Agreement between patient-reported and clinically documented symptoms of acute myeloid leukemia: Study protocol.

AIM: To describe our methods to compare patient-reported symptoms of acute myeloid leukemia and the corresponding documentation by healthcare providers in the electronic health record. BACKGROUND: Patients with acute myeloid leukemia experience many distressing symptoms, particularly related to chemotherapy. The timely recognition and provision of evidence-based interventions to manage these symptoms can improve outcomes. However, lack of standardized formatting for symptom documentation within electronic health records leads to challenges for clinicians when accessing and comprehending patients' symptom information, as it primarily exists in narrative forms in various parts of the electronic health record. This variability raises concerns about over- or under-reporting of symptoms. Consistency between patient-reported symptoms and clinician's symptom documentation is important for patient-centered symptom management, but little is known about the degree of agreement between patient reports and their documentation. This is a detailed description of the study's methodology, procedures and design to determine how patient-reported symptoms are similar or different from symptoms documented in electronic health records by clinicians. DESIGN: Exploratory, descriptive study. METHODS: Forty symptoms will be assessed as patient-reported outcomes using the modified version of the Memorial Symptom Assessment Scale. The research team will annotate symptoms from the electronic health record (clinical notes and flowsheets) corresponding to the 40 symptoms. The degree of agreement between patient reports and electronic health record documentation will be analyzed using positive and negative agreement, kappa statistics and McNemar's test. CONCLUSION: We present innovative methods to comprehensively compare the symptoms reported by acute myeloid leukemia patients with all available electronic health record documentation, including clinical notes and flowsheets, providing insights into symptom reporting in clinical practice. IMPACT: Findings from this study will provide foundational understanding and compelling evidence, suggesting the need for more thorough efforts to assess patients' symptoms. Methods presented in this paper are applicable to other symptom-intensive diseases.

Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain.

BACKGROUND: Chronic post-surgical pain (CPSP) significantly impacts patients' recovery and quality of life. Although environmental risk factors are well-established, genetic risk remains less understood. METHODS: A meta-analysis of genome-wide association studies followed by partitioned heritability was performed on 1350 individuals across five surgery types: hysterectomy, mastectomy, abdominal, hernia, and knee. In subsequent animal studies, withdrawal thresholds to evoked mechanical stimulation were measured in Rag1 null mutant and wild-type mice after plantar incision and laparotomy. Cell sorting by flow cytometry tracked recruitment of immune cell types. RESULTS: We discovered 77 genome-wide significant single-nucleotide polymorphism (SNP) hits, distributed among 24 loci and 244 genes. Meta-analysis of all cohorts estimated a SNP-based narrow-sense heritability for CPSP at ∼39%, indicating a substantial genetic contribution. Partitioned heritability analysis across a wide variety of tissues revealed enrichment of heritability in immune system-related genes, particularly those associated with B and T cells. Rag1 null mutant mice lacking both T and B cells exhibited exacerbated and prolonged allodynia up to 42 days after surgery, which was rescued by B-cell transfer. Recruitment patterns of B cells but not T cells differed significantly during the first 7 days after injury in the footpad, lymph nodes, and dorsal root ganglia. CONCLUSIONS: These findings suggest a key protective role for the adaptive immune system in the development of chronic post-surgical pain.

Predictive Modeling for One-Year Lower Extremity Endovascular Revascularization Failure in Black Persons.

INTRODUCTION: Black persons bear a disproportionate burden of peripheral artery disease (PAD) and experience higher rates of endovascular revascularization failure (ERF) when compared with non-Hispanic White persons. We aimed to identify predictors of ERF in Black persons using predictive modeling. METHODS: This retrospective study included all persons identifying as Black who underwent an initial endovascular revascularization procedure for PAD between 2011 and 2018 at a midwestern tertiary care center. Three predictive models were developed using (1) logistic regression, (2) penalized logistic regression (least absolute shrinkage and selection operator [LASSO]), and (3) random forest (RF). Predictive performance was evaluated under repeated cross-validation. RESULTS: Of the 163 individuals included in the study, 113 (63.1%) experienced ERF at 1 y. Those with ERF had significant differences in symptom status (P < 0.001), lesion location (P < 0.001), diabetes status (P = 0.037), and annual procedural volume of the attending surgeon (P < 0.001). Logistic regression and LASSO models identified tissue loss, smoking, femoro-popliteal lesion location, and diabetes control as risk factors for ERF. The RF model identified annual procedural volume, age, PAD symptoms, number of comorbidities, and lesion location as most predictive variables. LASSO and RF models were more sensitive than logistic regression but less specific, although all three methods had an overall accuracy of ≥75%. CONCLUSIONS: Black persons undergoing endovascular revascularization for PAD are at high risk of ERF, necessitating need for targeted intervention. Predictive models may be clinically useful for identifying high-risk patients, although individual predictors of ERF varied by model. Further exploration into these models may improve limb salvage for this population.

