A conserved pathway of transdifferentiation in murine Kupffer cells.

Abundant long-lived liver-resident macrophages, termed Kupffer cells, are activated during chronic liver injury. They secrete both pro-inflammatory and pro-fibrotic cytokines, which act on hepatic stellate cells causing their transdifferentiation into myofibroblasts that deposit collagen. In other tissues, wound-associated macrophages go further, and transdifferentiate into fibrocytes, secreting collagen themselves. We tested Kupffer cells for this property in two experimental models: mixed non-parenchymal cell culture, and precision-cut liver slice culture. Using the Emr1-Cre transgene as a driver and the RiboTag transgene as a reporter, we found that Kupffer cells undergo transdifferentiation under these circumstances. Over time, they lose the expression of both Kupffer cell-specific and macrophage-specific genes and the transcription factors that control their expression, and they begin to express multiple genes and proteins characteristic of either myofibroblasts or tissue fibroblasts. These effects were strongly conserved between non-parenchymal cell culture and liver tissue slice culture, arguing that such transdifferentiation is a conserved function of Kupffer cells. We conclude that in addition to supporting fibrosis through an action on stellate cells, Kupffer cells also participate in liver fibrosis through transdifferentiation into fibrocytes.

Management of acne in transgender and gender diverse youth part 1: Gender affirming care and risk factors for the development of acne.

Acne vulgaris is among the most common skin disorders afflicting adolescents worldwide, and though well-established guidelines of care exist for acne management, these guidelines do not uniformly consider or address the unique psychosocial and medical needs of transgender and gender diverse (TGD) youth. TGD youth may possess distinct goals of therapy when treating their acne; the use of medicines routinely employed to treat acne may also expose TGD adolescents receiving gender affirming medical therapy to greater risk of adverse events. Part 1 of this two-part review provides dermatologists an understanding of gender affirming care and its timing, as well as its potential impacts on the development of acne in TGD youth.

Management of acne in transgender and gender diverse youth Part 2: Unique considerations and strategies in medical treatment.

Acne vulgaris is among the most common skin disorders afflicting adolescents worldwide, and though well-established guidelines of care exist for acne management, these guidelines do not uniformly consider or address the unique psychosocial and medical needs of transgender and gender diverse (TGD) youth. Part 2 of this two-part review provides guidance on a stepwise approach to the medical treatment of acne in TGD youth, with an emphasis on safety, efficacy, and the delivery of medical care in a culturally humble, thoughtful, and gender-affirming manner.

Functional responses of resident human T cells in intact liver tissue.

The liver contains a rich mix of T cells, including activated T cells, tissue-resident memory T cells and cells undergoing apoptosis. When antigens are presented in this milieu the default result is functional tolerance. T cell tolerance in the liver could be constitutive, or it could be adaptive, in which case liver cells would become unresponsive after encountering antigen in the liver context. To test this model, we evaluated the potential of human liver T cells to respond to T cell receptor ligation in liver tissue slice cultures. These T cells contained an actively motile subset of CD4+ T cells marked by CCR7 and CD62L, and fully functional subsets of CD4+ and CD8+ T cells that synthesized effector cytokines but subsequently assumed an exhausted phenotype. These data favor the model that human liver T cells are not constitutively tolerant but undergo adaptive tolerance after activation.

The Unique and Interactive Effects of Patient Race, Patient Socioeconomic Status, and Provider Attitudes on Chronic Pain Care Decisions.

BACKGROUND: Compared to White and high socioeconomic status (SES) patients, Black and low SES patients receive less adequate pain care. Providers may contribute to these disparities by making biased decisions that are driven, in part, by their attitudes about race and SES. PURPOSE: We examined the effects of patient race and SES on providers' chronic pain decisions and the extent to which providers' implicit and explicit attitudes about race and SES were related to these decisions. METHODS: Physician residents/fellows (n = 436) made pain care decisions for 12 computer-simulated patients with chronic back pain that varied by race (Black/White) and SES (low/high). Physicians also completed measures assessing implicit and explicit attitudes about race and SES. RESULTS: There were three significant race-by-SES interactions: (a) For high SES patients, Black (vs. White) patients were rated as having more pain interference; the opposite race difference emerged for low SES patients. (b) For high SES patients, Black (vs. White) patients were rated as being in greater distress; no race difference emerged for low SES patients. (c) For low SES patients, White (vs. Black) patients were more likely to be recommended workplace accommodations; no race difference emerged for high SES patients. Additionally, providers were more likely to recommend opioids to Black (vs. White) and low (vs. high) SES patients, and were more likely to use opioid contracts with low (vs. high) SES patients. Providers' implicit and explicit attitudes predicted some, but not all, of their pain-related ratings. CONCLUSION: These results highlight the need to further examine the effects of patient race and SES simultaneously in the context of pain care.

