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: OBJECTIVE The combination of chronic musculoskeletal pain and depression is associated with worse clinical outcomes than either condition alone . In this study , we report the predictors of pain intensity and activity interference in primary care patients with co-morbid pain and depression . METHODS This is a secondary data analysis of the 250 persons who participated in a r and omized clinical trial design ed to test the effectiveness of 12 weeks of optimized antidepressant therapy for both depression and pain . Using multivariate linear regression analysis , we assessed the predictive value of baseline  self-efficacy , fear of movement , pain  beliefs  , and demographic and clinical factors on 3-month Grade d Chronic Pain Scale pain intensity and activity interference outcomes . RESULTS In the full model , significant sociodemographic predictors of less activity interference included being non-white ( beta-5.8 , P = 0.04 ) and being employed ( beta-13.3 , P < 0.0001 ) . The latter was also predictive of less pain intensity ( beta-5.6 , P = 0.01 ) . As expected , the optimized antidepressant treatment arm was associated with improved outcomes ( pain intensity : beta-3.7 , P = 0.0005 and activity interference : beta-6.4 , P = 0.01 ) . Whereas stronger perceived pain control ( beta 3.6 , P = 0.01 ) was associated with greater activity interference , higher degree of fear of movement ( or fear avoidance ) predicted greater pain intensity ( beta 0.46 , P = 0.04 ) and activity interference ( beta 0.57 , P = 0.05 ) . Neither the location ( low back vs hip/knee ) nor duration of pain were predictive of pain intensity or interference outcomes . CONCLUSION The findings are consistent with a bio-psychosocial model , implicating the need to consider the impact of sociodemographic variables and pain-related beliefs and cognition on pain-related outcomes for patients with co-morbid musculoskeletal pain and depression Objective To assess the effect of lateral wedge insoles compared with flat control insoles on improving symptoms and slowing structural disease progression in medial knee osteoarthritis . Design R and omised controlled trial . Setting Community in Melbourne , Australia . Participants 200 people aged 50 or more with clinical and radiographic diagnosis of mild to moderately severe medial knee osteoarthritis . Interventions Full length 5 degree lateral wedged insoles or flat control insoles worn inside the shoes daily for 12 months . Main outcome measures Primary symptomatic outcome was change in overall knee pain ( past week ) measured on an 11 point numerical rating scale . Primary structural outcome was change in volume of medial tibial cartilage from magnetic resonance imaging scans . Secondary clinical outcomes included changes in measures of pain , function , stiffness , and health related quality of life . Secondary structural outcomes included progression of medial cartilage defects and bone marrow lesions . Results Between group differences did not differ significantly for the primary outcomes of change in overall pain ( −0.3 points , 95 % confidence intervals −1.0 to 0.3 ) and change in medial tibial cartilage volume ( −0.4 mm3 , 95 % confidence interval −15.4 to 14.6 ) , and confidence intervals did not include minimal clinical ly important differences . None of the changes in secondary outcomes showed differences between groups . Conclusion Lateral wedge insoles worn for 12 months provided no symptomatic or structural benefits compared with flat control insoles . Trial registration Australian New Zeal and Clinical Trials Registry ACTR12605000503628 and Clinical Trials.gov NCT00415259 OBJECTIVES To determine the effect of newly developed knee pain on general health and physical function of people > or=50 yrs living in the community . METHODS Prospect i ve cohort study of 3907 people aged 50 + registered with three general practice s in North Staffordshire , in the UK . The main outcome measures were self-reported knee pain ; general health and physical function as measured by the Short Form 36 ( SF-36 ) . RESULTS Of those with no knee pain at baseline , 24 % ( n = 501 ) reported it at follow-up . There was a steep decline in physical function in this group ( mean fall in SF-36 score at follow-up 10.3 points ) compared with the 1558 persons who had no knee pain at baseline or follow-up ( mean fall 3.3 ) . Those with knee pain at baseline whose pain had resolved at 3-yr follow-up ( n = 409 ) showed only minor improvements in physical functioning scores at follow-up ( mean improvement -1.3 ) . CONCLUSIONS The