Relationship Between Post-Traumatic Stress Disorder Symptoms and Chronic Pain-Related Symptom Domains Among Military Active Duty Service Members.

OBJECTIVE: This study examined the relationships between symptom domains relevant to post-traumatic stress disorder (PTSD) diagnosis, PTSD screening, and chronic pain-related symptoms (pain intensity, pain interference, physical function, fatigue, depression, anxiety, anger, satisfaction with social roles) experienced by active duty military service members with chronic pain. DESIGN: ross-sectional study. SETTING: This study was conducted at the Interdisciplinary Pain Management Center (IPMC) at Madigan Army Medical Center between 2014 and 2018. SUBJECTS: Active duty service members receiving care at IPMC (n = 2745) were included in this study. METHODS: Independent sample t test was conducted to compare pain intensity and pain-related measures of physical, emotional, and social functioning among patients with and without a PTSD diagnosis or PTSD positive screen (≥3 symptoms). Relative weight analysis was used to identify the relative importance of each PTSD symptom cluster (e.g., intrusion, avoidance, hyperarousal, emotional numbness) to pain and related domains. RESULTS: Approximately 27.9% of the patients had a positive screen for PTSD, and 30.5% of the patients had a PTSD diagnosis. Patients with PTSD diagnosis and positive screening had higher pain interference and lower physical function and social satisfaction scores (P < 0.001) and had increased anger, anxiety, fatigue, and depression scores (P < 0.001). Emotional numbness accounted for the largest proportion of variance in average pain intensity, pain interference, and psychological functioning, and avoidance accounted for the largest proportion of variance in physical function. CONCLUSION: To improve treatment effectiveness and overall functioning for active duty military patients, integrated treatment and therapies targeted to reducing chronic pain and PTSD symptoms (focus on emotional numbness and avoidance) are recommended.

Association of personality profiles with coping and adjustment to cancer among patients undergoing chemotherapy.

OBJECTIVE: Specific personality traits are associated with differential use of various coping strategies. Few studies have examined the relationship between personality and coping in oncology patients undergoing chemotherapy. We, therefore, examined the relationship between previously identified personality profiles (ie, Distressed [14.3% of total sample], Normative [53.8%], Resilient [31.9%]) and measures of coping and adjustment. METHODS: Patients (n = 1248) undergoing chemotherapy for breast, gastrointestinal, gynecological, or lung cancer completed measures of personality (NEO-Five Factor Inventory), coping (Brief COPE), and psychological adjustment to cancer (Mental Adjustment to Cancer [MAC] scale). Differences in coping and adjustment among the three personality profiles were evaluated using analysis of variance. RESULTS: On the Brief COPE, the Distressed class endorsed lower use of Active Coping, Positive Reframing, Acceptance, Emotional Support (ie, "engagement" coping); and greater use of Denial, Venting, Behavioral Disengagement, Self-Blame (ie, "disengagement" coping) compared to the Normative and Resilient classes. On the MAC scale, the Distressed class scored higher on Anxious Preoccupation, Helplessness/Hopelessness, Fatalism, and Avoidance, and lower on Fighting Spirit, compared to the other two classes. CONCLUSIONS: In this sample of oncology patients receiving chemotherapy, patients in the Distressed personality class showed a reduced repertoire of adaptive coping strategies, while those in the Resilient class reported greater use of adaptive or engagement coping strategies. Further work should examine the potential mediating or moderating role of coping and adjustment in the relationships between personality and patient outcomes. Interventions to enhance beneficial and reduce harmful coping strategies in cancer patients should be evaluated.

Pain Management Telementoring, Long-term Opioid Prescribing, and Patient-Reported Outcomes.

OBJECTIVE: Benefits of primary care provider (PCP) participation in pain management telementoring have been reported; however, no studies have examined within-patient changes in dose or discontinuation of long-term opioid therapy (LOT). The objectives of this nonrandomized study were to evaluate the relationship between telementoring participation and 1) LOT dose reduction and 2) LOT discontinuation and to 3) explore the relationship between LOT dose changes and patient-reported outcomes. METHODS: PCPs were recruited from a US Army medical center. Intervention group PCPs (N = 12) attended telementoring sessions; control group providers (N = 13) did not. Morphine equivalent daily doses (MEDD) for patients of study providers (N = 396) were extracted from the study site's opioid database. The intervention group was subdivided based on number of sessions attended (i.e., active and low participation). Intent-to-treat and as-treated analyses were conducted using generalized estimating equations. Separate analyses evaluated the association between within-patient changes in MEDD and pain impact, depression, and anxiety (N = 40). RESULTS: Intent-to-treat analysis revealed no significant difference in MEDD reduction; however, a higher proportion of patients of intervention PCPs discontinued LOT (25% ± 3.6%) compared with control PCPs (16% ± 3.6%, P < 0.05). As-treated analyses revealed differences in MEDD reduction between active (13.2 ± 3.0) and low-participating (2.6 ± 3.0) PCPs (P < 0.01). Further, a higher proportion of patients of actively participating PCPs discontinued LOT (29% ± 4.9%) compared with control PCPs (16% ± 3.6%, P = 0.01). We found no evidence that decreased MEDD was associated with poorer self-reported outcomes within patients. CONCLUSIONS: Pain management telementoring supports PCPs' efforts to reduce reliance on LOT for chronic pain management and highlights the need for actively engaged PCP pain champions.

