Duloxetine and Cognitive Behavioral Therapy with Phone-based Support for the Treatment of Chronic Musculoskeletal Pain: Study Protocol of the PRECICE Randomized Control Trial.

Background: Chronic musculoskeletal pain (CMP) is the most common, disabling, and costly of all pain conditions. While evidence exists for the efficacy of both duloxetine and web-based cognitive behavioral therapy (CBT) as monotherapy, there is a clear need to consider study of treatment components that may complement each other. In addition, given the reported association between patient's adherence and treatment outcomes, strategies are needed to enhance participant's motivation to adopt and maintain continued use of newly learned pain coping skills from CBT. Methods: Two hundred eighty participants will be recruited from the primary care clinics of a large academic health care system in North Carolina. Participants with CMP will be randomized to one of 3 treatment arms: (1) combination treatment (duloxetine + web-based self-guided CBT) with phone-based motivational interviewing (MI), (2) combination treatment without phone-based MI and (3) duloxetine monotherapy. Participants will be in the study for 24 weeks and will be assessed at baseline, week 13, and week 25. The primary outcome is the Brief Pain Inventory (BPI)-Global Pain Severity score, which combines BPI pain severity and BPI pain interference. Secondary measures include between-group comparisons in mean BPI pain severity and BPI pain interference scores. Data collection and outcome assessment will be blinded to treatment group assignment. Discussion: This randomized controlled trial (RCT) will determine if combination treatment with duloxetine and web-based CBT is superior to duloxetine monotherapy for the management of CMP. Furthermore, this RCT will determine the effectiveness of phone-based motivational interviewing in promoting the continued practice of pain coping skills; thereby, enhancing treatment outcomes. Trial Registration: NCT04395001. Registered in ClinicalTrials.gov on May 15, 2020.

Duloxetine and cognitive behavioral therapy with phone-based support for the treatment of chronic musculoskeletal pain: study protocol of the PRECICE randomized control trial.

BACKGROUND: Chronic musculoskeletal pain (CMP) is the most common, disabling, and costly of all pain conditions. While evidence exists for the efficacy of both duloxetine and web-based cognitive behavioral therapy (CBT) as monotherapy, there is a clear need to consider study of treatment components that may complement each other. In addition, given the reported association between patient's adherence and treatment outcomes, strategies are needed to enhance participant's motivation to adopt and maintain continued use of newly learned pain coping skills from CBT. METHODS: Two hundred eighty participants will be recruited from the primary care clinics of a large academic health care system in North Carolina. Participants with CMP will be randomized to one of three treatment arms: (1) combination treatment (duloxetine + web-based self-guided CBT) with phone-based motivational interviewing (MI), (2) combination treatment without phone-based MI, and (3) duloxetine monotherapy. Participants will be in the study for 24 weeks and will be assessed at baseline, week 13, and week 25. The primary outcome is the Brief Pain Inventory (BPI)-Global Pain Severity score, which combines BPI pain severity and BPI pain interference. Secondary measures include between-group comparisons in mean BPI pain severity and BPI pain interference scores. Data collection and outcome assessment will be blinded to treatment group assignment. DISCUSSION: This randomized controlled trial (RCT) will determine if combination treatment with duloxetine and web-based CBT is superior to duloxetine monotherapy for the management of CMP. Furthermore, this RCT will determine the effectiveness of phone-based motivational interviewing in promoting the continued practice of pain coping skills, thereby enhancing treatment outcomes. TRIAL REGISTRATION: NCT04395001 ClinicalTrials.gov. Registered on May 15, 2020.

Nurse-Supported Web-Based Cognitive Behavioral Therapy for Chronic Musculoskeletal Pain: A Randomized Controlled Trial.