onset of knee pain is associated with a substantial and persistent reduction of physical function in older adults living in the community . Since knee pain is common , and reduced physical function in mid to older ages is a strong predictor of future disability and dependency , effective prevention or early treatment of knee pain at these ages is likely to have a major influence on healthy ageing in the population BACKGROUND pain is the leading symptom of osteoarthritis ( OA ) and is often chronic in nature , leading to significant morbidity and decreased quality of life . Duloxetine , a selective serotonin norepinephrine reuptake inhibitor has been demonstrated to have a central ly acting analgesic effect . OBJECTIVES the aim of the present study was to investigate the efficacy of duloxetine in reducing pain in older adults with knee OA . METHODS totally , 288 patients aged 65 years and above with primary knee OA were enrolled in this study . Patients were r and omised 1:1 . Totally , 144 received 60 mg/day of duloxetine HCL and 144 received placebo for 16 weeks . Outcome measures included pain reduction and improvement in physical functioning scores . Pain was assessed using the visual analogue pain scale ( VAS ; 0 - 100 mm ) . The Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) scores were used to assess function . RESULTS two-hundred and seventy four of the 288 patients completed the study . There was a statistically significant reduction in pain and a significant improvement in WOMAC scores at 16 weeks in the duloxetine group versus the placebo group . No serious side effects were reported . CONCLUSIONS the findings of the present study provide evidence for the efficacy and tolerability of duloxetine in reducing pain and subsequently improving function in older adults with knee OA . TRIAL REGISTRATION NCT01425827 QUESTIONS Does the PEDro scale measure only one construct ie , the method ological quality of clinical trials ? What is the hierarchy of items of the PEDro scale from least to most adhered to ? Is there any effect of year of publication of trials on item adherence ? Are PEDro scale ordinal scores equivalent to interval data ? DESIGN Rasch analysis of two independent sample s of 100 clinical trials from the PEDro data base scored using the PEDro scale . RESULTS Both sample s of PEDro data showed fit to the Rasch model with no item misfit . The  PEDro scale item hierarchy was the same in both sample s , ranging from the most adhered to item r and om allocation , to the least adhered to item therapist blinding . There was no differential item functioning by year of publication . Original PEDro ordinal scores were highly correlated with transformed PEDro interval scores ( r = 0.99 ) . CONCLUSION The PEDro scale is a valid measure of the method ological quality of clinical trials . It is valid to sum PEDro scale item scores to obtain a total score that can be treated as interval level measurement and subjected to parametric statistical analysis UNLABELLED Osteoarthritis pain is a significant problem for our aging population . Antidepressants that are serotonin-norepinephrine reuptake inhibitors are effective for other forms of chronic pain and may provide a new treatment option for osteoarthritis pain . We performed a single-blind , placebo run-in trial of 60 to 90 mg of duloxetine in 25 subjects with activity-limiting osteoarthritis pain . Each subject received 2 weeks of placebo followed by 10 weeks of duloxetine . The primary outcome was reduction in average pain intensity between 2 and 12 weeks for subjects completing the trial . Average pain on the Brief Pain Inventory ( BPI ) was 5.7 at baseline , 4.8 after the 2-week placebo run-in , and 3.5 at 12 weeks for the 17 patients completing the trial ( 28 % decrease between 2 and 12 weeks , P = .122 ) . Eight of 15 study completers who had nonmissing BPI results ( 53 % ) reported at least 30 % pain reduction between weeks 2 and 12 . The Western Ontario McMaster Osteoarthritis Index ( WOMAC ) pain score at baseline was 2.3 , 1.8 after 2 weeks , and 1.3 after 12 weeks ( 30 % decrease between 2 and 12 weeks , P = .018 ) . Ten of 17 patients ( 59 % ) reported at least 30 % pain relief between weeks 2 and 12 on the WOMAC . Significant improvements in self-reported physical and role function were reported but observed physical function did not improve . PERSPECTIVE Duloxetine did not significantly reduce pain intensity on the BPI but did improve pain intensity and self-reported function on the WOMAC . Duloxetine warrants further investigation as a novel treatment for osteoarthritis pain OBJECTIVE To investigate