Evaluation of the Impact of an Online Opioid Education Program for Acute Pain Management.

OBJECTIVE: The University of Washington instituted a policy requiring all credentialed clinicians who prescribe opioids to complete a one-time education activity about safe and responsible opioid prescribing. A scenario-based, interactive online learning module was developed for opioid management of acute pain in hospitalized adults. This study examined the impact of the education module on learners' knowledge, perceived competence, and use of guideline-adherent practices. METHODS: Clinicians who completed the education module participated in a voluntary de-identified online survey approximately six months after the learning activity. Survey questions were related to 1) the perception of improved knowledge; 2) impact on learner's use of three guideline-adherent practices; and 3) perceived competence in managing opioids for acute pain. Descriptive statistics were generated, and multiple linear regression models were used for analysis. RESULTS: Clinicians (N = 167) reported improvement in knowledge and perceived competence. Controlling for other aspects of knowledge evaluated, learning to construct a safe opioid taper plan for acute pain, distinguishing between short- and long-acting opioids, and safely initiating opioids for acute pain were significantly associated with increased self-reported likelihood of incorporating the Washington state Prescription Monitoring Program (P = 0.003), using multimodal analgesia (P = 0.022), and reducing the duration of opioids prescribed (P = 0.016). Only improvement in knowledge of how to construct a safe opioid taper plan was significantly associated with increased perceived competence (P = 0.002). CONCLUSIONS: Our findings suggest that this online education module about safe opioid prescribing for acute pain management was effective at improving knowledge, increasing the likelihood of using guideline-adherent clinical practices, and increasing perceived competence.

Evaluation of an interprofessional active learning session on acute pain and opioid use disorder using the interprofessional collaborative competency attainment scale.

Pain is complex and best managed using an interprofessional approach. A complicating factor is the high prevalence of co-existing opioid use disorder (OUD). Interprofessional education (IPE) may be an important strategy for transforming pain and OUD care. The objective of this study was to evaluate the impact of an interactive, case-based IPE session related to acute pain management in persons with OUD on pre-licensure health science students' perceived achievement of core competencies for interprofessional collaborative practice. Students completed a self-assessment of competency before and after the IPE session, using the Interprofessional Collaborative Competency Attainment Scale. Paired samples t-tests determined differences between pre- and post-session assessments and Cohen's d effect sizes evaluated the magnitude of change. Learners (n = 160) included students from pharmacy (30.9%), social work (21.9%), dentistry (16.3%), nursing (14.4%), medicine (9.4%), and other professional schools (7.4%). Learners showed significant improvement in perceived competency for all items (all p ≤ 0.002). Using a Collaborative Patient-Centered Approach and Team Functioning demonstrated the greatest overall improvement (Cohen's d > 0. 80). Findings suggest that an interactive IPE session is associated with perceived achievement of core interprofessional competencies for acute pain management in persons with OUD.

How Theory Can Help Facilitate Implementing Relaxation as a Complementary Pain Management Approach.

Complementary therapies provide cancer survivors and clinicians with options for managing chronic pain. Recent published clinical guidelines and research findings support the use of relaxation therapy for managing chronic pain in cancer survivors. However, translating research findings into clinical practice remains a challenge. Using theory to guide implementation of a new practice can increase the likelihood of successful adoption. This article uses relaxation therapy for cancer survivors to describe how clinicians could use Rogers' Diffusion of Innovation Theory and the related Collaborative Research Utilization Model to implement a complementary therapy and ensure that it becomes standard practice.

Use of Self-management Interventions for Chronic Pain Management: A Comparison between Rural and Nonrural Residents.

