Piplartine eliminates CD34 + AML stem/progenitor cells by inducing oxidative stress and suppressing NF-κB signalling.

Acute myeloid leukaemia (AML) is a haematological malignancy characterised by the accumulation of transformed myeloid progenitors in the bone marrow. Piplartine (PL), also known as piperlongumine, is a pro-oxidant small molecule extracted from peppers that has demonstrated antineoplastic potential in solid tumours and other haematological malignancies. In this work, we explored the potential of PL to treat AML through the use of a combination of cellular and molecular analyses of primary and cultured leukaemia cells in vitro and in vivo. We showed that PL exhibits in vitro cytotoxicity against AML cells, including CD34+ leukaemia-propagating cells, but not healthy haematopoietic progenitors, suggesting anti-leukaemia selectivity. Mechanistically, PL treatment increased reactive oxygen species (ROS) levels and induced ROS-mediated apoptosis in AML cells, which could be prevented by treatment with the antioxidant scavenger N-acetyl-cysteine and the pancaspase inhibitor Z-VAD(OMe)-FMK. PL treatment reduced NFKB1 gene transcription and the level of NF-κB p65 (pS536), which was depleted from the nucleus of AML cells, indicating suppression of NF-κB p65 signalling. Significantly, PL suppressed AML development in a mouse xenograft model, and its combination with current AML treatments (cytarabine, daunorubicin and azacytidine) had synergistic effects, indicating translational therapeutic potential. Taken together, these data position PL as a novel anti-AML candidate drug that can target leukaemia stem/progenitors and is amenable to combinatorial therapeutic strategies.

A Self-Help Crisis Outreach Effort for At-Risk Primary Care Patients: A Pilot Study of Veterans During the COVID-19 Pandemic.

Stressful events can exacerbate symptoms of psychiatric disorders among primary care patients, putting them at increased risk for suicide. In a pilot study that ran from August to December of 2020, researchers evaluated the acceptability and implementation of Managing Emotions in Disaster and Crisis (MEDIC), a self-help intervention designed to assist at-risk primary care patients. A total of 108 at-risk veterans completed baseline and 6-week assessments. Results were promising, with high patient acceptability and engagement along with improvement in all measures of mental illness symptoms from baseline to posttreatment. Self-help interventions like MEDIC may offer a low-burden way for primary care providers to support more patients.

Integrating stakeholder feedback into the design of a peer-delivered primary care wellness program: A rapid qualitative study.

BACKGROUND: Individuals seen in Primary Care with behavioral health concerns who decline behavioral health treatment may benefit from the support of peers (consumers in recovery from behavioral health concerns employed to support other consumers). Whole Health STEPS is a new intervention for Veterans in Primary Care with behavioral health concerns which combines essential elements of peers' role and the Whole Health model using a stepped-care design. We incorporated stakeholder feedback in the Whole Health STEPS design to improve fit with Veterans, peers, and primary care settings. METHODS: We conducted semi-structured qualitative interviews with VA staff using questions derived from the Consolidated Framework for Implementation Research (CFIR). Participants were recruited via a maximum variation strategy across a national sample and interviewed between January 2021-April 2021. The analytic design was a rapid qualitative analysis. Interviews addressed design decisions and potential barriers and facilitators to future implementation. Then, we made adaptations to Whole Health STEPS and catalogued changes using the Framework for Adaptations and Modifications-Enhanced (FRAME). A VA peer conducted the interviews, participated in analyses, assisted with design modifications, and co-wrote this paper. RESULTS: Sixteen staff members from 9 VA primary care peer programs participated (8 peers and 8 supervisors/administrators). Feedback themes included: capitalizing on peer skills (e.g., navigation), ensuring patient-centered and flexible design, and making it easy and efficient (e.g., reducing session length). Understanding the structure of primary care peers' roles and their interactions with other programs helped us identify role conflicts (e.g., overlap with Whole Health Coaches and Health Behavior Coordinators), which led to design modifications to carve out a unique role for Whole Health STEPS. Staff also made recommendations about marketing materials and training tools to support Whole Health STEPS roll out. CONCLUSIONS: Feedback from frontline staff, including peers, in the design process was crucial to identifying essential modifications that would not have been possible after initial trials without re-evaluating efficacy due to the extent of the changes. Whole Health STEPS was adapted to fit within a range of program structures, emphasize peers' unique contributions, and streamline delivery. Lessons learned can be applied to other interventions.

