F1 9.8 Tf  [(At lower levels of function, smaller increases in 6MWD result in meaningful change in quality of life \(QoL\) instrument scores. At )] TJ ET
BT 26.250 190.366 Td /F1 9.8 Tf  [(higher levels of function, larger increases may be necessary to achieve the same QoL change score.)] TJ ET
BT 26.250 153.764 Td /F4 12.0 Tf  [(Funding Statement)] TJ ET
BT 26.250 133.809 Td /F1 9.8 Tf  [(This project was funded through grants from the U.S. Department of Education/NIDRR \(#H133B031118, #H133B090001\), the )] TJ ET
BT 26.250 121.905 Td /F1 9.8 Tf  [(U.S. Department of Defense \(W81XWH-09-1-0592\), the National Institutes of Health \(1R01AR061875, 1R01AR062380\) and a )] TJ ET
BT 26.250 110.000 Td /F1 9.8 Tf  [(research grant from PTC Therapeutics.)] TJ ET
BT 26.250 80.897 Td /F4 12.0 Tf  [(Background)] TJ ET
BT 26.250 60.943 Td /F1 9.8 Tf  [(Duchenne muscular dystrophy \(DMD\) is an X-linked developmental disorder caused by mutations of the dystrophin gene)] TJ ET
0.267 0.267 0.267 rg
BT 545.915 62.450 Td /F4 8.7 Tf  [(1)] TJ ET
0.271 0.267 0.267 rg
BT 550.734 60.943 Td /F1 9.8 Tf  [( and )] TJ ET
BT 26.250 49.038 Td /F1 9.8 Tf  [(subsequent alteration or loss of production of dystrophin protein isoforms in muscle, central nervous system \(CNS\), and other )] TJ ET
BT 26.250 37.134 Td /F1 9.8 Tf  [(tissues. Affecting approximately 1/3500 males)] TJ ET
0.267 0.267 0.267 rg
BT 224.584 38.641 Td /F4 8.7 Tf  [(2)] TJ ET
0.271 0.267 0.267 rg
BT 229.403 37.134 Td /F1 9.8 Tf  [( , the disease is characterized by progressive loss of muscle strength that is )] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(1)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Muscular Dystrophy)] TJ ET

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BT 325.370 654.341 Td /F4 8.7 Tf  [(7)] TJ ET
0.271 0.267 0.267 rg
BT 330.189 652.833 Td /F1 9.8 Tf  [( .)] TJ ET
BT 26.250 633.429 Td /F1 9.8 Tf  [(While current practices have reduced rates of disease progression and have improved preservation of function for many with )] TJ ET
BT 26.250 621.524 Td /F1 9.8 Tf  [(DMD, none of the available treatments has been directed toward restoration of the damaged gene or protein product. However, )] TJ ET
BT 26.250 609.619 Td /F1 9.8 Tf  [(promising new therapies including nonsense mutation suppression via stop codon read through and exon skipping via antisense )] TJ ET
BT 26.250 597.714 Td /F1 9.8 Tf  [(oligonucleotides and morpholinos have been introduced into registration-directed clinical trials using international multicenter )] TJ ET
BT 26.250 585.810 Td /F1 9.8 Tf  [(collaborations. Both safety and efficacy trials have involved both ambulatory and nonambulatory subgroups of DMD populations)] TJ ET
0.267 0.267 0.267 rg
BT 576.296 587.317 Td /F4 8.7 Tf  [(8)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 577.793 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 28.659 575.412 Td /F4 8.7 Tf  [(9)] TJ ET
0.271 0.267 0.267 rg
BT 33.478 577.793 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 35.887 575.412 Td /F4 8.7 Tf  [(10)] TJ ET
0.271 0.267 0.267 rg
BT 45.525 573.905 Td /F1 9.8 Tf  [( . The research community has faced the need to identify and develop clinically meaningful outcome measures in DMD for )] TJ ET
BT 26.250 562.000 Td /F1 9.8 Tf  [(use in pivotal therapeutic trials.)] TJ ET
BT 26.250 542.595 Td /F1 9.8 Tf  [(In boys with DMD, walking abnormalities are a major disease manifestation that has great importance to patients and families. )] TJ ET
BT 26.250 530.691 Td /F1 9.8 Tf  [(Ambulation has been noted to be a prerequisite for normal physical functioning in humans)] TJ ET
0.267 0.267 0.267 rg
BT 413.188 532.198 Td /F4 8.7 Tf  [(11)] TJ ET
0.271 0.267 0.267 rg
BT 422.826 530.691 Td /F1 9.8 Tf  [( ; the major goal of medical and )] TJ ET
BT 26.250 518.786 Td /F1 9.8 Tf  [(physical therapy intervention during the ambulatory phase of DMD is to maintain ambulation for as long as possible)] TJ ET
0.267 0.267 0.267 rg
BT 522.086 520.293 Td /F4 8.7 Tf  [(3)] TJ ET
0.271 0.267 0.267 rg
BT 526.905 522.674 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 529.314 520.293 Td /F4 8.7 Tf  [(12)] TJ ET
0.271 0.267 0.267 rg
BT 538.952 522.674 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 541.361 520.293 Td /F4 8.7 Tf  [(13)] TJ ET
0.271 0.267 0.267 rg
BT 550.998 522.674 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 553.408 520.293 Td /F4 8.7 Tf  [(14)] TJ ET
0.271 0.267 0.267 rg
BT 563.045 518.786 Td /F1 9.8 Tf  [( . )] TJ ET
BT 26.250 506.881 Td /F1 9.8 Tf  [(Given that ambulatory compromise is a key component of the DMD disease process and that ambulation measures the function )] TJ ET
BT 26.250 494.976 Td /F1 9.8 Tf  [(of multiple muscle groups as well as cardiovascular activity, ambulation-related outcome measures are the most relevant )] TJ ET
BT 26.250 483.072 Td /F1 9.8 Tf  [(endpoints in DMD patients who are still able to walk. We previously reported that the modified 6-minute Walk Test \(6MWT\) is )] TJ ET
BT 26.250 471.167 Td /F1 9.8 Tf  [(feasible, safe, and reliable in boys with DMD who have not yet transitioned to full time wheelchair use)] TJ ET
0.267 0.267 0.267 rg
BT 462.475 472.674 Td /F4 8.7 Tf  [(15)] TJ ET
0.271 0.267 0.267 rg
BT 472.112 475.055 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 474.521 472.674 Td /F4 8.7 Tf  [(16)] TJ ET
0.271 0.267 0.267 rg
BT 484.159 471.167 Td /F1 9.8 Tf  [( . We also )] TJ ET
BT 26.250 459.262 Td /F1 9.8 Tf  [(documented that they have markedly compromised ambulation relative to healthy boys and correlated 6-minute walk distance )] TJ ET
BT 26.250 447.357 Td /F1 9.8 Tf  [(\(6MWD\) with age, anthropometric characteristics, and measures which change with disease progression, including stride length )] TJ ET
BT 26.250 435.453 Td /F1 9.8 Tf  [(and cadence. In addition, 6MWD can be considered a proxy measure for the energy cost of locomotion in DMD)] TJ ET
0.267 0.267 0.267 rg
BT 504.751 436.960 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 514.388 435.453 Td /F1 9.8 Tf  [( . The 6MWT )] TJ ET
BT 26.250 423.548 Td /F1 9.8 Tf  [(was been shown to be an integrated global measure of ambulatory function in DMD that is influenced by decreased lower )] TJ ET
BT 26.250 411.643 Td /F1 9.8 Tf  [(extremity strength, biomechanical inefficiencies during gait, diminished endurance, and compromised cardio-respiratory status)] TJ ET
0.267 0.267 0.267 rg
BT 569.198 413.150 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 399.738 Td /F1 9.8 Tf  [(. Longitudinal data concerning the 6MWT in DMD have supported the clinically meaningful change in 6MWD to be in the range )] TJ ET
BT 26.250 387.834 Td /F1 9.8 Tf  [(of 20 to 30 meters, which can serve as the targeted treatment effect in 12-month trials in ambulatory DMD)] TJ ET
0.267 0.267 0.267 rg
BT 481.985 389.341 Td /F4 8.7 Tf  [(18)] TJ ET
0.271 0.267 0.267 rg
BT 491.622 387.834 Td /F1 9.8 Tf  [( . It appears that a )] TJ ET
BT 26.250 375.929 Td /F1 9.8 Tf  [(decline of approximately 30 meters from an average performance on the 6MWT in DMD to a threshold 6MWD of < 325 meters )] TJ ET
BT 26.250 364.024 Td /F1 9.8 Tf  [(or < 55%-predicted would place a patient with DMD at risk for more precipitous decline in ambulatory function over the )] TJ ET
BT 26.250 352.119 Td /F1 9.8 Tf  [(subsequent year. Given the limitations of other measures in DMD including surrogate biomarkers, strength by myometry, and )] TJ ET
BT 26.250 340.215 Td /F1 9.8 Tf  [(timed function tests \(TFTs\), the 6MWD has become the recommended primary outcome measure in ambulatory DMD.)] TJ ET
BT 26.250 320.810 Td /F1 9.8 Tf  [(Consumers, clinical researchers, the Food and Drug Administration \(FDA\), and industry have increasingly recognized the )] TJ ET
BT 26.250 308.905 Td /F1 9.8 Tf  [(importance of person-reported outcome \(PRO\) measures in the determination of clinically meaningful outcomes and validation )] TJ ET
BT 26.250 297.000 Td /F1 9.8 Tf  [(of clinical and surrogate endpoints for therapeutic trials)] TJ ET
0.267 0.267 0.267 rg
BT 262.522 298.508 Td /F4 8.7 Tf  [(19)] TJ ET
0.271 0.267 0.267 rg
BT 272.159 297.000 Td /F1 9.8 Tf  [( . There are regulatory requirements that registration studies must )] TJ ET
BT 26.250 285.096 Td /F1 9.8 Tf  [(incorporate primary endpoints that objectively measure clinically meaningful �life-changing� events with significant impact on )] TJ ET
BT 26.250 273.191 Td /F1 9.8 Tf  [(health and well-being. In addition, the FDA has strongly recommended inclusion of PRO measures such as health-related )] TJ ET
BT 26.250 261.286 Td /F1 9.8 Tf  [(quality of life assessments as an endpoints in all clinical trials)] TJ ET
0.267 0.267 0.267 rg
BT 289.598 262.793 Td /F4 8.7 Tf  [(20)] TJ ET
0.271 0.267 0.267 rg
BT 299.235 265.174 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 301.644 262.793 Td /F4 8.7 Tf  [(21)] TJ ET
0.271 0.267 0.267 rg
BT 311.282 261.286 Td /F1 9.8 Tf  [( .)] TJ ET
BT 26.250 241.881 Td /F1 9.8 Tf  [(The specific strength or function measures chosen to serve as the best primary and secondary clinical endpoints for a trial )] TJ ET
BT 26.250 229.977 Td /F1 9.8 Tf  [(depends on the mechanism of action of the proposed therapeutic agent as well as the age and stage of disease targeted by the )] TJ ET
BT 26.250 218.072 Td /F1 9.8 Tf  [(clinical trial design. Recently, investigators have cross-validated the 6MWD with many measures of strength and function )] TJ ET
BT 26.250 206.167 Td /F1 9.8 Tf  [(historically used in DMD trials)] TJ ET
0.267 0.267 0.267 rg
BT 154.102 207.674 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 163.739 206.167 Td /F1 9.8 Tf  [(, and also with other newer gross motor indices of disease progression in DMD such as the )] TJ ET
BT 26.250 194.262 Td /F1 9.8 Tf  [(Northstar Ambulatory Assessment \(NSAA\))] TJ ET
0.267 0.267 0.267 rg
BT 209.921 195.770 Td /F4 8.7 Tf  [(22)] TJ ET
0.271 0.267 0.267 rg
BT 219.558 194.262 Td /F1 9.8 Tf  [( .)] TJ ET
BT 26.250 174.858 Td /F1 9.8 Tf  [(A potential limitation of the 6MWT and many other functional and strength-based performance measures is that while they do )] TJ ET
BT 26.250 162.953 Td /F1 9.8 Tf  [(measure components of a clinically meaningful function \(e.g., walking\), they do not directly assess the patient�s health-related )] TJ ET
BT 26.250 151.048 Td /F1 9.8 Tf  [(quality of life or participation in daily activities. While regulatory agencies have called for the inclusion of PRO measures in )] TJ ET
BT 26.250 139.143 Td /F1 9.8 Tf  [(clinical trials, the sensitivity of these measures to short-term changes expected with treatment over a typical one year clinical )] TJ ET
BT 26.250 127.239 Td /F1 9.8 Tf  [(trial duration has not been determined in DMD. The choice of PRO measures employed in DMD trials has unfortunately )] TJ ET
BT 26.250 115.334 Td /F1 9.8 Tf  [(frequently been based on the availability of large normative data or translated test forms as opposed to natural history data that )] TJ ET
BT 26.250 103.429 Td /F1 9.8 Tf  [(confirm that specific PRO measures are sensitive to expected treatment effects over the study duration. Expert groups in )] TJ ET
BT 26.250 91.524 Td /F1 9.8 Tf  [(neuromuscular disease research and related fields have identified the need for development, validation and characterization of )] TJ ET
BT 26.250 79.620 Td /F1 9.8 Tf  [(PRO measures of health, participation, and quality of life in different disease groups, as well as cross-validation of those )] TJ ET
BT 26.250 67.715 Td /F1 9.8 Tf  [(measures with �traditional� clinical measures of strength and function)] TJ ET
0.267 0.267 0.267 rg
BT 322.650 69.222 Td /F4 8.7 Tf  [(19)] TJ ET
0.271 0.267 0.267 rg
BT 332.287 71.603 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 334.697 69.222 Td /F4 8.7 Tf  [(23)] TJ ET
0.271 0.267 0.267 rg
BT 344.334 71.603 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 346.743 69.222 Td /F4 8.7 Tf  [(24)] TJ ET
0.271 0.267 0.267 rg
BT 356.381 67.715 Td /F1 9.8 Tf  [( .)] TJ ET
BT 26.250 48.310 Td /F1 9.8 Tf  [(In 2010, McDonald et al. )] TJ ET
0.267 0.267 0.267 rg
BT 134.641 49.817 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 144.278 48.310 Td /F1 9.8 Tf  [( reported cross-sectional performance of traditional clinical outcome measures of lower limb function )] TJ ET
BT 26.250 36.405 Td /F1 9.8 Tf  [(\(Vignos functional scale, isometric knee extension strength, timed stand from supine, timed stair climb, walking velocity\) in 56 )] TJ ET
Q
q
15.000 22.120 577.500 754.880 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(frequently identified in the early toddler years as children begin to miss developmental motor milestones)] TJ ET
0.267 0.267 0.267 rg
BT 473.307 768.983 Td /F4 8.7 Tf  [(3)] TJ ET
0.271 0.267 0.267 rg
BT 478.126 767.476 Td /F1 9.8 Tf  [( . Loss of dystrophin in )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(CNS tissue is also evident in subpopulations of boys with DMD, although cognitive and sensorimotor sequelae of that loss are )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(less well understood)] TJ ET
0.267 0.267 0.267 rg
BT 114.575 745.174 Td /F4 8.7 Tf  [(4)] TJ ET
0.271 0.267 0.267 rg
BT 119.394 743.667 Td /F1 9.8 Tf  [( .)] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(Prior to widespread use of glucocorticoids \(GCs\) as a primary method for maintaining muscle strength, mean age to loss of )] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(ambulation in DMD patients was around 9 years with an overall life expectancy into the mid-teen years or early twenties)] TJ ET
0.267 0.267 0.267 rg
BT 541.577 713.864 Td /F4 8.7 Tf  [(5)] TJ ET
0.271 0.267 0.267 rg
BT 546.395 712.357 Td /F1 9.8 Tf  [( . )] TJ ET
BT 26.250 700.452 Td /F1 9.8 Tf  [(Natural history studies of the disease published in the 1980s and early 1990s did not differ significantly from case reports by )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(Duchenne a century earlier)] TJ ET
0.267 0.267 0.267 rg
BT 143.299 690.055 Td /F4 8.7 Tf  [(6)] TJ ET
0.271 0.267 0.267 rg
BT 148.117 688.548 Td /F1 9.8 Tf  [( . Recent adoption of practice guidelines for GC use in ambulatory boys and a growing consensus )] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(that GCs may benefit nonambulatory boys as well through support of upper limb, cardiac, and respiratory function has )] TJ ET
BT 26.250 664.738 Td /F1 9.8 Tf  [(contributed to an altered natural history of the disease, with decreased rates of progression, reductions in incidence of )] TJ ET
BT 26.250 652.833 Td /F1 9.8 Tf  [(secondary conditions, and improved survival well into early adulthood)] TJ ET
0.267 0.267 0.267 rg
BT 325.370 654.341 Td /F4 8.7 Tf  [(7)] TJ ET
0.271 0.267 0.267 rg
BT 330.189 652.833 Td /F1 9.8 Tf  [( .)] TJ ET
BT 26.250 633.429 Td /F1 9.8 Tf  [(While current practices have reduced rates of disease progression and have improved preservation of function for many with )] TJ ET
BT 26.250 621.524 Td /F1 9.8 Tf  [(DMD, none of the available treatments has been directed toward restoration of the damaged gene or protein product. However, )] TJ ET
BT 26.250 609.619 Td /F1 9.8 Tf  [(promising new therapies including nonsense mutation suppression via stop codon read through and exon skipping via antisense )] TJ ET
BT 26.250 597.714 Td /F1 9.8 Tf  [(oligonucleotides and morpholinos have been introduced into registration-directed clinical trials using international multicenter )] TJ ET
BT 26.250 585.810 Td /F1 9.8 Tf  [(collaborations. Both safety and efficacy trials have involved both ambulatory and nonambulatory subgroups of DMD populations)] TJ ET
0.267 0.267 0.267 rg
BT 576.296 587.317 Td /F4 8.7 Tf  [(8)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 577.793 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 28.659 575.412 Td /F4 8.7 Tf  [(9)] TJ ET
0.271 0.267 0.267 rg
BT 33.478 577.793 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 35.887 575.412 Td /F4 8.7 Tf  [(10)] TJ ET
0.271 0.267 0.267 rg
BT 45.525 573.905 Td /F1 9.8 Tf  [( . The research community has faced the need to identify and develop clinically meaningful outcome measures in DMD for )] TJ ET
BT 26.250 562.000 Td /F1 9.8 Tf  [(use in pivotal therapeutic trials.)] TJ ET
BT 26.250 542.595 Td /F1 9.8 Tf  [(In boys with DMD, walking abnormalities are a major disease manifestation that has great importance to patients and families. )] TJ ET
BT 26.250 530.691 Td /F1 9.8 Tf  [(Ambulation has been noted to be a prerequisite for normal physical functioning in humans)] TJ ET
0.267 0.267 0.267 rg
BT 413.188 532.198 Td /F4 8.7 Tf  [(11)] TJ ET
0.271 0.267 0.267 rg
BT 422.826 530.691 Td /F1 9.8 Tf  [( ; the major goal of medical and )] TJ ET
BT 26.250 518.786 Td /F1 9.8 Tf  [(physical therapy intervention during the ambulatory phase of DMD is to maintain ambulation for as long as possible)] TJ ET
0.267 0.267 0.267 rg
BT 522.086 520.293 Td /F4 8.7 Tf  [(3)] TJ ET
0.271 0.267 0.267 rg
BT 526.905 522.674 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 529.314 520.293 Td /F4 8.7 Tf  [(12)] TJ ET
0.271 0.267 0.267 rg
BT 538.952 522.674 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 541.361 520.293 Td /F4 8.7 Tf  [(13)] TJ ET
0.271 0.267 0.267 rg
BT 550.998 522.674 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 553.408 520.293 Td /F4 8.7 Tf  [(14)] TJ ET
0.271 0.267 0.267 rg
BT 563.045 518.786 Td /F1 9.8 Tf  [( . )] TJ ET
BT 26.250 506.881 Td /F1 9.8 Tf  [(Given that ambulatory compromise is a key component of the DMD disease process and that ambulation measures the function )] TJ ET
BT 26.250 494.976 Td /F1 9.8 Tf  [(of multiple muscle groups as well as cardiovascular activity, ambulation-related outcome measures are the most relevant )] TJ ET
BT 26.250 483.072 Td /F1 9.8 Tf  [(endpoints in DMD patients who are still able to walk. We previously reported that the modified 6-minute Walk Test \(6MWT\) is )] TJ ET
BT 26.250 471.167 Td /F1 9.8 Tf  [(feasible, safe, and reliable in boys with DMD who have not yet transitioned to full time wheelchair use)] TJ ET
0.267 0.267 0.267 rg
BT 462.475 472.674 Td /F4 8.7 Tf  [(15)] TJ ET
0.271 0.267 0.267 rg
BT 472.112 475.055 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 474.521 472.674 Td /F4 8.7 Tf  [(16)] TJ ET
0.271 0.267 0.267 rg
BT 484.159 471.167 Td /F1 9.8 Tf  [( . We also )] TJ ET
BT 26.250 459.262 Td /F1 9.8 Tf  [(documented that they have markedly compromised ambulation relative to healthy boys and correlated 6-minute walk distance )] TJ ET
BT 26.250 447.357 Td /F1 9.8 Tf  [(\(6MWD\) with age, anthropometric characteristics, and measures which change with disease progression, including stride length )] TJ ET
BT 26.250 435.453 Td /F1 9.8 Tf  [(and cadence. In addition, 6MWD can be considered a proxy measure for the energy cost of locomotion in DMD)] TJ ET
0.267 0.267 0.267 rg
BT 504.751 436.960 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 514.388 435.453 Td /F1 9.8 Tf  [( . The 6MWT )] TJ ET
BT 26.250 423.548 Td /F1 9.8 Tf  [(was been shown to be an integrated global measure of ambulatory function in DMD that is influenced by decreased lower )] TJ ET
BT 26.250 411.643 Td /F1 9.8 Tf  [(extremity strength, biomechanical inefficiencies during gait, diminished endurance, and compromised cardio-respiratory status)] TJ ET
0.267 0.267 0.267 rg
BT 569.198 413.150 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 399.738 Td /F1 9.8 Tf  [(. Longitudinal data concerning the 6MWT in DMD have supported the clinically meaningful change in 6MWD to be in the range )] TJ ET
BT 26.250 387.834 Td /F1 9.8 Tf  [(of 20 to 30 meters, which can serve as the targeted treatment effect in 12-month trials in ambulatory DMD)] TJ ET
0.267 0.267 0.267 rg
BT 481.985 389.341 Td /F4 8.7 Tf  [(18)] TJ ET
0.271 0.267 0.267 rg
BT 491.622 387.834 Td /F1 9.8 Tf  [( . It appears that a )] TJ ET
BT 26.250 375.929 Td /F1 9.8 Tf  [(decline of approximately 30 meters from an average performance on the 6MWT in DMD to a threshold 6MWD of < 325 meters )] TJ ET
BT 26.250 364.024 Td /F1 9.8 Tf  [(or < 55%-predicted would place a patient with DMD at risk for more precipitous decline in ambulatory function over the )] TJ ET
BT 26.250 352.119 Td /F1 9.8 Tf  [(subsequent year. Given the limitations of other measures in DMD including surrogate biomarkers, strength by myometry, and )] TJ ET
BT 26.250 340.215 Td /F1 9.8 Tf  [(timed function tests \(TFTs\), the 6MWD has become the recommended primary outcome measure in ambulatory DMD.)] TJ ET
BT 26.250 320.810 Td /F1 9.8 Tf  [(Consumers, clinical researchers, the Food and Drug Administration \(FDA\), and industry have increasingly recognized the )] TJ ET
BT 26.250 308.905 Td /F1 9.8 Tf  [(importance of person-reported outcome \(PRO\) measures in the determination of clinically meaningful outcomes and validation )] TJ ET
BT 26.250 297.000 Td /F1 9.8 Tf  [(of clinical and surrogate endpoints for therapeutic trials)] TJ ET
0.267 0.267 0.267 rg
BT 262.522 298.508 Td /F4 8.7 Tf  [(19)] TJ ET
0.271 0.267 0.267 rg
BT 272.159 297.000 Td /F1 9.8 Tf  [( . There are regulatory requirements that registration studies must )] TJ ET
BT 26.250 285.096 Td /F1 9.8 Tf  [(incorporate primary endpoints that objectively measure clinically meaningful �life-changing� events with significant impact on )] TJ ET
BT 26.250 273.191 Td /F1 9.8 Tf  [(health and well-being. In addition, the FDA has strongly recommended inclusion of PRO measures such as health-related )] TJ ET
BT 26.250 261.286 Td /F1 9.8 Tf  [(quality of life assessments as an endpoints in all clinical trials)] TJ ET
0.267 0.267 0.267 rg
BT 289.598 262.793 Td /F4 8.7 Tf  [(20)] TJ ET
0.271 0.267 0.267 rg
BT 299.235 265.174 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 301.644 262.793 Td /F4 8.7 Tf  [(21)] TJ ET
0.271 0.267 0.267 rg
BT 311.282 261.286 Td /F1 9.8 Tf  [( .)] TJ ET
BT 26.250 241.881 Td /F1 9.8 Tf  [(The specific strength or function measures chosen to serve as the best primary and secondary clinical endpoints for a trial )] TJ ET
BT 26.250 229.977 Td /F1 9.8 Tf  [(depends on the mechanism of action of the proposed therapeutic agent as well as the age and stage of disease targeted by the )] TJ ET
BT 26.250 218.072 Td /F1 9.8 Tf  [(clinical trial design. Recently, investigators have cross-validated the 6MWD with many measures of strength and function )] TJ ET
BT 26.250 206.167 Td /F1 9.8 Tf  [(historically used in DMD trials)] TJ ET
0.267 0.267 0.267 rg
BT 154.102 207.674 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 163.739 206.167 Td /F1 9.8 Tf  [(, and also with other newer gross motor indices of disease progression in DMD such as the )] TJ ET
BT 26.250 194.262 Td /F1 9.8 Tf  [(Northstar Ambulatory Assessment \(NSAA\))] TJ ET
0.267 0.267 0.267 rg
BT 209.921 195.770 Td /F4 8.7 Tf  [(22)] TJ ET
0.271 0.267 0.267 rg
BT 219.558 194.262 Td /F1 9.8 Tf  [( .)] TJ ET
BT 26.250 174.858 Td /F1 9.8 Tf  [(A potential limitation of the 6MWT and many other functional and strength-based performance measures is that while they do )] TJ ET
BT 26.250 162.953 Td /F1 9.8 Tf  [(measure components of a clinically meaningful function \(e.g., walking\), they do not directly assess the patient�s health-related )] TJ ET
BT 26.250 151.048 Td /F1 9.8 Tf  [(quality of life or participation in daily activities. While regulatory agencies have called for the inclusion of PRO measures in )] TJ ET
BT 26.250 139.143 Td /F1 9.8 Tf  [(clinical trials, the sensitivity of these measures to short-term changes expected with treatment over a typical one year clinical )] TJ ET
BT 26.250 127.239 Td /F1 9.8 Tf  [(trial duration has not been determined in DMD. The choice of PRO measures employed in DMD trials has unfortunately )] TJ ET
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15.000 26.744 577.500 750.256 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(ambulatory boys with DMD between 4 and 15 years of age against two commonly used health-related quality of life \(HrQOL\) )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(measures, the Pediatric Quality of Life Inventory)] TJ ET
BT 233.798 759.460 Td /F1 8.7 Tf  [(TM)] TJ ET
BT 246.313 755.571 Td /F1 9.8 Tf  [( \(PedsQL\))] TJ ET
0.267 0.267 0.267 rg
BT 290.744 757.079 Td /F4 8.7 Tf  [(26)] TJ ET
0.271 0.267 0.267 rg
BT 300.381 759.460 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 302.790 757.079 Td /F4 8.7 Tf  [(27)] TJ ET
0.271 0.267 0.267 rg
BT 312.428 759.460 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 314.837 757.079 Td /F4 8.7 Tf  [(28)] TJ ET
0.271 0.267 0.267 rg
BT 324.474 755.571 Td /F1 9.8 Tf  [( and the Pediatric Society of North America \(POSNA\) )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Pediatric Musculoskeletal Functional Health Questionnaire \(also referred to as the Pediatric Outcomes Data Collection )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Instrument � PODCI\))] TJ ET
0.267 0.267 0.267 rg
BT 117.276 733.269 Td /F4 8.7 Tf  [(29)] TJ ET
0.271 0.267 0.267 rg
BT 126.913 735.650 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 129.323 733.269 Td /F4 8.7 Tf  [(30)] TJ ET
0.271 0.267 0.267 rg
BT 138.960 735.650 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 141.369 733.269 Td /F4 8.7 Tf  [(31)] TJ ET
0.271 0.267 0.267 rg
BT 151.007 731.762 Td /F1 9.8 Tf  [( . We will refer to this instrument as the PODCI throughout this paper. The PedsQL is a 23-item )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(patient self-report or parent proxy instrument designed to measure core health dimensions in children between 5 and 17 years )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(of age. The instrument consists of four major scales, including physical functioning, emotional functioning, social functioning and )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(school functioning. Items are scored in aggregate, for major scales independently, and as a psychosocial score including all but )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(the physical function scale. The PODCI is a patient self-report or parent-proxy measure of functional ability in children with )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(orthopedic limitations. Primary scales of the measure include upper extremity function, transfers and mobility, sports and )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(physical function, comfort and pain, happiness and satisfaction, and expectations for treatment. In their study, McDonald et al )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(demonstrated that both measures differentiate between boys with DMD and typically-developing controls, and that there are )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(age-related effects associated with DMD disease severity on PedsQL physical function and PODCI transfer and basic mobility, )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(sports and physical function and global scales)] TJ ET
0.267 0.267 0.267 rg
BT 224.594 626.126 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 234.232 624.619 Td /F1 9.8 Tf  [( . They also demonstrated moderate correlation of those PODCI scales \(r=0.38-)] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(0.53\) and weaker correlation of the PedsQL physical function scale \(r=0.2-0.41\) to variations in disease involvement as )] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(measured by functional evaluations, quantitative strength and functional evaluation. Those correlations demonstrated a )] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(relationship between patient-reported HrQOL and clinician-measured functional performance tools, and lent support to the )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(concept that those commonly used tools are �clinically meaningful� in the context of a patient�s day-to-day life. The authors cited )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(a need for additional longitudinal data to assess responsiveness of those measures over time in order to determine the utility of )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(the HrQOL tools as outcome measures in clinical trials.)] TJ ET
BT 26.250 533.786 Td /F1 9.8 Tf  [(Given the demonstration of a moderately strong relationship between HrQOL and physical function, it stands to reason that it )] TJ ET
BT 26.250 521.881 Td /F1 9.8 Tf  [(may not always be accurate to assume that a uniform 30-meter change in walking ability by 6MWT will always be clinically )] TJ ET
BT 26.250 509.976 Td /F1 9.8 Tf  [(meaningful from the standpoint of an individual�s self-reported abilities and QoL. Instead, it may be the case that smaller or )] TJ ET
BT 26.250 498.072 Td /F1 9.8 Tf  [(larger changes in ability will contribute to meaningful patient-reported function at differing levels of baseline ability.)] TJ ET
BT 26.250 461.469 Td /F4 12.0 Tf  [(Specific Aims)] TJ ET
BT 26.250 441.515 Td /F1 9.8 Tf  [(In the current study, we describe the longitudinal characteristics of the 6MWT, PedsQL, and PODCI instruments in ambulatory )] TJ ET
BT 26.250 429.610 Td /F1 9.8 Tf  [(boys with DMD and typically-developing controls. We set out to: 1\) further characterize correlation between measures at )] TJ ET
BT 26.250 417.705 Td /F1 9.8 Tf  [(baseline for ambulatory DMD boys and controls, as well as the combined ranges of both; 2\) describe significant 1-year change )] TJ ET
BT 26.250 405.801 Td /F1 9.8 Tf  [(in the measures, and to describe the correlation of 1-year changes between the measures; and 3\) determine whether )] TJ ET
BT 26.250 393.896 Td /F1 9.8 Tf  [(regression estimates could be used to describe relationships between measures over time. Fourth, we further aimed to describe )] TJ ET
BT 26.250 381.991 Td /F1 9.8 Tf  [(the estimated minimal clinically important difference \(MCID\) for each measure using baseline statistical distribution properties, )] TJ ET
BT 26.250 370.086 Td /F1 9.8 Tf  [(and to determine whether the MCIDs of HrQOL measures would be associated with different estimates of meaningful changes )] TJ ET
BT 26.250 358.182 Td /F1 9.8 Tf  [(in walking distance across the spectrum of walking abilities in DMD.)] TJ ET
BT 26.250 321.579 Td /F4 12.0 Tf  [(Participants and Methods)] TJ ET
BT 26.250 301.625 Td /F5 9.8 Tf  [(Study Subjects)] TJ ET
BT 26.250 282.220 Td /F1 9.8 Tf  [(The institutional review board \(IRB\) reviewed and approved the study protocol. Informed consent/assent was obtained for each )] TJ ET
BT 26.250 270.315 Td /F1 9.8 Tf  [(participant prior to initiation of any study procedures. Participants included boys with DMD and typically developing controls )] TJ ET
BT 26.250 258.411 Td /F1 9.8 Tf  [(between the ages of 4 and 12 years. Boys with DMD were required to have a clinical picture consistent with the disease and )] TJ ET
BT 26.250 246.506 Td /F1 9.8 Tf  [(confirmation by at least one of the following methods: 1\) documentation of a mutation of the dystrophin gene consistent with a )] TJ ET
BT 26.250 234.601 Td /F1 9.8 Tf  [(diagnosis of DMD; 2\) complete loss of dystrophin on muscle biopsy; or 3\) elevated serum creatine kinase and a family history of )] TJ ET
BT 26.250 222.696 Td /F1 9.8 Tf  [(DMD in a primary male relative who satisfied conditions \(1\) or \(2\). All participants were required to be able to walk ?10 meters, )] TJ ET
BT 26.250 210.792 Td /F1 9.8 Tf  [(be free of any medications that would affect heart rate or metabolism, and be free of concomitant illness or contraindications to )] TJ ET
BT 26.250 198.887 Td /F1 9.8 Tf  [(exercise. All participants had to be able to follow simple instructions. English- and Spanish-speaking boys with DMD were )] TJ ET
BT 26.250 186.982 Td /F1 9.8 Tf  [(recruited from our neuromuscular disease clinic and the northern California region. Typically-developing controls were recruited )] TJ ET
BT 26.250 175.077 Td /F1 9.8 Tf  [(through locally-posted English and Spanish advertisements.)] TJ ET
BT 26.250 155.673 Td /F5 9.8 Tf  [(Evaluation Methods)] TJ ET
BT 26.250 136.268 Td /F1 9.8 Tf  [(Methods for the DMD-specific Six-minute Walk Test \(6MWT\) have been previously reported by our group)] TJ ET
0.267 0.267 0.267 rg
BT 478.679 137.775 Td /F4 8.7 Tf  [(15)] TJ ET
0.271 0.267 0.267 rg
BT 488.317 140.156 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 490.726 137.775 Td /F4 8.7 Tf  [(16)] TJ ET
0.271 0.267 0.267 rg
BT 500.363 136.268 Td /F1 9.8 Tf  [(. The 6MWT was )] TJ ET
BT 26.250 124.363 Td /F1 9.8 Tf  [(administered at baseline at the end of a test battery that also included anthropometric measures, timed standing from supine, )] TJ ET
BT 26.250 112.458 Td /F1 9.8 Tf  [(timed 4-stair climb, and timed 10- and 25-meter walk/run tests as previously described. Participants viewed a short orientation )] TJ ET
BT 26.250 100.554 Td /F1 9.8 Tf  [(video that was developed to address potential attention and verbal working memory limitations, and then underwent testing on a )] TJ ET
BT 26.250 88.649 Td /F1 9.8 Tf  [(25-meter indoor course. Participants were instructed to travel as far and as fast as possible in six minutes without running in a )] TJ ET
BT 26.250 76.744 Td /F1 9.8 Tf  [(manner that demonstrated consistency with published normative studies)] TJ ET
0.267 0.267 0.267 rg
BT 337.841 78.251 Td /F4 8.7 Tf  [(32)] TJ ET
0.271 0.267 0.267 rg
BT 347.478 80.632 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 349.887 78.251 Td /F4 8.7 Tf  [(33)] TJ ET
0.271 0.267 0.267 rg
BT 359.525 76.744 Td /F1 9.8 Tf  [(. Participants were provided with regular periodic )] TJ ET
BT 26.250 64.839 Td /F1 9.8 Tf  [(verbal encouragement, and were followed by a �safety� chaser who responded in the event of a fall. PedsQL and PODCI )] TJ ET
BT 26.250 52.935 Td /F1 9.8 Tf  [(instruments were provided as paper-based reports in English or Spanish and were completed by the parent or primary caregiver )] TJ ET
BT 26.250 41.030 Td /F1 9.8 Tf  [(during the evaluation visit. Instrument scores were compiled according to scoring paradigms published with each instrument. )] TJ ET
Q
q
15.000 26.744 577.500 750.256 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(ambulatory boys with DMD between 4 and 15 years of age against two commonly used health-related quality of life \(HrQOL\) )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(measures, the Pediatric Quality of Life Inventory)] TJ ET
BT 233.798 759.460 Td /F1 8.7 Tf  [(TM)] TJ ET
BT 246.313 755.571 Td /F1 9.8 Tf  [( \(PedsQL\))] TJ ET
0.267 0.267 0.267 rg
BT 290.744 757.079 Td /F4 8.7 Tf  [(26)] TJ ET
0.271 0.267 0.267 rg
BT 300.381 759.460 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 302.790 757.079 Td /F4 8.7 Tf  [(27)] TJ ET
0.271 0.267 0.267 rg
BT 312.428 759.460 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 314.837 757.079 Td /F4 8.7 Tf  [(28)] TJ ET
0.271 0.267 0.267 rg
BT 324.474 755.571 Td /F1 9.8 Tf  [( and the Pediatric Society of North America \(POSNA\) )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Pediatric Musculoskeletal Functional Health Questionnaire \(also referred to as the Pediatric Outcomes Data Collection )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Instrument � PODCI\))] TJ ET
0.267 0.267 0.267 rg
BT 117.276 733.269 Td /F4 8.7 Tf  [(29)] TJ ET
0.271 0.267 0.267 rg
BT 126.913 735.650 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 129.323 733.269 Td /F4 8.7 Tf  [(30)] TJ ET
0.271 0.267 0.267 rg
BT 138.960 735.650 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 141.369 733.269 Td /F4 8.7 Tf  [(31)] TJ ET
0.271 0.267 0.267 rg
BT 151.007 731.762 Td /F1 9.8 Tf  [( . We will refer to this instrument as the PODCI throughout this paper. The PedsQL is a 23-item )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(patient self-report or parent proxy instrument designed to measure core health dimensions in children between 5 and 17 years )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(of age. The instrument consists of four major scales, including physical functioning, emotional functioning, social functioning and )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(school functioning. Items are scored in aggregate, for major scales independently, and as a psychosocial score including all but )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(the physical function scale. The PODCI is a patient self-report or parent-proxy measure of functional ability in children with )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(orthopedic limitations. Primary scales of the measure include upper extremity function, transfers and mobility, sports and )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(physical function, comfort and pain, happiness and satisfaction, and expectations for treatment. In their study, McDonald et al )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(demonstrated that both measures differentiate between boys with DMD and typically-developing controls, and that there are )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(age-related effects associated with DMD disease severity on PedsQL physical function and PODCI transfer and basic mobility, )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(sports and physical function and global scales)] TJ ET
0.267 0.267 0.267 rg
BT 224.594 626.126 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 234.232 624.619 Td /F1 9.8 Tf  [( . They also demonstrated moderate correlation of those PODCI scales \(r=0.38-)] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(0.53\) and weaker correlation of the PedsQL physical function scale \(r=0.2-0.41\) to variations in disease involvement as )] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(measured by functional evaluations, quantitative strength and functional evaluation. Those correlations demonstrated a )] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(relationship between patient-reported HrQOL and clinician-measured functional performance tools, and lent support to the )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(concept that those commonly used tools are �clinically meaningful� in the context of a patient�s day-to-day life. The authors cited )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(a need for additional longitudinal data to assess responsiveness of those measures over time in order to determine the utility of )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(the HrQOL tools as outcome measures in clinical trials.)] TJ ET
BT 26.250 533.786 Td /F1 9.8 Tf  [(Given the demonstration of a moderately strong relationship between HrQOL and physical function, it stands to reason that it )] TJ ET
BT 26.250 521.881 Td /F1 9.8 Tf  [(may not always be accurate to assume that a uniform 30-meter change in walking ability by 6MWT will always be clinically )] TJ ET
BT 26.250 509.976 Td /F1 9.8 Tf  [(meaningful from the standpoint of an individual�s self-reported abilities and QoL. Instead, it may be the case that smaller or )] TJ ET
BT 26.250 498.072 Td /F1 9.8 Tf  [(larger changes in ability will contribute to meaningful patient-reported function at differing levels of baseline ability.)] TJ ET
BT 26.250 461.469 Td /F4 12.0 Tf  [(Specific Aims)] TJ ET
BT 26.250 441.515 Td /F1 9.8 Tf  [(In the current study, we describe the longitudinal characteristics of the 6MWT, PedsQL, and PODCI instruments in ambulatory )] TJ ET
BT 26.250 429.610 Td /F1 9.8 Tf  [(boys with DMD and typically-developing controls. We set out to: 1\) further characterize correlation between measures at )] TJ ET
BT 26.250 417.705 Td /F1 9.8 Tf  [(baseline for ambulatory DMD boys and controls, as well as the combined ranges of both; 2\) describe significant 1-year change )] TJ ET
BT 26.250 405.801 Td /F1 9.8 Tf  [(in the measures, and to describe the correlation of 1-year changes between the measures; and 3\) determine whether )] TJ ET
BT 26.250 393.896 Td /F1 9.8 Tf  [(regression estimates could be used to describe relationships between measures over time. Fourth, we further aimed to describe )] TJ ET
BT 26.250 381.991 Td /F1 9.8 Tf  [(the estimated minimal clinically important difference \(MCID\) for each measure using baseline statistical distribution properties, )] TJ ET
BT 26.250 370.086 Td /F1 9.8 Tf  [(and to determine whether the MCIDs of HrQOL measures would be associated with different estimates of meaningful changes )] TJ ET
BT 26.250 358.182 Td /F1 9.8 Tf  [(in walking distance across the spectrum of walking abilities in DMD.)] TJ ET
BT 26.250 321.579 Td /F4 12.0 Tf  [(Participants and Methods)] TJ ET
BT 26.250 301.625 Td /F5 9.8 Tf  [(Study Subjects)] TJ ET
BT 26.250 282.220 Td /F1 9.8 Tf  [(The institutional review board \(IRB\) reviewed and approved the study protocol. Informed consent/assent was obtained for each )] TJ ET
BT 26.250 270.315 Td /F1 9.8 Tf  [(participant prior to initiation of any study procedures. Participants included boys with DMD and typically developing controls )] TJ ET
BT 26.250 258.411 Td /F1 9.8 Tf  [(between the ages of 4 and 12 years. Boys with DMD were required to have a clinical picture consistent with the disease and )] TJ ET
