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 OBJECTIVES To compare the differences or correlation between the results obtained from a generic and a disease-specific instrument for the study group and to assess the short-term effects of spa therapy on quality of life of patients with knee osteoarthritis . PATIENTS AND METHODS Fifty patients with knee osteoarthritis were r and omly recruited . They underwent a comprehensive spa therapy program for 21 days . Forty-six patients completed the study . The results were evaluated with Medical Outcomes Study 36-Item Short Form-36 ( SF-36 ) and Arthritis Impact Measurement Scale 2 ( AIMS 2 ) . RESULTS Statistically significant improvement was observed in all subscales of SF-36 . All subscales of AIMS 2 improved too , but only half of them were significant . Correlation between matching subscales of each test was also significant , except physical activity . CONCLUSION Comprehensive spa therapy seems to increase the quality of life of patients with knee osteoarthritis for short term 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 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 The aims of this study were to evaluate whether balneotherapy with mineral sulphate – bicarbonate – calcium water could determine substantial symptomatic improvement , and to detect any changes in the quality of life ( QoL ) of patients with symptomatic knee osteoarthritis ( OA ) . This was a prospect i ve r and omized , single blind controlled trial . Sixty out patients with primary bilateral knee OA , according to ACR criteria , were included in the study and r and omized to one of two groups : group I ( 30 patients ) was treated with a daily sulphate – bicarbonate – calcium mineral water bath ; group II ( 30 patients ) , the control group , continued their regular outpatient care routine . At baseline , after 15 days and after 12 weeks , patients were evaluated by Visual Analogue Scale ( VAS ) for spontaneous pain , Lequesne and Womac Index for gonarthrosis , SF-36 , Arthritis Impact Measurement Scale ( AIMS ) and symptomatic drugs consumption . We observed a significant improvement of all parameters at the end of the cycle of balneotherapy which persisted throughout the follow-up period , whereas in the control group no significant differences were noted . This symptomatic effect was confirmed by the significant reduction of symptomatic drugs consumption . The differences between the two groups were significant for all considered parameters already from the 15th day and persisted during follow-up . Tolerability of balneotherapy  seemed to be good , with light and transitory side effects . Our results confirm that the beneficial effects of balneotherapy in patients with knee OA last over time , with positive effects on the painful symptomatology , a significant improvement on functional capacities and QoL.  Balneotherapy can represent a useful backup to pharmacological treatment of knee OA or a valid alternative for patients who do not tolerate pharmacological treatments Nitric oxide ( NO ) has recently been proposed as an important mediator in inflammatory phases and in loss of cartilage . In inflammatory arthritis NO levels are correlated with disease activity and articular cartilage is able to produce large amounts of NO with the appropriate inducing factors such as cytokines and /or endotoxin . Neutrophils also play an important role in inflammatory reactions and the level of myeloperoxidase , a constituent of neutrophil granules , is related to the intensity of the inflammation . Because there is evidence that suggests that mud packs influence the main cytokines involved in cartilage damage , we tried to determine whether NO and myeloperoxidase are involved in the mechanisms of action of mud bath treatment .  We enrolled 37 subjects and r and omly assigned them to two groups : 19 patients underwent mud bath treatment ( group A )  while 18 patients underwent bath treatment alone .  Blood sample s were obtained before and after the treatment cycles to assay serum levels of NO , myeloperoxidase ( MPO ) and glutathione (GSH)-peroxidase . The results showed a statistically significant decrease in NO and myeloperoxidase serum values in groups A and B , while GSH-peroxidase was not significantly increase in either of the groups ; no correlation was found between NO , myeloperoxidase and GSH-peroxidase serum values .  Mud bath treatment can exert beneficial effects on cartilage homeostasis and inflammatory reactions , influencing NO and decreasing myeloperoxidase serum values . The increase in GSH-peroxidase was not correlated with the reduction of other biochemical markers , suggesting that mud bath treatment has different mechanisms of action Spa therapy and short wave therapy are two of the most commonly used non-pharmacological approaches for  osteoarthritis .  