BACKGROUND: Web-based cognitive behavioral therapy (CBT) has increased access to effective pain management. Though efficacy of web-based and face-to-face CBT may be comparable, fewer studies have examined whether remote clinical support in addition to web-based CBT can improve pain-related outcomes. OBJECTIVES: The objectives of this study were to determine if the addition of phone-based support to web-based CBT could enhance pain-related outcomes in patients with chronic musculoskeletal pain (CMP). STUDY DESIGN: Randomized controlled clinical trial. SETTING: The internal medicine and rheumatology clinics at Atrium Health Wake Forest Baptist. METHODS: Patients were recruited from a major academic medical center. Sixty patients were randomized to web-based CBT with 6 phone calls (nurse support group, n = 30) vs web-based CBT alone (control group, n = 30). The purpose of the calls was to enhance patients' engagement in the online program. All patients had access to the program from baseline to week 16. Outcome measures were collected at baseline, week 8, and week 16. Adjusting for baseline measurements, analysis of covariance  was used to determine within- and between-group differences. RESULTS: Both nurse support and control groups demonstrated significant within-group improvements in Brief Pain Inventory (BPI) pain interference (-1.3 [-2.0, -0.7, P < 0.05] and -1.7 [-2.3, -1.0, P < 0.05]), BPI pain intensity (-1.2 [-1.7, -0.6, P < 0.05] and -1.3 [-1.8, -0.8, P < 0.05]), Patient-Reported Outcomes Measurement System (PROMIS) pain interference (-5.0 [-6.9, -3.2, P < 0.05] and -5.4 [-7.2, -3.5, P < 0.05]), and PROMIS pain intensity (-1.4 [-2.0, -0.9, P < 0.05] and -1.4 [-1.9, -0.8, P < 0.05]), respectively. However, there were no significant between-group differences amongst the 2 treatment groups in all measures, except PROMIS sleep disturbance that favored the nurse support group (50.5 ± 1.3 vs 54.3 ± 1.3, P < 0.05). LIMITATIONS: Small sample size and lack of treatment fidelity assessment. CONCLUSIONS: Web-based CBT was effective with and without motivational support from nurses. Phone-based support did not enhance pain-related outcomes of web-based CBT. If confirmed in a larger study, web-based CBT without motivational support may be considered as a low-cost treatment intervention for patients with CMP.

The Pain Outcomes Comparing Yoga vs. Structured Exercise (POYSE) Trial in Veterans With Fibromyalgia: Study Design and Methods.

Background: Fibromyalgia is a common pain condition that often leads to significant disability. Unfortunately, the effectiveness of most medications for fibromyalgia is limited, and there is a need for alternative, non-pharmacological therapies. Yoga and aerobic exercise are both evidence-based non-pharmacological treatments for fibromyalgia. However, no prior studies have directly compared the effectiveness of yoga vs. exercise. Objective: This article describes the study design and recruitment outcomes of the Pain Outcomes comparing Yoga vs. Structured Exercise (POYSE) Trial, a two-arm randomized comparative effectiveness trial. Methods: Veterans with fibromyalgia, defined by the 2010 American College of Rheumatology diagnostic criteria, who also experienced at least moderate pain severity were enrolled. The participants were randomized to a 12-week yoga-based or a structured exercise program (SEP) and will undergo comprehensive outcome assessments at baseline, 1, 3, 6, and 9 months by interviewers blinded to treatment assignment. The primary outcome will be the overall severity of fibromyalgia as measured by the total Fibromyalgia Impact Questionnaire-Revised. Secondary outcomes included depression, anxiety, health-related quality of life, pain beliefs, fatigue, sleep, and self-efficacy. Results: A total of 2,671 recruitment letters were sent to potential participants with fibromyalgia. Of the potential participants, 623 (23.3%) were able to be contacted by telephone and had their eligibility assessed. Three hundred seventy-one of those interviewed were found to be eligible (59.6%) and 256 (69.0%) agreed to participate and were randomized to the YOGA (n = 129) or the SEP (n = 127) arm of the trial. Conclusions: Clinicians are faced with numerous challenges in treating patients with fibromyalgia. The interventions being tested in the POYSE trial have the potential to provide primary care and other care settings with new treatment options for clinicians while simultaneously providing a much needed relief for patients suffering from fibromyalgia. Trial Registration: Funded by VA Rehabilitation Research and Development (D1100-R); Trial registration: ClinicalTrials.gov, NCT01797263.

Predictors of Physical Activity in Patients With Fibromyalgia: A Path Analysis.

