***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: In a highly influential paper , Baron and Kenny ( 1986 ) proposed a statistical procedure to conduct a causal mediation analysis and identify possible causal mechanisms . This procedure has been widely used across many branches of the social and medical sciences and especially in psychology and epidemiology . However , one major limitation of this approach is that it is based on a set of linear regressions and can not be easily extended to more complex situations that are frequently encountered in applied research . In this paper , we propose an approach that generalizes the Baron-Kenny procedure . Our method can accommo date linear and nonlinear relationships , parametric and nonparametric models , continuous and discrete mediators , and various types of outcome variables . We also provide a formal statistical justification for the proposed generalization of the Baron-Kenny procedure by placing causal mediation analysis within the widely-accepted counterfactual framework of causal inference . Finally , we develop a set of sensitivity analyses that allow applied research ers to quantify the robustness of their empirical conclusions . Such sensitivity analysis is important because as we show the Baron-Kenny procedure and our generalization of it rest on a strong and untestable assumption even in r and omized experiments . We illustrate the proposed methods by applying them to a r and omized field experiment , the Job Search Intervention Study ( JOBS II ) . We also offer easy-to-use software that implements all of our proposed methods Background The contribution of kinesiophobia ( fear of movement ) to the pain experience among older adults has been poorly evaluated . The aim of this study was to study prevalence at baseline , development over a 12-month period and cognitive-affective variables of kinesiophobia in a population -based sample of older adults with chronic pain . Methods The study included 433 older adults ( + 65 years ) with chronic pain ( mean age 74.8 years ) r and omly selected using a Swedish register of inhabitants .  Kinesiophobia  was measured at baseline and 12-month follow-up with the 11-item version of the Tampa Scale of Kinesiophobia ( TSK-11 ) . Associations of demographic- , cognitive affective - and pain-related variables to kinesiophobia were analysed with linear regression analyses . Results The mean level of kinesiophobia was low . Worsening and recovering from kinesiophobia occurred over time , but the mean level of kinesiophobia remained unchanged ( p = 0.972 ) . High levels of kinesiophobia ( TSK ≥35 ) were found among frailer and older adults predominately living in care homes , but not dependent on sex . Poor self-perceived health ( OR = 8.84 ) and high pain intensity ( OR = 1.22 ) were significantly associated with kinesiophobia . Conclusion Results indicate that potential interventions regarding kinesiophobia among older adults should aim to decrease pain intensity and strengthen health beliefs Objective : To identify predictors of pain and disability in knee osteoarthritis . Design : A one-year prospect i ve analysis of determinants of pain and functioning in knee osteoarthritis . Study setting : Primary care providers in a medium-sized city . Patients : A total of 111 patients aged from 35 to 75 with clinical symptoms and radiographic grading ( Kellgren-Lawrence 2–4 ) of knee osteoarthritis who participated in a r and omized controlled trial . Main measures : The outcome measures were self-reported pain and function , which were recorded at 0 , 3 and 12 months . Disease-specific pain and functioning were assessed using the pain and function subscales of the Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index . Generic physical and mental functioning were assessed using the R AND -36 subscales for function , and physical and mental component summary scores . Possible baseline predictors for these outcomes were 1 ) demographic , socioeconomic and disease-related variables , and 2 ) psychological measures of re sources , distress , fear of movement and catastrophizing . Results : Multivariate linear mixed model analyses revealed that normal mood at baseline measured with the Beck Anxiety Inventory predicted significantly better results in all measures of pain ( WOMAC P=0.02 ) and function ( WOMAC P=0.002 , R AND -36 P=0.002 ) during the one-year follow-up . Psychological re source factors ( pain self-efficacy P=0.012 , satisfaction with life P=0.002 ) predicted better function ( R AND -36 ) . Pain catastrophizing predicted higher WOMAC pain levels ( P=0.013 ) , whereas fear of movement ( kinesiophobia ) predicted poorer functioning ( WOMAC P=0.046 , R AND -36 P=0.024 ) . Conclusions : Multiple psychological factors in people with knee osteoarthritis pain are associated with the development of disability and longer term