BT 26.250 246.506 Td /F1 9.8 Tf  [(confirmation by at least one of the following methods: 1\) documentation of a mutation of the dystrophin gene consistent with a )] TJ ET
BT 26.250 234.601 Td /F1 9.8 Tf  [(diagnosis of DMD; 2\) complete loss of dystrophin on muscle biopsy; or 3\) elevated serum creatine kinase and a family history of )] TJ ET
BT 26.250 222.696 Td /F1 9.8 Tf  [(DMD in a primary male relative who satisfied conditions \(1\) or \(2\). All participants were required to be able to walk ?10 meters, )] TJ ET
BT 26.250 210.792 Td /F1 9.8 Tf  [(be free of any medications that would affect heart rate or metabolism, and be free of concomitant illness or contraindications to )] TJ ET
BT 26.250 198.887 Td /F1 9.8 Tf  [(exercise. All participants had to be able to follow simple instructions. English- and Spanish-speaking boys with DMD were )] TJ ET
BT 26.250 186.982 Td /F1 9.8 Tf  [(recruited from our neuromuscular disease clinic and the northern California region. Typically-developing controls were recruited )] TJ ET
BT 26.250 175.077 Td /F1 9.8 Tf  [(through locally-posted English and Spanish advertisements.)] TJ ET
BT 26.250 155.673 Td /F5 9.8 Tf  [(Evaluation Methods)] TJ ET
BT 26.250 136.268 Td /F1 9.8 Tf  [(Methods for the DMD-specific Six-minute Walk Test \(6MWT\) have been previously reported by our group)] TJ ET
0.267 0.267 0.267 rg
BT 478.679 137.775 Td /F4 8.7 Tf  [(15)] TJ ET
0.271 0.267 0.267 rg
BT 488.317 140.156 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 490.726 137.775 Td /F4 8.7 Tf  [(16)] TJ ET
0.271 0.267 0.267 rg
BT 500.363 136.268 Td /F1 9.8 Tf  [(. The 6MWT was )] TJ ET
BT 26.250 124.363 Td /F1 9.8 Tf  [(administered at baseline at the end of a test battery that also included anthropometric measures, timed standing from supine, )] TJ ET
BT 26.250 112.458 Td /F1 9.8 Tf  [(timed 4-stair climb, and timed 10- and 25-meter walk/run tests as previously described. Participants viewed a short orientation )] TJ ET
BT 26.250 100.554 Td /F1 9.8 Tf  [(video that was developed to address potential attention and verbal working memory limitations, and then underwent testing on a )] TJ ET
BT 26.250 88.649 Td /F1 9.8 Tf  [(25-meter indoor course. Participants were instructed to travel as far and as fast as possible in six minutes without running in a )] TJ ET
BT 26.250 76.744 Td /F1 9.8 Tf  [(manner that demonstrated consistency with published normative studies)] TJ ET
0.267 0.267 0.267 rg
BT 337.841 78.251 Td /F4 8.7 Tf  [(32)] TJ ET
0.271 0.267 0.267 rg
BT 347.478 80.632 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 349.887 78.251 Td /F4 8.7 Tf  [(33)] TJ ET
0.271 0.267 0.267 rg
BT 359.525 76.744 Td /F1 9.8 Tf  [(. Participants were provided with regular periodic )] TJ ET
BT 26.250 64.839 Td /F1 9.8 Tf  [(verbal encouragement, and were followed by a �safety� chaser who responded in the event of a fall. PedsQL and PODCI )] TJ ET
BT 26.250 52.935 Td /F1 9.8 Tf  [(instruments were provided as paper-based reports in English or Spanish and were completed by the parent or primary caregiver )] TJ ET
BT 26.250 41.030 Td /F1 9.8 Tf  [(during the evaluation visit. Instrument scores were compiled according to scoring paradigms published with each instrument. )] TJ ET
Q
q
15.000 26.744 577.500 750.256 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(ambulatory boys with DMD between 4 and 15 years of age against two commonly used health-related quality of life \(HrQOL\) )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(measures, the Pediatric Quality of Life Inventory)] TJ ET
BT 233.798 759.460 Td /F1 8.7 Tf  [(TM)] TJ ET
BT 246.313 755.571 Td /F1 9.8 Tf  [( \(PedsQL\))] TJ ET
0.267 0.267 0.267 rg
BT 290.744 757.079 Td /F4 8.7 Tf  [(26)] TJ ET
0.271 0.267 0.267 rg
BT 300.381 759.460 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 302.790 757.079 Td /F4 8.7 Tf  [(27)] TJ ET
0.271 0.267 0.267 rg
BT 312.428 759.460 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 314.837 757.079 Td /F4 8.7 Tf  [(28)] TJ ET
0.271 0.267 0.267 rg
BT 324.474 755.571 Td /F1 9.8 Tf  [( and the Pediatric Society of North America \(POSNA\) )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Pediatric Musculoskeletal Functional Health Questionnaire \(also referred to as the Pediatric Outcomes Data Collection )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Instrument � PODCI\))] TJ ET
0.267 0.267 0.267 rg
BT 117.276 733.269 Td /F4 8.7 Tf  [(29)] TJ ET
0.271 0.267 0.267 rg
BT 126.913 735.650 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 129.323 733.269 Td /F4 8.7 Tf  [(30)] TJ ET
0.271 0.267 0.267 rg
BT 138.960 735.650 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 141.369 733.269 Td /F4 8.7 Tf  [(31)] TJ ET
0.271 0.267 0.267 rg
BT 151.007 731.762 Td /F1 9.8 Tf  [( . We will refer to this instrument as the PODCI throughout this paper. The PedsQL is a 23-item )] TJ ET
BT 26.250 719.857 Td /F1 9.8 Tf  [(patient self-report or parent proxy instrument designed to measure core health dimensions in children between 5 and 17 years )] TJ ET
BT 26.250 707.952 Td /F1 9.8 Tf  [(of age. The instrument consists of four major scales, including physical functioning, emotional functioning, social functioning and )] TJ ET
BT 26.250 696.048 Td /F1 9.8 Tf  [(school functioning. Items are scored in aggregate, for major scales independently, and as a psychosocial score including all but )] TJ ET
BT 26.250 684.143 Td /F1 9.8 Tf  [(the physical function scale. The PODCI is a patient self-report or parent-proxy measure of functional ability in children with )] TJ ET
BT 26.250 672.238 Td /F1 9.8 Tf  [(orthopedic limitations. Primary scales of the measure include upper extremity function, transfers and mobility, sports and )] TJ ET
BT 26.250 660.333 Td /F1 9.8 Tf  [(physical function, comfort and pain, happiness and satisfaction, and expectations for treatment. In their study, McDonald et al )] TJ ET
BT 26.250 648.429 Td /F1 9.8 Tf  [(demonstrated that both measures differentiate between boys with DMD and typically-developing controls, and that there are )] TJ ET
BT 26.250 636.524 Td /F1 9.8 Tf  [(age-related effects associated with DMD disease severity on PedsQL physical function and PODCI transfer and basic mobility, )] TJ ET
BT 26.250 624.619 Td /F1 9.8 Tf  [(sports and physical function and global scales)] TJ ET
0.267 0.267 0.267 rg
BT 224.594 626.126 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 234.232 624.619 Td /F1 9.8 Tf  [( . They also demonstrated moderate correlation of those PODCI scales \(r=0.38-)] TJ ET
BT 26.250 612.714 Td /F1 9.8 Tf  [(0.53\) and weaker correlation of the PedsQL physical function scale \(r=0.2-0.41\) to variations in disease involvement as )] TJ ET
BT 26.250 600.810 Td /F1 9.8 Tf  [(measured by functional evaluations, quantitative strength and functional evaluation. Those correlations demonstrated a )] TJ ET
BT 26.250 588.905 Td /F1 9.8 Tf  [(relationship between patient-reported HrQOL and clinician-measured functional performance tools, and lent support to the )] TJ ET
BT 26.250 577.000 Td /F1 9.8 Tf  [(concept that those commonly used tools are �clinically meaningful� in the context of a patient�s day-to-day life. The authors cited )] TJ ET
BT 26.250 565.095 Td /F1 9.8 Tf  [(a need for additional longitudinal data to assess responsiveness of those measures over time in order to determine the utility of )] TJ ET
BT 26.250 553.191 Td /F1 9.8 Tf  [(the HrQOL tools as outcome measures in clinical trials.)] TJ ET
BT 26.250 533.786 Td /F1 9.8 Tf  [(Given the demonstration of a moderately strong relationship between HrQOL and physical function, it stands to reason that it )] TJ ET
BT 26.250 521.881 Td /F1 9.8 Tf  [(may not always be accurate to assume that a uniform 30-meter change in walking ability by 6MWT will always be clinically )] TJ ET
BT 26.250 509.976 Td /F1 9.8 Tf  [(meaningful from the standpoint of an individual�s self-reported abilities and QoL. Instead, it may be the case that smaller or )] TJ ET
BT 26.250 498.072 Td /F1 9.8 Tf  [(larger changes in ability will contribute to meaningful patient-reported function at differing levels of baseline ability.)] TJ ET
BT 26.250 461.469 Td /F4 12.0 Tf  [(Specific Aims)] TJ ET
BT 26.250 441.515 Td /F1 9.8 Tf  [(In the current study, we describe the longitudinal characteristics of the 6MWT, PedsQL, and PODCI instruments in ambulatory )] TJ ET
BT 26.250 429.610 Td /F1 9.8 Tf  [(boys with DMD and typically-developing controls. We set out to: 1\) further characterize correlation between measures at )] TJ ET
BT 26.250 417.705 Td /F1 9.8 Tf  [(baseline for ambulatory DMD boys and controls, as well as the combined ranges of both; 2\) describe significant 1-year change )] TJ ET
BT 26.250 405.801 Td /F1 9.8 Tf  [(in the measures, and to describe the correlation of 1-year changes between the measures; and 3\) determine whether )] TJ ET
BT 26.250 393.896 Td /F1 9.8 Tf  [(regression estimates could be used to describe relationships between measures over time. Fourth, we further aimed to describe )] TJ ET
BT 26.250 381.991 Td /F1 9.8 Tf  [(the estimated minimal clinically important difference \(MCID\) for each measure using baseline statistical distribution properties, )] TJ ET
BT 26.250 370.086 Td /F1 9.8 Tf  [(and to determine whether the MCIDs of HrQOL measures would be associated with different estimates of meaningful changes )] TJ ET
BT 26.250 358.182 Td /F1 9.8 Tf  [(in walking distance across the spectrum of walking abilities in DMD.)] TJ ET
BT 26.250 321.579 Td /F4 12.0 Tf  [(Participants and Methods)] TJ ET
BT 26.250 301.625 Td /F5 9.8 Tf  [(Study Subjects)] TJ ET
BT 26.250 282.220 Td /F1 9.8 Tf  [(The institutional review board \(IRB\) reviewed and approved the study protocol. Informed consent/assent was obtained for each )] TJ ET
BT 26.250 270.315 Td /F1 9.8 Tf  [(participant prior to initiation of any study procedures. Participants included boys with DMD and typically developing controls )] TJ ET
BT 26.250 258.411 Td /F1 9.8 Tf  [(between the ages of 4 and 12 years. Boys with DMD were required to have a clinical picture consistent with the disease and )] TJ ET
BT 26.250 246.506 Td /F1 9.8 Tf  [(confirmation by at least one of the following methods: 1\) documentation of a mutation of the dystrophin gene consistent with a )] TJ ET
BT 26.250 234.601 Td /F1 9.8 Tf  [(diagnosis of DMD; 2\) complete loss of dystrophin on muscle biopsy; or 3\) elevated serum creatine kinase and a family history of )] TJ ET
BT 26.250 222.696 Td /F1 9.8 Tf  [(DMD in a primary male relative who satisfied conditions \(1\) or \(2\). All participants were required to be able to walk ?10 meters, )] TJ ET
BT 26.250 210.792 Td /F1 9.8 Tf  [(be free of any medications that would affect heart rate or metabolism, and be free of concomitant illness or contraindications to )] TJ ET
BT 26.250 198.887 Td /F1 9.8 Tf  [(exercise. All participants had to be able to follow simple instructions. English- and Spanish-speaking boys with DMD were )] TJ ET
BT 26.250 186.982 Td /F1 9.8 Tf  [(recruited from our neuromuscular disease clinic and the northern California region. Typically-developing controls were recruited )] TJ ET
BT 26.250 175.077 Td /F1 9.8 Tf  [(through locally-posted English and Spanish advertisements.)] TJ ET
BT 26.250 155.673 Td /F5 9.8 Tf  [(Evaluation Methods)] TJ ET
BT 26.250 136.268 Td /F1 9.8 Tf  [(Methods for the DMD-specific Six-minute Walk Test \(6MWT\) have been previously reported by our group)] TJ ET
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BT 478.679 137.775 Td /F4 8.7 Tf  [(15)] TJ ET
0.271 0.267 0.267 rg
BT 488.317 140.156 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 490.726 137.775 Td /F4 8.7 Tf  [(16)] TJ ET
0.271 0.267 0.267 rg
BT 500.363 136.268 Td /F1 9.8 Tf  [(. The 6MWT was )] TJ ET
BT 26.250 124.363 Td /F1 9.8 Tf  [(administered at baseline at the end of a test battery that also included anthropometric measures, timed standing from supine, )] TJ ET
BT 26.250 112.458 Td /F1 9.8 Tf  [(timed 4-stair climb, and timed 10- and 25-meter walk/run tests as previously described. Participants viewed a short orientation )] TJ ET
BT 26.250 100.554 Td /F1 9.8 Tf  [(video that was developed to address potential attention and verbal working memory limitations, and then underwent testing on a )] TJ ET
BT 26.250 88.649 Td /F1 9.8 Tf  [(25-meter indoor course. Participants were instructed to travel as far and as fast as possible in six minutes without running in a )] TJ ET
BT 26.250 76.744 Td /F1 9.8 Tf  [(manner that demonstrated consistency with published normative studies)] TJ ET
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BT 337.841 78.251 Td /F4 8.7 Tf  [(32)] TJ ET
0.271 0.267 0.267 rg
BT 347.478 80.632 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 349.887 78.251 Td /F4 8.7 Tf  [(33)] TJ ET
0.271 0.267 0.267 rg
BT 359.525 76.744 Td /F1 9.8 Tf  [(. Participants were provided with regular periodic )] TJ ET
BT 26.250 64.839 Td /F1 9.8 Tf  [(verbal encouragement, and were followed by a �safety� chaser who responded in the event of a fall. PedsQL and PODCI )] TJ ET
BT 26.250 52.935 Td /F1 9.8 Tf  [(instruments were provided as paper-based reports in English or Spanish and were completed by the parent or primary caregiver )] TJ ET
BT 26.250 41.030 Td /F1 9.8 Tf  [(during the evaluation visit. Instrument scores were compiled according to scoring paradigms published with each instrument. )] TJ ET
Q
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BT 291.710 19.825 Td /F1 11.0 Tf  [(3)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Muscular Dystrophy)] TJ ET

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BT 26.250 767.476 Td /F1 9.8 Tf  [(Participants were evaluated at baseline and using identical methods at a 1-year follow-up visit.)] TJ ET
BT 26.250 748.071 Td /F5 9.8 Tf  [(Statistical Methods)] TJ ET
BT 26.250 728.667 Td /F1 9.8 Tf  [(Because this was a pilot study with no )] TJ ET
BT 193.160 728.667 Td /F6 9.8 Tf  [(a priori)] TJ ET
BT 222.956 728.667 Td /F1 9.8 Tf  [( hypotheses, we sought to enroll at least 20 participants in the DMD and control )] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(arms of the study, with a balance of children in 4-6, 7-9 and 10-12 year age groups at enrollment. All data was transformed as )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(necessary to meet assumptions of OLS regression, and were back-transformed for reporting purposes. P-values <0.05 were )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(considered statistically significant. Baseline characteristics were summarized using standard descriptive statistics, and )] TJ ET
BT 26.250 681.048 Td /F1 9.8 Tf  [(differences between groups were assessed using standard between-group mean comparison tests. MCID was calculated at 1/3 )] TJ ET
BT 26.250 669.143 Td /F1 9.8 Tf  [(of a measure�s standard deviation for the DMD group at the baseline evaluation)] TJ ET
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BT 368.748 670.650 Td /F4 8.7 Tf  [(34)] TJ ET
0.271 0.267 0.267 rg
BT 378.385 669.143 Td /F1 9.8 Tf  [( . Correlation of measures at baseline were )] TJ ET
BT 26.250 657.238 Td /F1 9.8 Tf  [(calculated using the Pearson method. Annual change scores for each measure were calculated as the difference between the )] TJ ET
BT 26.250 645.333 Td /F1 9.8 Tf  [(baseline and 1-year visits; significance of change scores was evaluated using one-way analysis of variance with visits 1/2 and )] TJ ET
BT 26.250 633.429 Td /F1 9.8 Tf  [(DMD/control as grouping variables. Correlation of change between measures was calculated using the Pearson method. To )] TJ ET
BT 26.250 621.524 Td /F1 9.8 Tf  [(evaluate the relationship between 6MWD and HrQOL measures, we sequentially evaluated multiple regression models from our )] TJ ET
BT 26.250 609.619 Td /F1 9.8 Tf  [(data using PedsQL and PODCI domains previously identified by McDonald et al.)] TJ ET
0.267 0.267 0.267 rg
BT 373.067 611.126 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 382.705 609.619 Td /F1 9.8 Tf  [( to demonstrate a relationship between )] TJ ET
BT 26.250 597.714 Td /F1 9.8 Tf  [(physical function and participation as well as age at evaluation, height, and weight that have been demonstrated to affect )] TJ ET
BT 26.250 585.810 Td /F1 9.8 Tf  [(predicted values of 6MWD)] TJ ET
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BT 140.579 587.317 Td /F4 8.7 Tf  [(32)] TJ ET
0.271 0.267 0.267 rg
BT 150.216 589.698 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 152.625 587.317 Td /F4 8.7 Tf  [(33)] TJ ET
0.271 0.267 0.267 rg
BT 162.263 585.810 Td /F1 9.8 Tf  [( . In selecting our model, we determined our �best fit� equation based on: 1\) presence of only )] TJ ET
BT 26.250 573.905 Td /F1 9.8 Tf  [(statistically significant \(p<0.05\) explanatory variables in the model; 2\) maximized r)] TJ ET
BT 378.722 577.793 Td /F1 8.7 Tf  [(2)] TJ ET
BT 383.541 573.905 Td /F1 9.8 Tf  [( statistic, and 3\) the highest significant F )] TJ ET
BT 26.250 562.000 Td /F1 9.8 Tf  [(statistic with the fewest degrees of freedom in the model. To evaluate differences in 6MWD MCID using the �best fit� model, we )] TJ ET
BT 26.250 550.095 Td /F1 9.8 Tf  [(calculated predicted 6MWD values at the mean of age, height, and weight that represented upper and lower limits of the MCID )] TJ ET
BT 26.250 538.191 Td /F1 9.8 Tf  [(range of the HrQOL instrument across the observed range of 6MWT performance \(range of 6MWD\).)] TJ ET
BT 26.250 501.588 Td /F4 12.0 Tf  [(Results)] TJ ET
BT 26.250 481.634 Td /F1 9.8 Tf  [(Twenty-four boys with DMD and 36 typically-developing control boys between the ages of 4 and 12 years of age underwent )] TJ ET
BT 26.250 469.729 Td /F1 9.8 Tf  [(evaluation at baseline. Descriptive statistics and MCID values for outcome measures in DMD and control participants is shown )] TJ ET
BT 26.250 457.824 Td /F1 9.8 Tf  [(in Table 1. The 10 meter run/walk velocity was also assessed because of the high correlation between this readily obtainable )] TJ ET
BT 26.250 445.920 Td /F1 9.8 Tf  [(secondary endpoint for ambulatory function and the 6MWD)] TJ ET
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BT 280.949 447.427 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 290.587 449.808 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 292.996 447.427 Td /F4 8.7 Tf  [(18)] TJ ET
0.271 0.267 0.267 rg
BT 302.633 445.920 Td /F1 9.8 Tf  [( . The groups did not differ significantly by age or weight, )] TJ ET
BT 26.250 434.015 Td /F1 9.8 Tf  [(although DMD boys were on average 10cm shorter than controls, which is consistent with previous reports. Also consistent with )] TJ ET
BT 26.250 422.110 Td /F1 9.8 Tf  [(previous reports)] TJ ET
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BT 96.148 423.617 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 105.785 422.110 Td /F1 9.8 Tf  [( , the 6MWD, 10 meter run/walk velocity, PedsQL total and physical function scores and the PODCI global )] TJ ET
BT 26.250 410.205 Td /F1 9.8 Tf  [(scor, transfer and basic mobility score, and sports and physical function score all demonstrated significant differences between )] TJ ET
BT 26.250 398.301 Td /F1 9.8 Tf  [(DMD and control boys \(p<0.00001\).)] TJ ET
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BT 26.250 377.431 Td /F1 9.8 Tf  [(Table 1: Descriptive statistics at baseline)] TJ ET
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27.000 354.154 191.316 12.280 re f
0.267 0.267 0.267 rg
26.625 366.058 191.691 0.750 re f
26.625 353.779 0.750 13.030 re f
0.965 0.965 0.965 rg
218.316 354.154 59.035 12.280 re f
0.267 0.267 0.267 rg
218.316 366.058 59.035 0.750 re f
0.271 0.267 0.267 rg
BT 222.816 356.910 Td /F4 9.8 Tf  [(DMD)] TJ ET
0.965 0.965 0.965 rg
277.351 354.154 49.662 12.280 re f
0.267 0.267 0.267 rg
277.351 366.058 49.662 0.750 re f
0.965 0.965 0.965 rg
327.013 354.154 59.928 12.280 re f
0.267 0.267 0.267 rg
327.013 366.058 59.928 0.750 re f
0.965 0.965 0.965 rg
386.941 354.154 75.489 12.280 re f
0.267 0.267 0.267 rg
386.941 366.058 75.489 0.750 re f
0.271 0.267 0.267 rg
BT 391.441 356.910 Td /F4 9.8 Tf  [(Control)] TJ ET
0.965 0.965 0.965 rg
462.430 354.154 49.662 12.280 re f
0.267 0.267 0.267 rg
462.430 366.058 49.662 0.750 re f
0.965 0.965 0.965 rg
512.092 354.154 68.408 12.280 re f
0.267 0.267 0.267 rg
512.092 366.058 68.783 0.750 re f
580.125 353.779 0.750 13.030 re f
26.625 353.779 192.066 0.750 re f
26.625 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 343.924 Td /F1 9.8 Tf  [(Variable)] TJ ET
0.267 0.267 0.267 rg
217.941 353.779 59.785 0.750 re f
217.941 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 343.924 Td /F1 9.8 Tf  [(Mean)] TJ ET
0.267 0.267 0.267 rg
276.976 353.779 50.412 0.750 re f
276.976 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 343.924 Td /F1 9.8 Tf  [(SD)] TJ ET
0.267 0.267 0.267 rg
326.638 353.779 60.678 0.750 re f
326.638 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 343.924 Td /F1 9.8 Tf  [(MCID)] TJ ET
0.267 0.267 0.267 rg
386.566 353.779 76.239 0.750 re f
386.566 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 343.924 Td /F1 9.8 Tf  [(Mean)] TJ ET
0.267 0.267 0.267 rg
462.055 353.779 50.412 0.750 re f
462.055 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 343.924 Td /F1 9.8 Tf  [(SD)] TJ ET
0.267 0.267 0.267 rg
511.717 353.779 69.158 0.750 re f
511.717 337.897 0.750 16.631 re f
580.125 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 343.924 Td /F1 9.8 Tf  [(P)] TJ ET
0.267 0.267 0.267 rg
26.625 337.897 192.066 0.750 re f
26.625 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 328.042 Td /F1 9.8 Tf  [(Age \(years\))] TJ ET
0.267 0.267 0.267 rg
217.941 337.897 59.785 0.750 re f
217.941 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 328.042 Td /F1 9.8 Tf  [(7.9)] TJ ET
0.267 0.267 0.267 rg
276.976 337.897 50.412 0.750 re f
276.976 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 328.042 Td /F1 9.8 Tf  [(2.3)] TJ ET
0.267 0.267 0.267 rg
326.638 337.897 60.678 0.750 re f
326.638 322.016 0.750 16.631 re f
386.566 337.897 76.239 0.750 re f
386.566 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 328.042 Td /F1 9.8 Tf  [(8.7)] TJ ET
0.267 0.267 0.267 rg
462.055 337.897 50.412 0.750 re f
462.055 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 328.042 Td /F1 9.8 Tf  [(2.6)] TJ ET
0.267 0.267 0.267 rg
511.717 337.897 69.158 0.750 re f
511.717 322.016 0.750 16.631 re f
580.125 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 328.042 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 322.016 192.066 0.750 re f
26.625 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 312.161 Td /F1 9.8 Tf  [(Height \(cm\))] TJ ET
0.267 0.267 0.267 rg
217.941 322.016 59.785 0.750 re f
217.941 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 312.161 Td /F1 9.8 Tf  [(123.0)] TJ ET
0.267 0.267 0.267 rg
276.976 322.016 50.412 0.750 re f
276.976 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 312.161 Td /F1 9.8 Tf  [(14.8)] TJ ET
0.267 0.267 0.267 rg
326.638 322.016 60.678 0.750 re f
326.638 306.135 0.750 16.631 re f
386.566 322.016 76.239 0.750 re f
386.566 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 312.161 Td /F1 9.8 Tf  [(133.4)] TJ ET
0.267 0.267 0.267 rg
462.055 322.016 50.412 0.750 re f
462.055 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 312.161 Td /F1 9.8 Tf  [(16.6)] TJ ET
0.267 0.267 0.267 rg
511.717 322.016 69.158 0.750 re f
511.717 306.135 0.750 16.631 re f
580.125 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 312.161 Td /F1 9.8 Tf  [(0.0087)] TJ ET
0.267 0.267 0.267 rg
26.625 306.135 192.066 0.750 re f
26.625 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 296.280 Td /F1 9.8 Tf  [(Weight \(kg\))] TJ ET
0.267 0.267 0.267 rg
217.941 306.135 59.785 0.750 re f
217.941 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 296.280 Td /F1 9.8 Tf  [(33.2)] TJ ET
0.267 0.267 0.267 rg
276.976 306.135 50.412 0.750 re f
276.976 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 296.280 Td /F1 9.8 Tf  [(16.6)] TJ ET
0.267 0.267 0.267 rg
326.638 306.135 60.678 0.750 re f
326.638 290.254 0.750 16.631 re f
386.566 306.135 76.239 0.750 re f
386.566 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 296.280 Td /F1 9.8 Tf  [(35.5)] TJ ET
0.267 0.267 0.267 rg
462.055 306.135 50.412 0.750 re f
462.055 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 296.280 Td /F1 9.8 Tf  [(17.2)] TJ ET
0.267 0.267 0.267 rg
511.717 306.135 69.158 0.750 re f
511.717 290.254 0.750 16.631 re f
580.125 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 296.280 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 290.254 192.066 0.750 re f
26.625 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 280.399 Td /F1 9.8 Tf  [(6MWD \(meters\))] TJ ET
0.267 0.267 0.267 rg
217.941 290.254 59.785 0.750 re f
217.941 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 280.399 Td /F1 9.8 Tf  [(369.5)] TJ ET
0.267 0.267 0.267 rg
276.976 290.254 50.412 0.750 re f
276.976 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 280.399 Td /F1 9.8 Tf  [(79.3)] TJ ET
0.267 0.267 0.267 rg
326.638 290.254 60.678 0.750 re f
326.638 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 280.399 Td /F1 9.8 Tf  [(26.4)] TJ ET
0.267 0.267 0.267 rg
386.566 290.254 76.239 0.750 re f
386.566 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 280.399 Td /F1 9.8 Tf  [(613.3)] TJ ET
0.267 0.267 0.267 rg
462.055 290.254 50.412 0.750 re f
462.055 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 280.399 Td /F1 9.8 Tf  [(73.6)] TJ ET
0.267 0.267 0.267 rg
511.717 290.254 69.158 0.750 re f
511.717 274.372 0.750 16.631 re f
580.125 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 280.399 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 274.372 192.066 0.750 re f
26.625 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 264.517 Td /F1 9.8 Tf  [(10-meter run/walk velocity \(m/s\))] TJ ET
0.267 0.267 0.267 rg
217.941 274.372 59.785 0.750 re f
217.941 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 264.517 Td /F1 9.8 Tf  [(1.68)] TJ ET
0.267 0.267 0.267 rg
276.976 274.372 50.412 0.750 re f
276.976 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 264.517 Td /F1 9.8 Tf  [(0.56)] TJ ET
0.267 0.267 0.267 rg
326.638 274.372 60.678 0.750 re f
326.638 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 264.517 Td /F1 9.8 Tf  [(0.19)] TJ ET
0.267 0.267 0.267 rg
386.566 274.372 76.239 0.750 re f
386.566 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 264.517 Td /F1 9.8 Tf  [(3.32)] TJ ET
0.267 0.267 0.267 rg
462.055 274.372 50.412 0.750 re f
462.055 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 264.517 Td /F1 9.8 Tf  [(0.36)] TJ ET
0.267 0.267 0.267 rg
511.717 274.372 69.158 0.750 re f
511.717 258.491 0.750 16.631 re f
580.125 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 264.517 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 258.491 192.066 0.750 re f
26.625 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 248.636 Td /F1 9.8 Tf  [(PedsQL Total Score)] TJ ET
0.267 0.267 0.267 rg
217.941 258.491 59.785 0.750 re f
217.941 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 248.636 Td /F1 9.8 Tf  [(57.3)] TJ ET
0.267 0.267 0.267 rg
276.976 258.491 50.412 0.750 re f
276.976 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 248.636 Td /F1 9.8 Tf  [(10.1)] TJ ET
0.267 0.267 0.267 rg
326.638 258.491 60.678 0.750 re f
326.638 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 248.636 Td /F1 9.8 Tf  [(3.5)] TJ ET
0.267 0.267 0.267 rg
386.566 258.491 76.239 0.750 re f
386.566 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 248.636 Td /F1 9.8 Tf  [(88.8)] TJ ET
0.267 0.267 0.267 rg
462.055 258.491 50.412 0.750 re f
462.055 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 248.636 Td /F1 9.8 Tf  [(10.6)] TJ ET
0.267 0.267 0.267 rg
511.717 258.491 69.158 0.750 re f
511.717 242.610 0.750 16.631 re f
580.125 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 248.636 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 242.610 192.066 0.750 re f
26.625 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 232.755 Td /F1 9.8 Tf  [(PedsQL Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
217.941 242.610 59.785 0.750 re f
217.941 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 232.755 Td /F1 9.8 Tf  [(48.0)] TJ ET
0.267 0.267 0.267 rg
276.976 242.610 50.412 0.750 re f
276.976 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 232.755 Td /F1 9.8 Tf  [(20.0)] TJ ET
0.267 0.267 0.267 rg
326.638 242.610 60.678 0.750 re f
326.638 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 232.755 Td /F1 9.8 Tf  [(6.7)] TJ ET
0.267 0.267 0.267 rg
386.566 242.610 76.239 0.750 re f
386.566 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 232.755 Td /F1 9.8 Tf  [(92.9)] TJ ET
0.267 0.267 0.267 rg
462.055 242.610 50.412 0.750 re f
462.055 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 232.755 Td /F1 9.8 Tf  [(12.5)] TJ ET
0.267 0.267 0.267 rg
511.717 242.610 69.158 0.750 re f
511.717 226.729 0.750 16.631 re f
580.125 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 232.755 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 226.729 192.066 0.750 re f
26.625 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 216.874 Td /F1 9.8 Tf  [(PODCI Global Score)] TJ ET
0.267 0.267 0.267 rg
217.941 226.729 59.785 0.750 re f
217.941 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 216.874 Td /F1 9.8 Tf  [(73.8)] TJ ET
0.267 0.267 0.267 rg
276.976 226.729 50.412 0.750 re f
276.976 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 216.874 Td /F1 9.8 Tf  [(11.5)] TJ ET
0.267 0.267 0.267 rg
326.638 226.729 60.678 0.750 re f
326.638 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 216.874 Td /F1 9.8 Tf  [(3.8)] TJ ET
0.267 0.267 0.267 rg
386.566 226.729 76.239 0.750 re f
386.566 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 216.874 Td /F1 9.8 Tf  [(97.9)] TJ ET
0.267 0.267 0.267 rg
462.055 226.729 50.412 0.750 re f
462.055 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 216.874 Td /F1 9.8 Tf  [(3.0)] TJ ET
0.267 0.267 0.267 rg
511.717 226.729 69.158 0.750 re f
511.717 210.847 0.750 16.631 re f
580.125 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 216.874 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 210.847 192.066 0.750 re f
26.625 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 200.992 Td /F1 9.8 Tf  [(PODCI Transfer / Basic Mobility Score)] TJ ET
0.267 0.267 0.267 rg
217.941 210.847 59.785 0.750 re f
217.941 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 200.992 Td /F1 9.8 Tf  [(79.5)] TJ ET
0.267 0.267 0.267 rg
276.976 210.847 50.412 0.750 re f
276.976 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 200.992 Td /F1 9.8 Tf  [(13.5)] TJ ET
0.267 0.267 0.267 rg
326.638 210.847 60.678 0.750 re f
326.638 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 200.992 Td /F1 9.8 Tf  [(4.5)] TJ ET
0.267 0.267 0.267 rg
386.566 210.847 76.239 0.750 re f
386.566 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 200.992 Td /F1 9.8 Tf  [(100.3)] TJ ET
0.267 0.267 0.267 rg
462.055 210.847 50.412 0.750 re f
462.055 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 200.992 Td /F1 9.8 Tf  [(1.6)] TJ ET
0.267 0.267 0.267 rg
511.717 210.847 69.158 0.750 re f
511.717 194.966 0.750 16.631 re f
580.125 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 200.992 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 194.966 192.066 0.750 re f
26.625 171.454 192.066 0.750 re f
26.625 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 185.111 Td /F1 9.8 Tf  [(PODCI Sports and Physical Function )] TJ ET
BT 31.875 177.480 Td /F1 9.8 Tf  [(Score)] TJ ET
0.267 0.267 0.267 rg
217.941 194.966 59.785 0.750 re f
217.941 171.454 59.785 0.750 re f
217.941 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 223.191 185.111 Td /F1 9.8 Tf  [(55.0)] TJ ET
0.267 0.267 0.267 rg
276.976 194.966 50.412 0.750 re f
276.976 171.454 50.412 0.750 re f
276.976 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 282.226 185.111 Td /F1 9.8 Tf  [(21.2)] TJ ET
0.267 0.267 0.267 rg
326.638 194.966 60.678 0.750 re f
326.638 171.454 60.678 0.750 re f
326.638 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 331.888 185.111 Td /F1 9.8 Tf  [(7.1)] TJ ET
0.267 0.267 0.267 rg
386.566 194.966 76.239 0.750 re f
386.566 171.454 76.239 0.750 re f
386.566 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 391.816 185.111 Td /F1 9.8 Tf  [(95.8)] TJ ET
0.267 0.267 0.267 rg
462.055 194.966 50.412 0.750 re f
462.055 171.454 50.412 0.750 re f
462.055 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 467.305 185.111 Td /F1 9.8 Tf  [(5.8)] TJ ET
0.267 0.267 0.267 rg
511.717 194.966 69.158 0.750 re f
511.717 171.454 69.158 0.750 re f
511.717 171.454 0.750 24.263 re f
580.125 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 516.967 185.111 Td /F1 9.8 Tf  [(0.0001)] TJ ET
BT 26.250 116.555 Td /F1 9.8 Tf  [(Correlation are shown between the 6MWD and PROs \(Table 2\) and the 10 meter run/walk velocity and PRO measures \(Table )] TJ ET
BT 26.250 104.650 Td /F1 9.8 Tf  [(3\). In boys with DMD, 6MWD was strongly correlated with PODCI measures, with the transfer and basic mobility scale showing )] TJ ET
BT 26.250 92.745 Td /F1 9.8 Tf  [(the strongest relationship \(r=0.79\). In addition, the 10 meter run/walk velocity was also strongly correlated with the PODCI )] TJ ET
BT 26.250 80.841 Td /F1 9.8 Tf  [(measures, including the transfer and basic mobility scale \(r=0.76\). In the DMD group 6MWD and 10 meter run/walk velocity was )] TJ ET
BT 26.250 68.936 Td /F1 9.8 Tf  [(weakly correlated with PedsQL items. In controls, PedsQL physical function and PODCI global score showed weak correlations )] TJ ET
BT 26.250 57.031 Td /F1 9.8 Tf  [(with ambulatory measures. Across the full range of both 6MWD and HrQOL measures with the groups combined, 6MWD )] TJ ET
BT 26.250 45.126 Td /F1 9.8 Tf  [(demonstrated strong to very strong correlations with both PODCI and PedsQL measures \(r=0.85-0.88 and r=0.71, respectively\). )] TJ ET
Q
q
15.000 30.841 577.500 746.159 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Participants were evaluated at baseline and using identical methods at a 1-year follow-up visit.)] TJ ET
BT 26.250 748.071 Td /F5 9.8 Tf  [(Statistical Methods)] TJ ET
BT 26.250 728.667 Td /F1 9.8 Tf  [(Because this was a pilot study with no )] TJ ET
BT 193.160 728.667 Td /F6 9.8 Tf  [(a priori)] TJ ET
BT 222.956 728.667 Td /F1 9.8 Tf  [( hypotheses, we sought to enroll at least 20 participants in the DMD and control )] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(arms of the study, with a balance of children in 4-6, 7-9 and 10-12 year age groups at enrollment. All data was transformed as )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(necessary to meet assumptions of OLS regression, and were back-transformed for reporting purposes. P-values <0.05 were )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(considered statistically significant. Baseline characteristics were summarized using standard descriptive statistics, and )] TJ ET
BT 26.250 681.048 Td /F1 9.8 Tf  [(differences between groups were assessed using standard between-group mean comparison tests. MCID was calculated at 1/3 )] TJ ET
BT 26.250 669.143 Td /F1 9.8 Tf  [(of a measure�s standard deviation for the DMD group at the baseline evaluation)] TJ ET
0.267 0.267 0.267 rg
BT 368.748 670.650 Td /F4 8.7 Tf  [(34)] TJ ET
0.271 0.267 0.267 rg
BT 378.385 669.143 Td /F1 9.8 Tf  [( . Correlation of measures at baseline were )] TJ ET
BT 26.250 657.238 Td /F1 9.8 Tf  [(calculated using the Pearson method. Annual change scores for each measure were calculated as the difference between the )] TJ ET
BT 26.250 645.333 Td /F1 9.8 Tf  [(baseline and 1-year visits; significance of change scores was evaluated using one-way analysis of variance with visits 1/2 and )] TJ ET
BT 26.250 633.429 Td /F1 9.8 Tf  [(DMD/control as grouping variables. Correlation of change between measures was calculated using the Pearson method. To )] TJ ET
BT 26.250 621.524 Td /F1 9.8 Tf  [(evaluate the relationship between 6MWD and HrQOL measures, we sequentially evaluated multiple regression models from our )] TJ ET
BT 26.250 609.619 Td /F1 9.8 Tf  [(data using PedsQL and PODCI domains previously identified by McDonald et al.)] TJ ET
0.267 0.267 0.267 rg
BT 373.067 611.126 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 382.705 609.619 Td /F1 9.8 Tf  [( to demonstrate a relationship between )] TJ ET
BT 26.250 597.714 Td /F1 9.8 Tf  [(physical function and participation as well as age at evaluation, height, and weight that have been demonstrated to affect )] TJ ET
BT 26.250 585.810 Td /F1 9.8 Tf  [(predicted values of 6MWD)] TJ ET
0.267 0.267 0.267 rg
BT 140.579 587.317 Td /F4 8.7 Tf  [(32)] TJ ET
0.271 0.267 0.267 rg
BT 150.216 589.698 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 152.625 587.317 Td /F4 8.7 Tf  [(33)] TJ ET
0.271 0.267 0.267 rg
BT 162.263 585.810 Td /F1 9.8 Tf  [( . In selecting our model, we determined our �best fit� equation based on: 1\) presence of only )] TJ ET
BT 26.250 573.905 Td /F1 9.8 Tf  [(statistically significant \(p<0.05\) explanatory variables in the model; 2\) maximized r)] TJ ET
BT 378.722 577.793 Td /F1 8.7 Tf  [(2)] TJ ET
BT 383.541 573.905 Td /F1 9.8 Tf  [( statistic, and 3\) the highest significant F )] TJ ET
BT 26.250 562.000 Td /F1 9.8 Tf  [(statistic with the fewest degrees of freedom in the model. To evaluate differences in 6MWD MCID using the �best fit� model, we )] TJ ET
BT 26.250 550.095 Td /F1 9.8 Tf  [(calculated predicted 6MWD values at the mean of age, height, and weight that represented upper and lower limits of the MCID )] TJ ET
BT 26.250 538.191 Td /F1 9.8 Tf  [(range of the HrQOL instrument across the observed range of 6MWT performance \(range of 6MWD\).)] TJ ET
BT 26.250 501.588 Td /F4 12.0 Tf  [(Results)] TJ ET
BT 26.250 481.634 Td /F1 9.8 Tf  [(Twenty-four boys with DMD and 36 typically-developing control boys between the ages of 4 and 12 years of age underwent )] TJ ET
BT 26.250 469.729 Td /F1 9.8 Tf  [(evaluation at baseline. Descriptive statistics and MCID values for outcome measures in DMD and control participants is shown )] TJ ET
BT 26.250 457.824 Td /F1 9.8 Tf  [(in Table 1. The 10 meter run/walk velocity was also assessed because of the high correlation between this readily obtainable )] TJ ET
BT 26.250 445.920 Td /F1 9.8 Tf  [(secondary endpoint for ambulatory function and the 6MWD)] TJ ET
0.267 0.267 0.267 rg
BT 280.949 447.427 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 290.587 449.808 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 292.996 447.427 Td /F4 8.7 Tf  [(18)] TJ ET
0.271 0.267 0.267 rg
BT 302.633 445.920 Td /F1 9.8 Tf  [( . The groups did not differ significantly by age or weight, )] TJ ET
BT 26.250 434.015 Td /F1 9.8 Tf  [(although DMD boys were on average 10cm shorter than controls, which is consistent with previous reports. Also consistent with )] TJ ET
BT 26.250 422.110 Td /F1 9.8 Tf  [(previous reports)] TJ ET
0.267 0.267 0.267 rg
BT 96.148 423.617 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 105.785 422.110 Td /F1 9.8 Tf  [( , the 6MWD, 10 meter run/walk velocity, PedsQL total and physical function scores and the PODCI global )] TJ ET
BT 26.250 410.205 Td /F1 9.8 Tf  [(scor, transfer and basic mobility score, and sports and physical function score all demonstrated significant differences between )] TJ ET
BT 26.250 398.301 Td /F1 9.8 Tf  [(DMD and control boys \(p<0.00001\).)] TJ ET
q
26.250 374.683 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 377.431 Td /F1 9.8 Tf  [(Table 1: Descriptive statistics at baseline)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 171.079 555.000 196.105 re f
0.965 0.965 0.965 rg
27.000 354.154 191.316 12.280 re f
0.267 0.267 0.267 rg
26.625 366.058 191.691 0.750 re f
26.625 353.779 0.750 13.030 re f
0.965 0.965 0.965 rg
218.316 354.154 59.035 12.280 re f
0.267 0.267 0.267 rg
218.316 366.058 59.035 0.750 re f
0.271 0.267 0.267 rg
BT 222.816 356.910 Td /F4 9.8 Tf  [(DMD)] TJ ET
0.965 0.965 0.965 rg
277.351 354.154 49.662 12.280 re f
0.267 0.267 0.267 rg
277.351 366.058 49.662 0.750 re f
0.965 0.965 0.965 rg
327.013 354.154 59.928 12.280 re f
0.267 0.267 0.267 rg
327.013 366.058 59.928 0.750 re f
0.965 0.965 0.965 rg
386.941 354.154 75.489 12.280 re f
0.267 0.267 0.267 rg
386.941 366.058 75.489 0.750 re f
0.271 0.267 0.267 rg
BT 391.441 356.910 Td /F4 9.8 Tf  [(Control)] TJ ET
0.965 0.965 0.965 rg
462.430 354.154 49.662 12.280 re f
0.267 0.267 0.267 rg
462.430 366.058 49.662 0.750 re f
0.965 0.965 0.965 rg
512.092 354.154 68.408 12.280 re f
0.267 0.267 0.267 rg
512.092 366.058 68.783 0.750 re f
580.125 353.779 0.750 13.030 re f
26.625 353.779 192.066 0.750 re f
26.625 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 343.924 Td /F1 9.8 Tf  [(Variable)] TJ ET
0.267 0.267 0.267 rg
217.941 353.779 59.785 0.750 re f
217.941 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 343.924 Td /F1 9.8 Tf  [(Mean)] TJ ET
