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 Mechanical factors , in particular increased medial knee joint load , are believed to be important in the structural progression of knee osteoarthritis . This study evaluated the relationship of medial knee load during walking to indices of structural disease progression , measured on MRI , in people with medial knee osteoarthritis . Methods A longitudinal cohort design utilising a subset of participants ( n=144 , 72 % ) enrolled in a r and omised controlled trial of lateral wedge insoles was employed .  Medial knee load parameters including the peak knee adduction moment ( KAM ) and the KAM impulse  were measured at baseline using three-dimensional gait analysis during walking . MRI at baseline and at 12 months was used to assess structural indices . Multiple regression with adjustment for covariates assessed the relationship between medial knee load parameters and the annual change in medial tibial cartilage volume . Binary logistic regression was used for the dichotomous variables of progression of medial tibiofemoral cartilage defects and bone marrow lesions ( BML ) . Results A higher KAM impulse , but not peak KAM , at baseline was independently associated with greater loss of medial tibial cartilage volume over 12 months ( β=29.9 , 95 % CI 6.3 to 53.5 , p=0.01 ) . No significant relationships were seen between medial knee load parameters and the progression of medial tibiofemoral cartilage defects or BML . Conclusion This study suggests knee loading , in particular the KAM impulse , may be a risk factor for loss of medial tibial cartilage volume . As knee load is modifiable , load-modifying treatments may potentially slow disease progression STUDY DESIGN Prospect i ve cohort study . OBJECTIVES To characterize knee cartilage change in individuals with knee osteoarthritis ( KOA ) who have completed a therapeutic exercise program .  BACKGROUND While therapeutic exercise is frequently used successfully to improve pain and function in individuals with KOA , no studies have reported the volume of cartilage change or individual factors that may impact volume of cartilage change in those completing an exercise program  for KOA . METHODS Thirteen individuals with KOA underwent  magnetic resonance imaging to quantify cartilage volume change in the weight-bearing regions of the medial and lateral femoral condyles and the entire surface of the tibial plateaus from baseline to 1-year follow-up . Body structure and function measures were taken for body mass index , knee axis alignment , knee motion , and knee strength . Activity limitations and activity levels were also measured prior to the therapeutic exercise program , using the Western Ontario and McMaster Universities Osteoarthritis Index and the Physical Activity Scale for the Elderly . At 6 months from baseline , follow-up clinical measurements of knee strength and motion were performed . At 1 year from baseline , imaging of the knee cartilage and knee alignment were performed , and participants completed the Western Ontario and McMaster Universities Osteoarthritis Index and Physical Activity Scale for the Elderly . RESULTS The central region of the medial femoral condyle ( cMF ) had a median volume of cartilage loss of 3.8 % . The other 3 knee tibiofemoral articular surfaces had minimal median cartilage volume change . Individuals were dichotomized into progressors ( n = 6 ) and nonprogressors ( n = 7 ) , based on the st and ard error of measurement of cartilage volume change for the cMF . Progressors were younger , had a larger body mass index , had a higher Kellgren-Lawrence grade in the medial compartment of the knee , and had a greater increase in knee varus alignment from baseline to 1-year follow-up . The progressors also had frontal plane hip and knee kinetics during baseline gait analysis that potentially increased medial knee joint loading . CONCLUSION The loss of cMF cartilage volume was highly variable and the median loss of cartilage was within the range previously reported . Seven of the 13 individuals did not have cMF cartilage volume loss greater than the st and ard error of measurement . Change in cartilage volume of the cMF may be influenced to a greater extent by personal factors than by completion of a therapeutic exercise program . Additional research is needed to decipher the interactions among therapeutic exercise and personal characteristics that impact knee cartilage loss Objective This study aim ed to determine whether the effect of laterally wedged insoles on the adduction moment in knee osteoarthritis ( OA ) declined after one month of wear , and whether higher reported use of insoles was associated with a reduced effect on the adduction moment at one month . Methods Twenty people with medial compartment OA underwent gait analysis in their own shoes wearing i ) no insoles and ; ii ) insoles wedged laterally 5 ° in r and om order .  