Influence of Transcutaneous Electrical Nerve Stimulation (TENS) on Pressure Pain Thresholds and Conditioned Pain Modulation in a Randomized Controlled Trial in Women With Fibromyalgia.

Transcutaneous electrical nerve stimulation (TENS) effectively reduces pain in fibromyalgia (FM). The purpose of this study was to examine the influence of TENS use on pressure pain thresholds (PPT) and conditioned pain modulation (CPM) in individuals with FM using data from the Fibromyalgia Activity Study with TENS trial (NCT01888640). Individuals with FM were randomly assigned to receive active TENS, placebo TENS, or no TENS for 4 weeks. A total of 238 females satisfied the per-protocol analysis among the active TENS (n = 76), placebo TENS (n = 68), and no TENS (n = 94) groups. Following 4 weeks of group allocation, the active TENS group continued for an additional 4 weeks of active TENS totaling 8 weeks (n = 66), the placebo and no TENS groups transitioned to receive 4 weeks of active TENS (delayed TENS, n = 161). Assessment of resting pain, movement-evoked pain (MEP), PPT, and CPM occurred prior to and following active, placebo, or no TENS. There were no significant changes in PPT or CPM among the active TENS, placebo TENS, or no TENS groups after 4 weeks. Individuals who reported clinically relevant improvements in MEP (≥30% decrease) demonstrated increases in PPT (P < .001), but not CPM, when compared to MEP non-responders. There were no significant correlations among the change in PPT or CPM compared to MEP and resting pain following active TENS use (active TENS + delayed TENS). PPT and CPM may provide insight to underlying mechanisms contributing to pain; however, these measures may not relate to self-reported pain symptoms. PERSPECTIVE: Pressure pain threshold increased in individuals with clinically relevant improvement (≥30%) in MEP, indicating the clinical relevance of PPT for understanding mechanisms contributing to pain. CPM was not a reliable indicator of treatment response in MEP responders.

Genome-wide association study suggests a critical contribution of the adaptive immune system to chronic post-surgical pain.

Chronic post-surgical pain affects a large proportion of people undergoing surgery, delaying recovery time and worsening quality of life. Although many environmental variables have been established as risk factors, less is known about genetic risk. To uncover genetic risk factors we performed genome-wide association studies in post-surgical cohorts of five surgery types- hysterectomy, mastectomy, abdominal, hernia, and knee- totaling 1350 individuals. Genetic associations between post-surgical chronic pain levels on a numeric rating scale (NRS) and additive genetic effects at common SNPs were evaluated. We observed genome-wide significant hits in almost all cohorts that displayed significance at the SNP, gene, and pathway levels. The cohorts were then combined via a GWAS meta-analysis framework for further analyses. Using partitioned heritability, we found that loci at genes specifically expressed in the immune system carried enriched heritability, especially genes related to B and T cells. The relevance of B cells in particular was then demonstrated in mouse postoperative pain assays. Taken altogether, our results suggest a role for the adaptive immune system in chronic post-surgical pain.

Translating Outcomes from the Clinical Setting to Preclinical Models: Chronic Pain and Functionality in Chronic Musculoskeletal Pain.

