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: Several authors have demonstrated the pivotal role of proinflammatory cytokines in inducing progressive cartilage degradation and secondary inflammation of the synovial membrane in osteoarthritis ( OA ) . It has recently been established that tumor necrosis factor (TNF)-alpha plays a well-defined role in the pathophysiology of inflammatory joint diseases and that binding to circulating soluble TNF-alpha receptors can inactivate it . We investigated the influence of mud pack treatment , which is able to diminish TNF-alpha serum values , on specific TNF receptor ( sTNF-R ) levels . Thirty-six patients with OA were enrolled and r and omized into two groups . Group A underwent mud pack treatment and group B underwent thermal bath treatment .  A group of 20 healthy untreated subjects was used as a control . Blood sample s were collected at baseline and after treatment , and assays of sTNF-R55 and sTNF-R75 were performed in both groups . We found small changes in sTNF-Rs serum values but these were not statistically significant . sTNF-R55 serum values decreased by 0.4 % after the therapy in group A , while in group B the decrease was -17.7 % . sTNF-R75 was reduced by -21.17 % in group A and by -10.6 % in group B. In conclusion , through its thermic and ant/inflammatory activity mud pack treatment shows complex interaction with the most common factors of inflammatory and cartilage degradation . Our results suggest that the thermic component of this natural treatment is mainly involved in modulating inflammatory reaction and cartilage damage through binding of the circulating TNF , which controls the activation of the cells responsible for the production of proinflammatory cytokines The purpose of the present investigation was to evaluate whether an anti-inflammatory effect together with an improvement of the regulation of the interaction between the inflammatory and stress responses underlies the clinical benefits of pelotherapy in osteoarthritis ( OA ) patients . This study evaluated the effects of a 10-day cycle of pelotherapy at the spa centre ‘ El Raposo ’ ( Spain ) in a group of 21 OA patients diagnosed with primary knee OA . Clinical assessment s included pain intensity using a visual analog scale ; pain , stiffness and physical function using the Western Ontario and McMaster Universities Arthritis Index ; and health-related quality of life using the EuroQol-5D question naire . Serum inflammatory cytokine levels ( IL-1β , TNF-α , IL-8 , IL-6 , IL-10 and TGF-β ) were evaluated using the Bio-Plex ® Luminex ® system . Circulating neuroendocrine-stress biomarkers , such as cortisol and extracellular 72 kDa heat shock protein ( eHsp72 ) , were measured by ELISA . After the cycle of mud therapy , OA patients improved the knee flexion angle and OA-related pain , stiffness and physical function , and they reported a better health-related quality of life . Serum concentrations of IL-1β , TNF-α , IL-8 , IL-6 and TGF-β , as well as eHsp72 , were markedly decreased . Besides , systemic levels of cortisol increased significantly . These results confirm that the clinical benefits of mud therapy may well be mediated , at least in part , by its systemic anti-inflammatory effects and neuroendocrine-immune regulation in OA patients . Thus , mud therapy could be an effective alternative treatment in the management of OA Mud-bath therapy plays a primary role in the treatment and prevention of  osteoarthritis  that has been recognised since antiquity . Numerous studies have demonstrated its clinical benefits and its effects on inflammatory mediators ( interleukins ) , the immune system , cenesthesic factors ( endorphins ) , and the diencephalic – pituitary – adrenal axis . This study was conducted to assess the efficacy of mud-bath therapy with mineral water from the Sillene Spring at Italy ’s Chianciano Spa in patients with osteoarthritis of the knee . Patients ( n = 61 ) were divided into two groups . Group A underwent three cycles of mud-based spa therapy over a year ’s time , whereas group B did not . Clinical conditions , visual analogue scale pain ratings , and Lequesne indexes of the two groups were compared . We also compared these same parameters in the patients of the two groups that were following the therapy with drugs and in the patients of the group A before and after