Testing occurred at baseline and after one month of use of the insoles . Participants recorded daily use of insoles in a log-book . Outcomes were the first and second peak external knee adduction moment and the adduction angular impulse , compared across conditions and time with repeated measures general linear models . Correlations were obtained between total insole use and change in gait parameters with used insoles at one month , and change scores were compared between high and low users of insoles using general linear models . Results There was a significant main effect for condition , whereby insoles significantly reduced the adduction moment ( all p < 0.001 ) . However there was no significant main effect for time , nor was an interaction effect evident . No significant associations were observed between total insole use and change in gait parameters with used insoles at one month , nor was there a difference in effectiveness of insoles between high and low users of the insoles at this time . Conclusion Effects of laterally wedged insoles on the adduction moment do not appear to decline after one month of continuous use , suggesting that significant wedge degradation does not occur over the short-term In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Objective To assess the effect of lateral wedge insoles compared with flat control insoles on improving symptoms and slowing structural disease progression in medial knee osteoarthritis . Design R and omised controlled trial . Setting Community in Melbourne , Australia . Participants 200 people aged 50 or more with clinical and radiographic diagnosis of mild to moderately severe medial knee osteoarthritis . Interventions Full length 5 degree lateral wedged insoles or flat control insoles worn inside the shoes daily for 12 months . Main outcome measures Primary symptomatic outcome was change in overall knee pain ( past week ) measured on an 11 point numerical rating scale . Primary structural outcome was change in volume of medial tibial cartilage from magnetic resonance imaging scans . Secondary clinical outcomes included changes in measures of pain , function , stiffness , and health related quality of life . Secondary structural outcomes included progression of medial cartilage defects and bone marrow lesions . Results Between group differences did not differ significantly for the primary outcomes of change in overall pain ( −0.3 points , 95 % confidence intervals −1.0 to 0.3 ) and change in medial tibial cartilage volume ( −0.4 mm3 , 95 % confidence interval −15.4 to 14.6 ) , and confidence intervals did not include minimal clinical ly important differences . None of the changes in secondary outcomes showed differences between groups . Conclusion Lateral wedge insoles worn for 12 months provided no symptomatic or structural benefits compared with flat control insoles . Trial registration Australian New Zeal and Clinical Trials Registry ACTR12605000503628 and Clinical Trials.gov NCT00415259 Background Osteoarthritis of the knee involving predominantly the medial tibiofemoral compartment is common in older people , giving rise to pain and loss of function . Many people experience progressive worsening of the disease over time , particularly those with varus malalignment and increased medial knee joint load . Therefore , interventions that can reduce excessive medial knee loading may be beneficial in reducing the risk of structural progression . Traditional quadriceps strengthening can improve pain and function in people with knee osteoarthritis but does not appear to reduce medial knee load . A neuromuscular exercise program , emphasising optimal alignment of the trunk and lower limb joints relative to one another , as well as quality of movement performance , while dynamically and functionally strengthening the lower limb muscles , may be able to reduce medial knee load . Such a program may also be superior to traditional quadriceps strengthening with respect to improved pain and physical function because of the functional and dynamic nature . This r and omised controlled trial will investigate the effect of a neuromuscular exercise program on medial knee joint loading , pain and function in individuals with medial knee joint osteoarthritis . We hypothesise that the neuromuscular program will reduce medial knee load as well as pain and functional limitations to a greater extent than a traditional quadriceps strengthening program . Methods / Design 100 people with medial knee pain , radiographic medial compartment osteoarthritis and varus malalignment will be recruited and r and omly allocated to one of two 12-week exercise programs : quadriceps strengthening or neuromuscular exercise . Each program will involve 14 supervised exercise sessions with a physiotherapist plus four unsupervised sessions per week at home . The primary outcomes are medial knee load during walking ( the peak external knee adduction moment from 3D gait analysis ) , pain , and self-reported physical function measured at baseline and immediately following the program . Secondary outcomes include the external knee adduction moment angular impulse , electromyographic muscle activation patterns , knee and hip muscle strength , balance , functional ability , and quality -of-life . Discussion The findings will help determine whether neuromuscular exercise is superior to traditional quadriceps strengthening regarding effects on knee load , pain and physical function in people with medial knee osteoarthritis and varus malalignment . Trial Registration Australian New Zeal and Clinical Trials Registry reference : Osteoarthritic knee pain affects patient mobility . Relief of knee pain in osteoarthritis has been reported to increase loading of the knee during gait , but it is unknown whether such pain relief enhances knee loading during more dem and ing activities such as stair-stepping . The gait of 19 patients and stair-stepping of 14 patients with painful medial compartment osteoarthritis of the knee was assessed before and after pain-relieving intraarticular injection of the knee and compared with those of 21 healthy