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: Purpose Osteoarthritic pain is largely considered to be inflammatory pain . Sensory nerve fibers innervating the knee have been shown to be significantly damaged in rat models of knee osteoarthritis ( OA ) in which the subchondral bone junction is destroyed , and this induces neuropathic pain ( NP ) . Pregabalin was developed as a pain killer for NP ; however , there are no reports on pregabalin use in OA patients . The purpose of this study was to investigate the efficacy of pregabalin for pain in OA patients . Material s and Methods Eighty-nine knee OA patients were evaluated in this r and omized prospect i ve study . Patients were divided into meloxicam , pregabalin , and meloxicam+pregabalin groups . Pain scores were evaluated before and 4 weeks after drug application using a visual analogue scale ( VAS ) , and Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Pain scales among groups were compared using a Kruskal-Wallis test . Results Before drug application , there was no significant difference in VAS and WOMAC scores among the three groups ( p>0.05 ) . Significant pain relief was seen in the meloxicam+pregabalin group in VAS at 1 , 2 , and 4 weeks , and WOMAC score at 4 weeks , compared with the other groups ( p<0.05 ) . No significant pain relief was seen in the meloxicam only group in VAS during 4 weeks and WOMAC score at 4 weeks compared with the pregabalin only group ( p>0.05 ) . Conclusion Meloxicam+pregabalin was effective for pain in OA patients . This finding suggests that OA pain is a combination of inflammatory and NP Background Tapentadol prolonged release ( PR ; 100–250 mg twice daily ) has been efficacious and well tolerated for managing moderate-to-severe , chronic osteoarthritis hip or knee pain in phase 3 studies with washout of previous analgesic treatment . Objective The objective of this study was to evaluate the effectiveness and tolerability of tapentadol PR ( 50–250 mg twice daily ) after direct rotation from World Health Organization ( WHO ) step III opioids in patients with severe osteoarthritis knee pain who previously responded to WHO step III therapy but showed poor tolerability . Methods This open-label , phase 3b study ( NCT00982280 ) was conducted from October 2009 through June 2010 ( prematurely terminated due to slow recruitment and study drug shortages ) in clinical care setting s in Europe and Australia . The study population included patients with severe , chronic osteoarthritis knee pain who had taken WHO step III opioids daily for ≥2 weeks before screening , responded to therapy ( average pain intensity [ 11-point numerical rating scale-3 ( NRS-3 ) ] ≤5 at screening ) , and reported opioid-related adverse effects  as their reason for changing analgesics . Patients switched directly from WHO step III therapy to tapentadol . Patients received oral tapentadol PR ( 50–250 mg twice daily ) during 5-week titration and 7-week maintenance periods . Oral tapentadol immediate release ( IR ) was permitted ( ≤twice/day , ≥4 h apart ) for acute pain episodes due to index pain or withdrawal symptoms following discontinuation of previous opioids ( combined dose of tapentadol [ PR and IR ] ≤500 mg/day ) . This study was planned to evaluate conversion  to tapentadol PR , based on responder rate 1 ( percentage of patients with same/less pain [ NRS-3 ] versus Week −1 ) at Week 6 ( primary endpoint ) , adverse events ( AEs ) , and discontinuation rates . Equianalgesic ratios were calculated for tapentadol prior to WHO step III opioids ( PR and PR plus IR formulations ) . Results Of 82 patients enrolled , 63 received study medication . In the per- protocol population , responder rate 1 at Week 6 ( last observation carried forward ) was 94.3 % ( 50/53 ; P < 0.0001 vs. the null hypothesis rate [ < 60 % ] ) . Mean ( st and ard deviation ) pain intensity scores were 4.7 ( 0.66 ) at baseline , 2.5 ( 1.46 ) at Week 6 , and 1.8 ( 1.41 ) at Week 12 in the main analysis population ( change from baseline at Weeks 6 and 12 , P < 0.0001 ) . Tapentadol to transdermal buprenorphine equianalgesic ratios ( PR [ n = 48 ] , 262.9:1 ; PR plus IR [ n = 48 ] , 281.1:1 ) and tapentadol to oral oxycodone equianalgesic ratios ( PR [ n = 4 ] , 4.3:1 ; PR plus IR [ n = 6 ] , 4.6:1 ) were calculated for the main analysis population . In the safety population , prevalence of AEs reported as associated with prior opioids at Week −1 ( reasons for rotation ) and related to tapentadol treatment at Week 12 decreased over time ; the most common were nausea ( 46.0 vs. 24.1 % ) and constipation ( 31.7 vs. 7.4 % ) . Overall , 14.3 % of patients discontinued the study early ; reasons included AEs ( 9.5 % ) , lack of efficacy ( 3.2 % ) , and withdrawal of consent ( 1.6 % ) . Conclusions