spa treatment . The percentage of patients with no symptoms or mild symptoms was higher in group A than in group B. Within group A , this percentage was higher after treatment than before spa therapy . Even in the comparison between the patients of the two groups that were following the therapy with drug , the results was that in group A the percentage of patients with no symptoms or mild symptoms was higher than in group B. Statistical analyses based on various tests revealed that almost all these differences were highly significant . No adverse effects were observed in any of the patients in group A. In conclusion , the mud-bath therapy performed at Chianciano Spa with Sillene Spring water remarkably improved the clinical conditions of patients with knee arthritis and significantly reduces the frequency and severity of symptoms and the disability they cause Mud pack therapy is an alternative mode of treatment for rheumatic diseases . It is based on the application of heated mud packs to the entire body or to specific areas , such as over joints . The aim of the current study was to evaluate the efficacy of treatment with mud compresses at patients ’ homes for osteoarthritis of the knee . Fifty-eight patients with osteoarthritis of the knee were enrolled in a prospect i ve , double-blinded , controlled study . Forty patients were treated with natural mineral-rich mud compresses and 18 patients were treated with mineral-depleted mud compresses . Mud compresses were applied 5 times each week during 3 weeks for a total of 15 treatments . Patients were assessed at baseline , at completion of the 3-week treatment period , and twice after the conclusion of the treatment period — after 1 month and after 3 months . The main outcome measures were the Lequesne Index of severity of knee osteoarthritis , patient self- assessment of pain , and severity of knee pain on a visual analog scale . A reduction of 20 % or more in the pain scores was considered clinical ly significant . In the group treated with natural mud compresses , a significant reduction in knee pain was observed at all assessment s. Similarly , improvement in the Lequesne Index was seen at the end of therapy and a month after treatment . In the control group , given mineral-depleted mud compresses , no significant change in knee pain was seen at any assessment . Improvement in the Lequesne Index was seen 1 and 3 months after completion of the therapy , but not at the end of therapy . Seventy-two percent of the patients in the treatment group had an improvement of > 20 % in self- assessment of knee pain , compared with 33 % in the control group ( p = 0.005).The data suggest that treatment with mud compresses , but only in their natural form , temporarily relieves pain in patients with osteoarthritis of the knees . We believe that treatment with mud compresses might augment conventional medical therapy in these patients Effects of balneotherapy on gait properties of patients with osteoarthritis of the knee were investigated prospect ively . A total of 30 patients with knee osteoarthritis received balneotherapy consisting of two daily thermomineral water baths for 2 weeks . Patients were evaluated using gait analysis and clinical scores , both within 2 weeks , before and after spa treatment . Patients were walking faster in their control analyses ( 0.81 ± 0.21 to 0.89 ± 0.19 m/s ; P = 0.017 ) , with a shorter mean stance time ( 63.0 ± 3.3 to 61.8 ± 2.5 % stride ; P = 0.007 ) , an increased cadence ( 96 ± 13.1 to 100 ± 11.9 steps/min ; P = 0.094 ) and stride length ( 996 ± 174 to 1,058 ± 142 mm ; P = 0.017 ) . Balneotherapy also result ed in a significant decrease in Lequesne knee osteoarthritis index ( 12.1 ± 3.7 to 10.0 ± 3.3 points ; P = 0.003 ) , VAS for pain ( 58 ± 25 to 33 ± 15 ; P = 0.0001 ) , VAS for patients ’ ( 56 ± 24 to 29 ± 19 ; P < 0.001 ) and investigator ’s global assessment ( 55 ± 20 to 26 ± 15 ; P < 0.0001 ) and WOMAC score ( 2.1 ± 0.7 to 1.6 ± 0.8 ; P = 0.0004 ) . Balneotherapy has positive effects on gait properties and clinical health quality parameters of patients with knee osteoarthritis in short-term evaluations Objective To determine whether spa therapy , plus home exercises and usual medical treatment provides any benefit over exercises and usual treatment , in the management of knee osteoarthritis . Methods Large multicentre r and omised