0.267 0.267 0.267 rg
276.976 353.779 50.412 0.750 re f
276.976 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 343.924 Td /F1 9.8 Tf  [(SD)] TJ ET
0.267 0.267 0.267 rg
326.638 353.779 60.678 0.750 re f
326.638 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 343.924 Td /F1 9.8 Tf  [(MCID)] TJ ET
0.267 0.267 0.267 rg
386.566 353.779 76.239 0.750 re f
386.566 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 343.924 Td /F1 9.8 Tf  [(Mean)] TJ ET
0.267 0.267 0.267 rg
462.055 353.779 50.412 0.750 re f
462.055 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 343.924 Td /F1 9.8 Tf  [(SD)] TJ ET
0.267 0.267 0.267 rg
511.717 353.779 69.158 0.750 re f
511.717 337.897 0.750 16.631 re f
580.125 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 343.924 Td /F1 9.8 Tf  [(P)] TJ ET
0.267 0.267 0.267 rg
26.625 337.897 192.066 0.750 re f
26.625 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 328.042 Td /F1 9.8 Tf  [(Age \(years\))] TJ ET
0.267 0.267 0.267 rg
217.941 337.897 59.785 0.750 re f
217.941 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 328.042 Td /F1 9.8 Tf  [(7.9)] TJ ET
0.267 0.267 0.267 rg
276.976 337.897 50.412 0.750 re f
276.976 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 328.042 Td /F1 9.8 Tf  [(2.3)] TJ ET
0.267 0.267 0.267 rg
326.638 337.897 60.678 0.750 re f
326.638 322.016 0.750 16.631 re f
386.566 337.897 76.239 0.750 re f
386.566 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 328.042 Td /F1 9.8 Tf  [(8.7)] TJ ET
0.267 0.267 0.267 rg
462.055 337.897 50.412 0.750 re f
462.055 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 328.042 Td /F1 9.8 Tf  [(2.6)] TJ ET
0.267 0.267 0.267 rg
511.717 337.897 69.158 0.750 re f
511.717 322.016 0.750 16.631 re f
580.125 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 328.042 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 322.016 192.066 0.750 re f
26.625 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 312.161 Td /F1 9.8 Tf  [(Height \(cm\))] TJ ET
0.267 0.267 0.267 rg
217.941 322.016 59.785 0.750 re f
217.941 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 312.161 Td /F1 9.8 Tf  [(123.0)] TJ ET
0.267 0.267 0.267 rg
276.976 322.016 50.412 0.750 re f
276.976 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 312.161 Td /F1 9.8 Tf  [(14.8)] TJ ET
0.267 0.267 0.267 rg
326.638 322.016 60.678 0.750 re f
326.638 306.135 0.750 16.631 re f
386.566 322.016 76.239 0.750 re f
386.566 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 312.161 Td /F1 9.8 Tf  [(133.4)] TJ ET
0.267 0.267 0.267 rg
462.055 322.016 50.412 0.750 re f
462.055 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 312.161 Td /F1 9.8 Tf  [(16.6)] TJ ET
0.267 0.267 0.267 rg
511.717 322.016 69.158 0.750 re f
511.717 306.135 0.750 16.631 re f
580.125 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 312.161 Td /F1 9.8 Tf  [(0.0087)] TJ ET
0.267 0.267 0.267 rg
26.625 306.135 192.066 0.750 re f
26.625 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 296.280 Td /F1 9.8 Tf  [(Weight \(kg\))] TJ ET
0.267 0.267 0.267 rg
217.941 306.135 59.785 0.750 re f
217.941 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 296.280 Td /F1 9.8 Tf  [(33.2)] TJ ET
0.267 0.267 0.267 rg
276.976 306.135 50.412 0.750 re f
276.976 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 296.280 Td /F1 9.8 Tf  [(16.6)] TJ ET
0.267 0.267 0.267 rg
326.638 306.135 60.678 0.750 re f
326.638 290.254 0.750 16.631 re f
386.566 306.135 76.239 0.750 re f
386.566 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 296.280 Td /F1 9.8 Tf  [(35.5)] TJ ET
0.267 0.267 0.267 rg
462.055 306.135 50.412 0.750 re f
462.055 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 296.280 Td /F1 9.8 Tf  [(17.2)] TJ ET
0.267 0.267 0.267 rg
511.717 306.135 69.158 0.750 re f
511.717 290.254 0.750 16.631 re f
580.125 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 296.280 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 290.254 192.066 0.750 re f
26.625 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 280.399 Td /F1 9.8 Tf  [(6MWD \(meters\))] TJ ET
0.267 0.267 0.267 rg
217.941 290.254 59.785 0.750 re f
217.941 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 280.399 Td /F1 9.8 Tf  [(369.5)] TJ ET
0.267 0.267 0.267 rg
276.976 290.254 50.412 0.750 re f
276.976 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 280.399 Td /F1 9.8 Tf  [(79.3)] TJ ET
0.267 0.267 0.267 rg
326.638 290.254 60.678 0.750 re f
326.638 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 280.399 Td /F1 9.8 Tf  [(26.4)] TJ ET
0.267 0.267 0.267 rg
386.566 290.254 76.239 0.750 re f
386.566 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 280.399 Td /F1 9.8 Tf  [(613.3)] TJ ET
0.267 0.267 0.267 rg
462.055 290.254 50.412 0.750 re f
462.055 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 280.399 Td /F1 9.8 Tf  [(73.6)] TJ ET
0.267 0.267 0.267 rg
511.717 290.254 69.158 0.750 re f
511.717 274.372 0.750 16.631 re f
580.125 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 280.399 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 274.372 192.066 0.750 re f
26.625 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 264.517 Td /F1 9.8 Tf  [(10-meter run/walk velocity \(m/s\))] TJ ET
0.267 0.267 0.267 rg
217.941 274.372 59.785 0.750 re f
217.941 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 264.517 Td /F1 9.8 Tf  [(1.68)] TJ ET
0.267 0.267 0.267 rg
276.976 274.372 50.412 0.750 re f
276.976 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 264.517 Td /F1 9.8 Tf  [(0.56)] TJ ET
0.267 0.267 0.267 rg
326.638 274.372 60.678 0.750 re f
326.638 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 264.517 Td /F1 9.8 Tf  [(0.19)] TJ ET
0.267 0.267 0.267 rg
386.566 274.372 76.239 0.750 re f
386.566 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 264.517 Td /F1 9.8 Tf  [(3.32)] TJ ET
0.267 0.267 0.267 rg
462.055 274.372 50.412 0.750 re f
462.055 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 264.517 Td /F1 9.8 Tf  [(0.36)] TJ ET
0.267 0.267 0.267 rg
511.717 274.372 69.158 0.750 re f
511.717 258.491 0.750 16.631 re f
580.125 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 264.517 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 258.491 192.066 0.750 re f
26.625 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 248.636 Td /F1 9.8 Tf  [(PedsQL Total Score)] TJ ET
0.267 0.267 0.267 rg
217.941 258.491 59.785 0.750 re f
217.941 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 248.636 Td /F1 9.8 Tf  [(57.3)] TJ ET
0.267 0.267 0.267 rg
276.976 258.491 50.412 0.750 re f
276.976 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 248.636 Td /F1 9.8 Tf  [(10.1)] TJ ET
0.267 0.267 0.267 rg
326.638 258.491 60.678 0.750 re f
326.638 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 248.636 Td /F1 9.8 Tf  [(3.5)] TJ ET
0.267 0.267 0.267 rg
386.566 258.491 76.239 0.750 re f
386.566 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 248.636 Td /F1 9.8 Tf  [(88.8)] TJ ET
0.267 0.267 0.267 rg
462.055 258.491 50.412 0.750 re f
462.055 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 248.636 Td /F1 9.8 Tf  [(10.6)] TJ ET
0.267 0.267 0.267 rg
511.717 258.491 69.158 0.750 re f
511.717 242.610 0.750 16.631 re f
580.125 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 248.636 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 242.610 192.066 0.750 re f
26.625 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 232.755 Td /F1 9.8 Tf  [(PedsQL Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
217.941 242.610 59.785 0.750 re f
217.941 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 232.755 Td /F1 9.8 Tf  [(48.0)] TJ ET
0.267 0.267 0.267 rg
276.976 242.610 50.412 0.750 re f
276.976 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 232.755 Td /F1 9.8 Tf  [(20.0)] TJ ET
0.267 0.267 0.267 rg
326.638 242.610 60.678 0.750 re f
326.638 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 232.755 Td /F1 9.8 Tf  [(6.7)] TJ ET
0.267 0.267 0.267 rg
386.566 242.610 76.239 0.750 re f
386.566 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 232.755 Td /F1 9.8 Tf  [(92.9)] TJ ET
0.267 0.267 0.267 rg
462.055 242.610 50.412 0.750 re f
462.055 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 232.755 Td /F1 9.8 Tf  [(12.5)] TJ ET
0.267 0.267 0.267 rg
511.717 242.610 69.158 0.750 re f
511.717 226.729 0.750 16.631 re f
580.125 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 232.755 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 226.729 192.066 0.750 re f
26.625 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 216.874 Td /F1 9.8 Tf  [(PODCI Global Score)] TJ ET
0.267 0.267 0.267 rg
217.941 226.729 59.785 0.750 re f
217.941 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 216.874 Td /F1 9.8 Tf  [(73.8)] TJ ET
0.267 0.267 0.267 rg
276.976 226.729 50.412 0.750 re f
276.976 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 216.874 Td /F1 9.8 Tf  [(11.5)] TJ ET
0.267 0.267 0.267 rg
326.638 226.729 60.678 0.750 re f
326.638 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 216.874 Td /F1 9.8 Tf  [(3.8)] TJ ET
0.267 0.267 0.267 rg
386.566 226.729 76.239 0.750 re f
386.566 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 216.874 Td /F1 9.8 Tf  [(97.9)] TJ ET
0.267 0.267 0.267 rg
462.055 226.729 50.412 0.750 re f
462.055 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 216.874 Td /F1 9.8 Tf  [(3.0)] TJ ET
0.267 0.267 0.267 rg
511.717 226.729 69.158 0.750 re f
511.717 210.847 0.750 16.631 re f
580.125 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 216.874 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 210.847 192.066 0.750 re f
26.625 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 200.992 Td /F1 9.8 Tf  [(PODCI Transfer / Basic Mobility Score)] TJ ET
0.267 0.267 0.267 rg
217.941 210.847 59.785 0.750 re f
217.941 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 200.992 Td /F1 9.8 Tf  [(79.5)] TJ ET
0.267 0.267 0.267 rg
276.976 210.847 50.412 0.750 re f
276.976 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 200.992 Td /F1 9.8 Tf  [(13.5)] TJ ET
0.267 0.267 0.267 rg
326.638 210.847 60.678 0.750 re f
326.638 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 200.992 Td /F1 9.8 Tf  [(4.5)] TJ ET
0.267 0.267 0.267 rg
386.566 210.847 76.239 0.750 re f
386.566 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 200.992 Td /F1 9.8 Tf  [(100.3)] TJ ET
0.267 0.267 0.267 rg
462.055 210.847 50.412 0.750 re f
462.055 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 200.992 Td /F1 9.8 Tf  [(1.6)] TJ ET
0.267 0.267 0.267 rg
511.717 210.847 69.158 0.750 re f
511.717 194.966 0.750 16.631 re f
580.125 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 200.992 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 194.966 192.066 0.750 re f
26.625 171.454 192.066 0.750 re f
26.625 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 185.111 Td /F1 9.8 Tf  [(PODCI Sports and Physical Function )] TJ ET
BT 31.875 177.480 Td /F1 9.8 Tf  [(Score)] TJ ET
0.267 0.267 0.267 rg
217.941 194.966 59.785 0.750 re f
217.941 171.454 59.785 0.750 re f
217.941 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 223.191 185.111 Td /F1 9.8 Tf  [(55.0)] TJ ET
0.267 0.267 0.267 rg
276.976 194.966 50.412 0.750 re f
276.976 171.454 50.412 0.750 re f
276.976 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 282.226 185.111 Td /F1 9.8 Tf  [(21.2)] TJ ET
0.267 0.267 0.267 rg
326.638 194.966 60.678 0.750 re f
326.638 171.454 60.678 0.750 re f
326.638 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 331.888 185.111 Td /F1 9.8 Tf  [(7.1)] TJ ET
0.267 0.267 0.267 rg
386.566 194.966 76.239 0.750 re f
386.566 171.454 76.239 0.750 re f
386.566 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 391.816 185.111 Td /F1 9.8 Tf  [(95.8)] TJ ET
0.267 0.267 0.267 rg
462.055 194.966 50.412 0.750 re f
462.055 171.454 50.412 0.750 re f
462.055 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 467.305 185.111 Td /F1 9.8 Tf  [(5.8)] TJ ET
0.267 0.267 0.267 rg
511.717 194.966 69.158 0.750 re f
511.717 171.454 69.158 0.750 re f
511.717 171.454 0.750 24.263 re f
580.125 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 516.967 185.111 Td /F1 9.8 Tf  [(0.0001)] TJ ET
BT 26.250 116.555 Td /F1 9.8 Tf  [(Correlation are shown between the 6MWD and PROs \(Table 2\) and the 10 meter run/walk velocity and PRO measures \(Table )] TJ ET
BT 26.250 104.650 Td /F1 9.8 Tf  [(3\). In boys with DMD, 6MWD was strongly correlated with PODCI measures, with the transfer and basic mobility scale showing )] TJ ET
BT 26.250 92.745 Td /F1 9.8 Tf  [(the strongest relationship \(r=0.79\). In addition, the 10 meter run/walk velocity was also strongly correlated with the PODCI )] TJ ET
BT 26.250 80.841 Td /F1 9.8 Tf  [(measures, including the transfer and basic mobility scale \(r=0.76\). In the DMD group 6MWD and 10 meter run/walk velocity was )] TJ ET
BT 26.250 68.936 Td /F1 9.8 Tf  [(weakly correlated with PedsQL items. In controls, PedsQL physical function and PODCI global score showed weak correlations )] TJ ET
BT 26.250 57.031 Td /F1 9.8 Tf  [(with ambulatory measures. Across the full range of both 6MWD and HrQOL measures with the groups combined, 6MWD )] TJ ET
BT 26.250 45.126 Td /F1 9.8 Tf  [(demonstrated strong to very strong correlations with both PODCI and PedsQL measures \(r=0.85-0.88 and r=0.71, respectively\). )] TJ ET
Q
q
15.000 30.841 577.500 746.159 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Participants were evaluated at baseline and using identical methods at a 1-year follow-up visit.)] TJ ET
BT 26.250 748.071 Td /F5 9.8 Tf  [(Statistical Methods)] TJ ET
BT 26.250 728.667 Td /F1 9.8 Tf  [(Because this was a pilot study with no )] TJ ET
BT 193.160 728.667 Td /F6 9.8 Tf  [(a priori)] TJ ET
BT 222.956 728.667 Td /F1 9.8 Tf  [( hypotheses, we sought to enroll at least 20 participants in the DMD and control )] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(arms of the study, with a balance of children in 4-6, 7-9 and 10-12 year age groups at enrollment. All data was transformed as )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(necessary to meet assumptions of OLS regression, and were back-transformed for reporting purposes. P-values <0.05 were )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(considered statistically significant. Baseline characteristics were summarized using standard descriptive statistics, and )] TJ ET
BT 26.250 681.048 Td /F1 9.8 Tf  [(differences between groups were assessed using standard between-group mean comparison tests. MCID was calculated at 1/3 )] TJ ET
BT 26.250 669.143 Td /F1 9.8 Tf  [(of a measure�s standard deviation for the DMD group at the baseline evaluation)] TJ ET
0.267 0.267 0.267 rg
BT 368.748 670.650 Td /F4 8.7 Tf  [(34)] TJ ET
0.271 0.267 0.267 rg
BT 378.385 669.143 Td /F1 9.8 Tf  [( . Correlation of measures at baseline were )] TJ ET
BT 26.250 657.238 Td /F1 9.8 Tf  [(calculated using the Pearson method. Annual change scores for each measure were calculated as the difference between the )] TJ ET
BT 26.250 645.333 Td /F1 9.8 Tf  [(baseline and 1-year visits; significance of change scores was evaluated using one-way analysis of variance with visits 1/2 and )] TJ ET
BT 26.250 633.429 Td /F1 9.8 Tf  [(DMD/control as grouping variables. Correlation of change between measures was calculated using the Pearson method. To )] TJ ET
BT 26.250 621.524 Td /F1 9.8 Tf  [(evaluate the relationship between 6MWD and HrQOL measures, we sequentially evaluated multiple regression models from our )] TJ ET
BT 26.250 609.619 Td /F1 9.8 Tf  [(data using PedsQL and PODCI domains previously identified by McDonald et al.)] TJ ET
0.267 0.267 0.267 rg
BT 373.067 611.126 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 382.705 609.619 Td /F1 9.8 Tf  [( to demonstrate a relationship between )] TJ ET
BT 26.250 597.714 Td /F1 9.8 Tf  [(physical function and participation as well as age at evaluation, height, and weight that have been demonstrated to affect )] TJ ET
BT 26.250 585.810 Td /F1 9.8 Tf  [(predicted values of 6MWD)] TJ ET
0.267 0.267 0.267 rg
BT 140.579 587.317 Td /F4 8.7 Tf  [(32)] TJ ET
0.271 0.267 0.267 rg
BT 150.216 589.698 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 152.625 587.317 Td /F4 8.7 Tf  [(33)] TJ ET
0.271 0.267 0.267 rg
BT 162.263 585.810 Td /F1 9.8 Tf  [( . In selecting our model, we determined our �best fit� equation based on: 1\) presence of only )] TJ ET
BT 26.250 573.905 Td /F1 9.8 Tf  [(statistically significant \(p<0.05\) explanatory variables in the model; 2\) maximized r)] TJ ET
BT 378.722 577.793 Td /F1 8.7 Tf  [(2)] TJ ET
BT 383.541 573.905 Td /F1 9.8 Tf  [( statistic, and 3\) the highest significant F )] TJ ET
BT 26.250 562.000 Td /F1 9.8 Tf  [(statistic with the fewest degrees of freedom in the model. To evaluate differences in 6MWD MCID using the �best fit� model, we )] TJ ET
BT 26.250 550.095 Td /F1 9.8 Tf  [(calculated predicted 6MWD values at the mean of age, height, and weight that represented upper and lower limits of the MCID )] TJ ET
BT 26.250 538.191 Td /F1 9.8 Tf  [(range of the HrQOL instrument across the observed range of 6MWT performance \(range of 6MWD\).)] TJ ET
BT 26.250 501.588 Td /F4 12.0 Tf  [(Results)] TJ ET
BT 26.250 481.634 Td /F1 9.8 Tf  [(Twenty-four boys with DMD and 36 typically-developing control boys between the ages of 4 and 12 years of age underwent )] TJ ET
BT 26.250 469.729 Td /F1 9.8 Tf  [(evaluation at baseline. Descriptive statistics and MCID values for outcome measures in DMD and control participants is shown )] TJ ET
BT 26.250 457.824 Td /F1 9.8 Tf  [(in Table 1. The 10 meter run/walk velocity was also assessed because of the high correlation between this readily obtainable )] TJ ET
BT 26.250 445.920 Td /F1 9.8 Tf  [(secondary endpoint for ambulatory function and the 6MWD)] TJ ET
0.267 0.267 0.267 rg
BT 280.949 447.427 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 290.587 449.808 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 292.996 447.427 Td /F4 8.7 Tf  [(18)] TJ ET
0.271 0.267 0.267 rg
BT 302.633 445.920 Td /F1 9.8 Tf  [( . The groups did not differ significantly by age or weight, )] TJ ET
BT 26.250 434.015 Td /F1 9.8 Tf  [(although DMD boys were on average 10cm shorter than controls, which is consistent with previous reports. Also consistent with )] TJ ET
BT 26.250 422.110 Td /F1 9.8 Tf  [(previous reports)] TJ ET
0.267 0.267 0.267 rg
BT 96.148 423.617 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 105.785 422.110 Td /F1 9.8 Tf  [( , the 6MWD, 10 meter run/walk velocity, PedsQL total and physical function scores and the PODCI global )] TJ ET
BT 26.250 410.205 Td /F1 9.8 Tf  [(scor, transfer and basic mobility score, and sports and physical function score all demonstrated significant differences between )] TJ ET
BT 26.250 398.301 Td /F1 9.8 Tf  [(DMD and control boys \(p<0.00001\).)] TJ ET
q
26.250 374.683 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 377.431 Td /F1 9.8 Tf  [(Table 1: Descriptive statistics at baseline)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 171.079 555.000 196.105 re f
0.965 0.965 0.965 rg
27.000 354.154 191.316 12.280 re f
0.267 0.267 0.267 rg
26.625 366.058 191.691 0.750 re f
26.625 353.779 0.750 13.030 re f
0.965 0.965 0.965 rg
218.316 354.154 59.035 12.280 re f
0.267 0.267 0.267 rg
218.316 366.058 59.035 0.750 re f
0.271 0.267 0.267 rg
BT 222.816 356.910 Td /F4 9.8 Tf  [(DMD)] TJ ET
0.965 0.965 0.965 rg
277.351 354.154 49.662 12.280 re f
0.267 0.267 0.267 rg
277.351 366.058 49.662 0.750 re f
0.965 0.965 0.965 rg
327.013 354.154 59.928 12.280 re f
0.267 0.267 0.267 rg
327.013 366.058 59.928 0.750 re f
0.965 0.965 0.965 rg
386.941 354.154 75.489 12.280 re f
0.267 0.267 0.267 rg
386.941 366.058 75.489 0.750 re f
0.271 0.267 0.267 rg
BT 391.441 356.910 Td /F4 9.8 Tf  [(Control)] TJ ET
0.965 0.965 0.965 rg
462.430 354.154 49.662 12.280 re f
0.267 0.267 0.267 rg
462.430 366.058 49.662 0.750 re f
0.965 0.965 0.965 rg
512.092 354.154 68.408 12.280 re f
0.267 0.267 0.267 rg
512.092 366.058 68.783 0.750 re f
580.125 353.779 0.750 13.030 re f
26.625 353.779 192.066 0.750 re f
26.625 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 343.924 Td /F1 9.8 Tf  [(Variable)] TJ ET
0.267 0.267 0.267 rg
217.941 353.779 59.785 0.750 re f
217.941 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 343.924 Td /F1 9.8 Tf  [(Mean)] TJ ET
0.267 0.267 0.267 rg
276.976 353.779 50.412 0.750 re f
276.976 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 343.924 Td /F1 9.8 Tf  [(SD)] TJ ET
0.267 0.267 0.267 rg
326.638 353.779 60.678 0.750 re f
326.638 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 343.924 Td /F1 9.8 Tf  [(MCID)] TJ ET
0.267 0.267 0.267 rg
386.566 353.779 76.239 0.750 re f
386.566 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 343.924 Td /F1 9.8 Tf  [(Mean)] TJ ET
0.267 0.267 0.267 rg
462.055 353.779 50.412 0.750 re f
462.055 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 343.924 Td /F1 9.8 Tf  [(SD)] TJ ET
0.267 0.267 0.267 rg
511.717 353.779 69.158 0.750 re f
511.717 337.897 0.750 16.631 re f
580.125 337.897 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 343.924 Td /F1 9.8 Tf  [(P)] TJ ET
0.267 0.267 0.267 rg
26.625 337.897 192.066 0.750 re f
26.625 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 328.042 Td /F1 9.8 Tf  [(Age \(years\))] TJ ET
0.267 0.267 0.267 rg
217.941 337.897 59.785 0.750 re f
217.941 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 328.042 Td /F1 9.8 Tf  [(7.9)] TJ ET
0.267 0.267 0.267 rg
276.976 337.897 50.412 0.750 re f
276.976 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 328.042 Td /F1 9.8 Tf  [(2.3)] TJ ET
0.267 0.267 0.267 rg
326.638 337.897 60.678 0.750 re f
326.638 322.016 0.750 16.631 re f
386.566 337.897 76.239 0.750 re f
386.566 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 328.042 Td /F1 9.8 Tf  [(8.7)] TJ ET
0.267 0.267 0.267 rg
462.055 337.897 50.412 0.750 re f
462.055 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 328.042 Td /F1 9.8 Tf  [(2.6)] TJ ET
0.267 0.267 0.267 rg
511.717 337.897 69.158 0.750 re f
511.717 322.016 0.750 16.631 re f
580.125 322.016 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 328.042 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 322.016 192.066 0.750 re f
26.625 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 312.161 Td /F1 9.8 Tf  [(Height \(cm\))] TJ ET
0.267 0.267 0.267 rg
217.941 322.016 59.785 0.750 re f
217.941 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 312.161 Td /F1 9.8 Tf  [(123.0)] TJ ET
0.267 0.267 0.267 rg
276.976 322.016 50.412 0.750 re f
276.976 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 312.161 Td /F1 9.8 Tf  [(14.8)] TJ ET
0.267 0.267 0.267 rg
326.638 322.016 60.678 0.750 re f
326.638 306.135 0.750 16.631 re f
386.566 322.016 76.239 0.750 re f
386.566 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 312.161 Td /F1 9.8 Tf  [(133.4)] TJ ET
0.267 0.267 0.267 rg
462.055 322.016 50.412 0.750 re f
462.055 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 312.161 Td /F1 9.8 Tf  [(16.6)] TJ ET
0.267 0.267 0.267 rg
511.717 322.016 69.158 0.750 re f
511.717 306.135 0.750 16.631 re f
580.125 306.135 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 312.161 Td /F1 9.8 Tf  [(0.0087)] TJ ET
0.267 0.267 0.267 rg
26.625 306.135 192.066 0.750 re f
26.625 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 296.280 Td /F1 9.8 Tf  [(Weight \(kg\))] TJ ET
0.267 0.267 0.267 rg
217.941 306.135 59.785 0.750 re f
217.941 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 296.280 Td /F1 9.8 Tf  [(33.2)] TJ ET
0.267 0.267 0.267 rg
276.976 306.135 50.412 0.750 re f
276.976 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 296.280 Td /F1 9.8 Tf  [(16.6)] TJ ET
0.267 0.267 0.267 rg
326.638 306.135 60.678 0.750 re f
326.638 290.254 0.750 16.631 re f
386.566 306.135 76.239 0.750 re f
386.566 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 296.280 Td /F1 9.8 Tf  [(35.5)] TJ ET
0.267 0.267 0.267 rg
462.055 306.135 50.412 0.750 re f
462.055 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 296.280 Td /F1 9.8 Tf  [(17.2)] TJ ET
0.267 0.267 0.267 rg
511.717 306.135 69.158 0.750 re f
511.717 290.254 0.750 16.631 re f
580.125 290.254 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 296.280 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 290.254 192.066 0.750 re f
26.625 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 280.399 Td /F1 9.8 Tf  [(6MWD \(meters\))] TJ ET
0.267 0.267 0.267 rg
217.941 290.254 59.785 0.750 re f
217.941 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 280.399 Td /F1 9.8 Tf  [(369.5)] TJ ET
0.267 0.267 0.267 rg
276.976 290.254 50.412 0.750 re f
276.976 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 280.399 Td /F1 9.8 Tf  [(79.3)] TJ ET
0.267 0.267 0.267 rg
326.638 290.254 60.678 0.750 re f
326.638 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 280.399 Td /F1 9.8 Tf  [(26.4)] TJ ET
0.267 0.267 0.267 rg
386.566 290.254 76.239 0.750 re f
386.566 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 280.399 Td /F1 9.8 Tf  [(613.3)] TJ ET
0.267 0.267 0.267 rg
462.055 290.254 50.412 0.750 re f
462.055 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 280.399 Td /F1 9.8 Tf  [(73.6)] TJ ET
0.267 0.267 0.267 rg
511.717 290.254 69.158 0.750 re f
511.717 274.372 0.750 16.631 re f
580.125 274.372 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 280.399 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 274.372 192.066 0.750 re f
26.625 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 264.517 Td /F1 9.8 Tf  [(10-meter run/walk velocity \(m/s\))] TJ ET
0.267 0.267 0.267 rg
217.941 274.372 59.785 0.750 re f
217.941 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 264.517 Td /F1 9.8 Tf  [(1.68)] TJ ET
0.267 0.267 0.267 rg
276.976 274.372 50.412 0.750 re f
276.976 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 264.517 Td /F1 9.8 Tf  [(0.56)] TJ ET
0.267 0.267 0.267 rg
326.638 274.372 60.678 0.750 re f
326.638 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 264.517 Td /F1 9.8 Tf  [(0.19)] TJ ET
0.267 0.267 0.267 rg
386.566 274.372 76.239 0.750 re f
386.566 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 264.517 Td /F1 9.8 Tf  [(3.32)] TJ ET
0.267 0.267 0.267 rg
462.055 274.372 50.412 0.750 re f
462.055 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 264.517 Td /F1 9.8 Tf  [(0.36)] TJ ET
0.267 0.267 0.267 rg
511.717 274.372 69.158 0.750 re f
511.717 258.491 0.750 16.631 re f
580.125 258.491 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 264.517 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 258.491 192.066 0.750 re f
26.625 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 248.636 Td /F1 9.8 Tf  [(PedsQL Total Score)] TJ ET
0.267 0.267 0.267 rg
217.941 258.491 59.785 0.750 re f
217.941 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 248.636 Td /F1 9.8 Tf  [(57.3)] TJ ET
0.267 0.267 0.267 rg
276.976 258.491 50.412 0.750 re f
276.976 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 248.636 Td /F1 9.8 Tf  [(10.1)] TJ ET
0.267 0.267 0.267 rg
326.638 258.491 60.678 0.750 re f
326.638 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 248.636 Td /F1 9.8 Tf  [(3.5)] TJ ET
0.267 0.267 0.267 rg
386.566 258.491 76.239 0.750 re f
386.566 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 248.636 Td /F1 9.8 Tf  [(88.8)] TJ ET
0.267 0.267 0.267 rg
462.055 258.491 50.412 0.750 re f
462.055 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 248.636 Td /F1 9.8 Tf  [(10.6)] TJ ET
0.267 0.267 0.267 rg
511.717 258.491 69.158 0.750 re f
511.717 242.610 0.750 16.631 re f
580.125 242.610 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 248.636 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 242.610 192.066 0.750 re f
26.625 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 232.755 Td /F1 9.8 Tf  [(PedsQL Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
217.941 242.610 59.785 0.750 re f
217.941 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 232.755 Td /F1 9.8 Tf  [(48.0)] TJ ET
0.267 0.267 0.267 rg
276.976 242.610 50.412 0.750 re f
276.976 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 232.755 Td /F1 9.8 Tf  [(20.0)] TJ ET
0.267 0.267 0.267 rg
326.638 242.610 60.678 0.750 re f
326.638 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 232.755 Td /F1 9.8 Tf  [(6.7)] TJ ET
0.267 0.267 0.267 rg
386.566 242.610 76.239 0.750 re f
386.566 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 232.755 Td /F1 9.8 Tf  [(92.9)] TJ ET
0.267 0.267 0.267 rg
462.055 242.610 50.412 0.750 re f
462.055 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 232.755 Td /F1 9.8 Tf  [(12.5)] TJ ET
0.267 0.267 0.267 rg
511.717 242.610 69.158 0.750 re f
511.717 226.729 0.750 16.631 re f
580.125 226.729 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 232.755 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 226.729 192.066 0.750 re f
26.625 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 216.874 Td /F1 9.8 Tf  [(PODCI Global Score)] TJ ET
0.267 0.267 0.267 rg
217.941 226.729 59.785 0.750 re f
217.941 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 216.874 Td /F1 9.8 Tf  [(73.8)] TJ ET
0.267 0.267 0.267 rg
276.976 226.729 50.412 0.750 re f
276.976 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 216.874 Td /F1 9.8 Tf  [(11.5)] TJ ET
0.267 0.267 0.267 rg
326.638 226.729 60.678 0.750 re f
326.638 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 216.874 Td /F1 9.8 Tf  [(3.8)] TJ ET
0.267 0.267 0.267 rg
386.566 226.729 76.239 0.750 re f
386.566 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 216.874 Td /F1 9.8 Tf  [(97.9)] TJ ET
0.267 0.267 0.267 rg
462.055 226.729 50.412 0.750 re f
462.055 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 216.874 Td /F1 9.8 Tf  [(3.0)] TJ ET
0.267 0.267 0.267 rg
511.717 226.729 69.158 0.750 re f
511.717 210.847 0.750 16.631 re f
580.125 210.847 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 216.874 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 210.847 192.066 0.750 re f
26.625 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 200.992 Td /F1 9.8 Tf  [(PODCI Transfer / Basic Mobility Score)] TJ ET
0.267 0.267 0.267 rg
217.941 210.847 59.785 0.750 re f
217.941 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 223.191 200.992 Td /F1 9.8 Tf  [(79.5)] TJ ET
0.267 0.267 0.267 rg
276.976 210.847 50.412 0.750 re f
276.976 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 282.226 200.992 Td /F1 9.8 Tf  [(13.5)] TJ ET
0.267 0.267 0.267 rg
326.638 210.847 60.678 0.750 re f
326.638 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 331.888 200.992 Td /F1 9.8 Tf  [(4.5)] TJ ET
0.267 0.267 0.267 rg
386.566 210.847 76.239 0.750 re f
386.566 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.816 200.992 Td /F1 9.8 Tf  [(100.3)] TJ ET
0.267 0.267 0.267 rg
462.055 210.847 50.412 0.750 re f
462.055 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 467.305 200.992 Td /F1 9.8 Tf  [(1.6)] TJ ET
0.267 0.267 0.267 rg
511.717 210.847 69.158 0.750 re f
511.717 194.966 0.750 16.631 re f
580.125 194.966 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 516.967 200.992 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 194.966 192.066 0.750 re f
26.625 171.454 192.066 0.750 re f
26.625 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 185.111 Td /F1 9.8 Tf  [(PODCI Sports and Physical Function )] TJ ET
BT 31.875 177.480 Td /F1 9.8 Tf  [(Score)] TJ ET
0.267 0.267 0.267 rg
217.941 194.966 59.785 0.750 re f
217.941 171.454 59.785 0.750 re f
217.941 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 223.191 185.111 Td /F1 9.8 Tf  [(55.0)] TJ ET
0.267 0.267 0.267 rg
276.976 194.966 50.412 0.750 re f
276.976 171.454 50.412 0.750 re f
276.976 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 282.226 185.111 Td /F1 9.8 Tf  [(21.2)] TJ ET
0.267 0.267 0.267 rg
326.638 194.966 60.678 0.750 re f
326.638 171.454 60.678 0.750 re f
326.638 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 331.888 185.111 Td /F1 9.8 Tf  [(7.1)] TJ ET
0.267 0.267 0.267 rg
386.566 194.966 76.239 0.750 re f
386.566 171.454 76.239 0.750 re f
386.566 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 391.816 185.111 Td /F1 9.8 Tf  [(95.8)] TJ ET
0.267 0.267 0.267 rg
462.055 194.966 50.412 0.750 re f
462.055 171.454 50.412 0.750 re f
462.055 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 467.305 185.111 Td /F1 9.8 Tf  [(5.8)] TJ ET
0.267 0.267 0.267 rg
511.717 194.966 69.158 0.750 re f
511.717 171.454 69.158 0.750 re f
511.717 171.454 0.750 24.263 re f
580.125 171.454 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 516.967 185.111 Td /F1 9.8 Tf  [(0.0001)] TJ ET
BT 26.250 116.555 Td /F1 9.8 Tf  [(Correlation are shown between the 6MWD and PROs \(Table 2\) and the 10 meter run/walk velocity and PRO measures \(Table )] TJ ET
BT 26.250 104.650 Td /F1 9.8 Tf  [(3\). In boys with DMD, 6MWD was strongly correlated with PODCI measures, with the transfer and basic mobility scale showing )] TJ ET
BT 26.250 92.745 Td /F1 9.8 Tf  [(the strongest relationship \(r=0.79\). In addition, the 10 meter run/walk velocity was also strongly correlated with the PODCI )] TJ ET
BT 26.250 80.841 Td /F1 9.8 Tf  [(measures, including the transfer and basic mobility scale \(r=0.76\). In the DMD group 6MWD and 10 meter run/walk velocity was )] TJ ET
BT 26.250 68.936 Td /F1 9.8 Tf  [(weakly correlated with PedsQL items. In controls, PedsQL physical function and PODCI global score showed weak correlations )] TJ ET
BT 26.250 57.031 Td /F1 9.8 Tf  [(with ambulatory measures. Across the full range of both 6MWD and HrQOL measures with the groups combined, 6MWD )] TJ ET
BT 26.250 45.126 Td /F1 9.8 Tf  [(demonstrated strong to very strong correlations with both PODCI and PedsQL measures \(r=0.85-0.88 and r=0.71, respectively\). )] TJ ET
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q
15.000 -18.928 577.500 795.928 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Similarly, across the full range of both 10 meter run/walk velocities and PROs, the 10 meter run/walk velocity demonstrated very )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(strong correlations with both PODCI and PedsQL measures \(r=0.78-0.82 and r=0.71-0.72, respectively\).)] TJ ET
q
26.250 731.954 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 734.701 Td /F1 9.8 Tf  [(Table 2: Pearson�s Correlation of 6MWD and PedsQL and PODCI Measures)] TJ ET
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1.000 1.000 1.000 rg
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0.965 0.965 0.965 rg
27.000 711.424 232.148 12.280 re f
0.267 0.267 0.267 rg
26.625 723.329 232.523 0.750 re f
26.625 711.049 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 31.500 714.180 Td /F4 9.8 Tf  [(6MWD vs. Person-Reported Measures)] TJ ET
0.965 0.965 0.965 rg
259.148 711.424 59.308 12.280 re f
0.267 0.267 0.267 rg
259.148 723.329 59.308 0.750 re f
0.271 0.267 0.267 rg
BT 263.648 714.180 Td /F4 9.8 Tf  [(DMD)] TJ ET
0.965 0.965 0.965 rg
318.456 711.424 82.994 12.280 re f
0.267 0.267 0.267 rg
318.456 723.329 82.994 0.750 re f
0.271 0.267 0.267 rg
BT 322.956 714.180 Td /F4 9.8 Tf  [(Control)] TJ ET
0.965 0.965 0.965 rg
401.450 711.424 179.050 12.280 re f
0.267 0.267 0.267 rg
401.450 723.329 179.425 0.750 re f
580.125 711.049 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 405.950 714.180 Td /F4 9.8 Tf  [(Combined\(Full Range\))] TJ ET
0.267 0.267 0.267 rg
26.625 711.049 232.898 0.750 re f
26.625 695.168 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 701.194 Td /F1 9.8 Tf  [(PedsQL Total Score)] TJ ET
0.267 0.267 0.267 rg
258.773 711.049 60.058 0.750 re f
258.773 695.168 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 264.023 701.194 Td /F1 9.8 Tf  [(0.21)] TJ ET
0.267 0.267 0.267 rg
318.081 711.049 83.744 0.750 re f
318.081 695.168 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 323.331 701.194 Td /F1 9.8 Tf  [(-0.02)] TJ ET
0.267 0.267 0.267 rg
401.075 711.049 179.800 0.750 re f
401.075 695.168 0.750 16.631 re f
580.125 695.168 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 406.325 701.194 Td /F1 9.8 Tf  [(0.71)] TJ ET
0.267 0.267 0.267 rg
26.625 695.168 232.898 0.750 re f
26.625 679.287 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 685.313 Td /F1 9.8 Tf  [(PedsQL Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
258.773 695.168 60.058 0.750 re f
258.773 679.287 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 264.023 685.313 Td /F1 9.8 Tf  [(0.18)] TJ ET
0.267 0.267 0.267 rg
318.081 695.168 83.744 0.750 re f
318.081 679.287 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 323.331 685.313 Td /F1 9.8 Tf  [(0.19)] TJ ET
0.267 0.267 0.267 rg
401.075 695.168 179.800 0.750 re f
401.075 679.287 0.750 16.631 re f
580.125 679.287 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 406.325 685.313 Td /F1 9.8 Tf  [(0.71)] TJ ET
0.267 0.267 0.267 rg
26.625 679.287 232.898 0.750 re f
26.625 663.406 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 669.432 Td /F1 9.8 Tf  [(PODCI Global Score)] TJ ET
0.267 0.267 0.267 rg
258.773 679.287 60.058 0.750 re f
258.773 663.406 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 264.023 669.432 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.267 0.267 0.267 rg
318.081 679.287 83.744 0.750 re f
318.081 663.406 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 323.331 669.432 Td /F1 9.8 Tf  [(0.28)] TJ ET
0.267 0.267 0.267 rg
401.075 679.287 179.800 0.750 re f
401.075 663.406 0.750 16.631 re f
580.125 663.406 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 406.325 669.432 Td /F1 9.8 Tf  [(0.88)] TJ ET
0.267 0.267 0.267 rg
26.625 663.406 232.898 0.750 re f
26.625 647.524 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 653.551 Td /F1 9.8 Tf  [(PODCI Transfer / Basic Mobility Score)] TJ ET
0.267 0.267 0.267 rg
258.773 663.406 60.058 0.750 re f
258.773 647.524 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 264.023 653.551 Td /F1 9.8 Tf  [(0.79)] TJ ET
0.267 0.267 0.267 rg
318.081 663.406 83.744 0.750 re f
318.081 647.524 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 323.331 653.551 Td /F1 9.8 Tf  [(0.01)] TJ ET
0.267 0.267 0.267 rg
401.075 663.406 179.800 0.750 re f
401.075 647.524 0.750 16.631 re f
580.125 647.524 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 406.325 653.551 Td /F1 9.8 Tf  [(0.86)] TJ ET
0.267 0.267 0.267 rg
26.625 647.524 232.898 0.750 re f
26.625 631.643 232.898 0.750 re f
26.625 631.643 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 637.669 Td /F1 9.8 Tf  [(PODCI Sports and Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
258.773 647.524 60.058 0.750 re f
258.773 631.643 60.058 0.750 re f
258.773 631.643 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 264.023 637.669 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.267 0.267 0.267 rg
318.081 647.524 83.744 0.750 re f
318.081 631.643 83.744 0.750 re f
318.081 631.643 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 323.331 637.669 Td /F1 9.8 Tf  [(0.12)] TJ ET
0.267 0.267 0.267 rg
401.075 647.524 179.800 0.750 re f
401.075 631.643 179.800 0.750 re f
401.075 631.643 0.750 16.631 re f
580.125 631.643 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 406.325 637.669 Td /F1 9.8 Tf  [(0.85)] TJ ET
q
26.250 572.532 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 575.279 Td /F1 9.8 Tf  [(Table 3: Pearson�s correlation of 10-meter run/walk velocity and PedsQL and PODCI measures)] TJ ET
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0.271 0.267 0.267 rg
BT 291.625 554.758 Td /F4 9.8 Tf  [(DMD)] TJ ET
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341.787 540.097 76.492 24.185 re f
0.267 0.267 0.267 rg
341.787 563.907 76.492 0.750 re f
0.271 0.267 0.267 rg
BT 346.287 554.758 Td /F4 9.8 Tf  [(Control)] TJ ET
0.965 0.965 0.965 rg
418.279 540.097 162.221 24.185 re f
0.267 0.267 0.267 rg
418.279 563.907 162.596 0.750 re f
580.125 539.722 0.750 24.935 re f
0.271 0.267 0.267 rg
BT 422.779 554.758 Td /F4 9.8 Tf  [(Combined\(Full Range\))] TJ ET
0.267 0.267 0.267 rg
26.625 539.722 260.875 0.750 re f
26.625 523.841 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 529.867 Td /F1 9.8 Tf  [(PedsQL Total Score)] TJ ET
0.267 0.267 0.267 rg
286.750 539.722 55.412 0.750 re f
286.750 523.841 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 292.000 529.867 Td /F1 9.8 Tf  [(0.15)] TJ ET
0.267 0.267 0.267 rg
341.412 539.722 77.242 0.750 re f
341.412 523.841 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 346.662 529.867 Td /F1 9.8 Tf  [(0.14)] TJ ET
0.267 0.267 0.267 rg
417.904 539.722 162.971 0.750 re f
417.904 523.841 0.750 16.631 re f
580.125 523.841 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 423.154 529.867 Td /F1 9.8 Tf  [(0.71)] TJ ET
0.267 0.267 0.267 rg
26.625 523.841 260.875 0.750 re f
26.625 507.960 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 513.986 Td /F1 9.8 Tf  [(PedsQL Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
286.750 523.841 55.412 0.750 re f
286.750 507.960 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 292.000 513.986 Td /F1 9.8 Tf  [(0.21)] TJ ET
