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 Aromatase inhibitors ( AIs ) frequently lead to the AI-induced musculoskeletal syndrome ( AIMS S ) . Looking into its pathophysiology , 6 months of AI therapy thickens the tendon sheath with intra-articular fluid ( IAF ) retention and loss of grip strength . We here report 24-month follow-up data . PATIENTS AND METHODS A prospect i ve cohort study of 33 postmenopausal breast cancer patients received adjuvant endocrine therapy ; 27 received an AI and 6 received tamoxifen .  At baseline , 6 and 24 months patients had a rheumatologic examination , including a grip strength test , and magnetic resonance imaging of both h and s and wrists . The primary end point was tenosynovial changes ; secondary end points were changes in morning stiffness , grip strength and IAF . RESULTS Twenty-three AI and 5 tamoxifen patients completed all investigations . Between month 6 and 24 , IAF further increased in AI users ( P = 0.04 ) but not in tamoxifen users , and grip strength further decreased in both groups . The worsened tenosynovial changes were strongly correlated with a decrease in grip strength . At 24 months , morning stiffness continued to be present in over a third of AI users . CONCLUSION AIMS S represents a substantial problem in breast cancer patients . It is associated with tenosynovial changes , IAF retention , joint stiffness and loss of grip strength that do not improve with prolonged use BACKGROUND Arthralgia is a common and debilitating side-effect experienced by breast cancer patients receiving aromatase inhibitors ( AIs ) and often results in premature drug discontinuation . METHODS We conducted a r and omised controlled trial of electro-acupuncture ( EA ) as compared to waitlist control ( WLC ) and sham acupuncture ( SA ) in postmenopausal women with breast cancer who self-reported arthralgia attributable to AIs . Acupuncturists performed 10 EA/SA treatments over 8 weeks using a manualised protocol with 2 Hz electro-stimulation delivered by a TENS unit . Acupuncturists administered SA using Streitberger ( non-penetrating ) needles at non-traditional acupuncture points without electro-stimulation . The primary end-point was pain severity by Brief Pain Inventory ( BPI ) between EA and WLC at Week 8 ; durability of response at Week 12 and comparison of EA to SA were secondary aims . FINDINGS Of the 67 r and omly assigned patients , mean reduction in pain severity was greater in the EA group than in the WLC group at Week 8 ( -2.2 versus -0.2 , p=0.0004 ) and at Week 12 ( -2.4 versus -0.2 , p<0.0001 ) . Pain-related interference measured by BPI also improved in the EA group compared to the WLC group at both Week 8 ( -2.0 versus 0.2 , p=0.0006 ) and Week 12 ( -2.1 versus -0.1 , p=0.0034 ) . SA produced a magnitude of change in pain severity and pain-related interference at Week 8 ( -2.3 , -1.5 respectively ) and Week 12 ( -1.7 , -1.3 respectively ) similar to that of EA . Participants in both EA and SA groups reported few minor adverse events . INTERPRETATIONS Compared to usual care , EA produced clinical ly important and durable improvement in arthralgia related to AIs in breast cancer patients , and SA had a similar effect . Both EA and SA were safe Up to 50 % of women receiving aromatase inhibitor ( AI ) complain of AI-associated musculoskeletal symptoms ( AIMS S ) and 15 % discontinue treatment . We conducted a r and omized , sham-controlled trial to evaluate whether acupuncture improves AIMS S and to explore potential mechanisms . Postmenopausal women with early stage breast cancer , experiencing AIMS S were r and omized to eight weekly real or sham acupuncture sessions . We evaluated changes in the Health Assessment Question naire Disability Index ( HAQ-DI ) and pain visual analog scale ( VAS ) following the intervention compared to baseline . Serum estradiol , β-endorphin , and proinflammatory cytokine concentrations were measured pre and post-intervention . We enrolled 51 women of whom 47 were evaluable , including 23 r and omized to real and 24 to sham acupuncture . Baseline characteristics were balanced between groups with the exception of a higher HAQ-DI score in the real acupuncture group ( p = 0.047 ) . We did not observe a statistically significant difference in reduction of HAQ-DI ( p = 0.30 ) or VAS ( p = 0.31 ) between the two groups . Following eight weekly treatments , we observed a statistically significant reduction of IL-17 ( p ≤ 0.009 ) in both groups . No significant modulation was seen in estradiol , β-endorphin , or other proinflammatory cytokine concentrations in either group . We did not observe a significant difference in AIMS S changes between real and sham acupuncture . As sham acupuncture used in this study may not be equivalent to placebo , further studies with a non-acupuncture arm may be required to establish whether acupuncture is beneficial for the treatment of AIMS Background Aromatase inhibitors ( AIs ) are recommended as adjuvant hormone treatment for postmenopausal women with early breast cancer . A substantial proportion of women taking AIs experience joint pain and stiffness . Studies have suggested that acupuncture may be effective in treating joint pain . Objective A pilot study was conducted to evaluate the feasibility , safety and efficacy of using acupuncture to treat AI-induced arthralgia . Methods A total of 32 patients were r and omised to receive either sham or real electroacupuncture ( EA ) twice weekly for 6 weeks . Outcomes of joint pain , stiffness and physical function were measured with the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , overall pain severity and interference with the BPI-SF and quality of life ( QOL ) with the Functional Assessment of Cancer Therapy-General ( FACT-G ) instrument . H and strength was assessed by a grip test , and a serum marker of inflammation ( C reactive protein ( CRP ) ) was also measured . All assessment s were performed at baseline , 6 weeks and 12 weeks , except for blood sample s at baseline and 6 weeks only . Results No serious adverse events were reported during or after acupuncture treatments . There were no significant differences in outcome measures . However , positive trends were observed in stiffness and physical function at week 12 in favour of real EA . Conclusions Findings suggest that acupuncture is feasible and safe in patients with breast cancer with joint pain caused by AI . A larger study with adequately powered to confirm these results and detect clinical ly relevant effects is needed Background . Arthralgia affects postmenopausal women receiving aromatase inhibitors ( AIs ) for breast cancer . Given the existing evidence for electroacupuncture ( EA ) for treatment of osteoarthritis in the general population , this study aims to establish the feasibility of study ing EA for treating AI-related arthralgia . Patients and Methods . Postmenopausal women with stage I-III breast cancer who reported AI-related arthral gia were enrolled in a single-arm feasibility trial . EA was provided twice a week for 2 weeks followed by 6 weekly treatments . The protocol was based on Chinese medicine diagnosis of “ Bi ” syndrome with electrostimulation of needles around the painful joint(s ) . Pain severity of the modified Brief Pain Inventory was used as the primary outcome . Joint stiffness , joint interference , and Patient Global Impression of Change ( PGIC ) were secondary outcomes . Paired t tests were used for analysis . Results . Twelve women were enrolled and all provided data for analysis . From baseline to the end of intervention , patients reported reduction in pain severity ( from 5.3 to 1.9 ) , stiffness ( from 6.9 to 2.4 ) , and joint symptom interference ( from 4.7 to 0.8 ) , all P < .001 ; 11/12 considered joint symptoms “ very much better ” based on the PGIC . Subjects also reported significant decrease in fatigue ( from 4.4 to 1.9 , P = .005 ) and anxiety ( from 7.1 to 4.8 , P = .01 ) . No infection or development or worsening of lymphedema was observed . Conclusion . Preliminary data establish the feasibility of recruitment and acceptance as well as promising preliminary safety and effectiveness . A r and omized controlled trial is warranted to establish the efficacy of EA for AI-related arthralgia in breast cancer survivors Several vali date d sham acupuncture devices have recently become available . While some debate exists on whether such needles are the best placebo control for an RCT of acupuncture , practical advice based on research experience is missing from the literature . This paper shares our concrete