Significant improvements in effectiveness were observed for tapentadol PR ( 50–250 mg twice daily ) versus WHO step III opioids in patients with severe , chronic osteoarthritis knee pain who previously responded to WHO step III therapy . Equianalgesic ratios were calculated for tapentadol to transdermal buprenorphine and oral oxycodone and were in line with observations from previous phase 3 studies Abstract Objective : To determine the efficacy , tolerability , and safety of duloxetine when added to oral nonsteroidal anti-inflammatory drugs ( NSAIDs ) in patients with osteoarthritis ( OA ) of the knee with pain of moderate or greater severity . Research design and methods : This was a 10-week r and omized , double-blind , flexible-dose ( duloxetine 60/120 mg/day ) , placebo-controlled trial that enrolled adult out patients who had persistent moderate pain ( ≥4 on a 0–10 numerical rating scale ) due to OA of the knee , despite , per protocol , having received optimized oral NSAID therapy  ( specific drug , dose , and frequency at investigator discretion ) . Clinical trials registration : Trial registration : Clinical Trials.gov identifier : NCT01018680 . Main outcome measure : Patients entered daily pain ratings in a telephone-based diary . The primary efficacy outcome was the weekly mean of the daily average pain rating at week 8 . Safety outcomes were assessed during the entire 10-week study . Results : A total of 524 patients r and omly received duloxetine 60/120 mg/day ( N = 264 ) or placebo ( N = 260 ) . In total , 74 % of the patients completed the study . Mean age was 61 years ( SD 9.2 ) , 57 % were female , and 81 % were white .  Duloxetine-treated patients had significantly greater pain reduction at week 8 ( p < 0.001 ) than placebo-treated patients . In addition , relative to placebo at week 8 , duloxetine-treated patients had significant improvements in physical function as measured by the Western Ontario and McMaster Universities Osteoarthritis Index ( p < 0.001 ) , and Patient Global Impression of Improvement ( p < 0.001 ) . Compared to placebo , significantly more nausea , dry mouth , constipation , fatigue and decreased appetite were reported by patients taking duloxetine ( each p < 0.05 ) . Discontinuation due to adverse events occurred more commonly in the duloxetine group than the placebo group ( p = 0.03 ) . Conclusion : Duloxetine added to oral NSAID therapy provided additional significant pain reduction , improved function , and patient-rated impression of improvement . Adverse events were consistent with those seen in previous duloxetine trials . The short duration of the study may not reflect the longer term efficacy and safety of NSAID/duloxetine cotherapy OBJECTIVE To evaluate the efficacy and safety of duloxetine in the treatment of chronic pain due to osteoarthritis of the knee . METHODS This was a 13-week , r and omized , double-blind , placebo-controlled trial in patients meeting American College of Rheumatology clinical and radiographic criteria for osteoarthritis of the knee . At baseline , patients were required to have a ≥ 4 weekly mean of the 24-hour average pain ratings . Patients were r and omized to either duloxetine 60 mg once daily ( QD ) or placebo . At week 7 , the duloxetine dosage was increased , in a blinded fashion , to 120-mg QD in patients reporting < 30 % pain reduction . The primary efficacy measure was Brief Pain Inventory ( BPI ) 24-hour average pain . Secondary efficacy measures included Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) ; Clinical Global Impressions of Severity ( CGI-S ) . Safety and tolerability was also assessed . RESULTS Of the total ( n = 256 ) patients , 111 ( 86.7 % ) in placebo group and 93 ( 72.7 % ) in duloxetine group completed the study . Patients treated with duloxetine had significantly ( P ≤ 0.001 ) greater improvement at all time points on BPI average pain and had significantly greater improvement on BPI pain severity ratings ( P ≤ 0.05 ) , WOMAC total ( P = 0.044 ) and physical functioning scores ( P = 0.016 ) , and CGI-S ( P = 0.009 ) at the study endpoint . Frequency of treatment-emergent nausea , constipation , and hyperhidrosis were significantly higher in the duloxetine group ( P ≤ 0.05 ) . Significantly more duloxetine-treated patients discontinued the trial because of adverse events ( P = 0.002 ) . CONCLUSIONS Treatment with duloxetine 60 mg to 120 mg QD was associated with significant pain reduction and improved function in patients with pain due to osteoarthritis of the knee 
    Output:
    
agent
Results There is good evidence for a role of central sensitisation in chronic OA pain in a subgroup of patients .
Biomarkers may be helpful for confirming the presence of central sensitisation , especially when there is diagnostic uncertainty .
