Assessing Depression Improvement with the Remission Evaluation and Mood Inventory Tool (REMIT)

Objective The Remission Evaluation and Mood Inventory Tool (REMIT) was developed as a brief complementary measure to provide a more robust assessment of depression improvement than tracking DSM-V symptom improvement alone. This study provides further validation of the REMIT tool and examines its utility in predicting depression improvement. Methods The sample comprised 294 primary care patients enrolled in a telecare trial of pain plus depression and/or anxiety. Assessments collected included: REMIT, PHQ-9 and measures assessing anxiety, pain, sleep, fatigue, somatization, health-related quality of life and disability. Data was analyzed to assess the REMIT's validity, its minimally important difference (MID), and its utility in predicting 6-month depression improvement. Results Convergent and construct validity of REMIT was supported by moderate correlations with mental health measures and weaker correlation with physical health measures. MID of approximately 2 points for REMIT was estimated by two metrics: 0.5 standard deviation and 1 standard error of measurement. Both baseline and 3-month change in REMIT scores predicted depression improvement at 6 months. Indeed, REMIT was as good or better predictor than the PHQ-9. Conclusion The REMIT measure is a brief 5-item tool that augments core DSM-V symptom-oriented metrics in assessing and predicting recovery from major depression

Composite measures of pain, anxiety, and depressive (PAD) symptoms: Construct and predictive validity

Objective Pain, anxiety, and depression (PAD) are common, co-occurring symptoms that adversely affect one another and may respond to common treatments. PAD composite measures would be useful for tracking treatment response in patients with PAD symptoms. The goal of this study is to compare 3 different PAD composite scales in terms of construct validity, responsiveness, and utility in predicting global improvement. Method The sample consisted of 294 primary care patients enrolled in a telecare trial for treating pain, anxiety, and depression. Assessments at baseline and 3 months included the Brief Pain Inventory, PHQ-9 depression scale, GAD-7 anxiety scale, PROMIS measures, Medical Outcomes Study Short-Form items, disability measures, and patient-reported global improvement. Construct validity of the PAD composite measures, their responsiveness, and their ability to predict global improvement was analyzed using Pearson correlations, standardized response means, and receiver operating characteristics analysis. Results PAD composite measures correlated strongly with one another, and moderately with measures of function, vitality, and disability. Each PAD composite measure demonstrated similar responsiveness in detecting improvement at 3 months as assessed by standardized response means (SRMs) and area under the curve (AUC analyses).The SRMs for partial and substantial global improvement corresponded to moderate (Cohen's d of 0.58 to 0.69) and large (0.81 to 0.93) effect sizes, respectively. Conclusions Three different PAD composite measures demonstrate good construct validity as well as responsiveness in detecting global improvement of pain, anxiety and depression at 3 months

Opioid Use as a Predictor of Pain Outcomes in Iraq and Afghanistan Veterans with Chronic Pain: Analysis of a Randomized Controlled Trial

OBJECTIVE: 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

Design and methods of the Care Management for the Effective Use of Opioids (CAMEO) trial

Low back pain is the most common pain condition seen in primary care, with the most common treatment being analgesic medications, including opioids. A dramatic increase in opioid prescriptions for low back pain over the past few decades has led to increased non-medical use and opioid overdose deaths. Cognitive behavioral therapy (CBT) for chronic pain is an evidence-based non-pharmacological treatment for pain with demonstrated efficacy when delivered using collaborative care models. No previous studies have tested CBT compared to analgesic optimization that includes opioid management in primary care. This paper describes the study design and methods of the CAre Management for the Effective use of Opioids (CAMEO) trial, a 2-arm, randomized comparative effectiveness trial in seven primary care clinics. CAMEO enrolled 261 primary care veterans with chronic (6 months or longer) low back pain of at least moderate severity who were receiving long-term opioid therapy and randomized them to either nurse care management focused on analgesic treatment and optimization (MED) or cognitive behavioral therapy (CBT). All subjects undergo comprehensive outcome assessments at baseline, 3, 6, 9, and 12 months by interviewers blinded to treatment assignment. The primary outcome is pain severity and interference, measured by the Brief Pain Inventory (BPI) total score. Secondary outcomes include health-related quality of life, fatigue, sleep, functional improvement, pain disability, pain beliefs, alcohol and opioid problems, depression, anxiety, and stress