PET imaging of TREM1 identifies CNS-infiltrating myeloid cells in a mouse model of multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) that causes substantial morbidity and diminished quality of life. Evidence highlights the central role of myeloid lineage cells in the initiation and progression of MS. However, existing imaging strategies for detecting myeloid cells in the CNS cannot distinguish between beneficial and harmful immune responses. Thus, imaging strategies that specifically identify myeloid cells and their activation states are critical for MS disease staging and monitoring of therapeutic responses. We hypothesized that positron emission tomography (PET) imaging of triggering receptor expressed on myeloid cells 1 (TREM1) could be used to monitor deleterious innate immune responses and disease progression in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. We first validated TREM1 as a specific marker of proinflammatory, CNS-infiltrating, peripheral myeloid cells in mice with EAE. We show that the 64Cu-radiolabeled TREM1 antibody-based PET tracer monitored active disease with 14- to 17-fold higher sensitivity than translocator protein 18 kDa (TSPO)-PET imaging, the established approach for detecting neuroinflammation in vivo. We illustrate the therapeutic potential of attenuating TREM1 signaling both genetically and pharmacologically in the EAE mice and show that TREM1-PET imaging detected responses to an FDA-approved MS therapy with siponimod (BAF312) in these animals. Last, we observed TREM1+ cells in clinical brain biopsy samples from two treatment-naïve patients with MS but not in healthy control brain tissue. Thus, TREM1-PET imaging has potential for aiding in the diagnosis of MS and monitoring of therapeutic responses to drug treatment.

Implementing evidence-based telephone coaching for health behavior program enrollment: A quality improvement project.

INTRODUCTION: This program evaluation describes the use of implementation facilitation to support uptake of a telephone-based engagement coaching intervention, ACTIVATE, using paraprofessional staff, to support health behavior program enrollment. METHOD: The RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework guided the formative evaluation. A mixed-methods approach was used to integrate qualitative (i.e., rapid analysis approach) and quantitative (i.e., descriptive statistics, chi-square test of independence, logistic regression) analyses for each outcome. RESULTS: Most patients (95%; 319 of 335) were offered ACTIVATE, and 82 patients completed ACTIVATE. Delivery with paraprofessional staff was feasible with adaptations for translation from research to a clinical setting, which are described. External facilitation (a form of implementation facilitation) was associated with higher reach. DISCUSSION: Delivery of telephone-based coaching by paraprofessional staff to support health behavior program enrollment was feasible. External facilitation was important to the translation of ACTIVATE from research to clinical practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Effects of Acute and Repeated Administration of Ketamine on Memory, Behavior, and Plasma Corticosterone Levels in Female Mice.

Ketamine is an anesthetic drug that has recently been approved for the treatment of treatment-resistant depression. Females are diagnosed with Major Depressive Disorder at higher rates than males, yet most of the pre-clinical research on ketamine has been conducted in male subjects. Additionally, the literature on the acute and long-term behavioral and cognitive effects of ketamine shows conflicting results. It is important to examine the acute and long-term cognitive and behavioral effects of ketamine exposure at lower sub-anesthetic doses, as the recreational use of the drug at higher doses is associated with cognitive and memory impairments. The current study examined the effects of acute and repeated ketamine exposure on anxiety-like behavior, novel object recognition memory, depression-like behavior, and plasma corticosterone levels in 20 adult female C57BL/6J mice. Mice were exposed acutely or repeatedly for 10 consecutive days to saline or 15 mg/kg ketamine and behavior was measured in the open field test, novel object recognition test, and the Porsolt forced swim test. Plasma corticosterone levels were measured following behavioral testing. Acute ketamine exposure decreased locomotor activity and increased anxiety-like behavior in the open field test compared to controls, while repeated ketamine exposure impaired memory in the novel object recognition test. There were no effects of acute or repeated ketamine exposure on depression-like behavior in the Porsolt forced swim test or on plasma corticosterone levels. These findings suggest that a subanesthetic dose of ketamine alters behavior and cognition in female mice and the effects are dependent on the duration of exposure.

Variation within the visually evoked neurovascular coupling response of the posterior cerebral artery is not influenced by age or sex.