BACKGROUND/OBJECTIVE: The aim of this study was to identify psychological factors that influence moderate-vigorous physical activity (MVPA) participation in patients with fibromyalgia. METHODS: In this secondary data analysis, 170 patients received personalized exercise plans and completed baseline and follow-up assessments of self-reported physical activity at weeks 12, 24, and 36. Structural equation modeling was used to examine the predictive strengths of psychological factors (exercise self-efficacy, perceived barriers, and intention) on MVPA participation. RESULTS: Using a threshold increase in MVPA of 10 or greater metabolic equivalent hours per week (MET h/wk), 3 groups were defined based on subjects who achieved a minimum increase of 10 MET h/wk that was sustained for at least 12 weeks (SUS-PA), achieved an increase of 10 MET h/wk that was not sustained for at least 12 weeks (UNSUS-PA), and did not achieve an increase of 10 MET h/wk (LO-PA). Increases in exercise self-efficacy and intention and reductions in perceived barriers were associated with increased volume of PA, showing the greatest change in the SUS-PA, followed by UNSUS-PA. For the LO-PA group, there was no change in exercise self-efficacy, a decrease in intention, and an increase in barriers. Using path analysis, exercise self-efficacy and perceived barriers were associated with higher volumes of physical activity via greater intention to engage in MVPA. CONCLUSIONS: For patients with fibromyalgia, exercise self-efficacy, perceived barriers, and intention to exercise are important constructs for increasing physical activity. Our findings provide guidance for practitioners who seek to promote physical activity in fibromyalgia and suggestions for researchers aiming to improve prediction models.

Opioid Use as a Predictor of Pain Outcomes in Iraq and Afghanistan Veterans with Chronic Pain: Analysis of a Randomized Controlled Trial.

OBJECTIVE: Our objectives were to: 1) assess the relationship between self-reported opioid use and baseline demographics, clinical characteristics and pain outcomes; and 2) examine whether baseline opioid use moderated the intervention effect on outcomes at 9 months. DESIGN: We conducted a secondary analysis of data from the Evaluation of Stepped Care for Chronic Pain (ESCAPE) trial, which found stepped-care to be effective for chronic pain in military veterans. SETTING: A post-deployment clinic and five general medicine clinics at a Veteran Affairs Medical Center. SUBJECTS: In total 241 veterans with chronic musculoskeletal pain; 220 with complete data at 9 months. METHODS: Examination of baseline relationships and multivariable linear regression to examine baseline opioid use as a moderator of pain-related outcomes including Roland Morris Disability Questionnaire (RMDQ), Brief Pain Inventory (BPI) Interference scale, and Graded Chronic Pain Scale (GCPS) at 9 months. RESULTS: Veterans reporting baseline opioid use (n = 80) had significantly worse RMDQ (16.0 ± 4.9 vs. 13.4 ± 4.2, P < .0001), GCPS (68.7 ± 12.0 vs. 65.0 ± 14.4, P = .049), BPI Interference (6.2 ± 2.2 vs. 5.0 ± 2.1, P < .0001), and depression (PHQ-9 12.5 ± 6.2 vs. 10.6 ± 5.7, P = .016) compared to veterans not reporting baseline opioid use. Using multivariable modeling we found that baseline opioid use moderated the intervention effect on pain-related disability (RMDQ) at 9 months (interaction Beta = -3.88, P = .0064) but not pain intensity or interference. CONCLUSIONS: In a stepped-care trial for pain, patients reporting baseline opioid use had greater improvement in pain disability at 9 months compared to patients not reporting opioid use.

Multifocal Pain as a Predictor of Pain Outcomes in Military Veterans with Chronic Musculoskeletal Pain: A Secondary Data Analysis of a Randomized Controlled Trial.

OBJECTIVE: We aimed to examine 1) the relationship between multifocal pain and clinical characteristics, including demographics, pain outcomes, somatic symptoms, health-related quality of life, depression, and anxiety, and 2) whether multifocal pain was independently associated with treatment response. METHODS: We conducted a secondary data analysis on veterans with chronic pain enrolled in the Evaluation of Stepped Care for Chronic Pain (ESCAPE) trial with complete data at 9 months (n = 222). We examined baseline relationships and used multivariable linear regression to examine whether multifocal pain was independently associated with outcomes that included Brief Pain Inventory (BPI) Interference scale and Graded Chronic Pain Scale (GCPS) scores between baseline and 9 months. RESULTS: The sample had a mean BPI Interference score of 5.3 ± 2.2 and a mean GCPS score of 65.6 ± 13.7, 55% had significant depression (Patient Health Questionnaire 9-item depression scale [PHQ-9] score of ≥10), and 42% had significant anxiety (Generalized Anxiety Disorder Scale [GAD-7] score of ≥10). Veterans reporting three or more pain sites (the "more diffuse pain" group) had significantly less improvement on GCPS (b = 4.6, standard error [SE] = 2.3, P = 0.045), BPI Interference (b = 1.0, SE = 0.2, P = 0.0011), and health-related quality of life (Short-Form 36-item scale, Physical Component Summary) (b = 4.1, SE = 1.0, P < 0.0001) than did veterans reporting fewer than three pain sites (the "less diffuse pain" group). More diffuse pain was not associated with changes in PHQ-9 or GAD-7 scores. CONCLUSIONS: Multifocal pain predicted worse pain outcomes between baseline and 9 months in veterans enrolled in a trial for treating chronic musculoskeletal pain.