The aim of this study was to assess their efficacy in comparison to conventional therapy in patients with osteoarthritis of the knee in a single blind , r and omized , controlled trial . Seventy-four out patients were enrolled ; 30 patients were treated with a combination of daily local mud packs and arsenical ferruginous mineral bath water from the thermal resort of Levico Terme ( Trento , Italy ) for 3 weeks ; 24 patients were treated with short wave therapy for the same period and 20 patients continued regular , routine ambulatory care . Patients were assessed at baseline , upon completion of the 3-week treatment period , and 12 weeks later . Spa therapy and short wave therapy both demonstrated effective symptomatic treatment in osteoarthritis of the knee at the end of the treatment , but only the spa therapy was shown to have efficacy persistent over time . Our study demonstrated the superiority of arsenical ferruginous spa therapy compared to short wave therapy in the treatment of osteoarthritis of the knee , probably in relationship to the specific effects of the minerals in this water The objective of the study was to investigate the efficacy and tolerability of the peloid plasters in the group of 20 patients with osteoarthritis of peripheral joints ( 10 patients with gonarthrosis and 10 with omarthrosis ) and 20 patients with spondylosis . This form of the pelotherapy  decreased pain in joints after 10 days of the treatment . No allergic or other side effects were observed . Peloid plasters through the analgesic action improve the comfort of life and reduce the use of oral analgesic drugs We have previously shown that thermal mud therapy is able to influence chondrocyte activity of osteoarthrosic patients by modulating the production of serum cytokines , such as interleukin 1 , and this was related to the presence of an anti-inflammatory principle in mature thermal mud . Mud therapy influences many biochemical processes of the body , independently of the thermic stimulation alone and the present paper documents specific increases of insulin growth factor 1 and decreases of tumor nec 
    Output:
    
agent
CONCLUSION Mud pack therapy is considered an alternative and effective therapy in the clinical management 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: 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 OBJECTIVES To compare the differences or correlation between the results obtained from a generic and a disease-specific instrument for the study group and to assess the short-term effects of spa therapy on quality of life of patients with knee osteoarthritis . PATIENTS AND METHODS Fifty patients with knee osteoarthritis were r and omly recruited . They underwent a comprehensive spa therapy program for 21 days . Forty-six patients completed the study . The results were evaluated with Medical Outcomes Study 36-Item Short Form-36 ( SF-36 ) and Arthritis Impact Measurement Scale 2 ( AIMS 2 ) . RESULTS Statistically significant improvement was observed in all subscales of SF-36 . All subscales of AIMS 2 improved too , but only half of them were significant . Correlation between matching subscales of each test was also significant , except physical activity . CONCLUSION Comprehensive spa therapy seems to increase the quality of life of patients with knee osteoarthritis for short term 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 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 The aims of this study were to evaluate whether balneotherapy with mineral sulphate – bicarbonate – calcium water could determine substantial symptomatic improvement , and to detect any changes in the quality of life ( QoL ) of patients with symptomatic knee osteoarthritis ( OA ) . This was a prospect i ve r and omized , single blind controlled trial . Sixty out patients with primary bilateral knee OA , according to ACR criteria , were included in the study and r and omized to one of two groups : group I ( 30 patients ) was treated with a daily sulphate – bicarbonate – calcium mineral water bath ; group II ( 30 patients ) , the control group , continued their regular outpatient care routine . At baseline , after 15 days and after 12 weeks , patients were evaluated by Visual Analogue Scale ( VAS ) for spontaneous pain , Lequesne and Womac Index for gonarthrosis , SF-36 , Arthritis Impact Measurement Scale ( AIMS ) and symptomatic drugs consumption . We observed a significant improvement of all parameters at the end of the cycle of balneotherapy which persisted throughout the follow-up period , whereas in the control group no significant differences were noted . This symptomatic effect was confirmed by the significant reduction of symptomatic drugs consumption . The differences between the two groups were significant for all considered parameters already from the 15th day and persisted during follow-up . Tolerability of balneotherapy  seemed to be good , with light and transitory side effects . Our results confirm that the beneficial effects of balneotherapy in patients with knee OA last over time , with positive effects on the painful symptomatology , a significant improvement on functional capacities and QoL.  