human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE To confirm the efficacy and safety of recombinant human alpha-L-iduronidase ( laronidase ) in patients with mucopolysaccharidosis I ( MPS I ) . STUDY DESIGN This was a r and omized , double-blinded , multinational study of 45 patients with MPS I administered 100 U/kg ( 0.58 mg/kg ) laronidase , or placebo intravenously weekly for 26 weeks . The co primary efficacy end points compared the median change from baseline to week 26 between groups in percentage of predicted normal forced vital capacity ( FVC ) and in 6-minute walk test ( 6MWT ) distance through the use of the Wilcoxon rank sum test . RESULTS The laronidase ( n=22 ) and placebo ( n=23 ) groups had similar baseline characteristics . After 26 weeks , patients receiving laronidase compared with placebo showed mean improvements of 5.6 percentage points in percent of predicted normal FVC ( median , 3.0 ; P=.009 ) and 38.1 meters in 6MWT distance ( median , 38.5 ; P=.066 ; P=.039 , analysis of covariance ) . Laronidase also significantly reduced hepatomegaly and urinary glycosaminoglycans , and , in more severely affected patients , improved sleep apnea/hypopnea and shoulder flexion .  Laronidase was well-tolerated . Nearly all patients receiving enzyme had development of IgG antibodies , without apparent clinical effects . CONCLUSIONS In patients with MPS I , laronidase significantly improves respiratory function and physical capacity , reduces glycosaminoglycan storage , and has a favorable safety profile Study Design . Clinical prospect i ve , r and om study . Objective . Analyze the results of the six-minute walk test ( 6MWT ) in patients with adolescent idiopathic scoliosis . Summary of Background Data . Although it is widely believed that Adolescent Idiopathic Scoliosis ( AIS ) causes cardiorespiratory dysfunctions , there is no report in literature of objective measurements of this restriction in the ventilatory performance during physical exertion . Methods . One hundred twenty-six adolescents matched by gender and age were prospect ively studied at a tertiary teaching institution : 40 patients without spine deformities ( group I – controls ) , and 86 patients with AIS with a spine curve ranging from 45 ° to 138 ° ( group II ) . All patients underwent radiographic evaluations and the 6MWT . Results . Normal controls presented significantly lower mean heart rate and Borg scores , as well as higher oxygen saturation and walked longer distances on the 6MWT . Conclusion . The 6MWT effectively demonstrated the cardiorespiratory restrictions presented by patients with AIS RATIONALE The 6-minute-walk test ( 6MWT ) is a practical and clinical ly meaningful measure of exercise tolerance with favorable performance characteristics in various cardiac and pulmonary diseases . Performance characteristics in patients with idiopathic pulmonary fibrosis ( IPF ) have not been systematic ally evaluated . OBJECTIVES To assess the reliability , validity , and responsiveness of the 6MWT and estimate the minimal clinical ly important difference ( MCID ) in patients with IPF . METHODS The study population included all subjects completing a 6MWT in a clinical trial evaluating interferon gamma-1b ( n = 822 ) .  Six-minute walk distance ( 6MWD )  and other parameters were measured at baseline and at 24-week intervals using a st and ardized protocol . Parametric and distribution-independent correlation coefficients were used to assess the strength of the relationships between 6MWD and measures of pulmonary function , dyspnea , and health-related quality of life . Both distribution-based and anchor-based methods were used to estimate the MCID . MEASUREMENTS AND MAIN RESULTS Comparison of two proximal measures of 6MWD ( mean interval , 24 d ) demonstrated good reliability ( coefficient = 0.83 ; P < 0.001 ) . 