experience using the most commonly used such sham needle ( the ‘ Streitberger needle ’ and its paired verum needle ) in a large RCT ( n=135 ) which included a two-week run-in period . The placebo run-in gave us an opportunity to use the sham device on all participants , who were then re-r and omised to receive genuine acupuncture or to continue treatment with the device . The blinding was successful both at the end of the run-in and at the conclusion of the trial despite the re-r and omisation . We also report our experience with the sham needle in neuroimaging experiments where the magnetic machinery poses considerable challenges for acupuncture research BACKGROUND Tamoxifen , taken for five years , is the st and ard adjuvant treatment for postmenopausal women with primary , estrogen-receptor-positive breast cancer . Despite this treatment , however , some patients have a relapse . METHODS We conducted a double-blind , r and omized trial to test whether , after two to three years of tamoxifen therapy , switching to exemestane was more effective than continuing tamoxifen therapy for the remainder of the five years of treatment . The primary end point was disease-free survival . RESULTS Of the 4742 patients enrolled , 2362 were r and omly assigned to switch to exemestane , and 2380 to continue to receive tamoxifen .  After a median follow-up of 30.6 months , 449 first events ( local or metastatic recurrence , contralateral breast cancer , or death ) were reported--183 in the exemestane group and 266 in the tamoxifen group . The unadjusted hazard ratio in the exemestane group as compared with the tamoxifen group was 0.68 ( 95 percent confidence interval , 0.56 to 0.82 ; P<0.001 by the log-rank test ) , representing a 32 percent reduction in risk and corresponding to an absolute benefit in terms of disease-free survival of 4.7 percent ( 95 percent confidence interval , 2.6 to 6.8 ) at three years after r and omization . Overall survival was not significantly different in the two groups , with 93 deaths occurring in the exemestane group and 106 in the tamoxifen group . Severe toxic effects of exemestane were rare . Contralateral breast cancer occurred in 20 patients in the tamoxifen group and 9 in the exemestane group ( P=0.04 ) . CONCLUSIONS Exemestane therapy after two to three years of tamoxifen therapy significantly improved disease-free survival as compared with the st and ard five years of tamoxifen treatment PURPOSE Women with breast cancer ( BC ) treated with aromatase inhibitors ( AIs ) may experience joint symptoms that can lead to discontinuation of effective therapy . We examined whether acupuncture improves AI-induced arthralgias in women with early-stage BC . METHODS We conducted a r and omized , controlled , blinded study comparing true acupuncture ( TA ) versus sham acupuncture ( SA ) twice weekly for 6 weeks in postmenopuasal women with BC who had self-reported musculoskeletal pain related to AIs .  TA included full body/auricular acupuncture and joint-specific point prescriptions , whereas SA involved superficial needle insertion at nonacupoint locations . Outcome measures included the Brief Pain Inventory-Short Form ( BPI-SF ) , Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , and Modified Score for the Assessment of Chronic Rheumatoid Affections of the H and s ( M-SACRAH ) obtained at baseline and at 3 and 6 weeks . Results Of 51 women enrolled , 43 women were r and omly assigned and 38 were evaluable . Baseline characteristics were comparable between the two groups . Our primary end point was the difference in mean BPI-SF worst pain scores at 6 weeks , which was lower for TA compared with SA ( 3.0 v 5.5 ; P < .001 ) . We also found differences between TA and SA in pain severity ( 2.6 v 4.5 ; P = .003 ) and pain-related interference ( 2.5 v 4.5 ; P = .002 ) at 6 weeks . Similar findings were seen for the WOMAC and M-SACRAH scores . The acupuncture intervention was well-tolerated . CONCLUSION Women with AI-induced arthralgias treated with TA had significant improvement of joint pain and stiffness , which was not seen with SA . Acupuncture is an effective and well-tolerated strategy for managing this common treatment-related side effect BACKGROUND In the adjuvant setting , tamoxifen is the established treatment for post 