Differences in Mexican Americans' Prevalence of Chronic Pain and Co-Occurring Analgesic Medication and Substance Use Relative to Non-Hispanic White and Black Americans: Results from NHANES 1999-2004.

OBJECTIVE: Little is known about the burgeoning Mexican American (MA) population's pain experience. METHODS: Using 1999-2004 National Health and Nutrition Examination Survey (NHANES) data, prevalence of chronic pain, analgesic medication use, and substance use were examined among MA, non-Hispanic White (NHW), and non-Hispanic Black (NHB) respondents. Logistic and linear regression models examined racial/ethnic differences in: 1) chronic pain prevalence among all respondents, 2) location and number of pain sites among respondents with chronic pain, and 3) analgesic medication and substance use among respondents with chronic pain. RESULTS: Compared to NHWs and NHBs, MAs were less likely to report any chronic pain. Among respondents with chronic pain, MAs had higher odds of reporting headache, abdominal pain, and a greater number of pain sites than NHWs. Compared to NHWs, MAs with chronic pain had lower odds of reporting past-month analgesic medication and COX-2 inhibitor use. MAs with chronic pain had lower odds of being a current cigarette smoker and heavy alcohol drinker but had similar street drug/cocaine use relative to NHWs. CONCLUSIONS: Results suggest that: 1) MAs are less likely to develop chronic pain than NHWs, 2) MAs with chronic pain report greater headache and abdominal pain than NHWs, and 3) MAs with chronic pain are less likely to use analgesic medications and other substances compared to NHWs. These results suggest that providers should consider taking extra time to discuss analgesic medications with MAs. Future investigations should examine reasons underlying these racial/ethnic differences in chronic pain, as well as differences in the use of other substances, such as marijuana.

A comparison of race-related pain stereotypes held by White and Black individuals.

Pain judgments are the basis for pain management. The purpose of this study was to assess Black and White participants' race-related pain stereotypes. Undergraduates (n=551) rated the pain sensitivity and willingness to report pain for the typical Black person, White person, and themselves. Participants, regardless of race, rated the typical White person as being more pain sensitive and more willing to report pain than the typical Black person. White participants rated themselves as less sensitive and less willing to report pain than same-race peers; however, Black participants rated themselves as more pain sensitive and more willing to report pain than same-race peers. These findings highlight similarities and differences in racial stereotypic pain beliefs held by Black and White individuals.

Impact of race and sex on pain management by medical trainees: a mixed methods pilot study of decision making and awareness of influence.

OBJECTIVE: Previous research suggests female and black patients receive less optimal treatment for their chronic pain compared with male and white patients. Provider-related factors are hypothesized to contribute to unequal treatment, but these factors have not been examined extensively. This mixed methods investigation examined the influence of patients' demographic characteristics on providers' treatment decisions and providers' awareness of these influences on their treatment decisions. METHODS: Twenty medical trainees made treatment decisions (opioid, antidepressant, physical therapy) for 16 virtual patients with chronic low back pain; patient sex and race were manipulated across patients. Participants then indicated from a provided list the factors that influenced their treatment decisions, including patient demographics. Finally, individual interviews were conducted to discuss the role of patient demographics on providers' clinical decisions. RESULTS: Individual regression analyses indicated that 30% of participants were reliably influenced by patient sex and 15% by patient race when making their decisions (P < 0.05 or P < 0.10). Group analyses indicated that white patients received higher antidepressant recommendations, on average, than black patients (P < 0.05). Half of the medical trainees demonstrated awareness of the influence of demographic characteristics on their decision making. Participants, regardless of whether they were influenced by patients' demographics, discussed themes related to patient sex and race; however, participants' discussion of patient demographics in the interviews did not always align with their online study results. CONCLUSIONS: These findings suggest there is a considerable variability in the extent to which medical trainees are influenced by patient demographics and their awareness of these decision making influences.