6MWD was weakly correlated with measures of physiologic function and health-related quality of life ; however , values were consistently and significantly lower for patients with the poorest functional status , suggesting good construct validity . Importantly , change in 6MWD was highly predictive of mortality ; a 24-week decline of greater than 50 m was associated with a fourfold increase in risk of death at 1 year ( hazard ratio , 4.27 ; 95 % confidence interval , 2.57- 7.10 ; P < 0.001 ) . The estimated MCID was 24 - 45 m. CONCLUSIONS The 6MWT is a reliable , valid , and responsive measure of disease status and a valid endpoint for clinical trials in IPF PURPOSE We assessed the exercise tolerance and cardiorespiratory responses during 2-month weight-loss programmes using the 6-minute walking test ( 6MWT ) in obese children . METHODS Twenty-eight male obese children were r and omly assigned to either a control group ( C ) , an energy restriction group ( R ) , an exercise training at maximum lipid-oxidation ( LIPOXmax ) group ( E ) , or an energy restriction/training group ( RE ) . The body composition , the submaximal incremental cycling exercise , and the 6MWT were performed before and after the 2-month programme . RESULTS . After the programme , RE group showed a significant improvement of body composition ( body weight reduced by 6.3 ± 1.5 kg , p < 0.01 ) , and an increase of 6-minute walking distance ( 6MWD ) ( + 13.7 % , p < 0.01 ) . Similarly , maximum oxygen uptake calculated according to the American College of Science Medicine guideline ( VO(2max ) ACSM ) and VO(2max ) predicted from 6MWD were respectively higher ( + 12.9 % and + 10.0 % , p < 0.01 ) than the R or E groups . Bl and -Altman analysis highlighted an agreement of these two methods of VO(2max ) measurement . Moreover , in all participants the 6MWD was significantly correlated with VO(2max ) ACSM and LIPOXmax ( r = 0.77 , p < 0.001 and r = 0.67 , p < 0.01 ; respectively ) before the programme as well as their changes in percentage over the programme ( r = 0.85 and r = 0.86 , p < 0.0001 ; respectively ) . CONCLUSIONS We concluded that a 2-month weight-loss programme including energy restriction and exercise training targeted at LIPOXmax improved body composition and cardiorespiratory tolerance in obese children . Furthermore , the 6MWT could be considered as a useful and reliable tool for the assessment and the follow-up of cardiorespiratory responses during weight-loss programme in obese children BACKGROUND Local intramuscular administration of the antisense oligonucleotide PRO051 in patients with Duchenne 's muscular dystrophy with relevant mutations was previously reported to induce the skipping of exon 51 during pre-messenger RNA splicing of the dystrophin gene and to facilitate new dystrophin expression in muscle-fiber membranes . The present phase 1 - 2a study aim ed to assess the safety , pharmacokinetics , and molecular and clinical effects of systemically administered PRO051 . METHODS We administered weekly abdominal subcutaneous injections of PRO051 for 5 weeks in 12 patients , with each of four possible doses ( 0.5 , 2.0 , 4.0 , and 6.0 mg per kilogram of body weight ) given to 3 patients . Changes in RNA splicing and protein levels in the tibialis anterior muscle were assessed at two time points . All patients subsequently entered a 12-week open-label extension phase , during which they all received PRO051 at a dose of 6.0 mg per kilogram per week . Safety , pharmacokinetics , serum creatine kinase levels , and muscle strength and function were assessed . RESULTS The most common adverse events were irritation at the administration site and , during the extension phase , mild and variable proteinuria and increased urinary α(1)-microglobulin levels ; there were no serious adverse events . The mean terminal half-life of PRO051 in the circulation was 29 days . PRO051 induced detectable , specific exon-51 skipping at doses of 2.0 mg or more per kilogram . New dystrophin expression was observed between approximately 60 % and 100 % of muscle fibers in 10 of the 12 patients , as measured on post-treatment biopsy , which increased in a dose-dependent manner to up to 15.6 % of the expression in healthy muscle . After the 12-week extension phase , there was a mean ( ±SD ) improvement of 35.2±28.7 m ( from the baseline of 384±121 m ) on the 6-minute walk test . CONCLUSIONS Systemically administered PRO051 showed dose-dependent molecular efficacy in patients with Duchenne 's muscular dystrophy , with a modest improvement in the 6-minute walk test after 12 weeks of extended treatment . ( Funded by Prosensa Therapeutics ; Netherl and s National Trial Register number , NTR1241 . ) OBJECTIVE To estimate the minimal clinical ly important difference ( MCID ) for the 6-minute walk test ( 6MWT ) and the 200-m fast-walk test ( FWT ) in patients with coronary artery disease ( CAD ) during a cardiac rehabilitation