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: BACKGROUND Glucosamine and chondroitin sulfate are used to treat osteoarthritis . The multicenter , double-blind , placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial ( GAIT ) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis . METHODS We r and omly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily , 1200 mg of chondroitin sulfate daily , both glucosamine and chondroitin sulfate , 200 mg of celecoxib daily , or placebo for 24 weeks . Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia . Assignment was stratified according to the severity of knee pain ( mild [ N=1229 ] vs. moderate to severe [ N=354 ] ) . The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24 . RESULTS The mean age of the patients was 59 years , and 64 percent were women . Overall , glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent . As compared with the rate of response to placebo ( 60.1 percent ) , the rate of response to glucosamine was 3.9 percentage points higher ( P=0.30 ) , the rate of response to chondroitin sulfate was 5.3 percentage points higher ( P=0.17 ) , and the rate of response to combined treatment was 6.5 percentage points higher ( P=0.09 ) . The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group ( P=0.008 ) . For patients with moderate-to-severe pain at baseline , the rate of response was significantly higher with combined therapy than with placebo ( 79.2 percent vs. 54.3 percent , P=0.002 ) . Adverse events were mild , infrequent , and evenly distributed among the groups . CONCLUSIONS Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee . Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain . ( Clinical Trials.gov number , NCT00032890 . ) OBJECTIVE To assess the efficacy of glucosamine sulfate in knee osteoarthritis ( OA ) . METHODS A 4-center , 6-month , r and omized , double-blind , placebo-controlled glucosamine discontinuation trial was conducted in 137 current users of glucosamine with knee OA who had experienced at least moderate improvement in knee pain after starting glucosamine .  Study medication dosage was equivalent to the dosage of glucosamine taken prior to the study ( maximum 1,500 mg/day ) . Followup continued for 6 months or until disease flare , whichever occurred first . The primary outcome was the proportion of disease flares in the glucosamine and placebo groups using an intent-to-treat analysis . Secondary outcomes included time to disease flare ; analgesic medication use ; severity of disease flare ; and change in pain , stiffness , function and quality of life in the glucosamine and placebo groups . RESULTS Disease flare was seen in 28 ( 42 % ) of 66 placebo patients and 32 ( 45 % ) of 71 glucosamine patients ( difference -3 % ; 95 % confidence interval [ 95 % CI ] -19 , 14 ; P = 0.76 ) . In the Cox regression analysis , after adjustment for sex , study site , and OA radiographic severity , time to disease flare was not significantly different in the glucosamine compared with placebo group ( hazard ratio of flare = 0.8 ; 95 % CI 0.5 , 1.4 ; P = 0.45 ) . At final study visit ,  acetaminophen  was used in 27 % and 21 % of placebo and glucosamine patients , respectively ( P = 0.40 ) , nonsteroidal antiinflammatory drugs were used in 29 % and 30 % ( P = 0.92 ) , and both were used in 20 % and 21 % ( P = 0.84 ) . No differences were found in severity of disease flare or other secondary outcomes between placebo and glucosamine patients . CONCLUSION In patients with knee OA with at least moderate subjective improvement with prior glucosamine use , this study provides no evidence of symptomatic benefit from continued use of glucosamine sulfate OBJECTIVE To determine whether it is possible to specify different score patterns for hip and knee osteoarthritis ( OA ) , and to identify the degree of responsiveness and the validity of the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) factors , which are alternative health dimensions obtained by factor analysis of the WOMAC items . METHODS  WOMAC scales and WOMAC factors  were compared in a prospect i ve setting examining patients with hip and knee OA before and after rehabilitative inpatient intervention ( n = 317 ) . In a partial sample ( n = 103 ) , the validity of the WOMAC factors was determined by a global rating of their activities . RESULTS The WOMAC factor " ascending/descending " was significantly different for hip and knee OA in the health state before therapy ( score in hip 5.09 , in knee 6.59 ; p < 0.001 ) ; this was also true of the effect size after therapy ( hip 0.39 , knee 0.65 ; p = 0.012 ) . The WOMAC scales did not differ for the 2 conditions . The WOMAC factor " ascending/descending " was the most responsive dimension in knee OA ( effect size 0.65 ) , but in hip OA the WOMAC pain scale was most responsive ( effect size 0.55 ) . Most of the