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Item Associations Between Dysmenorrhea Symptom-Based Phenotypes and Vaginal Microbiome: A Pilot Study(Wolters Kluwer, 2021) Chen, Chen X.; Carpenter, Janet S.; Gao, Xiang; Toh, Evelyn; Dong, Qunfeng; Nelson, David E.; Mitchell, Caroline; Fortenberry, J. DennisBACKGROUND: Dysmenorrhea is highly prevalent; it places women at risk for other chronic pain conditions. There is a high degree of individual variability in menstrual pain severity, the number of painful sites, and co-occurring gastrointestinal symptoms. Distinct dysmenorrhea symptom-based phenotypes were previously identified, but the biological underpinnings of these phenotypes are less known. One underexplored contributor is the vaginal microbiome. The vaginal microbiota differs significantly among reproductive-age women and may modulate as well as amplify reproductive tract inflammation, which may contribute to dysmenorrhea symptoms. OBJECTIVES: The objective of this study was to examine associations between dysmenorrhea symptom-based phenotypes and vaginal microbiome compositions on- and off-menses. METHODS: We conducted a prospective, longitudinal, pilot study of 20 women (aged 15-24 years) grouped into three dysmenorrhea symptom-based phenotypes: "mild localized pain," "severe localized pain," and "severe multiple pain and gastrointestinal symptoms." Over one menstrual cycle, participants provided vaginal swabs when they were on- and off-menses. We assayed the vaginal microbiome using 16S rRNA gene sequencing. Permutational multivariate analysis of variance tests were used to compare microbiome compositions across phenotypes, with heat maps generated to visualize the relative abundance of bacterial taxa. RESULTS: The vaginal microbiome compositions (n = 40) were different across the three phenotypes. After separating the on-menses (n = 20) and off-menses (n = 20) specimens, the statistically significant difference was seen on-menses, but not off-menses. Compared to the "mild localized pain" phenotype, participants in the "multiple severe symptoms" phenotype had a lower lactobacilli level and a higher abundance of Prevotella, Atopobium, and Gardnerella when on-menses. We also observed trends of differences across phenotypes in vaginal microbiome change from off- to on-menses. DISCUSSION: The study provides proof-of-concept data to support larger studies on associations between dysmenorrhea symptom-based phenotypes and vaginal microbiome that might lead to new intervention targets and/or biomarkers for dysmenorrhea. This line of research has the potential to inform precision dysmenorrhea treatment that can improve women's quality of life.Item Coping is Complicated: Examining the Roles of Coping Strategies and Pain Self-Efficacy for Black Veterans with Chronic Pain(2024-12) Procento, Philip Matthew; Hirsh, Adam T.; Matthias, Marianne S.; Rand, Kevin L.; Stewart, Jesse C.Black patients with chronic pain routinely receive insufficient pain management, which contributes to myriad worse outcomes. This inadequate care stems from various factors, including systemic marginalization, provider bias, and patient-level factors. The present study focused on two patient factors: pain self-efficacy and coping strategies. It explored whether the relationship of pain intensity and pain interference was explained by active (less interference) and passive (greater interference) coping strategies, and it investigated if pain self-efficacy strengthened or weakened these mediating relationships. As part of a larger study, Black veterans with chronic pain completed measures assessing pain interference, coping strategies, and self-efficacy. Simple mediation analyses indicated that the relationship between pain intensity and interference was mediated by passive, but not active, coping. Higher pain intensity predicted greater passive coping, which led to worse pain interference. A parallel mediation analysis affirmed this mediating effect when controlling for active coping. Moderated mediation analyses found that pain self-efficacy moderated the mediating effect of passive, but not active, coping. Participants with lower (vs. higher) pain self-efficacy used more passive coping (in absolute terms) across pain intensity levels, but those with higher (vs. lower) self-efficacy experienced greater increases in their passive coping as their pain intensity increased. A parallel moderated mediation analysis affirmed this moderated mediation effect when controlling for active coping. These results suggest that passive coping is