Racial Differences in Pain and Function Following Knee Arthroplasty: A Secondary Analysis From a Multicenter Randomized Clinical Trial.

OBJECTIVE: The assessment of racial differences in pain and function outcome following knee arthroplasty (KA) has received little attention despite very substantial literature exploring a variety of other prognostic factors. The present study was undertaken to determine whether race was associated with KA outcome after accounting for potential confounding factors. METHODS: We conducted a secondary analysis of a randomized clinical trial of 384 participants with moderate-to-high pain catastrophizing who underwent KA. Preoperative measures included race/ethnicity status as well as a variety of potential confounders, including socioeconomic status, comorbidity, and bodily pain. Outcome measures were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scales as well as performance measures. Linear mixed-effects models compared outcomes over a 1-year follow-up period for African American versus non-African American participants. RESULTS: WOMAC pain scores differences for African American versus non-African American participants averaged ~2 points in unadjusted analyses and 1-1.5 points in adjusted analyses. In adjusted analyses, follow-up WOMAC function scores differed by 6 points for African Americans compared to non-African Americans (P = 0.002). CONCLUSION: African Americans generally had worse pain, function, and performance prior to KA and worse scores after surgery, but differences were small and attenuated by ~25-50% after adjustment for potential confounding. Only WOMAC function scores showed clinically important postsurgical differences in adjusted analyses. Clinicians should be aware that after adjustment for potential confounders, African Americans have approximately equivalent outcomes compared to others, with the exception of WOMAC function score.

Disentangling trait versus state characteristics of the Pain Catastrophizing Scale and the PHQ-8 Depression Scale.

BACKGROUND: Research on the role of trait versus state characteristics of a variety of measures among persons experiencing pain has been a focus for the past few decades. Studying the trait versus state nature of the Pain Catastrophizing Scale (PCS) and the Patient Health Questionnaire (PHQ-8) depression scale would be highly informative given both are commonly measured in pain populations and neither scale has been studied for trait/state contributions. METHODS: The PHQ-8 and PCS were obtained on persons undergoing knee arthroplasty at baseline, 2-, 6- and 12-month post-surgery (N = 402). The multi-trait generalization of the latent trait-state model was used to partition trait and state variability in PCS and PHQ-8 item responses simultaneously. A set of variables were used to predict trait catastrophizing and trait depression. RESULTS: For total scores, the latent traits and latent states explain 63.2% (trait = 43.2%; state = 20.0%) and 50.2% (trait = 29.4%; state = 20.8%) of the variability in PCS and PHQ-8, respectively. Patients with a high number of bodily pain sites, high levels of anxiety, young patients and African-American patients had high levels of trait catastrophizing and trait depression. The PCS and the PHQ-8 consist of both enduring trait and dynamic state characteristics, with trait characteristics dominating for both measures. CONCLUSION: Clinicians and researchers using these scales should not assume the obtained measurements solely reflect either trait- or state-based characteristics. SIGNIFICANCE: Clinicians and researchers using the PCS or PHQ-8 scales are measuring both state and trait characteristics and not just trait- or state-based characteristics.

Pain and Psychological Outcomes Among Iraq and Afghanistan Veterans with Chronic Pain and PTSD: ESCAPE Trial Longitudinal Results.