prospect i ve clinical trial of patients with knee osteoarthritis according to the American College of Rheumatology criteria , attending French spa resorts as out patients between June 2006 and April 2007 . Zelen r and omisation was used so patients were ignorant of the other group and spa personnel were not told which patients were participating . The main endpoint criteria were patient self-assessed . All patients continued usual treatments and performed daily st and ardised home exercises . The spa therapy group also received 18 days of spa therapy ( massages , showers , mud and pool sessions ) . Main Endpoint The number of patients achieving minimal clinical ly important improvement ( MCII ) at 6 months , defined as ≥19.9 mm on the visual analogue pain scale and /or ≥9.1 points in a normalised Western Ontario and McMaster Universities osteoarthritis index function score and no knee surgery . Results The intention to treat analysis included 187 controls and 195 spa therapy patients . At 6 months , 99/195 ( 50.8 % ) spa group patients had MCII and 68/187 ( 36.4 % ) controls ( χ2=8.05 ; df=1 ; p=0.005 ) . However , no improvement in quality of life ( Short Form 36 ) or patient acceptable symptom state was observed at 6 months . Conclusion For patients with knee osteoarthritis a 3-week course of spa therapy together with home exercises and usual pharmacological treatments offers benefit after 6 months compared with exercises and usual treatment alone , and is well tolerated . Trial registration number NCT00348777 BACKGROUND Osteoarthritis is a degenerative disease associated with pain , reduced range of motion , and impaired function . Balneotherapy or bathing in thermal or mineral waters is used as a non-invasive treatment for various rheumatic diseases . AIM To evaluate the effectiveness of hot sulfurous and non-sulfurous waters in the treatment of  knee osteoarthritis  . DESIGN A r and omized , assessor-blind , controlled trial . SETTING A spa resort . POPULATION One hundred and forty patients of both genders , mean age of 64.8±8.9 years , with knee osteoarthritis and chronic knee pain . METHODS Patients were r and omized into three groups : the sulfurous water ( SW ) group ( N.=47 ) , non-sulfurous water ( NSW ) group ( N.=50 ) , or control group ( N.=43 ) who received no treatment . Patients were not blinded to treatment allocation . Treatment groups received 30 individual thermal baths ( three 20-minute baths a week for 10 weeks ) at 37 - 39 ° C . The outcome measures were pain ( visual analog scale , VAS ) , physical function ( Western Ontario and McMaster Universities Osteoarthritis Index , WOMAC ; Lequesne Algofunctional Index , LAFI ; Stanford Health Assessment Question naire , HAQ ) , and use of pain medication . Patients were assessed before treatment ( T1 ) , at treatment endpoint ( T2 ) , and two months post-intervention ( T3 ) . Intra- and intergroup comparisons were performed at a significance level of 0.05 ( P<0.05 ) . RESULTS A significant decrease in VAS pain scores ( pain during movement , at rest , and at night ) and use of pain medication , and improvement in WOMAC , LAFI and HAQ scores were observed from baseline to T2 and T3 within treatment groups ( P<0.001 ) , and between controls and both treatment groups at T2 and T3 ( P<0.001 ) . No significant differences in these variables were observed between treatment groups at T2 , but patients in the SW group reported less pain and better functional status than those in the NSW group at T3 , showing a lasting effect of sulfurous water baths . CONCLUSIONS Both therapeutic methods were effective in the treatment of knee osteoarthritis ; however , sulfurous baths yielded longer-lasting effects than non-sulfurous water baths . CLINICAL REHABILITATION IMPACT Baths in thermal waters , especially those in sulfurous waters , are effective in reducing pain and improving physical function in patients with knee osteoarthritis BACKGROUND Balneotherapy is an established treatment modality for musculoskeletal disease , but few studies have examined the efficacy of spa therapy in elderly patients with degenerative spine and joint diseases . OBJECTIVES To assess the effects of balneother 
    Output:
    
agent
Among all the studies , the most relevant indexes used to measure effectiveness of spa therapy were improved including VAS , Lequesne , and WOMAC Score .