Neurovascular coupling (NVC) is the temporal and spatial coordination between local neuronal activity and regional cerebral blood flow. The literature is unsettled on whether age and/or sex affect NVC, which may relate to differences in methodology and the quantification of NVC in small sample-sized studies. The aim of this study was to 1) determine the relative and combined contribution of age and sex to the variation observed across several distinct NVC metrics (n = 125, 21-66 yr; 41 males) and 2) present an approach for the comprehensive systematic assessment of the NVC response using transcranial Doppler ultrasound. NVC was measured as the relative change from baseline (absolute and percent change) assessing peak, mean, and total area under the curve (tAUC) of cerebral blood velocity through the posterior cerebral artery (PCAv) during intermittent photic stimulation. In addition, the NVC waveform was compartmentalized into distinct regions, acute (0-9 s), mid (10-19 s), and late (20-30 s), following the onset of photic stimulation. Hierarchical multiple regression modeling was used to determine the extent of variation within each NVC metric attributable to demographic differences in age and sex. After controlling for differences in baseline PCAv, the R2 data suggest that 1.6%, 6.1%, 1.1%, 3.4%, 2.5%, and 4.2% of the variance observed within mean, peak, tAUC, acute, mid, and late response magnitude is attributable to the combination of age and sex. Our study reveals that variability in NVC response magnitude is independent of age and sex in healthy human participants, aged 21-66 yr.NEW & NOTEWORTHY We assessed the variability within the neurovascular coupling response attributable to age and sex (n = 125, 21-66 yr; 41 male). Based on the assessment of posterior cerebral artery responses to visual stimulation, 0%-6% of the variance observed within several metrics of NVC response magnitude are attributable to the combination of age and sex. Therefore, observed differences between age groups and/or sexes are likely a result of other physiological factors.

Practical and Emotional Peer Support Tailored for Life's Challenges: Personalized Support for Progress Randomized Clinical Pilot Trial in a Veterans Health Administration Women's Clinic.

INTRODUCTION: Women Veterans experience a broad range of stressors (e.g., family, relationship, and financial) and high rates of mental health and physical health conditions, all of which contribute to high levels of stress. Personalized Support for Progress (PSP), an evidence-based intervention, is well suited to support women Veterans with high stress as it involves a card-sort task to prioritize concerns as well as pragmatic and emotional support to develop and implement a personalized plan addressing those concerns. Our aims were to explore the population and context for delivery and evaluate the feasibility, acceptability, and utility of PSP delivered by a peer specialist to complement existing services in a Veterans Health Administration (VHA) Women's Wellness Center. MATERIALS AND METHODS: This randomized controlled pilot trial compared treatment as usual plus PSP to treatment as usual and used the a priori Go/No-Go criteria to establish success for each outcome. We interviewed staff regarding the population and delivery context at a VHA Women's Wellness Center and analyzed interviews using a rapid qualitative approach. For the rapid qualitative analysis, we created templated summaries of each interview to identify key concepts within each a priori theme, reviewed each theme's content across all interviews, and finally reviewed key concepts across themes. We evaluated feasibility using recruitment and retention rates; acceptability via Veteran satisfaction, working relationship with the peer, and staff satisfaction; and utility based on the proportion of Veterans who experienced a large change in outcomes (e.g., stress, mental health symptoms, and quality of life). The Syracuse VA Human Subjects Institutional Review Board approved all procedures. RESULTS: Staff interviews highlight that women Veterans have numerous unmet social needs and concerns common among women which increase the complexity of their care; call for a supportive, consistent, trusting relationship with someone on their health care team; and require many resources (e.g., staff such as social workers, services such as legal support, and physical items such as diapers) to support their needs (some of which are available within VHA but may need support for staffing or access, and some of which are unavailable). Feasibility outcomes suggest a need to modify PSP and research methods to enhance intervention and assessment retention before the larger trial; the recruitment rate was acceptable by the end of the trial. Veteran acceptability of PSP was high. Veteran outcomes demonstrate promise for utility to improve stress, mental health symptoms, and quality of life for women Veterans. CONCLUSIONS: Given the high acceptability and promising outcomes for utility, changes to the design to enhance the feasibility outcomes which failed to meet the a priori Go/No-Go criteria are warranted. These outcomes support future trials of PSP within VHA Women's Wellness Centers.

Shock wave formation from head-on collision of two subsonic vortex rings.