Fibromyalgia (FM) is a chronic pain disorder characterized by chronic widespread musculoskeletal pain (CWP), resting pain, movement-evoked pain (MEP), and other somatic symptoms that interfere with daily functioning and quality of life. In clinical studies, this symptomology is assessed, while preclinical models of CWP are limited to nociceptive assays. The aim of the study was to investigate the human-to-model translatability of clinical behavioral assessments for spontaneous (or resting) pain and MEP in a preclinical model of CWP. For preclinical measures, the acidic saline model of FM was used to induce widespread muscle pain in adult female mice. Two intramuscular injections of acidic or neutral pH saline were administered following baseline measures, 5 days apart. An array of adapted evoked and spontaneous pain measures and functional assays were assessed for 3 weeks. A novel paradigm for MEP assessment showed increased spontaneous pain following activity. For clinical measures, resting and movement-evoked pain and function were assessed in adult women with FM. Moreover, we assessed correlations between the preclinical model of CWP and in women with fibromyalgia to examine whether similar relationships between pain assays that comprise resting and MEP existed in both settings. For both preclinical and clinical outcomes, MEP was significantly associated with mechanical pain sensitivity. Preclinically, it is imperative to expand how the field assesses spontaneous pain and MEP when studying multi-symptom disorders like FM. Targeted pain assessments to match those performed clinically is an important aspect of improving preclinical to clinical translatability of animal models.

The Influence of Opioids on Transcutaneous Electrical Nerve Stimulation Effects in Women With Fibromyalgia.

Transcutaneous electrical nerve stimulation (TENS) uses endogenous opioids to produce analgesia, and effectiveness can be reduced in opioid-tolerant individuals'. We examined TENS effectiveness (primary aim), and differences in fibromyalgia symptoms (secondary aim), in women with fibromyalgia regularly taking opioid (RTO) medications compared with women not- regularly taking opioids (not-RTO). Women (RTO n = 79; not-RTO not-n = 222) with fibromyalgia with daily pain levels ≥4 were enrolled and categorized into RTO (taking opioids at least 5 of 7 days in last 30 days) or not-RTO groups. Participants were categorized into tramadol n = 52 (65.8%) and other opioids n = 27 (34.2%) for the RTO group. Participants were phenotyped across multiple domains including demographics, fibromyalgia characteristics pain, fatigue, sleep, psychosocial factors, and activity. Participants were randomized to active TENS (n = 101), placebo TENS (n = 99), or no TENS (n = 99) for 1-month with randomization stratified by opioid use. Active TENS was equally effective in movement-evoked pain in those in the RTO and not-RTO groups. Women with fibromyalgia in the RTO group were older (P = .002), lower-income (P = .035), more likely to smoke (P = .014), and more likely to report depression (P = .013), hypertension (P = .005) or osteoarthritis (P = .027). The RTO group demonstrated greater bodily pain on SF-36 (P = .005), lower quality of life on the physical health component of the SF-36 (P = .040), and greater fatigue (MAF-ADL P = .047; fatigue with sit to stand test (P = .047) These differences were small of and unclear clinical significance. In summary, regular use of opioid analgesics does not interfere with the effectiveness of TENS for movement-evoked pain. Clinical Trial Registration Number: NCT01888640. PERSPECTIVE: Individuals treated with mixed frequency TENS at a strong but comfortable intensity that was taking prescription opioid analgesics showed a significant reduction in movement-evoked pain and fatigue. These data support the use of TENS, using appropriate parameters of stimulation, as an intervention for individuals with fibromyalgia taking opioid analgesics.

Test-Retest Reliability and Responsiveness of PROMIS Sleep Short Forms Within an RCT in Women With Fibromyalgia.