WOMAC factors correlated moderately ( r = 0.52 - 0.69 ) with the patient 's self-rating on the validation question naire . CONCLUSION The WOMAC factors are valid measures . Analyzing the WOMAC by the WOMAC factors facilitates and improves the differential relevance and accuracy of the WOMAC for specific conditions such as hip and knee OA Objectives To compare the effect of acupuncture ( manual and electroacupuncture ) with that of a non-penetrating sham ( ‘ placebo ’ needle ) in patients with osteoarthritic knee pain and disability who are blind to the treatment allocation . Methods Acupuncture naive patients with symptomatic and radiological evidence of osteoarthritis of the knee were r and omly allocated to a course of either acupuncture or non-penetrating sham acupuncture using a sheathed ‘ placebo ’ needle system . Acupuncture points for pain and stiffness were selected according to acupuncture theory for treating Bi syndrome . Both manual and electrical stimulation were used . Response was assessed using the WOMAC index for osteoarthritis of the knee , self reported pain scale , the EuroQol score and plasma β-endorphin . The effectiveness of blinding was assessed . Results There were 34 patients in each group . The primary end point was the change in WOMAC pain score after the course of treatment . Comparison between the two treatment groups found a significantly greater improvement with acupuncture ( mean difference 60 , 95 % CI 5 to 116 , P=0.035 ) than with sham . Within the acupuncture group there was a significant improvement in pain ( baseline 294 , mean change 95 , 95 % CI 60 to 130 , P<0.001 ) which was not seen by those who had sham acupuncture ( baseline 261 , mean change 35 , 95 % CI-10 to 80 , P=0.12 ) . Similar effects within group , but not between groups , were seen with the secondary end points of WOMAC stiffness , WOMAC function , and self reported pain . One month after treatment the between group pain difference had been lost ( mean difference 46 ; 95 % CI −9 to 100 , P=0.10 ) although the acupuncture group was still benefiting compared to baseline ( mean difference 59 ; 95 % CI 16 to 102 , P=0.009 ) . The EuroQol score , a generic measure of health related quality of life , was not altered by the treatments . A minority of patients correctly guessed their treatment group ( 41 % in the acupuncture group and 44 % in the control group ) . Plasma β-endorphin levels were not affected by either treatment . Conclusions Acupuncture gives symptomatic improvement for patients with osteoarthritis of the knee , and is significantly superior to non-penetrating sham acupuncture . The study did not confirm earlier reports of release of plasma β-endorphin during acupuncture Background Using an open r and omised controlled study , we examined the effectiveness of manual and electroacupuncture on symptom relief for patients with osteoarthritis of the knee . Methods Patients with symptomatic osteoarthritis of the knee were r and omised to one of three treatment groups . Group A had acupuncture alone , group B had acupuncture but continued on their symptomatic medication , and group C used their symptomatic medication for the first five weeks and then had a course of acupuncture added . Patients receiving acupuncture were treated twice weekly over five weeks . Needles were inserted ( with manual and electrical stimulation ) in acupuncture points for pain and stiffness , selected according to traditional acupuncture theory for treating Bi syndrome . Patients were assessed by a blinded observer before treatment , after five weeks ’ treatment and at one month follow up , using a visual analogue pain scale ( VAS ) and the Western Ontario McMaster ( WOMAC ) question naire for osteoarthritis of the knee . Results The 30 patients in our study were well matched for age , body mass index , disease duration , baseline VAS pain score and baseline WOMAC scores . Repeated measure analyses gave a highly significant improvement in pain ( VAS ) after the courses of acupuncture in groups A ( P=0.012 ) and B ( P=0.001 ) ; there was no change in group C until after the course of acupuncture , when the improvement was significant ( P=0.001 ) . Similarly significant changes were seen with the WOMAC pain and stiffness scores . These benefits were maintained during the one month after the course of acupuncture . Patients ’ rating of global assessment was higher than that of the acupuncturist . Conclusion We conclude that manual and electroacupuncture causes a significant improvement in the symptoms of osteoarthritis  of the knee , either on its own or as an adjunct therapy , with no loss of benefit after one month Clinical and experimental data indicate that most acupuncture clinical results are mediated by the central nervous system , but the specific effects of acupuncture on the human brain remain unclear . Even less is known about