Conclusions The mud-pack therapy , balneotherapy , mud-bath therapy , and spa therapy have proved to be effective in the treatment and in the secondary prevention of knee osteoarthritis , by reducing pain , nonsteroidal anti-inflammatory drug consumption , and functional limitation and improving quality of life of affected patients
***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: Several authors have demonstrated the pivotal role of proinflammatory cytokines in inducing progressive cartilage degradation and secondary inflammation of the synovial membrane in osteoarthritis ( OA ) . It has recently been established that tumor necrosis factor (TNF)-alpha plays a well-defined role in the pathophysiology of inflammatory joint diseases and that binding to circulating soluble TNF-alpha receptors can inactivate it . We investigated the influence of mud pack treatment , which is able to diminish TNF-alpha serum values , on specific TNF receptor ( sTNF-R ) levels . Thirty-six patients with OA were enrolled and r and omized into two groups . Group A underwent mud pack treatment and group B underwent thermal bath treatment .  A group of 20 healthy untreated subjects was used as a control . Blood sample s were collected at baseline and after treatment , and assays of sTNF-R55 and sTNF-R75 were performed in both groups . We found small changes in sTNF-Rs serum values but these were not statistically significant . sTNF-R55 serum values decreased by 0.4 % after the therapy in group A , while in group B the decrease was -17.7 % . sTNF-R75 was reduced by -21.17 % in group A and by -10.6 % in group B. In conclusion , through its thermic and ant/inflammatory activity mud pack treatment shows complex interaction with the most common factors of inflammatory and cartilage degradation . Our results suggest that the thermic component of this natural treatment is mainly involved in modulating inflammatory reaction and cartilage damage through binding of the circulating TNF , which controls the activation of the cells responsible for the production of proinflammatory cytokines The purpose of the present investigation was to evaluate whether an anti-inflammatory effect together with an improvement of the regulation of the interaction between the inflammatory and stress responses underlies the clinical benefits of pelotherapy in osteoarthritis ( OA ) patients . This study evaluated the effects of a 10-day cycle of pelotherapy at the spa centre ‘ El Raposo ’ ( Spain ) in a group of 21 OA patients diagnosed with primary knee OA . Clinical assessment s included pain intensity using a visual analog scale ; pain , stiffness and physical function using the Western Ontario and McMaster Universities Arthritis Index ; and health-related quality of life using the EuroQol-5D question naire . Serum inflammatory cytokine levels ( IL-1β , TNF-α , IL-8 , IL-6 , IL-10 and TGF-β ) were evaluated using the Bio-Plex ® Luminex ® system . Circulating neuroendocrine-stress biomarkers , such as cortisol and extracellular 72 kDa heat shock protein ( eHsp72 ) , were measured by ELISA . After the cycle of mud therapy , OA patients improved the knee flexion angle and OA-related pain , stiffness and physical function , and they reported a better health-related quality of life . Serum concentrations of IL-1β , TNF-α , IL-8 , IL-6 and TGF-β , as well as eHsp72 , were markedly decreased . Besides , systemic levels of cortisol increased significantly . These results confirm that the clinical benefits of mud therapy may well be mediated , at least in part , by its systemic anti-inflammatory effects and neuroendocrine-immune regulation in OA patients . Thus , mud therapy could be an effective alternative treatment in the management of OA Mud-bath therapy plays a primary role in the treatment and prevention of  osteoarthritis  that has been recognised since antiquity . Numerous studies have demonstrated its clinical benefits and its effects on inflammatory mediators ( interleukins ) , the immune system , cenesthesic factors ( endorphins ) , and the diencephalic – pituitary – adrenal axis . This study was conducted to assess the efficacy of mud-bath therapy with mineral water from the Sillene Spring at Italy ’s Chianciano Spa in patients with osteoarthritis of the knee . Patients ( n = 61 ) were divided into two groups . Group A underwent three cycles of mud-based spa therapy over a year ’s time , whereas group B did not . Clinical