program . DESIGN Prospect i ve study using distribution- and anchor-based methods . SETTING Out patients from a cardiac rehabilitation unit . PARTICIPANTS Stable patients with CAD ( N=81 ; 77 men ; mean±SD age , 58.1±8.7y ) enrolled 31±12.1 days after an acute coronary syndrome ( ACS ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES  6MWT and 200-m FWT results before and after an 8-week cardiac rehabilitation program and at the 6th and 12th sessions . Patients and physiotherapists who supervised the training were asked to provide a global rating of perceived change in walking ability while blinded to changes in walk test performances . RESULTS Mean change in 6MWT distance ( 6MWD ) in patients who reported no change was -6.5 m versus 23.3 m in those who believed their performance had improved ( P<.001 ) . This result was consistent with the MCID determined by using the distribution method ( 23 m ) . Considering a 25-m cutoff , positive and negative predictive values were 0.9 and .63 , respectively . Conversely , there was no difference in 200-m FWT performance between these 2 groups ( 0.1 vs -1.4s , respectively ) . There was poor agreement with the physiotherapist 's perceived change . CONCLUSIONS The MCID for 6MWD in patients with CAD after ACS was 25 m . This result will help physicians interpret 6MWD change and help research ers estimate sample sizes in further studies using 6MWD as an endpoint OBJECTIVE To investigate the feasibility and effects of a physical exercise programme on functioning and health-related quality of life in adults with myotonic dystrophy type 1 . DESIGN A r and omized controlled trial . SUBJECTS Thirty-five adults with myotonic dystrophy type 1 . METHODS After stratification for level of functioning , study participants were assigned by lot to either a training group or a control group . Training-group participants attended a 60-minute comprehensive group-training programme , Friskis&Svettis ® Open Doors , twice a week for 14 weeks . The six-minute walk test was the primary outcome measure and the timed-st and s test , the timed up- and -go test , the Epworth sleepiness scale and the Short Form-36 health survey were secondary outcome measures . RESULTS Intention-to-treat analyses revealed no significant differences in any outcome measures , except for an increased between-group difference after intervention in the Short Form-36 mental health subscale and a decrease in the vitality subscale for the control group . The programme was well tolerated and many training-group participants perceived subjective changes for the better . No negative effects were reported . CONCLUSION The Friskis&Svettis ® Open Doors programme was feasible for adults with myotonic dystrophy type 1 who had been screened for cardiac involvement , had distal or mild-to-moderate proximal muscle impairment , and no severe cognitive impairments . No beneficial or detrimental effects were evident Objectives For the measurement of  patient-reported outcomes , such as ( health-related ) quality of life , often many measurement instruments exist that intend to measure the same construct . To facilitate instrument selection , our aim was to develop a highly sensitive search filter for finding studies on measurement properties of measurement instruments in PubMed and a more precise search filter that needs less abstract s to be screened , but at a higher risk of missing relevant studies . Methods A r and om sample of 10,000 PubMed records ( 01 - 01 - 1990 to 31 - 12 - 2006 ) was used as a gold st and ard . Studies on measurement properties were identified using an exclusion filter and h and search ing . Search terms were selected from the relevant records in the gold st and ard as well as from 100 systematic review s of measurement properties and combined based on sensitivity and precision . The performance of the filters was tested in the gold st and ard as well as in two validation sets , by calculating sensitivity , precision , specificity , and number needed to read . Results We identified 116 studies on measurement properties in the gold st and ard . The sensitive search filter was able to retrieve 113 of these 116 studies ( sensitivity 97.4 
    Output:
    
agent
Limited evidence to strong evidence was found for reliability in various chronic conditions .
Little evidence was available for responsiveness and measurement error .