OBJECTIVE: To compare pain and psychological outcomes in veterans with chronic musculoskeletal pain and comorbid post-traumatic stress disorder (PTSD) or pain alone and to determine if veterans with comorbidity respond differently to a stepped-care intervention than those with pain alone. DESIGN: Secondary analysis of data from the Evaluation of Stepped Care for Chronic Pain (ESCAPE) trial. SETTING: Six Veterans Health Affairs clinics. SUBJECTS: Iraq and Afghanistan veterans (N = 222) with chronic musculoskeletal pain. METHODS: Longitudinal analysis of veterans with chronic musculoskeletal pain and PTSD or pain alone and available baseline and nine-month trial data. Participants randomized to either usual care or a stepped-care intervention were analyzed. The pain-PTSD comorbidity group screened positive for PTSD and had a PTSD Checklist-Civilian score ≥41 at baseline. RESULTS: T tests demonstrated statistically significant differences and worse outcomes on pain severity, pain cognitions, and psychological outcomes in veterans with comorbid pain and PTSD compared with those with pain alone. Analysis of covariance (ANCOVA) modeling change scores from baseline to nine months indicated no statistically significant differences, controlling for PTSD, on pain severity, pain centrality, or pain self-efficacy. Significant differences emerged for pain catastrophizing (t = 3.10, P < 0.01), depression (t = 3.39, P < 0.001), and anxiety (t = 3.80, P < 0.001). The interaction between PTSD and the stepped-care intervention was not significant. CONCLUSIONS: Veterans with the pain-PTSD comorbidity demonstrated worse pain and psychological outcomes than those with chronic pain alone. These findings indicate a more intense chronic pain experience for veterans when PTSD co-occurs with pain. PTSD did not lead to a differential response to a stepped-care intervention.

Targeting Mesenchymal Stromal Cells/Pericytes (MSCs) With Pulsed Electromagnetic Field (PEMF) Has the Potential to Treat Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of synovium (synovitis), with inflammatory/immune cells and resident fibroblast-like synoviocytes (FLS) acting as major players in the pathogenesis of this disease. The resulting inflammatory response poses considerable risks as loss of bone and cartilage progresses, destroying the joint surface, causing joint damage, joint failure, articular dysfunction, and pre-mature death if left untreated. At the cellular level, early changes in RA synovium include inflammatory cell infiltration, synovial hyperplasia, and stimulation of angiogenesis to the site of injury. Different angiogenic factors promote this disease, making the role of anti-angiogenic therapy a focus of RA treatment. To control angiogenesis, mesenchymal stromal cells/pericytes (MSCs) in synovial tissue play a vital role in tissue repair. While recent evidence reports that MSCs found in joint tissues can differentiate to repair damaged tissue, this repair function can be repressed by the inflammatory milieu. Extremely-low frequency pulsed electromagnetic field (PEMF), a biophysical form of stimulation, has an anti-inflammatory effect by causing differentiation of MSCs. PEMF has also been reported to increase the functional activity of MSCs to improve differentiation to chondrocytes and osteocytes. Moreover, PEMF has been demonstrated to accelerate cell differentiation, increase deposition of collagen, and potentially return vascular dysfunction back to homeostasis. The aim of this report is to review the effects of PEMF on MSC modulation of cytokines, growth factors, and angiogenesis, and describe its effect on MSC regeneration of synovial tissue to further understand its potential role in the treatment of RA.

Pain Coping Skills Training for Patients Who Catastrophize About Pain Prior to Knee Arthroplasty: A Multisite Randomized Clinical Trial.

BACKGROUND: Pain catastrophizing has been identified as a prognostic indicator of poor outcome following knee arthroplasty. Interventions to address pain catastrophizing, to our knowledge, have not been tested in patients undergoing knee arthroplasty. The purpose of this study was to determine whether pain coping skills training in persons with moderate to high pain catastrophizing undergoing knee arthroplasty improves outcomes 12 months postoperatively compared with usual care or arthritis education. METHODS: A multicenter, 3-arm, single-blinded, randomized comparative effectiveness trial was performed involving 5 university-based medical centers in the United States. There were 402 randomized participants. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Scale, measured at baseline, 2 months, 6 months, and 12 months following the surgical procedure. RESULTS: Participants were recruited from January 2013 to June 2016. In 402 participants, 66% were women and the mean age of the participants (and standard deviation) was 63.2 ± 8.0 years. Three hundred and forty-six participants (90% of those who underwent a surgical procedure) completed a 12-month follow-up. All 3 treatment groups had large improvements in 12-month WOMAC pain scores with no significant differences (p > 0.05) among the 3 treatment arms. No differences were found between WOMAC pain scores at 12 months for the pain coping skills and arthritis education groups (adjusted mean difference, 0.3 [95% confidence interval (CI), -0.9 to 1.5]) or between the pain coping and usual-care groups (adjusted mean difference, 0.4 [95% CI, -0.7 to 1.5]). Secondary outcomes also showed no significant differences (p > 0.05) among the 3 groups. CONCLUSIONS: Among adults with pain catastrophizing undergoing knee arthroplasty, cognitive behaviorally based pain coping skills training did not confer pain or functional benefit beyond the large improvements achieved with usual surgical and postoperative care. Future research should develop interventions for the approximately 20% of patients undergoing knee arthroplasty who experience persistent function-limiting pain. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Opioid use prior to knee arthroplasty in patients who catastrophize about their pain: preoperative data from a multisite randomized clinical trial.