Examining influential factors in providers' chronic pain treatment decisions: a comparison of physicians and medical students.

BACKGROUND: Chronic 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. METHODS: Eighty-five participants (35 medical students, 50 physicians) made treatment decisions for 16 computer-simulated patients with chronic pain. Participants then selected from provided lists the information they used and the information they would have used (had it been available) to make their chronic pain treatment decisions for the patient vignettes. RESULTS: Frequency analyses indicated that most participants reported using patients' pain histories (97.6 %) and pain description (95.3 %) when making treatment decisions, and they would have used information about patients' previous treatments (97.6 %) and average and current pain ratings (96.5 %) had this information been available. Compared to physicians, medical students endorsed more frequently that they would have used patients' employment and/or disability status (p < 0.05). A greater proportion of medical students wanted information on patients' use of illicit drugs and alcohol to make treatment decisions; while a greater proportion of physicians reported using personal experience to inform their decisions. DISCUSSION: This study found providers use patients' information and their own experiences and intuition to make chronic pain treatment decisions. Also, participants of different training levels report using different patient and personal factors to guide their treatment decisions. CONCLUSIONS: These results highlight the complexity of chronic pain care and suggest a need for more chronic pain education aimed at medical students and practicing providers.

Language Use and Generation Status are Associated with Chronic Pain Differences in Mexican Americans.

Little is known about the pain experience of the Mexican American (MA) population. We investigated the associations between language use and generation status with chronic pain prevalence, health insurance coverage, and analgesic medication use. We examined 3373 MA respondents from the National Health and Nutrition Examination Survey. We found higher levels of English use and generation status were associated with higher odds of reporting chronic pain. For respondents reporting chronic pain, higher levels of English use and generation status were associated with higher odds of being covered by health insurance, lower odds of having a period of time last year without health insurance, and higher odds of being prescribed any analgesic medication, especially opioid medications. We found language use and generation status play a role in MAs' experience, access, and treatment of chronic pain. Patient-, provider-, and systems-level interventions may be needed to reduce these disparities.

Response of Human Liver Tissue to Innate Immune Stimuli.

Precision-cut human liver slice cultures (PCLS) have become an important alternative immunological platform in preclinical testing. To further evaluate the capacity of PCLS, we investigated the innate immune response to TLR3 agonist (poly-I:C) and TLR4 agonist (LPS) using normal and diseased liver tissue. Pathological liver tissue was obtained from patients with active chronic HCV infection, and patients with former chronic HCV infection cured by recent Direct-Acting Antiviral (DAA) drug therapy. We found that hepatic innate immunity in response to TLR3 and TLR4 agonists was not suppressed but enhanced in the HCV-infected tissue, compared with the healthy controls. Furthermore, despite recent HCV elimination, DAA-cured liver tissue manifested ongoing abnormalities in liver immunity: sustained abnormal immune gene expression in DAA-cured samples was identified in direct ex vivo measurements and in TLR3 and TLR4 stimulation assays. Genes that were up-regulated in chronic HCV-infected liver tissue were mostly characteristic of the non-parenchymal cell compartment. These results demonstrated the utility of PCLS in studying both liver pathology and innate immunity.

Altered vitamin A metabolism in human liver slices corresponds to fibrogenesis.