the relationship between anxiety and depression and reporting of knee pain in the community . METHODS Subjects ( n = 374 ) were community volunteers aged 40 years and above who are participants in the Baltimore Longitudinal Study of Aging , a prospect i ve multidisciplinary research study of normative aging . Knee pain was defined by the First National Health and Nutrition Examination Survey question " have you ever had pain in or around your knee on most days for at least one month ? " ; anxiety and depression were measured by the relevant subscales of the Arthritis Impact Measurement Scales question naire . All subjects had st and ing anteroposterior radiographs  , read for Kellgren and Lawrence ( K + L ) grade . RESULTS After adjustment for age , women reporting " ever " knee pain had significantly higher anxiety scores than those reporting " never " pain ( 3.06 + /- 0.26 versus 2.35 + /- 0.17 ; P = 0.025 ) . Pain reporting was related neither to anxiety scores in men , nor to depression in either sex . Analysis stratified by radiographic severity , adjusted for age and gender , showed that differences in anxiety were confined to those reporting knee pain in the absence of radiographic change ( i.e. , K + L grade 0 ) . CONCLUSIONS In the community , women reporting knee pain in the absence of radiographic osteoarthritis have higher anxiety scores than those without pain . Depression was not significantly related to knee pain in this population . Psychosocial factors may explain some of the discrepancy between reported knee pain and structural change as seen on x-ray UNLABELLED Pain and depression are the most prevalent physical and psychological symptom-based disorders , respectively , and co-occur 30 to 50 % of the time . However , their reciprocal relationship and potentially causative effects on one another have been inadequately studied . Longitudinal data analysis involving 500 primary care patients with persistent back , hip , or knee pain were enrolled in the Stepped Care for Affective Disorders and Musculoskeletal Pain ( SCAMP ) study . Half of the participants had comorbid depression and were r and omized to a stepped care intervention ( n = 123 ) or treatment as usual ( n = 127 ) . Another 250 nondepressed patients with similar pain were followed in a parallel cohort . Outcomes were assessed at baseline , 3 , 6 , and 12 months . Mixed effects model repeated measures ( MMRM ) multivariable analyses were conducted to determine if change in pain severity predicted subsequent depression severity , and vice versa . Change in pain was a strong predictor of subsequent depression severity ( t-value = 6.63 , P < .0001 ) . Likewise , change in depression severity was an equally strong predictor of subsequent pain severity ( t-value = 7.28 , P < .0001 ) . Results from the full cohort were similar in the clinical trial subgroup . In summary , pain and depression have strong and similar effects on one another when assessed longitudinally over 12 months . PERSPECTIVE This study strengthens the evidence for a bidirectional and potentially causative influence of pain and depression on one another . A change in severity of either symptom predicts subsequent severity of the other symptom . Thus , recognition and management of both conditions may be warranted , particularly when treatment focused on 1 condition is not leading to an optimal response BACKGROUND Previous cross-sectional studies have shown an association between pain and depression , but it is unclear which comes first . Our objectives were to determine the temporal relationship between pain and depression , and to investigate whether these two syndromes share predictors . METHODS A 2-year , population -based , prospect i ve , observational study of 3654 older adults aged 65 and above selected from the English Longitudinal Study of Ageing Waves 1 and 2 .  Pain , 8-item CES-D , socio-economic variables , health indicators , and social support were assessed . RESULTS Logistic regression analyses revealed that pain at baseline was an independent predictor of becoming depressed 2 years later and depression at baseline was a predictor of developing pain at 2 years . Individuals with mobility disability and poor sight were at risk of becoming depressed as well as developing pain . Moreover , older age , poor sight and mobility disability were common predict 
    Output:
    
agent
We found a strong level of evidence for a relationship between depression and knee pain , limited evidence for no relationship between anxiety and knee pain , and minimal evidence for no relationship between poor mental health and knee pain .