BACKGROUND: Opioid use rates prior to knee arthroplasty (KA) among people who catastrophize about their pain are unknown. We determined prevalence of opioid use and compared patterns of preoperative opioid use and oral morphine equivalent (OME), a measure of daily opioid dose, across varied geographic sites. We also determined which baseline variables were associated with opioid use and OME. PATIENTS AND METHODS: Preoperative opioid use data described type of opioid, dosage, and frequency among 397 patients scheduled for KA. Demographic, knee-related pain, and psychological distress dimensions were examined to identify variables associated with opioid use and opioid dose (OME). Opioid use prevalence and OME were compared across the four sites. A three-level censored regression determined variables associated with opioid use and OME. RESULTS: The overall opioid use prevalence was 31.7% (95% confidence interval [CI] = 27.0, 36.3) and varied across sites from 15.9% (95% CI = 9.0, 22.8) to 51.2% (95% CI = 40.5, 61.9). After adjustment, patients using opioids were more likely to be younger, African American, and have higher self-efficacy and comorbidity scores (P < 0.05). The only variable independently associated with OME was lower depressive symptoms (P < 0.05). CONCLUSION: People who catastrophized prior to KA did not demonstrate increased preoperative opioid use based on current evidence, but variation in the prevalence of opioid use across study sites was substantial. Variables associated with opioid use were non-modifiable demographic and comorbidity variables.

Do Pain Coping and Pain Beliefs Associate With Outcome Measures Before Knee Arthroplasty in Patients Who Catastrophize About Pain? A Cross-sectional Analysis From a Randomized Clinical Trial.

BACKGROUND: Pain-coping strategies and appraisals are responses to the pain experience. They can influence patient-reported and physical performance outcome measures in a variety of disorders, but the associations between a comprehensive profile of pain-coping responses and preoperative pain/function and physical performance measures in patients scheduled for knee arthroplasty have not been examined. Patients with moderate to high pain catastrophizing (a pain appraisal approach associated with an exaggerated focus on the threat value of pain) may represent an excellent study population in which to address this knowledge gap. QUESTIONS/PURPOSES: We asked the following questions among patients with high levels of pain catastrophizing who were scheduled for TKA: (1) Do maladaptive pain responses correlate with worse self-reported pain intensity and function and physical performance? (2) Do adaptive pain-coping responses show the opposite pattern? As an exploratory hypothesis, we also asked: (3) Do maladaptive responses show more consistent associations with measures of pain, function, and performance as compared with adaptive responses? METHODS: A total of 384 persons identified with moderate to high levels of pain catastrophizing and who consented to have knee arthroplasty were recruited. The sample was 67% (257 of 384) women and the mean age was 63 years. Subjects were consented between 1 and 8 weeks before scheduled surgery. All subjects completed the WOMAC pain and function scales in addition to a comprehensive profile of pain coping and appraisal measures and psychologic health measures. Subjects also completed the Short Physical Performance Battery and the 6-minute walk test. For the current study, all measures were obtained at a single point in time at the preoperative visit with no followup. Multilevel multivariate multiple regression was used to test the hypotheses and potential confounders were adjusted for in the models. RESULTS: Maladaptive pain responses were associated with worse preoperative pain and function measures. For example, the maladaptive pain-coping strategy of guarding and the pain catastrophizing appraisal measures were associated with WOMAC pain scores such that higher guarding scores (ß = 0.12, p = 0.007) and higher pain catastrophizing (ß = 0.31, p < 0.001) were associated with worse WOMAC pain; no adaptive responses were associated with better WOMAC pain or physical performance scores. Maladaptive responses were also more consistently associated with worse self-reported and performance-based measure scores (six of 16 associations were significant in the hypothesized direction), whereas adaptive responses did not associate with better scores (zero of 16 scores were significant in the hypothesized direction). CONCLUSIONS: The maladaptive responses of guarding, resting, and pain catastrophizing were associated with worse scores on preoperative pain and performance measures. These are pain-related responses surgeons should consider when assessing patients before knee arthroplasty. TKA candidates found to have these pain responses may be targets for treatments that may improve postoperative outcome given that these responses are modifiable. Future intervention-based research should target this trio of maladaptive pain responses to determine if intervention leads to improvements in postsurgical health outcomes. LEVEL OF EVIDENCE: Level I, prognostic study.