Studies showed large variability in test procedures despite existing guidelines for the performance of the 6MWT .
Evidence for measurement properties of the 6MWT  varies largely among chronic pediatric conditions .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE To confirm the efficacy and safety of recombinant human alpha-L-iduronidase ( laronidase ) in patients with mucopolysaccharidosis I ( MPS I ) . STUDY DESIGN This was a r and omized , double-blinded , multinational study of 45 patients with MPS I administered 100 U/kg ( 0.58 mg/kg ) laronidase , or placebo intravenously weekly for 26 weeks . The co primary efficacy end points compared the median change from baseline to week 26 between groups in percentage of predicted normal forced vital capacity ( FVC ) and in 6-minute walk test ( 6MWT ) distance through the use of the Wilcoxon rank sum test . RESULTS The laronidase ( n=22 ) and placebo ( n=23 ) groups had similar baseline characteristics . After 26 weeks , patients receiving laronidase compared with placebo showed mean improvements of 5.6 percentage points in percent of predicted normal FVC ( median , 3.0 ; P=.009 ) and 38.1 meters in 6MWT distance ( median , 38.5 ; P=.066 ; P=.039 , analysis of covariance ) . Laronidase also significantly reduced hepatomegaly and urinary glycosaminoglycans , and , in more severely affected patients , improved sleep apnea/hypopnea and shoulder flexion .  Laronidase was well-tolerated . Nearly all patients receiving enzyme had development of IgG antibodies , without apparent clinical effects . CONCLUSIONS In patients with MPS I , laronidase significantly improves respiratory function and physical capacity , reduces glycosaminoglycan storage , and has a favorable safety profile Study Design . Clinical prospect i ve , r and om study . Objective . Analyze the results of the six-minute walk test ( 6MWT ) in patients with adolescent idiopathic scoliosis . Summary of Background Data . Although it is widely believed that Adolescent Idiopathic Scoliosis ( AIS ) causes cardiorespiratory dysfunctions , there is no report in literature of objective measurements of this restriction in the ventilatory performance during physical exertion . Methods . One hundred twenty-six adolescents matched by gender and age were prospect ively studied at a tertiary teaching institution : 40 patients without spine deformities ( group I – controls ) , and 86 patients with AIS with a spine curve ranging from 45 ° to 138 ° ( group II ) . All patients underwent radiographic evaluations and the 6MWT . Results . Normal controls presented significantly lower mean heart rate and Borg scores , as well as higher oxygen saturation and walked longer distances on the 6MWT . Conclusion . The 6MWT effectively demonstrated the cardiorespiratory restrictions presented by patients with AIS RATIONALE The 6-minute-walk test ( 6MWT ) is a practical and clinical ly meaningful measure of exercise tolerance with favorable performance characteristics in various cardiac and pulmonary diseases . Performance characteristics in patients with idiopathic pulmonary fibrosis ( IPF ) have not been systematic ally evaluated . OBJECTIVES To assess the reliability , validity , and responsiveness of the 6MWT and estimate the minimal clinical ly important difference ( MCID ) in patients with IPF . METHODS The study population included all subjects completing a 6MWT in a clinical trial evaluating interferon gamma-1b ( n = 822 ) .  Six-minute walk distance ( 6MWD )  and other parameters were measured at baseline and at 24-week intervals using a st and ardized protocol . Parametric and distribution-independent correlation coefficients were used to assess the strength of the relationships between 6MWD and measures of pulmonary function , dyspnea , and health-related quality of life . Both distribution-based and anchor-based methods were used to estimate the MCID . MEASUREMENTS AND MAIN RESULTS Comparison of two proximal measures of 6MWD ( mean interval , 24 d ) demonstrated good reliability ( coefficient = 0.83 ; P < 0.001 ) . 