Background: Nonrestorative sleep is commonly reported by individuals with fibromyalgia, but there is limited information on the reliability and responsiveness of self-reported sleep measures in this population. Objectives: (1) Examine the reliability and validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) sleep measures in women with fibromyalgia, and (2) Determine the responsiveness of the PROMIS sleep measures to a daily transcutaneous electrical nerve stimulation (TENS) intervention in women with fibromyalgia over 4 weeks compared with other measures of restorative sleep. Methods: In a double-blinded, dual-site clinical trial, 301 women with fibromyalgia were randomly assigned to utilize either Active-TENS, Placebo-TENS, or No-TENS at home. Measures were collected at baseline and after 4 weeks of treatment. To assess self-reported sleep, the participants completed three PROMIS short forms: Sleep Disturbance, Sleep-Related Impairment, Fatigue, and the Pittsburgh Sleep Quality Index (PSQI). To assess device-measured sleep, actigraphy was used to quantify total sleep time, wake after sleep onset, and sleep efficiency. Linear mixed models were used to examine the effects of treatment, time, and treatment*time interactions. Results: The PROMIS short forms had moderate test-retest reliability (ICC 0.62 to 0.71) and high internal consistency (Cronbach's alpha 0.89 to 0.92). The PROMIS sleep measures [mean change over 4 weeks, 95% confidence interval (CI)], Sleep Disturbance: -1.9 (-3.6 to -0.3), Sleep-Related Impairment: -3 (-4.6 to -1.4), and Fatigue: -2.4 (-3.9 to -0.9) were responsive to improvement in restorative sleep and specific to the Active-TENS group but not in the Placebo-TENS [Sleep Disturbance: -1.3 (-3 to 0.3), Sleep-Related Impairment: -1.2 (-2.8 to 0.4), Fatigue: -1.1 (-2.7 to 0.9)] or No-TENS [Sleep Disturbance: -0.1 (-1.6 to 1.5), Sleep-Related Impairment: -0.2 (-1.7 to 1.4), Fatigue: -.3 (-1.8 to 1.2)] groups. The PSQI was responsive but not specific with improvement detected in both the Active-TENS: -0.9 (-1.7 to -0.1) and Placebo-TENS: -0.9 (-1.7 to 0) groups but not in the No-TENS group: -0.3 (-1.1 to 0.5). Actigraphy was not sensitive to any changes in restorative sleep with Active-TENS [Sleep Efficiency: -1 (-2.8 to 0.9), Total Sleep Time: 3.3 (-19.8 to 26.4)]. Conclusion: The PROMIS sleep measures are reliable, valid, and responsive to improvement in restorative sleep in women with fibromyalgia. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01888640.

IL-5 mediates monocyte phenotype and pain outcomes in fibromyalgia.

ABSTRACT: Fibromyalgia (FM) is characterized by widespread chronic pain, fatigue, and somatic symptoms. The influence of phenotypic changes in monocytes on symptoms associated with FM is not fully understood. The primary aim of this study was to take a comprehensive whole-body to molecular approach in characterizing relationships between monocyte phenotype and FM symptoms in relevant clinical populations. Lipopolysaccharide-evoked and spontaneous secretion of IL-5 and other select cytokines from circulating monocytes was higher in women with FM compared to women without pain. In addition, greater secretion of IL-5 was significantly associated with pain and other clinically relevant psychological and somatic symptoms of FM. Furthermore, higher levels of pain and pain-related symptoms were associated with a lower percentage of intermediate monocytes (CD14++/CD16+) and a greater percentage of nonclassical monocytes (CD14+/CD16++) in women with FM. Based on findings from individuals with FM, we examined the role of IL-5, an atypical cytokine secreted from monocytes, in an animal model of widespread muscle pain. Results from the animal model show that IL-5 produces analgesia and polarizes monocytes toward an anti-inflammatory phenotype (CD206+). Taken together, our data suggest that monocyte phenotype and their cytokine profiles are associated with pain-related symptoms in individuals with FM. Furthermore, our data show that IL-5 has a potential role in analgesia in an animal model of FM. Thus, targeting anti-inflammatory cytokines such as IL-5 secreted by circulating leukocytes could serve as a promising intervention to control pain and other somatic symptoms associated with FM.

Reduction in movement-evoked pain and fatigue during initial 30-minute transcutaneous electrical nerve stimulation treatment predicts transcutaneous electrical nerve stimulation responders in women with fibromyalgia.

ABSTRACT: We previously showed that 1 month of transcutaneous electrical nerve stimulation (TENS) reduces movement-evoked pain and fatigue in women with fibromyalgia (FM). Using data from this study (Fibromyalgia Activity Study with TENS [FAST]), we performed a responder analysis to identify predictors of clinical improvement in pain and fatigue with TENS, validated these models using receiver operator characteristic, and determined number needed to treat and number needed to harm. Participants were randomly assigned to active-TENS (2-125 Hz; highest-tolerable intensity), placebo-TENS, or no-TENS for 1 month. At the end of the randomized phase, placebo-TENS and no-TENS groups received active-TENS for 1 month. The predictor model was developed using data from the randomized phase for the active-TENS group (n = 103) and validated using data from placebo-TENS and no-TENS groups after active-TENS for 1 month (n = 155). Participant characteristics, initial response to TENS for pain and fatigue, sleep, psychological factors, and function were screened for association with changes in pain or fatigue using a logistic regression model. Predictors of clinical improvement in pain were initial response to pain and widespread pain index (area under the curve was 0.80; 95% confidence interval: 0.73-0.87). Predictors of clinical improvement in fatigue were marital status, sleep impairment, and initial response to TENS (area under the curve was 0.67; 95% confidence interval: 0.58-0.75). Number needed to treat for pain and fatigue ranged between 3.3 and 5.3. Number needed to harm ranged from 20 to 100 for minor TENS-related adverse events. The response to an initial 30-minute TENS treatment predicts who responds to longer-term TENS use in women with FM, making this a clinically useful procedure. Number needed to treat and number needed to harm suggest that TENS is effective and safe for managing pain and fatigue in FM.