All-trans-retinoic acid (atRA), the active metabolite of vitamin A, has antifibrogenic properties in vitro and in animal models. Liver vitamin A homeostasis is maintained by cell-specific enzymatic activities including storage in hepatic stellate cells (HSCs), secretion into circulation from hepatocytes, and formation and clearance of atRA. During chronic liver injury, HSC activation is associated with a decrease in liver retinyl esters and retinol concentrations. atRA is synthesized through two enzymatic steps from retinol, but it is unknown if the loss of retinoid stores is associated with changes in atRA formation and which cell types contribute to the metabolic changes. The aim of this study was to determine if the vitamin A metabolic flux is perturbed in acute liver injury, and if changes in atRA concentrations are associated with HSC activation and collagen expression. At basal levels, HSC and Kupffer cells expressed key genes involved in vitamin A metabolism, whereas after acute liver injury, complex changes to the metabolic flux were observed in liver slices. These changes include a reproducible spike in atRA tissue concentrations, decreased retinyl ester and atRA formation rate, and time-dependent changes to the expression of metabolizing enzymes. Kinetic simulations suggested that oxidoreductases are important in determining retinoid metabolic flux after liver injury. These early changes precede HSC activation and upregulation of profibrogenic gene expression, which were inversely correlated with atRA tissue concentrations, suggesting that HSC and Kupffer cells are key cells involved in changes to vitamin A metabolic flux and signaling after liver injury. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Vitamin A is metabolized in the liver for storage as retinyl esters in hepatic stellate cell (HSCs) or to all-trans-retinoic acid (atRA), an active metabolite with antifibrogenic properties. Following chronic liver injury, vitamin A metabolic flux is perturbed, and HSC activation leads to diminished retinoid stores. WHAT QUESTION DID THIS STUDY ADDRESS? Do changes in the expression of vitamin A metabolizing enzymes explain changes in atRA concentrations and the regulation of fibrosis following acute liver injury? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? In healthy liver, both HSC and Kupffer cells may mediate vitamin A homeostasis. Following acute liver injury, complex changes in metabolizing enzyme expression/activity alter the metabolic flux of retinoids, resulting in a transient peak in atRA concentrations. The atRA concentrations are inversely correlated with profibrogenic gene expression, HSC activation, and collagen deposition. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Improved understanding of altered vitamin A metabolic flux in acute liver injury may provide insight into cell-specific contributions to vitamin A loss and lead to novel interventions in liver fibrosis.

Intergroup anxiety in pain care: impact on treatment recommendations made by white providers for black patients.

Race disparities in pain care are well-documented. Given that most black patients are treated by white providers, patient-provider racial discordance is one hypothesized contributor to these disparities. Research and theory suggest that providers' trait-level intergroup anxiety impacts their state-level comfort while treating patients, which, in turn, impacts their pain treatment decisions. To test these hypothesized relationships, we conducted a planned secondary analysis of data from a randomized controlled trial of a perspective-taking intervention to reduce pain treatment disparities. Mediation analyses were conducted on treatment decision data from white providers for black virtual patients with chronic pain. Results indicated that white providers with higher trait-level intergroup anxiety reported lower state-level comfort treating black patients and were thereby more likely to recommend opioid (indirect effect = 0.76, 95% confidence interval [CI]: 0.21-1.51) and pain specialty (indirect effect = 0.91, 95% CI: 0.26-1.78) treatments and less likely to recommend nonopioid analgesics (indirect effect = -0.45, 95% CI: -0.94 to -0.12). Neither trait-level intergroup anxiety nor state-level comfort significantly influenced provider decisions for physical therapy. This study provides important new information about intrapersonal and interpersonal contributors to race disparities in chronic pain care. These findings suggest that intergroup anxiety and the resulting situational discomfort encroach on the clinical decision-making process by influencing white providers' decisions about which pain treatments to recommend to black patients. Should these findings be replicated in future studies, they would support interventions to help providers become more aware of their trait-level intergroup anxiety and manage their state-level reactions to patients who are racially/ethnically different from themselves.

Effects of a 12-week yoga versus a 12-week educational film intervention on symptoms of restless legs syndrome and related outcomes: an exploratory randomized controlled trial.

