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 We aim ed to evaluate the effectiveness of balneotherapy in  fibromyalgia management .  Fifty women with fibromyalgia under pharmacological treatment were r and omly assigned to either the balneotherapy ( 25 ) or the control ( 25 ) group . Four patients from the balneotherapy group and one patient from the control group left the study after r and omization . The patients in the balneotherapy group ( 21 ) had 2 thermomineral water baths daily for 2 weeks in Tuzla Spa Center . The patients in the control group ( 24 ) continued to have their medical treatment and routine daily life . An investigator who was blinded to the study arms assessed the patients . All patients were assessed four times ; at the beginning of the study , at the end of the 2nd week , the 1st month , and the 3rd month after balneotherapy . Outcome measures of the study were pain intensity , Fibromyalgia Impact Question naire ( FIQ ) , Beck Depression Inventory ( BDI ) , patient ’s global assessment , investigator ’s global assessment , SF-36 scores , and tender point count .  Balneotherapy was found to be superior at the end of the cure period in terms of pain intensity , FIQ , Beck Depression Inventory , patient ’s global assessment , investigator ’s global assessment scores , and tender point count as compared to the control group . The superiority of balneotherapy lasted up to the end of the 3rd month , except for the Beck Depression Inventory score and the investigator ’s global assessment score . Significant improvements were observed in PF , GH , and MH subscales of SF-36 during the study period in the balneotherapy group ; however , no such improvement was observed in the control group . Balneotherapy was superior only in VT subscale at the end of therapy and at the end of the third month after the therapy as compared to the controls . It was concluded that balneotherapy provides beneficial effects in patients with fibromyalgia The purpose of this study was to investigate the clinical effects of balneotherapy in the treatment of Fibromyalgia Syndrome ( FMS ) and to determine if balneotherapy influences serum levels of inflammation markers , IL-1 , PGE2 and LTB4 . 24 primary fibromyalgia female patients diagnosed according to American College of Rheumatology criteria were included to the study . Their ages ranged between 33 and 55 years . FMS patients were r and omly assigned in two groups as , group 1 ( n = 12 ) and group 2 ( n = 12 ) . Group 1 received 20-min bathing , once in a day for five days per week . Patients participated in the study for 3 weeks ( total of 15 sessions ) in Denizli . Group 2 did not receive balneotherapy . FMS patients were evaluated by tenderness measurements ( tender point count and algometry ) , Visual Analogue Scale , Beck ’s Depression Index , Fibromyalgia Impact Question naire .  Ten healthy women recruited group three as the controls .  Serum PGE2 , LTB4 and IL1-α levels were measured in all three groups . The biochemical measurements and clinical assessment s were performed before and at the end of general period of therapy . Statistically significant alterations in algometric score , Visual Analogue score , Beck ’s Depression Index and PGE2 levels ( P < 0.001 ) , numbers of tender points ( P < 0.01 ) and Fibromyalgia Impact Question naire score ( P < 0.05 ) were found after the balneotherapy between group 1 and 2 . Mean PGE2 level of FMS patients were higher compared to healthy control group ( P < 0.0001 ) and decreased after the treatment period , only in group 1 ( P < 0.05 ) . As in the group 2 and 3 , detectable IL-1 and LTB4 measurements were insufficient , statistical analysis was performed , only in group 1 . After balneotherapy  IL-1 and LTB4 significantly decreased in group 1 ( P < 0.05 ) . In conclusion , balneotherapy is an effective choice of treatment in patients with FMS relieving the clinical symptoms , and possibly influencing the inflammatory mediators Multidisciplinary treatment has proven to be the best therapeutic option to fibromyalgia ( FM ) and physiotherapy has an important role in this approach . Considering the controversial results of electrotherapy in this condition , the aim of this study was to assess the effects of combined therapy with pulsed ultrasound and interferential current ( CTPI ) on pain and sleep in FM . Seventeen patients fulfilling FM criteria were divided into two groups , CTPI and SHAM , and su bmi tted to pain and sleep evaluations . Pain was evaluated by body map ( BM ) of the painful areas ; quantification of pain intensity by visual analog scale ( VAS ) ; tender point ( TP ) count and tenderness threshold ( TT ) . Sleep was assessed by inventory and polysomnography ( PSG ) . After 12 sessions of CTPI or SHAM procedure , patients were evaluated by the same initial protocol . After treatment , CTPI group showed , before and after sleep , subjective improvement of pain in terms of number ( BM ) and intensity ( VAS ) of painful areas ( P<0.001 , both ) ; as well as objective improvement , with decrease in TP count and increase in TT ( P<0.001 , both ) . Subjective sleep improvements observed after CTPI treatment included decrease in morning fatigue and in non‐refreshing sleep complaint ( P<0.001 , both ) . Objective ly , PSG in this group showed decrease in sleep latency ( P<0.001 ) and in the percentage of stage 1 ( P<0.001 ) , increase in the percentage of slow wave sleep ( P<0.001 ) and in sleep cycle count ( P<0.001 ) . Decrease in arousal index ( P<0.001 ) , number of sleep stage changes ( P<0.05 ) and wake time after sleep onset ( P<0.05 ) , were also observed and no difference regarding pain or sleep parameters were verified after SHAM procedure . This study shows that CTPI can be an effective therapeutic approach for pain and sleep manifestations in FM Fibromyalgia ( FM ) is a nonarticular rheumatological syndrome associated with diverse clinical and psychological features . One of the major complaints in FM is reduced pain tolerance , especially in tender points ( TP ) for which patients derive significant benefit from nonsteroidal antiinflammatory drugs or corticosteroids .  Patients with FM also have altered reactivity of the hypothalamic pituitary adrenal ( HPA ) axis where the predominant feature is reduced containment of the stress response system through diminished adrenocortical output and feedback resistance . Our results show that mud packs together with antidepressant treatment are able to influence the HPA axis , stimulating increased levels of adrenocorticotropic hormone , cortisol and beta-endorphin serum levels . The discharge of corticoids in the blood and the increase in beta-endorphin serum levels are followed by a reduction in pain symptoms , which is closely related to an improvement in disability , depression and quality of life . It seems that the synergic association between a pharmacological treatment ( trazodone ) and mud packs acts by helping the physiological responses to achieve homeostasis and to rebalance the stress response system . To clarify and optimize the effectiveness of this synergic association , studies involving a larger number of FM patients and a different pharmacological treatment are needed Objective The aim of this study was to compare pool-based exercise and balneotherapy in fibromyalgia syndrome ( FMS ) patients . Methods Fifty female patients diagnosed with FMS according to the American College of Rheumatism ( ACR ) criteria were r and omly assigned to two groups : group 1 ( n=25 ) with pool-based exercise , and in group 2 ( n=25 ) balneotherapy was applied in the same pool without any exercise for 35 min three times a week for 12 weeks . In both groups , pre- ( week 0 ) and post-treatment ( weeks 12 and 24 ) evaluation was performed by one of the authors , who was blind to the patient group . Evaluation parameters included pain , morning stiffness , sleep , tender points , global evaluation by the patient and the physician , fibromyalgia impact question naire , chair test , and Beck depression inventory . Statistical analysis was done on data collected from three evaluation stages . Results Twenty-four exercise and 22 balneotherapy patients completed the study . Pretreatment ( week 0 ) measurements did not show any difference between the groups . In group 1 , statistically significant improvement was observed in all parameters ( P<0.01 ) except for the chair test at both weeks 12 and 24 . In group 2 , week 12 measurements showed significant improvement in all parameters ( P<0.01 ) except for the chair test and Beck depression inventory . Week 24 evaluation results in group 2 showed significant improvements in pain and fatigue according to visual analogue scale ( VAS ) , 5-point scale , number of tender points , algometric and myalgic scores , and patient and physician global evaluation ( P<0.01 and P<0.05 , respectively ) , while improvements were nonsignificant in morning stiffness , sleep , fibromyalgia impact question naire ( FIQ ) , chair test , and Beck depression inventory parameters in this group . Comparison of the two groups based on the post-treatment ( weeks 12 and 24 ) percent changes and difference scores relative to pretreatment ( week 0 ) values failed to show a significant difference between the groups for any parameter except Beck depression inventory ( P<0.01 ) . Conclusion The results of our study showed that pool-based exercise had a longer-lasting effect on some of the FMS symptoms , but statistical analysis failed to show a significant superiority of pool-based exercise over balneotherapy without exercise . While we believe that exercise is a gold st and ard in FMS treatment , we also suggest in light of our results that balneotherapy is among the valid treatment options in FMS , and further research regarding the type and duration of the exercise programs is necessary OBJECTIVE It is a traditional practice