its effects on the cerebellum . This fMRI study demonstrated that manual acupuncture at ST 36 ( Stomach 36 , Zusanli ) , a main acupoint on the leg , modulated neural activity at multiple levels of the cerebro-cerebellar and limbic systems . The pattern of hemodynamic response depended on the psychophysical response to needle manipulation . Acupuncture stimulation typically elicited a composite of sensations termed deqi that is related to clinical efficacy according to traditional Chinese medicine . The limbic and paralimbic structures of cortical and subcortical regions in the telencephalon , diencephalon , brainstem and cerebellum demonstrated a concerted attenuation of signal intensity when the subjects experienced deqi . When deqi was mixed with sharp pain , the hemodynamic response was mixed , showing a predominance of signal increases instead . Tactile stimulation as control also elicited a predominance of signal increase in a subset of these regions . The study provides preliminary evidence for an integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 that correlates with the psychophysical response A prospect i ve , controlled clinical trial was undertaken to assess the relative efficacies of physiotherapy and electroacupuncture in the treatment of cervical spondylosis . The results suggested that , while both methods were effective , electroacupuncture produced an earlier symptomatic improvement with increased neck movement , especially in patients with mild degenerative changes of the cervical spine OBJECTIVE The purpose of this study was to investigate the efficacy of acupuncture as an adjunctive therapy to st and ard care for the relief of pain and dysfunction in elderly patients with osteoarthritis ( OA ) of the knee . METHODS Seventy-three patients with symptomatic OA of the knee were r and omly assigned to treatment ( acupuncture ) or st and ard care ( control ) . Analysis was performed on last score carried forward to account for patients who dropped out before completion . Patients self-scored Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and Lequesne indices at baseline and at 4 , 8 and 12 weeks . Patients in the control group were offered acupuncture treatment after 12 weeks . The data for these patients are pooled with those from the original acupuncture group for within-group analysis . RESULTS Patients r and omized to acupuncture improved on both WOMAC and 
    Output:
    
agent
***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: BACKGROUND Glucosamine and chondroitin sulfate are used to treat osteoarthritis . The multicenter , double-blind , placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial ( GAIT ) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis . METHODS We r and omly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily , 1200 mg of chondroitin sulfate daily , both glucosamine and chondroitin sulfate , 200 mg of celecoxib daily , or placebo for 24 weeks . Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia . Assignment was stratified according to the severity of knee pain ( mild [ N=1229 ] vs. moderate to severe [ N=354 ] ) . The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24 . RESULTS The mean age of the patients was 59 years , and 64 percent were women . Overall , glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent . As compared with the rate of response to placebo ( 60.1 percent ) , the rate of response to glucosamine was 3.9 percentage points higher ( P=0.30 ) , the rate of response to chondroitin sulfate was 5.3 percentage points higher ( P=0.17 ) , and the rate of response to combined treatment was 6.5 percentage points higher ( P=0.09 ) . The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group ( P=0.008 ) . For patients with moderate-to-severe pain at baseline , the rate of response was significantly higher with combined therapy than with placebo ( 79.2 percent vs. 54.3 percent , P=0.002 ) . Adverse events were mild , infrequent , and evenly distributed among the groups . CONCLUSIONS Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee . Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain . ( Clinical Trials.gov number , NCT00032890 . ) OBJECTIVE To assess the efficacy of glucosamine sulfate in knee osteoarthritis ( OA ) . METHODS A 4-center , 6-month , r and omized , double-blind , placebo-controlled glucosamine discontinuation trial was conducted in 137 current users of glucosamine with knee OA who had experienced at least moderate improvement in knee pain after starting glucosamine .  