Obesity Moderates the Effects of Motivational Interviewing Treatment Outcomes in Fibromyalgia.

OBJECTIVE: Obesity is a common comorbid condition among patients with fibromyalgia (FM). Our objective was to assess if obesity moderates the treatment benefits of exercise-based motivational interviewing (MI) for FM. MATERIALS AND METHODS: This is a secondary data analysis of a completed clinical trial of 198 FM patients who were randomized to receive either MI or attention control (AC). Using body mass index (BMI) to divide participants into obese (BMI≥30 kg/m) and nonobese (BMI<30 kg m) groups, mixed linear models were used to determine interaction between treatment arms and obesity status with regards to the primary outcome of global FM symptom severity (Fibromyalgia Impact Questionnaire, FIQ). Secondary measures included pain intensity (Brief Pain Inventory), 6-Minute Walk Test, and self-reported physical activity (Community Health Activities Model Program for Seniors). RESULTS: Of the 198 participants, 91 (46%) were nonobese and 107 (54%) were obese. On global FM symptom severity (FIQ), the interaction between treatment arms and obesity status was significant (P=0.02). In the nonobese group, MI was associated with a greater improvement in FIQ than AC. In the obese group, MI participants reported less improvement in FIQ compared with AC. The interaction analysis was also significant for Brief Pain Inventory pain intensity (P=0.01), but not for the walk test and self-reported physical activity. DISCUSSION: This is the first study to show that obesity negatively affects the treatment efficacy of MI in patients with FM. Our findings suggest that exercise-based MI may be more effective if initiated after weight loss is achieved.

Construct validation and correlates of preoperative expectations of postsurgical recovery in persons undergoing knee replacement: baseline findings from a randomized clinical trial.

BACKGROUND: A patient's recovery expectations prior to knee arthroplasty influence postsurgical outcome and satisfaction but a unidimensional measure of expectation has not been reported in the literature. Our primary purpose was to determine the extent to which a patient expectations scale reflects a unidimensional construct. Our second purpose was to identify pre-operative variables associated with patients' expectations. We hypothesized that previously identified predictors of the latent expectation scale score would be associated with expectations and that previously unexplored variables of pain catastrophizing, depressive and anxiety symptoms, self-efficacy and number of painful body regions would also associate with pre-operative expectations. METHODS: Our randomized clinical trial had 384 patients assessed prior to knee replacement surgery. The expectations scale along with several predictor variables including WOMAC, psychological distress, and sociodemographic variables were obtained. Confirmatory factor analysis tested the unidimensionality of the measure and structural equation modeling identified predictors of the latent expectations measure. RESULTS: The expectations scale was found to be unidimensional with superior model fit (χ2 = 1.481; df = 2; p = 0.224; RMSEA = 0.035; 90% CI = [0-0.146]; CFI = 0.999; TLI = 0.993). The only variable significantly associated with expectations in the multivariate model was self-efficacy. CONCLUSIONS: The expectations scale used in our study demonstrated unidimensionality and has strong potential for clinical application. Poor self-efficacy is a potential target for intervention given its independent association with expectation. Addressing expectations directly and indirectly through self-efficacy assessment may assist in better aligning patient's expectations with likely outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT01620983 .

Biologic Therapies for Autoimmune and Connective Tissue Diseases.

Biologic therapy continues to revolutionize the treatment of autoimmune disease, especially in rheumatology as the pathophysiology of both inflammation and autoimmune disease becomes better understood. These therapies are designed to dampen the response of the inflammatory cascades. Although the first biologic therapies were approved many years ago, expanding indications and new agents continue to challenge the traditional treatment strategies for rheumatic diseases. This article reviews the data supporting the current use of biologic therapies, including off-label indications, in a subset of rheumatic diseases including rheumatoid arthritis, lupus, inflammatory myositis, ankylosing spondylitis, psoriatic arthritis, vasculitis, and gout.