in the Alpine region of Trentino and Alto Adige ( Italy ) to use phytothermotherapeutic treatment with fermenting grass ( " hay baths " ) for rheumatic diseases . However , despite its long history and popularity , a clinical validation of the efficacy and tolerability of the treatment has yet to be found in current literature . Fibromyalgia syndrome ( FMS ) is characterised by generalised musculoskeletal pain , high tender point counts , sleep disturbance , fatigue , headaches , irritable bowel syndrome , frequent psychological distress and depressed mood . There is no st and ard therapy regime for FMS and the variety of medical treatments used have given limited benefits . The aim of this study was to assess the efficacy and tolerability of a cycle of phytothermotherapy through a single-blind , controlled , r and omised trial , in patients with primary FMS . METHODS Fifty-six patients with primary FMS according to the ACR criteria were r and omly allocated to two groups : 30 were su bmi tted to phytothermotherapy at the thermal resort of Garniga Terme ( Trento , Italy ) and the other 26 were considered as controls . All patients were evaluated by FIQ , Tender Points Count , HAQ and AIMS 1 at baseline , after 10 days , then after 12 and 24 weeks . RESULTS Patients su bmi tted to phytothermotherapy showed visible and significant improvement of all evaluation parameters at the end of the treatment , which persisted during the follow-up period . No significant difference was found in the control group . Regarding the tolerability , none of the patients presented side effects . CONCLUSIONS Our results suggest the efficacy and the tolerability of phytothermotherapy in patients with primary FMS The efficacy of balneotherapy in fibromyalgia syndrome ( FS ) has been well demonstrated , while controlled studies using mud packs are lacking . We performed a r and omized clinical trial to evaluate the effects and the tolerability of mud-bath treatment in FS patients , who are poor responders to pharmacological therapy . Eighty patients with primary FS , according to ACR criteria , were r and omly allocated to two groups : 40 were su bmi tted to a cycle of 12 mud packs and thermal baths  , and 40 were considered as controls .  At baseline , after thermal treatment and after 16 weeks , patients were evaluated by FIQ , tender points count , VAS for “ minor ” symptoms , AIMS 1 
    Output:
    
agent
CONCLUSION Study data confirms that spa therapy could improve the symptoms of fibromyalgia including pain , depression and minor symptoms
***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 We aim ed to evaluate the effectiveness of balneotherapy in  fibromyalgia management .  Fifty women with fibromyalgia under pharmacological treatment were r and omly assigned to either the balneotherapy ( 25 ) or the control ( 25 ) group . Four patients from the balneotherapy group and one patient from the control group left the study after r and omization . The patients in the balneotherapy group ( 21 ) had 2 thermomineral water baths daily for 2 weeks in Tuzla Spa Center . The patients in the control group ( 24 ) continued to have their medical treatment and routine daily life . An investigator who was blinded to the study arms assessed the patients . All patients were assessed four times ; at the beginning of the study , at the end of the 2nd week , the 1st month , and the 3rd month after balneotherapy . Outcome measures of the study were pain intensity , Fibromyalgia Impact Question naire ( FIQ ) , Beck Depression Inventory ( BDI ) , patient ’s global assessment , investigator ’s global assessment , SF-36 scores , and tender point count .  Balneotherapy was found to be superior at the end of the cure period in terms of pain intensity , FIQ , Beck Depression Inventory , patient ’s global assessment , investigator ’s global assessment scores , and tender point count as compared to the control group . The superiority of balneotherapy lasted up to the end of the 3rd month , except for the Beck Depression Inventory score and the investigator ’s global assessment score . Significant improvements were observed in PF , GH , and MH subscales of SF-36 during the study period in the balneotherapy group ; however , no such improvement was observed in the control group . Balneotherapy was superior only in VT subscale at the end of therapy and at the end of the third month after the therapy as compared to the controls . It was concluded that balneotherapy provides beneficial effects in patients with fibromyalgia The purpose of this study was to investigate the clinical effects of balneotherapy in the treatment of Fibromyalgia Syndrome ( FMS ) and to determine if balneotherapy influences serum levels of inflammation markers , IL-1 , PGE2 and LTB4 . 