Study medication dosage was equivalent to the dosage of glucosamine taken prior to the study ( maximum 1,500 mg/day ) . Followup continued for 6 months or until disease flare , whichever occurred first . The primary outcome was the proportion of disease flares in the glucosamine and placebo groups using an intent-to-treat analysis . Secondary outcomes included time to disease flare ; analgesic medication use ; severity of disease flare ; and change in pain , stiffness , function and quality of life in the glucosamine and placebo groups . RESULTS Disease flare was seen in 28 ( 42 % ) of 66 placebo patients and 32 ( 45 % ) of 71 glucosamine patients ( difference -3 % ; 95 % confidence interval [ 95 % CI ] -19 , 14 ; P = 0.76 ) . In the Cox regression analysis , after adjustment for sex , study site , and OA radiographic severity , time to disease flare was not significantly different in the glucosamine compared with placebo group ( hazard ratio of flare = 0.8 ; 95 % CI 0.5 , 1.4 ; P = 0.45 ) . At final study visit ,  acetaminophen  was used in 27 % and 21 % of placebo and glucosamine patients , respectively ( P = 0.40 ) , nonsteroidal antiinflammatory drugs were used in 29 % and 30 % ( P = 0.92 ) , and both were used in 20 % and 21 % ( P = 0.84 ) . No differences were found in severity of disease flare or other secondary outcomes between placebo and glucosamine patients . CONCLUSION In patients with knee OA with at least moderate subjective improvement with prior glucosamine use , this study provides no evidence of symptomatic benefit from continued use of glucosamine sulfate OBJECTIVE To determine whether it is possible to specify different score patterns for hip and knee osteoarthritis ( OA ) , and to identify the degree of responsiveness and the validity of the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) factors , which are alternative health dimensions obtained by factor analysis of the WOMAC items . METHODS  WOMAC scales and WOMAC factors  were compared in a prospect i ve setting examining patients with hip and knee OA before and after rehabilitative inpatient intervention ( n = 317 ) . In a partial sample ( n = 103 ) , the validity of the WOMAC factors was determined by a global rating of their activities . RESULTS The WOMAC factor " ascending/descending " was significantly different for hip and knee OA in the health state before therapy ( score in hip 5.09 , in knee 6.59 ; p < 0.001 ) ; this was also true of the effect size after therapy ( hip 0.39 , knee 0.65 ; p = 0.012 ) . The WOMAC scales did not differ for the 2 conditions . The WOMAC factor " ascending/descending " was the most responsive dimension in knee OA ( effect size 0.65 ) , but in hip OA the WOMAC pain scale was most responsive ( effect size 0.55 ) . Most of the WOMAC factors correlated moderately ( r = 0.52 - 0.69 ) with the patient 's self-rating on the validation question naire . CONCLUSION The WOMAC factors are valid measures . Analyzing the WOMAC by the WOMAC factors facilitates and improves the differential relevance and accuracy of the WOMAC for specific conditions such as hip and knee OA Objectives To compare the effect of acupuncture ( manual and electroacupuncture ) with that of a non-penetrating sham ( ‘ placebo ’ needle ) in patients with osteoarthritic knee pain and disability who are blind to the treatment allocation . Methods Acupuncture naive patients with symptomatic and radiological evidence of osteoarthritis of the knee were r and omly allocated to a course of either acupuncture or non-penetrating sham acupuncture using a sheathed ‘ placebo ’ needle system . Acupuncture points for pain and stiffness were selected according to acupuncture theory for treating Bi syndrome . Both manual and electrical stimulation were used . Response was assessed using the WOMAC index for osteoarthritis of the knee , self reported pain scale , the EuroQol score and plasma β-endorphin . The effectiveness of blinding was assessed . Results There were 34 patients in each group . The primary end point was the change in WOMAC pain score after the course of treatment . Comparison between the two treatment groups found a significantly greater improvement with acupuncture ( mean difference 60 , 95 % CI 5 to 116 , P=0.035 ) than with sham . Within the acupuncture group there was a significant improvement in pain ( baseline 294 , mean change 95 , 95 % CI 60 to 130 , P<0.001 ) which was not seen by those who had sham acupuncture ( baseline 261 , mean change 35 , 95 % CI-10 to 80 , P=0.12 ) . Similar effects within group , but not between groups , were seen with the secondary end points of WOMAC stiffness , WOMAC function , and self reported pain . One month after treatment the between group pain difference had been lost ( mean difference 46 ; 95 % CI −9 to 100 , P=0.10 ) although the acupuncture group was still benefiting compared to baseline ( mean difference 59 ; 95 % CI 16 to 102 , P=0.009 ) . The EuroQol score , a generic measure of health related quality of life , was not altered by the treatments . A minority of patients correctly guessed their treatment group ( 41 % in the acupuncture group and 44 % in the control group ) . Plasma β-endorphin levels were not affected by