Several non‐pharmacological and pharmacological treatments may be effective in OA patients with central sensitisation features .
Multimodal therapy may be required to achieve control of 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: Purpose Osteoarthritic pain is largely considered to be inflammatory pain . Sensory nerve fibers innervating the knee have been shown to be significantly damaged in rat models of knee osteoarthritis ( OA ) in which the subchondral bone junction is destroyed , and this induces neuropathic pain ( NP ) . Pregabalin was developed as a pain killer for NP ; however , there are no reports on pregabalin use in OA patients . The purpose of this study was to investigate the efficacy of pregabalin for pain in OA patients . Material s and Methods Eighty-nine knee OA patients were evaluated in this r and omized prospect i ve study . Patients were divided into meloxicam , pregabalin , and meloxicam+pregabalin groups . Pain scores were evaluated before and 4 weeks after drug application using a visual analogue scale ( VAS ) , and Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Pain scales among groups were compared using a Kruskal-Wallis test . Results Before drug application , there was no significant difference in VAS and WOMAC scores among the three groups ( p>0.05 ) . Significant pain relief was seen in the meloxicam+pregabalin group in VAS at 1 , 2 , and 4 weeks , and WOMAC score at 4 weeks , compared with the other groups ( p<0.05 ) . No significant pain relief was seen in the meloxicam only group in VAS during 4 weeks and WOMAC score at 4 weeks compared with the pregabalin only group ( p>0.05 ) . Conclusion Meloxicam+pregabalin was effective for pain in OA patients . This finding suggests that OA pain is a combination of inflammatory and NP Background Tapentadol prolonged release ( PR ; 100–250 mg twice daily ) has been efficacious and well tolerated for managing moderate-to-severe , chronic osteoarthritis hip or knee pain in phase 3 studies with washout of previous analgesic treatment . Objective The objective of this study was to evaluate the effectiveness and tolerability of tapentadol PR ( 50–250 mg twice daily ) after direct rotation from World Health Organization ( WHO ) step III opioids in patients with severe osteoarthritis knee pain who previously responded to WHO step III therapy but showed poor tolerability . Methods This open-label , phase 3b study ( NCT00982280 ) was conducted from October 2009 through June 2010 ( prematurely terminated due to slow recruitment and study drug shortages ) in clinical care setting s in Europe and Australia . The study population included patients with severe , chronic osteoarthritis knee pain who had taken WHO step III opioids daily for ≥2 weeks before screening , responded to therapy ( average pain intensity [ 11-point numerical rating scale-3 ( NRS-3 ) ] ≤5 at screening ) , and reported opioid-related adverse effects  as their reason for changing analgesics . Patients switched directly from WHO step III therapy to tapentadol . Patients received oral tapentadol PR ( 50–250 mg twice daily ) during 5-week titration and 7-week maintenance periods . Oral tapentadol immediate release ( IR ) was permitted ( ≤twice/day , ≥4 h apart ) for acute pain episodes due to index pain or withdrawal symptoms following discontinuation of previous opioids ( combined dose of tapentadol [ PR and IR ] ≤500 mg/day ) . This study was planned to evaluate conversion  to tapentadol PR , based on responder rate 1 ( percentage of patients with same/less pain [ NRS-3 ] versus Week −1 ) at Week 6 ( primary endpoint ) , adverse events ( AEs ) , and discontinuation rates . Equianalgesic ratios were calculated for tapentadol prior to WHO step III opioids ( PR and PR plus IR formulations ) . Results Of 82 patients enrolled , 63 received study medication . In the per- protocol population , responder rate 1 at Week 6 ( last observation carried forward ) was 94.3 % ( 50/53 ; P < 0.0001 vs. the null hypothesis rate [ < 60 % ] ) . Mean ( st and ard deviation ) pain intensity scores were 4.7 ( 0.66 ) at baseline , 2.5 ( 1.46 ) at Week 6 , and 1.8 ( 1.41 ) at Week 12 in the main analysis population ( change from baseline at Weeks 6 and 12 , P < 0.0001 ) . Tapentadol to transdermal buprenorphine equianalgesic ratios ( PR [ n = 48 ] , 262.9:1 ; PR plus IR [ n = 48 ] , 281.1:1 ) and tapentadol to oral oxycodone equianalgesic ratios ( PR [ n = 4 ] , 4.3:1 ; PR plus IR [ n = 6 ] , 4.6:1 ) were calculated for the main analysis population . In the safety population , prevalence of AEs reported as associated with prior opioids at Week −1 ( reasons for rotation ) and related to tapentadol treatment at Week 12 decreased over time ; the most common were nausea ( 46.0 vs. 24.1 % ) and constipation ( 31.7 vs. 7.4 % ) . Overall , 14.3 % of patients discontinued the study early ; reasons included AEs ( 9.5 % ) , lack of efficacy ( 3.2 % ) , and withdrawal of consent ( 1.6 % ) . Conclusions Significant improvements in effectiveness were observed for tapentadol PR ( 50–250 mg twice daily ) versus WHO step III opioids in patients with severe , chronic osteoarthritis knee pain who previously responded to WHO step III therapy . Equianalgesic ratios were calculated for tapentadol to transdermal buprenorphine and oral oxycodone and were in line with observations from previous phase 3 studies Abstract Objective : To determine the efficacy , tolerability , and safety of duloxetine when added to oral nonsteroidal anti-inflammatory drugs ( NSAIDs ) in patients with osteoarthritis ( OA ) of the knee with pain of moderate or greater severity . Research design and methods : This was a 10-week r and omized , double-blind , flexible-dose ( duloxetine 60/120 mg/day ) , placebo-controlled trial that enrolled adult out patients who had persistent moderate pain ( ≥4 on a 0–10 numerical rating scale ) due to OA of the knee , despite , per protocol , having received optimized oral NSAID therapy  ( specific drug , dose , and frequency at investigator discretion ) . Clinical trials registration : Trial registration : Clinical Trials.gov identifier : NCT01018680 . Main outcome measure : Patients entered daily pain ratings in a telephone-based diary . The primary efficacy outcome was the weekly mean of the daily average pain rating at week 8 . Safety outcomes were assessed during the entire 10-week study . Results : A total of 524 patients r and omly received duloxetine 60/120 mg/day ( N = 264 ) or placebo ( N = 260 ) . In total , 74 % of the patients completed the study . Mean age was 61 years ( SD 9.2 ) , 57 % were female , and 81 % were white .  Duloxetine-treated patients had significantly greater pain reduction at week 8 ( p < 0.001 ) than placebo-treated patients . In addition , relative to placebo at week 8 , duloxetine-treated patients had significant improvements in physical function as measured by the Western Ontario and McMaster Universities Osteoarthritis Index ( p < 0.001 ) , and Patient Global Impression of Improvement ( p < 0.001 ) . Compared to placebo , significantly more nausea , dry mouth , constipation , fatigue and decreased appetite were reported by patients taking duloxetine ( each p < 0.05 ) . Discontinuation due to adverse events occurred more commonly in the duloxetine group than the placebo group ( p = 0.03 ) . Conclusion : Duloxetine added to oral NSAID therapy provided additional significant pain reduction , improved function , and patient-rated impression of improvement . Adverse events were consistent with those seen in previous duloxetine trials . The short duration of the study may not reflect the longer term efficacy and safety of NSAID/duloxetine cotherapy OBJECTIVE To evaluate the efficacy and safety of duloxetine in the treatment of chronic pain due to osteoarthritis of the knee . METHODS This was a 13-week , r and omized , double-blind , placebo-controlled trial in patients meeting American College of Rheumatology clinical and radiographic criteria for osteoarthritis of the knee . At baseline , patients were required to have a ≥ 4 weekly mean of the 24-hour average pain ratings . Patients were r and omized to either duloxetine 60 mg once daily ( QD ) or placebo . At week 7 , the duloxetine dosage was increased , in a blinded fashion , to 120-mg QD in patients reporting < 30 % pain reduction . The primary efficacy measure was Brief Pain Inventory ( BPI ) 24-hour average pain . Secondary efficacy measures included Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) ; Clinical Global Impressions of Severity ( CGI-S ) . Safety and tolerability was also assessed . RESULTS Of the total ( n = 256 ) patients , 111 ( 86.7 % ) in placebo group and 93 ( 72.7 % ) in duloxetine group completed the study . Patients treated with duloxetine had significantly ( P ≤ 0.001 ) greater improvement at all time points on BPI average pain and had significantly greater improvement on BPI pain severity ratings ( P ≤ 0.05 ) , WOMAC total ( P = 0.044 ) and physical functioning scores ( P = 0.016 ) , and CGI-S ( P = 0.009 ) at the study endpoint . Frequency of treatment-emergent nausea , constipation , and hyperhidrosis were significantly higher in the duloxetine group ( P ≤ 0.05 ) . Significantly more duloxetine-treated patients discontinued the trial because of adverse events ( P = 0.002 ) . CONCLUSIONS Treatment with duloxetine 60 mg to 120 mg QD was associated with significant pain reduction and improved function in patients with pain due to osteoarthritis of the knee 
    Output:
    