    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 Aromatase inhibitors ( AIs ) frequently lead to the AI-induced musculoskeletal syndrome ( AIMS S ) . Looking into its pathophysiology , 6 months of AI therapy thickens the tendon sheath with intra-articular fluid ( IAF ) retention and loss of grip strength . We here report 24-month follow-up data . PATIENTS AND METHODS A prospect i ve cohort study of 33 postmenopausal breast cancer patients received adjuvant endocrine therapy ; 27 received an AI and 6 received tamoxifen .  At baseline , 6 and 24 months patients had a rheumatologic examination , including a grip strength test , and magnetic resonance imaging of both h and s and wrists . The primary end point was tenosynovial changes ; secondary end points were changes in morning stiffness , grip strength and IAF . RESULTS Twenty-three AI and 5 tamoxifen patients completed all investigations . Between month 6 and 24 , IAF further increased in AI users ( P = 0.04 ) but not in tamoxifen users , and grip strength further decreased in both groups . The worsened tenosynovial changes were strongly correlated with a decrease in grip strength . At 24 months , morning stiffness continued to be present in over a third of AI users . CONCLUSION AIMS S represents a substantial problem in breast cancer patients . It is associated with tenosynovial changes , IAF retention , joint stiffness and loss of grip strength that do not improve with prolonged use BACKGROUND Arthralgia is a common and debilitating side-effect experienced by breast cancer patients receiving aromatase inhibitors ( AIs ) and often results in premature drug discontinuation . METHODS We conducted a r and omised controlled trial of electro-acupuncture ( EA ) as compared to waitlist control ( WLC ) and sham acupuncture ( SA ) in postmenopausal women with breast cancer who self-reported arthralgia attributable to AIs . Acupuncturists performed 10 EA/SA treatments over 8 weeks using a manualised protocol with 2 Hz electro-stimulation delivered by a TENS unit . Acupuncturists administered SA using Streitberger ( non-penetrating ) needles at non-traditional acupuncture points without electro-stimulation . The primary end-point was pain severity by Brief Pain Inventory ( BPI ) between EA and WLC at Week 8 ; durability of response at Week 12 and comparison of EA to SA were secondary aims . FINDINGS Of the 67 r and omly assigned patients , mean reduction in pain severity was greater in the EA group than in the WLC group at Week 8 ( -2.2 versus -0.2 , p=0.0004 ) and at Week 12 ( -2.4 versus -0.2 , p<0.0001 ) . Pain-related interference measured by BPI also improved in the EA group compared to the WLC group at both Week 8 ( -2.0 versus 0.2 , p=0.0006 ) and Week 12 ( -2.1 versus -0.1 , p=0.0034 ) . SA produced a magnitude of change in pain severity and pain-related interference at Week 8 ( -2.3 , -1.5 respectively ) and Week 12 ( -1.7 , -1.3 respectively ) similar to that of EA . Participants in both EA and SA groups reported few minor adverse events . INTERPRETATIONS Compared to usual care , EA produced clinical ly important and durable improvement in arthralgia related to AIs in breast cancer patients , and SA had a similar effect . Both EA and SA were safe Up to 50 % of women receiving aromatase inhibitor ( AI ) complain of AI-associated musculoskeletal symptoms ( AIMS S ) and 15 % discontinue treatment . We conducted a r and omized , sham-controlled trial to evaluate whether acupuncture improves AIMS S and to explore potential mechanisms . Postmenopausal women with early stage breast cancer , experiencing AIMS S were r and omized to eight weekly real or sham acupuncture sessions . We evaluated changes in the Health Assessment Question naire Disability Index ( HAQ-DI ) and pain visual analog scale ( VAS ) following the intervention compared to baseline . Serum estradiol , β-endorphin , and proinflammatory cytokine concentrations were measured pre and post-intervention . We enrolled 51 women of whom 47 were evaluable , including 23 r and omized to real and 24 to sham acupuncture . Baseline characteristics were balanced between groups with the exception of a higher HAQ-DI score in the real acupuncture group ( p = 0.047 ) . We did not observe a statistically significant difference in reduction of HAQ-DI ( p = 