Balneotherapy can represent a useful backup to pharmacological treatment of knee OA or a valid alternative for patients who do not tolerate pharmacological treatments Nitric oxide ( NO ) has recently been proposed as an important mediator in inflammatory phases and in loss of cartilage . In inflammatory arthritis NO levels are correlated with disease activity and articular cartilage is able to produce large amounts of NO with the appropriate inducing factors such as cytokines and /or endotoxin . Neutrophils also play an important role in inflammatory reactions and the level of myeloperoxidase , a constituent of neutrophil granules , is related to the intensity of the inflammation . Because there is evidence that suggests that mud packs influence the main cytokines involved in cartilage damage , we tried to determine whether NO and myeloperoxidase are involved in the mechanisms of action of mud bath treatment .  We enrolled 37 subjects and r and omly assigned them to two groups : 19 patients underwent mud bath treatment ( group A )  while 18 patients underwent bath treatment alone .  Blood sample s were obtained before and after the treatment cycles to assay serum levels of NO , myeloperoxidase ( MPO ) and glutathione (GSH)-peroxidase . The results showed a statistically significant decrease in NO and myeloperoxidase serum values in groups A and B , while GSH-peroxidase was not significantly increase in either of the groups ; no correlation was found between NO , myeloperoxidase and GSH-peroxidase serum values .  Mud bath treatment can exert beneficial effects on cartilage homeostasis and inflammatory reactions , influencing NO and decreasing myeloperoxidase serum values . The increase in GSH-peroxidase was not correlated with the reduction of other biochemical markers , suggesting that mud bath treatment has different mechanisms of action Spa therapy and short wave therapy are two of the most commonly used non-pharmacological approaches for  osteoarthritis .  The aim of this study was to assess their efficacy in comparison to conventional therapy in patients with osteoarthritis of the knee in a single blind , r and omized , controlled trial . Seventy-four out patients were enrolled ; 30 patients were treated with a combination of daily local mud packs and arsenical ferruginous mineral bath water from the thermal resort of Levico Terme ( Trento , Italy ) for 3 weeks ; 24 patients were treated with short wave therapy for the same period and 20 patients continued regular , routine ambulatory care . Patients were assessed at baseline , upon completion of the 3-week treatment period , and 12 weeks later . Spa therapy and short wave therapy both demonstrated effective symptomatic treatment in osteoarthritis of the knee at the end of the treatment , but only the spa therapy was shown to have efficacy persistent over time . Our study demonstrated the superiority of arsenical ferruginous spa therapy compared to short wave therapy in the treatment of osteoarthritis of the knee , probably in relationship to the specific effects of the minerals in this water The objective of the study was to investigate the efficacy and tolerability of the peloid plasters in the group of 20 patients with osteoarthritis of peripheral joints ( 10 patients with gonarthrosis and 10 with omarthrosis ) and 20 patients with spondylosis . This form of the pelotherapy  decreased pain in joints after 10 days of the treatment . No allergic or other side effects were observed . Peloid plasters through the analgesic action improve the comfort of life and reduce the use of oral analgesic drugs We have previously shown that thermal mud therapy is able to influence chondrocyte activity of osteoarthrosic patients by modulating the production of serum cytokines , such as interleukin 1 , and this was related to the presence of an anti-inflammatory principle in mature thermal mud . Mud therapy influences many biochemical processes of the body , independently of the thermic stimulation alone and the present paper documents specific increases of insulin growth factor 1 and decreases of tumor nec 
    Output:
    