Individuals with chronic pain who live in rural communities often lack access to pain specialists and rely on primary care providers who may be less prepared. Research has indicated that rural residents with chronic pain are more likely to receive an opioid prescription than nonrural residents. Although self-management approaches are available for chronic pain management, it is unclear to what extent rural residents use these interventions. This study compares usage of self-management interventions and opioid-based analgesics for chronic pain management between rural and nonrural residents. This study is a secondary analysis of baseline data from a randomized controlled trial evaluating a telehealth intervention for chronic pain management. Participants, recruited from primary care clinics, were 65 rural residents and 144 nonrural residents with similar demographic characteristics. Differences in the use of self-management interventions, pain intensity, and opioid dose were evaluated between rural and nonrural residents. Rural residents (n = 50, 77%) were less likely to use self-management interventions compared with nonrural residents (n = 133, 92%) (p = .019). Opioids were taken for pain relief by 76% of the rural residents compared with 52% of the nonrural residents. A disparity exists in the use of self-management interventions for chronic pain management by rural residents compared with nonrural residents. Further study is needed to determine if this is related to the lack of access to specialists and/or pain management training of primary care providers. Nurses can play an essential role in addressing this disparity by educating patients about self-management interventions.

Comparison of subgroups of breast cancer patients on pain and co-occurring symptoms following chemotherapy.

PURPOSE: The purposes of this study, in a sample of women with breast cancer receiving chemotherapy (CTX), were to identify subgroups of women with distinct experiences with the symptom cluster of pain, fatigue, sleep disturbance, and depressive symptoms and evaluate differences in demographic and clinical characteristics, differences in psychological symptoms, and differences in pain characteristics among these subgroups. METHODS: Patients completed symptom questionnaires in the week following CTX administration. Latent class profile analysis (LCPA) was used to determine the patient subgroups. RESULTS: Three subgroups were identified: 140 patients (35.8 %) in the "low," 189 patients (48.3 %) in the "moderate," and 62 patients (15.9 %) in the "all high" latent class. Patients in the all high class had a lower functional status, a higher comorbidity profile, a higher symptom burden, and a poorer quality of life. CONCLUSIONS: Study findings provide evidence of the utility of LCPA to explain inter-individual variability in the symptom experience of patients undergoing CTX. The ability to characterize subgroups of patients with distinct symptom experiences allows for the identification of high-risk patients and may guide the design of targeted interventions that are tailored to an individual's symptom profile.

Cytokine gene variations associated with trait and state anxiety in oncology patients and their family caregivers.

PURPOSE: Anxiety is common among cancer patients and their family caregivers (FCs) and is associated with poorer outcomes. Recently, associations between inflammation and anxiety were identified. However, the relationship between variations in cytokine genes and anxiety warrants investigation. Therefore, phenotypic and genotypic characteristics associated with trait and state anxiety were evaluated in a sample of 167 oncology patients with breast, prostate, lung, or brain cancer and 85 of their FCs. METHODS: Using multiple regression analyses, the associations between participants' demographic and clinical characteristics as well as variations in cytokine genes and trait and state anxiety were evaluated. RESULTS: In the bivariate analyses, a number of phenotypic characteristics were associated with both trait and state anxiety (e.g., age, functional status). However, some associations were specific only to trait anxiety (e.g., number of comorbid conditions) or state anxiety (e.g., participation with a FC). Variations in three cytokine genes (i.e., interleukin (IL) 1 beta, IL1 receptor 2 (IL1R2), nuclear factor kappa beta 2 (NFKB2)) were associated with trait anxiety, and variations in two genes (i.e., IL1R2, tumor necrosis factor alpha (TNFA)) were associated with state anxiety. CONCLUSIONS: These findings suggest that both trait and state anxiety need to be assessed in oncology patients and their FCs. Furthermore, variations in cytokine genes may contribute to higher levels of anxiety in oncology patients and their FCs.

Trajectories of fear of recurrence in women with breast cancer.