Upregulation of complement proteins in lung cancer cells mediates tumor progression

IntroductionIn vivo, cancer cells respond to signals from the tumor microenvironment resulting in changes in expression of proteins that promote tumor progression and suppress anti-tumor immunity. This study employed an orthotopic immunocompetent model of lung cancer to define pathways that are altered in cancer cells recovered from tumors compared to cells grown in culture.MethodsStudies used four murine cell lines implanted into the lungs of syngeneic mice. Cancer cells were recovered using FACS, and transcriptional changes compared to cells grown in culture were determined by RNA-seq.ResultsChanges in interferon response, antigen presentation and cytokine signaling were observed in all tumors. In addition, we observed induction of the complement pathway. We previously demonstrated that activation of complement is critical for tumor progression in this model. Complement can play both a pro-tumorigenic role through production of anaphylatoxins, and an anti-tumorigenic role by promoting complement-mediated cell killing of cancer cells. While complement proteins are produced by the liver, expression of complement proteins by cancer cells has been described. Silencing cancer cell-specific C3 inhibited tumor growth In vivo. We hypothesized that induction of complement regulatory proteins was critical for blocking the anti-tumor effects of complement activation. Silencing complement regulatory proteins also inhibited tumor growth, with different regulatory proteins acting in a cell-specific manner.DiscussionBased on these data we propose that localized induction of complement in cancer cells is a common feature of lung tumors that promotes tumor progression, with induction of complement regulatory proteins protecting cells from complement mediated-cell killing

Whole-Genome Analysis Reveals That Active Heat Shock Factor Binding Sites Are Mostly Associated with Non-Heat Shock Genes in Drosophila melanogaster

During heat shock (HS) and other stresses, HS gene transcription in eukaryotes is up-regulated by the transcription factor heat shock factor (HSF). While the identities of the major HS genes have been known for more than 30 years, it has been suspected that HSF binds to numerous other genes and potentially regulates their transcription. In this study, we have used a chromatin immunoprecipitation and microarray (ChIP-chip) approach to identify 434 regions in the Drosophila genome that are bound by HSF. We have also performed a transcript analysis of heat shocked Kc167 cells and third instar larvae and compared them to HSF binding sites. The heat-induced transcription profiles were quite different between cells and larvae and surprisingly only about 10% of the genes associated with HSF binding sites show changed transcription. There were also genes that showed changes in transcript levels that did not appear to correlate with HSF binding sites. Analysis of the locations of the HSF binding sites revealed that 57% were contained within genes with approximately 2/3rds of these sites being in introns. We also found that the insulator protein, BEAF, has enriched binding prior to HS to promoters of genes that are bound by HSF upon HS but that are not transcriptionally induced during HS. When the genes associated with HSF binding sites in promoters were analyzed for gene ontology terms, categories such as stress response and transferase activity were enriched whereas analysis of genes having HSF binding sites in introns identified those categories plus ones related to developmental processes and reproduction. These results suggest that Drosophila HSF may be regulating many genes besides the known HS genes and that some of these genes may be regulated during non-stress conditions

Effect of medication optimization vs cognitive behavioral therapy among us veterans with chronic low back pain receiving long-term opioid therapy: a randomized clinical trial.

Importance: Medication management and cognitive behavioral therapy (CBT) are commonly used treatments for chronic low back pain (CLBP). However, little evidence is available comparing the effectiveness of these approaches. Question: What are the most effective pain treatments for patients prescribed opioids? Findings: In this randomized clinical trial of 261 veterans with chronic low back pain prescribed opioids, pain improvement on the Brief Pain Inventory was greater with medication optimization (decrease of 1.10 points) than cognitive behavioral therapy (decrease of 0.68 points) for 12 months, a significant but clinically modest difference. Meaning: Both pharmacological and behavioral approaches are reasonable options for treating chronic low back pain in patients prescribed opioids