Conclusions Despite the heterogeneity of the included studies , these data show that depression plays a significant role in knee pain , and that a biopsychosocial approach to the management of this condition is integral to optimising outcomes for knee pain
***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: OBJECTIVE The combination of chronic musculoskeletal pain and depression is associated with worse clinical outcomes than either condition alone . In this study , we report the predictors of pain intensity and activity interference in primary care patients with co-morbid pain and depression . METHODS This is a secondary data analysis of the 250 persons who participated in a r and omized clinical trial design ed to test the effectiveness of 12 weeks of optimized antidepressant therapy for both depression and pain . Using multivariate linear regression analysis , we assessed the predictive value of baseline  self-efficacy , fear of movement , pain  beliefs  , and demographic and clinical factors on 3-month Grade d Chronic Pain Scale pain intensity and activity interference outcomes . RESULTS In the full model , significant sociodemographic predictors of less activity interference included being non-white ( beta-5.8 , P = 0.04 ) and being employed ( beta-13.3 , P < 0.0001 ) . The latter was also predictive of less pain intensity ( beta-5.6 , P = 0.01 ) . As expected , the optimized antidepressant treatment arm was associated with improved outcomes ( pain intensity : beta-3.7 , P = 0.0005 and activity interference : beta-6.4 , P = 0.01 ) . Whereas stronger perceived pain control ( beta 3.6 , P = 0.01 ) was associated with greater activity interference , higher degree of fear of movement ( or fear avoidance ) predicted greater pain intensity ( beta 0.46 , P = 0.04 ) and activity interference ( beta 0.57 , P = 0.05 ) . Neither the location ( low back vs hip/knee ) nor duration of pain were predictive of pain intensity or interference outcomes . CONCLUSION The findings are consistent with a bio-psychosocial model , implicating the need to consider the impact of sociodemographic variables and pain-related beliefs and cognition on pain-related outcomes for patients with co-morbid musculoskeletal pain and depression Objective To assess the effect of lateral wedge insoles compared with flat control insoles on improving symptoms and slowing structural disease progression in medial knee osteoarthritis . Design R and omised controlled trial . Setting Community in Melbourne , Australia . Participants 200 people aged 50 or more with clinical and radiographic diagnosis of mild to moderately severe medial knee osteoarthritis . Interventions Full length 5 degree lateral wedged insoles or flat control insoles worn inside the shoes daily for 12 months . Main outcome measures Primary symptomatic outcome was change in overall knee pain ( past week ) measured on an 11 point numerical rating scale . Primary structural outcome was change in volume of medial tibial cartilage from magnetic resonance imaging scans . Secondary clinical outcomes included changes in measures of pain , function , stiffness , and health related quality of life . Secondary structural outcomes included progression of medial cartilage defects and bone marrow lesions . Results Between group differences did not differ significantly for the primary outcomes of change in overall pain ( −0.3 points , 95 % confidence intervals −1.0 to 0.3 ) and change in medial tibial cartilage volume ( −0.4 mm3 , 95 % confidence interval −15.4 to 14.6 ) , and confidence intervals did not include minimal clinical ly important differences . None of the changes in secondary outcomes showed differences between groups . Conclusion Lateral wedge insoles worn for 12 months provided no symptomatic or structural benefits compared with flat control insoles . Trial registration Australian New Zeal and Clinical Trials Registry ACTR12605000503628 and Clinical Trials.gov NCT00415259 OBJECTIVES To determine the effect of newly developed knee pain on general health and physical function of people > or=50 yrs living in the community . METHODS Prospect i ve cohort study of 3907 people aged 50 + registered with three general practice s in North Staffordshire , in the UK . The main outcome measures were self-reported knee pain ; general health and physical function as measured by the Short Form 36 ( SF-36 ) . RESULTS Of those with no knee pain at baseline , 24 % ( n = 501 ) reported it at follow-up . There was a steep decline in physical function in this group ( mean fall in SF-36 score at follow-up 10.3 points ) compared with the 1558 persons who had no knee