PURPOSE: Although fear of recurrence (FCR) is common among cancer survivors, it remains unclear what factors predict initial levels (e.g., prior to surgery) or changes in FCR in the post-treatment period. Among women treated for breast cancer, this study evaluated the effects of demographic, clinical, symptom, and psychosocial adjustment characteristics on the initial (preoperative) levels of FCR and trajectories of FCR over 6 months following surgery. METHODS: Prior to and for 6 months following breast cancer surgery, 396 women were assessed for demographic and clinical (disease and treatment) characteristics, symptoms, psychological adjustment characteristics, and quality of life (QOL). FCR was assessed using a four-item subscale from the QOL instrument. Hierarchical linear modeling was used to examine changes in FCR scores and to identify predictors of inter-individual differences in preoperative FCR levels and trajectories over 6 months. RESULTS: From before surgery to 6 months post-operatively, women with breast cancer showed a high degree of inter-individual variability in FCR. Preoperatively, women who lived with someone, experienced greater changes in spiritual life, had higher state anxiety, had more difficulty coping, or experienced more distress due to diagnosis or distress to family members reported higher FCR scores. Patients who reported better overall physical health and higher FCR scores at enrollment demonstrated a steeper decrease in FCR scores over time. CONCLUSIONS: These findings highlight inter-individual heterogeneity in initial levels and changes in FCR over time among women undergoing breast cancer surgery. Further work is needed to identify and provide interventions for women experiencing FCR during and after breast cancer treatment.

Disease and treatment characteristics do not predict symptom occurrence profiles in oncology outpatients receiving chemotherapy.

BACKGROUND: A large amount of interindividual variability exists in the occurrence of symptoms in patients receiving chemotherapy (CTX). The purposes of the current study, which was performed in a sample of 582 oncology outpatients who were receiving CTX, were to identify subgroups of patients based on their distinct experiences with 25 commonly occurring symptoms and to identify demographic and clinical characteristics associated with subgroup membership. In addition, differences in quality of life outcomes were evaluated. METHODS: Oncology outpatients with breast, gastrointestinal, gynecological, or lung cancer completed the Memorial Symptom Assessment Scale before their next cycle of CTX. Latent class analysis was used to identify subgroups of patients with distinct symptom experiences. RESULTS: Three distinct subgroups of patients were identified (ie, 36.1% in Low class; 50.0% in Moderate class, and 13.9% in All High class). Patients in the All High class were significantly younger and more likely to be female and nonwhite, and had lower levels of social support, lower socioeconomic status, poorer functional status, and a higher level of comorbidity. CONCLUSIONS: Findings from the current study support the clinical observation that some oncology patients experience a differentially higher symptom burden during CTX. These high-risk patients experience significant decrements in quality of life.

Association between an interleukin 1 receptor, type I promoter polymorphism and self-reported attentional function in women with breast cancer.

Subgroups of patients with breast cancer may be at greater risk for cytokine-induced changes in cognitive function after diagnosis and during treatment. The purposes of this study were to identify subgroups of patients with distinct trajectories of attentional function and evaluate for phenotypic and genotypic (i.e., cytokine gene polymorphisms) predictors of subgroup membership. Self-reported attentional function was evaluated in 397 patients with breast cancer using the Attentional Function Index before surgery and for six months after surgery (i.e., seven time points). Using growth mixture modeling, three attentional function latent classes were identified: High (41.6%), Moderate (25.4%), and Low-moderate (33.0%). Patients in the Low-moderate class were significantly younger than those in the High class, with more comorbidities and lower functional status than the other two classes. No differences were found among the classes in years of education, race/ethnicity, or other clinical characteristics. DNA was recovered from 302 patients' samples. Eighty-two single nucleotide polymorphisms among 15 candidate genes were included in the genetic association analyses. After controlling for age, comorbidities, functional status, and population stratification due to race/ethnicity, IL1R1 rs949963 remained a significant genotypic predictor of class membership in the multivariable model. Carrying the rare "A" allele (i.e., GA+AA) was associated with a twofold increase in the odds of belonging to a lower attentional function class (OR: 1.98; 95% CI: 1.18, 3.30; p=.009). Findings provide evidence of subgroups of women with breast cancer who report distinct trajectories of attentional function and of a genetic association between subgroup membership and an IL1R1 promoter polymorphism.

Variations in potassium channel genes are associated with breast pain in women prior to breast cancer surgery.

Preoperative breast pain in women with breast cancer may result from a number of causes. Previous work from our team found that breast pain occurred in 28.2% of women (n = 398) who were about to undergo breast cancer surgery. The occurrence of preoperative breast pain was associated with a number of demographic and clinical characteristics, as well as variation in two cytokine genes. Given that ion channels regulate excitability of sensory neurons, we hypothesized that variations in potassium channel genes would be associated with preoperative breast pain in these patients. Therefore, in this study, we evaluated for associations between single-nucleotide polymorphisms and inferred haplotypes among 10 potassium channel genes and the occurrence of preoperative breast pain in patients scheduled to undergo breast cancer surgery. Multivariable logistic regression analyses were used to identify those genetic variations that were associated with the occurrence of preoperative breast pain while controlling for age and genomic estimates of and self-reported race/ethnicity. Variations in four potassium channel genes: (1) potassium voltage-gated channel, delayed rectifier, subfamily S, member 1 (KCNS1); (2) potassium inwardly rectifying channel, subfamily J, member 3 (KCNJ3); (3) KCNJ6; and (4) potassium channel, subfamily K, member 9 (KCNK9) were associated with the occurrence of breast pain. Findings from this study warrant replication in an independent sample of women who report breast pain following one or more breast biopsies.