either treatment . Conclusions Acupuncture gives symptomatic improvement for patients with osteoarthritis of the knee , and is significantly superior to non-penetrating sham acupuncture . The study did not confirm earlier reports of release of plasma β-endorphin during acupuncture Background Using an open r and omised controlled study , we examined the effectiveness of manual and electroacupuncture on symptom relief for patients with osteoarthritis of the knee . Methods Patients with symptomatic osteoarthritis of the knee were r and omised to one of three treatment groups . Group A had acupuncture alone , group B had acupuncture but continued on their symptomatic medication , and group C used their symptomatic medication for the first five weeks and then had a course of acupuncture added . Patients receiving acupuncture were treated twice weekly over five weeks . Needles were inserted ( with manual and electrical stimulation ) in acupuncture points for pain and stiffness , selected according to traditional acupuncture theory for treating Bi syndrome . Patients were assessed by a blinded observer before treatment , after five weeks ’ treatment and at one month follow up , using a visual analogue pain scale ( VAS ) and the Western Ontario McMaster ( WOMAC ) question naire for osteoarthritis of the knee . Results The 30 patients in our study were well matched for age , body mass index , disease duration , baseline VAS pain score and baseline WOMAC scores . Repeated measure analyses gave a highly significant improvement in pain ( VAS ) after the courses of acupuncture in groups A ( P=0.012 ) and B ( P=0.001 ) ; there was no change in group C until after the course of acupuncture , when the improvement was significant ( P=0.001 ) . Similarly significant changes were seen with the WOMAC pain and stiffness scores . These benefits were maintained during the one month after the course of acupuncture . Patients ’ rating of global assessment was higher than that of the acupuncturist . Conclusion We conclude that manual and electroacupuncture causes a significant improvement in the symptoms of osteoarthritis  of the knee , either on its own or as an adjunct therapy , with no loss of benefit after one month Clinical and experimental data indicate that most acupuncture clinical results are mediated by the central nervous system , but the specific effects of acupuncture on the human brain remain unclear . Even less is known about its effects on the cerebellum . This fMRI study demonstrated that manual acupuncture at ST 36 ( Stomach 36 , Zusanli ) , a main acupoint on the leg , modulated neural activity at multiple levels of the cerebro-cerebellar and limbic systems . The pattern of hemodynamic response depended on the psychophysical response to needle manipulation . Acupuncture stimulation typically elicited a composite of sensations termed deqi that is related to clinical efficacy according to traditional Chinese medicine . The limbic and paralimbic structures of cortical and subcortical regions in the telencephalon , diencephalon , brainstem and cerebellum demonstrated a concerted attenuation of signal intensity when the subjects experienced deqi . When deqi was mixed with sharp pain , the hemodynamic response was mixed , showing a predominance of signal increases instead . Tactile stimulation as control also elicited a predominance of signal increase in a subset of these regions . The study provides preliminary evidence for an integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 that correlates with the psychophysical response A prospect i ve , controlled clinical trial was undertaken to assess the relative efficacies of physiotherapy and electroacupuncture in the treatment of cervical spondylosis . The results suggested that , while both methods were effective , electroacupuncture produced an earlier symptomatic improvement with increased neck movement , especially in patients with mild degenerative changes of the cervical spine OBJECTIVE The purpose of this study was to investigate the efficacy of acupuncture as an adjunctive therapy to st and ard care for the relief of pain and dysfunction in elderly patients with osteoarthritis ( OA ) of the knee . METHODS Seventy-three patients with symptomatic OA of the knee were r and omly assigned to treatment ( acupuncture ) or st and ard care ( control ) . Analysis was performed on last score carried forward to account for patients who dropped out before completion . Patients self-scored Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and Lequesne indices at baseline and at 4 , 8 and 12 weeks . Patients in the control group were offered acupuncture treatment after 12 weeks . The data for these patients are pooled with those from the original acupuncture group for within-group analysis . RESULTS Patients r and omized to acupuncture improved on both WOMAC and 
    Output:
    