Brief cognitive behavioral therapy in primary care: a hybrid type 2 patient-randomized effectiveness-implementation design

BACKGROUND: Despite the availability of evidence-based psychotherapies for depression and anxiety, they are underused in non-mental health specialty settings such as primary care. Hybrid effectiveness-implementation designs have the potential to evaluate clinical and implementation outcomes of evidence-based psychotherapies to improve their translation into routine clinical care practices. METHODS: This protocol article discusses the study methodology and implementation strategies employed in an ongoing, hybrid, type 2 randomized controlled trial with two primary aims: (1) to determine whether a brief, manualized cognitive behavioral therapy administered by Veterans Affairs Primary Care Mental Health Integration program clinicians is effective in treating depression and anxiety in a sample of medically ill (chronic cardiopulmonary diseases) primary care patients and (2) to examine the acceptability, feasibility, and preliminary outcomes of a focused implementation strategy on improving adoption and fidelity of brief cognitive behavioral therapy at two Primary Care-Mental Health Integration clinics. The study uses a hybrid type 2 effectiveness/implementation design to simultaneously test clinical effectiveness and to collect pilot data on a multifaceted implementation strategy that includes an online training program, audit and feedback of session content, and internal and external facilitation. Additionally, the study engages the participation of an advisory council consisting of stakeholders from Primary Care-Mental Health Integration, as well as regional and national mental health leaders within the Veterans Administration. It targets recruitment of 320 participants randomized to brief cognitive behavioral therapy (n = 200) or usual care (n = 120). Both effectiveness and implementation outcomes are being assessed using mixed methods, including quantitative evaluation (e.g., intent-to-treat analyses across multiple time points) and qualitative methods (e.g., focus interviews and surveys from patients and providers). Patient-effectiveness outcomes include measures of depression, anxiety, and physical health functioning using blinded independent evaluators. Implementation outcomes include patient engagement and adherence and clinician brief cognitive behavioral therapy adoption and fidelity. CONCLUSIONS: Hybrid designs are needed to advance clinical effectiveness and implementation knowledge to improve healthcare practices. The current article describes the rationale and challenges associated with the use of a hybrid design for the study of brief cognitive behavioral therapy in primary care. Although trade-offs exist between scientific control and external validity, hybrid designs are part of an emerging approach that has the potential to rapidly advance both science and practice. TRIAL REGISTRATION: NCT01149772 at http://www.clinicaltrials.gov/ct2/show/NCT0114977

Behavioral health coaching for rural-living older adults with diabetes and depression: an open pilot of the HOPE Study

BACKGROUND: Patients with diabetes are at increased risk for depression, compounding the burden of disease. When comorbid with diabetes, depression leads to poorer health outcomes and often complicates diabetes self-management. Unfortunately, treatment options for these complex patients are limited and comprehensive services are rarely available for patients in rural settings. METHODS: A small open trial was conducted to test the acceptability, feasibility and preliminary outcomes of a telephone-delivered coaching intervention for rural-dwelling older adults with uncontrolled diabetes and comorbid, clinically significant depressive symptoms. A total of eight older adults were enrolled in Healthy Outcomes through Patient Empowerment (HOPE), a 10-session (12-week), telephone-based coaching intervention. Primary study constructs included measures of diabetes control (Hemoglobin [Hb] A1c), depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]), and diabetes-related distress (Problem Areas in Diabetes Scale [PAID]). Assessments were conducted at baseline, post-intervention, and 6-month follow-up. Acceptability and feasibility were evaluated using patient surveys, focused exit interviews, and session attendance data. RESULTS: Clinically significant improvements were realized post-intervention and at 6-month follow-up for outcomes related to diabetes and depression. Effect sizes using Cohen's d were determined post-intervention and at 6-month follow-up, respectively, for HbA1c (d=0.36; d=0.28), PHQ-9 (d=1.48; d=1.67, and PAID (d=1.50; d=1.06) scores. Among study participants, HbA1c improved from baseline by a mean (M) of 1.13 (SD=1.70) post-intervention and M=0.84 (SD=1.62) at 6 months. Depression scores, measured by the PHQ-9, improved from baseline by M=5.14 (SD=2.27) post-intervention and M=7.03 (SD=4.43) at 6-month follow-up. PAID scores also improved by M=17.68 (SD=10.7) post-intervention and M=20.42 (SD=20.66) from baseline to 6-month follow-up. Case examples are provided for additional context and to more fully articulate salient intervention concepts. CONCLUSION: Although preliminary, data from this small open trial suggest that HOPE holds the potential to improve both physical (diabetes) and emotional (diabetes distress, depression) health outcomes and that changes can be maintained over a 6-month time period. As envisioned by the authors, HOPE may function as an extension of traditional primary care for rural-dwelling older adults with multiple comorbidities. A future randomized clinical trial will test HOPE’s broader effectiveness with rural-dwelling older adults. TRIAL REGISTRATION: NCT0127471