0.267 0.267 0.267 rg
341.412 523.841 77.242 0.750 re f
341.412 507.960 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 346.662 513.986 Td /F1 9.8 Tf  [(0.23)] TJ ET
0.267 0.267 0.267 rg
417.904 523.841 162.971 0.750 re f
417.904 507.960 0.750 16.631 re f
580.125 507.960 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 423.154 513.986 Td /F1 9.8 Tf  [(0.72)] TJ ET
0.267 0.267 0.267 rg
26.625 507.960 260.875 0.750 re f
26.625 492.079 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 498.105 Td /F1 9.8 Tf  [(PODCI Global Score)] TJ ET
0.267 0.267 0.267 rg
286.750 507.960 55.412 0.750 re f
286.750 492.079 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 292.000 498.105 Td /F1 9.8 Tf  [(0.62)] TJ ET
0.267 0.267 0.267 rg
341.412 507.960 77.242 0.750 re f
341.412 492.079 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 346.662 498.105 Td /F1 9.8 Tf  [(0.28)] TJ ET
0.267 0.267 0.267 rg
417.904 507.960 162.971 0.750 re f
417.904 492.079 0.750 16.631 re f
580.125 492.079 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 423.154 498.105 Td /F1 9.8 Tf  [(0.82)] TJ ET
0.267 0.267 0.267 rg
26.625 492.079 260.875 0.750 re f
26.625 476.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 482.224 Td /F1 9.8 Tf  [(PODCI Transfer / Basic Mobility Score)] TJ ET
0.267 0.267 0.267 rg
286.750 492.079 55.412 0.750 re f
286.750 476.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 292.000 482.224 Td /F1 9.8 Tf  [(0.76)] TJ ET
0.267 0.267 0.267 rg
341.412 492.079 77.242 0.750 re f
341.412 476.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 346.662 482.224 Td /F1 9.8 Tf  [(-0.05)] TJ ET
0.267 0.267 0.267 rg
417.904 492.079 162.971 0.750 re f
417.904 476.197 0.750 16.631 re f
580.125 476.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 423.154 482.224 Td /F1 9.8 Tf  [(0.78)] TJ ET
0.267 0.267 0.267 rg
26.625 476.197 260.875 0.750 re f
26.625 460.316 260.875 0.750 re f
26.625 460.316 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 466.342 Td /F1 9.8 Tf  [(PODCI Sports and Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
286.750 476.197 55.412 0.750 re f
286.750 460.316 55.412 0.750 re f
286.750 460.316 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 292.000 466.342 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
341.412 476.197 77.242 0.750 re f
341.412 460.316 77.242 0.750 re f
341.412 460.316 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 346.662 466.342 Td /F1 9.8 Tf  [(0.29)] TJ ET
0.267 0.267 0.267 rg
417.904 476.197 162.971 0.750 re f
417.904 460.316 162.971 0.750 re f
417.904 460.316 0.750 16.631 re f
580.125 460.316 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 423.154 466.342 Td /F1 9.8 Tf  [(0.82)] TJ ET
BT 26.250 405.417 Td /F1 9.8 Tf  [(The distribution of 6MWD versus PRO measures are shown for PODCI transfer and basic mobility scale scores \(Figure 1a\), )] TJ ET
BT 26.250 393.513 Td /F1 9.8 Tf  [(PedsQL physical function scores \(Figure 1b\), PODCI global scores \(Figure 2a\) and PedsQL total scores \(Figure 2b\). The )] TJ ET
BT 26.250 381.608 Td /F1 9.8 Tf  [(distribution of 10 meter run/walk velocities versus PRO measures are shown for PODCI transfer and basic mobility scale scores )] TJ ET
BT 26.250 369.703 Td /F1 9.8 Tf  [(\(Figure 3a\), PedsQL physical function scores \(Figure 3b\), PODCI global scores \(Figure 4a\) and PedsQL total scores \(Figure 4b\).)] TJ ET
0.965 0.965 0.965 rg
26.250 172.322 555.000 187.500 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 359.822 m 581.250 359.822 l 581.250 359.072 l 26.250 359.072 l  f
26.250 172.322 m 581.250 172.322 l 581.250 173.072 l 26.250 173.072 l  f
q
225.000 0 0 168.000 35.250 182.072 cm /I3 Do
Q 
q
35.250 176.072 537.000 0.000 re W n
Q
0.965 0.965 0.965 rg
26.250 -18.928 555.000 183.750 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 164.822 m 581.250 164.822 l 581.250 164.072 l 26.250 164.072 l  f
q
225.000 0 0 168.000 35.250 -12.928 cm /I4 Do
Q 
q
35.250 -18.928 537.000 0.000 re W n
Q
Q
q
15.000 -18.928 577.500 795.928 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Similarly, across the full range of both 10 meter run/walk velocities and PROs, the 10 meter run/walk velocity demonstrated very )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(strong correlations with both PODCI and PedsQL measures \(r=0.78-0.82 and r=0.71-0.72, respectively\).)] TJ ET
q
26.250 731.954 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 734.701 Td /F1 9.8 Tf  [(Table 2: Pearson�s Correlation of 6MWD and PedsQL and PODCI Measures)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 631.268 555.000 93.186 re f
0.965 0.965 0.965 rg
27.000 711.424 232.148 12.280 re f
0.267 0.267 0.267 rg
26.625 723.329 232.523 0.750 re f
26.625 711.049 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 31.500 714.180 Td /F4 9.8 Tf  [(6MWD vs. Person-Reported Measures)] TJ ET
0.965 0.965 0.965 rg
259.148 711.424 59.308 12.280 re f
0.267 0.267 0.267 rg
259.148 723.329 59.308 0.750 re f
0.271 0.267 0.267 rg
BT 263.648 714.180 Td /F4 9.8 Tf  [(DMD)] TJ ET
0.965 0.965 0.965 rg
318.456 711.424 82.994 12.280 re f
0.267 0.267 0.267 rg
318.456 723.329 82.994 0.750 re f
0.271 0.267 0.267 rg
BT 322.956 714.180 Td /F4 9.8 Tf  [(Control)] TJ ET
0.965 0.965 0.965 rg
401.450 711.424 179.050 12.280 re f
0.267 0.267 0.267 rg
401.450 723.329 179.425 0.750 re f
580.125 711.049 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 405.950 714.180 Td /F4 9.8 Tf  [(Combined\(Full Range\))] TJ ET
0.267 0.267 0.267 rg
26.625 711.049 232.898 0.750 re f
26.625 695.168 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 701.194 Td /F1 9.8 Tf  [(PedsQL Total Score)] TJ ET
0.267 0.267 0.267 rg
258.773 711.049 60.058 0.750 re f
258.773 695.168 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 264.023 701.194 Td /F1 9.8 Tf  [(0.21)] TJ ET
0.267 0.267 0.267 rg
318.081 711.049 83.744 0.750 re f
318.081 695.168 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 323.331 701.194 Td /F1 9.8 Tf  [(-0.02)] TJ ET
0.267 0.267 0.267 rg
401.075 711.049 179.800 0.750 re f
401.075 695.168 0.750 16.631 re f
580.125 695.168 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 406.325 701.194 Td /F1 9.8 Tf  [(0.71)] TJ ET
0.267 0.267 0.267 rg
26.625 695.168 232.898 0.750 re f
26.625 679.287 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 685.313 Td /F1 9.8 Tf  [(PedsQL Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
258.773 695.168 60.058 0.750 re f
258.773 679.287 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 264.023 685.313 Td /F1 9.8 Tf  [(0.18)] TJ ET
0.267 0.267 0.267 rg
318.081 695.168 83.744 0.750 re f
318.081 679.287 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 323.331 685.313 Td /F1 9.8 Tf  [(0.19)] TJ ET
0.267 0.267 0.267 rg
401.075 695.168 179.800 0.750 re f
401.075 679.287 0.750 16.631 re f
580.125 679.287 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 406.325 685.313 Td /F1 9.8 Tf  [(0.71)] TJ ET
0.267 0.267 0.267 rg
26.625 679.287 232.898 0.750 re f
26.625 663.406 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 669.432 Td /F1 9.8 Tf  [(PODCI Global Score)] TJ ET
0.267 0.267 0.267 rg
258.773 679.287 60.058 0.750 re f
258.773 663.406 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 264.023 669.432 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.267 0.267 0.267 rg
318.081 679.287 83.744 0.750 re f
318.081 663.406 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 323.331 669.432 Td /F1 9.8 Tf  [(0.28)] TJ ET
0.267 0.267 0.267 rg
401.075 679.287 179.800 0.750 re f
401.075 663.406 0.750 16.631 re f
580.125 663.406 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 406.325 669.432 Td /F1 9.8 Tf  [(0.88)] TJ ET
0.267 0.267 0.267 rg
26.625 663.406 232.898 0.750 re f
26.625 647.524 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 653.551 Td /F1 9.8 Tf  [(PODCI Transfer / Basic Mobility Score)] TJ ET
0.267 0.267 0.267 rg
258.773 663.406 60.058 0.750 re f
258.773 647.524 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 264.023 653.551 Td /F1 9.8 Tf  [(0.79)] TJ ET
0.267 0.267 0.267 rg
318.081 663.406 83.744 0.750 re f
318.081 647.524 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 323.331 653.551 Td /F1 9.8 Tf  [(0.01)] TJ ET
0.267 0.267 0.267 rg
401.075 663.406 179.800 0.750 re f
401.075 647.524 0.750 16.631 re f
580.125 647.524 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 406.325 653.551 Td /F1 9.8 Tf  [(0.86)] TJ ET
0.267 0.267 0.267 rg
26.625 647.524 232.898 0.750 re f
26.625 631.643 232.898 0.750 re f
26.625 631.643 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 637.669 Td /F1 9.8 Tf  [(PODCI Sports and Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
258.773 647.524 60.058 0.750 re f
258.773 631.643 60.058 0.750 re f
258.773 631.643 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 264.023 637.669 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.267 0.267 0.267 rg
318.081 647.524 83.744 0.750 re f
318.081 631.643 83.744 0.750 re f
318.081 631.643 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 323.331 637.669 Td /F1 9.8 Tf  [(0.12)] TJ ET
0.267 0.267 0.267 rg
401.075 647.524 179.800 0.750 re f
401.075 631.643 179.800 0.750 re f
401.075 631.643 0.750 16.631 re f
580.125 631.643 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 406.325 637.669 Td /F1 9.8 Tf  [(0.85)] TJ ET
q
26.250 572.532 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 575.279 Td /F1 9.8 Tf  [(Table 3: Pearson�s correlation of 10-meter run/walk velocity and PedsQL and PODCI measures)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 459.941 555.000 105.091 re f
0.965 0.965 0.965 rg
27.000 540.097 260.125 24.185 re f
0.267 0.267 0.267 rg
26.625 563.907 260.500 0.750 re f
26.625 539.722 0.750 24.935 re f
0.271 0.267 0.267 rg
BT 31.500 554.758 Td /F4 9.8 Tf  [(10-meter run/walk velocity vs. person-reported )] TJ ET
BT 31.500 542.853 Td /F4 9.8 Tf  [(measures)] TJ ET
0.965 0.965 0.965 rg
287.125 540.097 54.662 24.185 re f
0.267 0.267 0.267 rg
287.125 563.907 54.662 0.750 re f
0.271 0.267 0.267 rg
BT 291.625 554.758 Td /F4 9.8 Tf  [(DMD)] TJ ET
0.965 0.965 0.965 rg
341.787 540.097 76.492 24.185 re f
0.267 0.267 0.267 rg
341.787 563.907 76.492 0.750 re f
0.271 0.267 0.267 rg
BT 346.287 554.758 Td /F4 9.8 Tf  [(Control)] TJ ET
0.965 0.965 0.965 rg
418.279 540.097 162.221 24.185 re f
0.267 0.267 0.267 rg
418.279 563.907 162.596 0.750 re f
580.125 539.722 0.750 24.935 re f
0.271 0.267 0.267 rg
BT 422.779 554.758 Td /F4 9.8 Tf  [(Combined\(Full Range\))] TJ ET
0.267 0.267 0.267 rg
26.625 539.722 260.875 0.750 re f
26.625 523.841 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 529.867 Td /F1 9.8 Tf  [(PedsQL Total Score)] TJ ET
0.267 0.267 0.267 rg
286.750 539.722 55.412 0.750 re f
286.750 523.841 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 292.000 529.867 Td /F1 9.8 Tf  [(0.15)] TJ ET
0.267 0.267 0.267 rg
341.412 539.722 77.242 0.750 re f
341.412 523.841 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 346.662 529.867 Td /F1 9.8 Tf  [(0.14)] TJ ET
0.267 0.267 0.267 rg
417.904 539.722 162.971 0.750 re f
417.904 523.841 0.750 16.631 re f
580.125 523.841 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 423.154 529.867 Td /F1 9.8 Tf  [(0.71)] TJ ET
0.267 0.267 0.267 rg
26.625 523.841 260.875 0.750 re f
26.625 507.960 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 513.986 Td /F1 9.8 Tf  [(PedsQL Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
286.750 523.841 55.412 0.750 re f
286.750 507.960 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 292.000 513.986 Td /F1 9.8 Tf  [(0.21)] TJ ET
0.267 0.267 0.267 rg
341.412 523.841 77.242 0.750 re f
341.412 507.960 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 346.662 513.986 Td /F1 9.8 Tf  [(0.23)] TJ ET
0.267 0.267 0.267 rg
417.904 523.841 162.971 0.750 re f
417.904 507.960 0.750 16.631 re f
580.125 507.960 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 423.154 513.986 Td /F1 9.8 Tf  [(0.72)] TJ ET
0.267 0.267 0.267 rg
26.625 507.960 260.875 0.750 re f
26.625 492.079 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 498.105 Td /F1 9.8 Tf  [(PODCI Global Score)] TJ ET
0.267 0.267 0.267 rg
286.750 507.960 55.412 0.750 re f
286.750 492.079 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 292.000 498.105 Td /F1 9.8 Tf  [(0.62)] TJ ET
0.267 0.267 0.267 rg
341.412 507.960 77.242 0.750 re f
341.412 492.079 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 346.662 498.105 Td /F1 9.8 Tf  [(0.28)] TJ ET
0.267 0.267 0.267 rg
417.904 507.960 162.971 0.750 re f
417.904 492.079 0.750 16.631 re f
580.125 492.079 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 423.154 498.105 Td /F1 9.8 Tf  [(0.82)] TJ ET
0.267 0.267 0.267 rg
26.625 492.079 260.875 0.750 re f
26.625 476.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 482.224 Td /F1 9.8 Tf  [(PODCI Transfer / Basic Mobility Score)] TJ ET
0.267 0.267 0.267 rg
286.750 492.079 55.412 0.750 re f
286.750 476.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 292.000 482.224 Td /F1 9.8 Tf  [(0.76)] TJ ET
0.267 0.267 0.267 rg
341.412 492.079 77.242 0.750 re f
341.412 476.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 346.662 482.224 Td /F1 9.8 Tf  [(-0.05)] TJ ET
0.267 0.267 0.267 rg
417.904 492.079 162.971 0.750 re f
417.904 476.197 0.750 16.631 re f
580.125 476.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 423.154 482.224 Td /F1 9.8 Tf  [(0.78)] TJ ET
0.267 0.267 0.267 rg
26.625 476.197 260.875 0.750 re f
26.625 460.316 260.875 0.750 re f
26.625 460.316 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 466.342 Td /F1 9.8 Tf  [(PODCI Sports and Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
286.750 476.197 55.412 0.750 re f
286.750 460.316 55.412 0.750 re f
286.750 460.316 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 292.000 466.342 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
341.412 476.197 77.242 0.750 re f
341.412 460.316 77.242 0.750 re f
341.412 460.316 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 346.662 466.342 Td /F1 9.8 Tf  [(0.29)] TJ ET
0.267 0.267 0.267 rg
417.904 476.197 162.971 0.750 re f
417.904 460.316 162.971 0.750 re f
417.904 460.316 0.750 16.631 re f
580.125 460.316 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 423.154 466.342 Td /F1 9.8 Tf  [(0.82)] TJ ET
BT 26.250 405.417 Td /F1 9.8 Tf  [(The distribution of 6MWD versus PRO measures are shown for PODCI transfer and basic mobility scale scores \(Figure 1a\), )] TJ ET
BT 26.250 393.513 Td /F1 9.8 Tf  [(PedsQL physical function scores \(Figure 1b\), PODCI global scores \(Figure 2a\) and PedsQL total scores \(Figure 2b\). The )] TJ ET
BT 26.250 381.608 Td /F1 9.8 Tf  [(distribution of 10 meter run/walk velocities versus PRO measures are shown for PODCI transfer and basic mobility scale scores )] TJ ET
BT 26.250 369.703 Td /F1 9.8 Tf  [(\(Figure 3a\), PedsQL physical function scores \(Figure 3b\), PODCI global scores \(Figure 4a\) and PedsQL total scores \(Figure 4b\).)] TJ ET
0.965 0.965 0.965 rg
26.250 172.322 555.000 187.500 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 359.822 m 581.250 359.822 l 581.250 359.072 l 26.250 359.072 l  f
26.250 172.322 m 581.250 172.322 l 581.250 173.072 l 26.250 173.072 l  f
q
225.000 0 0 168.000 35.250 182.072 cm /I3 Do
Q 
q
35.250 176.072 537.000 0.000 re W n
Q
0.965 0.965 0.965 rg
26.250 -18.928 555.000 183.750 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 164.822 m 581.250 164.822 l 581.250 164.072 l 26.250 164.072 l  f
q
225.000 0 0 168.000 35.250 -12.928 cm /I4 Do
Q 
q
35.250 -18.928 537.000 0.000 re W n
Q
Q
q
15.000 -18.928 577.500 795.928 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Similarly, across the full range of both 10 meter run/walk velocities and PROs, the 10 meter run/walk velocity demonstrated very )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(strong correlations with both PODCI and PedsQL measures \(r=0.78-0.82 and r=0.71-0.72, respectively\).)] TJ ET
q
26.250 731.954 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 734.701 Td /F1 9.8 Tf  [(Table 2: Pearson�s Correlation of 6MWD and PedsQL and PODCI Measures)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 631.268 555.000 93.186 re f
0.965 0.965 0.965 rg
27.000 711.424 232.148 12.280 re f
0.267 0.267 0.267 rg
26.625 723.329 232.523 0.750 re f
26.625 711.049 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 31.500 714.180 Td /F4 9.8 Tf  [(6MWD vs. Person-Reported Measures)] TJ ET
0.965 0.965 0.965 rg
259.148 711.424 59.308 12.280 re f
0.267 0.267 0.267 rg
259.148 723.329 59.308 0.750 re f
0.271 0.267 0.267 rg
BT 263.648 714.180 Td /F4 9.8 Tf  [(DMD)] TJ ET
0.965 0.965 0.965 rg
318.456 711.424 82.994 12.280 re f
0.267 0.267 0.267 rg
318.456 723.329 82.994 0.750 re f
0.271 0.267 0.267 rg
BT 322.956 714.180 Td /F4 9.8 Tf  [(Control)] TJ ET
0.965 0.965 0.965 rg
401.450 711.424 179.050 12.280 re f
0.267 0.267 0.267 rg
401.450 723.329 179.425 0.750 re f
580.125 711.049 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 405.950 714.180 Td /F4 9.8 Tf  [(Combined\(Full Range\))] TJ ET
0.267 0.267 0.267 rg
26.625 711.049 232.898 0.750 re f
26.625 695.168 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 701.194 Td /F1 9.8 Tf  [(PedsQL Total Score)] TJ ET
0.267 0.267 0.267 rg
258.773 711.049 60.058 0.750 re f
258.773 695.168 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 264.023 701.194 Td /F1 9.8 Tf  [(0.21)] TJ ET
0.267 0.267 0.267 rg
318.081 711.049 83.744 0.750 re f
318.081 695.168 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 323.331 701.194 Td /F1 9.8 Tf  [(-0.02)] TJ ET
0.267 0.267 0.267 rg
401.075 711.049 179.800 0.750 re f
401.075 695.168 0.750 16.631 re f
580.125 695.168 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 406.325 701.194 Td /F1 9.8 Tf  [(0.71)] TJ ET
0.267 0.267 0.267 rg
26.625 695.168 232.898 0.750 re f
26.625 679.287 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 685.313 Td /F1 9.8 Tf  [(PedsQL Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
258.773 695.168 60.058 0.750 re f
258.773 679.287 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 264.023 685.313 Td /F1 9.8 Tf  [(0.18)] TJ ET
0.267 0.267 0.267 rg
318.081 695.168 83.744 0.750 re f
318.081 679.287 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 323.331 685.313 Td /F1 9.8 Tf  [(0.19)] TJ ET
0.267 0.267 0.267 rg
401.075 695.168 179.800 0.750 re f
401.075 679.287 0.750 16.631 re f
580.125 679.287 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 406.325 685.313 Td /F1 9.8 Tf  [(0.71)] TJ ET
0.267 0.267 0.267 rg
26.625 679.287 232.898 0.750 re f
26.625 663.406 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 669.432 Td /F1 9.8 Tf  [(PODCI Global Score)] TJ ET
0.267 0.267 0.267 rg
258.773 679.287 60.058 0.750 re f
258.773 663.406 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 264.023 669.432 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.267 0.267 0.267 rg
318.081 679.287 83.744 0.750 re f
318.081 663.406 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 323.331 669.432 Td /F1 9.8 Tf  [(0.28)] TJ ET
0.267 0.267 0.267 rg
401.075 679.287 179.800 0.750 re f
401.075 663.406 0.750 16.631 re f
580.125 663.406 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 406.325 669.432 Td /F1 9.8 Tf  [(0.88)] TJ ET
0.267 0.267 0.267 rg
26.625 663.406 232.898 0.750 re f
26.625 647.524 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 653.551 Td /F1 9.8 Tf  [(PODCI Transfer / Basic Mobility Score)] TJ ET
0.267 0.267 0.267 rg
258.773 663.406 60.058 0.750 re f
258.773 647.524 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 264.023 653.551 Td /F1 9.8 Tf  [(0.79)] TJ ET
0.267 0.267 0.267 rg
318.081 663.406 83.744 0.750 re f
318.081 647.524 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 323.331 653.551 Td /F1 9.8 Tf  [(0.01)] TJ ET
0.267 0.267 0.267 rg
401.075 663.406 179.800 0.750 re f
401.075 647.524 0.750 16.631 re f
580.125 647.524 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 406.325 653.551 Td /F1 9.8 Tf  [(0.86)] TJ ET
0.267 0.267 0.267 rg
26.625 647.524 232.898 0.750 re f
26.625 631.643 232.898 0.750 re f
26.625 631.643 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 637.669 Td /F1 9.8 Tf  [(PODCI Sports and Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
258.773 647.524 60.058 0.750 re f
258.773 631.643 60.058 0.750 re f
258.773 631.643 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 264.023 637.669 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.267 0.267 0.267 rg
318.081 647.524 83.744 0.750 re f
318.081 631.643 83.744 0.750 re f
318.081 631.643 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 323.331 637.669 Td /F1 9.8 Tf  [(0.12)] TJ ET
0.267 0.267 0.267 rg
401.075 647.524 179.800 0.750 re f
401.075 631.643 179.800 0.750 re f
401.075 631.643 0.750 16.631 re f
580.125 631.643 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 406.325 637.669 Td /F1 9.8 Tf  [(0.85)] TJ ET
q
26.250 572.532 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 575.279 Td /F1 9.8 Tf  [(Table 3: Pearson�s correlation of 10-meter run/walk velocity and PedsQL and PODCI measures)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 459.941 555.000 105.091 re f
0.965 0.965 0.965 rg
27.000 540.097 260.125 24.185 re f
0.267 0.267 0.267 rg
26.625 563.907 260.500 0.750 re f
26.625 539.722 0.750 24.935 re f
0.271 0.267 0.267 rg
BT 31.500 554.758 Td /F4 9.8 Tf  [(10-meter run/walk velocity vs. person-reported )] TJ ET
BT 31.500 542.853 Td /F4 9.8 Tf  [(measures)] TJ ET
0.965 0.965 0.965 rg
287.125 540.097 54.662 24.185 re f
0.267 0.267 0.267 rg
287.125 563.907 54.662 0.750 re f
0.271 0.267 0.267 rg
BT 291.625 554.758 Td /F4 9.8 Tf  [(DMD)] TJ ET
0.965 0.965 0.965 rg
341.787 540.097 76.492 24.185 re f
0.267 0.267 0.267 rg
341.787 563.907 76.492 0.750 re f
0.271 0.267 0.267 rg
BT 346.287 554.758 Td /F4 9.8 Tf  [(Control)] TJ ET
0.965 0.965 0.965 rg
418.279 540.097 162.221 24.185 re f
0.267 0.267 0.267 rg
418.279 563.907 162.596 0.750 re f
580.125 539.722 0.750 24.935 re f
0.271 0.267 0.267 rg
BT 422.779 554.758 Td /F4 9.8 Tf  [(Combined\(Full Range\))] TJ ET
0.267 0.267 0.267 rg
26.625 539.722 260.875 0.750 re f
26.625 523.841 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 529.867 Td /F1 9.8 Tf  [(PedsQL Total Score)] TJ ET
0.267 0.267 0.267 rg
286.750 539.722 55.412 0.750 re f
286.750 523.841 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 292.000 529.867 Td /F1 9.8 Tf  [(0.15)] TJ ET
0.267 0.267 0.267 rg
341.412 539.722 77.242 0.750 re f
341.412 523.841 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 346.662 529.867 Td /F1 9.8 Tf  [(0.14)] TJ ET
0.267 0.267 0.267 rg
417.904 539.722 162.971 0.750 re f
417.904 523.841 0.750 16.631 re f
580.125 523.841 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 423.154 529.867 Td /F1 9.8 Tf  [(0.71)] TJ ET
0.267 0.267 0.267 rg
26.625 523.841 260.875 0.750 re f
26.625 507.960 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 513.986 Td /F1 9.8 Tf  [(PedsQL Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
286.750 523.841 55.412 0.750 re f
286.750 507.960 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 292.000 513.986 Td /F1 9.8 Tf  [(0.21)] TJ ET
0.267 0.267 0.267 rg
341.412 523.841 77.242 0.750 re f
341.412 507.960 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 346.662 513.986 Td /F1 9.8 Tf  [(0.23)] TJ ET
0.267 0.267 0.267 rg
417.904 523.841 162.971 0.750 re f
417.904 507.960 0.750 16.631 re f
580.125 507.960 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 423.154 513.986 Td /F1 9.8 Tf  [(0.72)] TJ ET
0.267 0.267 0.267 rg
26.625 507.960 260.875 0.750 re f
26.625 492.079 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 498.105 Td /F1 9.8 Tf  [(PODCI Global Score)] TJ ET
0.267 0.267 0.267 rg
286.750 507.960 55.412 0.750 re f
286.750 492.079 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 292.000 498.105 Td /F1 9.8 Tf  [(0.62)] TJ ET
0.267 0.267 0.267 rg
341.412 507.960 77.242 0.750 re f
341.412 492.079 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 346.662 498.105 Td /F1 9.8 Tf  [(0.28)] TJ ET
0.267 0.267 0.267 rg
417.904 507.960 162.971 0.750 re f
417.904 492.079 0.750 16.631 re f
580.125 492.079 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 423.154 498.105 Td /F1 9.8 Tf  [(0.82)] TJ ET
0.267 0.267 0.267 rg
26.625 492.079 260.875 0.750 re f
26.625 476.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 482.224 Td /F1 9.8 Tf  [(PODCI Transfer / Basic Mobility Score)] TJ ET
0.267 0.267 0.267 rg
286.750 492.079 55.412 0.750 re f
286.750 476.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 292.000 482.224 Td /F1 9.8 Tf  [(0.76)] TJ ET
0.267 0.267 0.267 rg
341.412 492.079 77.242 0.750 re f
341.412 476.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 346.662 482.224 Td /F1 9.8 Tf  [(-0.05)] TJ ET
0.267 0.267 0.267 rg
417.904 492.079 162.971 0.750 re f
417.904 476.197 0.750 16.631 re f
580.125 476.197 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 423.154 482.224 Td /F1 9.8 Tf  [(0.78)] TJ ET
0.267 0.267 0.267 rg
26.625 476.197 260.875 0.750 re f
26.625 460.316 260.875 0.750 re f
26.625 460.316 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 466.342 Td /F1 9.8 Tf  [(PODCI Sports and Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
286.750 476.197 55.412 0.750 re f
286.750 460.316 55.412 0.750 re f
286.750 460.316 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 292.000 466.342 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
341.412 476.197 77.242 0.750 re f
341.412 460.316 77.242 0.750 re f
341.412 460.316 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 346.662 466.342 Td /F1 9.8 Tf  [(0.29)] TJ ET
0.267 0.267 0.267 rg
417.904 476.197 162.971 0.750 re f
417.904 460.316 162.971 0.750 re f
417.904 460.316 0.750 16.631 re f
580.125 460.316 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 423.154 466.342 Td /F1 9.8 Tf  [(0.82)] TJ ET
BT 26.250 405.417 Td /F1 9.8 Tf  [(The distribution of 6MWD versus PRO measures are shown for PODCI transfer and basic mobility scale scores \(Figure 1a\), )] TJ ET
BT 26.250 393.513 Td /F1 9.8 Tf  [(PedsQL physical function scores \(Figure 1b\), PODCI global scores \(Figure 2a\) and PedsQL total scores \(Figure 2b\). The )] TJ ET
BT 26.250 381.608 Td /F1 9.8 Tf  [(distribution of 10 meter run/walk velocities versus PRO measures are shown for PODCI transfer and basic mobility scale scores )] TJ ET
BT 26.250 369.703 Td /F1 9.8 Tf  [(\(Figure 3a\), PedsQL physical function scores \(Figure 3b\), PODCI global scores \(Figure 4a\) and PedsQL total scores \(Figure 4b\).)] TJ ET
0.965 0.965 0.965 rg
26.250 172.322 555.000 187.500 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 359.822 m 581.250 359.822 l 581.250 359.072 l 26.250 359.072 l  f
26.250 172.322 m 581.250 172.322 l 581.250 173.072 l 26.250 173.072 l  f
q
225.000 0 0 168.000 35.250 182.072 cm /I3 Do
Q 
q
35.250 176.072 537.000 0.000 re W n
Q
0.965 0.965 0.965 rg
26.250 -18.928 555.000 183.750 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 164.822 m 581.250 164.822 l 581.250 164.072 l 26.250 164.072 l  f
q
225.000 0 0 168.000 35.250 -12.928 cm /I4 Do
Q 
q
35.250 -18.928 537.000 0.000 re W n
Q
Q
q
225.000 0 0 168.000 35.250 182.072 cm /I3 Do
Q 
q
225.000 0 0 168.000 35.250 -12.928 cm /I4 Do
Q 
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(5)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Muscular Dystrophy)] TJ ET

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26.250 582.000 555.000 0.000 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 582.000 m 581.250 582.000 l 581.250 581.250 l 26.250 581.250 l  f
26.250 582.000 m 581.250 582.000 l 581.250 582.750 l 26.250 582.750 l  f
q
35.250 572.250 537.000 0.000 re W n
Q
0.271 0.267 0.267 rg
BT 26.250 572.476 Td /F1 9.8 Tf  [(One-year follow-up scores were obtained in 13 DMD and 18 control participants. Annual mean change scores for 6MWD, 10 )] TJ ET
BT 26.250 560.571 Td /F1 9.8 Tf  [(meter run/walk velocity, and HrQOL measures are shown in Table 4. In boys with DMD, only 6MWD, 10-meter run/walk velocity, )] TJ ET
BT 26.250 548.667 Td /F1 9.8 Tf  [(and PODCI global and transfer and basic mobility scales demonstrated statistically significant change over the 1-year interval. )] TJ ET
BT 26.250 536.762 Td /F1 9.8 Tf  [(In DMD subjects, the natural history change for those four tests exceeded the amount of change estimated to represent the )] TJ ET
BT 26.250 524.857 Td /F1 9.8 Tf  [(MCID using baseline values. The control group demonstrated significant 1-year change in only 10 meter run/walk velocity.)] TJ ET
q
26.250 501.240 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 503.987 Td /F1 9.8 Tf  [(Table 4: 1-year change in 6MWD, 10-meter run/walk velocity and person-reported functional measures)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 330.016 555.000 163.724 re f
0.965 0.965 0.965 rg
27.000 480.710 130.088 12.280 re f
0.267 0.267 0.267 rg
26.625 492.615 130.463 0.750 re f
26.625 480.335 0.750 13.030 re f
0.965 0.965 0.965 rg
157.088 480.710 70.106 12.280 re f
0.267 0.267 0.267 rg
157.088 492.615 70.106 0.750 re f
0.271 0.267 0.267 rg
BT 161.588 483.466 Td /F4 9.8 Tf  [(DMD \(n=13\))] TJ ET
0.965 0.965 0.965 rg
227.193 480.710 51.580 12.280 re f
0.267 0.267 0.267 rg
227.193 492.615 51.580 0.750 re f
0.965 0.965 0.965 rg
278.774 480.710 51.580 12.280 re f
0.267 0.267 0.267 rg
278.774 492.615 51.580 0.750 re f
0.965 0.965 0.965 rg
330.354 480.710 56.653 12.280 re f
0.267 0.267 0.267 rg
330.354 492.615 56.653 0.750 re f
0.965 0.965 0.965 rg
387.007 480.710 82.143 12.280 re f
0.267 0.267 0.267 rg
387.007 492.615 82.143 0.750 re f
0.271 0.267 0.267 rg
BT 391.507 483.466 Td /F4 9.8 Tf  [(Control \(n=18\))] TJ ET
0.965 0.965 0.965 rg
469.150 480.710 51.580 12.280 re f
0.267 0.267 0.267 rg
469.150 492.615 51.580 0.750 re f
0.965 0.965 0.965 rg
520.730 480.710 59.770 12.280 re f
0.267 0.267 0.267 rg
520.730 492.615 60.145 0.750 re f
580.125 480.335 0.750 13.030 re f
26.625 480.335 130.838 0.750 re f
26.625 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 470.480 Td /F1 9.8 Tf  [(Outcome Measure)] TJ ET
0.267 0.267 0.267 rg
156.713 480.335 70.856 0.750 re f
156.713 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 161.963 470.480 Td /F1 9.8 Tf  [(Mean)] TJ ET
0.267 0.267 0.267 rg
226.818 480.335 52.330 0.750 re f
226.818 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 232.068 470.480 Td /F1 9.8 Tf  [(SE)] TJ ET
0.267 0.267 0.267 rg
278.399 480.335 52.330 0.750 re f
278.399 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 283.649 470.480 Td /F1 9.8 Tf  [(p)] TJ ET
0.267 0.267 0.267 rg
329.979 480.335 57.403 0.750 re f
329.979 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.229 470.480 Td /F1 9.8 Tf  [(> MCID)] TJ ET
0.267 0.267 0.267 rg
386.632 480.335 82.893 0.750 re f
386.632 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.882 470.480 Td /F1 9.8 Tf  [(Mean)] TJ ET
0.267 0.267 0.267 rg
468.775 480.335 52.330 0.750 re f
468.775 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 474.025 470.480 Td /F1 9.8 Tf  [(SE)] TJ ET
0.267 0.267 0.267 rg
520.355 480.335 60.520 0.750 re f
520.355 464.454 0.750 16.631 re f
580.125 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 525.605 470.480 Td /F1 9.8 Tf  [(p)] TJ ET
0.267 0.267 0.267 rg
26.625 464.454 130.838 0.750 re f
26.625 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 454.599 Td /F1 9.8 Tf  [(6MWD \(meters\))] TJ ET
0.267 0.267 0.267 rg
156.713 464.454 70.856 0.750 re f
156.713 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 161.963 454.599 Td /F1 9.8 Tf  [(-53.67)] TJ ET
0.267 0.267 0.267 rg
226.818 464.454 52.330 0.750 re f
226.818 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 232.068 454.599 Td /F1 9.8 Tf  [(25.96)] TJ ET
0.267 0.267 0.267 rg
278.399 464.454 52.330 0.750 re f
278.399 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 283.649 454.599 Td /F1 9.8 Tf  [(0.027)] TJ ET
0.267 0.267 0.267 rg
329.979 464.454 57.403 0.750 re f
329.979 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.229 454.599 Td /F1 9.8 Tf  [(Yes)] TJ ET
0.267 0.267 0.267 rg
386.632 464.454 82.893 0.750 re f
386.632 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.882 454.599 Td /F1 9.8 Tf  [(16.5)] TJ ET
0.267 0.267 0.267 rg
468.775 464.454 52.330 0.750 re f
468.775 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 474.025 454.599 Td /F1 9.8 Tf  [(11.46)] TJ ET
0.267 0.267 0.267 rg
520.355 464.454 60.520 0.750 re f
520.355 448.573 0.750 16.631 re f
580.125 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 525.605 454.599 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 448.573 130.838 0.750 re f
26.625 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 438.718 Td /F1 9.8 Tf  [(10-meter run/walk velocity )] TJ ET
BT 31.875 431.086 Td /F1 9.8 Tf  [(\(m/sec\))] TJ ET
0.267 0.267 0.267 rg
156.713 448.573 70.856 0.750 re f
156.713 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 161.963 438.718 Td /F1 9.8 Tf  [(-0.25)] TJ ET
0.267 0.267 0.267 rg
226.818 448.573 52.330 0.750 re f
226.818 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 232.068 438.718 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.267 0.267 0.267 rg
278.399 448.573 52.330 0.750 re f
278.399 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 283.649 438.718 Td /F1 9.8 Tf  [(0.007)] TJ ET
0.267 0.267 0.267 rg
329.979 448.573 57.403 0.750 re f
329.979 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 335.229 438.718 Td /F1 9.8 Tf  [(Yes)] TJ ET
0.267 0.267 0.267 rg
386.632 448.573 82.893 0.750 re f
386.632 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 391.882 438.718 Td /F1 9.8 Tf  [(0.33)] TJ ET
0.267 0.267 0.267 rg
468.775 448.573 52.330 0.750 re f
468.775 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 474.025 438.718 Td /F1 9.8 Tf  [(0.07)] TJ ET
0.267 0.267 0.267 rg
520.355 448.573 60.520 0.750 re f
520.355 425.060 0.750 24.263 re f
580.125 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 525.605 438.718 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 425.060 130.838 0.750 re f
26.625 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 415.205 Td /F1 9.8 Tf  [(PedsQL Total Score)] TJ ET
0.267 0.267 0.267 rg
156.713 425.060 70.856 0.750 re f
156.713 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 161.963 415.205 Td /F1 9.8 Tf  [(-0.13)] TJ ET
0.267 0.267 0.267 rg
226.818 425.060 52.330 0.750 re f
226.818 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 232.068 415.205 Td /F1 9.8 Tf  [(2.67)] TJ ET
0.267 0.267 0.267 rg
278.399 425.060 52.330 0.750 re f
278.399 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 283.649 415.205 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
329.979 425.060 57.403 0.750 re f
329.979 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.229 415.205 Td /F1 9.8 Tf  [(No)] TJ ET
0.267 0.267 0.267 rg
386.632 425.060 82.893 0.750 re f
386.632 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.882 415.205 Td /F1 9.8 Tf  [(1.03)] TJ ET
0.267 0.267 0.267 rg
468.775 425.060 52.330 0.750 re f
468.775 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 474.025 415.205 Td /F1 9.8 Tf  [(3.26)] TJ ET
0.267 0.267 0.267 rg
520.355 425.060 60.520 0.750 re f
520.355 409.179 0.750 16.631 re f
580.125 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 525.605 415.205 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 409.179 130.838 0.750 re f
26.625 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 399.324 Td /F1 9.8 Tf  [(PedsQL Physical Function )] TJ ET
BT 31.875 391.693 Td /F1 9.8 Tf  [(Score)] TJ ET
0.267 0.267 0.267 rg
156.713 409.179 70.856 0.750 re f
156.713 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 161.963 399.324 Td /F1 9.8 Tf  [(-2.08)] TJ ET
0.267 0.267 0.267 rg
226.818 409.179 52.330 0.750 re f
226.818 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 232.068 399.324 Td /F1 9.8 Tf  [(6.96)] TJ ET
0.267 0.267 0.267 rg
278.399 409.179 52.330 0.750 re f
278.399 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 283.649 399.324 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
329.979 409.179 57.403 0.750 re f
329.979 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 335.229 399.324 Td /F1 9.8 Tf  [(No)] TJ ET
0.267 0.267 0.267 rg
386.632 409.179 82.893 0.750 re f
386.632 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 391.882 399.324 Td /F1 9.8 Tf  [(3.74)] TJ ET
0.267 0.267 0.267 rg
468.775 409.179 52.330 0.750 re f
468.775 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 474.025 399.324 Td /F1 9.8 Tf  [(4.71)] TJ ET
0.267 0.267 0.267 rg
520.355 409.179 60.520 0.750 re f
520.355 385.666 0.750 24.263 re f
580.125 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 525.605 399.324 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 385.666 130.838 0.750 re f
26.625 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 375.811 Td /F1 9.8 Tf  [(PODCI Global)] TJ ET
0.267 0.267 0.267 rg
156.713 385.666 70.856 0.750 re f
156.713 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 161.963 375.811 Td /F1 9.8 Tf  [(-5.05)] TJ ET
0.267 0.267 0.267 rg
226.818 385.666 52.330 0.750 re f
226.818 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 232.068 375.811 Td /F1 9.8 Tf  [(2.24)] TJ ET
0.267 0.267 0.267 rg
278.399 385.666 52.330 0.750 re f
278.399 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 283.649 375.811 Td /F1 9.8 Tf  [(0.027)] TJ ET
0.267 0.267 0.267 rg
329.979 385.666 57.403 0.750 re f
329.979 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.229 375.811 Td /F1 9.8 Tf  [(Yes)] TJ ET
0.267 0.267 0.267 rg
386.632 385.666 82.893 0.750 re f
386.632 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.882 375.811 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
468.775 385.666 52.330 0.750 re f
468.775 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 474.025 375.811 Td /F1 9.8 Tf  [(0.46)] TJ ET
0.267 0.267 0.267 rg
520.355 385.666 60.520 0.750 re f
520.355 369.785 0.750 16.631 re f
580.125 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 525.605 375.811 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 369.785 130.838 0.750 re f
26.625 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 359.930 Td /F1 9.8 Tf  [(PODCI Transfer / Basic )] TJ ET
BT 31.875 352.299 Td /F1 9.8 Tf  [(Mobility)] TJ ET
0.267 0.267 0.267 rg
156.713 369.785 70.856 0.750 re f
156.713 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 161.963 359.930 Td /F1 9.8 Tf  [(-9.95)] TJ ET
0.267 0.267 0.267 rg
226.818 369.785 52.330 0.750 re f
226.818 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 232.068 359.930 Td /F1 9.8 Tf  [(3.94)] TJ ET
0.267 0.267 0.267 rg
278.399 369.785 52.330 0.750 re f
278.399 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 283.649 359.930 Td /F1 9.8 Tf  [(0.013)] TJ ET
0.267 0.267 0.267 rg
329.979 369.785 57.403 0.750 re f
329.979 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 335.229 359.930 Td /F1 9.8 Tf  [(Yes)] TJ ET
0.267 0.267 0.267 rg
386.632 369.785 82.893 0.750 re f
386.632 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 391.882 359.930 Td /F1 9.8 Tf  [(0.31)] TJ ET
0.267 0.267 0.267 rg
468.775 369.785 52.330 0.750 re f
468.775 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 474.025 359.930 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
520.355 369.785 60.520 0.750 re f
520.355 346.273 0.750 24.263 re f
580.125 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 525.605 359.930 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 346.273 130.838 0.750 re f
26.625 330.391 130.838 0.750 re f
26.625 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 336.418 Td /F1 9.8 Tf  [(PODCI Sports)] TJ ET
0.267 0.267 0.267 rg
156.713 346.273 70.856 0.750 re f
156.713 330.391 70.856 0.750 re f
156.713 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 161.963 336.418 Td /F1 9.8 Tf  [(-3.11)] TJ ET
0.267 0.267 0.267 rg
226.818 346.273 52.330 0.750 re f
226.818 330.391 52.330 0.750 re f
226.818 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 232.068 336.418 Td /F1 9.8 Tf  [(4.04)] TJ ET
0.267 0.267 0.267 rg
278.399 346.273 52.330 0.750 re f
278.399 330.391 52.330 0.750 re f
278.399 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 283.649 336.418 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
329.979 346.273 57.403 0.750 re f
329.979 330.391 57.403 0.750 re f
329.979 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.229 336.418 Td /F1 9.8 Tf  [(No)] TJ ET
0.267 0.267 0.267 rg
386.632 346.273 82.893 0.750 re f
386.632 330.391 82.893 0.750 re f
386.632 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.882 336.418 Td /F1 9.8 Tf  [(1.49)] TJ ET
0.267 0.267 0.267 rg
468.775 346.273 52.330 0.750 re f
468.775 330.391 52.330 0.750 re f
468.775 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 474.025 336.418 Td /F1 9.8 Tf  [(0.99)] TJ ET
0.267 0.267 0.267 rg
520.355 346.273 60.520 0.750 re f
520.355 330.391 60.520 0.750 re f
520.355 330.391 0.750 16.631 re f
580.125 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 525.605 336.418 Td /F1 9.8 Tf  [(ns)] TJ ET