STUDY OBJECTIVES: To assess the effects of a yoga versus educational film (EF) program on restless legs syndrome (RLS) symptoms and related outcomes in adults with RLS. METHODS: Forty-one community-dwelling, ambulatory nonpregnant adults with moderate to severe RLS were randomized to a 12-week yoga (n = 19) or EF program (n = 22). In addition to attending classes, all participants completed practice/treatment logs. Yoga group participants were asked to practice at home 30 minutes per day on nonclass days; EF participants were instructed to record any RLS treatments used on their daily logs. Core outcomes assessed pretreatment and posttreatment were RLS symptoms and symptom severity (International RLS Study Group Scale (IRLS) and RLS ordinal scale), sleep quality, mood, perceived stress, and quality of life (QOL). RESULTS: Thirty adults (13 yoga, 17 EF), aged 24 to 73 (mean = 50.4 ± 2.4 years), completed the 12-week study (78% female, 80.5% white). Post-intervention, both groups showed significant improvement in RLS symptoms and severity, perceived stress, mood, and QOL-mental health (P ≤ .04). Relative to the EF group, yoga participants demonstrated significantly greater reductions in RLS symptoms and symptom severity (P ≤ .01), and greater improvements in perceived stress and mood (P ≤ .04), as well as sleep quality (P = .09); RLS symptoms decreased to minimal/mild in 77% of yoga group participants, with none scoring in the severe range by week 12, versus 24% and 12%, respectively, in EF participants. In the yoga group, IRLS and RLS severity scores declined with increasing minutes of homework practice (r = .7, P = .009 and r = .6, P = .03, respectively), suggesting a possible dose-response relationship. CONCLUSIONS: Findings of this exploratory RCT suggest that yoga may be effective in reducing RLS symptoms and symptom severity, decreasing perceived stress, and improving mood and sleep in adults with RLS. CLINICAL TRIAL REGISTRATION: Registry: Clinicaltrials.gov; Title: Yoga vs. Education for Restless Legs: a Feasibility Study; Identifier: NCT03570515; URL: https://clinicaltrials.gov/ct2/show/NCT03570515.

Human Liver Macrophage Subsets Defined by CD32.

Human liver myeloid cells are imperfectly defined, but it is broadly agreed that cells of stellate appearance in situ, expressing the markers CD11b and CD68, are the liver's resident macrophages, classically termed Kupffer cells. Recent investigations using single cell RNA sequencing and unsupervised clustering algorithms suggest there are two populations of cells with the characteristics of tissue macrophages in human liver. We therefore analyzed dissociated human liver tissue using the markers CD11b and CD68 to define macrophage-like cells and found within this population two subsets that differ in their expression of multiple surface markers. These subsets were FACS-sorted based on CD32 expression, and gene expression analysis identified them with human liver myeloid cell subsets that were previously defined by two independent single cell RNA sequencing studies. Using qRT-PCR we found that the two subsets differed in the expression of genes associated with T cell activation and immunosuppression, suggesting distinct roles in T cell tolerance. In addition, one subset expressed two markers, CD1C and CD11c, more often seen on classical dendritic cells. Criteria used to distinguish macrophages from dendritic cells in other tissues may need to be revised in the human liver.

A randomized controlled trial testing a virtual perspective-taking intervention to reduce race and socioeconomic status disparities in pain care.

We conducted a randomized controlled trial of an individually tailored, virtual perspective-taking intervention to reduce race and socioeconomic status (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 1 week later. Compared with 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 with 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.

Associations between immigrant status and pharmacological treatments for diabetes in U.S. adults.

OBJECTIVES: Although treatment disparities in diabetes have been documented along racial/ethnic lines, it is unclear if immigrant groups in the United States experience similar treatment disparities. Our objective was to determine whether immigrant status is associated with differences in pharmacological treatment of diabetes in a nationally representative sample of adults with diabetes. We were specifically interested in differences in treatment with oral hypoglycemic agents (OHA) and insulin. METHOD: Respondents were 2,260 adults from National Health and Nutritional Examination Survey (NHANES) 2003-2012 with a self-reported diabetes diagnosis. Immigrant status was indicated by birth within (U.S.-born) or outside (foreign-born) the 50 U.S. States or Washington, DC. Multinomial logistic regression analyses examined associations between immigrant status and (a) treatment with OHAs only and (b) treatment with insulin only or insulin and OHA combination therapy, using no treatment as the reference group. RESULTS: Adjusting for demographics, diabetes severity and duration, cardiovascular disease (CVD), and CVD risk factors, being foreign-born versus U.S.-born was not associated with treatment with OHAs only (odds ratio [OR] = 1.59; 95% confidence interval [CI] [0.97, 2.60]). However, being foreign-born was associated with decreased odds (OR = 0.53; 95% CI [0.28, 0.99]) of treatment with insulin. CONCLUSIONS: Pharmacological treatment of diabetes differs along immigrant status lines. To understand these findings, studies capturing the processes underlying treatment differences in diabetes among immigrants are needed. Findings raise the possibility that integrating information about a patient's immigrant status, in addition to racial/ethnic identity, may be an important component of culturally sensitive diabetes care. (PsycINFO Database Record

The Pain Experience of Hispanic Americans: A Critical Literature Review and Conceptual Model.

