Dennis C. Ang

Evaluation of Stepped Care for Chronic Pain (ESCAPE) in Veterans of the Iraq and Afghanistan Conflicts: A Randomized Clinical Trial

IMPORTANCE Despite the prevalence and the functional, psychological, and economic impact of chronic pain, few intervention studies of treatment of chronic pain in veterans have been performed. OBJECTIVE To determine whether a stepped-care intervention is more effective than usual care, as hypothesized, in reducing pain-related disability, pain interference, and pain severity. DESIGN, SETTING, AND PARTICIPANTS We performed a randomized clinical trial comparing stepped care with usual care for chronic pain. We enrolled 241 veterans from Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn with chronic (>3 months) and disabling (Roland Morris Disability Scale score, ≥7) musculoskeletal pain of the cervical or lumbar spine or extremities (shoulders, knees, and hips) in the Evaluation of Stepped Care for Chronic Pain (ESCAPE) trial from December 20, 2007, through June 30, 2011. The 9-month follow-up was completed by April 2012. Patients received treatment at a postdeployment clinic and 5 general medicine clinics at a Veterans Affairs medical center. INTERVENTIONS Step 1 included 12 weeks of analgesic treatment and optimization according to an algorithm coupled with pain self-management strategies; step 2, 12 weeks of cognitive behavioral therapy. All intervention aspects were delivered by nurse care managers. MAIN OUTCOMES AND MEASURES Pain-related disability (Roland Morris Disability Scale), pain interference (Brief Pain Inventory), and pain severity (Graded Chronic Pain Scale). RESULTS The primary analysis included 121 patients receiving the stepped-care intervention and 120 patients receiving usual care. At 9 months, the mean decrease from baseline in the Roland Morris Disability Scale score was 1.7 (95% CI, -2.6 to -0.9) points in the usual care group and 3.7 (95% CI, -4.5 to -2.8) points in the intervention group (between-group difference, -1.9 [95% CI, -3.2 to -0.7] points; P=.002). The mean decrease from baseline in the Pain Interference subscale score of the Brief Pain Inventory was 0.9 points in the usual care group and 1.7 points in the intervention group (between-group difference, -0.8 [95% CI, -1.3 to -0.3] points; P=.003). The Graded Chronic Pain Scale severity score was reduced by 4.5 points in the usual care group and 11.1 points in the intervention group (between-group difference, -6.6 [95% CI, -10.5 to -2.7] points; P=.001). CONCLUSIONS AND RELEVANCE A stepped-care intervention that combined analgesics, self-management strategies, and brief cognitive behavioral therapy resulted in statistically significant reductions in pain-related disability, pain interference, and pain severity in veterans with chronic musculoskeletal pain. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00386243.

Pain experience of Iraq and Afghanistan Veterans with comorbid chronic pain and posttraumatic stress

Chronic pain and posttraumatic stress disorder (PTSD) co-occur at high rates, and Veterans from recent wars in Iraq and Afghanistan may be particularly vulnerable to both conditions. The objective of this study was to identify key aspects of chronic pain, cognitions, and psychological distress associated with comorbid PTSD among this sample of Veterans. Baseline data were analyzed from a randomized controlled trial testing a stepped-care intervention for chronic musculoskeletal pain. Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Veterans with chronic pain only (n = 173) were compared with those with chronic pain and clinically significant posttraumatic stress symptoms (n = 68). Group differences on pain characteristics, pain cognitions, and psychological distress were evaluated. Results demonstrated that OIF/OEF Veterans with comorbid chronic musculoskeletal pain and PTSD experienced higher pain severity, greater pain-related disability and increased pain interference, more maladaptive pain cognitions (e.g., catastrophizing, self-efficacy, pain centrality), and higher affective distress than those with chronic pain alone. Veterans of recent military conflicts in Iraq and Afghanistan may be particularly vulnerable to the compounded adverse effects of chronic pain and PTSD. These results highlight a more intense and disabling pain and psychological experience for those with chronic pain and PTSD than for those without PTSD.

A phase III randomized three-arm trial of physical therapist delivered pain coping skills training for patients with total knee arthroplasty: the KASTPain protocol

BackgroundApproximately 20% of patients report persistent and disabling pain following total knee arthroplasty (TKA) despite an apparently normally functioning prosthesis. One potential risk factor for unexplained persistent pain is high levels of pain catastrophizing. We designed a three-arm trial to determine if a pain coping skills training program, delivered prior to TKA, effectively reduces function-limiting pain following the procedure in patients with high levels of pain catastrophizing.Methods/designThe trial will be conducted at four University-based sites in the US. A sample of 402 patients with high levels of pain catastrophizing will be randomly assigned to either a pain coping skills training arm, an arthritis education control arm or usual care. Pain coping skills will be delivered by physical therapists trained and supervised by clinical psychologist experts. Arthritis education will be delivered by nurses trained in the delivery of arthritis-related content. The primary outcome will be change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain scale score 12 months following surgery. A variety of secondary clinical and economic outcomes also will be evaluated.DiscussionThe trial will be conducted at four University-based sites in the US. A sample of 402 patients with high levels of pain catastrophizing will be randomly assigned to either a pain coping skills training arm, an arthritis education control arm or usual care. Pain coping skills will be delivered by physical therapists trained and supervised by clinical psychologist experts. Arthritis education will be delivered by nurses trained in the delivery of arthritis-related content. The primary outcome will be change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain scale score 12 months following surgery. A variety of secondary clinical and economic outcomes also will be evaluated.Trial RegistrationNCT01620983