6MWD was weakly correlated with measures of physiologic function and health-related quality of life ; however , values were consistently and significantly lower for patients with the poorest functional status , suggesting good construct validity . Importantly , change in 6MWD was highly predictive of mortality ; a 24-week decline of greater than 50 m was associated with a fourfold increase in risk of death at 1 year ( hazard ratio , 4.27 ; 95 % confidence interval , 2.57- 7.10 ; P < 0.001 ) . The estimated MCID was 24 - 45 m. CONCLUSIONS The 6MWT is a reliable , valid , and responsive measure of disease status and a valid endpoint for clinical trials in IPF PURPOSE We assessed the exercise tolerance and cardiorespiratory responses during 2-month weight-loss programmes using the 6-minute walking test ( 6MWT ) in obese children . METHODS Twenty-eight male obese children were r and omly assigned to either a control group ( C ) , an energy restriction group ( R ) , an exercise training at maximum lipid-oxidation ( LIPOXmax ) group ( E ) , or an energy restriction/training group ( RE ) . The body composition , the submaximal incremental cycling exercise , and the 6MWT were performed before and after the 2-month programme . RESULTS . After the programme , RE group showed a significant improvement of body composition ( body weight reduced by 6.3 ± 1.5 kg , p < 0.01 ) , and an increase of 6-minute walking distance ( 6MWD ) ( + 13.7 % , p < 0.01 ) . Similarly , maximum oxygen uptake calculated according to the American College of Science Medicine guideline ( VO(2max ) ACSM ) and VO(2max ) predicted from 6MWD were respectively higher ( + 12.9 % and + 10.0 % , p < 0.01 ) than the R or E groups . Bl and -Altman analysis highlighted an agreement of these two methods of VO(2max ) measurement . Moreover , in all participants the 6MWD was significantly correlated with VO(2max ) ACSM and LIPOXmax ( r = 0.77 , p < 0.001 and r = 0.67 , p < 0.01 ; respectively ) before the programme as well as their changes in percentage over the programme ( r = 0.85 and r = 0.86 , p < 0.0001 ; respectively ) . CONCLUSIONS We concluded that a 2-month weight-loss programme including energy restriction and exercise training targeted at LIPOXmax improved body composition and cardiorespiratory tolerance in obese children . Furthermore , the 6MWT could be considered as a useful and reliable tool for the assessment and the follow-up of cardiorespiratory responses during weight-loss programme in obese children BACKGROUND Local intramuscular administration of the antisense oligonucleotide PRO051 in patients with Duchenne 's muscular dystrophy with relevant mutations was previously reported to induce the skipping of exon 51 during pre-messenger RNA splicing of the dystrophin gene and to facilitate new dystrophin expression in muscle-fiber membranes . The present phase 1 - 2a study aim ed to assess the safety , pharmacokinetics , and molecular and clinical effects of systemically administered PRO051 . METHODS We administered weekly abdominal subcutaneous injections of PRO051 for 5 weeks in 12 patients , with each of four possible doses ( 0.5 , 2.0 , 4.0 , and 6.0 mg per kilogram of body weight ) given to 3 patients . Changes in RNA splicing and protein levels in the tibialis anterior muscle were assessed at two time points . All patients subsequently entered a 12-week open-label extension phase , during which they all received PRO051 at a dose of 6.0 mg per kilogram per week . Safety , pharmacokinetics , serum creatine kinase levels , and muscle strength and function were assessed . RESULTS The most common adverse events were irritation at the administration site and , during the extension phase , mild and variable proteinuria and increased urinary α(1)-microglobulin levels ; there were no serious adverse events . The mean terminal half-life of PRO051 in the circulation was 29 days . PRO051 induced detectable , specific exon-51 skipping at doses of 2.0 mg or more per kilogram . New dystrophin expression was observed between approximately 60 % and 100 % of muscle fibers in 10 of the 12 patients , as measured on post-treatment biopsy , which increased in a dose-dependent manner to up to 15.6 % of the expression in healthy muscle . After the 12-week extension phase , there was a mean ( ±SD ) improvement of 35.2±28.7 m ( from the baseline of 384±121 m ) on the 6-minute walk test . CONCLUSIONS Systemically administered PRO051 showed dose-dependent molecular efficacy in patients with Duchenne 's muscular dystrophy , with a modest improvement in the 6-minute walk test after 12 weeks of extended treatment . ( Funded by Prosensa Therapeutics ; Netherl and s National Trial Register number , NTR1241 . ) OBJECTIVE To estimate the minimal