24 primary fibromyalgia female patients diagnosed according to American College of Rheumatology criteria were included to the study . Their ages ranged between 33 and 55 years . FMS patients were r and omly assigned in two groups as , group 1 ( n = 12 ) and group 2 ( n = 12 ) . Group 1 received 20-min bathing , once in a day for five days per week . Patients participated in the study for 3 weeks ( total of 15 sessions ) in Denizli . Group 2 did not receive balneotherapy . FMS patients were evaluated by tenderness measurements ( tender point count and algometry ) , Visual Analogue Scale , Beck ’s Depression Index , Fibromyalgia Impact Question naire .  Ten healthy women recruited group three as the controls .  Serum PGE2 , LTB4 and IL1-α levels were measured in all three groups . The biochemical measurements and clinical assessment s were performed before and at the end of general period of therapy . Statistically significant alterations in algometric score , Visual Analogue score , Beck ’s Depression Index and PGE2 levels ( P < 0.001 ) , numbers of tender points ( P < 0.01 ) and Fibromyalgia Impact Question naire score ( P < 0.05 ) were found after the balneotherapy between group 1 and 2 . Mean PGE2 level of FMS patients were higher compared to healthy control group ( P < 0.0001 ) and decreased after the treatment period , only in group 1 ( P < 0.05 ) . As in the group 2 and 3 , detectable IL-1 and LTB4 measurements were insufficient , statistical analysis was performed , only in group 1 . After balneotherapy  IL-1 and LTB4 significantly decreased in group 1 ( P < 0.05 ) . In conclusion , balneotherapy is an effective choice of treatment in patients with FMS relieving the clinical symptoms , and possibly influencing the inflammatory mediators Multidisciplinary treatment has proven to be the best therapeutic option to fibromyalgia ( FM ) and physiotherapy has an important role in this approach . Considering the controversial results of electrotherapy in this condition , the aim of this study was to assess the effects of combined therapy with pulsed ultrasound and interferential current ( CTPI ) on pain and sleep in FM . Seventeen patients fulfilling FM criteria were divided into two groups , CTPI and SHAM , and su bmi tted to pain and sleep evaluations . Pain was evaluated by body map ( BM ) of the painful areas ; quantification of pain intensity by visual analog scale ( VAS ) ; tender point ( TP ) count and tenderness threshold ( TT ) . Sleep was assessed by inventory and polysomnography ( PSG ) . After 12 sessions of CTPI or SHAM procedure , patients were evaluated by the same initial protocol . After treatment , CTPI group showed , before and after sleep , subjective improvement of pain in terms of number ( BM ) and intensity ( VAS ) of painful areas ( P<0.001 , both ) ; as well as objective improvement , with decrease in TP count and increase in TT ( P<0.001 , both ) . Subjective sleep improvements observed after CTPI treatment included decrease in morning fatigue and in non‐refreshing sleep complaint ( P<0.001 , both ) . Objective ly , PSG in this group showed decrease in sleep latency ( P<0.001 ) and in the percentage of stage 1 ( P<0.001 ) , increase in the percentage of slow wave sleep ( P<0.001 ) and in sleep cycle count ( P<0.001 ) . Decrease in arousal index ( P<0.001 ) , number of sleep stage changes ( P<0.05 ) and wake time after sleep onset ( P<0.05 ) , were also observed and no difference regarding pain or sleep parameters were verified after SHAM procedure . This study shows that CTPI can be an effective therapeutic approach for pain and sleep manifestations in FM Fibromyalgia ( FM ) is a nonarticular rheumatological syndrome associated with diverse clinical and psychological features . One of the major complaints in FM is reduced pain tolerance , especially in tender points ( TP ) for which patients derive significant benefit from nonsteroidal antiinflammatory drugs or corticosteroids .  Patients with FM also have altered reactivity of the hypothalamic pituitary adrenal ( HPA ) axis where the predominant feature is reduced containment of the stress response system through diminished adrenocortical output and feedback resistance . Our results show that mud packs together with antidepressant treatment are able to influence the HPA axis , stimulating increased levels of adrenocorticotropic hormone , cortisol and beta-endorphin serum levels . The discharge of corticoids in the blood and the increase in beta-endorphin serum levels are followed by a reduction in pain symptoms , which is closely related to an improvement in disability , depression and quality of life . It seems that the synergic association between a pharmacological treatment ( trazodone ) and mud packs acts by helping the physiological responses to achieve homeostasis and to rebalance the stress response system . To clarify and optimize the effectiveness of this synergic association , studies involving a larger number of FM patients and a different pharmacological treatment are needed Objective The aim of this study was to compare pool-based exercise and balneotherapy in fibromyalgia syndrome ( FMS ) patients . Methods Fifty female patients diagnosed with FMS according to the American College of Rheumatism ( ACR ) criteria were r and omly assigned to two groups : group 1 ( n=25 ) with pool-based exercise , and in group 2 ( n=25 ) balneotherapy was applied in the same pool without any exercise for 35 min three times a week for 12 weeks . In both groups , pre- ( week 0 ) and post-treatment ( weeks 12 and 24 ) evaluation was performed by one of the authors , who was blind to the patient group . Evaluation parameters included pain , morning stiffness , sleep , tender points , global evaluation by the patient and the physician , fibromyalgia impact question naire , chair test , and Beck depression inventory . Statistical analysis was done on data collected from three evaluation stages . Results Twenty-four exercise and 22 balneotherapy patients completed the study . Pretreatment ( week 0 ) measurements did not show any difference between the groups . In group 1 , statistically significant improvement was observed in all parameters ( P<0.01 ) except for the chair test at both weeks 12 and 24 . In group 2 , week 12 measurements showed significant improvement in all parameters ( P<0.01 ) except for the chair test and Beck depression inventory . Week 24 evaluation results in group 2 showed significant improvements in pain and fatigue according to visual analogue scale ( VAS ) , 5-point scale , number of tender points , algometric and myalgic scores , and patient and physician global evaluation ( P<0.01 and P<0.05 , respectively ) , while improvements were nonsignificant in morning stiffness , sleep , fibromyalgia impact question naire ( FIQ ) , chair test , and Beck depression inventory parameters in this group . Comparison of the two groups based on the post-treatment ( weeks 12 and 24 ) percent changes and difference scores relative to pretreatment ( week 0 ) values failed to show a significant difference between the groups for any parameter except Beck depression inventory ( P<0.01 ) . Conclusion The results of our study showed that pool-based exercise had a longer-lasting effect on some of the FMS symptoms , but statistical analysis failed to show a significant superiority of pool-based exercise over balneotherapy without exercise . While we believe that exercise is a gold st and ard in FMS treatment , we also suggest in light of our results that balneotherapy is among the valid treatment options in FMS , and further research regarding the type and duration of the exercise programs is necessary OBJECTIVE It is a traditional practice in the Alpine region of Trentino and Alto Adige ( Italy ) to use phytothermotherapeutic treatment with fermenting grass ( " hay baths " ) for rheumatic diseases . However , despite its long history and popularity , a clinical validation of the efficacy and tolerability of the treatment has yet to be found in current literature . Fibromyalgia syndrome ( FMS ) is characterised by generalised musculoskeletal pain , high tender point counts , sleep disturbance , fatigue , headaches , irritable bowel syndrome , frequent psychological distress and depressed mood . There is no st and ard therapy regime for FMS and the variety of medical treatments used have given limited benefits . The aim of this study was to assess the efficacy and tolerability of a cycle of phytothermotherapy through a single-blind , controlled , r and omised trial , in patients with primary FMS . METHODS Fifty-six patients with primary FMS according to the ACR criteria were r and omly allocated to two groups : 30 were su bmi tted to phytothermotherapy at the thermal resort of Garniga Terme ( Trento , Italy ) and the other 26 were considered as controls . All patients were evaluated by FIQ , Tender Points Count , HAQ and AIMS 1 at baseline , after 10 days , then after 12 and 24 weeks . RESULTS Patients su bmi tted to phytothermotherapy showed visible and significant improvement of all evaluation parameters at the end of the treatment , which persisted during the follow-up period . No significant difference was found in the control group . Regarding the tolerability , none of the patients presented side effects . CONCLUSIONS Our results suggest the efficacy and the tolerability of phytothermotherapy in patients with primary FMS The efficacy of balneotherapy in fibromyalgia syndrome ( FS ) has been well demonstrated , while controlled studies using mud packs are lacking . We performed a r and omized clinical trial to evaluate the effects and the tolerability of mud-bath treatment in FS patients , who are poor responders to pharmacological therapy . Eighty patients with primary FS , according to ACR criteria , were r and omly allocated to two groups : 40 were su bmi tted to a cycle of 12 mud packs and thermal baths  , and 40 were considered as controls .  At baseline , after thermal treatment and after 16 weeks , patients were evaluated by FIQ , tender points count , VAS for “ minor ” symptoms , AIMS 1 
    Output:
    