pain at baseline or follow-up ( mean fall 3.3 ) . Those with knee pain at baseline whose pain had resolved at 3-yr follow-up ( n = 409 ) showed only minor improvements in physical functioning scores at follow-up ( mean improvement -1.3 ) . CONCLUSIONS The onset of knee pain is associated with a substantial and persistent reduction of physical function in older adults living in the community . Since knee pain is common , and reduced physical function in mid to older ages is a strong predictor of future disability and dependency , effective prevention or early treatment of knee pain at these ages is likely to have a major influence on healthy ageing in the population BACKGROUND pain is the leading symptom of osteoarthritis ( OA ) and is often chronic in nature , leading to significant morbidity and decreased quality of life . Duloxetine , a selective serotonin norepinephrine reuptake inhibitor has been demonstrated to have a central ly acting analgesic effect . OBJECTIVES the aim of the present study was to investigate the efficacy of duloxetine in reducing pain in older adults with knee OA . METHODS totally , 288 patients aged 65 years and above with primary knee OA were enrolled in this study . Patients were r and omised 1:1 . Totally , 144 received 60 mg/day of duloxetine HCL and 144 received placebo for 16 weeks . Outcome measures included pain reduction and improvement in physical functioning scores . Pain was assessed using the visual analogue pain scale ( VAS ; 0 - 100 mm ) . The Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) scores were used to assess function . RESULTS two-hundred and seventy four of the 288 patients completed the study . There was a statistically significant reduction in pain and a significant improvement in WOMAC scores at 16 weeks in the duloxetine group versus the placebo group . No serious side effects were reported . CONCLUSIONS the findings of the present study provide evidence for the efficacy and tolerability of duloxetine in reducing pain and subsequently improving function in older adults with knee OA . TRIAL REGISTRATION NCT01425827 QUESTIONS Does the PEDro scale measure only one construct ie , the method ological quality of clinical trials ? What is the hierarchy of items of the PEDro scale from least to most adhered to ? Is there any effect of year of publication of trials on item adherence ? Are PEDro scale ordinal scores equivalent to interval data ? DESIGN Rasch analysis of two independent sample s of 100 clinical trials from the PEDro data base scored using the PEDro scale . RESULTS Both sample s of PEDro data showed fit to the Rasch model with no item misfit . The  PEDro scale item hierarchy was the same in both sample s , ranging from the most adhered to item r and om allocation , to the least adhered to item therapist blinding . There was no differential item functioning by year of publication . Original PEDro ordinal scores were highly correlated with transformed PEDro interval scores ( r = 0.99 ) . CONCLUSION The PEDro scale is a valid measure of the method ological quality of clinical trials . It is valid to sum PEDro scale item scores to obtain a total score that can be treated as interval level measurement and subjected to parametric statistical analysis UNLABELLED Osteoarthritis pain is a significant problem for our aging population . Antidepressants that are serotonin-norepinephrine reuptake inhibitors are effective for other forms of chronic pain and may provide a new treatment option for osteoarthritis pain . We performed a single-blind , placebo run-in trial of 60 to 90 mg of duloxetine in 25 subjects with activity-limiting osteoarthritis pain . Each subject received 2 weeks of placebo followed by 10 weeks of duloxetine . The primary outcome was reduction in average pain intensity between 2 and 12 weeks for subjects completing the trial . Average pain on the Brief Pain Inventory ( BPI ) was 5.7 at baseline , 4.8 after the 2-week placebo run-in , and 3.5 at 12 weeks for the 17 patients completing the trial ( 28 % decrease between 2 and 12 weeks , P = .122 ) . Eight of 15 study completers who had nonmissing BPI results ( 53 % ) reported at least 30 % pain reduction between weeks 2 and 12 . The Western Ontario McMaster Osteoarthritis Index ( WOMAC ) pain score at baseline was 2.3 , 1.8 after 2 weeks , and 1.3 after 12 weeks ( 30 % decrease between 2 and 12 weeks , P = .018 ) . Ten of 17 patients ( 59 % ) reported at least 30 % pain relief between weeks 2 and 12 on the WOMAC . Significant improvements in self-reported physical and role function were reported but observed physical function did not improve . PERSPECTIVE