The Complex Relationship between Pain Intensity and Physical Functioning in Fibromyalgia: The Mediating Role of Depression.

PURPOSE: Fibromyalgia (FM) is typically associated with the experience of diffuse pain and physical impairment. Depression also commonly co-exists in patients with FM, and has been correlated with pain intensity and physical functioning. Previous research suggests an association between pain intensity and physical functioning; however, the direct causal relationship between improvements in pain intensity and in functioning is not observed in many FM patients. This may suggest that another factor such as depression is mediating this relationship. The present work examined mediating role of depression. METHODS: 216 patients with FM completed measures of pain intensity, depression, and physical function as part of a larger longitudinal study. Assessments were completed at baseline, 12, 24, and 36 weeks. RESULTS: Longitudinal mediational analyses indicated that depression is a partial mediator of the relationship between pain intensity and physical functioning at all four assessment points. Beta coefficients for the path from pain to physical functioning ranged from 0.18 - 0.36, with attenuated path coefficients ranging from 0.03 - 0.08, still showing significant but decreased associations when depression was added as a mediator. CONCLUSIONS: Clinical implication includes the importance of treating co-morbid depression in patients with fibromyalgia early in the course of treatment to prevent engagement in the cycle of disability.

Sustained Benefits of Exercise-based Motivational Interviewing, but Only among Nonusers of Opioids in Patients with Fibromyalgia.

OBJECTIVE: Given the known side effects of opioids and their potential effects on cognition, we sought to evaluate the benefits of motivational interviewing (MI) to promote physical activity on 2 subsets of participants with fibromyalgia (FM): nonusers and users of opioids. METHODS: This was a secondary data analysis of a 36-week randomized controlled trial to assess the efficacy of MI to promote physical activity among participants with FM. Participants were randomized to 1 of 2 treatment arms: 6 phone-based MI sessions (n = 107) or 6 sessions of FM self-management instructions [attention control (AC), n = 109]. The primary outcomes were changes in physical function (Medical Outcomes Study Short Form-36), pain severity (Brief Pain Inventory), global FM symptom severity (Fibromyalgia Impact Questionnaire), and the amount of light to moderate physical activity (LMPA) from baseline to each followup visit. At study entry, subjects were categorized as opioid nonusers versus users. Repeated measures ANOVA was used to assess treatment effects adjusting for potential confounders. RESULTS: Of the 216 participants, 145 (67%) were nonusers and 71 (33%) were opioid users. Among nonusers, MI was associated with improved physical function, reduced pain severity, and global FM severity, and increased LMPA at 6-month followup. Among opioid users, there were no significant differences in any outcome measures between the MI and AC groups. CONCLUSION: Exercise-based MI was associated with sustained clinical benefits 6 months after completion of therapy, but only for those who were not taking opioids.

Determining the Minimal Clinically Important Difference for 6-Minute Walk Distance in Fibromyalgia.

OBJECTIVE: The aim of this study was to estimate the minimal clinically important difference (MCID) for 6-min walk distance (6MWD) in patients with fibromyalgia. DESIGN: Data from a recently completed trial that included 187 patients who completed the 6-min walk test, Fibromyalgia Impact Questionnaire (FIQ), and Short-Form 36 (SF36) at 12 and 36 wks were used to examine longitudinal changes in 6MWD. An anchor-based approach that used linear regression analyses was used to determine the MCID for 6MWD, using the total FIQ score (FIQ-Total) and SF36-physical function domain as clinical anchors. RESULTS: The mean (SD) change in 6MWD from baseline to week 36 was 34.4 (65.2) m (P < 0.001). The anchor-based MCIDs for the 6MWD were 156 and 167 m for the FIQ and SF36-physical function domain, respectively. These MCIDs correspond with clinically meaningful improvements in FIQ (14% reduction) and SF36-physical function domain (10-point increase). CONCLUSION: The MCID for 6MWD in patients with fibromyalgia was 156 to 167 m. These findings provide the first evidence of the change in 6MWD that is perceived by patients to be clinically meaningful. Further research using other MCID calculation methods is needed to refine estimates of the MCID for 6MWD in patients with fibromyalgia.