Real World Studies of Psoriasis and Mental Illness in Newfoundland and Labrador.

BACKGROUND: Psoriasis is a chronic, immune-mediated inflammatory disease with an implied connection to psychiatric disorders. OBJECTIVE: This study aims to illustrate an association between psoriasis and psychiatric disorders using real world data gathered from the Newfoundland and Labrador population. METHODS: Data on 15,100 patients with psoriasis and 75,500 controls (1:5) was collected from the Newfoundland and Labrador Centre for Health Information's Electronic Health Records. The cases and controls were matched for age, sex, and geography. Indicators for psychiatric disorders include diagnosis of mental illnesses from physician's visits and hospitalization records (all coded for mental health using ICD-9 and ICD-10 codes). RESULTS: 9,991 (66.2%) cases were identified to have at least one visit with a diagnostic code for mental illness compared to 42,276 (56.0%), P < .0001 in the control group. The percentage of people coded for anxiety was 36.50% compared to 28.95%, P < .0001; depression was 37.04% compared to 30.19%, P < .0001; and adjustment disorder was 6.89% versus 5.48%, P < .0001, among those with and without psoriasis, respectively. The greatest risk for anxiety [OR 1.4 (1.20, 1.67)] and depression [OR 1.65 (1.36, 2.00)] among psoriasis patients was between the 0 to 20 age group. Women with psoriasis are more likely to have anxiety [OR 1.08 (1.03, 1.13)], depression [OR 1.04 (1.01, 1.09)] and adjustment disorder [OR 1.07 (0.98, 1.17)] compared to female controls. CONCLUSION: Our result shows that patients with psoriasis have an increased prevalence of mental illness. Using real world data to carry out further investigations will better elucidate this association and provide an increased understanding of the association between psoriasis and mental disorders.

Laying the foundation for Real-world evidence studies: a case study from Newfoundland and Labrador.

The Janssen and Newfoundland and Labrador Health Innovation Partnership (JANL-HIP) was established to carry out Real-World Evidence (RWE) projects to generate evidence about disease pathways, healthcare delivery, the effects of clinical interventions. Doing so will support and influence clinical decision-making in Newfoundland and Labrador (NL). This case study describes the foundational elements necessary for a real-world evidence generation project in NL and may provide learning for the effective execution of real-world studies in other jurisdictions. It uses an ongoing project in psoriatic disease in NL to illustrate the partnership and the benefits of RWE studies. Ultimately, the JANL-HIP RWE project aims to inform decisions that will drive improvements in health outcomes, system delivery, and policy mutually beneficial to health ecosystem stakeholders.

A pilot study of an autologous tumor-derived autophagosome vaccine with docetaxel in patients with stage IV non-small cell lung cancer.

BACKGROUND: Tumor-derived autophagosome vaccines (DRibbles) have the potential to broaden immune response to poorly immunogenic tumors. METHODS: Autologous vaccine generated from tumor cells harvested from pleural effusions was administered to patients with advanced NSCLC with the objectives of assessing safety and immune response. Four patients were vaccinated and evaluable for immune response; each received two to four doses of vaccine. Study therapy included two cycles of docetaxel 75 mg/m2 on days 1 and 29 to treat the tumor, release hidden antigens and produce lymphopenia. DRibbles were to be administered intradermally on days 14, 43, 57, 71, and 85, together with GM-CSF (50 µg/d x 6d, administered via SQ mini pump). Peripheral blood was tested for immune parameters at baseline and at each vaccination. RESULTS: Three of four patients had tumor cells available for testing. Autologous tumor-specific immune response was seen in two of the three, manifested by IL-5 (1 patient after 3 doses), and IFN-γ, TNF-α, IL-5, IL-10 (after 4 doses in one patient). All 4 patients had evidence of specific antibody responses against potential tumor antigens. All patients came off study after 4 or fewer vaccine treatments due to progression of disease. No significant immune toxicities were seen during the course of the study. CONCLUSIONS: DRibble vaccine given with GM-CSF appeared safe and capable of inducing an immune response against tumor cells in this small, pilot study. There was no evidence of efficacy in this small poor-prognosis patient population, with treatment not feasible. Trial registration NCT00850785, initial registration date February 23, 2009.

Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses.

PURPOSE: To measure the CD8+ T-cell response to a melanoma peptide vaccine and to compare an every-2-weeks with an every-3-weeks vaccination schedule. PATIENTS AND METHODS: Thirty HLA-A2-positive patients with resected stage I to III melanoma were randomly assigned to receive vaccinations every 2 weeks (13 vaccines) or every 3 weeks (nine vaccines) for 6 months. The synthetic, modified gp100 peptide, g209-2M, and a control peptide, HPV16 E7, were mixed in incomplete Freund's adjuvant and injected subcutaneously. Peripheral blood mononuclear cells obtained before and after vaccination by leukapheresis were analyzed using a fluorescence-based HLA/peptide-tetramer binding assay and cytokine flow cytometry. RESULTS: Vaccination induced an increase in peptide-specific T cells in 28 of 29 patients. The median frequency of CD8+ T cells specific for the g209-2M peptide increased markedly from 0.02% before to 0.34% after vaccination (P <.0001). Eight patients (28%) exhibited peptide-specific CD8+ T-cell frequencies greater than 1%, including two patients with frequencies of 4.96% and 8.86%, respectively. Interferon alfa-2b-treated patients also had significant increases in tetramer-binding cells (P <.0001). No difference was observed between the every-2-weeks and the every-3-weeks vaccination schedules (P =.59). CONCLUSION: Flow cytometric analysis of HLA/peptide-tetramer binding cells was a reliable means of quantifying the CD8+ T-cell response to peptide immunization. This assay may be suitable for use in future trials to optimize different vaccination strategies. Concurrent interferon treatment did not inhibit the development of a peptide-specific immune response and vaccination every 2 weeks, and every 3 weeks produced similar results.

OX40 is a potent immune-stimulating target in late-stage cancer patients.

OX40 is a potent costimulatory receptor that can potentiate T-cell receptor signaling on the surface of T lymphocytes, leading to their activation by a specifically recognized antigen. In particular, OX40 engagement by ligands present on dendritic cells dramatically increases the proliferation, effector function, and survival of T cells. Preclinical studies have shown that OX40 agonists increase antitumor immunity and improve tumor-free survival. In this study, we performed a phase I clinical trial using a mouse monoclonal antibody (mAb) that agonizes human OX40 signaling in patients with advanced cancer. Patients treated with one course of the anti-OX40 mAb showed an acceptable toxicity profile and regression of at least one metastatic lesion in 12 of 30 patients. Mechanistically, this treatment increased T and B cell responses to reporter antigen immunizations, led to preferential upregulation of OX40 on CD4(+) FoxP3(+) regulatory T cells in tumor-infiltrating lymphocytes, and increased the antitumor reactivity of T and B cells in patients with melanoma. Our findings clinically validate OX40 as a potent immune-stimulating target for treatment in patients with cancer, providing a generalizable tool to favorably influence the antitumor properties of circulating T cells, B cells, and intratumoral regulatory T cells.

Lessons learned from the mothers' overweight management study in 4 West Virginia WIC offices.

A pilot was conducted to test the feasibility and compare the effectiveness of a group approach (facilitated group discussions) to that of a self-guided approach (newsletters) to weight management in postpartum women enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (baseline n = 151; final n = 64). Mean group attendance was 3.6/10 sessions. Being older and meeting with the dietitian were related to greater attendance (P < .01). At 1 year, there were no significant differences in weight between groups. There is a critical need for weight-management interventions in the postpartum period. Lessons learned are presented.