Vortex ring collisions have attracted intense interest in both water and air studies (Baird in Proc R Soc Lond Ser Math Phys Sci 409:59-65, 1987, Poudel et al. in Phys Fluids 33:096105, 2021, Lim and Nickels in Nature 357:225, 1992, New et al. in Exp Fluids 57:109, 2016, Suzuki et al. in Geophys Res Lett 34, 2007, Yan et al. in J Fluids Eng 140:054502, 2018, New et al. in J Fluid Mech 899, 2020, Cheng et al. in Phys Fluids 31:067107, 2019, Hernández and Reyes in 29:103604, 2017, Mishra et al. in Phys Rev Fluids, 2021, Zednikova et al. in Chem Eng Technol 42:843-850, 2019, Kwon et al. in Nature 600:64-69, 2021). These toroidal structures spin around a central axis and travel in the original direction of impulse while spinning around the core until inertial forces become predominant causing the vortex flow to spontaneously decay to turbulence (Vortex Rings, https://projects.iq.harvard.edu/smrlab/vortex-rings ). Previous studies have shown the collision of subsonic vortex rings resulting in reconnected vortex rings, but the production of a shock wave from the collision has not been demonstrated visibly (Lim and Nickels in Nature 357:225, 1992, Cheng et al. in Phys Fluids 31:067107, 2019). Here we present the formation of a shock wave due to the collision of explosively formed subsonic vortex rings. As the vortex rings travel at Mach 0.66 toward the collision point, they begin to trap high pressure air between them. Upon collision, high pressure air was imploded and released radially away from the axis of the collision, generating a visible shock wave traveling through and away from the colliding vortices at Mach 1.22. Our results demonstrate a pressure gradient with high pressure release creating a shock wave. We anticipate our study to be a starting point for more explosively formed vortex collisions. For example, explosives with different velocities of detonation could be tested to produce vortex rings of varying velocities.

Leveraging Integrated Primary Care to Address Patients' and Families' Unmet Social Needs: Aligning Practice with National Academy of Sciences, Engineering and Medicine Recommendations.

Primary care is well-poised to address unmet social needs that affect health. Integrated primary care is increasingly common and can be leveraged to facilitate identification of practice and clinician-level modifiable characteristics and assist practices to address unmet social needs for patients and families. A recent National Academies of Sciences, Engineering, and Medicine (NASEM)'s consensus report identified 5 critical system-level activities to facilitate the integration of addressing social needs into health care: awareness (ask patients), adjustment (flexible intervention delivery), assistance (intervention to address the social need), alignment (link with community resources), and advocacy (policy change). This article outlines how integrated primary care characteristics, such as routine screening, functional workflows, interprofessional team communication, and patient-centered practices, exemplify the NASEM report's activities and offer robust biopsychosocial tools for addressing social needs. We provide a case to illustrate how these strategies might be used in practice.

Engagement, experience, and satisfaction with peer-delivered whole health coaching for veterans with PTSD: A mixed methods process evaluation.

To describe the process of peer-delivered Whole Health Coaching, a primary care-based intervention in which peers provide patients with individualized support to set and work toward wellness goals. Fifteen primary care Veterans with PTSD participated in peer-delivered Whole Health Coaching during a multiple baseline design study. This is a planned mixed methods concurrent equal status analysis of the process of peer-delivered Whole Health Coaching including patient engagement, patient experience, fidelity to the coaching and peer roles, and patient satisfaction. Data sources were feedback interviews, electronic medical record reviews, self-report assessments, and observer fidelity ratings of session recordings. Qualitative data were used to expand the interpretation of quantitative descriptive data. A rapid assessment approach was used for qualitative analysis. Retention in peer-delivered Whole Health Coaching was 11 of 15 participants, and factors facilitating engagement were peers as providers and flexibility in scheduling/modality of sessions. Peers demonstrated high fidelity to coaching skills, Whole Health Coaching phases and stages, and the peer role. Participants expressed high satisfaction and perceived peer-delivered Whole Health Coaching as helpful with making progress on individualized wellness goals. Results build on the literature describing the expansion of peer services into primary care and implementation of interventions such as wellness coaching. This initial small study suggests that peers can deliver high-quality wellness coaching, and this description of the process can guide the integration of peers doing wellness coaching in similar clinical settings and for future research trials. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Cost of Cancer: The Association of Financial and Cancer-Related Stress on Maladaptive Coping Styles in Families with a Cancer Diagnosis.