Does Increasing Steps Per Day Predict Improvement in Physical Function and Pain Interference in Adults With Fibromyalgia

To examine the concurrent and predictive associations between the number of steps taken per day and clinical outcomes in patients with fibromyalgia (FM).

Moderate-vigorous physical activity improves long-term clinical outcomes without worsening pain in fibromyalgia

To evaluate the relationship between long‐term maintenance of moderate to vigorous physical activity (MVPA) and clinical outcomes in fibromyalgia (FM).

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.

Metformin: Potential analgesic?

OBJECTIVE To determine the association of self-report use of metformin and pain intensity. DESIGN Survey-based cross sectional. SETTING Primary care in an academic medical center. SUBJECTS Three hundred and twenty nine participants with diabetes. METHODS A total of 329 men and women, aged 18-65, completed a phone-based survey. We utilized the Brief Pain Inventory to assess for pain intensity ratings; Leeds Assessment of Neuropathic Symptoms and Signs to screen for neuropathy; and the Personal Health Questionnaire (PHQ8) Depression Scale to assess for depression. RESULTS Three hundred and twenty nine diabetics (mean age 54- ± 8-year old) completed the study (162 metformin users, 167 nonusers). Compared with non-users, metformin users were used more often [38% vs 20%, P = 0.001]; had lower mean depression scores [6.8 vs 8.3; P = 0.026] and fewer comorbidities [1.5 vs 1.8, P = 0.022]. Adjusting for those three variables, pain scores were not significantly different between groups. In a subset analyses of those with neuropathic pain (n = 156), there were no differences in pain scores found between groups. CONCLUSIONS In a clinic sample of patients with diabetes, the use of metformin at an average dose of 1,432 mg (SD = 596 mg) was not associated with lower pain scores. Given the anti-nociceptive effects of metformin in the animal models of pain, and the relative safety of metformin, future research should evaluate the effect of the higher dose of metformin as a potential analgesic.

Trajectory of change in pain, depression, and physical functioning after physical activity adoption in fibromyalgia

Fibromyalgia is associated with widespread pain, depression, and declines in physical functioning. The purpose of this study was to examine the trajectory of these symptoms over time related to physical activity adoption and maintenance via motivational interviewing versus education, to increase physical activity. There were no treatment group differences; we divided the sample (n = 184) based on changes in physical activity. Repeated measures analyses demonstrated differential patterns in depression, pain, and physical functioning at 24 and 36 weeks. Findings suggest increased physical activity may serve as a multiple-target intervention that provides moderate to large, long-lasting benefits for individuals with fibromyalgia.

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.

Mast Cell Stabilizer (Ketotifen) in Fibromyalgia: Phase 1 Randomized Controlled Clinical Trial.

Objectives:Compared with pain-free controls, patients with fibromyalgia (FM) have more mast cells in the skin. Whether mast cells are involved in the pathogenesis of FM is unclear. We sought to determine the effects of a mast cell stabilizer (ketotifen) on FM symptoms. Materials and Methods:Fifty-one FM patients were randomized to daily oral ketotifen 2 mg bid (n=24) for 8 weeks or placebo (N=27). Mean age of patients was 51.2 years (SD=8.4); 88% were female and 88% were white; 22% were taking concomitant opiates; and mean pressure pain sensitivity (range, 0 to 20) was 10.0 (0.4). At study entry, the weekly average pain intensity was 6.4 (1.1) and the mean score on the Revised Fibromyalgia Impact Questionnaire-Revised was 66.8 (14.0). Results:We found no statistically significant treatment group differences from baseline in either group for the 2 primary measures: weekly average pain intensity (ketotifen −1.3 [1.9] vs. placebo −1.5 [1.9], P=0.7); and Fibromyalgia Impact Questionnaire-Revised score (−12.1 [19.5] vs. −12.2 [18.1], P=0.9). No secondary outcome measures (Brief Pain Inventory pain intensity and pressure pain sensitivity) reached statistical significance; results did not differ in the intent-to-treat and completer analyses. Other than transient sedation (6 [28.6%] vs. 1 [4.0%]), ketotifen was well tolerated. Discussion:The study results question whether skin mast cells play a major role in the pathogenesis of FM. However, given the role of mast cells in peripheral and central nociception, and the minimal side effects of ketotifen, a randomized clinical trial using increasing doses of ketotifen may be warranted.