control subjects . There were significant increases in gait velocity , cadence , maximum external knee adduction moment ( indicating increased loading in the medial compartment of the knee ) , and maximum external hip adduction and ankle abduction moments immediately after the injection . With the exception of velocity and ankle abduction moment , these variables were returned to levels that were not statistically different from those of the control subjects . However , no significant differences were found during stair-stepping in the external adduction-abduction moments about the knee , hip , or ankle after injection . Furthermore , the postinjection magnitudes of these variables during stair-stepping were significantly less than those of the controls . Therefore , although the relief of knee pain is sufficient to enhance gait function in osteoarthritis of the knee , it is insufficient to enhance stair-stepping function OBJECTIVE To evaluate the effects of a modified shoe that incorporates both lateral wedging and a variable-stiffness sole on knee joint loading in 3 population s : individuals with symptomatic and radiographic knee osteoarthritis ( OA ) , asymptomatic overweight individuals , and asymptomatic healthy weight individuals . METHODS Ninety participants ( 30 per group ) underwent a 3-dimensional gait analysis  across 3 test conditions : modified shoes , st and ard control shoes , and barefoot . For each condition , the first peak knee adduction moment ( KAM ) and knee flexion moment ( KFM ) ( both expressed as Nm/[body weight × height]% ) as well as the KAM impulse ( expressed as Nm.s/[body weight × height]% ) were determined . RESULTS The modified shoes significantly reduced the peak KAM as compared to the control shoes in both the OA ( P = 0.002 ) and the overweight ( P = 0.03 ) groups . In the OA group , there was no significant difference in peak KAM when walking in the modified shoe as compared to walking barefoot . In the overweight and the healthy weight groups , the peak KAM when walking in the modified shoe was significantly higher than that when walking barefoot ( P < 0.001 ) . Irrespective of group , the KAM impulse was significantly reduced when walking in the modified shoe as compared to the control shoe ( P < 0.001 ) and was significantly higher during both shoe conditions as compared to walking barefoot ( P < 0.001 ) . There was no change in the KFM between walking conditions for any group . CONCLUSION The findings illustrate that a shoe incorporating both a lateral wedge and a variable-stiffness sole can significantly reduce medial knee joint load . Further research examining the effects of these 
    Output:
    
agent
There is very limited and low- quality evidence to support for a causal link between knee joint loading during walking and structural progression of knee OA .
***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 Mechanical factors , in particular increased medial knee joint load , are believed to be important in the structural progression of knee osteoarthritis . This study evaluated the relationship of medial knee load during walking to indices of structural disease progression , measured on MRI , in people with medial knee osteoarthritis . Methods A longitudinal cohort design utilising a subset of participants ( n=144 , 72 % ) enrolled in a r and omised controlled trial of lateral wedge insoles was employed .  Medial knee load parameters including the peak knee adduction moment ( KAM ) and the KAM impulse  were measured at baseline using three-dimensional gait analysis during walking . MRI at baseline and at 12 months was used to assess structural indices . Multiple regression with adjustment for covariates assessed the relationship between medial knee load parameters and the annual change in medial tibial cartilage volume . Binary logistic regression was used for the dichotomous variables of progression of medial tibiofemoral cartilage defects and bone marrow lesions ( BML ) . Results A higher KAM impulse , but not peak KAM , at baseline was independently associated with greater loss of medial tibial cartilage volume over 12 months ( β=29.9 , 95 % CI 6.3 to 53.5 , p=0.01 ) . No significant relationships were seen between medial knee load parameters and the progression of medial tibiofemoral cartilage defects or BML . Conclusion This study suggests knee loading , in particular the KAM impulse , may be a risk factor for loss of medial tibial cartilage volume . As knee load is modifiable , load-modifying treatments may potentially slow disease progression STUDY DESIGN Prospect i ve cohort study . OBJECTIVES To characterize knee cartilage change in individuals with knee osteoarthritis ( KOA ) who have completed a therapeutic exercise program .  