Multisensory Sensitivity is Related to Deep-Tissue but Not Cutaneous Pain Sensitivity in Healthy Individuals.

PURPOSE: Some individuals with chronic pain find daily life sensations (eg, noise, light, or touch) aversive. This amplification of multisensory sensations has been associated with centrally mediated plasticity; for example, greater multisensory sensitivity (MSS) occurs in patients with fibromyalgia than rheumatoid arthritis. However, whether MSS preferentially relates to pain measures which reflect central influences (eg, dynamic quantitative sensory testing (QST) or referred pain), or whether the MSS-pain relationship requires priming from chronic pain, is unknown. Thus, this cross-sectional study investigated the relationships between MSS assessed in a pain-free state and evoked pain sensitivity. METHODS: Experimental intramuscular infusion pain and multiple static and dynamic QST were assessed in 465 healthy, pain-free adults: pain thresholds using pressure (PPTs) and heat (HPTs), temporal summation of pain (TSP) using pressure, heat or punctate stimuli, and conditioned pain modulation (CPM) using pressure or heat test stimuli. MSS was assessed using 7 items from Barsky's Somatosensory Amplification Scale. Differences in pain and QST between sex-specific MSS quartiles were assessed, adjusting for multiple comparisons. All participants completed at least one intramuscular infusion condition, but not all were asked to complete each QST (n=166-465). RESULTS: Both static and dynamic QST differed between highest and lowest MSS quartiles using pressure stimuli: lower PPTs (adjusted-p<0.01); increased pressure TSP (adjusted-p=0.02); lower pressure CPM (adjusted-p=0.01). However, none of the heat or punctate QST measures (HPTs, TSP, or CPM) differed between MSS quartiles (adjusted-p>0.05). Odds of experiencing TSP or referred pain was not greater, whereas CPM was 8-fold less likely, in those with highest MSS. CONCLUSION: Normal variation in non-noxious MSS is related to both static and dynamic pain sensitivity, without sensitization associated with chronic pain, but is dependent on the QST stimulus. Thus, common influences on MSS and pain sensitivity may involve central mechanisms but are likely more complex than previously recognized.

One-day Acceptance and Commitment Therapy workshop for preventing persistent post-surgical pain and dysfunction in at-risk veterans: A randomized controlled trial protocol.

OBJECTIVE: Persistent post-surgical pain is common among patients undergoing surgery, is detrimental to patients' quality of life, and can precipitate long-term opioid use. The purpose of this randomized controlled trial is to assess the effects of a behavioral intervention offered prior to surgery for patients at risk for poor post-surgical outcomes, including persistent pain and impaired functioning. METHODS: Described herein is an ongoing randomized, patient- and assessor-blind, attention-controlled multisite clinical trial. Four hundred and thirty Veterans indicated for total knee arthroplasty (TKA) with distress and/or pain will be recruited for this study. Participants will be randomly assigned to a one-day (~5 h) Acceptance and Commitment Therapy workshop or one-day education and attention control workshop. Approximately two weeks following their TKA surgery, patients receive an individualized booster session via phone. Following their TKA, patients complete assessments at 1 week, 6 weeks, 3 months, and 6 months. RESULTS: The primary outcomes are pain intensity and knee-specific functioning; secondary outcomes are symptoms of distress and coping skills. Mediation analyses will examine whether changes in symptoms of distress and coping skills have an impact on pain and functioning at 6 months in Veterans receiving ACT. This study is conducted mostly with older Veterans; therefore, results may not generalize to women and younger adults who are underrepresented in this veteran population. CONCLUSIONS: The results of this study will provide the first evidence from a large-scale, patient- and assessor-blind controlled trial on the effectiveness of a brief behavioral intervention for the prevention of persistent post-surgical pain and dysfunction.

Somatic symptom presentations in women with fibromyalgia are differentially associated with elevated depression and anxiety.