Use of patient-reported global assessment measures in clinical trials of chronic pain treatments: ACTTION systematic review and considerations.

ABSTRACT: Establishing clinically meaningful changes in pain experiences remains important for clinical trials of chronic pain treatments. Regulatory guidance and pain measurement initiatives have recommended including patient-reported global assessment measures (eg, Patient-Global Impression of Change [PGIC]) to aid interpretation of within-patient differences in domain-specific clinical trial outcomes (eg, pain intensity). The objectives of this systematic review were to determine the frequency of global assessment measures inclusion, types of measures, domains assessed, number and types of response options, and how measures were analyzed. Of 4172 abstracts screened across 6 pain specialty journals, we reviewed 96 clinical trials of chronic pain treatments. Fifty-two (54.2%) studies included a global assessment measure. The PGIC was most common (n = 28; 53.8%), with relatively infrequent use of other measures. The majority of studies that used a global assessment measure (n = 31; 59.6%) assessed change or improvement in an unspecified domain. Others assessed overall condition severity (n = 9; 17.3%), satisfaction (n = 8; 15.4%), or overall health status/recovery (n = 5; 9.6%). The number, range, and type of response options were variable and frequently not reported. Response options and reference periods even differed within the PGIC. Global assessment measures were most commonly analyzed as continuous variables (n = 24; 46.2%) or as dichotomous variables with positive categories combined to calculate the proportion of participants with a positive response to treatment (n = 18; 34.6%). This review highlights the substantial work necessary to clarify measurement and use of patient global assessment in chronic pain trials and provides short- and long-term considerations for measure selection, reporting and analysis, and measure development.

Patient engagement in designing, conducting, and disseminating clinical pain research: IMMPACT recommended considerations.

ABSTRACT: In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are engaged as partners in research. Although this approach has become commonplace in some fields of clinical research, it remains the exception in clinical pain research. As such, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials convened a meeting with patient partners and international representatives from academia, patient advocacy groups, government regulatory agencies, research funding organizations, academic journals, and the biopharmaceutical industry to develop consensus recommendations for advancing patient engagement in all stages of clinical pain research in an effective and purposeful manner. This article summarizes the results of this meeting and offers considerations for meaningful and authentic engagement of patient partners in clinical pain research, including recommendations for representation, timing, continuous engagement, measurement, reporting, and research dissemination.

Coding of facial expressions of pain in the laboratory mouse.

Facial expression is widely used as a measure of pain in infants; whether nonhuman animals display such pain expressions has never been systematically assessed. We developed the mouse grimace scale (MGS), a standardized behavioral coding system with high accuracy and reliability; assays involving noxious stimuli of moderate duration are accompanied by facial expressions of pain. This measure of spontaneously emitted pain may provide insight into the subjective pain experience of mice.

Covariate Adjustment in Chronic Pain Trials: An Oft-Missed Opportunity.

Self-reported pain intensity, frequently used as an outcome in randomized clinical trials (RCTs) of chronic pain, is often highly variable and could be associated with multiple baseline factors. Thus, the assay sensitivity of pain trials (ie, the ability of the trial to detect a true treatment effect) could be improved by including prespecified baseline factors in the primary statistical model. The objective of this focus article was to characterize the baseline factors included in statistical analyses of chronic pain RCTs. Seventy-three RCTs published between 2016 and 2021 that investigated interventions for chronic pain were included. The majority of trials identified a single primary analysis (72.6%; n = 53). Of these, 60.4% (n = 32) included one or more covariates in the primary statistical model, most commonly baseline value of the primary outcome, study site, sex, and age. Only one of the trials reported information regarding associations between covariates and outcomes (ie, information that could inform prioritization of covariates for prespecification in future analyses). These findings demonstrate inconsistent use of covariates in the statistical models in chronic pain clinical trials. Prespecified adjustments for baseline covariates that could increase precision and assay sensitivity should be considered in future clinical trials of chronic pain treatments. PERSPECTIVE: This review demonstrates inconsistent inclusion and potential underutilization of covariate adjustment in analyses of chronic pain RCTs. This article highlights areas for possible improvement in design and reporting related to covariate adjustment to improve efficiency in future RCTs.