BT 26.250 275.493 Td /F1 9.8 Tf  [(Correlation of 1-year changes in 6MWD and HrQOL measures is shown in Table 5. In boys with DMD, change in 6MWD was )] TJ ET
BT 26.250 263.588 Td /F1 9.8 Tf  [(most highly correlated with change in PODCI global and PODCI transfer and basic mobility scores \(r=0.76 and r=0.93, )] TJ ET
BT 26.250 251.683 Td /F1 9.8 Tf  [(respectively\).)] TJ ET
q
26.250 228.066 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 230.813 Td /F1 9.8 Tf  [(Table 5: Pearson�s correlation of 1-year change in 6MWD, PedsQL and PODCI measures)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 115.475 555.000 105.091 re f
0.965 0.965 0.965 rg
27.000 195.631 207.656 24.185 re f
0.267 0.267 0.267 rg
26.625 219.441 208.031 0.750 re f
26.625 195.256 0.750 24.935 re f
0.271 0.267 0.267 rg
BT 31.500 210.292 Td /F4 9.8 Tf  [(6MWD vs. Person-Reported Measures )] TJ ET
BT 31.500 198.387 Td /F4 9.8 Tf  [(\(Change\))] TJ ET
0.965 0.965 0.965 rg
234.656 195.631 80.106 24.185 re f
0.267 0.267 0.267 rg
234.656 219.441 80.106 0.750 re f
0.271 0.267 0.267 rg
BT 239.156 210.292 Td /F4 9.8 Tf  [(DMD \(n=13\))] TJ ET
0.965 0.965 0.965 rg
314.762 195.631 94.124 24.185 re f
0.267 0.267 0.267 rg
314.762 219.441 94.124 0.750 re f
0.271 0.267 0.267 rg
BT 319.262 210.292 Td /F4 9.8 Tf  [(Control \(n=18\))] TJ ET
0.965 0.965 0.965 rg
408.886 195.631 171.614 24.185 re f
0.267 0.267 0.267 rg
408.886 219.441 171.989 0.750 re f
580.125 195.256 0.750 24.935 re f
0.271 0.267 0.267 rg
BT 413.386 210.292 Td /F4 9.8 Tf  [(Combined\(Full Range, n=31\))] TJ ET
0.267 0.267 0.267 rg
26.625 195.256 208.406 0.750 re f
26.625 179.375 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 185.401 Td /F1 9.8 Tf  [(PedsQL Total Score)] TJ ET
0.267 0.267 0.267 rg
234.281 195.256 80.856 0.750 re f
234.281 179.375 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 239.531 185.401 Td /F1 9.8 Tf  [(0.01)] TJ ET
0.267 0.267 0.267 rg
314.387 195.256 94.874 0.750 re f
314.387 179.375 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.637 185.401 Td /F1 9.8 Tf  [(-0.13)] TJ ET
0.267 0.267 0.267 rg
408.511 195.256 172.364 0.750 re f
408.511 179.375 0.750 16.631 re f
580.125 179.375 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.761 185.401 Td /F1 9.8 Tf  [(-0.17)] TJ ET
0.267 0.267 0.267 rg
26.625 179.375 208.406 0.750 re f
26.625 163.494 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 169.520 Td /F1 9.8 Tf  [(PedsQL Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
234.281 179.375 80.856 0.750 re f
234.281 163.494 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 239.531 169.520 Td /F1 9.8 Tf  [(-0.36)] TJ ET
0.267 0.267 0.267 rg
314.387 179.375 94.874 0.750 re f
314.387 163.494 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.637 169.520 Td /F1 9.8 Tf  [(-0.06)] TJ ET
0.267 0.267 0.267 rg
408.511 179.375 172.364 0.750 re f
408.511 163.494 0.750 16.631 re f
580.125 163.494 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.761 169.520 Td /F1 9.8 Tf  [(-0.38)] TJ ET
0.267 0.267 0.267 rg
26.625 163.494 208.406 0.750 re f
26.625 147.613 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 153.639 Td /F1 9.8 Tf  [(PODCI Global Score)] TJ ET
0.267 0.267 0.267 rg
234.281 163.494 80.856 0.750 re f
234.281 147.613 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 239.531 153.639 Td /F1 9.8 Tf  [(0.76)] TJ ET
0.267 0.267 0.267 rg
314.387 163.494 94.874 0.750 re f
314.387 147.613 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.637 153.639 Td /F1 9.8 Tf  [(0.07)] TJ ET
0.267 0.267 0.267 rg
408.511 163.494 172.364 0.750 re f
408.511 147.613 0.750 16.631 re f
580.125 147.613 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.761 153.639 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.267 0.267 0.267 rg
26.625 147.613 208.406 0.750 re f
26.625 131.731 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 137.758 Td /F1 9.8 Tf  [(PODCI Transfer / Basic Mobility)] TJ ET
0.267 0.267 0.267 rg
234.281 147.613 80.856 0.750 re f
234.281 131.731 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 239.531 137.758 Td /F1 9.8 Tf  [(0.93)] TJ ET
0.267 0.267 0.267 rg
314.387 147.613 94.874 0.750 re f
314.387 131.731 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.637 137.758 Td /F1 9.8 Tf  [(-0.05)] TJ ET
0.267 0.267 0.267 rg
408.511 147.613 172.364 0.750 re f
408.511 131.731 0.750 16.631 re f
580.125 131.731 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.761 137.758 Td /F1 9.8 Tf  [(0.76)] TJ ET
0.267 0.267 0.267 rg
26.625 131.731 208.406 0.750 re f
26.625 115.850 208.406 0.750 re f
26.625 115.850 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 121.876 Td /F1 9.8 Tf  [(PODCI Sports)] TJ ET
0.267 0.267 0.267 rg
234.281 131.731 80.856 0.750 re f
234.281 115.850 80.856 0.750 re f
234.281 115.850 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 239.531 121.876 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
314.387 131.731 94.874 0.750 re f
314.387 115.850 94.874 0.750 re f
314.387 115.850 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.637 121.876 Td /F1 9.8 Tf  [(-0.60)] TJ ET
0.267 0.267 0.267 rg
408.511 131.731 172.364 0.750 re f
408.511 115.850 172.364 0.750 re f
408.511 115.850 0.750 16.631 re f
580.125 115.850 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.761 121.876 Td /F1 9.8 Tf  [(0.37)] TJ ET
BT 26.250 60.951 Td /F1 9.8 Tf  [(Best-fit regression equations estimating 6MWD for each of the HrQOL items is listed in Table 6. Consistent with the higher )] TJ ET
BT 26.250 49.047 Td /F1 9.8 Tf  [(degrees of correlation between 6MWD and PODCI measures and change in those measures over time, the PODCI global and )] TJ ET
BT 26.250 37.142 Td /F1 9.8 Tf  [(PODCI transfer and basic mobility scales provided the best estimates of 6MWT performance. We selected the latter to best )] TJ ET
Q
q
15.000 22.856 577.500 754.144 re W n
0.965 0.965 0.965 rg
26.250 777.000 555.000 0.000 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 777.000 m 581.250 777.000 l 581.250 777.750 l 26.250 777.750 l  f
q
35.250 777.000 537.000 0.000 re W n
Q
0.965 0.965 0.965 rg
26.250 589.500 555.000 187.500 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 777.000 m 581.250 777.000 l 581.250 776.250 l 26.250 776.250 l  f
26.250 589.500 m 581.250 589.500 l 581.250 590.250 l 26.250 590.250 l  f
q
225.000 0 0 168.000 35.250 599.250 cm /I9 Do
Q 
q
35.250 593.250 537.000 0.000 re W n
Q
0.965 0.965 0.965 rg
26.250 582.000 555.000 0.000 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 582.000 m 581.250 582.000 l 581.250 581.250 l 26.250 581.250 l  f
26.250 582.000 m 581.250 582.000 l 581.250 582.750 l 26.250 582.750 l  f
q
35.250 572.250 537.000 0.000 re W n
Q
0.271 0.267 0.267 rg
BT 26.250 572.476 Td /F1 9.8 Tf  [(One-year follow-up scores were obtained in 13 DMD and 18 control participants. Annual mean change scores for 6MWD, 10 )] TJ ET
BT 26.250 560.571 Td /F1 9.8 Tf  [(meter run/walk velocity, and HrQOL measures are shown in Table 4. In boys with DMD, only 6MWD, 10-meter run/walk velocity, )] TJ ET
BT 26.250 548.667 Td /F1 9.8 Tf  [(and PODCI global and transfer and basic mobility scales demonstrated statistically significant change over the 1-year interval. )] TJ ET
BT 26.250 536.762 Td /F1 9.8 Tf  [(In DMD subjects, the natural history change for those four tests exceeded the amount of change estimated to represent the )] TJ ET
BT 26.250 524.857 Td /F1 9.8 Tf  [(MCID using baseline values. The control group demonstrated significant 1-year change in only 10 meter run/walk velocity.)] TJ ET
q
26.250 501.240 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 503.987 Td /F1 9.8 Tf  [(Table 4: 1-year change in 6MWD, 10-meter run/walk velocity and person-reported functional measures)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 330.016 555.000 163.724 re f
0.965 0.965 0.965 rg
27.000 480.710 130.088 12.280 re f
0.267 0.267 0.267 rg
26.625 492.615 130.463 0.750 re f
26.625 480.335 0.750 13.030 re f
0.965 0.965 0.965 rg
157.088 480.710 70.106 12.280 re f
0.267 0.267 0.267 rg
157.088 492.615 70.106 0.750 re f
0.271 0.267 0.267 rg
BT 161.588 483.466 Td /F4 9.8 Tf  [(DMD \(n=13\))] TJ ET
0.965 0.965 0.965 rg
227.193 480.710 51.580 12.280 re f
0.267 0.267 0.267 rg
227.193 492.615 51.580 0.750 re f
0.965 0.965 0.965 rg
278.774 480.710 51.580 12.280 re f
0.267 0.267 0.267 rg
278.774 492.615 51.580 0.750 re f
0.965 0.965 0.965 rg
330.354 480.710 56.653 12.280 re f
0.267 0.267 0.267 rg
330.354 492.615 56.653 0.750 re f
0.965 0.965 0.965 rg
387.007 480.710 82.143 12.280 re f
0.267 0.267 0.267 rg
387.007 492.615 82.143 0.750 re f
0.271 0.267 0.267 rg
BT 391.507 483.466 Td /F4 9.8 Tf  [(Control \(n=18\))] TJ ET
0.965 0.965 0.965 rg
469.150 480.710 51.580 12.280 re f
0.267 0.267 0.267 rg
469.150 492.615 51.580 0.750 re f
0.965 0.965 0.965 rg
520.730 480.710 59.770 12.280 re f
0.267 0.267 0.267 rg
520.730 492.615 60.145 0.750 re f
580.125 480.335 0.750 13.030 re f
26.625 480.335 130.838 0.750 re f
26.625 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 470.480 Td /F1 9.8 Tf  [(Outcome Measure)] TJ ET
0.267 0.267 0.267 rg
156.713 480.335 70.856 0.750 re f
156.713 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 161.963 470.480 Td /F1 9.8 Tf  [(Mean)] TJ ET
0.267 0.267 0.267 rg
226.818 480.335 52.330 0.750 re f
226.818 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 232.068 470.480 Td /F1 9.8 Tf  [(SE)] TJ ET
0.267 0.267 0.267 rg
278.399 480.335 52.330 0.750 re f
278.399 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 283.649 470.480 Td /F1 9.8 Tf  [(p)] TJ ET
0.267 0.267 0.267 rg
329.979 480.335 57.403 0.750 re f
329.979 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.229 470.480 Td /F1 9.8 Tf  [(> MCID)] TJ ET
0.267 0.267 0.267 rg
386.632 480.335 82.893 0.750 re f
386.632 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.882 470.480 Td /F1 9.8 Tf  [(Mean)] TJ ET
0.267 0.267 0.267 rg
468.775 480.335 52.330 0.750 re f
468.775 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 474.025 470.480 Td /F1 9.8 Tf  [(SE)] TJ ET
0.267 0.267 0.267 rg
520.355 480.335 60.520 0.750 re f
520.355 464.454 0.750 16.631 re f
580.125 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 525.605 470.480 Td /F1 9.8 Tf  [(p)] TJ ET
0.267 0.267 0.267 rg
26.625 464.454 130.838 0.750 re f
26.625 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 454.599 Td /F1 9.8 Tf  [(6MWD \(meters\))] TJ ET
0.267 0.267 0.267 rg
156.713 464.454 70.856 0.750 re f
156.713 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 161.963 454.599 Td /F1 9.8 Tf  [(-53.67)] TJ ET
0.267 0.267 0.267 rg
226.818 464.454 52.330 0.750 re f
226.818 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 232.068 454.599 Td /F1 9.8 Tf  [(25.96)] TJ ET
0.267 0.267 0.267 rg
278.399 464.454 52.330 0.750 re f
278.399 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 283.649 454.599 Td /F1 9.8 Tf  [(0.027)] TJ ET
0.267 0.267 0.267 rg
329.979 464.454 57.403 0.750 re f
329.979 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.229 454.599 Td /F1 9.8 Tf  [(Yes)] TJ ET
0.267 0.267 0.267 rg
386.632 464.454 82.893 0.750 re f
386.632 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.882 454.599 Td /F1 9.8 Tf  [(16.5)] TJ ET
0.267 0.267 0.267 rg
468.775 464.454 52.330 0.750 re f
468.775 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 474.025 454.599 Td /F1 9.8 Tf  [(11.46)] TJ ET
0.267 0.267 0.267 rg
520.355 464.454 60.520 0.750 re f
520.355 448.573 0.750 16.631 re f
580.125 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 525.605 454.599 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 448.573 130.838 0.750 re f
26.625 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 438.718 Td /F1 9.8 Tf  [(10-meter run/walk velocity )] TJ ET
BT 31.875 431.086 Td /F1 9.8 Tf  [(\(m/sec\))] TJ ET
0.267 0.267 0.267 rg
156.713 448.573 70.856 0.750 re f
156.713 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 161.963 438.718 Td /F1 9.8 Tf  [(-0.25)] TJ ET
0.267 0.267 0.267 rg
226.818 448.573 52.330 0.750 re f
226.818 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 232.068 438.718 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.267 0.267 0.267 rg
278.399 448.573 52.330 0.750 re f
278.399 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 283.649 438.718 Td /F1 9.8 Tf  [(0.007)] TJ ET
0.267 0.267 0.267 rg
329.979 448.573 57.403 0.750 re f
329.979 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 335.229 438.718 Td /F1 9.8 Tf  [(Yes)] TJ ET
0.267 0.267 0.267 rg
386.632 448.573 82.893 0.750 re f
386.632 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 391.882 438.718 Td /F1 9.8 Tf  [(0.33)] TJ ET
0.267 0.267 0.267 rg
468.775 448.573 52.330 0.750 re f
468.775 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 474.025 438.718 Td /F1 9.8 Tf  [(0.07)] TJ ET
0.267 0.267 0.267 rg
520.355 448.573 60.520 0.750 re f
520.355 425.060 0.750 24.263 re f
580.125 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 525.605 438.718 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 425.060 130.838 0.750 re f
26.625 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 415.205 Td /F1 9.8 Tf  [(PedsQL Total Score)] TJ ET
0.267 0.267 0.267 rg
156.713 425.060 70.856 0.750 re f
156.713 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 161.963 415.205 Td /F1 9.8 Tf  [(-0.13)] TJ ET
0.267 0.267 0.267 rg
226.818 425.060 52.330 0.750 re f
226.818 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 232.068 415.205 Td /F1 9.8 Tf  [(2.67)] TJ ET
0.267 0.267 0.267 rg
278.399 425.060 52.330 0.750 re f
278.399 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 283.649 415.205 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
329.979 425.060 57.403 0.750 re f
329.979 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.229 415.205 Td /F1 9.8 Tf  [(No)] TJ ET
0.267 0.267 0.267 rg
386.632 425.060 82.893 0.750 re f
386.632 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.882 415.205 Td /F1 9.8 Tf  [(1.03)] TJ ET
0.267 0.267 0.267 rg
468.775 425.060 52.330 0.750 re f
468.775 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 474.025 415.205 Td /F1 9.8 Tf  [(3.26)] TJ ET
0.267 0.267 0.267 rg
520.355 425.060 60.520 0.750 re f
520.355 409.179 0.750 16.631 re f
580.125 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 525.605 415.205 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 409.179 130.838 0.750 re f
26.625 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 399.324 Td /F1 9.8 Tf  [(PedsQL Physical Function )] TJ ET
BT 31.875 391.693 Td /F1 9.8 Tf  [(Score)] TJ ET
0.267 0.267 0.267 rg
156.713 409.179 70.856 0.750 re f
156.713 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 161.963 399.324 Td /F1 9.8 Tf  [(-2.08)] TJ ET
0.267 0.267 0.267 rg
226.818 409.179 52.330 0.750 re f
226.818 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 232.068 399.324 Td /F1 9.8 Tf  [(6.96)] TJ ET
0.267 0.267 0.267 rg
278.399 409.179 52.330 0.750 re f
278.399 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 283.649 399.324 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
329.979 409.179 57.403 0.750 re f
329.979 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 335.229 399.324 Td /F1 9.8 Tf  [(No)] TJ ET
0.267 0.267 0.267 rg
386.632 409.179 82.893 0.750 re f
386.632 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 391.882 399.324 Td /F1 9.8 Tf  [(3.74)] TJ ET
0.267 0.267 0.267 rg
468.775 409.179 52.330 0.750 re f
468.775 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 474.025 399.324 Td /F1 9.8 Tf  [(4.71)] TJ ET
0.267 0.267 0.267 rg
520.355 409.179 60.520 0.750 re f
520.355 385.666 0.750 24.263 re f
580.125 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 525.605 399.324 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 385.666 130.838 0.750 re f
26.625 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 375.811 Td /F1 9.8 Tf  [(PODCI Global)] TJ ET
0.267 0.267 0.267 rg
156.713 385.666 70.856 0.750 re f
156.713 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 161.963 375.811 Td /F1 9.8 Tf  [(-5.05)] TJ ET
0.267 0.267 0.267 rg
226.818 385.666 52.330 0.750 re f
226.818 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 232.068 375.811 Td /F1 9.8 Tf  [(2.24)] TJ ET
0.267 0.267 0.267 rg
278.399 385.666 52.330 0.750 re f
278.399 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 283.649 375.811 Td /F1 9.8 Tf  [(0.027)] TJ ET
0.267 0.267 0.267 rg
329.979 385.666 57.403 0.750 re f
329.979 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.229 375.811 Td /F1 9.8 Tf  [(Yes)] TJ ET
0.267 0.267 0.267 rg
386.632 385.666 82.893 0.750 re f
386.632 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.882 375.811 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
468.775 385.666 52.330 0.750 re f
468.775 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 474.025 375.811 Td /F1 9.8 Tf  [(0.46)] TJ ET
0.267 0.267 0.267 rg
520.355 385.666 60.520 0.750 re f
520.355 369.785 0.750 16.631 re f
580.125 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 525.605 375.811 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 369.785 130.838 0.750 re f
26.625 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 359.930 Td /F1 9.8 Tf  [(PODCI Transfer / Basic )] TJ ET
BT 31.875 352.299 Td /F1 9.8 Tf  [(Mobility)] TJ ET
0.267 0.267 0.267 rg
156.713 369.785 70.856 0.750 re f
156.713 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 161.963 359.930 Td /F1 9.8 Tf  [(-9.95)] TJ ET
0.267 0.267 0.267 rg
226.818 369.785 52.330 0.750 re f
226.818 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 232.068 359.930 Td /F1 9.8 Tf  [(3.94)] TJ ET
0.267 0.267 0.267 rg
278.399 369.785 52.330 0.750 re f
278.399 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 283.649 359.930 Td /F1 9.8 Tf  [(0.013)] TJ ET
0.267 0.267 0.267 rg
329.979 369.785 57.403 0.750 re f
329.979 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 335.229 359.930 Td /F1 9.8 Tf  [(Yes)] TJ ET
0.267 0.267 0.267 rg
386.632 369.785 82.893 0.750 re f
386.632 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 391.882 359.930 Td /F1 9.8 Tf  [(0.31)] TJ ET
0.267 0.267 0.267 rg
468.775 369.785 52.330 0.750 re f
468.775 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 474.025 359.930 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
520.355 369.785 60.520 0.750 re f
520.355 346.273 0.750 24.263 re f
580.125 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 525.605 359.930 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 346.273 130.838 0.750 re f
26.625 330.391 130.838 0.750 re f
26.625 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 336.418 Td /F1 9.8 Tf  [(PODCI Sports)] TJ ET
0.267 0.267 0.267 rg
156.713 346.273 70.856 0.750 re f
156.713 330.391 70.856 0.750 re f
156.713 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 161.963 336.418 Td /F1 9.8 Tf  [(-3.11)] TJ ET
0.267 0.267 0.267 rg
226.818 346.273 52.330 0.750 re f
226.818 330.391 52.330 0.750 re f
226.818 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 232.068 336.418 Td /F1 9.8 Tf  [(4.04)] TJ ET
0.267 0.267 0.267 rg
278.399 346.273 52.330 0.750 re f
278.399 330.391 52.330 0.750 re f
278.399 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 283.649 336.418 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
329.979 346.273 57.403 0.750 re f
329.979 330.391 57.403 0.750 re f
329.979 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.229 336.418 Td /F1 9.8 Tf  [(No)] TJ ET
0.267 0.267 0.267 rg
386.632 346.273 82.893 0.750 re f
386.632 330.391 82.893 0.750 re f
386.632 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.882 336.418 Td /F1 9.8 Tf  [(1.49)] TJ ET
0.267 0.267 0.267 rg
468.775 346.273 52.330 0.750 re f
468.775 330.391 52.330 0.750 re f
468.775 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 474.025 336.418 Td /F1 9.8 Tf  [(0.99)] TJ ET
0.267 0.267 0.267 rg
520.355 346.273 60.520 0.750 re f
520.355 330.391 60.520 0.750 re f
520.355 330.391 0.750 16.631 re f
580.125 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 525.605 336.418 Td /F1 9.8 Tf  [(ns)] TJ ET
BT 26.250 275.493 Td /F1 9.8 Tf  [(Correlation of 1-year changes in 6MWD and HrQOL measures is shown in Table 5. In boys with DMD, change in 6MWD was )] TJ ET
BT 26.250 263.588 Td /F1 9.8 Tf  [(most highly correlated with change in PODCI global and PODCI transfer and basic mobility scores \(r=0.76 and r=0.93, )] TJ ET
BT 26.250 251.683 Td /F1 9.8 Tf  [(respectively\).)] TJ ET
q
26.250 228.066 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 230.813 Td /F1 9.8 Tf  [(Table 5: Pearson�s correlation of 1-year change in 6MWD, PedsQL and PODCI measures)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 115.475 555.000 105.091 re f
0.965 0.965 0.965 rg
27.000 195.631 207.656 24.185 re f
0.267 0.267 0.267 rg
26.625 219.441 208.031 0.750 re f
26.625 195.256 0.750 24.935 re f
0.271 0.267 0.267 rg
BT 31.500 210.292 Td /F4 9.8 Tf  [(6MWD vs. Person-Reported Measures )] TJ ET
BT 31.500 198.387 Td /F4 9.8 Tf  [(\(Change\))] TJ ET
0.965 0.965 0.965 rg
234.656 195.631 80.106 24.185 re f
0.267 0.267 0.267 rg
234.656 219.441 80.106 0.750 re f
0.271 0.267 0.267 rg
BT 239.156 210.292 Td /F4 9.8 Tf  [(DMD \(n=13\))] TJ ET
0.965 0.965 0.965 rg
314.762 195.631 94.124 24.185 re f
0.267 0.267 0.267 rg
314.762 219.441 94.124 0.750 re f
0.271 0.267 0.267 rg
BT 319.262 210.292 Td /F4 9.8 Tf  [(Control \(n=18\))] TJ ET
0.965 0.965 0.965 rg
408.886 195.631 171.614 24.185 re f
0.267 0.267 0.267 rg
408.886 219.441 171.989 0.750 re f
580.125 195.256 0.750 24.935 re f
0.271 0.267 0.267 rg
BT 413.386 210.292 Td /F4 9.8 Tf  [(Combined\(Full Range, n=31\))] TJ ET
0.267 0.267 0.267 rg
26.625 195.256 208.406 0.750 re f
26.625 179.375 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 185.401 Td /F1 9.8 Tf  [(PedsQL Total Score)] TJ ET
0.267 0.267 0.267 rg
234.281 195.256 80.856 0.750 re f
234.281 179.375 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 239.531 185.401 Td /F1 9.8 Tf  [(0.01)] TJ ET
0.267 0.267 0.267 rg
314.387 195.256 94.874 0.750 re f
314.387 179.375 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.637 185.401 Td /F1 9.8 Tf  [(-0.13)] TJ ET
0.267 0.267 0.267 rg
408.511 195.256 172.364 0.750 re f
408.511 179.375 0.750 16.631 re f
580.125 179.375 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.761 185.401 Td /F1 9.8 Tf  [(-0.17)] TJ ET
0.267 0.267 0.267 rg
26.625 179.375 208.406 0.750 re f
26.625 163.494 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 169.520 Td /F1 9.8 Tf  [(PedsQL Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
234.281 179.375 80.856 0.750 re f
234.281 163.494 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 239.531 169.520 Td /F1 9.8 Tf  [(-0.36)] TJ ET
0.267 0.267 0.267 rg
314.387 179.375 94.874 0.750 re f
314.387 163.494 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.637 169.520 Td /F1 9.8 Tf  [(-0.06)] TJ ET
0.267 0.267 0.267 rg
408.511 179.375 172.364 0.750 re f
408.511 163.494 0.750 16.631 re f
580.125 163.494 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.761 169.520 Td /F1 9.8 Tf  [(-0.38)] TJ ET
0.267 0.267 0.267 rg
26.625 163.494 208.406 0.750 re f
26.625 147.613 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 153.639 Td /F1 9.8 Tf  [(PODCI Global Score)] TJ ET
0.267 0.267 0.267 rg
234.281 163.494 80.856 0.750 re f
234.281 147.613 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 239.531 153.639 Td /F1 9.8 Tf  [(0.76)] TJ ET
0.267 0.267 0.267 rg
314.387 163.494 94.874 0.750 re f
314.387 147.613 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.637 153.639 Td /F1 9.8 Tf  [(0.07)] TJ ET
0.267 0.267 0.267 rg
408.511 163.494 172.364 0.750 re f
408.511 147.613 0.750 16.631 re f
580.125 147.613 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.761 153.639 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.267 0.267 0.267 rg
26.625 147.613 208.406 0.750 re f
26.625 131.731 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 137.758 Td /F1 9.8 Tf  [(PODCI Transfer / Basic Mobility)] TJ ET
0.267 0.267 0.267 rg
234.281 147.613 80.856 0.750 re f
234.281 131.731 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 239.531 137.758 Td /F1 9.8 Tf  [(0.93)] TJ ET
0.267 0.267 0.267 rg
314.387 147.613 94.874 0.750 re f
314.387 131.731 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.637 137.758 Td /F1 9.8 Tf  [(-0.05)] TJ ET
0.267 0.267 0.267 rg
408.511 147.613 172.364 0.750 re f
408.511 131.731 0.750 16.631 re f
580.125 131.731 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.761 137.758 Td /F1 9.8 Tf  [(0.76)] TJ ET
0.267 0.267 0.267 rg
26.625 131.731 208.406 0.750 re f
26.625 115.850 208.406 0.750 re f
26.625 115.850 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 121.876 Td /F1 9.8 Tf  [(PODCI Sports)] TJ ET
0.267 0.267 0.267 rg
234.281 131.731 80.856 0.750 re f
234.281 115.850 80.856 0.750 re f
234.281 115.850 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 239.531 121.876 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
314.387 131.731 94.874 0.750 re f
314.387 115.850 94.874 0.750 re f
314.387 115.850 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.637 121.876 Td /F1 9.8 Tf  [(-0.60)] TJ ET
0.267 0.267 0.267 rg
408.511 131.731 172.364 0.750 re f
408.511 115.850 172.364 0.750 re f
408.511 115.850 0.750 16.631 re f
580.125 115.850 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.761 121.876 Td /F1 9.8 Tf  [(0.37)] TJ ET
BT 26.250 60.951 Td /F1 9.8 Tf  [(Best-fit regression equations estimating 6MWD for each of the HrQOL items is listed in Table 6. Consistent with the higher )] TJ ET
BT 26.250 49.047 Td /F1 9.8 Tf  [(degrees of correlation between 6MWD and PODCI measures and change in those measures over time, the PODCI global and )] TJ ET
BT 26.250 37.142 Td /F1 9.8 Tf  [(PODCI transfer and basic mobility scales provided the best estimates of 6MWT performance. We selected the latter to best )] TJ ET
Q
q
15.000 22.856 577.500 754.144 re W n
0.965 0.965 0.965 rg
26.250 777.000 555.000 0.000 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 777.000 m 581.250 777.000 l 581.250 777.750 l 26.250 777.750 l  f
q
35.250 777.000 537.000 0.000 re W n
Q
0.965 0.965 0.965 rg
26.250 589.500 555.000 187.500 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 777.000 m 581.250 777.000 l 581.250 776.250 l 26.250 776.250 l  f
26.250 589.500 m 581.250 589.500 l 581.250 590.250 l 26.250 590.250 l  f
q
225.000 0 0 168.000 35.250 599.250 cm /I9 Do
Q 
q
35.250 593.250 537.000 0.000 re W n
Q
0.965 0.965 0.965 rg
26.250 582.000 555.000 0.000 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 582.000 m 581.250 582.000 l 581.250 581.250 l 26.250 581.250 l  f
26.250 582.000 m 581.250 582.000 l 581.250 582.750 l 26.250 582.750 l  f
q
35.250 572.250 537.000 0.000 re W n
Q
0.271 0.267 0.267 rg
BT 26.250 572.476 Td /F1 9.8 Tf  [(One-year follow-up scores were obtained in 13 DMD and 18 control participants. Annual mean change scores for 6MWD, 10 )] TJ ET
BT 26.250 560.571 Td /F1 9.8 Tf  [(meter run/walk velocity, and HrQOL measures are shown in Table 4. In boys with DMD, only 6MWD, 10-meter run/walk velocity, )] TJ ET
BT 26.250 548.667 Td /F1 9.8 Tf  [(and PODCI global and transfer and basic mobility scales demonstrated statistically significant change over the 1-year interval. )] TJ ET
BT 26.250 536.762 Td /F1 9.8 Tf  [(In DMD subjects, the natural history change for those four tests exceeded the amount of change estimated to represent the )] TJ ET
BT 26.250 524.857 Td /F1 9.8 Tf  [(MCID using baseline values. The control group demonstrated significant 1-year change in only 10 meter run/walk velocity.)] TJ ET
q
26.250 501.240 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 503.987 Td /F1 9.8 Tf  [(Table 4: 1-year change in 6MWD, 10-meter run/walk velocity and person-reported functional measures)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 330.016 555.000 163.724 re f
0.965 0.965 0.965 rg
27.000 480.710 130.088 12.280 re f
0.267 0.267 0.267 rg
26.625 492.615 130.463 0.750 re f
26.625 480.335 0.750 13.030 re f
0.965 0.965 0.965 rg
157.088 480.710 70.106 12.280 re f
0.267 0.267 0.267 rg
157.088 492.615 70.106 0.750 re f
0.271 0.267 0.267 rg
BT 161.588 483.466 Td /F4 9.8 Tf  [(DMD \(n=13\))] TJ ET
0.965 0.965 0.965 rg
227.193 480.710 51.580 12.280 re f
0.267 0.267 0.267 rg
227.193 492.615 51.580 0.750 re f
0.965 0.965 0.965 rg
278.774 480.710 51.580 12.280 re f
0.267 0.267 0.267 rg
278.774 492.615 51.580 0.750 re f
0.965 0.965 0.965 rg
330.354 480.710 56.653 12.280 re f
0.267 0.267 0.267 rg
330.354 492.615 56.653 0.750 re f
0.965 0.965 0.965 rg
387.007 480.710 82.143 12.280 re f
0.267 0.267 0.267 rg
387.007 492.615 82.143 0.750 re f
0.271 0.267 0.267 rg
BT 391.507 483.466 Td /F4 9.8 Tf  [(Control \(n=18\))] TJ ET
0.965 0.965 0.965 rg
469.150 480.710 51.580 12.280 re f
0.267 0.267 0.267 rg
469.150 492.615 51.580 0.750 re f
0.965 0.965 0.965 rg
520.730 480.710 59.770 12.280 re f
0.267 0.267 0.267 rg
520.730 492.615 60.145 0.750 re f
580.125 480.335 0.750 13.030 re f
26.625 480.335 130.838 0.750 re f
26.625 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 470.480 Td /F1 9.8 Tf  [(Outcome Measure)] TJ ET
0.267 0.267 0.267 rg
156.713 480.335 70.856 0.750 re f
156.713 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 161.963 470.480 Td /F1 9.8 Tf  [(Mean)] TJ ET
0.267 0.267 0.267 rg
226.818 480.335 52.330 0.750 re f
226.818 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 232.068 470.480 Td /F1 9.8 Tf  [(SE)] TJ ET
0.267 0.267 0.267 rg
278.399 480.335 52.330 0.750 re f
278.399 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 283.649 470.480 Td /F1 9.8 Tf  [(p)] TJ ET
0.267 0.267 0.267 rg
329.979 480.335 57.403 0.750 re f
329.979 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.229 470.480 Td /F1 9.8 Tf  [(> MCID)] TJ ET
0.267 0.267 0.267 rg
386.632 480.335 82.893 0.750 re f
386.632 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.882 470.480 Td /F1 9.8 Tf  [(Mean)] TJ ET
0.267 0.267 0.267 rg
468.775 480.335 52.330 0.750 re f
468.775 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 474.025 470.480 Td /F1 9.8 Tf  [(SE)] TJ ET
0.267 0.267 0.267 rg
520.355 480.335 60.520 0.750 re f
520.355 464.454 0.750 16.631 re f
580.125 464.454 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 525.605 470.480 Td /F1 9.8 Tf  [(p)] TJ ET
0.267 0.267 0.267 rg
26.625 464.454 130.838 0.750 re f
26.625 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 454.599 Td /F1 9.8 Tf  [(6MWD \(meters\))] TJ ET
0.267 0.267 0.267 rg
156.713 464.454 70.856 0.750 re f
156.713 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 161.963 454.599 Td /F1 9.8 Tf  [(-53.67)] TJ ET
0.267 0.267 0.267 rg
226.818 464.454 52.330 0.750 re f
226.818 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 232.068 454.599 Td /F1 9.8 Tf  [(25.96)] TJ ET
0.267 0.267 0.267 rg
278.399 464.454 52.330 0.750 re f
278.399 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 283.649 454.599 Td /F1 9.8 Tf  [(0.027)] TJ ET
0.267 0.267 0.267 rg
329.979 464.454 57.403 0.750 re f
329.979 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.229 454.599 Td /F1 9.8 Tf  [(Yes)] TJ ET
0.267 0.267 0.267 rg
386.632 464.454 82.893 0.750 re f
386.632 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.882 454.599 Td /F1 9.8 Tf  [(16.5)] TJ ET
0.267 0.267 0.267 rg
468.775 464.454 52.330 0.750 re f
468.775 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 474.025 454.599 Td /F1 9.8 Tf  [(11.46)] TJ ET
0.267 0.267 0.267 rg
520.355 464.454 60.520 0.750 re f
520.355 448.573 0.750 16.631 re f
580.125 448.573 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 525.605 454.599 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 448.573 130.838 0.750 re f
26.625 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 438.718 Td /F1 9.8 Tf  [(10-meter run/walk velocity )] TJ ET
BT 31.875 431.086 Td /F1 9.8 Tf  [(\(m/sec\))] TJ ET
0.267 0.267 0.267 rg
156.713 448.573 70.856 0.750 re f
156.713 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 161.963 438.718 Td /F1 9.8 Tf  [(-0.25)] TJ ET
0.267 0.267 0.267 rg
226.818 448.573 52.330 0.750 re f
226.818 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 232.068 438.718 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.267 0.267 0.267 rg
278.399 448.573 52.330 0.750 re f
278.399 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 283.649 438.718 Td /F1 9.8 Tf  [(0.007)] TJ ET
0.267 0.267 0.267 rg
329.979 448.573 57.403 0.750 re f
329.979 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 335.229 438.718 Td /F1 9.8 Tf  [(Yes)] TJ ET
0.267 0.267 0.267 rg
386.632 448.573 82.893 0.750 re f
386.632 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 391.882 438.718 Td /F1 9.8 Tf  [(0.33)] TJ ET
0.267 0.267 0.267 rg
468.775 448.573 52.330 0.750 re f
468.775 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 474.025 438.718 Td /F1 9.8 Tf  [(0.07)] TJ ET
0.267 0.267 0.267 rg
520.355 448.573 60.520 0.750 re f
520.355 425.060 0.750 24.263 re f
580.125 425.060 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 525.605 438.718 Td /F1 9.8 Tf  [(0.0001)] TJ ET
0.267 0.267 0.267 rg
26.625 425.060 130.838 0.750 re f
26.625 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 415.205 Td /F1 9.8 Tf  [(PedsQL Total Score)] TJ ET
0.267 0.267 0.267 rg
156.713 425.060 70.856 0.750 re f
156.713 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 161.963 415.205 Td /F1 9.8 Tf  [(-0.13)] TJ ET
0.267 0.267 0.267 rg
226.818 425.060 52.330 0.750 re f
226.818 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 232.068 415.205 Td /F1 9.8 Tf  [(2.67)] TJ ET
0.267 0.267 0.267 rg
278.399 425.060 52.330 0.750 re f
278.399 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 283.649 415.205 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
329.979 425.060 57.403 0.750 re f
329.979 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.229 415.205 Td /F1 9.8 Tf  [(No)] TJ ET
0.267 0.267 0.267 rg
386.632 425.060 82.893 0.750 re f
386.632 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.882 415.205 Td /F1 9.8 Tf  [(1.03)] TJ ET
0.267 0.267 0.267 rg
468.775 425.060 52.330 0.750 re f
468.775 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 474.025 415.205 Td /F1 9.8 Tf  [(3.26)] TJ ET
0.267 0.267 0.267 rg
520.355 425.060 60.520 0.750 re f
520.355 409.179 0.750 16.631 re f
580.125 409.179 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 525.605 415.205 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 409.179 130.838 0.750 re f
26.625 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 399.324 Td /F1 9.8 Tf  [(PedsQL Physical Function )] TJ ET
BT 31.875 391.693 Td /F1 9.8 Tf  [(Score)] TJ ET
0.267 0.267 0.267 rg
156.713 409.179 70.856 0.750 re f
156.713 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 161.963 399.324 Td /F1 9.8 Tf  [(-2.08)] TJ ET
0.267 0.267 0.267 rg
226.818 409.179 52.330 0.750 re f
226.818 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 232.068 399.324 Td /F1 9.8 Tf  [(6.96)] TJ ET
0.267 0.267 0.267 rg
278.399 409.179 52.330 0.750 re f
278.399 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 283.649 399.324 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
329.979 409.179 57.403 0.750 re f
329.979 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 335.229 399.324 Td /F1 9.8 Tf  [(No)] TJ ET
0.267 0.267 0.267 rg
386.632 409.179 82.893 0.750 re f
386.632 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 391.882 399.324 Td /F1 9.8 Tf  [(3.74)] TJ ET
0.267 0.267 0.267 rg
468.775 409.179 52.330 0.750 re f
468.775 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 474.025 399.324 Td /F1 9.8 Tf  [(4.71)] TJ ET
0.267 0.267 0.267 rg
520.355 409.179 60.520 0.750 re f
520.355 385.666 0.750 24.263 re f
580.125 385.666 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 525.605 399.324 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 385.666 130.838 0.750 re f
26.625 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 375.811 Td /F1 9.8 Tf  [(PODCI Global)] TJ ET
0.267 0.267 0.267 rg
156.713 385.666 70.856 0.750 re f
156.713 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 161.963 375.811 Td /F1 9.8 Tf  [(-5.05)] TJ ET
0.267 0.267 0.267 rg
226.818 385.666 52.330 0.750 re f
226.818 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 232.068 375.811 Td /F1 9.8 Tf  [(2.24)] TJ ET
0.267 0.267 0.267 rg
278.399 385.666 52.330 0.750 re f
278.399 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 283.649 375.811 Td /F1 9.8 Tf  [(0.027)] TJ ET
0.267 0.267 0.267 rg
329.979 385.666 57.403 0.750 re f
329.979 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.229 375.811 Td /F1 9.8 Tf  [(Yes)] TJ ET
0.267 0.267 0.267 rg
386.632 385.666 82.893 0.750 re f
386.632 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.882 375.811 Td /F1 9.8 Tf  [(0.43)] TJ ET
0.267 0.267 0.267 rg
468.775 385.666 52.330 0.750 re f
468.775 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 474.025 375.811 Td /F1 9.8 Tf  [(0.46)] TJ ET
0.267 0.267 0.267 rg
520.355 385.666 60.520 0.750 re f
520.355 369.785 0.750 16.631 re f
580.125 369.785 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 525.605 375.811 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 369.785 130.838 0.750 re f
26.625 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 359.930 Td /F1 9.8 Tf  [(PODCI Transfer / Basic )] TJ ET
BT 31.875 352.299 Td /F1 9.8 Tf  [(Mobility)] TJ ET
0.267 0.267 0.267 rg
156.713 369.785 70.856 0.750 re f
156.713 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 161.963 359.930 Td /F1 9.8 Tf  [(-9.95)] TJ ET
0.267 0.267 0.267 rg
226.818 369.785 52.330 0.750 re f
226.818 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 232.068 359.930 Td /F1 9.8 Tf  [(3.94)] TJ ET
0.267 0.267 0.267 rg
278.399 369.785 52.330 0.750 re f
278.399 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 283.649 359.930 Td /F1 9.8 Tf  [(0.013)] TJ ET
0.267 0.267 0.267 rg
329.979 369.785 57.403 0.750 re f
329.979 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 335.229 359.930 Td /F1 9.8 Tf  [(Yes)] TJ ET
0.267 0.267 0.267 rg
386.632 369.785 82.893 0.750 re f
386.632 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 391.882 359.930 Td /F1 9.8 Tf  [(0.31)] TJ ET
0.267 0.267 0.267 rg
468.775 369.785 52.330 0.750 re f
468.775 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 474.025 359.930 Td /F1 9.8 Tf  [(0.51)] TJ ET
0.267 0.267 0.267 rg
520.355 369.785 60.520 0.750 re f
520.355 346.273 0.750 24.263 re f
580.125 346.273 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 525.605 359.930 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
26.625 346.273 130.838 0.750 re f
26.625 330.391 130.838 0.750 re f
26.625 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 336.418 Td /F1 9.8 Tf  [(PODCI Sports)] TJ ET
0.267 0.267 0.267 rg
156.713 346.273 70.856 0.750 re f
156.713 330.391 70.856 0.750 re f
156.713 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 161.963 336.418 Td /F1 9.8 Tf  [(-3.11)] TJ ET
0.267 0.267 0.267 rg
226.818 346.273 52.330 0.750 re f
226.818 330.391 52.330 0.750 re f
226.818 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 232.068 336.418 Td /F1 9.8 Tf  [(4.04)] TJ ET
0.267 0.267 0.267 rg
278.399 346.273 52.330 0.750 re f
278.399 330.391 52.330 0.750 re f
278.399 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 283.649 336.418 Td /F1 9.8 Tf  [(ns)] TJ ET
0.267 0.267 0.267 rg
329.979 346.273 57.403 0.750 re f
329.979 330.391 57.403 0.750 re f
329.979 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 335.229 336.418 Td /F1 9.8 Tf  [(No)] TJ ET
0.267 0.267 0.267 rg
386.632 346.273 82.893 0.750 re f
386.632 330.391 82.893 0.750 re f
386.632 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 391.882 336.418 Td /F1 9.8 Tf  [(1.49)] TJ ET
0.267 0.267 0.267 rg
468.775 346.273 52.330 0.750 re f
468.775 330.391 52.330 0.750 re f
468.775 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 474.025 336.418 Td /F1 9.8 Tf  [(0.99)] TJ ET
0.267 0.267 0.267 rg
520.355 346.273 60.520 0.750 re f
520.355 330.391 60.520 0.750 re f
520.355 330.391 0.750 16.631 re f
580.125 330.391 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 525.605 336.418 Td /F1 9.8 Tf  [(ns)] TJ ET
BT 26.250 275.493 Td /F1 9.8 Tf  [(Correlation of 1-year changes in 6MWD and HrQOL measures is shown in Table 5. In boys with DMD, change in 6MWD was )] TJ ET
BT 26.250 263.588 Td /F1 9.8 Tf  [(most highly correlated with change in PODCI global and PODCI transfer and basic mobility scores \(r=0.76 and r=0.93, )] TJ ET
BT 26.250 251.683 Td /F1 9.8 Tf  [(respectively\).)] TJ ET
q
26.250 228.066 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 230.813 Td /F1 9.8 Tf  [(Table 5: Pearson�s correlation of 1-year change in 6MWD, PedsQL and PODCI measures)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 115.475 555.000 105.091 re f
0.965 0.965 0.965 rg
27.000 195.631 207.656 24.185 re f
0.267 0.267 0.267 rg
26.625 219.441 208.031 0.750 re f
26.625 195.256 0.750 24.935 re f
0.271 0.267 0.267 rg
BT 31.500 210.292 Td /F4 9.8 Tf  [(6MWD vs. Person-Reported Measures )] TJ ET
BT 31.500 198.387 Td /F4 9.8 Tf  [(\(Change\))] TJ ET
0.965 0.965 0.965 rg
234.656 195.631 80.106 24.185 re f
0.267 0.267 0.267 rg