This study examined whether depression and anxiety differentially relate to fatigue, sleep disturbance, pain catastrophizing, fear of movement, and pain severity in women with fibromyalgia. Baseline data from the Fibromyalgia Activity Study with Transcutaneous Electrical Nerve Stimulation were analyzed. Of 191 participants, 50 percent reported high anxiety and/or depression (17% high anxiety, 9% high depression, and 24% both). Fatigue and sleep impairment were associated with high depression (p < 0.05). Pain severity, pain catastrophizing, and fear of movement were associated with high anxiety and high depression (p < 0.05). Possible implications for underlying mechanisms and the need for targeted treatments are discussed.

Patient-Reported Outcomes Measurement Information System (PROMIS) Instruments: Reliability and Validity in Veterans Following Orthopedic Surgery.

The patient-reported outcomes measurement information system (PROMIS) offers standardized assessment measures of clinically relevant patient-reported outcomes. This study evaluated the reliability and validity of select PROMIS measures with U.S. military veterans following orthopedic surgery. Data for the current study were collected as part of a pilot randomized control trial assessing the efficacy of a 1-day Acceptance and Commitment Therapy workshop on persistent postsurgical pain in at-risk veterans undergoing orthopedic surgery. Sixty-seven participants completed surveys 3 months after surgery. Participants completed the following PROMIS instruments: PROMIS Anxiety Short Form 8a, PROMIS Depression Short Form 8b, and PROMIS Pain Interference Short Form 8a. PROMIS measures were compared to the Generalized Anxiety Disorder 7-Item Scale, the Patient Health Questionnaire 9-Item Scale, and the Brief Pain Inventory Pain Interference subscale, respectively. All three PROMIS measures demonstrated excellent internal consistency (Cronbach's αs ranged from .93 to .96) and each loaded onto a single factor. The PROMIS measures were moderately correlated with their respective comparison measures (r = .69 to .76). The PROMIS anxiety and PROMIS depression measures were highly correlated to one another (r = .91). Findings highlight the potential utility of these PROMIS measures in veterans following orthopedic surgery and the overlap between the PROMIS depression and anxiety measures in this sample.

Transcutaneous Electrical Nerve Stimulation Reduces Movement-Evoked Pain and Fatigue: A Randomized, Controlled Trial.

OBJECTIVE: Fibromyalgia (FM) is characterized by pain and fatigue, particularly during physical activity. Transcutaneous electrical nerve stimulation (TENS) activates endogenous pain inhibitory mechanisms. This study was undertaken to investigate if using TENS during activity would improve movement-evoked pain and other patient-reported outcomes in women with FM. METHODS: Participants were randomly assigned to receive active TENS (n = 103), placebo TENS (n = 99), or no TENS (n = 99) and instructed to use it at home during activity 2 hours each day for 4 weeks. TENS was applied to the lumbar and cervicothoracic regions using a modulated frequency (2-125 Hz) at the highest tolerable intensity. Participants rated movement-evoked pain (primary outcome measure) and fatigue on an 11-point scale before and during application of TENS. The primary outcome measure and secondary patient-reported outcomes were assessed at baseline (time of randomization) and at 4 weeks. RESULTS: After 4 weeks, a greater reduction in movement-evoked pain was reported in the active TENS group versus the placebo TENS group (group mean difference -1.0 [95% confidence interval -1.8, -0.2]; P = 0.008) and versus the no TENS group (group mean difference -1.8 [95% confidence interval -2.6, -1.0]; P < 0.0001). A reduction in movement-evoked fatigue was also reported in the active TENS group versus the placebo TENS group (group mean difference -1.4 [95% confidence interval -2.4, -0.4]; P = 0.001) and versus the no TENS group (group mean difference -1.9 [95% confidence interval -2.9, -0.9]; P = <0.0001). A greater percentage of the patients in the active TENS group reported improvement on the global impression of change compared to the placebo TENS group (70% versus 31%; P < 0.0001) and the no TENS group (9%; P < 0.0001). There were no TENS-related serious adverse events, and <5% of participants experienced minor adverse events from TENS. CONCLUSION: Among women who had FM and were on a stable medication regimen, 4 weeks of active TENS use compared to placebo TENS or no TENS resulted in a significant improvement in movement-evoked pain and other clinical outcomes. Further research is needed to examine effectiveness in a real-world setting to establish the clinical importance of these findings.