clinical ly important difference ( MCID ) for the 6-minute walk test ( 6MWT ) and the 200-m fast-walk test ( FWT ) in patients with coronary artery disease ( CAD ) during a cardiac rehabilitation program . DESIGN Prospect i ve study using distribution- and anchor-based methods . SETTING Out patients from a cardiac rehabilitation unit . PARTICIPANTS Stable patients with CAD ( N=81 ; 77 men ; mean±SD age , 58.1±8.7y ) enrolled 31±12.1 days after an acute coronary syndrome ( ACS ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES  6MWT and 200-m FWT results before and after an 8-week cardiac rehabilitation program and at the 6th and 12th sessions . Patients and physiotherapists who supervised the training were asked to provide a global rating of perceived change in walking ability while blinded to changes in walk test performances . RESULTS Mean change in 6MWT distance ( 6MWD ) in patients who reported no change was -6.5 m versus 23.3 m in those who believed their performance had improved ( P<.001 ) . This result was consistent with the MCID determined by using the distribution method ( 23 m ) . Considering a 25-m cutoff , positive and negative predictive values were 0.9 and .63 , respectively . Conversely , there was no difference in 200-m FWT performance between these 2 groups ( 0.1 vs -1.4s , respectively ) . There was poor agreement with the physiotherapist 's perceived change . CONCLUSIONS The MCID for 6MWD in patients with CAD after ACS was 25 m . This result will help physicians interpret 6MWD change and help research ers estimate sample sizes in further studies using 6MWD as an endpoint OBJECTIVE To investigate the feasibility and effects of a physical exercise programme on functioning and health-related quality of life in adults with myotonic dystrophy type 1 . DESIGN A r and omized controlled trial . SUBJECTS Thirty-five adults with myotonic dystrophy type 1 . METHODS After stratification for level of functioning , study participants were assigned by lot to either a training group or a control group . Training-group participants attended a 60-minute comprehensive group-training programme , Friskis&Svettis ® Open Doors , twice a week for 14 weeks . The six-minute walk test was the primary outcome measure and the timed-st and s test , the timed up- and -go test , the Epworth sleepiness scale and the Short Form-36 health survey were secondary outcome measures . RESULTS Intention-to-treat analyses revealed no significant differences in any outcome measures , except for an increased between-group difference after intervention in the Short Form-36 mental health subscale and a decrease in the vitality subscale for the control group . The programme was well tolerated and many training-group participants perceived subjective changes for the better . No negative effects were reported . CONCLUSION The Friskis&Svettis ® Open Doors programme was feasible for adults with myotonic dystrophy type 1 who had been screened for cardiac involvement , had distal or mild-to-moderate proximal muscle impairment , and no severe cognitive impairments . No beneficial or detrimental effects were evident Objectives For the measurement of  patient-reported outcomes , such as ( health-related ) quality of life , often many measurement instruments exist that intend to measure the same construct . To facilitate instrument selection , our aim was to develop a highly sensitive search filter for finding studies on measurement properties of measurement instruments in PubMed and a more precise search filter that needs less abstract s to be screened , but at a higher risk of missing relevant studies . Methods A r and om sample of 10,000 PubMed records ( 01 - 01 - 1990 to 31 - 12 - 2006 ) was used as a gold st and ard . Studies on measurement properties were identified using an exclusion filter and h and search ing . Search terms were selected from the relevant records in the gold st and ard as well as from 100 systematic review s of measurement properties and combined based on sensitivity and precision . The performance of the filters was tested in the gold st and ard as well as in two validation sets , by calculating sensitivity , precision , specificity , and number needed to read . Results We identified 116 studies on measurement properties in the gold st and ard . The sensitive search filter was able to retrieve 113 of these 116 studies ( sensitivity 97.4 
    Output:
    