Glutamine depletion by crisantaspase hinders the growth of human hepatocellular carcinoma xenografts

Background: A subset of human hepatocellular carcinomas (HCC) exhibit mutations of β-catenin gene CTNNB1 and overexpress Glutamine synthetase (GS). The CTNNB1-mutated HCC cell line HepG2 is sensitive to glutamine starvation induced in vitro with the antileukemic drug Crisantaspase and the GS inhibitor methionine-L-sulfoximine (MSO). Methods: Immunodeficient mice with subcutaneous xenografts of the CTNNB1-mutated HCC cell lines HepG2 and HC-AFW1 were treated with Crisantaspase and/or MSO, and tumour growth was monitored. At the end of treatment, tumour weight and histology were assessed. Serum and tissue amino acids were determined by HPLC. Gene and protein expression were estimated with RT-PCR and western blot and GS activity with a colorimetric method. mTOR activity was evaluated from the phosphorylation of p70S6K1. Results: Crisantaspase and MSO depleted serum glutamine, lowered glutamine in liver and tumour tissue, and inhibited liver GS activity. HepG2 tumour growth was significantly reduced by either Crisantaspase or MSO, and completely suppressed by the combined treatment. The combined treatment was also effective against xenografts of the HC-AFW1 cell line, which is Crisantaspase resistant in vitro. Conclusions: The combination of Crisantaspase and MSO reduces glutamine supply to CTNNB1-mutated HCC xenografts and hinders their growth

Metabolomics and Age-Related Macular Degeneration

Age-related macular degeneration (AMD) leads to irreversible visual loss, therefore, early intervention is desirable, but due to its multifactorial nature, diagnosis of early disease might be challenging. Identification of early markers for disease development and progression is key for disease diagnosis. Suitable biomarkers can potentially provide opportunities for clinical intervention at a stage of the disease when irreversible changes are yet to take place. One of the most metabolically active tissues in the human body is the retina, making the use of hypothesis-free techniques, like metabolomics, to measure molecular changes in AMD appealing. Indeed, there is increasing evidence that metabolic dysfunction has an important role in the development and progression of AMD. Therefore, metabolomics appears to be an appropriate platform to investigate disease-associated biomarkers. In this review, we explored what is known about metabolic changes in the retina, in conjunction with the emerging literature in AMD metabolomics research. Methods for metabolic biomarker identification in the eye have also been discussed, including the use of tears, vitreous, and aqueous humor, as well as imaging methods, like fluorescence lifetime imaging, that could be translated into a clinical diagnostic tool with molecular level resolution

Psychosocial Factors Associated with Treatment Outcomes in Women with Obesity and Major Depressive Disorder who Received Behavioral Activation for Depression

Behavioral activation is an empirically supported treatment for depression, but much is unknown about factors associated with treatment response. The present study aimed to determine whether baseline levels and subsequent changes in psychosocial factors were associated with improvement in depression in women with comorbid obesity who received behavioral activation treatment for depression and a lifestyle intervention. Multilevel modeling was used to estimate the associations between psychosocial factors and change in depression scores during the first 10 weeks of treatment and associations between changes in psychosocial factors from baseline to 6-month follow-up and change in depression over the same time period. No baseline psychosocial factors were associated with depression improvement during treatment (p = 0.110-0.613). However, greater improvement in hedonic capacity (p = 0.001), environmental reward (p = 0.004), and social impairment (p = 0.012) were associated with greater reductions in depression over 6 months. Findings highlight the differential relationship specific psychosocial factors have with depression treatment outcomes

What to do and what not to do in the management of cancer pain: A physician survey and expert recommendations

Background: Despite the prevalence of pain among patients with cancer and the availability of pertinent guidelines, the clinical management of oncological pain is decisively insuffi-cient. To address this issue, we evaluated current trends in clinical practice and subsequently generated a list of ten corrective actions—five things to do and five things not to do—for the diagnosis, management, and monitoring of cancer pain. Methods: The survey included 18 questions about clinical practice surrounding background pain and breakthrough cancer pain (BTcP). Survey questions were developed by a scientific board of 10 physician experts and communicated via email to an expanded panel of physicians in Italy. Responses were tabulated descriptively for analysis. Results: Of 51 invited physicians, 32 (63%) provided complete survey responses. The responses revealed several incongruencies with current guideline recommendations: physicians did not always diagnose or monitor pain using diagnostically validated or disease-specific instruments; frequently based clinical decision-making on time availability or convenience; and pharmacological therapy was often inappropriate (eg, prescribing NSAIDs or corticosteroids for BTcP). The list of corrective actions generated by the scientific board favored a guideline-oriented approach that systematically characterizes oncological pain and implements treatment based on pain character-istics (eg, fast-acting transmucosal opioids for BTcP) and evidence-based recommendations. Conclusion: Oncologists require better education and training about the diagnosis, treat-ment, and monitoring of oncological pain. Physicians should be aware of current guideline recommendations as well as available pharmacological tools for BTcP