a possible mechanism by which pain intensity leads to interference among Black veterans with chronic pain, and that self-efficacy modulates this effect. Future research should replicate these results in other patient samples, investigate other possible moderators (e.g., PTSD), and design interventions to reduce the use of passive coping strategies while simultaneously increasing pain self-efficacy.Item Development of the Chronic Pain Coding System (CPCS) for Characterizing Patient-Clinician Discussions About Chronic Pain and Opioids(Oxford Academic, 2016-10) Henry, Stephen G.; Chen, Meng; Matthias, Marianne S.; Bell, Robert A.; Kravitz, Richard L.; Communication Studies, School of Liberal ArtsObjective. To describe the development and initial application of the Chronic Pain Coding System., Design. Secondary analysis of data from a randomized clinical trial., Setting. Six primary care clinics in northern California., Subjects. Forty-five primary care visits involving 33 clinicians and 45 patients on opioids for chronic noncancer pain., Methods. The authors developed a structured coding system to accurately and objectively characterize discussions about pain and opioids. Two coders applied the final system to visit transcripts. Intercoder agreement for major coding categories was moderate to substantial (kappa = 0.5–0.7). Mixed effects regression was used to test six hypotheses to assess preliminary construct validity., Results. Greater baseline pain interference was associated with longer pain discussions (P = 0.007) and more patient requests for clinician action (P = 0.02) but not more frequent negative patient evaluations of pain (P = 0.15). Greater clinician-reported visit difficulty was associated with more frequent disagreements with clinician recommendations (P = 0.003) and longer discussions of opioid risks (P = 0.049) but not more frequent requests for clinician action (P = 0.11). Rates of agreement versus disagreement with patient requests and clinician recommendations were similar for opioid-related and non-opioid–related utterances., Conclusions. This coding system appears to be a reliable and valid tool for characterizing patient-clinician communication about opioids and chronic pain during clinic visits. Objective data on how patients and clinicians discuss chronic pain and opioids are necessary to identify communication patterns and strategies for improving the quality and productivity of discussions about chronic pain that may lead to more effective pain management and reduce inappropriate opioid prescribing.Item Examining influential factors in providers’ chronic pain treatment decisions: a comparison of physicians and medical students(BMC, 2015) Hollingshead, Nicole A.; Meints, Samantha; Middleton, Stephanie K.; Free, Charnelle A.; Hirsh, Adam T.; Department of Psychology, School of ScienceChronic pain treatment guidelines are unclear and conflicting, which contributes to inconsistent pain care. In order to improve pain care, it is important to understand the various factors that providers rely on to make treatment decisions. The purpose of this study was to examine factors that reportedly influence providers’ chronic pain treatment decisions. A secondary aim was to examine differences across participant training level.Item Examining the influence of Hispanic ethnicity and ethnic bias on medical students’ pain decisions(2016-05-09) Hollingshead, Nicole A.; Hirsh, Adam Todd; Ashburn-Nardo, Leslie; Stewart, Jesse; Maupomé, Gerardo; Grahame, Nicholas J.Hispanic patients receive disparate pain care compared to non-Hispanic White (NHW) patients. Healthcare providers’ ethnic bias may be one reason for pain disparities. This investigation sought to determine the influence of Hispanic ethnicity and ethnic bias on chronic pain management decisions. During an online experiment, 97 medical students made pain assessment and opioid treatment decisions for Hispanic and NHW virtual human patients with chronic pain. They also completed explicit and implicit measures of ethnic bias. Individual-level analyses found that 31% and 36% of participants demonstrated large effect sizes (dz>.50), indicating that patient ethnicity strongly influenced their pain assessment and opioid treatment decisions, respectively. At the group level of analysis, participants’ decisions did not differ significantly between NHW and Hispanic patients (all p values >.05). Participants did not report significant explicit ethnic bias (t[96]=1.88, p=.06; dz=.19; Hispanic mean rating=77.6[SD=18.7]; NHW mean rating=75.2[SD=19.4]) but