conditions , visual analogue scale pain ratings , and Lequesne indexes of the two groups were compared . We also compared these same parameters in the patients of the two groups that were following the therapy with drugs and in the patients of the group A before and after spa treatment . The percentage of patients with no symptoms or mild symptoms was higher in group A than in group B. Within group A , this percentage was higher after treatment than before spa therapy . Even in the comparison between the patients of the two groups that were following the therapy with drug , the results was that in group A the percentage of patients with no symptoms or mild symptoms was higher than in group B. Statistical analyses based on various tests revealed that almost all these differences were highly significant . No adverse effects were observed in any of the patients in group A. In conclusion , the mud-bath therapy performed at Chianciano Spa with Sillene Spring water remarkably improved the clinical conditions of patients with knee arthritis and significantly reduces the frequency and severity of symptoms and the disability they cause Mud pack therapy is an alternative mode of treatment for rheumatic diseases . It is based on the application of heated mud packs to the entire body or to specific areas , such as over joints . The aim of the current study was to evaluate the efficacy of treatment with mud compresses at patients ’ homes for osteoarthritis of the knee . Fifty-eight patients with osteoarthritis of the knee were enrolled in a prospect i ve , double-blinded , controlled study . Forty patients were treated with natural mineral-rich mud compresses and 18 patients were treated with mineral-depleted mud compresses . Mud compresses were applied 5 times each week during 3 weeks for a total of 15 treatments . Patients were assessed at baseline , at completion of the 3-week treatment period , and twice after the conclusion of the treatment period — after 1 month and after 3 months . The main outcome measures were the Lequesne Index of severity of knee osteoarthritis , patient self- assessment of pain , and severity of knee pain on a visual analog scale . A reduction of 20 % or more in the pain scores was considered clinical ly significant . In the group treated with natural mud compresses , a significant reduction in knee pain was observed at all assessment s. Similarly , improvement in the Lequesne Index was seen at the end of therapy and a month after treatment . In the control group , given mineral-depleted mud compresses , no significant change in knee pain was seen at any assessment . Improvement in the Lequesne Index was seen 1 and 3 months after completion of the therapy , but not at the end of therapy . Seventy-two percent of the patients in the treatment group had an improvement of > 20 % in self- assessment of knee pain , compared with 33 % in the control group ( p = 0.005).The data suggest that treatment with mud compresses , but only in their natural form , temporarily relieves pain in patients with osteoarthritis of the knees . We believe that treatment with mud compresses might augment conventional medical therapy in these patients Effects of balneotherapy on gait properties of patients with osteoarthritis of the knee were investigated prospect ively . A total of 30 patients with knee osteoarthritis received balneotherapy consisting of two daily thermomineral water baths for 2 weeks . Patients were evaluated using gait analysis and clinical scores , both within 2 weeks , before and after spa treatment . Patients were walking faster in their control analyses ( 0.81 ± 0.21 to 0.89 ± 0.19 m/s ; P = 0.017 ) , with a shorter mean stance time ( 63.0 ± 3.3 to 61.8 ± 2.5 % stride ; P = 0.007 ) , an increased cadence ( 96 ± 13.1 to 100 ± 11.9 steps/min ; P = 0.094 ) and stride length ( 996 ± 174 to 1,058 ± 142 mm ; P = 0.017 ) . Balneotherapy also result ed in a significant decrease in Lequesne knee osteoarthritis index ( 12.1 ± 3.7 to 10.0 ± 3.3 points ; P = 0.003 ) , VAS for pain ( 58 ± 25 to 33 ± 15 ; P = 0.0001 ) , VAS for patients ’ ( 56 ± 24 to 29 ± 19 ; P < 0.001 ) and investigator ’s global assessment ( 55 ± 20 to 26 ± 15 ; P < 0.0001 ) and WOMAC score ( 2.1 ± 0.7 to 1.6 ± 0.8 ; P = 0.0004 ) . Balneotherapy has positive effects on gait properties and clinical health quality parameters of patients with knee osteoarthritis in short-term evaluations Objective To