234.656 219.441 80.106 0.750 re f
0.271 0.267 0.267 rg
BT 239.156 210.292 Td /F4 9.8 Tf  [(DMD \(n=13\))] TJ ET
0.965 0.965 0.965 rg
314.762 195.631 94.124 24.185 re f
0.267 0.267 0.267 rg
314.762 219.441 94.124 0.750 re f
0.271 0.267 0.267 rg
BT 319.262 210.292 Td /F4 9.8 Tf  [(Control \(n=18\))] TJ ET
0.965 0.965 0.965 rg
408.886 195.631 171.614 24.185 re f
0.267 0.267 0.267 rg
408.886 219.441 171.989 0.750 re f
580.125 195.256 0.750 24.935 re f
0.271 0.267 0.267 rg
BT 413.386 210.292 Td /F4 9.8 Tf  [(Combined\(Full Range, n=31\))] TJ ET
0.267 0.267 0.267 rg
26.625 195.256 208.406 0.750 re f
26.625 179.375 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 185.401 Td /F1 9.8 Tf  [(PedsQL Total Score)] TJ ET
0.267 0.267 0.267 rg
234.281 195.256 80.856 0.750 re f
234.281 179.375 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 239.531 185.401 Td /F1 9.8 Tf  [(0.01)] TJ ET
0.267 0.267 0.267 rg
314.387 195.256 94.874 0.750 re f
314.387 179.375 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.637 185.401 Td /F1 9.8 Tf  [(-0.13)] TJ ET
0.267 0.267 0.267 rg
408.511 195.256 172.364 0.750 re f
408.511 179.375 0.750 16.631 re f
580.125 179.375 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.761 185.401 Td /F1 9.8 Tf  [(-0.17)] TJ ET
0.267 0.267 0.267 rg
26.625 179.375 208.406 0.750 re f
26.625 163.494 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 169.520 Td /F1 9.8 Tf  [(PedsQL Physical Function Score)] TJ ET
0.267 0.267 0.267 rg
234.281 179.375 80.856 0.750 re f
234.281 163.494 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 239.531 169.520 Td /F1 9.8 Tf  [(-0.36)] TJ ET
0.267 0.267 0.267 rg
314.387 179.375 94.874 0.750 re f
314.387 163.494 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.637 169.520 Td /F1 9.8 Tf  [(-0.06)] TJ ET
0.267 0.267 0.267 rg
408.511 179.375 172.364 0.750 re f
408.511 163.494 0.750 16.631 re f
580.125 163.494 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.761 169.520 Td /F1 9.8 Tf  [(-0.38)] TJ ET
0.267 0.267 0.267 rg
26.625 163.494 208.406 0.750 re f
26.625 147.613 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 153.639 Td /F1 9.8 Tf  [(PODCI Global Score)] TJ ET
0.267 0.267 0.267 rg
234.281 163.494 80.856 0.750 re f
234.281 147.613 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 239.531 153.639 Td /F1 9.8 Tf  [(0.76)] TJ ET
0.267 0.267 0.267 rg
314.387 163.494 94.874 0.750 re f
314.387 147.613 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.637 153.639 Td /F1 9.8 Tf  [(0.07)] TJ ET
0.267 0.267 0.267 rg
408.511 163.494 172.364 0.750 re f
408.511 147.613 0.750 16.631 re f
580.125 147.613 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.761 153.639 Td /F1 9.8 Tf  [(0.68)] TJ ET
0.267 0.267 0.267 rg
26.625 147.613 208.406 0.750 re f
26.625 131.731 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 137.758 Td /F1 9.8 Tf  [(PODCI Transfer / Basic Mobility)] TJ ET
0.267 0.267 0.267 rg
234.281 147.613 80.856 0.750 re f
234.281 131.731 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 239.531 137.758 Td /F1 9.8 Tf  [(0.93)] TJ ET
0.267 0.267 0.267 rg
314.387 147.613 94.874 0.750 re f
314.387 131.731 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.637 137.758 Td /F1 9.8 Tf  [(-0.05)] TJ ET
0.267 0.267 0.267 rg
408.511 147.613 172.364 0.750 re f
408.511 131.731 0.750 16.631 re f
580.125 131.731 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.761 137.758 Td /F1 9.8 Tf  [(0.76)] TJ ET
0.267 0.267 0.267 rg
26.625 131.731 208.406 0.750 re f
26.625 115.850 208.406 0.750 re f
26.625 115.850 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 121.876 Td /F1 9.8 Tf  [(PODCI Sports)] TJ ET
0.267 0.267 0.267 rg
234.281 131.731 80.856 0.750 re f
234.281 115.850 80.856 0.750 re f
234.281 115.850 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 239.531 121.876 Td /F1 9.8 Tf  [(0.45)] TJ ET
0.267 0.267 0.267 rg
314.387 131.731 94.874 0.750 re f
314.387 115.850 94.874 0.750 re f
314.387 115.850 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 319.637 121.876 Td /F1 9.8 Tf  [(-0.60)] TJ ET
0.267 0.267 0.267 rg
408.511 131.731 172.364 0.750 re f
408.511 115.850 172.364 0.750 re f
408.511 115.850 0.750 16.631 re f
580.125 115.850 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 413.761 121.876 Td /F1 9.8 Tf  [(0.37)] TJ ET
BT 26.250 60.951 Td /F1 9.8 Tf  [(Best-fit regression equations estimating 6MWD for each of the HrQOL items is listed in Table 6. Consistent with the higher )] TJ ET
BT 26.250 49.047 Td /F1 9.8 Tf  [(degrees of correlation between 6MWD and PODCI measures and change in those measures over time, the PODCI global and )] TJ ET
BT 26.250 37.142 Td /F1 9.8 Tf  [(PODCI transfer and basic mobility scales provided the best estimates of 6MWT performance. We selected the latter to best )] TJ ET
Q
q
225.000 0 0 168.000 35.250 599.250 cm /I9 Do
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q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(7)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Muscular Dystrophy)] TJ ET

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0.271 0.267 0.267 rg
BT 160.815 701.194 Td /F1 9.8 Tf  [(6MWD = 5.39\(PedsQL Total Score\)+4.4\(Height cm\)-)] TJ ET
BT 160.815 693.563 Td /F1 9.8 Tf  [(2.41\(Weight kg\)-399.55)] TJ ET
0.267 0.267 0.267 rg
438.375 711.049 76.278 0.750 re f
438.375 687.537 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 443.625 701.194 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
513.903 711.049 66.972 0.750 re f
513.903 687.537 0.750 24.263 re f
580.125 687.537 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 519.153 701.194 Td /F1 9.8 Tf  [(0.00001)] TJ ET
0.267 0.267 0.267 rg
26.625 687.537 129.690 0.750 re f
26.625 664.024 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 677.682 Td /F1 9.8 Tf  [(PedsQL Physical Function)] TJ ET
0.267 0.267 0.267 rg
155.565 687.537 283.560 0.750 re f
155.565 664.024 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 160.815 677.682 Td /F1 9.8 Tf  [(6MWD = 3.67\(PedsQL Physical Function Score\)+3.87\(Height )] TJ ET
BT 160.815 670.051 Td /F1 9.8 Tf  [(cm\)-2.21\(Weight kg\)-199.99)] TJ ET
0.267 0.267 0.267 rg
438.375 687.537 76.278 0.750 re f
438.375 664.024 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 443.625 677.682 Td /F1 9.8 Tf  [(0.56)] TJ ET
0.267 0.267 0.267 rg
513.903 687.537 66.972 0.750 re f
513.903 664.024 0.750 24.263 re f
580.125 664.024 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 519.153 677.682 Td /F1 9.8 Tf  [(0.00001)] TJ ET
0.267 0.267 0.267 rg
26.625 664.024 129.690 0.750 re f
26.625 637.561 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 31.875 654.169 Td /F1 9.8 Tf  [(PODCI Sports)] TJ ET
0.267 0.267 0.267 rg
155.565 664.024 283.560 0.750 re f
155.565 637.561 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 160.815 651.809 Td /F1 9.8 Tf  [(6MWD = 0.0003\(PODCI Sports)] TJ ET
BT 296.545 654.374 Td /F1 8.7 Tf  [(3)] TJ ET
BT 301.363 651.809 Td /F1 9.8 Tf  [(\)+3.35\(Height cm\)-)] TJ ET
BT 160.815 643.587 Td /F1 9.8 Tf  [(1.90\(Weight kg\)-56.35)] TJ ET
0.267 0.267 0.267 rg
438.375 664.024 76.278 0.750 re f
438.375 637.561 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 443.625 654.169 Td /F1 9.8 Tf  [(0.79)] TJ ET
0.267 0.267 0.267 rg
513.903 664.024 66.972 0.750 re f
513.903 637.561 0.750 27.213 re f
580.125 637.561 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 519.153 654.169 Td /F1 9.8 Tf  [(0.00001)] TJ ET
0.267 0.267 0.267 rg
26.625 637.561 129.690 0.750 re f
26.625 611.098 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 31.875 627.706 Td /F1 9.8 Tf  [(PODCI Global)] TJ ET
0.267 0.267 0.267 rg
155.565 637.561 283.560 0.750 re f
155.565 611.098 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 160.815 625.346 Td /F1 9.8 Tf  [(6MWD = 0.0004\(PODCI Global)] TJ ET
BT 296.545 627.911 Td /F1 8.7 Tf  [(3)] TJ ET
BT 301.363 625.346 Td /F1 9.8 Tf  [(\)+3.42\(Height cm\)-)] TJ ET
BT 160.815 617.124 Td /F1 9.8 Tf  [(2.31\(Weight kg\)-158.36)] TJ ET
0.267 0.267 0.267 rg
438.375 637.561 76.278 0.750 re f
438.375 611.098 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 443.625 627.706 Td /F1 9.8 Tf  [(0.83)] TJ ET
0.267 0.267 0.267 rg
513.903 637.561 66.972 0.750 re f
513.903 611.098 0.750 27.213 re f
580.125 611.098 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 519.153 627.706 Td /F1 9.8 Tf  [(0.00001)] TJ ET
0.267 0.267 0.267 rg
26.625 611.098 129.690 0.750 re f
26.625 584.635 129.690 0.750 re f
26.625 584.635 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 31.875 601.243 Td /F1 9.8 Tf  [(PODCI Transfer / Basic )] TJ ET
BT 31.875 593.612 Td /F1 9.8 Tf  [(Mobility)] TJ ET
0.267 0.267 0.267 rg
155.565 611.098 283.560 0.750 re f
155.565 584.635 283.560 0.750 re f
155.565 584.635 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 160.815 598.882 Td /F1 9.8 Tf  [(6MWD = 0.0004\(PODCI T&M)] TJ ET
BT 288.949 601.448 Td /F1 8.7 Tf  [(3)] TJ ET
BT 293.768 598.882 Td /F1 9.8 Tf  [(\)+4.41\(Height cm\)-2.80\(Weight )] TJ ET
BT 160.815 590.661 Td /F1 9.8 Tf  [(kg\)-310.79)] TJ ET
0.267 0.267 0.267 rg
438.375 611.098 76.278 0.750 re f
438.375 584.635 76.278 0.750 re f
438.375 584.635 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 443.625 601.243 Td /F1 9.8 Tf  [(0.83)] TJ ET
0.267 0.267 0.267 rg
513.903 611.098 66.972 0.750 re f
513.903 584.635 66.972 0.750 re f
513.903 584.635 0.750 27.213 re f
580.125 584.635 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 519.153 601.243 Td /F1 9.8 Tf  [(0.00001)] TJ ET
BT 26.250 529.736 Td /F1 9.8 Tf  [(Using the baseline calculated MCID for the PODCI transfer and basic mobility score of 4.5 points and mean height and weight )] TJ ET
BT 26.250 517.831 Td /F1 9.8 Tf  [(for the DMD group, we calculated 6MWD from a range of PODCI scores to demonstrate the degree of 6MWD change that )] TJ ET
BT 26.250 505.926 Td /F1 9.8 Tf  [(would be associated with a �meaningful� change in parent-proxy-related PODCI scores \(Table 7\). From a HrQOL-based )] TJ ET
BT 26.250 494.022 Td /F1 9.8 Tf  [(perspective, a �meaningful� change in mobility might be related to small changes in walking distance at lower levels of function. )] TJ ET
BT 26.250 482.117 Td /F1 9.8 Tf  [(For instance, a 4.5 point change in PODCI transfer and basic mobility score from 30 to 34.5 is associated with a 5.6m 6MWD )] TJ ET
BT 26.250 470.212 Td /F1 9.8 Tf  [(change from 150.3 to 155.9m. At the other end of the spectrum, PODCI levels closer to normative values and associated with )] TJ ET
BT 26.250 458.307 Td /F1 9.8 Tf  [(higher 6MWD values would require a greater change in 6MWD over one-year to affect a �meaningful� change of 4.5 in PODCI )] TJ ET
BT 26.250 446.403 Td /F1 9.8 Tf  [(transfer and basic scores. A 4.5 point change at this higher level of ambulatory function would be associated with a 6MWD )] TJ ET
BT 26.250 434.498 Td /F1 9.8 Tf  [(change of almost 46m.)] TJ ET
q
26.250 397.144 555.000 27.473 re W n
0.271 0.267 0.267 rg
BT 26.250 413.628 Td /F1 9.8 Tf  [(Table 7: Change in 6MWD necessary at different ranges of function to achieve a 4.5 point \(MCID\) change in PODCI Transfer )] TJ ET
BT 26.250 399.892 Td /F1 9.8 Tf  [(and Basic Mobility scale score)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 264.696 555.000 124.949 re f
0.965 0.965 0.965 rg
27.000 376.615 187.397 12.280 re f
0.267 0.267 0.267 rg
26.625 388.519 187.772 0.750 re f
26.625 376.240 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 31.500 379.371 Td /F4 9.8 Tf  [(PODCI Range \(pts\))] TJ ET
0.965 0.965 0.965 rg
214.397 376.615 175.506 12.280 re f
0.267 0.267 0.267 rg
214.397 388.519 175.506 0.750 re f
0.271 0.267 0.267 rg
BT 218.897 379.371 Td /F4 9.8 Tf  [(6MWD Range \(m\))] TJ ET
0.965 0.965 0.965 rg
389.903 376.615 190.597 12.280 re f
0.267 0.267 0.267 rg
389.903 388.519 190.972 0.750 re f
580.125 376.240 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 394.403 379.371 Td /F4 9.8 Tf  [(6MWD Change \(m\))] TJ ET
0.267 0.267 0.267 rg
26.625 376.240 188.147 0.750 re f
26.625 360.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 366.385 Td /F1 9.8 Tf  [(30 � 34.5)] TJ ET
0.267 0.267 0.267 rg
214.022 376.240 176.256 0.750 re f
214.022 360.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 366.385 Td /F1 9.8 Tf  [(150.3 � 155.9)] TJ ET
0.267 0.267 0.267 rg
389.528 376.240 191.347 0.750 re f
389.528 360.358 0.750 16.631 re f
580.125 360.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 366.385 Td /F1 9.8 Tf  [(5.6)] TJ ET
0.267 0.267 0.267 rg
26.625 360.358 188.147 0.750 re f
26.625 344.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 350.503 Td /F1 9.8 Tf  [(40 � 44.5)] TJ ET
0.267 0.267 0.267 rg
214.022 360.358 176.256 0.750 re f
214.022 344.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 350.503 Td /F1 9.8 Tf  [(165.0 � 174.7)] TJ ET
0.267 0.267 0.267 rg
389.528 360.358 191.347 0.750 re f
389.528 344.477 0.750 16.631 re f
580.125 344.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 350.503 Td /F1 9.8 Tf  [(9.7)] TJ ET
0.267 0.267 0.267 rg
26.625 344.477 188.147 0.750 re f
26.625 328.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 334.622 Td /F1 9.8 Tf  [(50 � 54.5)] TJ ET
0.267 0.267 0.267 rg
214.022 344.477 176.256 0.750 re f
214.022 328.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 334.622 Td /F1 9.8 Tf  [(189.5 � 202.2)] TJ ET
0.267 0.267 0.267 rg
389.528 344.477 191.347 0.750 re f
389.528 328.596 0.750 16.631 re f
580.125 328.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 334.622 Td /F1 9.8 Tf  [(12.7)] TJ ET
0.267 0.267 0.267 rg
26.625 328.596 188.147 0.750 re f
26.625 312.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 318.741 Td /F1 9.8 Tf  [(60 � 64.5)] TJ ET
0.267 0.267 0.267 rg
214.022 328.596 176.256 0.750 re f
214.022 312.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 318.741 Td /F1 9.8 Tf  [(225.9 � 246.8)] TJ ET
0.267 0.267 0.267 rg
389.528 328.596 191.347 0.750 re f
389.528 312.715 0.750 16.631 re f
580.125 312.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 318.741 Td /F1 9.8 Tf  [(20.9)] TJ ET
0.267 0.267 0.267 rg
26.625 312.715 188.147 0.750 re f
26.625 296.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 302.860 Td /F1 9.8 Tf  [(70 � 74.5)] TJ ET
0.267 0.267 0.267 rg
214.022 312.715 176.256 0.750 re f
214.022 296.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 302.860 Td /F1 9.8 Tf  [(276.7 � 304.9)] TJ ET
0.267 0.267 0.267 rg
389.528 312.715 191.347 0.750 re f
389.528 296.833 0.750 16.631 re f
580.125 296.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 302.860 Td /F1 9.8 Tf  [(28.2)] TJ ET
0.267 0.267 0.267 rg
26.625 296.833 188.147 0.750 re f
26.625 280.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 286.978 Td /F1 9.8 Tf  [(80 � 84.5)] TJ ET
0.267 0.267 0.267 rg
214.022 296.833 176.256 0.750 re f
214.022 280.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 286.978 Td /F1 9.8 Tf  [(344.3 � 380.8)] TJ ET
0.267 0.267 0.267 rg
389.528 296.833 191.347 0.750 re f
389.528 280.952 0.750 16.631 re f
580.125 280.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 286.978 Td /F1 9.8 Tf  [(36.5)] TJ ET
0.267 0.267 0.267 rg
26.625 280.952 188.147 0.750 re f
26.625 265.071 188.147 0.750 re f
26.625 265.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 271.097 Td /F1 9.8 Tf  [(90 � 94.5)] TJ ET
0.267 0.267 0.267 rg
214.022 280.952 176.256 0.750 re f
214.022 265.071 176.256 0.750 re f
214.022 265.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 271.097 Td /F1 9.8 Tf  [(431.1 � 477.0)] TJ ET
0.267 0.267 0.267 rg
389.528 280.952 191.347 0.750 re f
389.528 265.071 191.347 0.750 re f
389.528 265.071 0.750 16.631 re f
580.125 265.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 271.097 Td /F1 9.8 Tf  [(45.9)] TJ ET
BT 26.250 192.974 Td /F4 12.0 Tf  [(Discussion)] TJ ET
BT 26.250 173.020 Td /F5 9.8 Tf  [(The PODCI instrument is more sensitive to DMD disease progression than the PedsQL.)] TJ ET
BT 26.250 153.615 Td /F1 9.8 Tf  [(Here we expand on previous work by McDonald and colleagues)] TJ ET
0.267 0.267 0.267 rg
BT 301.531 155.123 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 311.169 153.615 Td /F1 9.8 Tf  [( to demonstrate relationship between clinician-measured )] TJ ET
BT 26.250 141.711 Td /F1 9.8 Tf  [(outcomes of function \(6MWT and 10 meter run/walk velocity\) and parent-reported HrQoL. In support of previous reports, both )] TJ ET
BT 26.250 129.806 Td /F1 9.8 Tf  [(PedsQL and PODCI significantly differentiate between DMD and typically-developing control subjects. In addition, in a )] TJ ET
BT 26.250 117.901 Td /F1 9.8 Tf  [(multicenter international clinical trial which included 174 DMD subjects over a wider range of ambulatory abilities, a modest )] TJ ET
BT 26.250 105.996 Td /F1 9.8 Tf  [(correlation was found between the 6MWD and PedsQL physical scale)] TJ ET
0.267 0.267 0.267 rg
BT 327.545 107.504 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 337.182 105.996 Td /F1 9.8 Tf  [( . In the current study, we demonstrate that the PODCI )] TJ ET
BT 26.250 94.092 Td /F1 9.8 Tf  [(instrument global, transfer and basic mobility, and sports physical function scales are more strongly correlated with 6WMD than )] TJ ET
BT 26.250 82.187 Td /F1 9.8 Tf  [(PedsQL total and physical function scale scores. Similarly, one-year changes in PODCI scores are more strongly correlated )] TJ ET
BT 26.250 70.282 Td /F1 9.8 Tf  [(with 1-year change in 6MWD than are PedsQL scores. These data provide support for the concept that functional performance )] TJ ET
BT 26.250 58.377 Td /F1 9.8 Tf  [(measures of ambulation in DMD such as the 6MWT and 10 meter run/walk velocity are �clinically-meaningful.� These )] TJ ET
BT 26.250 46.473 Td /F1 9.8 Tf  [(longitudinal data show that while PODCI and PedsQL both demonstrate associations with disease severity in DMD, the PODCI )] TJ ET
Q
q
15.000 32.187 577.500 744.813 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(represent the relationship between 6MWD and HrQOL measures due to the PODCI global score being derived in part from \(and )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(thus somewhat collinear with\) the transfer and basic mobility score.)] TJ ET
q
26.250 731.954 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 734.701 Td /F1 9.8 Tf  [(Table 6: Best-fit regression equations for mobility, strength and function)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 584.260 555.000 140.195 re f
0.965 0.965 0.965 rg
27.000 711.424 128.940 12.280 re f
0.267 0.267 0.267 rg
26.625 723.329 129.315 0.750 re f
26.625 711.049 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 31.500 714.180 Td /F4 9.8 Tf  [(Instrument)] TJ ET
0.965 0.965 0.965 rg
155.940 711.424 282.810 12.280 re f
0.267 0.267 0.267 rg
155.940 723.329 282.810 0.750 re f
0.271 0.267 0.267 rg
BT 160.440 714.180 Td /F4 9.8 Tf  [(Equation)] TJ ET
0.965 0.965 0.965 rg
438.750 711.424 75.528 12.280 re f
0.267 0.267 0.267 rg
438.750 723.329 75.528 0.750 re f
0.271 0.267 0.267 rg
BT 443.250 714.180 Td /F4 9.8 Tf  [(R-Squared)] TJ ET
0.965 0.965 0.965 rg
514.278 711.424 66.222 12.280 re f
0.267 0.267 0.267 rg
514.278 723.329 66.597 0.750 re f
580.125 711.049 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 518.778 714.180 Td /F4 9.8 Tf  [(Prof>F)] TJ ET
0.267 0.267 0.267 rg
26.625 711.049 129.690 0.750 re f
26.625 687.537 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 701.194 Td /F1 9.8 Tf  [(PedsQL Total)] TJ ET
0.267 0.267 0.267 rg
155.565 711.049 283.560 0.750 re f
155.565 687.537 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 160.815 701.194 Td /F1 9.8 Tf  [(6MWD = 5.39\(PedsQL Total Score\)+4.4\(Height cm\)-)] TJ ET
BT 160.815 693.563 Td /F1 9.8 Tf  [(2.41\(Weight kg\)-399.55)] TJ ET
0.267 0.267 0.267 rg
438.375 711.049 76.278 0.750 re f
438.375 687.537 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 443.625 701.194 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
513.903 711.049 66.972 0.750 re f
513.903 687.537 0.750 24.263 re f
580.125 687.537 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 519.153 701.194 Td /F1 9.8 Tf  [(0.00001)] TJ ET
0.267 0.267 0.267 rg
26.625 687.537 129.690 0.750 re f
26.625 664.024 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 677.682 Td /F1 9.8 Tf  [(PedsQL Physical Function)] TJ ET
0.267 0.267 0.267 rg
155.565 687.537 283.560 0.750 re f
155.565 664.024 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 160.815 677.682 Td /F1 9.8 Tf  [(6MWD = 3.67\(PedsQL Physical Function Score\)+3.87\(Height )] TJ ET
BT 160.815 670.051 Td /F1 9.8 Tf  [(cm\)-2.21\(Weight kg\)-199.99)] TJ ET
0.267 0.267 0.267 rg
438.375 687.537 76.278 0.750 re f
438.375 664.024 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 443.625 677.682 Td /F1 9.8 Tf  [(0.56)] TJ ET
0.267 0.267 0.267 rg
513.903 687.537 66.972 0.750 re f
513.903 664.024 0.750 24.263 re f
580.125 664.024 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 519.153 677.682 Td /F1 9.8 Tf  [(0.00001)] TJ ET
0.267 0.267 0.267 rg
26.625 664.024 129.690 0.750 re f
26.625 637.561 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 31.875 654.169 Td /F1 9.8 Tf  [(PODCI Sports)] TJ ET
0.267 0.267 0.267 rg
155.565 664.024 283.560 0.750 re f
155.565 637.561 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 160.815 651.809 Td /F1 9.8 Tf  [(6MWD = 0.0003\(PODCI Sports)] TJ ET
BT 296.545 654.374 Td /F1 8.7 Tf  [(3)] TJ ET
BT 301.363 651.809 Td /F1 9.8 Tf  [(\)+3.35\(Height cm\)-)] TJ ET
BT 160.815 643.587 Td /F1 9.8 Tf  [(1.90\(Weight kg\)-56.35)] TJ ET
0.267 0.267 0.267 rg
438.375 664.024 76.278 0.750 re f
438.375 637.561 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 443.625 654.169 Td /F1 9.8 Tf  [(0.79)] TJ ET
0.267 0.267 0.267 rg
513.903 664.024 66.972 0.750 re f
513.903 637.561 0.750 27.213 re f
580.125 637.561 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 519.153 654.169 Td /F1 9.8 Tf  [(0.00001)] TJ ET
0.267 0.267 0.267 rg
26.625 637.561 129.690 0.750 re f
26.625 611.098 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 31.875 627.706 Td /F1 9.8 Tf  [(PODCI Global)] TJ ET
0.267 0.267 0.267 rg
155.565 637.561 283.560 0.750 re f
155.565 611.098 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 160.815 625.346 Td /F1 9.8 Tf  [(6MWD = 0.0004\(PODCI Global)] TJ ET
BT 296.545 627.911 Td /F1 8.7 Tf  [(3)] TJ ET
BT 301.363 625.346 Td /F1 9.8 Tf  [(\)+3.42\(Height cm\)-)] TJ ET
BT 160.815 617.124 Td /F1 9.8 Tf  [(2.31\(Weight kg\)-158.36)] TJ ET
0.267 0.267 0.267 rg
438.375 637.561 76.278 0.750 re f
438.375 611.098 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 443.625 627.706 Td /F1 9.8 Tf  [(0.83)] TJ ET
0.267 0.267 0.267 rg
513.903 637.561 66.972 0.750 re f
513.903 611.098 0.750 27.213 re f
580.125 611.098 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 519.153 627.706 Td /F1 9.8 Tf  [(0.00001)] TJ ET
0.267 0.267 0.267 rg
26.625 611.098 129.690 0.750 re f
26.625 584.635 129.690 0.750 re f
26.625 584.635 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 31.875 601.243 Td /F1 9.8 Tf  [(PODCI Transfer / Basic )] TJ ET
BT 31.875 593.612 Td /F1 9.8 Tf  [(Mobility)] TJ ET
0.267 0.267 0.267 rg
155.565 611.098 283.560 0.750 re f
155.565 584.635 283.560 0.750 re f
155.565 584.635 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 160.815 598.882 Td /F1 9.8 Tf  [(6MWD = 0.0004\(PODCI T&M)] TJ ET
BT 288.949 601.448 Td /F1 8.7 Tf  [(3)] TJ ET
BT 293.768 598.882 Td /F1 9.8 Tf  [(\)+4.41\(Height cm\)-2.80\(Weight )] TJ ET
BT 160.815 590.661 Td /F1 9.8 Tf  [(kg\)-310.79)] TJ ET
0.267 0.267 0.267 rg
438.375 611.098 76.278 0.750 re f
438.375 584.635 76.278 0.750 re f
438.375 584.635 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 443.625 601.243 Td /F1 9.8 Tf  [(0.83)] TJ ET
0.267 0.267 0.267 rg
513.903 611.098 66.972 0.750 re f
513.903 584.635 66.972 0.750 re f
513.903 584.635 0.750 27.213 re f
580.125 584.635 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 519.153 601.243 Td /F1 9.8 Tf  [(0.00001)] TJ ET
BT 26.250 529.736 Td /F1 9.8 Tf  [(Using the baseline calculated MCID for the PODCI transfer and basic mobility score of 4.5 points and mean height and weight )] TJ ET
BT 26.250 517.831 Td /F1 9.8 Tf  [(for the DMD group, we calculated 6MWD from a range of PODCI scores to demonstrate the degree of 6MWD change that )] TJ ET
BT 26.250 505.926 Td /F1 9.8 Tf  [(would be associated with a �meaningful� change in parent-proxy-related PODCI scores \(Table 7\). From a HrQOL-based )] TJ ET
BT 26.250 494.022 Td /F1 9.8 Tf  [(perspective, a �meaningful� change in mobility might be related to small changes in walking distance at lower levels of function. )] TJ ET
BT 26.250 482.117 Td /F1 9.8 Tf  [(For instance, a 4.5 point change in PODCI transfer and basic mobility score from 30 to 34.5 is associated with a 5.6m 6MWD )] TJ ET
BT 26.250 470.212 Td /F1 9.8 Tf  [(change from 150.3 to 155.9m. At the other end of the spectrum, PODCI levels closer to normative values and associated with )] TJ ET
BT 26.250 458.307 Td /F1 9.8 Tf  [(higher 6MWD values would require a greater change in 6MWD over one-year to affect a �meaningful� change of 4.5 in PODCI )] TJ ET
BT 26.250 446.403 Td /F1 9.8 Tf  [(transfer and basic scores. A 4.5 point change at this higher level of ambulatory function would be associated with a 6MWD )] TJ ET
BT 26.250 434.498 Td /F1 9.8 Tf  [(change of almost 46m.)] TJ ET
q
26.250 397.144 555.000 27.473 re W n
0.271 0.267 0.267 rg
BT 26.250 413.628 Td /F1 9.8 Tf  [(Table 7: Change in 6MWD necessary at different ranges of function to achieve a 4.5 point \(MCID\) change in PODCI Transfer )] TJ ET
BT 26.250 399.892 Td /F1 9.8 Tf  [(and Basic Mobility scale score)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 264.696 555.000 124.949 re f
0.965 0.965 0.965 rg
27.000 376.615 187.397 12.280 re f
0.267 0.267 0.267 rg
26.625 388.519 187.772 0.750 re f
26.625 376.240 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 31.500 379.371 Td /F4 9.8 Tf  [(PODCI Range \(pts\))] TJ ET
0.965 0.965 0.965 rg
214.397 376.615 175.506 12.280 re f
0.267 0.267 0.267 rg
214.397 388.519 175.506 0.750 re f
0.271 0.267 0.267 rg
BT 218.897 379.371 Td /F4 9.8 Tf  [(6MWD Range \(m\))] TJ ET
0.965 0.965 0.965 rg
389.903 376.615 190.597 12.280 re f
0.267 0.267 0.267 rg
389.903 388.519 190.972 0.750 re f
580.125 376.240 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 394.403 379.371 Td /F4 9.8 Tf  [(6MWD Change \(m\))] TJ ET
0.267 0.267 0.267 rg
26.625 376.240 188.147 0.750 re f
26.625 360.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 366.385 Td /F1 9.8 Tf  [(30 � 34.5)] TJ ET
0.267 0.267 0.267 rg
214.022 376.240 176.256 0.750 re f
214.022 360.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 366.385 Td /F1 9.8 Tf  [(150.3 � 155.9)] TJ ET
0.267 0.267 0.267 rg
389.528 376.240 191.347 0.750 re f
389.528 360.358 0.750 16.631 re f
580.125 360.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 366.385 Td /F1 9.8 Tf  [(5.6)] TJ ET
0.267 0.267 0.267 rg
26.625 360.358 188.147 0.750 re f
26.625 344.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 350.503 Td /F1 9.8 Tf  [(40 � 44.5)] TJ ET
0.267 0.267 0.267 rg
214.022 360.358 176.256 0.750 re f
214.022 344.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 350.503 Td /F1 9.8 Tf  [(165.0 � 174.7)] TJ ET
0.267 0.267 0.267 rg
389.528 360.358 191.347 0.750 re f
389.528 344.477 0.750 16.631 re f
580.125 344.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 350.503 Td /F1 9.8 Tf  [(9.7)] TJ ET
0.267 0.267 0.267 rg
26.625 344.477 188.147 0.750 re f
26.625 328.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 334.622 Td /F1 9.8 Tf  [(50 � 54.5)] TJ ET
0.267 0.267 0.267 rg
214.022 344.477 176.256 0.750 re f
214.022 328.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 334.622 Td /F1 9.8 Tf  [(189.5 � 202.2)] TJ ET
0.267 0.267 0.267 rg
389.528 344.477 191.347 0.750 re f
389.528 328.596 0.750 16.631 re f
580.125 328.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 334.622 Td /F1 9.8 Tf  [(12.7)] TJ ET
0.267 0.267 0.267 rg
26.625 328.596 188.147 0.750 re f
26.625 312.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 318.741 Td /F1 9.8 Tf  [(60 � 64.5)] TJ ET
0.267 0.267 0.267 rg
214.022 328.596 176.256 0.750 re f
214.022 312.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 318.741 Td /F1 9.8 Tf  [(225.9 � 246.8)] TJ ET
0.267 0.267 0.267 rg
389.528 328.596 191.347 0.750 re f
389.528 312.715 0.750 16.631 re f
580.125 312.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 318.741 Td /F1 9.8 Tf  [(20.9)] TJ ET
0.267 0.267 0.267 rg
26.625 312.715 188.147 0.750 re f
26.625 296.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 302.860 Td /F1 9.8 Tf  [(70 � 74.5)] TJ ET
0.267 0.267 0.267 rg
214.022 312.715 176.256 0.750 re f
214.022 296.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 302.860 Td /F1 9.8 Tf  [(276.7 � 304.9)] TJ ET
0.267 0.267 0.267 rg
389.528 312.715 191.347 0.750 re f
389.528 296.833 0.750 16.631 re f
580.125 296.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 302.860 Td /F1 9.8 Tf  [(28.2)] TJ ET
0.267 0.267 0.267 rg
26.625 296.833 188.147 0.750 re f
26.625 280.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 286.978 Td /F1 9.8 Tf  [(80 � 84.5)] TJ ET
0.267 0.267 0.267 rg
214.022 296.833 176.256 0.750 re f
214.022 280.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 286.978 Td /F1 9.8 Tf  [(344.3 � 380.8)] TJ ET
0.267 0.267 0.267 rg
389.528 296.833 191.347 0.750 re f
389.528 280.952 0.750 16.631 re f
580.125 280.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 286.978 Td /F1 9.8 Tf  [(36.5)] TJ ET
0.267 0.267 0.267 rg
26.625 280.952 188.147 0.750 re f
26.625 265.071 188.147 0.750 re f
26.625 265.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 271.097 Td /F1 9.8 Tf  [(90 � 94.5)] TJ ET
0.267 0.267 0.267 rg
214.022 280.952 176.256 0.750 re f
214.022 265.071 176.256 0.750 re f
214.022 265.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 271.097 Td /F1 9.8 Tf  [(431.1 � 477.0)] TJ ET
0.267 0.267 0.267 rg
389.528 280.952 191.347 0.750 re f
389.528 265.071 191.347 0.750 re f
389.528 265.071 0.750 16.631 re f
580.125 265.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 271.097 Td /F1 9.8 Tf  [(45.9)] TJ ET
BT 26.250 192.974 Td /F4 12.0 Tf  [(Discussion)] TJ ET
BT 26.250 173.020 Td /F5 9.8 Tf  [(The PODCI instrument is more sensitive to DMD disease progression than the PedsQL.)] TJ ET
BT 26.250 153.615 Td /F1 9.8 Tf  [(Here we expand on previous work by McDonald and colleagues)] TJ ET
0.267 0.267 0.267 rg
BT 301.531 155.123 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 311.169 153.615 Td /F1 9.8 Tf  [( to demonstrate relationship between clinician-measured )] TJ ET
BT 26.250 141.711 Td /F1 9.8 Tf  [(outcomes of function \(6MWT and 10 meter run/walk velocity\) and parent-reported HrQoL. In support of previous reports, both )] TJ ET
BT 26.250 129.806 Td /F1 9.8 Tf  [(PedsQL and PODCI significantly differentiate between DMD and typically-developing control subjects. In addition, in a )] TJ ET
BT 26.250 117.901 Td /F1 9.8 Tf  [(multicenter international clinical trial which included 174 DMD subjects over a wider range of ambulatory abilities, a modest )] TJ ET
BT 26.250 105.996 Td /F1 9.8 Tf  [(correlation was found between the 6MWD and PedsQL physical scale)] TJ ET
0.267 0.267 0.267 rg
BT 327.545 107.504 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 337.182 105.996 Td /F1 9.8 Tf  [( . In the current study, we demonstrate that the PODCI )] TJ ET
BT 26.250 94.092 Td /F1 9.8 Tf  [(instrument global, transfer and basic mobility, and sports physical function scales are more strongly correlated with 6WMD than )] TJ ET
BT 26.250 82.187 Td /F1 9.8 Tf  [(PedsQL total and physical function scale scores. Similarly, one-year changes in PODCI scores are more strongly correlated )] TJ ET
BT 26.250 70.282 Td /F1 9.8 Tf  [(with 1-year change in 6MWD than are PedsQL scores. These data provide support for the concept that functional performance )] TJ ET
BT 26.250 58.377 Td /F1 9.8 Tf  [(measures of ambulation in DMD such as the 6MWT and 10 meter run/walk velocity are �clinically-meaningful.� These )] TJ ET
BT 26.250 46.473 Td /F1 9.8 Tf  [(longitudinal data show that while PODCI and PedsQL both demonstrate associations with disease severity in DMD, the PODCI )] TJ ET
Q
q
15.000 32.187 577.500 744.813 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(represent the relationship between 6MWD and HrQOL measures due to the PODCI global score being derived in part from \(and )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(thus somewhat collinear with\) the transfer and basic mobility score.)] TJ ET
q
26.250 731.954 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 734.701 Td /F1 9.8 Tf  [(Table 6: Best-fit regression equations for mobility, strength and function)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 584.260 555.000 140.195 re f
0.965 0.965 0.965 rg
27.000 711.424 128.940 12.280 re f
0.267 0.267 0.267 rg
26.625 723.329 129.315 0.750 re f
26.625 711.049 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 31.500 714.180 Td /F4 9.8 Tf  [(Instrument)] TJ ET
0.965 0.965 0.965 rg
155.940 711.424 282.810 12.280 re f
0.267 0.267 0.267 rg
155.940 723.329 282.810 0.750 re f
0.271 0.267 0.267 rg
BT 160.440 714.180 Td /F4 9.8 Tf  [(Equation)] TJ ET
0.965 0.965 0.965 rg
438.750 711.424 75.528 12.280 re f
0.267 0.267 0.267 rg
438.750 723.329 75.528 0.750 re f
0.271 0.267 0.267 rg
BT 443.250 714.180 Td /F4 9.8 Tf  [(R-Squared)] TJ ET
0.965 0.965 0.965 rg
514.278 711.424 66.222 12.280 re f
0.267 0.267 0.267 rg
514.278 723.329 66.597 0.750 re f
580.125 711.049 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 518.778 714.180 Td /F4 9.8 Tf  [(Prof>F)] TJ ET
0.267 0.267 0.267 rg
26.625 711.049 129.690 0.750 re f
26.625 687.537 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 701.194 Td /F1 9.8 Tf  [(PedsQL Total)] TJ ET
0.267 0.267 0.267 rg
155.565 711.049 283.560 0.750 re f
155.565 687.537 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 160.815 701.194 Td /F1 9.8 Tf  [(6MWD = 5.39\(PedsQL Total Score\)+4.4\(Height cm\)-)] TJ ET
BT 160.815 693.563 Td /F1 9.8 Tf  [(2.41\(Weight kg\)-399.55)] TJ ET
0.267 0.267 0.267 rg
438.375 711.049 76.278 0.750 re f
438.375 687.537 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 443.625 701.194 Td /F1 9.8 Tf  [(0.58)] TJ ET
0.267 0.267 0.267 rg
513.903 711.049 66.972 0.750 re f
513.903 687.537 0.750 24.263 re f
580.125 687.537 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 519.153 701.194 Td /F1 9.8 Tf  [(0.00001)] TJ ET
0.267 0.267 0.267 rg
26.625 687.537 129.690 0.750 re f
26.625 664.024 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 31.875 677.682 Td /F1 9.8 Tf  [(PedsQL Physical Function)] TJ ET
0.267 0.267 0.267 rg
155.565 687.537 283.560 0.750 re f
155.565 664.024 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 160.815 677.682 Td /F1 9.8 Tf  [(6MWD = 3.67\(PedsQL Physical Function Score\)+3.87\(Height )] TJ ET
BT 160.815 670.051 Td /F1 9.8 Tf  [(cm\)-2.21\(Weight kg\)-199.99)] TJ ET
0.267 0.267 0.267 rg
438.375 687.537 76.278 0.750 re f
438.375 664.024 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 443.625 677.682 Td /F1 9.8 Tf  [(0.56)] TJ ET
0.267 0.267 0.267 rg
513.903 687.537 66.972 0.750 re f
513.903 664.024 0.750 24.263 re f
580.125 664.024 0.750 24.263 re f
0.271 0.267 0.267 rg
BT 519.153 677.682 Td /F1 9.8 Tf  [(0.00001)] TJ ET
0.267 0.267 0.267 rg
26.625 664.024 129.690 0.750 re f
26.625 637.561 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 31.875 654.169 Td /F1 9.8 Tf  [(PODCI Sports)] TJ ET
0.267 0.267 0.267 rg
155.565 664.024 283.560 0.750 re f
155.565 637.561 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 160.815 651.809 Td /F1 9.8 Tf  [(6MWD = 0.0003\(PODCI Sports)] TJ ET
BT 296.545 654.374 Td /F1 8.7 Tf  [(3)] TJ ET
BT 301.363 651.809 Td /F1 9.8 Tf  [(\)+3.35\(Height cm\)-)] TJ ET
BT 160.815 643.587 Td /F1 9.8 Tf  [(1.90\(Weight kg\)-56.35)] TJ ET
0.267 0.267 0.267 rg
438.375 664.024 76.278 0.750 re f
438.375 637.561 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 443.625 654.169 Td /F1 9.8 Tf  [(0.79)] TJ ET
0.267 0.267 0.267 rg
513.903 664.024 66.972 0.750 re f
513.903 637.561 0.750 27.213 re f
580.125 637.561 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 519.153 654.169 Td /F1 9.8 Tf  [(0.00001)] TJ ET
0.267 0.267 0.267 rg
26.625 637.561 129.690 0.750 re f
26.625 611.098 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 31.875 627.706 Td /F1 9.8 Tf  [(PODCI Global)] TJ ET
0.267 0.267 0.267 rg
155.565 637.561 283.560 0.750 re f
155.565 611.098 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 160.815 625.346 Td /F1 9.8 Tf  [(6MWD = 0.0004\(PODCI Global)] TJ ET
BT 296.545 627.911 Td /F1 8.7 Tf  [(3)] TJ ET
BT 301.363 625.346 Td /F1 9.8 Tf  [(\)+3.42\(Height cm\)-)] TJ ET
BT 160.815 617.124 Td /F1 9.8 Tf  [(2.31\(Weight kg\)-158.36)] TJ ET
0.267 0.267 0.267 rg
438.375 637.561 76.278 0.750 re f
438.375 611.098 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 443.625 627.706 Td /F1 9.8 Tf  [(0.83)] TJ ET
0.267 0.267 0.267 rg
513.903 637.561 66.972 0.750 re f
513.903 611.098 0.750 27.213 re f
580.125 611.098 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 519.153 627.706 Td /F1 9.8 Tf  [(0.00001)] TJ ET
0.267 0.267 0.267 rg
26.625 611.098 129.690 0.750 re f
26.625 584.635 129.690 0.750 re f
26.625 584.635 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 31.875 601.243 Td /F1 9.8 Tf  [(PODCI Transfer / Basic )] TJ ET
BT 31.875 593.612 Td /F1 9.8 Tf  [(Mobility)] TJ ET
0.267 0.267 0.267 rg
155.565 611.098 283.560 0.750 re f
155.565 584.635 283.560 0.750 re f
155.565 584.635 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 160.815 598.882 Td /F1 9.8 Tf  [(6MWD = 0.0004\(PODCI T&M)] TJ ET
BT 288.949 601.448 Td /F1 8.7 Tf  [(3)] TJ ET
BT 293.768 598.882 Td /F1 9.8 Tf  [(\)+4.41\(Height cm\)-2.80\(Weight )] TJ ET
BT 160.815 590.661 Td /F1 9.8 Tf  [(kg\)-310.79)] TJ ET
0.267 0.267 0.267 rg
438.375 611.098 76.278 0.750 re f
438.375 584.635 76.278 0.750 re f
438.375 584.635 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 443.625 601.243 Td /F1 9.8 Tf  [(0.83)] TJ ET
0.267 0.267 0.267 rg
513.903 611.098 66.972 0.750 re f
513.903 584.635 66.972 0.750 re f
513.903 584.635 0.750 27.213 re f
580.125 584.635 0.750 27.213 re f
0.271 0.267 0.267 rg
BT 519.153 601.243 Td /F1 9.8 Tf  [(0.00001)] TJ ET
BT 26.250 529.736 Td /F1 9.8 Tf  [(Using the baseline calculated MCID for the PODCI transfer and basic mobility score of 4.5 points and mean height and weight )] TJ ET
BT 26.250 517.831 Td /F1 9.8 Tf  [(for the DMD group, we calculated 6MWD from a range of PODCI scores to demonstrate the degree of 6MWD change that )] TJ ET
BT 26.250 505.926 Td /F1 9.8 Tf  [(would be associated with a �meaningful� change in parent-proxy-related PODCI scores \(Table 7\). From a HrQOL-based )] TJ ET
BT 26.250 494.022 Td /F1 9.8 Tf  [(perspective, a �meaningful� change in mobility might be related to small changes in walking distance at lower levels of function. )] TJ ET
BT 26.250 482.117 Td /F1 9.8 Tf  [(For instance, a 4.5 point change in PODCI transfer and basic mobility score from 30 to 34.5 is associated with a 5.6m 6MWD )] TJ ET
BT 26.250 470.212 Td /F1 9.8 Tf  [(change from 150.3 to 155.9m. At the other end of the spectrum, PODCI levels closer to normative values and associated with )] TJ ET
BT 26.250 458.307 Td /F1 9.8 Tf  [(higher 6MWD values would require a greater change in 6MWD over one-year to affect a �meaningful� change of 4.5 in PODCI )] TJ ET
BT 26.250 446.403 Td /F1 9.8 Tf  [(transfer and basic scores. A 4.5 point change at this higher level of ambulatory function would be associated with a 6MWD )] TJ ET
BT 26.250 434.498 Td /F1 9.8 Tf  [(change of almost 46m.)] TJ ET
q
26.250 397.144 555.000 27.473 re W n
0.271 0.267 0.267 rg
BT 26.250 413.628 Td /F1 9.8 Tf  [(Table 7: Change in 6MWD necessary at different ranges of function to achieve a 4.5 point \(MCID\) change in PODCI Transfer )] TJ ET
BT 26.250 399.892 Td /F1 9.8 Tf  [(and Basic Mobility scale score)] TJ ET
Q
1.000 1.000 1.000 rg
26.250 264.696 555.000 124.949 re f
0.965 0.965 0.965 rg
27.000 376.615 187.397 12.280 re f
0.267 0.267 0.267 rg
26.625 388.519 187.772 0.750 re f
26.625 376.240 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 31.500 379.371 Td /F4 9.8 Tf  [(PODCI Range \(pts\))] TJ ET
0.965 0.965 0.965 rg
214.397 376.615 175.506 12.280 re f
0.267 0.267 0.267 rg
214.397 388.519 175.506 0.750 re f
0.271 0.267 0.267 rg
BT 218.897 379.371 Td /F4 9.8 Tf  [(6MWD Range \(m\))] TJ ET
0.965 0.965 0.965 rg
389.903 376.615 190.597 12.280 re f
0.267 0.267 0.267 rg
389.903 388.519 190.972 0.750 re f
580.125 376.240 0.750 13.030 re f
0.271 0.267 0.267 rg
BT 394.403 379.371 Td /F4 9.8 Tf  [(6MWD Change \(m\))] TJ ET
0.267 0.267 0.267 rg
26.625 376.240 188.147 0.750 re f
26.625 360.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 366.385 Td /F1 9.8 Tf  [(30 � 34.5)] TJ ET
0.267 0.267 0.267 rg
214.022 376.240 176.256 0.750 re f
214.022 360.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 366.385 Td /F1 9.8 Tf  [(150.3 � 155.9)] TJ ET
0.267 0.267 0.267 rg
389.528 376.240 191.347 0.750 re f