demonstrated a small-to-moderate implicit preference for NHWs relative to Hispanics (Mean=.31[SD=.41]). Patient ethnicity and implicit ethnic bias had an interactive effect on opioid treatment decisions (F[1, 95]=5.15, p<.05, generalized eta squared =.02); however, the direction of the effect was not as hypothesized. Participants with higher implicit ethnic bias gave significantly higher opioid ratings to Hispanics relative to NHWs (p=.05), whereas participants with lower bias gave marginally higher opioid ratings to NHWs relative to Hispanics (p=.20). Participants with higher vs. lower implicit ethnic bias differed only in their treatment ratings for NHW patients, such that participants with lower bias gave significantly higher opioid ratings to NHW patients than did participants with higher bias (p<.05). This investigation found that approximately one-third of participants made significantly different chronic pain management decisions for Hispanic vs. NHW patients. Participants’ implicit ethnic bias interacted with their opioid treatment decisions but not as expected. Future investigations should measure healthcare providers’ stereotypes about Hispanic patients with pain as this may better predict their pain decisions.Item Minimally Important Differences and Severity Thresholds are Estimated for the PROMIS Depression Scales from Three Randomized Clinical Trials(Elsevier, 2020-04-01) Kroenke, Kurt; Stump, Timothy E.; Chen, Chen X.; Kean, Jacob; Bair, Matthew J.; Damush, Teresa M.; Krebs, Erin E.; Monahan, Patrick O.BACKGROUND: Patient Reported Outcomes Measurement Information Systems (PROMIS) scales are increasingly being used to measure symptoms in research and practice. The purpose of this study was to determine the minimally important difference (MID) and severity thresholds (cut-points) for the four fixed-length PROMIS depression scales. METHODS: The study sample was adult participants in three randomized clinical trials (N=651). MID was estimated using multiple distribution- and anchor-based approaches including assessing correspondence between Patient Health Questionnaire (PHQ-9) and PROMIS depression scores. RESULTS: The best MID estimate was a PROMIS depression T-score of 3.5 points with most methods producing an MID in the 3 to 4 point range across all three samples. MID estimates were similar for all four PROMIS scales. A PHQ-9 1-point change equated to a PROMIS 1.25-point T-score change. PROMIS T-scores of 55, 60, 65, and 70 appeared to be reasonable thresholds for mild, moderate, moderately severe, and severe depression, respectively. LIMITATIONS: The study sample was predominantly male veterans with either chronic pain (2 trials) or previous stroke (1 trial). The severity of depression was mild to moderate. CONCLUSION: A T-score of 3 to 4 points is a reasonable MID for PROMIS depression scales and can be used to assess treatment effects in both practice and research as well to calculate sample sizes for clinical trials. Severity cut-points can help interpret the meaning of scores and action thresholds for treatment decisions.Item Opioid Use as a Predictor of Pain Outcomes in Iraq and Afghanistan Veterans with Chronic Pain: Analysis of a Randomized Controlled Trial(Oxford Academic, 2021) Bushey, Michael A.; Wu, Jingwei; Outcalt, Samantha D.; Krebs, Erin E.; Ang, Dennis; Kline, Matthew; Yu, Zhangsheng; Bair, Matthew J.; Psychiatry, School of MedicineOBJECTIVE: 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.Item Pain self-management in HIV-infected individuals with chronic pain: a qualitative study(Wiley Blackwell (Blackwell Publishing), 2015-04) Merlin, Jessica S.; Walcott, Melonie; Kerns, Robert; Bair, Matthew J.; Burgio, Kathryn L.; Turan, Janet M.; Department of Medicine, IU School of MedicineOBJECTIVE: Chronic pain in individuals with HIV is a common, impairing condition. Behavioral interventions for chronic pain specifically tailored to this population have yet to be developed. We assert that understanding self-management strategies already used by persons living with these conditions is an essential first step, and is the objective of this investigation. DESIGN: We conducted a thematic analysis of qualitative data from 25 in-depth interviews with individuals with HIV and chronic pain. RESULTS: The primary pain self-management strategies articulated by participants were: physical activity; cognitive and spiritual strategies; spending time with family and friends and social support; avoidance of physical/social activity; medication-centric pain management; and substance use. CONCLUSIONS: Some of these strategies may be viewed as beneficial and overlap with known HIV self-management strategies (cognitive strategies), whereas others may have negative health consequences (substance use). Interventions that incorporate healthy self-management strategies may be particularly effective in improving both HIV and pain outcomes.Item Patients’ Experiences with Telecare for Chronic Pain and Mood Symptoms: A Qualitative Study(Oxford, 2020-10) Matthias, Marianne S.; Evans, Erica; Porter, Brian; McCalley, Stephanie; Kroenke, Kurt; Medicine, School of MedicineObjective Pain, anxiety, and depression commonly co-occur, can have reciprocal effects, and are associated with substantial disability and health care costs. However, few interventions target treatment of pain and mood disorders as a whole. The Comprehensive vs. Assisted Management of Mood and Pain Symptoms (CAMMPS) trial was a randomized trial comparing two pragmatic telecare interventions, a high- vs low-resource approach to pain and anxiety/depression treatment. The purpose of the current study is to better understand patients’ perspectives on both intervention approaches, including intervention components, delivery, patient experiences, and patient outcomes. Design Qualitative, semistructured interviews. Setting A Veterans Affairs Medical Center. Subjects Twenty-five patients were purposefully sampled from both study arms. Methods Patients were interviewed about their experiences with pain and mood treatment, perceived benefits and changes, and experiences with the intervention model to which they were randomized. The constant comparison method guided analysis. Results Pain was more important than mood for most participants. Participants described developing increased awareness of their symptoms, including connecting pain and mood, which enabled better management. Participants in the high-resource intervention described the added value of the study nurse in their symptom management. Conclusions Patients in a telecare intervention for chronic pain and mood symptoms learned to connect pain and mood and be more aware of their symptoms, enabling more effective symptom management. Patients in the high-resource intervention described the added benefits of a nurse who provided informational and motivational support. Implications for tradeoffs between resource intensity and patient outcomes are discussed.Item A randomized controlled trial testing a virtual perspective-taking intervention to reduce race and socioeconomic status disparities in pain care(Wolters Kluwer, 2019-10-01) Hirsh, Adam T.; Miller, Megan M.; Hollingshead, Nicole A.; Anastas, Tracy; Carnell, Stephanie T.; Lok, Benjamin C.; Chu, Chenghao; Zhang, Ying; Robinson, Michael E.; Kroenke, Kurt; Ashburn-Nardo, Leslie; Psychology, School of ScienceWe conducted a randomized controlled trial of an individually-tailored, virtual perspective-taking intervention to reduce race and socioeconomic (SES) disparities in providers’ pain treatment decisions. Physician residents and fellows (n=436) were recruited from across the United States for this two-part online study. Providers first completed a bias assessment task in which they made treatment decisions for virtual patients with chronic pain who varied by race (Black/White) and SES (low/high). Providers who demonstrated a treatment bias were randomized to the intervention or control group. The intervention consisted of personalized feedback about their bias, real-time dynamic interactions with virtual patients, and videos depicting how pain impacts the patients’ lives. Treatment bias was re-assessed one week later. Compared to the control group, providers who received the tailored intervention had 85% lower odds of demonstrating a treatment bias against Black patients and 76% lower odds of demonstrating a treatment bias against low SES patients at follow-up. Providers who received the intervention for racial bias also showed increased compassion for patients compared to providers in the control condition. Group differences did not emerge for provider comfort in treating patients. Results suggest an online intervention that is tailored to providers according to their individual treatment biases, delivers feedback about these biases, and provides opportunities for increased contact with Black and low SES patients, can produce substantial changes in providers’ treatment decisions, resulting in more equitable pain care. Future studies should examine how these effects translate to real-world patient care, and the optimal timing/dose of the intervention.