determine whether spa therapy , plus home exercises and usual medical treatment provides any benefit over exercises and usual treatment , in the management of knee osteoarthritis . Methods Large multicentre r and omised prospect i ve clinical trial of patients with knee osteoarthritis according to the American College of Rheumatology criteria , attending French spa resorts as out patients between June 2006 and April 2007 . Zelen r and omisation was used so patients were ignorant of the other group and spa personnel were not told which patients were participating . The main endpoint criteria were patient self-assessed . All patients continued usual treatments and performed daily st and ardised home exercises . The spa therapy group also received 18 days of spa therapy ( massages , showers , mud and pool sessions ) . Main Endpoint The number of patients achieving minimal clinical ly important improvement ( MCII ) at 6 months , defined as ≥19.9 mm on the visual analogue pain scale and /or ≥9.1 points in a normalised Western Ontario and McMaster Universities osteoarthritis index function score and no knee surgery . Results The intention to treat analysis included 187 controls and 195 spa therapy patients . At 6 months , 99/195 ( 50.8 % ) spa group patients had MCII and 68/187 ( 36.4 % ) controls ( χ2=8.05 ; df=1 ; p=0.005 ) . However , no improvement in quality of life ( Short Form 36 ) or patient acceptable symptom state was observed at 6 months . Conclusion For patients with knee osteoarthritis a 3-week course of spa therapy together with home exercises and usual pharmacological treatments offers benefit after 6 months compared with exercises and usual treatment alone , and is well tolerated . Trial registration number NCT00348777 BACKGROUND Osteoarthritis is a degenerative disease associated with pain , reduced range of motion , and impaired function . Balneotherapy or bathing in thermal or mineral waters is used as a non-invasive treatment for various rheumatic diseases . AIM To evaluate the effectiveness of hot sulfurous and non-sulfurous waters in the treatment of  knee osteoarthritis  . DESIGN A r and omized , assessor-blind , controlled trial . SETTING A spa resort . POPULATION One hundred and forty patients of both genders , mean age of 64.8±8.9 years , with knee osteoarthritis and chronic knee pain . METHODS Patients were r and omized into three groups : the sulfurous water ( SW ) group ( N.=47 ) , non-sulfurous water ( NSW ) group ( N.=50 ) , or control group ( N.=43 ) who received no treatment . Patients were not blinded to treatment allocation . Treatment groups received 30 individual thermal baths ( three 20-minute baths a week for 10 weeks ) at 37 - 39 ° C . The outcome measures were pain ( visual analog scale , VAS ) , physical function ( Western Ontario and McMaster Universities Osteoarthritis Index , WOMAC ; Lequesne Algofunctional Index , LAFI ; Stanford Health Assessment Question naire , HAQ ) , and use of pain medication . Patients were assessed before treatment ( T1 ) , at treatment endpoint ( T2 ) , and two months post-intervention ( T3 ) . Intra- and intergroup comparisons were performed at a significance level of 0.05 ( P<0.05 ) . RESULTS A significant decrease in VAS pain scores ( pain during movement , at rest , and at night ) and use of pain medication , and improvement in WOMAC , LAFI and HAQ scores were observed from baseline to T2 and T3 within treatment groups ( P<0.001 ) , and between controls and both treatment groups at T2 and T3 ( P<0.001 ) . No significant differences in these variables were observed between treatment groups at T2 , but patients in the SW group reported less pain and better functional status than those in the NSW group at T3 , showing a lasting effect of sulfurous water baths . CONCLUSIONS Both therapeutic methods were effective in the treatment of knee osteoarthritis ; however , sulfurous baths yielded longer-lasting effects than non-sulfurous water baths . CLINICAL REHABILITATION IMPACT Baths in thermal waters , especially those in sulfurous waters , are effective in reducing pain and improving physical function in patients with knee osteoarthritis BACKGROUND Balneotherapy is an established treatment modality for musculoskeletal disease , but few studies have examined the efficacy of spa therapy in elderly patients with degenerative spine and joint diseases . OBJECTIVES To assess the effects of balneother 
    Output:
    