According to the American Cancer Society (2020), it is estimated that 1.8 million new cancer diagnoses will occur in 2019 in the United States. Due to the frequency of cancer diagnoses and the increasing costs of treatment, financial stress is common among cancer patients. Guided by the Family Systems Illness Model (FSI), a cross-sectional study of individuals and family members where there was an active cancer diagnosis (n = 53) was conducted. The study utilized structural equation modeling to examine the impact of cancer stress and financial stress on maladaptive family coping mechanisms, and in turn, their effect on family communication and satisfaction. Findings indicate individuals with higher financial stress reported greater cancer stress. In turn, individuals with higher cancer stress, reported higher rigidity in their family coping which was associated with less family satisfaction. Additionally, as individuals reported greater family disengagement and chaos, lower levels of family communication and satisfaction were found. These findings provide evidence to the complex stresses experienced by cancer patients and their families. Therapeutic implications of how emotionally focused therapy may support these families dealing with a cancer diagnosis are discussed.

Temperature alone is insufficient to understand hibernation energetics.

Energy conservation has long been a focal point in hibernation research. A long-standing assumption is that ambient temperature (Ta) largely defines the rate of energy expenditure because of well-known relationships between Ta, metabolic rate and frequency of arousal from torpor. Body condition and humidity also affect energy expenditure but are usually considered secondary factors. We held tricolored bats (Perimyotis subflavus) in captivity under multiple environmental conditions to directly compare the importance of Ta, fat mass and humidity for hibernation energy expenditure. Fat mass was the best predictor of female mass loss, followed by Ta and humidity. However, males had less fat and adopted a more energetically conservative hibernation strategy. Our results demonstrate that understanding the evolution of behavior, physiology and ecology of hibernation requires disentangling the relative contributions of multiple drivers of hibernation energetics, and that Ta is not always the most important factor driving energy expenditure.

Expanding access to psychosocial research studies during the COVID-19 pandemic through virtual modalities.

The COVID-19 pandemic has caused psychosocial researchers and clinicians to quickly shift from standard in-person practices to remote modalities. Despite calls to maintain current virtual care modalities due to the potential to improve access to health care, we are not yet aware of any scholarly works which explicitly describe specific modifications made in response to the restrictions to face-to-face care, resulting access, and implications for the field. This commentary describes how modifications to transition both clinical and research processes to fully virtual modalities in 2 ongoing integrated primary care clinical trials during the COVID-19 pandemic increased access. Given the feasibility of implementing these modifications and the success demonstrated by increased enrollment, we advocate for continued use of virtual modalities for both clinical work and research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Characteristics of Patients With Complex Limb Pain Evaluated Through an Interdisciplinary Approach Utilizing Magnetic Resonance Neurography.

Patients with persistent complex limb pain represent a substantial diagnostic challenge. Physical exam, and tests such as nerve conduction, are often normal even though the patient suffers from severe pain. In 2015, we initiated a team-based approach to evaluate such patients. The approach included physicians from several specialties (Anesthesiology/Pain Medicine, Radiology, Plastic Surgery, Neurosurgery) combined with the use of advanced imaging with Magnetic Resonance Neurography (MRN). This preliminary case series discusses MRN findings identified in patients with previously difficult-to-diagnose peripheral limb pain and describes how this combination of approaches influenced our diagnosis and treatment plans. We extracted demographics, patient characteristics, presenting features, diagnostic tests performed, treatments provided, referral diagnosis and the diagnosis after interdisciplinary team evaluation from patient charts. We evaluated MRN and electrodiagnostic studies (EDX) ability to identify injured nerves. We compared abnormal findings from these diagnostics to patient reported outcome after ultrasound-guided nerve block. A total of 58 patients, 17 males and 41 females, were identified. The majority of patients presented with lower extremity pain (75%) and had prior surgery (43%). The most commonly identified abnormality on MRN was nerve signal alteration on fluid sensitive sequences, followed by caliber change and impingement. Comparing the outcome of diagnostic nerve blocks with abnormal nerve findings on MRN or EDX, we found that MRN had a sensitivity of 67% and specificity of 100% while for EDX it was 45 and 0%, respectively. After interdisciplinary discussion and imaging review, a more specific diagnosis was produced in 78% of evaluated cases opening up additional treatment pathways such as nerve-targeted surgery, which was performed in 36% cases. This descriptive case series demonstrates that a majority of patients evaluated by our team for complex limb pain were women with lower extremity pain resulting from surgery. In addition, an interdisciplinary team evaluation and the use of the moderately sensitive but highly specific MRN imaging modality resulted in a change in diagnosis for a majority of patients with complex limb pain. Future studies investigating patient outcomes after diagnosis change are currently underway based on the findings of this preliminary study.