worse pain Study Design . Validation of 2 self-report question naires . Objective . To evaluate the internal consistency , reliability , and construct validity of the Persian versions of the fear avoidance beliefs question naire ( FABQ ) and the Tampa Scale of Kinesiophobia ( TSK ) in patients with acute and chronic neck pain . Summary of Background Data . The FABQ and TSK are 2 important measures to evaluate fear of pain and fear avoidance beliefs in patients with spinal pain . To date , the psychometric properties of these question naires have not been demonstrated in Persian-speaking patients with neck pain in Iran . Methods . One hundred sixty-six patients with acute and chronic neck pain participated in the study . The construct validity of the question naires was evaluated by measuring convergent and known-groups validity . The visual analogue scale measure of pain , neck disability index , hospital anxiety and depression scale , and the physical ( PCS-12 ) and mental ( MCS-12 ) summary scores of the Short Form health survey ( SF-12 ) were used to test construct validity of the Persian FABQ and TSK . In addition , 50 r and omly selected patients with chronic neck pain were asked to complete the question naires 48 hours later for the second time . Results . Cronbach & agr ; coefficient for the FABQ and TSK in patients with acute and chronic pain was in the range from 0.77 to 0.92 and 0.77 to 0.78 , respectively . The Persian FABQ and TSK showed satisfactory test-retest reliability with intraclass correlation coefficient of more than 0.80 . There were moderate to strong correlations between the Persian FABQ and TSK scores and the neck disability index ( r = 0.44–0.55 ) , Depression subscales of the hospital anxiety and depression scale ( r = 0.42–0.48 ) , and PCS-12 ( r = −0.34 to −0.62 ) . Conclusion . The Persian FABQ and TSK have acceptable reliability and validity for measuring pain related fear and avoidance beliefs among Persian-speaking patients with acute and chronic neck pain . However , considering the study limitations , the findings should be interpreted with caution . Level of Evidence : Study Design . A prospect i ve cross-sectional design . Objective . The objectives were to describe the occurrence and to investigate the association of the  fear-avoidance model variables ( pain intensity , kinesiophobia , depression , and disability ) in patients with specific or nonspecific chronic low back pain ( CLBP ) . Summary of Background Data . Affective factors , particularly fear , have proven to be central in the explanation and underst and ing of chronic pain . The fear-avoidance model has shown that fearful patients with CLBP are at risk of becoming trapped in a vicious cycle of pain , fear , disability , and depressive symptoms . Little is known about the relationship between these factors in patients subgrouped as specific or nonspecific CLBP . Methods . All 147 patients ( 81 women and 66 men ) were examined by an orthopedic surgeon and diagnosed as either specific or nonspecific CLBP on the basis of that examination .  Hierarchical multiple regression analysis was used to assess the ability of three independent variables  ( back pain intensity , VAS ; kinesiophobia , TSK ; depressed mood , Zung ) to predict levels of disability after controlling for the influence of age and sex . Results . Both groups ( specific and nonspecific CLBP ) presented elevated values on the fear-avoidance model variables . All the independent fear-avoidance variables contributed in a statistically significant manner to predict disability in patients with specific CLBP , 67.0 % , F ( 5 , 59 ) = 24.46 , P < 0.000 . In patients with nonspecific CLBP , all variables except kinesiophobia predicted disability in a statistically significant manner , 63.0 % , F ( 5 , 59 ) = 22.64 , P < 0.000 . Conclusion . We conclude that persistent musculoskeletal pain affects the individual in a similar manner , regardless of the cause of the pain . In clinical terms , this means that pain must be analyzed and treated as a parallel process to search ing for the cause of the pain Objective The influence of physical and psychosocial variables on self-rated disability in patients with chronic mechanical neck pain has not been fully determined . This study examined the relationship of pain , physical impairment , and pain-related fear to disability in individuals with chronic mechanical neck pain . Design A cross-sectional study was conducted . Ninety-seven ( n = 97 ) subjects ( 28 men , 69 women ; mean age , 39.3 yrs ) with chronic mechanical neck pain were prospect ively recruited .  