BACKGROUND While therapeutic exercise is frequently used successfully to improve pain and function in individuals with KOA , no studies have reported the volume of cartilage change or individual factors that may impact volume of cartilage change in those completing an exercise program  for KOA . METHODS Thirteen individuals with KOA underwent  magnetic resonance imaging to quantify cartilage volume change in the weight-bearing regions of the medial and lateral femoral condyles and the entire surface of the tibial plateaus from baseline to 1-year follow-up . Body structure and function measures were taken for body mass index , knee axis alignment , knee motion , and knee strength . Activity limitations and activity levels were also measured prior to the therapeutic exercise program , using the Western Ontario and McMaster Universities Osteoarthritis Index and the Physical Activity Scale for the Elderly . At 6 months from baseline , follow-up clinical measurements of knee strength and motion were performed . At 1 year from baseline , imaging of the knee cartilage and knee alignment were performed , and participants completed the Western Ontario and McMaster Universities Osteoarthritis Index and Physical Activity Scale for the Elderly . RESULTS The central region of the medial femoral condyle ( cMF ) had a median volume of cartilage loss of 3.8 % . The other 3 knee tibiofemoral articular surfaces had minimal median cartilage volume change . Individuals were dichotomized into progressors ( n = 6 ) and nonprogressors ( n = 7 ) , based on the st and ard error of measurement of cartilage volume change for the cMF . Progressors were younger , had a larger body mass index , had a higher Kellgren-Lawrence grade in the medial compartment of the knee , and had a greater increase in knee varus alignment from baseline to 1-year follow-up . The progressors also had frontal plane hip and knee kinetics during baseline gait analysis that potentially increased medial knee joint loading . CONCLUSION The loss of cMF cartilage volume was highly variable and the median loss of cartilage was within the range previously reported . Seven of the 13 individuals did not have cMF cartilage volume loss greater than the st and ard error of measurement . Change in cartilage volume of the cMF may be influenced to a greater extent by personal factors than by completion of a therapeutic exercise program . Additional research is needed to decipher the interactions among therapeutic exercise and personal characteristics that impact knee cartilage loss Objective This study aim ed to determine whether the effect of laterally wedged insoles on the adduction moment in knee osteoarthritis ( OA ) declined after one month of wear , and whether higher reported use of insoles was associated with a reduced effect on the adduction moment at one month . Methods Twenty people with medial compartment OA underwent gait analysis in their own shoes wearing i ) no insoles and ; ii ) insoles wedged laterally 5 ° in r and om order .  Testing occurred at baseline and after one month of use of the insoles . Participants recorded daily use of insoles in a log-book . Outcomes were the first and second peak external knee adduction moment and the adduction angular impulse , compared across conditions and time with repeated measures general linear models . Correlations were obtained between total insole use and change in gait parameters with used insoles at one month , and change scores were compared between high and low users of insoles using general linear models . Results There was a significant main effect for condition , whereby insoles significantly reduced the adduction moment ( all p < 0.001 ) . However there was no significant main effect for time , nor was an interaction effect evident . No significant associations were observed between total insole use and change in gait parameters with used insoles at one month , nor was there a difference in effectiveness of insoles between high and low users of the insoles at this time . Conclusion Effects of laterally wedged insoles on the adduction moment do not appear to decline after one month of continuous use , suggesting that significant wedge degradation does not occur over the short-term In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Objective To assess the effect of lateral wedge insoles compared with flat control insoles on improving symptoms and slowing structural disease progression in medial knee osteoarthritis . Design R and omised controlled trial . Setting Community in Melbourne , Australia . Participants 200 people aged 50 or more with clinical and radiographic diagnosis of mild to moderately severe medial knee osteoarthritis . Interventions Full length 5 degree lateral wedged insoles or flat control insoles worn inside the shoes daily for 12 months . Main outcome measures Primary symptomatic outcome was change in overall knee pain ( past week ) measured on an 11 point numerical rating scale . Primary structural outcome was change in volume of medial tibial cartilage from magnetic resonance imaging scans . Secondary clinical outcomes included changes in measures of pain , function , stiffness , and health related quality of life . Secondary structural outcomes included progression of medial cartilage defects and bone marrow lesions . Results Between group differences did not differ significantly for the primary outcomes of change in overall pain ( −0.3 points , 95 % confidence intervals −1.0 to 0.3 ) and change in medial tibial cartilage volume ( −0.4 mm3 , 95 % confidence interval −15.4 to 14.6 ) , and confidence intervals did not include minimal clinical ly important differences . None of the changes in secondary outcomes showed differences between groups . Conclusion Lateral wedge insoles worn for 12 months provided no symptomatic or structural benefits compared with flat control insoles . Trial registration Australian New Zeal and Clinical Trials Registry ACTR12605000503628 and Clinical Trials.gov NCT00415259 Background Osteoarthritis of the knee involving predominantly the medial tibiofemoral compartment is common in older people , giving rise to pain and loss of function . Many people experience progressive worsening of the disease over time , particularly those with varus malalignment and