389.528 360.358 0.750 16.631 re f
580.125 360.358 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 366.385 Td /F1 9.8 Tf  [(5.6)] TJ ET
0.267 0.267 0.267 rg
26.625 360.358 188.147 0.750 re f
26.625 344.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 350.503 Td /F1 9.8 Tf  [(40 � 44.5)] TJ ET
0.267 0.267 0.267 rg
214.022 360.358 176.256 0.750 re f
214.022 344.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 350.503 Td /F1 9.8 Tf  [(165.0 � 174.7)] TJ ET
0.267 0.267 0.267 rg
389.528 360.358 191.347 0.750 re f
389.528 344.477 0.750 16.631 re f
580.125 344.477 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 350.503 Td /F1 9.8 Tf  [(9.7)] TJ ET
0.267 0.267 0.267 rg
26.625 344.477 188.147 0.750 re f
26.625 328.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 334.622 Td /F1 9.8 Tf  [(50 � 54.5)] TJ ET
0.267 0.267 0.267 rg
214.022 344.477 176.256 0.750 re f
214.022 328.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 334.622 Td /F1 9.8 Tf  [(189.5 � 202.2)] TJ ET
0.267 0.267 0.267 rg
389.528 344.477 191.347 0.750 re f
389.528 328.596 0.750 16.631 re f
580.125 328.596 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 334.622 Td /F1 9.8 Tf  [(12.7)] TJ ET
0.267 0.267 0.267 rg
26.625 328.596 188.147 0.750 re f
26.625 312.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 318.741 Td /F1 9.8 Tf  [(60 � 64.5)] TJ ET
0.267 0.267 0.267 rg
214.022 328.596 176.256 0.750 re f
214.022 312.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 318.741 Td /F1 9.8 Tf  [(225.9 � 246.8)] TJ ET
0.267 0.267 0.267 rg
389.528 328.596 191.347 0.750 re f
389.528 312.715 0.750 16.631 re f
580.125 312.715 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 318.741 Td /F1 9.8 Tf  [(20.9)] TJ ET
0.267 0.267 0.267 rg
26.625 312.715 188.147 0.750 re f
26.625 296.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 302.860 Td /F1 9.8 Tf  [(70 � 74.5)] TJ ET
0.267 0.267 0.267 rg
214.022 312.715 176.256 0.750 re f
214.022 296.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 302.860 Td /F1 9.8 Tf  [(276.7 � 304.9)] TJ ET
0.267 0.267 0.267 rg
389.528 312.715 191.347 0.750 re f
389.528 296.833 0.750 16.631 re f
580.125 296.833 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 302.860 Td /F1 9.8 Tf  [(28.2)] TJ ET
0.267 0.267 0.267 rg
26.625 296.833 188.147 0.750 re f
26.625 280.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 286.978 Td /F1 9.8 Tf  [(80 � 84.5)] TJ ET
0.267 0.267 0.267 rg
214.022 296.833 176.256 0.750 re f
214.022 280.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 286.978 Td /F1 9.8 Tf  [(344.3 � 380.8)] TJ ET
0.267 0.267 0.267 rg
389.528 296.833 191.347 0.750 re f
389.528 280.952 0.750 16.631 re f
580.125 280.952 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 286.978 Td /F1 9.8 Tf  [(36.5)] TJ ET
0.267 0.267 0.267 rg
26.625 280.952 188.147 0.750 re f
26.625 265.071 188.147 0.750 re f
26.625 265.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 271.097 Td /F1 9.8 Tf  [(90 � 94.5)] TJ ET
0.267 0.267 0.267 rg
214.022 280.952 176.256 0.750 re f
214.022 265.071 176.256 0.750 re f
214.022 265.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 219.272 271.097 Td /F1 9.8 Tf  [(431.1 � 477.0)] TJ ET
0.267 0.267 0.267 rg
389.528 280.952 191.347 0.750 re f
389.528 265.071 191.347 0.750 re f
389.528 265.071 0.750 16.631 re f
580.125 265.071 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 394.778 271.097 Td /F1 9.8 Tf  [(45.9)] TJ ET
BT 26.250 192.974 Td /F4 12.0 Tf  [(Discussion)] TJ ET
BT 26.250 173.020 Td /F5 9.8 Tf  [(The PODCI instrument is more sensitive to DMD disease progression than the PedsQL.)] TJ ET
BT 26.250 153.615 Td /F1 9.8 Tf  [(Here we expand on previous work by McDonald and colleagues)] TJ ET
0.267 0.267 0.267 rg
BT 301.531 155.123 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 311.169 153.615 Td /F1 9.8 Tf  [( to demonstrate relationship between clinician-measured )] TJ ET
BT 26.250 141.711 Td /F1 9.8 Tf  [(outcomes of function \(6MWT and 10 meter run/walk velocity\) and parent-reported HrQoL. In support of previous reports, both )] TJ ET
BT 26.250 129.806 Td /F1 9.8 Tf  [(PedsQL and PODCI significantly differentiate between DMD and typically-developing control subjects. In addition, in a )] TJ ET
BT 26.250 117.901 Td /F1 9.8 Tf  [(multicenter international clinical trial which included 174 DMD subjects over a wider range of ambulatory abilities, a modest )] TJ ET
BT 26.250 105.996 Td /F1 9.8 Tf  [(correlation was found between the 6MWD and PedsQL physical scale)] TJ ET
0.267 0.267 0.267 rg
BT 327.545 107.504 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 337.182 105.996 Td /F1 9.8 Tf  [( . In the current study, we demonstrate that the PODCI )] TJ ET
BT 26.250 94.092 Td /F1 9.8 Tf  [(instrument global, transfer and basic mobility, and sports physical function scales are more strongly correlated with 6WMD than )] TJ ET
BT 26.250 82.187 Td /F1 9.8 Tf  [(PedsQL total and physical function scale scores. Similarly, one-year changes in PODCI scores are more strongly correlated )] TJ ET
BT 26.250 70.282 Td /F1 9.8 Tf  [(with 1-year change in 6MWD than are PedsQL scores. These data provide support for the concept that functional performance )] TJ ET
BT 26.250 58.377 Td /F1 9.8 Tf  [(measures of ambulation in DMD such as the 6MWT and 10 meter run/walk velocity are �clinically-meaningful.� These )] TJ ET
BT 26.250 46.473 Td /F1 9.8 Tf  [(longitudinal data show that while PODCI and PedsQL both demonstrate associations with disease severity in DMD, the PODCI )] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(8)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Muscular Dystrophy)] TJ ET

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0.271 0.267 0.267 rg
q
15.000 28.054 577.500 748.946 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(instrument�s increased sensitivity to change makes it better suited for use as an outcome measure in clinical trials due its ability )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(to show significant change over a 1-year time period commonly employed in current clinical trial designs.)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(The key to this increased level of sensitivity to change associated with disease progression of the PODCI may lie in the design )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(of the instruments themselves, which differ in their approach to self/proxy-reported ability. The PODCI items are framed in terms )] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(of ease or difficulty of a task, such as: �During the last week has it been easy or hard for your child to walk one block?� The )] TJ ET
BT 26.250 700.452 Td /F1 9.8 Tf  [(response options address the perceived physical difficulty of activities: �easy�, �a little hard�, �very hard�, or �can�t do at all�. In )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(contrast, the PedsQL framework addresses the frequency of difficulty with activities. Items are presented such as �In the past )] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(ONE month how much of a problem has your child had with walking more than one block?� Response choices include: �never�, )] TJ ET
BT 26.250 664.738 Td /F1 9.8 Tf  [(�almost never�, �sometimes�, �often�, and �almost always.� The PedsQL represents a subtly different and more participation-)] TJ ET
BT 26.250 652.833 Td /F1 9.8 Tf  [(oriented construct that accounts for not only perceived problems with an activity, but the self-selected frequency or importance )] TJ ET
BT 26.250 640.929 Td /F1 9.8 Tf  [(as well. This subtle difference helps to explain why PODCI transfer and basic mobility items scale items correlate better with )] TJ ET
BT 26.250 629.024 Td /F1 9.8 Tf  [(objective clinical measures of function such as 6MWD or 10 meter run/walk velocity and are more sensitive to changes in those )] TJ ET
BT 26.250 617.119 Td /F1 9.8 Tf  [(abilities over time. They represent a purer measure of locomotor ability that is less affected by behavior.)] TJ ET
BT 26.250 597.714 Td /F5 9.8 Tf  [(Changes in PODCI responses and walking velocity correlate strongly, but �clinical meaningfulness� may differ across )] TJ ET
BT 26.250 585.810 Td /F5 9.8 Tf  [(ranges of performance.)] TJ ET
BT 26.250 566.405 Td /F1 9.8 Tf  [(Regression estimates from this sample allow us to predict 6MWD based on PODCI score, and subsequently we can estimate )] TJ ET
BT 26.250 554.500 Td /F1 9.8 Tf  [(differences between MCID for each measure at differing levels of function. Using our regression estimates, it is possible to )] TJ ET
BT 26.250 542.595 Td /F1 9.8 Tf  [(conclude that a clinically-important difference in person-reported HrQOL via PODCI transfer and basic mobility score is )] TJ ET
BT 26.250 530.691 Td /F1 9.8 Tf  [(associated with a decreasing degree of change in achievable 6MWT velocities or distances as baseline function decreases. )] TJ ET
BT 26.250 518.786 Td /F1 9.8 Tf  [(Thus, the degree of perceived �meaningful change� in walking ability may differ according to functional capacity. Hence at )] TJ ET
BT 26.250 506.881 Td /F1 9.8 Tf  [(higher levels of function on the 6MWT closer to healthy control values, it may take a greater change in 6MWD to produce )] TJ ET
BT 26.250 494.976 Td /F1 9.8 Tf  [(clinically-meaningful changes on a PRO measure such as the PODCI transfer and basic mobility scale. At most levels of )] TJ ET
BT 26.250 483.072 Td /F1 9.8 Tf  [(function typically seen in ambulatory DMD subjects, the threshold change in 6MWD which would correspond to clinically )] TJ ET
BT 26.250 471.167 Td /F1 9.8 Tf  [(meaningful changes in the PODCI transfer and basic mobility scale would be up to 28 to 36 meters. For example, at a mean )] TJ ET
BT 26.250 459.262 Td /F1 9.8 Tf  [(6MWD for DMD of 356 meters documented in one trial)] TJ ET
BT 261.410 463.150 Td /F1 8.7 Tf  [(17)] TJ ET
BT 271.048 459.262 Td /F1 9.8 Tf  [(, the change in 6MWD associated with a clinically-meaningful 4.5 point )] TJ ET
BT 26.250 447.357 Td /F1 9.8 Tf  [(change in PODCI transfer and basic mobility scale would be 36 meters. At a 300 meter 6MWD that seems to represent a lower )] TJ ET
BT 26.250 435.453 Td /F1 9.8 Tf  [(limit threshold level of function placing DMD subjects at risk for loss of ambulation)] TJ ET
0.267 0.267 0.267 rg
BT 377.913 436.960 Td /F4 8.7 Tf  [(18)] TJ ET
0.271 0.267 0.267 rg
BT 387.550 435.453 Td /F1 9.8 Tf  [( , the MCID of 4.5 points on the PODCI )] TJ ET
BT 26.250 423.548 Td /F1 9.8 Tf  [(corresponds to a change in 6MWD of 28 meters. These are levels of ambulatory ability that are frequently seen in clinical trials )] TJ ET
BT 26.250 411.643 Td /F1 9.8 Tf  [(for ambulatory DMD boys, providing support for the 6MWD of 30m MCID and effect size that has been commonly proposed as )] TJ ET
BT 26.250 399.738 Td /F1 9.8 Tf  [(a basis for study power calculations. However, at low levels of function, smaller increases or changes due to treatment in )] TJ ET
BT 26.250 387.834 Td /F1 9.8 Tf  [(achievable walking distance are likely to result in �meaningful� changes in HrQoL.)] TJ ET
BT 26.250 351.231 Td /F4 12.0 Tf  [(Conclusions)] TJ ET
BT 26.250 331.277 Td /F1 9.8 Tf  [(There is ongoing development of regulatory agency guidance regarding the most appropriate measures for use as primary or co-)] TJ ET
BT 26.250 319.372 Td /F1 9.8 Tf  [(primary endpoints for clinical trials for individuals affected by Duchenne and Becker muscular dystrophies)] TJ ET
0.267 0.267 0.267 rg
BT 479.791 320.879 Td /F4 8.7 Tf  [(35)] TJ ET
0.271 0.267 0.267 rg
BT 489.428 319.372 Td /F1 9.8 Tf  [(. A major facet of )] TJ ET
BT 26.250 307.467 Td /F1 9.8 Tf  [(that discussion revolves around what endpoints, whether of muscle strength, functional capacity or QoL should be used as )] TJ ET
BT 556.260 307.467 Td /F6 9.8 Tf  [(a )] TJ ET
BT 26.250 295.563 Td /F6 9.8 Tf  [(priori)] TJ ET
BT 47.915 295.563 Td /F1 9.8 Tf  [( measures of �meaningful� success in clinical trials. Results of this small preliminary study suggest that the PODCI )] TJ ET
BT 26.250 283.658 Td /F1 9.8 Tf  [(instrument is superior to the PedsQL measure with regard to sensitivity to change over a 1-year period and is an appropriate )] TJ ET
BT 26.250 271.753 Td /F1 9.8 Tf  [(PRO measure of both function and HrQoL in DMD; confirmation in a larger DMD cohort is currently underway. Our early results, )] TJ ET
BT 26.250 259.848 Td /F1 9.8 Tf  [(however, suggest that in less functional individuals, small changes in household walking ability may represent a change in daily )] TJ ET
BT 26.250 247.944 Td /F1 9.8 Tf  [(function that could have a significant perceived impact on the individual. Conversely, at higher levels of function closer to the )] TJ ET
BT 26.250 236.039 Td /F1 9.8 Tf  [(norm, larger increases in achievable walking distance are necessary to gain a �meaningful� increase in HrQoL. At performance )] TJ ET
BT 26.250 224.134 Td /F1 9.8 Tf  [(levels closer to normative abilities that might be seen in milder Becker dystrophinopathies, changes in 6MWD needed to affect a )] TJ ET
BT 26.250 212.229 Td /F1 9.8 Tf  [(�meaningful� change in PODCI scores could be much larger and possibly outside of the level of change expected in a 1-year )] TJ ET
BT 26.250 200.325 Td /F1 9.8 Tf  [(clinical trial. We therefore suggest that regardless of whether clinician-derived functional measures and HrQoL measures are )] TJ ET
BT 26.250 188.420 Td /F1 9.8 Tf  [(used in concert or independently in clinical investigations, interpretation of achieved change in walking distances or ambulatory )] TJ ET
BT 26.250 176.515 Td /F1 9.8 Tf  [(velocity in clinical trials in DMD may vary by age or the magnitude of difference compared to healthy controls, and that these )] TJ ET
BT 26.250 164.610 Td /F1 9.8 Tf  [(factors may affect power calculations and sample sizes needed for clinical trials.)] TJ ET
BT 26.250 128.008 Td /F4 12.0 Tf  [(Competing Interests)] TJ ET
BT 26.250 108.054 Td /F1 9.8 Tf  [(E.K. Henricson: Mr. Henricson has served as a member of the Cooperative International Neuromuscular Research Group )] TJ ET
BT 26.250 96.149 Td /F1 9.8 Tf  [(\(CINRG\) Executive Committee, and as a consultant for Genzyme, Inc. and PTC Therapeutics, Inc.)] TJ ET
BT 26.250 76.744 Td /F1 9.8 Tf  [(R.T. Abresch: Mr. Abresch has served as a consultant for PTC Therapeutics, Inc.)] TJ ET
BT 26.250 57.339 Td /F1 9.8 Tf  [(J.J. Han: Dr Han has served as a consultant for Genzyme, Inc.)] TJ ET
Q
q
15.000 28.054 577.500 748.946 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(instrument�s increased sensitivity to change makes it better suited for use as an outcome measure in clinical trials due its ability )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(to show significant change over a 1-year time period commonly employed in current clinical trial designs.)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(The key to this increased level of sensitivity to change associated with disease progression of the PODCI may lie in the design )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(of the instruments themselves, which differ in their approach to self/proxy-reported ability. The PODCI items are framed in terms )] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(of ease or difficulty of a task, such as: �During the last week has it been easy or hard for your child to walk one block?� The )] TJ ET
BT 26.250 700.452 Td /F1 9.8 Tf  [(response options address the perceived physical difficulty of activities: �easy�, �a little hard�, �very hard�, or �can�t do at all�. In )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(contrast, the PedsQL framework addresses the frequency of difficulty with activities. Items are presented such as �In the past )] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(ONE month how much of a problem has your child had with walking more than one block?� Response choices include: �never�, )] TJ ET
BT 26.250 664.738 Td /F1 9.8 Tf  [(�almost never�, �sometimes�, �often�, and �almost always.� The PedsQL represents a subtly different and more participation-)] TJ ET
BT 26.250 652.833 Td /F1 9.8 Tf  [(oriented construct that accounts for not only perceived problems with an activity, but the self-selected frequency or importance )] TJ ET
BT 26.250 640.929 Td /F1 9.8 Tf  [(as well. This subtle difference helps to explain why PODCI transfer and basic mobility items scale items correlate better with )] TJ ET
BT 26.250 629.024 Td /F1 9.8 Tf  [(objective clinical measures of function such as 6MWD or 10 meter run/walk velocity and are more sensitive to changes in those )] TJ ET
BT 26.250 617.119 Td /F1 9.8 Tf  [(abilities over time. They represent a purer measure of locomotor ability that is less affected by behavior.)] TJ ET
BT 26.250 597.714 Td /F5 9.8 Tf  [(Changes in PODCI responses and walking velocity correlate strongly, but �clinical meaningfulness� may differ across )] TJ ET
BT 26.250 585.810 Td /F5 9.8 Tf  [(ranges of performance.)] TJ ET
BT 26.250 566.405 Td /F1 9.8 Tf  [(Regression estimates from this sample allow us to predict 6MWD based on PODCI score, and subsequently we can estimate )] TJ ET
BT 26.250 554.500 Td /F1 9.8 Tf  [(differences between MCID for each measure at differing levels of function. Using our regression estimates, it is possible to )] TJ ET
BT 26.250 542.595 Td /F1 9.8 Tf  [(conclude that a clinically-important difference in person-reported HrQOL via PODCI transfer and basic mobility score is )] TJ ET
BT 26.250 530.691 Td /F1 9.8 Tf  [(associated with a decreasing degree of change in achievable 6MWT velocities or distances as baseline function decreases. )] TJ ET
BT 26.250 518.786 Td /F1 9.8 Tf  [(Thus, the degree of perceived �meaningful change� in walking ability may differ according to functional capacity. Hence at )] TJ ET
BT 26.250 506.881 Td /F1 9.8 Tf  [(higher levels of function on the 6MWT closer to healthy control values, it may take a greater change in 6MWD to produce )] TJ ET
BT 26.250 494.976 Td /F1 9.8 Tf  [(clinically-meaningful changes on a PRO measure such as the PODCI transfer and basic mobility scale. At most levels of )] TJ ET
BT 26.250 483.072 Td /F1 9.8 Tf  [(function typically seen in ambulatory DMD subjects, the threshold change in 6MWD which would correspond to clinically )] TJ ET
BT 26.250 471.167 Td /F1 9.8 Tf  [(meaningful changes in the PODCI transfer and basic mobility scale would be up to 28 to 36 meters. For example, at a mean )] TJ ET
BT 26.250 459.262 Td /F1 9.8 Tf  [(6MWD for DMD of 356 meters documented in one trial)] TJ ET
BT 261.410 463.150 Td /F1 8.7 Tf  [(17)] TJ ET
BT 271.048 459.262 Td /F1 9.8 Tf  [(, the change in 6MWD associated with a clinically-meaningful 4.5 point )] TJ ET
BT 26.250 447.357 Td /F1 9.8 Tf  [(change in PODCI transfer and basic mobility scale would be 36 meters. At a 300 meter 6MWD that seems to represent a lower )] TJ ET
BT 26.250 435.453 Td /F1 9.8 Tf  [(limit threshold level of function placing DMD subjects at risk for loss of ambulation)] TJ ET
0.267 0.267 0.267 rg
BT 377.913 436.960 Td /F4 8.7 Tf  [(18)] TJ ET
0.271 0.267 0.267 rg
BT 387.550 435.453 Td /F1 9.8 Tf  [( , the MCID of 4.5 points on the PODCI )] TJ ET
BT 26.250 423.548 Td /F1 9.8 Tf  [(corresponds to a change in 6MWD of 28 meters. These are levels of ambulatory ability that are frequently seen in clinical trials )] TJ ET
BT 26.250 411.643 Td /F1 9.8 Tf  [(for ambulatory DMD boys, providing support for the 6MWD of 30m MCID and effect size that has been commonly proposed as )] TJ ET
BT 26.250 399.738 Td /F1 9.8 Tf  [(a basis for study power calculations. However, at low levels of function, smaller increases or changes due to treatment in )] TJ ET
BT 26.250 387.834 Td /F1 9.8 Tf  [(achievable walking distance are likely to result in �meaningful� changes in HrQoL.)] TJ ET
BT 26.250 351.231 Td /F4 12.0 Tf  [(Conclusions)] TJ ET
BT 26.250 331.277 Td /F1 9.8 Tf  [(There is ongoing development of regulatory agency guidance regarding the most appropriate measures for use as primary or co-)] TJ ET
BT 26.250 319.372 Td /F1 9.8 Tf  [(primary endpoints for clinical trials for individuals affected by Duchenne and Becker muscular dystrophies)] TJ ET
0.267 0.267 0.267 rg
BT 479.791 320.879 Td /F4 8.7 Tf  [(35)] TJ ET
0.271 0.267 0.267 rg
BT 489.428 319.372 Td /F1 9.8 Tf  [(. A major facet of )] TJ ET
BT 26.250 307.467 Td /F1 9.8 Tf  [(that discussion revolves around what endpoints, whether of muscle strength, functional capacity or QoL should be used as )] TJ ET
BT 556.260 307.467 Td /F6 9.8 Tf  [(a )] TJ ET
BT 26.250 295.563 Td /F6 9.8 Tf  [(priori)] TJ ET
BT 47.915 295.563 Td /F1 9.8 Tf  [( measures of �meaningful� success in clinical trials. Results of this small preliminary study suggest that the PODCI )] TJ ET
BT 26.250 283.658 Td /F1 9.8 Tf  [(instrument is superior to the PedsQL measure with regard to sensitivity to change over a 1-year period and is an appropriate )] TJ ET
BT 26.250 271.753 Td /F1 9.8 Tf  [(PRO measure of both function and HrQoL in DMD; confirmation in a larger DMD cohort is currently underway. Our early results, )] TJ ET
BT 26.250 259.848 Td /F1 9.8 Tf  [(however, suggest that in less functional individuals, small changes in household walking ability may represent a change in daily )] TJ ET
BT 26.250 247.944 Td /F1 9.8 Tf  [(function that could have a significant perceived impact on the individual. Conversely, at higher levels of function closer to the )] TJ ET
BT 26.250 236.039 Td /F1 9.8 Tf  [(norm, larger increases in achievable walking distance are necessary to gain a �meaningful� increase in HrQoL. At performance )] TJ ET
BT 26.250 224.134 Td /F1 9.8 Tf  [(levels closer to normative abilities that might be seen in milder Becker dystrophinopathies, changes in 6MWD needed to affect a )] TJ ET
BT 26.250 212.229 Td /F1 9.8 Tf  [(�meaningful� change in PODCI scores could be much larger and possibly outside of the level of change expected in a 1-year )] TJ ET
BT 26.250 200.325 Td /F1 9.8 Tf  [(clinical trial. We therefore suggest that regardless of whether clinician-derived functional measures and HrQoL measures are )] TJ ET
BT 26.250 188.420 Td /F1 9.8 Tf  [(used in concert or independently in clinical investigations, interpretation of achieved change in walking distances or ambulatory )] TJ ET
BT 26.250 176.515 Td /F1 9.8 Tf  [(velocity in clinical trials in DMD may vary by age or the magnitude of difference compared to healthy controls, and that these )] TJ ET
BT 26.250 164.610 Td /F1 9.8 Tf  [(factors may affect power calculations and sample sizes needed for clinical trials.)] TJ ET
BT 26.250 128.008 Td /F4 12.0 Tf  [(Competing Interests)] TJ ET
BT 26.250 108.054 Td /F1 9.8 Tf  [(E.K. Henricson: Mr. Henricson has served as a member of the Cooperative International Neuromuscular Research Group )] TJ ET
BT 26.250 96.149 Td /F1 9.8 Tf  [(\(CINRG\) Executive Committee, and as a consultant for Genzyme, Inc. and PTC Therapeutics, Inc.)] TJ ET
BT 26.250 76.744 Td /F1 9.8 Tf  [(R.T. Abresch: Mr. Abresch has served as a consultant for PTC Therapeutics, Inc.)] TJ ET
BT 26.250 57.339 Td /F1 9.8 Tf  [(J.J. Han: Dr Han has served as a consultant for Genzyme, Inc.)] TJ ET
Q
q
15.000 28.054 577.500 748.946 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(instrument�s increased sensitivity to change makes it better suited for use as an outcome measure in clinical trials due its ability )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(to show significant change over a 1-year time period commonly employed in current clinical trial designs.)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(The key to this increased level of sensitivity to change associated with disease progression of the PODCI may lie in the design )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(of the instruments themselves, which differ in their approach to self/proxy-reported ability. The PODCI items are framed in terms )] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(of ease or difficulty of a task, such as: �During the last week has it been easy or hard for your child to walk one block?� The )] TJ ET
BT 26.250 700.452 Td /F1 9.8 Tf  [(response options address the perceived physical difficulty of activities: �easy�, �a little hard�, �very hard�, or �can�t do at all�. In )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(contrast, the PedsQL framework addresses the frequency of difficulty with activities. Items are presented such as �In the past )] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(ONE month how much of a problem has your child had with walking more than one block?� Response choices include: �never�, )] TJ ET
BT 26.250 664.738 Td /F1 9.8 Tf  [(�almost never�, �sometimes�, �often�, and �almost always.� The PedsQL represents a subtly different and more participation-)] TJ ET
BT 26.250 652.833 Td /F1 9.8 Tf  [(oriented construct that accounts for not only perceived problems with an activity, but the self-selected frequency or importance )] TJ ET
BT 26.250 640.929 Td /F1 9.8 Tf  [(as well. This subtle difference helps to explain why PODCI transfer and basic mobility items scale items correlate better with )] TJ ET
BT 26.250 629.024 Td /F1 9.8 Tf  [(objective clinical measures of function such as 6MWD or 10 meter run/walk velocity and are more sensitive to changes in those )] TJ ET
BT 26.250 617.119 Td /F1 9.8 Tf  [(abilities over time. They represent a purer measure of locomotor ability that is less affected by behavior.)] TJ ET
BT 26.250 597.714 Td /F5 9.8 Tf  [(Changes in PODCI responses and walking velocity correlate strongly, but �clinical meaningfulness� may differ across )] TJ ET
BT 26.250 585.810 Td /F5 9.8 Tf  [(ranges of performance.)] TJ ET
BT 26.250 566.405 Td /F1 9.8 Tf  [(Regression estimates from this sample allow us to predict 6MWD based on PODCI score, and subsequently we can estimate )] TJ ET
BT 26.250 554.500 Td /F1 9.8 Tf  [(differences between MCID for each measure at differing levels of function. Using our regression estimates, it is possible to )] TJ ET
BT 26.250 542.595 Td /F1 9.8 Tf  [(conclude that a clinically-important difference in person-reported HrQOL via PODCI transfer and basic mobility score is )] TJ ET
BT 26.250 530.691 Td /F1 9.8 Tf  [(associated with a decreasing degree of change in achievable 6MWT velocities or distances as baseline function decreases. )] TJ ET
BT 26.250 518.786 Td /F1 9.8 Tf  [(Thus, the degree of perceived �meaningful change� in walking ability may differ according to functional capacity. Hence at )] TJ ET
BT 26.250 506.881 Td /F1 9.8 Tf  [(higher levels of function on the 6MWT closer to healthy control values, it may take a greater change in 6MWD to produce )] TJ ET
BT 26.250 494.976 Td /F1 9.8 Tf  [(clinically-meaningful changes on a PRO measure such as the PODCI transfer and basic mobility scale. At most levels of )] TJ ET
BT 26.250 483.072 Td /F1 9.8 Tf  [(function typically seen in ambulatory DMD subjects, the threshold change in 6MWD which would correspond to clinically )] TJ ET
BT 26.250 471.167 Td /F1 9.8 Tf  [(meaningful changes in the PODCI transfer and basic mobility scale would be up to 28 to 36 meters. For example, at a mean )] TJ ET
BT 26.250 459.262 Td /F1 9.8 Tf  [(6MWD for DMD of 356 meters documented in one trial)] TJ ET
BT 261.410 463.150 Td /F1 8.7 Tf  [(17)] TJ ET
BT 271.048 459.262 Td /F1 9.8 Tf  [(, the change in 6MWD associated with a clinically-meaningful 4.5 point )] TJ ET
BT 26.250 447.357 Td /F1 9.8 Tf  [(change in PODCI transfer and basic mobility scale would be 36 meters. At a 300 meter 6MWD that seems to represent a lower )] TJ ET
BT 26.250 435.453 Td /F1 9.8 Tf  [(limit threshold level of function placing DMD subjects at risk for loss of ambulation)] TJ ET
0.267 0.267 0.267 rg
BT 377.913 436.960 Td /F4 8.7 Tf  [(18)] TJ ET
0.271 0.267 0.267 rg
BT 387.550 435.453 Td /F1 9.8 Tf  [( , the MCID of 4.5 points on the PODCI )] TJ ET
BT 26.250 423.548 Td /F1 9.8 Tf  [(corresponds to a change in 6MWD of 28 meters. These are levels of ambulatory ability that are frequently seen in clinical trials )] TJ ET
BT 26.250 411.643 Td /F1 9.8 Tf  [(for ambulatory DMD boys, providing support for the 6MWD of 30m MCID and effect size that has been commonly proposed as )] TJ ET
BT 26.250 399.738 Td /F1 9.8 Tf  [(a basis for study power calculations. However, at low levels of function, smaller increases or changes due to treatment in )] TJ ET
BT 26.250 387.834 Td /F1 9.8 Tf  [(achievable walking distance are likely to result in �meaningful� changes in HrQoL.)] TJ ET
BT 26.250 351.231 Td /F4 12.0 Tf  [(Conclusions)] TJ ET
BT 26.250 331.277 Td /F1 9.8 Tf  [(There is ongoing development of regulatory agency guidance regarding the most appropriate measures for use as primary or co-)] TJ ET
BT 26.250 319.372 Td /F1 9.8 Tf  [(primary endpoints for clinical trials for individuals affected by Duchenne and Becker muscular dystrophies)] TJ ET
0.267 0.267 0.267 rg
BT 479.791 320.879 Td /F4 8.7 Tf  [(35)] TJ ET
0.271 0.267 0.267 rg
BT 489.428 319.372 Td /F1 9.8 Tf  [(. A major facet of )] TJ ET
BT 26.250 307.467 Td /F1 9.8 Tf  [(that discussion revolves around what endpoints, whether of muscle strength, functional capacity or QoL should be used as )] TJ ET
BT 556.260 307.467 Td /F6 9.8 Tf  [(a )] TJ ET
BT 26.250 295.563 Td /F6 9.8 Tf  [(priori)] TJ ET
BT 47.915 295.563 Td /F1 9.8 Tf  [( measures of �meaningful� success in clinical trials. Results of this small preliminary study suggest that the PODCI )] TJ ET
BT 26.250 283.658 Td /F1 9.8 Tf  [(instrument is superior to the PedsQL measure with regard to sensitivity to change over a 1-year period and is an appropriate )] TJ ET
BT 26.250 271.753 Td /F1 9.8 Tf  [(PRO measure of both function and HrQoL in DMD; confirmation in a larger DMD cohort is currently underway. Our early results, )] TJ ET
BT 26.250 259.848 Td /F1 9.8 Tf  [(however, suggest that in less functional individuals, small changes in household walking ability may represent a change in daily )] TJ ET
BT 26.250 247.944 Td /F1 9.8 Tf  [(function that could have a significant perceived impact on the individual. Conversely, at higher levels of function closer to the )] TJ ET
BT 26.250 236.039 Td /F1 9.8 Tf  [(norm, larger increases in achievable walking distance are necessary to gain a �meaningful� increase in HrQoL. At performance )] TJ ET
BT 26.250 224.134 Td /F1 9.8 Tf  [(levels closer to normative abilities that might be seen in milder Becker dystrophinopathies, changes in 6MWD needed to affect a )] TJ ET
BT 26.250 212.229 Td /F1 9.8 Tf  [(�meaningful� change in PODCI scores could be much larger and possibly outside of the level of change expected in a 1-year )] TJ ET
BT 26.250 200.325 Td /F1 9.8 Tf  [(clinical trial. We therefore suggest that regardless of whether clinician-derived functional measures and HrQoL measures are )] TJ ET
BT 26.250 188.420 Td /F1 9.8 Tf  [(used in concert or independently in clinical investigations, interpretation of achieved change in walking distances or ambulatory )] TJ ET
BT 26.250 176.515 Td /F1 9.8 Tf  [(velocity in clinical trials in DMD may vary by age or the magnitude of difference compared to healthy controls, and that these )] TJ ET
BT 26.250 164.610 Td /F1 9.8 Tf  [(factors may affect power calculations and sample sizes needed for clinical trials.)] TJ ET
BT 26.250 128.008 Td /F4 12.0 Tf  [(Competing Interests)] TJ ET
BT 26.250 108.054 Td /F1 9.8 Tf  [(E.K. Henricson: Mr. Henricson has served as a member of the Cooperative International Neuromuscular Research Group )] TJ ET
BT 26.250 96.149 Td /F1 9.8 Tf  [(\(CINRG\) Executive Committee, and as a consultant for Genzyme, Inc. and PTC Therapeutics, Inc.)] TJ ET
BT 26.250 76.744 Td /F1 9.8 Tf  [(R.T. Abresch: Mr. Abresch has served as a consultant for PTC Therapeutics, Inc.)] TJ ET
BT 26.250 57.339 Td /F1 9.8 Tf  [(J.J. Han: Dr Han has served as a consultant for Genzyme, Inc.)] TJ ET
Q
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BT 291.710 19.825 Td /F1 11.0 Tf  [(9)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Muscular Dystrophy)] TJ ET

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q
15.000 43.978 577.500 733.022 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(A. Nicorici: Ms. Nicorici has nothing to disclose.)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(E. Goude: Ms. Goude has nothing to disclose.)] TJ ET
BT 26.250 728.667 Td /F1 9.8 Tf  [(E. de Bie: Mr. de Bie has nothing to disclose.)] TJ ET
BT 26.250 709.262 Td /F1 9.8 Tf  [(CM McDonald: Dr. McDonald is a member of the Cooperative Neuromuscular Research Group \(CINRG\) Executive Committee )] TJ ET
BT 26.250 697.357 Td /F1 9.8 Tf  [(and has served on advisory committees for PTC Therapeutics, Inc., Sarepta Therapeutics, Inc., GlaxoSmithKline, PLC., )] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(Prosensa, Halo Therapeutics, Shire HGT, Cardero Therapeutics, Novartis AG, and Eli Lilly and Company.)] TJ ET
BT 26.250 648.850 Td /F4 12.0 Tf  [(Statistical Analysis)] TJ ET
BT 26.250 628.896 Td /F1 9.8 Tf  [(Erik K. Henricson, UC Davis Department of Physical Medicine & Rehabilitation)] TJ ET
BT 26.250 592.293 Td /F4 12.0 Tf  [(Corresponding Author)] TJ ET
BT 26.250 572.339 Td /F1 9.8 Tf  [(Erik K. Henricson, MPH)] TJ ET
BT 26.250 552.934 Td /F1 9.8 Tf  [(University of California, Davis School of Medicine)] TJ ET
BT 26.250 533.529 Td /F1 9.8 Tf  [(Sacramento, California 95817)] TJ ET
BT 26.250 514.125 Td /F1 9.8 Tf  [(Telephone: 916-734-0384)] TJ ET
BT 26.250 494.720 Td /F1 9.8 Tf  [(Fax: 916-734-7838)] TJ ET
BT 26.250 475.315 Td /F1 9.8 Tf  [(E-mail: erik.henricson@ucdmc.ucdavis.edu)] TJ ET
BT 26.250 438.713 Td /F4 12.0 Tf  [(Key Words / MESH Terms)] TJ ET
BT 26.250 418.758 Td /F1 9.8 Tf  [(Child \(Preschool\), Child, Adolescent, Disease Progression, Follow-Up Studies, Gait/physiology*, Humans, Male, Muscular )] TJ ET
BT 26.250 406.854 Td /F1 9.8 Tf  [(Dystrophy, Duchenne/physiopathology*, Walking/physiology*, Quality of Life, Marker/clinical, Marker/surrogate. 6-minute walk )] TJ ET
BT 26.250 394.949 Td /F1 9.8 Tf  [(test, 6MWT, PedsQL, PODCI)] TJ ET
BT 26.250 358.346 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 338.392 Td /F1 9.8 Tf  [(We thank the patients and volunteers who committed their time and effort, Avital Cnaan of Children�s National Medical Center )] TJ ET
BT 26.250 326.487 Td /F1 9.8 Tf  [(for concept review and statistical advice, and Amy Wagner of UC Davis for manuscript review.)] TJ ET
BT 26.250 297.385 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 269.931 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 269.931 Td /F1 9.8 Tf  [(Hoffman EP, Brown RH, Jr., Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell )] TJ ET
BT 26.250 258.026 Td /F1 9.8 Tf  [(1987;51\(6\):919-928.)] TJ ET
BT 26.250 238.621 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 238.621 Td /F1 9.8 Tf  [(Emery AE. Population frequencies of inherited neuromuscular diseases--a world survey. Neuromuscular disorders : NMD )] TJ ET
BT 26.250 226.716 Td /F1 9.8 Tf  [(1991;1\(1\):19-29.)] TJ ET
BT 26.250 207.312 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 207.312 Td /F1 9.8 Tf  [(Bushby K, Finkel R, Birnkrant D, Case L, Clemens P, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro )] TJ ET
BT 26.250 195.407 Td /F1 9.8 Tf  [(F, Tomezsko J, Constantin C, Group DCCW. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, )] TJ ET
BT 26.250 183.502 Td /F1 9.8 Tf  [(and pharmacological and psychosocial management. Lancet Neurology 2010;9\(1\):77-93.)] TJ ET
BT 26.250 164.097 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 164.097 Td /F1 9.8 Tf  [(Birnkrant JM, Bennett DS, Noritz GH, Birnkrant DJ. Developmental and behavioral disorders grown up: duchenne muscular )] TJ ET
BT 26.250 152.193 Td /F1 9.8 Tf  [(dystrophy. Journal of developmental and behavioral pediatrics : JDBP 2011;32\(8\):609-615.)] TJ ET
BT 26.250 132.788 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 132.788 Td /F1 9.8 Tf  [(McDonald CM, Henricson EK, Abresch RT, Han JJ, Escolar DM, Florence JM, Duong T, Arrieta A, Clemens PR, Hoffman )] TJ ET
BT 26.250 120.883 Td /F1 9.8 Tf  [(EP, Cnaan A. The cooperative international neuromuscular research group duchenne natural history study-a longitudinal )] TJ ET
BT 26.250 108.978 Td /F1 9.8 Tf  [(investigation in the era of glucocorticoid therapy: Design of protocol and the methods used. Muscle & nerve 2013.)] TJ ET
BT 26.250 89.574 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 89.574 Td /F1 9.8 Tf  [(Henricson EK, Abresch RT, Cnaan A, Hu F, Duong T, Arrieta A, Han J, Escolar DM, Florence JM, Clemens PR, Hoffman EP, )] TJ ET
BT 26.250 77.669 Td /F1 9.8 Tf  [(McDonald CM. The cooperative international neuromuscular research group Duchenne natural history study: Glucocorticoid )] TJ ET
BT 26.250 65.764 Td /F1 9.8 Tf  [(treatment preserves clinically meaningful functional milestones and reduces rate of disease progression as measured by )] TJ ET
BT 26.250 53.859 Td /F1 9.8 Tf  [(manual muscle testing and other commonly used clinical trial outcome measures. Muscle & nerve 2013.)] TJ ET
Q
q
15.000 43.978 577.500 733.022 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(A. Nicorici: Ms. Nicorici has nothing to disclose.)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(E. Goude: Ms. Goude has nothing to disclose.)] TJ ET
BT 26.250 728.667 Td /F1 9.8 Tf  [(E. de Bie: Mr. de Bie has nothing to disclose.)] TJ ET
BT 26.250 709.262 Td /F1 9.8 Tf  [(CM McDonald: Dr. McDonald is a member of the Cooperative Neuromuscular Research Group \(CINRG\) Executive Committee )] TJ ET
BT 26.250 697.357 Td /F1 9.8 Tf  [(and has served on advisory committees for PTC Therapeutics, Inc., Sarepta Therapeutics, Inc., GlaxoSmithKline, PLC., )] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(Prosensa, Halo Therapeutics, Shire HGT, Cardero Therapeutics, Novartis AG, and Eli Lilly and Company.)] TJ ET
BT 26.250 648.850 Td /F4 12.0 Tf  [(Statistical Analysis)] TJ ET
BT 26.250 628.896 Td /F1 9.8 Tf  [(Erik K. Henricson, UC Davis Department of Physical Medicine & Rehabilitation)] TJ ET
BT 26.250 592.293 Td /F4 12.0 Tf  [(Corresponding Author)] TJ ET
BT 26.250 572.339 Td /F1 9.8 Tf  [(Erik K. Henricson, MPH)] TJ ET
BT 26.250 552.934 Td /F1 9.8 Tf  [(University of California, Davis School of Medicine)] TJ ET
BT 26.250 533.529 Td /F1 9.8 Tf  [(Sacramento, California 95817)] TJ ET
BT 26.250 514.125 Td /F1 9.8 Tf  [(Telephone: 916-734-0384)] TJ ET
BT 26.250 494.720 Td /F1 9.8 Tf  [(Fax: 916-734-7838)] TJ ET
BT 26.250 475.315 Td /F1 9.8 Tf  [(E-mail: erik.henricson@ucdmc.ucdavis.edu)] TJ ET
BT 26.250 438.713 Td /F4 12.0 Tf  [(Key Words / MESH Terms)] TJ ET
BT 26.250 418.758 Td /F1 9.8 Tf  [(Child \(Preschool\), Child, Adolescent, Disease Progression, Follow-Up Studies, Gait/physiology*, Humans, Male, Muscular )] TJ ET
BT 26.250 406.854 Td /F1 9.8 Tf  [(Dystrophy, Duchenne/physiopathology*, Walking/physiology*, Quality of Life, Marker/clinical, Marker/surrogate. 6-minute walk )] TJ ET
BT 26.250 394.949 Td /F1 9.8 Tf  [(test, 6MWT, PedsQL, PODCI)] TJ ET
BT 26.250 358.346 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 338.392 Td /F1 9.8 Tf  [(We thank the patients and volunteers who committed their time and effort, Avital Cnaan of Children�s National Medical Center )] TJ ET
BT 26.250 326.487 Td /F1 9.8 Tf  [(for concept review and statistical advice, and Amy Wagner of UC Davis for manuscript review.)] TJ ET
BT 26.250 297.385 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 269.931 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 269.931 Td /F1 9.8 Tf  [(Hoffman EP, Brown RH, Jr., Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell )] TJ ET
BT 26.250 258.026 Td /F1 9.8 Tf  [(1987;51\(6\):919-928.)] TJ ET
BT 26.250 238.621 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 238.621 Td /F1 9.8 Tf  [(Emery AE. Population frequencies of inherited neuromuscular diseases--a world survey. Neuromuscular disorders : NMD )] TJ ET
BT 26.250 226.716 Td /F1 9.8 Tf  [(1991;1\(1\):19-29.)] TJ ET
BT 26.250 207.312 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 207.312 Td /F1 9.8 Tf  [(Bushby K, Finkel R, Birnkrant D, Case L, Clemens P, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro )] TJ ET
BT 26.250 195.407 Td /F1 9.8 Tf  [(F, Tomezsko J, Constantin C, Group DCCW. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, )] TJ ET
BT 26.250 183.502 Td /F1 9.8 Tf  [(and pharmacological and psychosocial management. Lancet Neurology 2010;9\(1\):77-93.)] TJ ET
BT 26.250 164.097 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 164.097 Td /F1 9.8 Tf  [(Birnkrant JM, Bennett DS, Noritz GH, Birnkrant DJ. Developmental and behavioral disorders grown up: duchenne muscular )] TJ ET
BT 26.250 152.193 Td /F1 9.8 Tf  [(dystrophy. Journal of developmental and behavioral pediatrics : JDBP 2011;32\(8\):609-615.)] TJ ET
BT 26.250 132.788 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 132.788 Td /F1 9.8 Tf  [(McDonald CM, Henricson EK, Abresch RT, Han JJ, Escolar DM, Florence JM, Duong T, Arrieta A, Clemens PR, Hoffman )] TJ ET