Demographic information , duration of pain symptoms , pain intensity , pain-related fear , and cervical range of motion  were collected on all subjects . Self-reported disability was measured with the Neck Disability Index . Correlation and regression analyses were performed to determine the association among the variables and to determine the proportions of explained variance in disability . Results Significant positive correlations existed between disability and previous history of neck pain ( r = 0.45 ; P < 0.001 ) , disability and pain intensity ( r = 0.32 , P = 0.01 ) , and disability and kinesiophobia ( r = 0.23 , P = 0.02 ) . In addition , a significant negative correlation existed between disability and cervical extension range of motion ( r = −0.18 , P = 0.04 ) . Stepwise regression analyses revealed that previous neck pain episodes , intensity of neck pain , kinesiophobia , and cervical extension range of motion were significant predictors of disability ( r 2 = 0.400 ; r 2 adjusted = 0.372 ; F = 14.64 ; P < 0.001 ) . Conclusions This study found that previous episodes of neck pain , pain intensity , pain-related fear , and cervical extension range of motion explained 37.2 % of the variability of self-report disability . Future longitudinal studies will help to determine the clinical implication s of these findings Background Knee osteoarthritis ( OA ) is the most common type of arthritis and imposes a heavy burden on individual welfare among elderly people . There is preliminary evidence that psychological factors play a role in functional ability and pain in knee OA patients , particularly with respect to the surgery outcome . Less is known about psychological factors among community-dwelling patients with knee OA . Objectives We aim ed to determine which psychological factors are associated with pain and functional ability among community-dwelling knee OA patients using a comprehensive set of psychological question naires . Methods In the cross-sectional baseline setting of a prospect i ve , r and omized controlled intervention study , 111 patients aged from 35 to 75 years with clinical symptoms and radiographic grading of knee OA were included . They completed a comprehensive set of psychological question naires , including measures of re sources and coping , fear and catastrophizing , and distress . Results In cross-sectional comparisons , pain self-efficacy , fear of movement , pain catastrophizing , and elevated anxiety were associated with pain and a poorer functional ability . In logistic regression analysis , independent association was seen between pain self-efficacy and poorer functioning . Knee OA patients also reported elevated levels of anxiety . Conclusions The results reveal that both pain self-efficacy and negatively charged emotion and expectations toward pain are important factors when dealing with knee OA patients . Failure to consider these will probably contribute to prolonged disability and further pain . The results call for the routine assessment of multiple psychological factors in knee OA OBJECTIVES To investigate aspects of the validity of the total scores of the Tampa Scale for Kinesiophobia ( TSK ) , Dutch Version , which was modified to make it an appropriate question naire for the assessment of kinesiophobia ( fear of movement ) in chronic fatigue syndrome ( CFS ) patients ( the Dutch TSK-CFS ) , and , using this assessment tool , to examine the associations between kinesiophobia , exercise capacity , and activity limitations and participation restrictions in patients with CFS . DESIGN Prospect i ve observational studies . SETTING An outpatient fatigue clinic . PARTICIPANTS In the first study , 40 patients fulfilling the 1994 US Centers for Disease Control and Prevention ( CDC ) criteria for CFS were enrolled . The sample of the second study consisted of 51 CDC-defined patients with CSF . INTERVENTIONS Not applicable . Main outcome measures Study 1 : Subjects completed a set of question naires ; the Utrechtse Coping List ( UCL ) , the Dutch TSK-CFS , and the Dutch Baecke Question naire of Habitual Physical Activity . Study 2 : All patients completed 2 question naires (  Chronic Fatigue Syndrome Activities and Participation Question naire [ CFS-APQ ] , Dutch TSK-CFS ) and performed a maximal exercise stress test on a bicycle ergometer . The heart rate was monitored continuously by use of an electrocardiograph .  Metabolic and ventilatory parameters were measured through spirometry . RESULTS Study 1 : The Cronbach alpha coefficient for the individual item 
    Output:
    
We found strong evidence for an association between a greater degree of kinesiophobia and greater levels of pain intensity and disability and moderate evidence between a greater degree of kinesiophobia and higher levels of pain severity and low quality of life .
A greater degree of kinesiophobia predicts the progression of disability overtime , with moderate evidence .
A greater degree of kinesiophobia also predicts greater levels of pain severity and low levels of quality of life at 6 months , but with limited evidence .
Kinesiophobia does not predict changes in pain intensity .