increased medial knee joint load . Therefore , interventions that can reduce excessive medial knee loading may be beneficial in reducing the risk of structural progression . Traditional quadriceps strengthening can improve pain and function in people with knee osteoarthritis but does not appear to reduce medial knee load . A neuromuscular exercise program , emphasising optimal alignment of the trunk and lower limb joints relative to one another , as well as quality of movement performance , while dynamically and functionally strengthening the lower limb muscles , may be able to reduce medial knee load . Such a program may also be superior to traditional quadriceps strengthening with respect to improved pain and physical function because of the functional and dynamic nature . This r and omised controlled trial will investigate the effect of a neuromuscular exercise program on medial knee joint loading , pain and function in individuals with medial knee joint osteoarthritis . We hypothesise that the neuromuscular program will reduce medial knee load as well as pain and functional limitations to a greater extent than a traditional quadriceps strengthening program . Methods / Design 100 people with medial knee pain , radiographic medial compartment osteoarthritis and varus malalignment will be recruited and r and omly allocated to one of two 12-week exercise programs : quadriceps strengthening or neuromuscular exercise . Each program will involve 14 supervised exercise sessions with a physiotherapist plus four unsupervised sessions per week at home . The primary outcomes are medial knee load during walking ( the peak external knee adduction moment from 3D gait analysis ) , pain , and self-reported physical function measured at baseline and immediately following the program . Secondary outcomes include the external knee adduction moment angular impulse , electromyographic muscle activation patterns , knee and hip muscle strength , balance , functional ability , and quality -of-life . Discussion The findings will help determine whether neuromuscular exercise is superior to traditional quadriceps strengthening regarding effects on knee load , pain and physical function in people with medial knee osteoarthritis and varus malalignment . Trial Registration Australian New Zeal and Clinical Trials Registry reference : Osteoarthritic knee pain affects patient mobility . Relief of knee pain in osteoarthritis has been reported to increase loading of the knee during gait , but it is unknown whether such pain relief enhances knee loading during more dem and ing activities such as stair-stepping . The gait of 19 patients and stair-stepping of 14 patients with painful medial compartment osteoarthritis of the knee was assessed before and after pain-relieving intraarticular injection of the knee and compared with those of 21 healthy control subjects . There were significant increases in gait velocity , cadence , maximum external knee adduction moment ( indicating increased loading in the medial compartment of the knee ) , and maximum external hip adduction and ankle abduction moments immediately after the injection . With the exception of velocity and ankle abduction moment , these variables were returned to levels that were not statistically different from those of the control subjects . However , no significant differences were found during stair-stepping in the external adduction-abduction moments about the knee , hip , or ankle after injection . Furthermore , the postinjection magnitudes of these variables during stair-stepping were significantly less than those of the controls . Therefore , although the relief of knee pain is sufficient to enhance gait function in osteoarthritis of the knee , it is insufficient to enhance stair-stepping function OBJECTIVE To evaluate the effects of a modified shoe that incorporates both lateral wedging and a variable-stiffness sole on knee joint loading in 3 population s : individuals with symptomatic and radiographic knee osteoarthritis ( OA ) , asymptomatic overweight individuals , and asymptomatic healthy weight individuals . METHODS Ninety participants ( 30 per group ) underwent a 3-dimensional gait analysis  across 3 test conditions : modified shoes , st and ard control shoes , and barefoot . For each condition , the first peak knee adduction moment ( KAM ) and knee flexion moment ( KFM ) ( both expressed as Nm/[body weight × height]% ) as well as the KAM impulse ( expressed as Nm.s/[body weight × height]% ) were determined . RESULTS The modified shoes significantly reduced the peak KAM as compared to the control shoes in both the OA ( P = 0.002 ) and the overweight ( P = 0.03 ) groups . In the OA group , there was no significant difference in peak KAM when walking in the modified shoe as compared to walking barefoot . In the overweight and the healthy weight groups , the peak KAM when walking in the modified shoe was significantly higher than that when walking barefoot ( P < 0.001 ) . Irrespective of group , the KAM impulse was significantly reduced when walking in the modified shoe as compared to the control shoe ( P < 0.001 ) and was significantly higher during both shoe conditions as compared to walking barefoot ( P < 0.001 ) . There was no change in the KFM between walking conditions for any group . CONCLUSION The findings illustrate that a shoe incorporating both a lateral wedge and a variable-stiffness sole can significantly reduce medial knee joint load . Further research examining the effects of these 
    Output:
    