BT 26.250 120.883 Td /F1 9.8 Tf  [(EP, Cnaan A. The cooperative international neuromuscular research group duchenne natural history study-a longitudinal )] TJ ET
BT 26.250 108.978 Td /F1 9.8 Tf  [(investigation in the era of glucocorticoid therapy: Design of protocol and the methods used. Muscle & nerve 2013.)] TJ ET
BT 26.250 89.574 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 89.574 Td /F1 9.8 Tf  [(Henricson EK, Abresch RT, Cnaan A, Hu F, Duong T, Arrieta A, Han J, Escolar DM, Florence JM, Clemens PR, Hoffman EP, )] TJ ET
BT 26.250 77.669 Td /F1 9.8 Tf  [(McDonald CM. The cooperative international neuromuscular research group Duchenne natural history study: Glucocorticoid )] TJ ET
BT 26.250 65.764 Td /F1 9.8 Tf  [(treatment preserves clinically meaningful functional milestones and reduces rate of disease progression as measured by )] TJ ET
BT 26.250 53.859 Td /F1 9.8 Tf  [(manual muscle testing and other commonly used clinical trial outcome measures. Muscle & nerve 2013.)] TJ ET
Q
q
15.000 43.978 577.500 733.022 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(A. Nicorici: Ms. Nicorici has nothing to disclose.)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(E. Goude: Ms. Goude has nothing to disclose.)] TJ ET
BT 26.250 728.667 Td /F1 9.8 Tf  [(E. de Bie: Mr. de Bie has nothing to disclose.)] TJ ET
BT 26.250 709.262 Td /F1 9.8 Tf  [(CM McDonald: Dr. McDonald is a member of the Cooperative Neuromuscular Research Group \(CINRG\) Executive Committee )] TJ ET
BT 26.250 697.357 Td /F1 9.8 Tf  [(and has served on advisory committees for PTC Therapeutics, Inc., Sarepta Therapeutics, Inc., GlaxoSmithKline, PLC., )] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(Prosensa, Halo Therapeutics, Shire HGT, Cardero Therapeutics, Novartis AG, and Eli Lilly and Company.)] TJ ET
BT 26.250 648.850 Td /F4 12.0 Tf  [(Statistical Analysis)] TJ ET
BT 26.250 628.896 Td /F1 9.8 Tf  [(Erik K. Henricson, UC Davis Department of Physical Medicine & Rehabilitation)] TJ ET
BT 26.250 592.293 Td /F4 12.0 Tf  [(Corresponding Author)] TJ ET
BT 26.250 572.339 Td /F1 9.8 Tf  [(Erik K. Henricson, MPH)] TJ ET
BT 26.250 552.934 Td /F1 9.8 Tf  [(University of California, Davis School of Medicine)] TJ ET
BT 26.250 533.529 Td /F1 9.8 Tf  [(Sacramento, California 95817)] TJ ET
BT 26.250 514.125 Td /F1 9.8 Tf  [(Telephone: 916-734-0384)] TJ ET
BT 26.250 494.720 Td /F1 9.8 Tf  [(Fax: 916-734-7838)] TJ ET
BT 26.250 475.315 Td /F1 9.8 Tf  [(E-mail: erik.henricson@ucdmc.ucdavis.edu)] TJ ET
BT 26.250 438.713 Td /F4 12.0 Tf  [(Key Words / MESH Terms)] TJ ET
BT 26.250 418.758 Td /F1 9.8 Tf  [(Child \(Preschool\), Child, Adolescent, Disease Progression, Follow-Up Studies, Gait/physiology*, Humans, Male, Muscular )] TJ ET
BT 26.250 406.854 Td /F1 9.8 Tf  [(Dystrophy, Duchenne/physiopathology*, Walking/physiology*, Quality of Life, Marker/clinical, Marker/surrogate. 6-minute walk )] TJ ET
BT 26.250 394.949 Td /F1 9.8 Tf  [(test, 6MWT, PedsQL, PODCI)] TJ ET
BT 26.250 358.346 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 338.392 Td /F1 9.8 Tf  [(We thank the patients and volunteers who committed their time and effort, Avital Cnaan of Children�s National Medical Center )] TJ ET
BT 26.250 326.487 Td /F1 9.8 Tf  [(for concept review and statistical advice, and Amy Wagner of UC Davis for manuscript review.)] TJ ET
BT 26.250 297.385 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 269.931 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 269.931 Td /F1 9.8 Tf  [(Hoffman EP, Brown RH, Jr., Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell )] TJ ET
BT 26.250 258.026 Td /F1 9.8 Tf  [(1987;51\(6\):919-928.)] TJ ET
BT 26.250 238.621 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 238.621 Td /F1 9.8 Tf  [(Emery AE. Population frequencies of inherited neuromuscular diseases--a world survey. Neuromuscular disorders : NMD )] TJ ET
BT 26.250 226.716 Td /F1 9.8 Tf  [(1991;1\(1\):19-29.)] TJ ET
BT 26.250 207.312 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 207.312 Td /F1 9.8 Tf  [(Bushby K, Finkel R, Birnkrant D, Case L, Clemens P, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro )] TJ ET
BT 26.250 195.407 Td /F1 9.8 Tf  [(F, Tomezsko J, Constantin C, Group DCCW. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, )] TJ ET
BT 26.250 183.502 Td /F1 9.8 Tf  [(and pharmacological and psychosocial management. Lancet Neurology 2010;9\(1\):77-93.)] TJ ET
BT 26.250 164.097 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 164.097 Td /F1 9.8 Tf  [(Birnkrant JM, Bennett DS, Noritz GH, Birnkrant DJ. Developmental and behavioral disorders grown up: duchenne muscular )] TJ ET
BT 26.250 152.193 Td /F1 9.8 Tf  [(dystrophy. Journal of developmental and behavioral pediatrics : JDBP 2011;32\(8\):609-615.)] TJ ET
BT 26.250 132.788 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 132.788 Td /F1 9.8 Tf  [(McDonald CM, Henricson EK, Abresch RT, Han JJ, Escolar DM, Florence JM, Duong T, Arrieta A, Clemens PR, Hoffman )] TJ ET
BT 26.250 120.883 Td /F1 9.8 Tf  [(EP, Cnaan A. The cooperative international neuromuscular research group duchenne natural history study-a longitudinal )] TJ ET
BT 26.250 108.978 Td /F1 9.8 Tf  [(investigation in the era of glucocorticoid therapy: Design of protocol and the methods used. Muscle & nerve 2013.)] TJ ET
BT 26.250 89.574 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 89.574 Td /F1 9.8 Tf  [(Henricson EK, Abresch RT, Cnaan A, Hu F, Duong T, Arrieta A, Han J, Escolar DM, Florence JM, Clemens PR, Hoffman EP, )] TJ ET
BT 26.250 77.669 Td /F1 9.8 Tf  [(McDonald CM. The cooperative international neuromuscular research group Duchenne natural history study: Glucocorticoid )] TJ ET
BT 26.250 65.764 Td /F1 9.8 Tf  [(treatment preserves clinically meaningful functional milestones and reduces rate of disease progression as measured by )] TJ ET
BT 26.250 53.859 Td /F1 9.8 Tf  [(manual muscle testing and other commonly used clinical trial outcome measures. Muscle & nerve 2013.)] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(10)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Muscular Dystrophy)] TJ ET

Q
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<<
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0.271 0.267 0.267 rg
q
15.000 39.262 577.500 737.738 re W n
0.271 0.267 0.267 rg
BT 26.250 759.976 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 759.976 Td /F1 9.8 Tf  [(Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne muscular dystrophy: )] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscular disorders : NMD )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(2002;12\(10\):926-929.)] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 716.762 Td /F1 9.8 Tf  [(Sarepta Therpeutics. Efficacy study of AVI-4658 to induce dystrophin expression in selected Duchenne muscular dystrophy )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(patients. ClinicalTrialsgov. Bethesda, MD: National Library of Medicine.)] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 685.452 Td /F1 9.8 Tf  [(GlaxoSmithKline. An exploratory study to assess two doses of GSK2402968 in the treatment of ambulant boys with )] TJ ET
BT 26.250 673.548 Td /F1 9.8 Tf  [(Duchenne muscular dystrophy \(DMD\). ClinicalTrialsgov. Bethesda, MD: National Library of Medicine.)] TJ ET
BT 26.250 654.143 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 654.143 Td /F1 9.8 Tf  [(PTC Therapeutics. Phase 2b study of PTC124 in Duchenne/Becker muscular dystrophy \(DMD/BMD\). ClinicalTrialsgov. )] TJ ET
BT 26.250 642.238 Td /F1 9.8 Tf  [(Bethesda, MD: National Library of Medicine.)] TJ ET
BT 26.250 622.833 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 622.833 Td /F1 9.8 Tf  [(Crespo CJ, Keteyian SJ, Heath GW, Sempos CT. Leisure-time physical activity among US adults. Results from the Third )] TJ ET
BT 26.250 610.929 Td /F1 9.8 Tf  [(National Health and Nutrition Examination Survey. Archives of internal medicine 1996;156\(1\):93-98.)] TJ ET
BT 26.250 591.524 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 591.524 Td /F1 9.8 Tf  [(Bushby K, Finkel R, Birnkrant D, Case L, Clemens P, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro )] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(F, Tomezsko J, Constantin C, Group DCCW. Diagnosis and management of Duchenne muscular dystrophy, part 2: )] TJ ET
BT 26.250 567.714 Td /F1 9.8 Tf  [(implementation of multidisciplinary care. Lancet Neurology 2010;9\(2\):177-189.)] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 548.310 Td /F1 9.8 Tf  [(Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley R, Florence J, King WM, Pandya S, Robison J, Schierbecker J, )] TJ ET
BT 26.250 536.405 Td /F1 9.8 Tf  [(et al. Duchenne muscular dystrophy: patterns of clinical progression and effects of supportive therapy. Neurology )] TJ ET
BT 26.250 524.500 Td /F1 9.8 Tf  [(1989;39\(4\):475-481.)] TJ ET
BT 26.250 505.095 Td /F1 9.8 Tf  [(14.)] TJ ET
BT 43.553 505.095 Td /F1 9.8 Tf  [(McDonald CM, Fowler WM, Jr. The role of the neuromuscular medicine and physiatry specialists in the multidisciplinary )] TJ ET
BT 26.250 493.191 Td /F1 9.8 Tf  [(management of neuromuscular disease. Physical medicine and rehabilitation clinics of North America 2012;23\(3\):475-493.)] TJ ET
BT 26.250 473.786 Td /F1 9.8 Tf  [(15.)] TJ ET
BT 43.553 473.786 Td /F1 9.8 Tf  [(McDonald CM, Henricson EK, Han JJ, Abresch RT, Nicorici A, Elfring GL, Atkinson L, Reha A, Hirawat S, Miller LL. The 6-)] TJ ET
BT 26.250 461.881 Td /F1 9.8 Tf  [(minute walk test as a new outcome measure in Duchenne muscular dystrophy. Muscle & nerve 2010;41\(4\):500-510.)] TJ ET
BT 26.250 442.476 Td /F1 9.8 Tf  [(16.)] TJ ET
BT 43.553 442.476 Td /F1 9.8 Tf  [(McDonald CM, Henricson EK, Han JJ, Abresch RT, Nicorici A, Atkinson L, Elfring GL, Reha A, Miller LL. The 6-minute walk )] TJ ET
BT 26.250 430.572 Td /F1 9.8 Tf  [(test in Duchenne/Becker muscular dystrophy: Longitudinal observations. Muscle & nerve 2010;42\(6\):966-974.)] TJ ET
BT 26.250 411.167 Td /F1 9.8 Tf  [(17.)] TJ ET
BT 43.553 411.167 Td /F1 9.8 Tf  [(McDonald CM, Henricson EK, Abresch RT, Florence J, Eagle M, Gappmaier E, Glanzman AM, Spiegel R, Barth J, Elfring )] TJ ET
BT 26.250 399.262 Td /F1 9.8 Tf  [(G, Reha A, Peltz SW. The 6-minute walk test and other clinical endpoints in Duchenne muscular dystrophy: Reliability, )] TJ ET
BT 26.250 387.357 Td /F1 9.8 Tf  [(concurrent validity, and minimal clinically important differences from a multicenter study. Muscle & nerve 2013.)] TJ ET
BT 26.250 367.953 Td /F1 9.8 Tf  [(18.)] TJ ET
BT 43.553 367.953 Td /F1 9.8 Tf  [(McDonald CM, Henricson EK, Abresch RT, Florence J, Eagle M, Gappmaier E, Glanzman AM, Spiegel R, Barth J, Elfring )] TJ ET
BT 26.250 356.048 Td /F1 9.8 Tf  [(G, Reha A, Peltz S. The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: Longitudinal natural history )] TJ ET
BT 26.250 344.143 Td /F1 9.8 Tf  [(observations over 48 weeks from a multicenter study. Muscle & nerve 2013.)] TJ ET
BT 26.250 324.738 Td /F1 9.8 Tf  [(19.)] TJ ET
BT 43.553 324.738 Td /F1 9.8 Tf  [(Mendell JR, Csimma C, McDonald CM, Escolar DM, Janis S, Porter JD, Hesterlee SE, Howell RR. Challenges in drug )] TJ ET
BT 26.250 312.834 Td /F1 9.8 Tf  [(development for muscle disease: a stakeholders' meeting. Muscle & nerve 2007;35\(1\):8-16.)] TJ ET
BT 26.250 293.429 Td /F1 9.8 Tf  [(20.)] TJ ET
BT 43.553 293.429 Td /F1 9.8 Tf  [(FDA. Guidance for Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to Support )] TJ ET
BT 26.250 281.524 Td /F1 9.8 Tf  [(Labeling Claims. In: Center for Drug Evaluation and Research FaDA, editor. December 9, 2009 ed. Volume 74, Federal )] TJ ET
BT 26.250 269.619 Td /F1 9.8 Tf  [(Register Online via GPO Access. Rockville, MD: Federal Register; 2009. p 85132-65133.)] TJ ET
BT 26.250 250.215 Td /F1 9.8 Tf  [(21.)] TJ ET
BT 43.553 250.215 Td /F1 9.8 Tf  [(Acquadro C BR, Dubois D, et al. . Incorporating the patient�s perspective into drug development and communication: an ad )] TJ ET
BT 26.250 238.310 Td /F1 9.8 Tf  [(hoc task force report of the Patient-Reported Outcomes \(PRO\) Harmonization Group meeting at the Food and Drug )] TJ ET
BT 26.250 226.405 Td /F1 9.8 Tf  [(Administration. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research )] TJ ET
BT 26.250 214.500 Td /F1 9.8 Tf  [(2003;6:522-531.)] TJ ET
BT 26.250 195.096 Td /F1 9.8 Tf  [(22.)] TJ ET
BT 43.553 195.096 Td /F1 9.8 Tf  [(Mazzone ES, Messina S, Vasco G, Main M, Eagle M, D'Amico A, Doglio L, Politano L, Cavallaro F, Frosini S, Bello L, Magri )] TJ ET
BT 26.250 183.191 Td /F1 9.8 Tf  [(F, Corlatti A, Zucchini E, Brancalion B, Rossi F, Ferretti M, Motta MG, Cecio MR, Berardinelli A, Alfieri P, Mongini T, Pini A, )] TJ ET
BT 26.250 171.286 Td /F1 9.8 Tf  [(Astrea G, Battini R, Comi G, Pegoraro E, Morandi L, Pane M, Angelini C, Bruno C, Villanova M, Vita G, Donati MA, Bertini E, )] TJ ET
BT 26.250 159.381 Td /F1 9.8 Tf  [(Mercuri E. Reliability of the North Star Ambulatory Assessment in a multicentric setting. Neuromuscular disorders : NMD )] TJ ET
BT 26.250 147.477 Td /F1 9.8 Tf  [(2009;19\(7\):458-461.)] TJ ET
BT 26.250 128.072 Td /F1 9.8 Tf  [(23.)] TJ ET
BT 43.553 128.072 Td /F1 9.8 Tf  [(Bushby K, Connor E. Clinical outcome measures for trials in Duchenne muscular dystrophy: report from International )] TJ ET
BT 26.250 116.167 Td /F1 9.8 Tf  [(Working Group meetings. Clinical investigation 2011;1\(9\):1217-1235.)] TJ ET
BT 26.250 96.762 Td /F1 9.8 Tf  [(24.)] TJ ET
BT 43.553 96.762 Td /F1 9.8 Tf  [(Lai JS, Nowinski C, Victorson D, Bode R, Podrabsky T, McKinney N, Straube D, Holmes GL, McDonald CM, Henricson E, )] TJ ET
BT 26.250 84.858 Td /F1 9.8 Tf  [(Abresch RT, Moy CS, Cella D. Quality-of-life measures in children with neurological conditions: pediatric Neuro-QOL. )] TJ ET
BT 26.250 72.953 Td /F1 9.8 Tf  [(Neurorehabilitation and neural repair 2012;26\(1\):36-47.)] TJ ET
BT 26.250 53.548 Td /F1 9.8 Tf  [(25.)] TJ ET
BT 43.553 53.548 Td /F1 9.8 Tf  [(McDonald CM, McDonald DA, Bagley A, Sienko Thomas S, Buckon CE, Henricson E, Nicorici A, Sussman MD. )] TJ ET
Q
q
15.000 39.262 577.500 737.738 re W n
0.271 0.267 0.267 rg
BT 26.250 759.976 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 759.976 Td /F1 9.8 Tf  [(Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne muscular dystrophy: )] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscular disorders : NMD )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(2002;12\(10\):926-929.)] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 716.762 Td /F1 9.8 Tf  [(Sarepta Therpeutics. Efficacy study of AVI-4658 to induce dystrophin expression in selected Duchenne muscular dystrophy )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(patients. ClinicalTrialsgov. Bethesda, MD: National Library of Medicine.)] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 685.452 Td /F1 9.8 Tf  [(GlaxoSmithKline. An exploratory study to assess two doses of GSK2402968 in the treatment of ambulant boys with )] TJ ET
BT 26.250 673.548 Td /F1 9.8 Tf  [(Duchenne muscular dystrophy \(DMD\). ClinicalTrialsgov. Bethesda, MD: National Library of Medicine.)] TJ ET
BT 26.250 654.143 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 654.143 Td /F1 9.8 Tf  [(PTC Therapeutics. Phase 2b study of PTC124 in Duchenne/Becker muscular dystrophy \(DMD/BMD\). ClinicalTrialsgov. )] TJ ET
BT 26.250 642.238 Td /F1 9.8 Tf  [(Bethesda, MD: National Library of Medicine.)] TJ ET
BT 26.250 622.833 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 622.833 Td /F1 9.8 Tf  [(Crespo CJ, Keteyian SJ, Heath GW, Sempos CT. Leisure-time physical activity among US adults. Results from the Third )] TJ ET
BT 26.250 610.929 Td /F1 9.8 Tf  [(National Health and Nutrition Examination Survey. Archives of internal medicine 1996;156\(1\):93-98.)] TJ ET
BT 26.250 591.524 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 591.524 Td /F1 9.8 Tf  [(Bushby K, Finkel R, Birnkrant D, Case L, Clemens P, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro )] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(F, Tomezsko J, Constantin C, Group DCCW. Diagnosis and management of Duchenne muscular dystrophy, part 2: )] TJ ET
BT 26.250 567.714 Td /F1 9.8 Tf  [(implementation of multidisciplinary care. Lancet Neurology 2010;9\(2\):177-189.)] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 548.310 Td /F1 9.8 Tf  [(Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley R, Florence J, King WM, Pandya S, Robison J, Schierbecker J, )] TJ ET
BT 26.250 536.405 Td /F1 9.8 Tf  [(et al. Duchenne muscular dystrophy: patterns of clinical progression and effects of supportive therapy. Neurology )] TJ ET
BT 26.250 524.500 Td /F1 9.8 Tf  [(1989;39\(4\):475-481.)] TJ ET
BT 26.250 505.095 Td /F1 9.8 Tf  [(14.)] TJ ET
BT 43.553 505.095 Td /F1 9.8 Tf  [(McDonald CM, Fowler WM, Jr. The role of the neuromuscular medicine and physiatry specialists in the multidisciplinary )] TJ ET
BT 26.250 493.191 Td /F1 9.8 Tf  [(management of neuromuscular disease. Physical medicine and rehabilitation clinics of North America 2012;23\(3\):475-493.)] TJ ET
BT 26.250 473.786 Td /F1 9.8 Tf  [(15.)] TJ ET
BT 43.553 473.786 Td /F1 9.8 Tf  [(McDonald CM, Henricson EK, Han JJ, Abresch RT, Nicorici A, Elfring GL, Atkinson L, Reha A, Hirawat S, Miller LL. The 6-)] TJ ET
BT 26.250 461.881 Td /F1 9.8 Tf  [(minute walk test as a new outcome measure in Duchenne muscular dystrophy. Muscle & nerve 2010;41\(4\):500-510.)] TJ ET
BT 26.250 442.476 Td /F1 9.8 Tf  [(16.)] TJ ET
BT 43.553 442.476 Td /F1 9.8 Tf  [(McDonald CM, Henricson EK, Han JJ, Abresch RT, Nicorici A, Atkinson L, Elfring GL, Reha A, Miller LL. The 6-minute walk )] TJ ET
BT 26.250 430.572 Td /F1 9.8 Tf  [(test in Duchenne/Becker muscular dystrophy: Longitudinal observations. Muscle & nerve 2010;42\(6\):966-974.)] TJ ET
BT 26.250 411.167 Td /F1 9.8 Tf  [(17.)] TJ ET
BT 43.553 411.167 Td /F1 9.8 Tf  [(McDonald CM, Henricson EK, Abresch RT, Florence J, Eagle M, Gappmaier E, Glanzman AM, Spiegel R, Barth J, Elfring )] TJ ET
BT 26.250 399.262 Td /F1 9.8 Tf  [(G, Reha A, Peltz SW. The 6-minute walk test and other clinical endpoints in Duchenne muscular dystrophy: Reliability, )] TJ ET
BT 26.250 387.357 Td /F1 9.8 Tf  [(concurrent validity, and minimal clinically important differences from a multicenter study. Muscle & nerve 2013.)] TJ ET
BT 26.250 367.953 Td /F1 9.8 Tf  [(18.)] TJ ET
BT 43.553 367.953 Td /F1 9.8 Tf  [(McDonald CM, Henricson EK, Abresch RT, Florence J, Eagle M, Gappmaier E, Glanzman AM, Spiegel R, Barth J, Elfring )] TJ ET
BT 26.250 356.048 Td /F1 9.8 Tf  [(G, Reha A, Peltz S. The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: Longitudinal natural history )] TJ ET
BT 26.250 344.143 Td /F1 9.8 Tf  [(observations over 48 weeks from a multicenter study. Muscle & nerve 2013.)] TJ ET
BT 26.250 324.738 Td /F1 9.8 Tf  [(19.)] TJ ET
BT 43.553 324.738 Td /F1 9.8 Tf  [(Mendell JR, Csimma C, McDonald CM, Escolar DM, Janis S, Porter JD, Hesterlee SE, Howell RR. Challenges in drug )] TJ ET
BT 26.250 312.834 Td /F1 9.8 Tf  [(development for muscle disease: a stakeholders' meeting. Muscle & nerve 2007;35\(1\):8-16.)] TJ ET
BT 26.250 293.429 Td /F1 9.8 Tf  [(20.)] TJ ET
BT 43.553 293.429 Td /F1 9.8 Tf  [(FDA. Guidance for Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to Support )] TJ ET
BT 26.250 281.524 Td /F1 9.8 Tf  [(Labeling Claims. In: Center for Drug Evaluation and Research FaDA, editor. December 9, 2009 ed. Volume 74, Federal )] TJ ET
BT 26.250 269.619 Td /F1 9.8 Tf  [(Register Online via GPO Access. Rockville, MD: Federal Register; 2009. p 85132-65133.)] TJ ET
BT 26.250 250.215 Td /F1 9.8 Tf  [(21.)] TJ ET
BT 43.553 250.215 Td /F1 9.8 Tf  [(Acquadro C BR, Dubois D, et al. . Incorporating the patient�s perspective into drug development and communication: an ad )] TJ ET
BT 26.250 238.310 Td /F1 9.8 Tf  [(hoc task force report of the Patient-Reported Outcomes \(PRO\) Harmonization Group meeting at the Food and Drug )] TJ ET
BT 26.250 226.405 Td /F1 9.8 Tf  [(Administration. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research )] TJ ET
BT 26.250 214.500 Td /F1 9.8 Tf  [(2003;6:522-531.)] TJ ET
BT 26.250 195.096 Td /F1 9.8 Tf  [(22.)] TJ ET
BT 43.553 195.096 Td /F1 9.8 Tf  [(Mazzone ES, Messina S, Vasco G, Main M, Eagle M, D'Amico A, Doglio L, Politano L, Cavallaro F, Frosini S, Bello L, Magri )] TJ ET
BT 26.250 183.191 Td /F1 9.8 Tf  [(F, Corlatti A, Zucchini E, Brancalion B, Rossi F, Ferretti M, Motta MG, Cecio MR, Berardinelli A, Alfieri P, Mongini T, Pini A, )] TJ ET
BT 26.250 171.286 Td /F1 9.8 Tf  [(Astrea G, Battini R, Comi G, Pegoraro E, Morandi L, Pane M, Angelini C, Bruno C, Villanova M, Vita G, Donati MA, Bertini E, )] TJ ET
BT 26.250 159.381 Td /F1 9.8 Tf  [(Mercuri E. Reliability of the North Star Ambulatory Assessment in a multicentric setting. Neuromuscular disorders : NMD )] TJ ET
BT 26.250 147.477 Td /F1 9.8 Tf  [(2009;19\(7\):458-461.)] TJ ET
BT 26.250 128.072 Td /F1 9.8 Tf  [(23.)] TJ ET
BT 43.553 128.072 Td /F1 9.8 Tf  [(Bushby K, Connor E. Clinical outcome measures for trials in Duchenne muscular dystrophy: report from International )] TJ ET
BT 26.250 116.167 Td /F1 9.8 Tf  [(Working Group meetings. Clinical investigation 2011;1\(9\):1217-1235.)] TJ ET
BT 26.250 96.762 Td /F1 9.8 Tf  [(24.)] TJ ET
BT 43.553 96.762 Td /F1 9.8 Tf  [(Lai JS, Nowinski C, Victorson D, Bode R, Podrabsky T, McKinney N, Straube D, Holmes GL, McDonald CM, Henricson E, )] TJ ET
BT 26.250 84.858 Td /F1 9.8 Tf  [(Abresch RT, Moy CS, Cella D. Quality-of-life measures in children with neurological conditions: pediatric Neuro-QOL. )] TJ ET
BT 26.250 72.953 Td /F1 9.8 Tf  [(Neurorehabilitation and neural repair 2012;26\(1\):36-47.)] TJ ET
BT 26.250 53.548 Td /F1 9.8 Tf  [(25.)] TJ ET
BT 43.553 53.548 Td /F1 9.8 Tf  [(McDonald CM, McDonald DA, Bagley A, Sienko Thomas S, Buckon CE, Henricson E, Nicorici A, Sussman MD. )] TJ ET
Q
q
15.000 39.262 577.500 737.738 re W n
0.271 0.267 0.267 rg
BT 26.250 759.976 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 759.976 Td /F1 9.8 Tf  [(Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne muscular dystrophy: )] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscular disorders : NMD )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(2002;12\(10\):926-929.)] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 716.762 Td /F1 9.8 Tf  [(Sarepta Therpeutics. Efficacy study of AVI-4658 to induce dystrophin expression in selected Duchenne muscular dystrophy )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(patients. ClinicalTrialsgov. Bethesda, MD: National Library of Medicine.)] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 685.452 Td /F1 9.8 Tf  [(GlaxoSmithKline. An exploratory study to assess two doses of GSK2402968 in the treatment of ambulant boys with )] TJ ET
BT 26.250 673.548 Td /F1 9.8 Tf  [(Duchenne muscular dystrophy \(DMD\). ClinicalTrialsgov. Bethesda, MD: National Library of Medicine.)] TJ ET
BT 26.250 654.143 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 654.143 Td /F1 9.8 Tf  [(PTC Therapeutics. Phase 2b study of PTC124 in Duchenne/Becker muscular dystrophy \(DMD/BMD\). ClinicalTrialsgov. )] TJ ET
BT 26.250 642.238 Td /F1 9.8 Tf  [(Bethesda, MD: National Library of Medicine.)] TJ ET
BT 26.250 622.833 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 622.833 Td /F1 9.8 Tf  [(Crespo CJ, Keteyian SJ, Heath GW, Sempos CT. Leisure-time physical activity among US adults. Results from the Third )] TJ ET
BT 26.250 610.929 Td /F1 9.8 Tf  [(National Health and Nutrition Examination Survey. Archives of internal medicine 1996;156\(1\):93-98.)] TJ ET
BT 26.250 591.524 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 591.524 Td /F1 9.8 Tf  [(Bushby K, Finkel R, Birnkrant D, Case L, Clemens P, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro )] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(F, Tomezsko J, Constantin C, Group DCCW. Diagnosis and management of Duchenne muscular dystrophy, part 2: )] TJ ET
BT 26.250 567.714 Td /F1 9.8 Tf  [(implementation of multidisciplinary care. Lancet Neurology 2010;9\(2\):177-189.)] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 548.310 Td /F1 9.8 Tf  [(Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley R, Florence J, King WM, Pandya S, Robison J, Schierbecker J, )] TJ ET
BT 26.250 536.405 Td /F1 9.8 Tf  [(et al. Duchenne muscular dystrophy: patterns of clinical progression and effects of supportive therapy. Neurology )] TJ ET
BT 26.250 524.500 Td /F1 9.8 Tf  [(1989;39\(4\):475-481.)] TJ ET
BT 26.250 505.095 Td /F1 9.8 Tf  [(14.)] TJ ET
BT 43.553 505.095 Td /F1 9.8 Tf  [(McDonald CM, Fowler WM, Jr. The role of the neuromuscular medicine and physiatry specialists in the multidisciplinary )] TJ ET
BT 26.250 493.191 Td /F1 9.8 Tf  [(management of neuromuscular disease. Physical medicine and rehabilitation clinics of North America 2012;23\(3\):475-493.)] TJ ET
BT 26.250 473.786 Td /F1 9.8 Tf  [(15.)] TJ ET
BT 43.553 473.786 Td /F1 9.8 Tf  [(McDonald CM, Henricson EK, Han JJ, Abresch RT, Nicorici A, Elfring GL, Atkinson L, Reha A, Hirawat S, Miller LL. The 6-)] TJ ET
BT 26.250 461.881 Td /F1 9.8 Tf  [(minute walk test as a new outcome measure in Duchenne muscular dystrophy. Muscle & nerve 2010;41\(4\):500-510.)] TJ ET
BT 26.250 442.476 Td /F1 9.8 Tf  [(16.)] TJ ET
BT 43.553 442.476 Td /F1 9.8 Tf  [(McDonald CM, Henricson EK, Han JJ, Abresch RT, Nicorici A, Atkinson L, Elfring GL, Reha A, Miller LL. The 6-minute walk )] TJ ET
BT 26.250 430.572 Td /F1 9.8 Tf  [(test in Duchenne/Becker muscular dystrophy: Longitudinal observations. Muscle & nerve 2010;42\(6\):966-974.)] TJ ET
BT 26.250 411.167 Td /F1 9.8 Tf  [(17.)] TJ ET
BT 43.553 411.167 Td /F1 9.8 Tf  [(McDonald CM, Henricson EK, Abresch RT, Florence J, Eagle M, Gappmaier E, Glanzman AM, Spiegel R, Barth J, Elfring )] TJ ET
BT 26.250 399.262 Td /F1 9.8 Tf  [(G, Reha A, Peltz SW. The 6-minute walk test and other clinical endpoints in Duchenne muscular dystrophy: Reliability, )] TJ ET
BT 26.250 387.357 Td /F1 9.8 Tf  [(concurrent validity, and minimal clinically important differences from a multicenter study. Muscle & nerve 2013.)] TJ ET
BT 26.250 367.953 Td /F1 9.8 Tf  [(18.)] TJ ET
BT 43.553 367.953 Td /F1 9.8 Tf  [(McDonald CM, Henricson EK, Abresch RT, Florence J, Eagle M, Gappmaier E, Glanzman AM, Spiegel R, Barth J, Elfring )] TJ ET
BT 26.250 356.048 Td /F1 9.8 Tf  [(G, Reha A, Peltz S. The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: Longitudinal natural history )] TJ ET
BT 26.250 344.143 Td /F1 9.8 Tf  [(observations over 48 weeks from a multicenter study. Muscle & nerve 2013.)] TJ ET
BT 26.250 324.738 Td /F1 9.8 Tf  [(19.)] TJ ET
BT 43.553 324.738 Td /F1 9.8 Tf  [(Mendell JR, Csimma C, McDonald CM, Escolar DM, Janis S, Porter JD, Hesterlee SE, Howell RR. Challenges in drug )] TJ ET
BT 26.250 312.834 Td /F1 9.8 Tf  [(development for muscle disease: a stakeholders' meeting. Muscle & nerve 2007;35\(1\):8-16.)] TJ ET
BT 26.250 293.429 Td /F1 9.8 Tf  [(20.)] TJ ET
BT 43.553 293.429 Td /F1 9.8 Tf  [(FDA. Guidance for Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to Support )] TJ ET
BT 26.250 281.524 Td /F1 9.8 Tf  [(Labeling Claims. In: Center for Drug Evaluation and Research FaDA, editor. December 9, 2009 ed. Volume 74, Federal )] TJ ET
BT 26.250 269.619 Td /F1 9.8 Tf  [(Register Online via GPO Access. Rockville, MD: Federal Register; 2009. p 85132-65133.)] TJ ET
BT 26.250 250.215 Td /F1 9.8 Tf  [(21.)] TJ ET
BT 43.553 250.215 Td /F1 9.8 Tf  [(Acquadro C BR, Dubois D, et al. . Incorporating the patient�s perspective into drug development and communication: an ad )] TJ ET
BT 26.250 238.310 Td /F1 9.8 Tf  [(hoc task force report of the Patient-Reported Outcomes \(PRO\) Harmonization Group meeting at the Food and Drug )] TJ ET
BT 26.250 226.405 Td /F1 9.8 Tf  [(Administration. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research )] TJ ET
BT 26.250 214.500 Td /F1 9.8 Tf  [(2003;6:522-531.)] TJ ET
BT 26.250 195.096 Td /F1 9.8 Tf  [(22.)] TJ ET
BT 43.553 195.096 Td /F1 9.8 Tf  [(Mazzone ES, Messina S, Vasco G, Main M, Eagle M, D'Amico A, Doglio L, Politano L, Cavallaro F, Frosini S, Bello L, Magri )] TJ ET
BT 26.250 183.191 Td /F1 9.8 Tf  [(F, Corlatti A, Zucchini E, Brancalion B, Rossi F, Ferretti M, Motta MG, Cecio MR, Berardinelli A, Alfieri P, Mongini T, Pini A, )] TJ ET
BT 26.250 171.286 Td /F1 9.8 Tf  [(Astrea G, Battini R, Comi G, Pegoraro E, Morandi L, Pane M, Angelini C, Bruno C, Villanova M, Vita G, Donati MA, Bertini E, )] TJ ET
BT 26.250 159.381 Td /F1 9.8 Tf  [(Mercuri E. Reliability of the North Star Ambulatory Assessment in a multicentric setting. Neuromuscular disorders : NMD )] TJ ET
BT 26.250 147.477 Td /F1 9.8 Tf  [(2009;19\(7\):458-461.)] TJ ET
BT 26.250 128.072 Td /F1 9.8 Tf  [(23.)] TJ ET
BT 43.553 128.072 Td /F1 9.8 Tf  [(Bushby K, Connor E. Clinical outcome measures for trials in Duchenne muscular dystrophy: report from International )] TJ ET
BT 26.250 116.167 Td /F1 9.8 Tf  [(Working Group meetings. Clinical investigation 2011;1\(9\):1217-1235.)] TJ ET
BT 26.250 96.762 Td /F1 9.8 Tf  [(24.)] TJ ET
BT 43.553 96.762 Td /F1 9.8 Tf  [(Lai JS, Nowinski C, Victorson D, Bode R, Podrabsky T, McKinney N, Straube D, Holmes GL, McDonald CM, Henricson E, )] TJ ET
BT 26.250 84.858 Td /F1 9.8 Tf  [(Abresch RT, Moy CS, Cella D. Quality-of-life measures in children with neurological conditions: pediatric Neuro-QOL. )] TJ ET
BT 26.250 72.953 Td /F1 9.8 Tf  [(Neurorehabilitation and neural repair 2012;26\(1\):36-47.)] TJ ET
BT 26.250 53.548 Td /F1 9.8 Tf  [(25.)] TJ ET
BT 43.553 53.548 Td /F1 9.8 Tf  [(McDonald CM, McDonald DA, Bagley A, Sienko Thomas S, Buckon CE, Henricson E, Nicorici A, Sussman MD. )] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(11)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Muscular Dystrophy)] TJ ET

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0.271 0.267 0.267 rg
q
15.000 425.095 577.500 351.905 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Relationship between clinical outcome measures and parent proxy reports of health-related quality of life in ambulatory children )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(with Duchenne muscular dystrophy. Journal of child neurology 2010;25\(9\):1130-1144.)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(26.)] TJ ET
BT 43.553 736.167 Td /F1 9.8 Tf  [(Varni JW, Seid M, Rode CA. The PedsQL: Measurement model for the pediatric quality of life inventory. Medical care )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(1999;37\(2\):126-139.)] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(27.)] TJ ET
BT 43.553 704.857 Td /F1 9.8 Tf  [(Varni JW, Seid M, Kurtin PS. PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(core scales in healthy and patient populations. Medical care 2001;39\(8\):800-812.)] TJ ET
BT 26.250 673.548 Td /F1 9.8 Tf  [(28.)] TJ ET
BT 43.553 673.548 Td /F1 9.8 Tf  [(Varni JW, Seid M, Knight TS, Uzark K, Szer IS. The PedsQL 4.0 Generic Core Scales: sensitivity, responsiveness, and )] TJ ET
BT 26.250 661.643 Td /F1 9.8 Tf  [(impact on clinical decision-making. Journal of behavioral medicine 2002;25\(2\):175-193.)] TJ ET
BT 26.250 642.238 Td /F1 9.8 Tf  [(29.)] TJ ET
BT 43.553 642.238 Td /F1 9.8 Tf  [(Daltroy LH, Fossel AH, Goldberg MJ. The POSNA pediatric musculoskeletal functional health questionnaire: report on )] TJ ET
BT 26.250 630.333 Td /F1 9.8 Tf  [(reliability, validity and sensitivity to change. Pediatric Outcomes Development Group. Pediatric Orthopaedic Society of America. )] TJ ET
BT 26.250 618.429 Td /F1 9.8 Tf  [(Journal of pediatric orthopedics 1998;18\(5\):561-571.)] TJ ET
BT 26.250 599.024 Td /F1 9.8 Tf  [(30.)] TJ ET
BT 43.553 599.024 Td /F1 9.8 Tf  [(Haynes RJ, Sullivan E. The Pediatric Orthopaedic Society of North America pediatric orthopaedic functional health )] TJ ET
BT 26.250 587.119 Td /F1 9.8 Tf  [(questionnaire: an analysis of normals. Journal of pediatric orthopedics 2001;21\(5\):619-621.)] TJ ET
BT 26.250 567.714 Td /F1 9.8 Tf  [(31.)] TJ ET
BT 43.553 567.714 Td /F1 9.8 Tf  [(Surgeons AAoO. Outcomes Instruments and Information: POSNA/PODCI Instruments.)] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(32.)] TJ ET
BT 43.553 548.310 Td /F1 9.8 Tf  [(Henricson E, Abresch R, Han JJ, Nicorici A, Goude Keller E, Elfring G, Reha A, Barth J, McDonald CM. Percent-Predicted 6-)] TJ ET
BT 26.250 536.405 Td /F1 9.8 Tf  [(Minute Walk Distance in Duchenne Muscular Dystrophy to Account for Maturational Influences. PLoS currents 2012;4:RRN1297.)] TJ ET
BT 26.250 517.000 Td /F1 9.8 Tf  [(33.)] TJ ET
BT 43.553 517.000 Td /F1 9.8 Tf  [(Geiger R, Strasak A, Treml B, Gasser K, Kleinsasser A, Fischer V, Geiger H, Loeckinger A, Stein JI. Six-minute walk test in )] TJ ET
BT 26.250 505.095 Td /F1 9.8 Tf  [(children and adolescents. The Journal of pediatrics 2007;150\(4\):395-399, 399 e391-392.)] TJ ET
BT 26.250 485.691 Td /F1 9.8 Tf  [(34.)] TJ ET
BT 43.553 485.691 Td /F1 9.8 Tf  [(Yost KJ, Eton DT. Combining distribution- and anchor-based approaches to determine minimally important differences: the )] TJ ET
BT 26.250 473.786 Td /F1 9.8 Tf  [(FACIT experience. Evaluation & the health professions 2005;28\(2\):172-191.)] TJ ET
BT 26.250 454.381 Td /F1 9.8 Tf  [(35.)] TJ ET
BT 43.553 454.381 Td /F1 9.8 Tf  [(European Medicines Agency. Guideline on the clinical investigation of medicinal products for the treatment of Duchenne )] TJ ET
BT 26.250 442.476 Td /F1 9.8 Tf  [(and Becker muscular dystrophy \(draft\). London: European Medicines Agency; 2013.)] TJ ET
Q
q
15.000 425.095 577.500 351.905 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Relationship between clinical outcome measures and parent proxy reports of health-related quality of life in ambulatory children )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(with Duchenne muscular dystrophy. Journal of child neurology 2010;25\(9\):1130-1144.)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(26.)] TJ ET
BT 43.553 736.167 Td /F1 9.8 Tf  [(Varni JW, Seid M, Rode CA. The PedsQL: Measurement model for the pediatric quality of life inventory. Medical care )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(1999;37\(2\):126-139.)] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(27.)] TJ ET
BT 43.553 704.857 Td /F1 9.8 Tf  [(Varni JW, Seid M, Kurtin PS. PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(core scales in healthy and patient populations. Medical care 2001;39\(8\):800-812.)] TJ ET
BT 26.250 673.548 Td /F1 9.8 Tf  [(28.)] TJ ET
BT 43.553 673.548 Td /F1 9.8 Tf  [(Varni JW, Seid M, Knight TS, Uzark K, Szer IS. The PedsQL 4.0 Generic Core Scales: sensitivity, responsiveness, and )] TJ ET
BT 26.250 661.643 Td /F1 9.8 Tf  [(impact on clinical decision-making. Journal of behavioral medicine 2002;25\(2\):175-193.)] TJ ET
BT 26.250 642.238 Td /F1 9.8 Tf  [(29.)] TJ ET
BT 43.553 642.238 Td /F1 9.8 Tf  [(Daltroy LH, Fossel AH, Goldberg MJ. The POSNA pediatric musculoskeletal functional health questionnaire: report on )] TJ ET
BT 26.250 630.333 Td /F1 9.8 Tf  [(reliability, validity and sensitivity to change. Pediatric Outcomes Development Group. Pediatric Orthopaedic Society of America. )] TJ ET
BT 26.250 618.429 Td /F1 9.8 Tf  [(Journal of pediatric orthopedics 1998;18\(5\):561-571.)] TJ ET
BT 26.250 599.024 Td /F1 9.8 Tf  [(30.)] TJ ET
BT 43.553 599.024 Td /F1 9.8 Tf  [(Haynes RJ, Sullivan E. The Pediatric Orthopaedic Society of North America pediatric orthopaedic functional health )] TJ ET
BT 26.250 587.119 Td /F1 9.8 Tf  [(questionnaire: an analysis of normals. Journal of pediatric orthopedics 2001;21\(5\):619-621.)] TJ ET
BT 26.250 567.714 Td /F1 9.8 Tf  [(31.)] TJ ET
BT 43.553 567.714 Td /F1 9.8 Tf  [(Surgeons AAoO. Outcomes Instruments and Information: POSNA/PODCI Instruments.)] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(32.)] TJ ET
BT 43.553 548.310 Td /F1 9.8 Tf  [(Henricson E, Abresch R, Han JJ, Nicorici A, Goude Keller E, Elfring G, Reha A, Barth J, McDonald CM. Percent-Predicted 6-)] TJ ET
BT 26.250 536.405 Td /F1 9.8 Tf  [(Minute Walk Distance in Duchenne Muscular Dystrophy to Account for Maturational Influences. PLoS currents 2012;4:RRN1297.)] TJ ET
BT 26.250 517.000 Td /F1 9.8 Tf  [(33.)] TJ ET
BT 43.553 517.000 Td /F1 9.8 Tf  [(Geiger R, Strasak A, Treml B, Gasser K, Kleinsasser A, Fischer V, Geiger H, Loeckinger A, Stein JI. Six-minute walk test in )] TJ ET
BT 26.250 505.095 Td /F1 9.8 Tf  [(children and adolescents. The Journal of pediatrics 2007;150\(4\):395-399, 399 e391-392.)] TJ ET
BT 26.250 485.691 Td /F1 9.8 Tf  [(34.)] TJ ET
BT 43.553 485.691 Td /F1 9.8 Tf  [(Yost KJ, Eton DT. Combining distribution- and anchor-based approaches to determine minimally important differences: the )] TJ ET
BT 26.250 473.786 Td /F1 9.8 Tf  [(FACIT experience. Evaluation & the health professions 2005;28\(2\):172-191.)] TJ ET
BT 26.250 454.381 Td /F1 9.8 Tf  [(35.)] TJ ET
BT 43.553 454.381 Td /F1 9.8 Tf  [(European Medicines Agency. Guideline on the clinical investigation of medicinal products for the treatment of Duchenne )] TJ ET
BT 26.250 442.476 Td /F1 9.8 Tf  [(and Becker muscular dystrophy \(draft\). London: European Medicines Agency; 2013.)] TJ ET
Q
q
15.000 425.095 577.500 351.905 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Relationship between clinical outcome measures and parent proxy reports of health-related quality of life in ambulatory children )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(with Duchenne muscular dystrophy. Journal of child neurology 2010;25\(9\):1130-1144.)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(26.)] TJ ET
BT 43.553 736.167 Td /F1 9.8 Tf  [(Varni JW, Seid M, Rode CA. The PedsQL: Measurement model for the pediatric quality of life inventory. Medical care )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(1999;37\(2\):126-139.)] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(27.)] TJ ET
BT 43.553 704.857 Td /F1 9.8 Tf  [(Varni JW, Seid M, Kurtin PS. PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(core scales in healthy and patient populations. Medical care 2001;39\(8\):800-812.)] TJ ET
BT 26.250 673.548 Td /F1 9.8 Tf  [(28.)] TJ ET
BT 43.553 673.548 Td /F1 9.8 Tf  [(Varni JW, Seid M, Knight TS, Uzark K, Szer IS. The PedsQL 4.0 Generic Core Scales: sensitivity, responsiveness, and )] TJ ET
BT 26.250 661.643 Td /F1 9.8 Tf  [(impact on clinical decision-making. Journal of behavioral medicine 2002;25\(2\):175-193.)] TJ ET
BT 26.250 642.238 Td /F1 9.8 Tf  [(29.)] TJ ET
BT 43.553 642.238 Td /F1 9.8 Tf  [(Daltroy LH, Fossel AH, Goldberg MJ. The POSNA pediatric musculoskeletal functional health questionnaire: report on )] TJ ET
BT 26.250 630.333 Td /F1 9.8 Tf  [(reliability, validity and sensitivity to change. Pediatric Outcomes Development Group. Pediatric Orthopaedic Society of America. )] TJ ET
BT 26.250 618.429 Td /F1 9.8 Tf  [(Journal of pediatric orthopedics 1998;18\(5\):561-571.)] TJ ET
BT 26.250 599.024 Td /F1 9.8 Tf  [(30.)] TJ ET
BT 43.553 599.024 Td /F1 9.8 Tf  [(Haynes RJ, Sullivan E. The Pediatric Orthopaedic Society of North America pediatric orthopaedic functional health )] TJ ET
BT 26.250 587.119 Td /F1 9.8 Tf  [(questionnaire: an analysis of normals. Journal of pediatric orthopedics 2001;21\(5\):619-621.)] TJ ET
BT 26.250 567.714 Td /F1 9.8 Tf  [(31.)] TJ ET
BT 43.553 567.714 Td /F1 9.8 Tf  [(Surgeons AAoO. Outcomes Instruments and Information: POSNA/PODCI Instruments.)] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(32.)] TJ ET
BT 43.553 548.310 Td /F1 9.8 Tf  [(Henricson E, Abresch R, Han JJ, Nicorici A, Goude Keller E, Elfring G, Reha A, Barth J, McDonald CM. Percent-Predicted 6-)] TJ ET
BT 26.250 536.405 Td /F1 9.8 Tf  [(Minute Walk Distance in Duchenne Muscular Dystrophy to Account for Maturational Influences. PLoS currents 2012;4:RRN1297.)] TJ ET
BT 26.250 517.000 Td /F1 9.8 Tf  [(33.)] TJ ET
BT 43.553 517.000 Td /F1 9.8 Tf  [(Geiger R, Strasak A, Treml B, Gasser K, Kleinsasser A, Fischer V, Geiger H, Loeckinger A, Stein JI. Six-minute walk test in )] TJ ET
BT 26.250 505.095 Td /F1 9.8 Tf  [(children and adolescents. The Journal of pediatrics 2007;150\(4\):395-399, 399 e391-392.)] TJ ET
BT 26.250 485.691 Td /F1 9.8 Tf  [(34.)] TJ ET
BT 43.553 485.691 Td /F1 9.8 Tf  [(Yost KJ, Eton DT. Combining distribution- and anchor-based approaches to determine minimally important differences: the )] TJ ET
BT 26.250 473.786 Td /F1 9.8 Tf  [(FACIT experience. Evaluation & the health professions 2005;28\(2\):172-191.)] TJ ET
BT 26.250 454.381 Td /F1 9.8 Tf  [(35.)] TJ ET
BT 43.553 454.381 Td /F1 9.8 Tf  [(European Medicines Agency. Guideline on the clinical investigation of medicinal products for the treatment of Duchenne )] TJ ET
BT 26.250 442.476 Td /F1 9.8 Tf  [(and Becker muscular dystrophy \(draft\). London: European Medicines Agency; 2013.)] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(12)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Muscular Dystrophy)] TJ ET

Q
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