Problem recognition and treatment beliefs relate to mental health utilization among veteran primary care patients.

Mental health concerns are prevalent among primary care patients, but many do not utilize services for these conditions. This study aims to conduct a comprehensive assessment of barriers and facilitators to mental health care utilization among veteran primary care patients with common mental health concerns. We hypothesized that beliefs and knowledge about mental illness and mental health care would be more strongly associated with recent mental health care utilization than stigma, help-seeking behaviors, or logistical barriers. Veterans (n = 116) enrolled in primary care with current symptoms of depression (58%), posttraumatic stress disorder (37%), and/or hazardous alcohol use (50%) who either recently used mental health services (47%) or had no recent mental health treatment utilization (53%) completed a telephone-based screening, medical records review, and mail survey of 10 measures of barriers and facilitators to mental health treatment utilization. Recognition of problems as a cause for concern, odds ratio = 5.95, 95% confidence interval [2.36, 15.01], and beliefs about psychotherapy, odds ratio = 2.53, 95% confidence interval [1.39, 4.60], emerged as stronger correlates of recent mental health care utilization than stigma, self-efficacy, and external barriers to treatment. Results suggest the use of specific theories, measures, and interventions that focus on patient recognition of problems and beliefs about treatment over those that focus on other treatment barriers and facilitators. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Of mice, microglia, and (wo)men: a case series and mechanistic investigation of hydroxychloroquine for complex regional pain syndrome.

INTRODUCTION: Complex regional pain syndrome (CRPS) is a condition that occurs after minor trauma characterized by sensory, trophic, and motor changes. Although preclinical studies have demonstrated that CRPS may be driven in part by autoinflammation, clinical use of immune-modulating drugs in CRPS is limited. Hydroxychloroquine (HCQ) is a disease-modifying antirheumatic drug used to treat malaria and autoimmune disorders that may provide benefit in CRPS. OBJECTIVES: To describe the use of HCQ in patients with refractory CRPS and investigate possible mechanisms of benefit in a mouse model of CRPS. METHODS: We initiated HCQ therapy in 7 female patients with refractory CRPS undergoing treatment at the Stanford Pain Management Center. We subsequently undertook studies in the mouse tibial fracture-casting model of CRPS to identify mechanisms underlying symptom reduction. We evaluated behavior using mechanical allodynia and spinal cord autoinflammation by immunohistochemistry and enzyme-linked immunosorbent assay. RESULTS: We treated 7 female patients with chronic, refractory CRPS with HCQ 200 mg twice daily for 2 months, followed by 200 mg daily thereafter. Two patients stopped HCQ secondary to lack of response or side effects. Overall, HCQ significantly improved average numerical rating scale pain from 6.8 ± 1.1 before HCQ to 3.8 ± 1.9 after HCQ treatment. In the tibial fracture-casting mouse model of CRPS, we observed reductions in allodynia, paw edema, and warmth following daily HCQ treatment starting at 3 weeks after injury. Spinal cord dorsal horn microglial activation and cytokine levels were also reduced by HCQ treatment. CONCLUSION: Together, these preclinical and clinical results suggest that HCQ may benefit patients with CRPS at least in part by modulating autoinflammation and support further investigation into the use of HCQ for CRPS.

Defining the things we can change to improve access to mental health care.

Access and utilization of mental health care are critical components of ensuring public health. In this conceptual article, we define modifiable factors affecting mental health care utilization with the goal of providing a pragmatic framework for providers and clinics to increase access to mental health care. Five shared constructs emerged from a review of prominent health behavior theories: (a) mental illness beliefs, knowledge, and recognition; (b) mental health treatment beliefs and knowledge; (c) stigma including perceived norms, public stigma, and self-stigma; (d) help-seeking behaviors including knowledge, motivation, self-efficacy, and skills; and (e) external barriers and facilitators such as cues, logistics, and social support. We explore how these constructs influence mental health care utilization including interpretation and perception of mental health symptoms, acceptability and awareness of treatment options, and skills and ability to find, schedule, and attend mental health care. Finally, we make recommendations on how this broader framework can be used by primary care clinician innovators to implement interventions to reduce disparities and improve access to mental health care. (PsycINFO Database Record (c) 2019 APA, all rights reserved).