0.30 ) or VAS ( p = 0.31 ) between the two groups . Following eight weekly treatments , we observed a statistically significant reduction of IL-17 ( p ≤ 0.009 ) in both groups . No significant modulation was seen in estradiol , β-endorphin , or other proinflammatory cytokine concentrations in either group . We did not observe a significant difference in AIMS S changes between real and sham acupuncture . As sham acupuncture used in this study may not be equivalent to placebo , further studies with a non-acupuncture arm may be required to establish whether acupuncture is beneficial for the treatment of AIMS Background Aromatase inhibitors ( AIs ) are recommended as adjuvant hormone treatment for postmenopausal women with early breast cancer . A substantial proportion of women taking AIs experience joint pain and stiffness . Studies have suggested that acupuncture may be effective in treating joint pain . Objective A pilot study was conducted to evaluate the feasibility , safety and efficacy of using acupuncture to treat AI-induced arthralgia . Methods A total of 32 patients were r and omised to receive either sham or real electroacupuncture ( EA ) twice weekly for 6 weeks . Outcomes of joint pain , stiffness and physical function were measured with the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , overall pain severity and interference with the BPI-SF and quality of life ( QOL ) with the Functional Assessment of Cancer Therapy-General ( FACT-G ) instrument . H and strength was assessed by a grip test , and a serum marker of inflammation ( C reactive protein ( CRP ) ) was also measured . All assessment s were performed at baseline , 6 weeks and 12 weeks , except for blood sample s at baseline and 6 weeks only . Results No serious adverse events were reported during or after acupuncture treatments . There were no significant differences in outcome measures . However , positive trends were observed in stiffness and physical function at week 12 in favour of real EA . Conclusions Findings suggest that acupuncture is feasible and safe in patients with breast cancer with joint pain caused by AI . A larger study with adequately powered to confirm these results and detect clinical ly relevant effects is needed Background . Arthralgia affects postmenopausal women receiving aromatase inhibitors ( AIs ) for breast cancer . Given the existing evidence for electroacupuncture ( EA ) for treatment of osteoarthritis in the general population , this study aims to establish the feasibility of study ing EA for treating AI-related arthralgia . Patients and Methods . Postmenopausal women with stage I-III breast cancer who reported AI-related arthral gia were enrolled in a single-arm feasibility trial . EA was provided twice a week for 2 weeks followed by 6 weekly treatments . The protocol was based on Chinese medicine diagnosis of “ Bi ” syndrome with electrostimulation of needles around the painful joint(s ) . Pain severity of the modified Brief Pain Inventory was used as the primary outcome . Joint stiffness , joint interference , and Patient Global Impression of Change ( PGIC ) were secondary outcomes . Paired t tests were used for analysis . Results . Twelve women were enrolled and all provided data for analysis . From baseline to the end of intervention , patients reported reduction in pain severity ( from 5.3 to 1.9 ) , stiffness ( from 6.9 to 2.4 ) , and joint symptom interference ( from 4.7 to 0.8 ) , all P < .001 ; 11/12 considered joint symptoms “ very much better ” based on the PGIC . Subjects also reported significant decrease in fatigue ( from 4.4 to 1.9 , P = .005 ) and anxiety ( from 7.1 to 4.8 , P = .01 ) . No infection or development or worsening of lymphedema was observed . Conclusion . Preliminary data establish the feasibility of recruitment and acceptance as well as promising preliminary safety and effectiveness . A r and omized controlled trial is warranted to establish the efficacy of EA for AI-related arthralgia in breast cancer survivors Several vali date d sham acupuncture devices have recently become available . While some debate exists on whether such needles are the best placebo control for an RCT of acupuncture , practical advice based on research experience is missing from the literature . This paper shares our concrete experience