UNLABELLED: Although the Hispanic population is a burgeoning ethnic group in the United States, little is known about their pain-related experience. To address this gap, we critically reviewed the existing literature on pain experience and management among Hispanic Americans (HAs). We focused our review on the literature on nonmalignant pain, pain behaviors, and pain treatment seeking among HAs. Pain management experiences were examined from HA patients' and health care providers' perspectives. Our literature search included variations of the term "Hispanic" with "AND pain" in PubMed, Embase, Web of Science, ScienceDirect, and PsycINFO databases. A total of 117 studies met our inclusion criteria. We organized the results into a conceptual model with separate categories for biological and/or psychological and sociocultural and/or systems-level influences on HAs' pain experience, response to pain, and seeking and receiving pain care. We also included information on health care providers' experience of treating HA patients with pain. For each category, we identified future areas of research. We conclude with a discussion of limitations and clinical implications. PERSPECTIVE: In this critical review of the literature we examined the pain and management experiences of the HA population. We propose a conceptual model, which highlights findings from the existing literature and future areas of research.

The interaction of patient race, provider bias, and clinical ambiguity on pain management decisions.

UNLABELLED: Although racial disparities in pain care are widely reported, much remains to be known about the role of provider and contextual factors. We used computer-simulated patients to examine the influence of patient race, provider racial bias, and clinical ambiguity on pain decisions. One hundred twenty-nine medical residents/fellows made assessment (pain intensity) and treatment (opioid and nonopioid analgesics) decisions for 12 virtual patients with acute pain. Race (black/white) and clinical ambiguity (high/low) were manipulated across vignettes. Participants completed the Implicit Association Test and feeling thermometers, which assess implicit and explicit racial biases, respectively. Individual- and group-level analyses indicated that race and ambiguity had an interactive effect on providers' decisions, such that decisions varied as a function of ambiguity for white but not for black patients. Individual differences across providers were observed for the effect of race and ambiguity on decisions; however, providers' implicit and explicit biases did not account for this variability. These data highlight the complexity of racial disparities and suggest that differences in care between white and black patients are, in part, attributable to the nature (ie, ambiguity) of the clinical scenario. The current study suggests that interventions to reduce disparities should differentially target patient, provider, and contextual factors. PERSPECTIVE: This study examined the unique and collective influence of patient race, provider racial bias, and clinical ambiguity on providers' pain management decisions. These results could inform the development of interventions aimed at reducing disparities and improving pain care.

Preferences, experience, and attitudes in the management of chronic pain and depression: a comparison of physicians and medical students.

OBJECTIVES: The current study investigated clinicians' treatment preferences for chronic pain and depression and the extent to which these preferences were related to clinicians' experience and attitudes. METHODS: Eighty-five participants (50 physicians, 35 medical students) made treatment recommendations for 8 virtual patients with chronic low back pain and depression. The 10 treatment options included pharmacological and nonpharmacological approaches. Participants also provided information about their clinical experience and completed measures assessing their attitudes toward patients with pain and depression. RESULTS: The highest recommended treatments were over-the-counter medications and topical modalities, whereas "no intervention," referral to a pain specialist, and opioid medication received the lowest ratings. Physicians gave higher ratings to physical therapy (P<0.05) and lifestyle activities (P<0.05) than did medical students. Students reported more negative attitudes about patients with depression (P<0.05) than did physicians. After controlling for participants' attitudes, the treatment preference×training level interaction was no longer significant (P>0.05). DISCUSSION: Physicians and medical students shared a general preference for "low-risk," self-management approaches for chronic pain and depression; however, they differed in their recommendations for some specific treatments. Participants' attitudes toward patients with pain and depression were associated with their preferences and accounted for the differences in their treatment decisions. These results suggest a need for early and continuing education to reduce clinicians' negative attitudes toward and improve the management of patients with chronic pain and depression.