Duloxetine did not significantly reduce pain intensity on the BPI but did improve pain intensity and self-reported function on the WOMAC . Duloxetine warrants further investigation as a novel treatment for osteoarthritis pain OBJECTIVE To investigate the relationship between anxiety and depression and reporting of knee pain in the community . METHODS Subjects ( n = 374 ) were community volunteers aged 40 years and above who are participants in the Baltimore Longitudinal Study of Aging , a prospect i ve multidisciplinary research study of normative aging . Knee pain was defined by the First National Health and Nutrition Examination Survey question " have you ever had pain in or around your knee on most days for at least one month ? " ; anxiety and depression were measured by the relevant subscales of the Arthritis Impact Measurement Scales question naire . All subjects had st and ing anteroposterior radiographs  , read for Kellgren and Lawrence ( K + L ) grade . RESULTS After adjustment for age , women reporting " ever " knee pain had significantly higher anxiety scores than those reporting " never " pain ( 3.06 + /- 0.26 versus 2.35 + /- 0.17 ; P = 0.025 ) . Pain reporting was related neither to anxiety scores in men , nor to depression in either sex . Analysis stratified by radiographic severity , adjusted for age and gender , showed that differences in anxiety were confined to those reporting knee pain in the absence of radiographic change ( i.e. , K + L grade 0 ) . CONCLUSIONS In the community , women reporting knee pain in the absence of radiographic osteoarthritis have higher anxiety scores than those without pain . Depression was not significantly related to knee pain in this population . Psychosocial factors may explain some of the discrepancy between reported knee pain and structural change as seen on x-ray UNLABELLED Pain and depression are the most prevalent physical and psychological symptom-based disorders , respectively , and co-occur 30 to 50 % of the time . However , their reciprocal relationship and potentially causative effects on one another have been inadequately studied . Longitudinal data analysis involving 500 primary care patients with persistent back , hip , or knee pain were enrolled in the Stepped Care for Affective Disorders and Musculoskeletal Pain ( SCAMP ) study . Half of the participants had comorbid depression and were r and omized to a stepped care intervention ( n = 123 ) or treatment as usual ( n = 127 ) . Another 250 nondepressed patients with similar pain were followed in a parallel cohort . Outcomes were assessed at baseline , 3 , 6 , and 12 months . Mixed effects model repeated measures ( MMRM ) multivariable analyses were conducted to determine if change in pain severity predicted subsequent depression severity , and vice versa . Change in pain was a strong predictor of subsequent depression severity ( t-value = 6.63 , P < .0001 ) . Likewise , change in depression severity was an equally strong predictor of subsequent pain severity ( t-value = 7.28 , P < .0001 ) . Results from the full cohort were similar in the clinical trial subgroup . In summary , pain and depression have strong and similar effects on one another when assessed longitudinally over 12 months . PERSPECTIVE This study strengthens the evidence for a bidirectional and potentially causative influence of pain and depression on one another . A change in severity of either symptom predicts subsequent severity of the other symptom . Thus , recognition and management of both conditions may be warranted , particularly when treatment focused on 1 condition is not leading to an optimal response BACKGROUND Previous cross-sectional studies have shown an association between pain and depression , but it is unclear which comes first . Our objectives were to determine the temporal relationship between pain and depression , and to investigate whether these two syndromes share predictors . METHODS A 2-year , population -based , prospect i ve , observational study of 3654 older adults aged 65 and above selected from the English Longitudinal Study of Ageing Waves 1 and 2 .  Pain , 8-item CES-D , socio-economic variables , health indicators , and social support were assessed . RESULTS Logistic regression analyses revealed that pain at baseline was an independent predictor of becoming depressed 2 years later and depression at baseline was a predictor of developing pain at 2 years . Individuals with mobility disability and poor sight were at risk of becoming depressed as well as developing pain . Moreover , older age , poor sight and mobility disability were common predict 
    Output:
    