using the most commonly used such sham needle ( the ‘ Streitberger needle ’ and its paired verum needle ) in a large RCT ( n=135 ) which included a two-week run-in period . The placebo run-in gave us an opportunity to use the sham device on all participants , who were then re-r and omised to receive genuine acupuncture or to continue treatment with the device . The blinding was successful both at the end of the run-in and at the conclusion of the trial despite the re-r and omisation . We also report our experience with the sham needle in neuroimaging experiments where the magnetic machinery poses considerable challenges for acupuncture research BACKGROUND Tamoxifen , taken for five years , is the st and ard adjuvant treatment for postmenopausal women with primary , estrogen-receptor-positive breast cancer . Despite this treatment , however , some patients have a relapse . METHODS We conducted a double-blind , r and omized trial to test whether , after two to three years of tamoxifen therapy , switching to exemestane was more effective than continuing tamoxifen therapy for the remainder of the five years of treatment . The primary end point was disease-free survival . RESULTS Of the 4742 patients enrolled , 2362 were r and omly assigned to switch to exemestane , and 2380 to continue to receive tamoxifen .  After a median follow-up of 30.6 months , 449 first events ( local or metastatic recurrence , contralateral breast cancer , or death ) were reported--183 in the exemestane group and 266 in the tamoxifen group . The unadjusted hazard ratio in the exemestane group as compared with the tamoxifen group was 0.68 ( 95 percent confidence interval , 0.56 to 0.82 ; P<0.001 by the log-rank test ) , representing a 32 percent reduction in risk and corresponding to an absolute benefit in terms of disease-free survival of 4.7 percent ( 95 percent confidence interval , 2.6 to 6.8 ) at three years after r and omization . Overall survival was not significantly different in the two groups , with 93 deaths occurring in the exemestane group and 106 in the tamoxifen group . Severe toxic effects of exemestane were rare . Contralateral breast cancer occurred in 20 patients in the tamoxifen group and 9 in the exemestane group ( P=0.04 ) . CONCLUSIONS Exemestane therapy after two to three years of tamoxifen therapy significantly improved disease-free survival as compared with the st and ard five years of tamoxifen treatment PURPOSE Women with breast cancer ( BC ) treated with aromatase inhibitors ( AIs ) may experience joint symptoms that can lead to discontinuation of effective therapy . We examined whether acupuncture improves AI-induced arthralgias in women with early-stage BC . METHODS We conducted a r and omized , controlled , blinded study comparing true acupuncture ( TA ) versus sham acupuncture ( SA ) twice weekly for 6 weeks in postmenopuasal women with BC who had self-reported musculoskeletal pain related to AIs .  TA included full body/auricular acupuncture and joint-specific point prescriptions , whereas SA involved superficial needle insertion at nonacupoint locations . Outcome measures included the Brief Pain Inventory-Short Form ( BPI-SF ) , Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , and Modified Score for the Assessment of Chronic Rheumatoid Affections of the H and s ( M-SACRAH ) obtained at baseline and at 3 and 6 weeks . Results Of 51 women enrolled , 43 women were r and omly assigned and 38 were evaluable . Baseline characteristics were comparable between the two groups . Our primary end point was the difference in mean BPI-SF worst pain scores at 6 weeks , which was lower for TA compared with SA ( 3.0 v 5.5 ; P < .001 ) . We also found differences between TA and SA in pain severity ( 2.6 v 4.5 ; P = .003 ) and pain-related interference ( 2.5 v 4.5 ; P = .002 ) at 6 weeks . Similar findings were seen for the WOMAC and M-SACRAH scores . The acupuncture intervention was well-tolerated . CONCLUSION Women with AI-induced arthralgias treated with TA had significant improvement of joint pain and stiffness , which was not seen with SA . Acupuncture is an effective and well-tolerated strategy for managing this common treatment-related side effect BACKGROUND In the adjuvant setting , tamoxifen is the established treatment for post 
    Output:
    