A single-session acceptance and commitment therapy intervention among women undergoing surgery for breast cancer: A randomized pilot trial to reduce persistent postsurgical pain.

OBJECTIVE: Oncologic breast surgeries carry a risk for persistent postsurgical pain. This study was a randomized pilot and feasibility study of a single-session Acceptance and Commitment Therapy (ACT) intervention compared with treatment as usual among women undergoing surgery for breast cancer or ductal carcinoma in situ. METHODS: Participants were recruited via letter of invitation and follow-up phone call from a single site in the United States from 2015 to 2017. Participants were at risk for persistent postsurgical pain, based on young age (<50), a preexisting chronic pain condition, or elevated anxiety, depression, or pain catastrophizing. RESULTS: The 54 participants were female with a mean age of 52.91 years (SD=11.80). At 3-month postsurgery, 11% of the sample reported moderate-severe pain (>3 on a 0-10 numeric rating scale) in the operative breast or with arm movement. Written qualitative responses indicated that the majority of participants who received the intervention understood the concepts presented and reported continued practice of exercises learned in the session. The between group effect sizes for moderate-severe pain and elevated anxiety at 3-month post-surgery were small (Phi=0.08 and 0.16, respectively). The between group effect sizes for depression, pain acceptance, and pain catastrophizing at 3-month postsurgery were minimal. CONCLUSIONS: This study found small positive effects on postsurgical pain and anxiety for a single-session ACT intervention among women with breast cancer. This study supports the use of ACT with this population.

Development of a method to maximize the transcutaneous electrical nerve stimulation intensity in women with fibromyalgia.

Introduction: Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological intervention clinically used for pain relief. The importance of utilizing the adequate stimulation intensity is well documented; however, clinical methods to achieve the highest possible intensity are not established. Objectives: Our primary aim was to determine if exposure to the full range of clinical levels of stimulation, from sensory threshold to noxious, would result in higher final stimulation intensities. A secondary aim explored the association of pain, disease severity, and psychological variables with the ability to achieve higher final stimulation intensity. Methods: Women with fibromyalgia (N=143) were recruited for a dual-site randomized controlled trial - Fibromyalgia Activity Study with TENS (FAST). TENS electrodes and stimulation were applied to the lumbar area, and intensity was increased to sensory threshold (ST), then to "strong but comfortable" (SC1), then to "noxious" (N). This was followed by a reduction to the final stimulation intensity of "strong but comfortable" (SC2). We called this the Setting of Intensity of TENS (SIT) test. Results: There was a significant increase from SC1 (37.5 mA IQR: 35.6-39.0) to SC2 (39.2 mA IQR: 37.1-45.3) (p<0.0001) with a mean increase of 1.7 mA (95% CI: 1.5, 2.2). Linear regression analysis showed that those with the largest increase between SC1 and N had the largest increase in SC2-SC1. Further, those with older age and higher anxiety were able to achieve greater increases in intensity (SC2-SC1) using the SIT test. Conclusion: The SC2-SC1 increase was significantly associated with age and anxiety, with greater mean increases associated with older age and higher anxiety. Thus, although all patients may benefit from this protocol, older women and women with elevated anxiety receive the greatest benefit.

Physical activity is related to function and fatigue but not pain in women with fibromyalgia: baseline analyses from the Fibromyalgia Activity Study with TENS (FAST).

BACKGROUND: Although exercise is an effective treatment for fibromyalgia, the relationships between lifestyle physical activity and multiple symptomology domains of fibromyalgia are not clear. Thus, the purpose of this study was to comprehensively examine the relationships between lifestyle physical activity with multiple outcome domains in women with fibromyalgia, including pain, fatigue, function, pain-related psychological constructs, and quality of life. METHODS: Women (N = 171), aged 20 to 70 years, diagnosed with fibromyalgia, recruited from an ongoing two-site clinical trial were included in this prespecified subgroup analysis of baseline data. Physical activity was assessed using self-report and accelerometry. Symptomology was assessed using questionnaires of perceived physical function, quality of life, fatigue, pain intensity and interference, disease impact, pain catastrophizing, and fear of movement. In addition, quantitative sensory testing of pain sensitivity and performance-based physical function were assessed. Correlation coefficients, regression analyses and between-group differences in symptomology by activity level were assessed, controlling for age and body mass index (BMI). RESULTS: Lifestyle physical activity was most closely associated with select measures of physical function and fatigue, regardless of age and BMI. Those who performed the lowest levels of lifestyle physical activity had poorer functional outcomes and greater fatigue than those with higher physical activity participation. No relationships between lifestyle physical activity and pain, pain sensitivity, or pain-related psychological constructs were observed. CONCLUSIONS: Lifestyle physical activity is not equally related to all aspects of fibromyalgia symptomology. Lifestyle physical activity levels have the strongest correlations with function, physical quality of life, and movement fatigue in women with fibromyalgia. No relationships between lifestyle physical activity and pain, pain sensitivity, or psychological constructs were observed. These data suggest that physical activity levels are more likely to affect function and fatigue, but have negligible relationships with pain and pain-related psychological constructs, in women with fibromyalgia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01888640 . Registered on 28 June 2013.

Acceptance and Commitment Therapy for Prevention of Chronic Postsurgical Pain and Opioid Use in At-Risk Veterans: A Pilot Randomized Controlled Study.

High levels of pain, significant anxiety, or depressive symptoms before surgery put patients at elevated risk for chronic pain and prolonged opioid use following surgery. The purpose of this preliminary study was to assess the efficacy of a 1-day Acceptance and Commitment Therapy (ACT) workshop in "at-risk" veterans for the prevention of chronic pain and opioid use following orthopedic surgery. In a randomized controlled trial, 88 at-risk veterans undergoing orthopedic surgery were assigned to treatment as usual (TAU; n = 44) or TAU plus a 1-day ACT workshop (n = 44). Pain levels and opioid use were assessed up to 3 months following surgery. Pain acceptance and values-based behavior were assessed at baseline and 3-month follow-up. Participants who completed the ACT workshop reached pain and opioid cessation sooner than those in TAU. Postoperative complications exhibited a moderating effect on these outcomes, such that the effects of ACT were greater in patients without complications. Increases in pain acceptance and values-based behavior, processes targeted in ACT, were related to better outcomes. These promising results merit further investigation in a larger clinical trial. Providing an intervention before surgery for at-risk veterans has the potential to change clinical practice from a focus on management of postoperative pain to prevention of chronic pain in at-risk individuals. PERSPECTIVE: This pilot study compared the effects of a 1-day preventive behavioral intervention (ACT) to TAU in at-risk veterans undergoing orthopedic surgery. Three months following the intervention, veterans receiving ACT exhibited quicker cessation of pain and opioid use. Focusing on preoperative pain management may help prevent chronic postsurgical pain.

Reliability and Construct Validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) Instruments in Women with Fibromyalgia.

OBJECTIVE: The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to standardize measurement of clinically relevant patient-reported outcomes. This study evaluated the reliability and construct validity of select PROMIS static short-form (SF) instruments in women with fibromyalgia. DESIGN: Analysis of baseline data from the Fibromyalgia Activity Study with TENS (FAST), a randomized controlled trial of the efficacy of transcutaneous electrical nerve stimulation. SETTING: Dual site, university-based outpatient clinics. SUBJECTS: Women aged 20 to 67 years diagnosed with fibromyalgia. METHODS: Participants completed the Revised Fibromyalgia Impact Questionnaire (FIQR) and 10 PROMIS static SF instruments. Internal consistency was calculated using Cronbach alpha. Convergent validity was examined against the FIQR using Pearson correlation and multiple regression analysis. RESULTS: PROMIS static SF instruments had fair to high internal consistency (Cronbach α = 0.58 to 0.94, P < 0.05). PROMIS 'physical function' domain score was highly correlated with FIQR 'function' score (r = -0.73). The PROMIS 'total' score was highly correlated with the FIQR total score (r = -0.72). Correlations with FIQR total score of each of the three PROMIS domain scores were r = -0.65 for 'physical function,' r = -0.63 for 'global,' and r = -0.57 for 'symptom' domain. PROMIS 'physical function,' 'global,' and 'symptom' scores explained 58% of the FIQR total score variance. CONCLUSIONS: Select PROMIS static SF instruments demonstrate convergent validity with the FIQR, a legacy measure of fibromyalgia disease severity. These results highlight the potential utility of select PROMIS static SFs for assessment and tracking of patient-reported outcomes in fibromyalgia.