Research Spotlight

McLaughlin, C., N. T. Kearns, M. Bennett, J. W. Roden-Foreman, K. Roden-Foreman, E. E. Rainey, G. Funk, M. B. Powers and A. M. Warren (2017). “Alcohol and drug toxicology screens at time of hospitalization do not predict ptsd or depression after traumatic injury.” Am J Surg 214(3): 390-396.

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BACKGROUND: Identifying risk factors for the development of PTSD and depression is critical for intervention and recovery after injury. Given research linking toxicology screens and substance use and the evidenced relationship between substance misuse and distress, the current study aimed to gauge the predictive value of toxicology testing on PTSD and depression. METHODS: Patients admitted to a Level I Trauma Center (N = 379) completed the PC-PTSD, PCL-C, and PHQ-8 at baseline, 3, 6, and 12 months. RESULTS: Results showed 52% of tested patients had a positive toxicology test, 51% screened for PTSD, and 54% screened for depression. Positive drug or alcohol toxicology tests were not significantly associated with PTSD or depression. CONCLUSIONS: Toxicology testing may not meaningful predict depression or PTSD in traumatic injury patients. Future research using validated measures of problematic substance use is needed to better understand how misuse may influence the development of psychological distress.

Menter, A., D. Thaci, J. J. Wu, W. Abramovits, F. Kerdel, D. Arikan, D. Guo, A. Ganguli, M. Bereswill, A. Camez and W. C. Valdecantos (2017). “Long-term safety and effectiveness of adalimumab for moderate to severe psoriasis: Results from 7-year interim analysis of the esprit registry.” Dermatol Ther (Heidelb): 2017 Aug [Epub ahead of print].

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INTRODUCTION: ESPRIT (NCT00799877) is an ongoing 10-year international prospective observational registry evaluating the long-term safety and effectiveness of originator adalimumab in routine clinical practice for adult patients with chronic plaque psoriasis. Herein, we report the long-term safety, effectiveness, and patient-reported outcomes (PROs) following adalimumab treatment over the first 7 years of the ESPRIT registry. METHODS: All treatment-emergent (All-TE) adverse events (AE) since the initial (first ever) dose of adalimumab were assessed. Physician Global Assessment (PGA) and PROs (PROs for US patients only) were evaluated during registry participation. RESULTS: As of 30 November 2015, 6051 patients in the ESPRIT registry were analyzed, representing 23,660.1 patient-years (PY) of overall adalimumab exposure. The incidence rates for All-TE serious AEs, serious infections, and malignancies were 4.4, 1.0, and 1.0 events per 100 PY (E/100PY), respectively. The standardized mortality ratio for TE deaths in the registry was 0.27 (95% CI 0.18-0.38). During the registry’s first 7 years, PGA “clear” or “minimal” was achieved by >50% of patients at each annual visit, and among US patients, the mean improvement from baseline in different PROs was maintained. CONCLUSION: No new safety signals were identified during the first 7 years of the registry, and safety was consistent with the known safety profile of adalimumab. The number of TE deaths was below the expected rate. During the registry’s first 7 years, most of the patients remained free of All-TE cardiovascular events, serious infections, and malignancy. As-observed effectiveness of adalimumab and improvements from baseline in PROs were maintained through 7 years of registry participation.

Lindner, P., A. Miloff, W. Hamilton, L. Reuterskiold, G. Andersson, M. B. Powers and P. Carlbring (2017). “Creating state of the art, next-generation virtual reality exposure therapies for anxiety disorders using consumer hardware platforms: Design considerations and future directions.” Cogn Behav Ther 46(5): 404-420.

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Decades of research and more than 20 randomized controlled trials show that Virtual Reality exposure therapy (VRET) is effective in reducing fear and anxiety. Unfortunately, few providers or patients have had access to the costly and technical equipment previously required. Recent technological advances in the form of consumer Virtual Reality (VR) systems (e.g. Oculus Rift and Samsung Gear), however, now make widespread use of VRET in clinical settings and as self-help applications possible. In this literature review, we detail the current state of VR technology and discuss important therapeutic considerations in designing self-help and clinician-led VRETs, such as platform choice, exposure progression design, inhibitory learning strategies, stimuli tailoring, gamification, virtual social learning and more. We illustrate how these therapeutic components can be incorporated and utilized in VRET applications, taking full advantage of the unique capabilities of virtual environments, and showcase some of these features by describing the development of a consumer-ready, gamified self-help VRET application for low-cost commercially available VR hardware. We also raise and discuss challenges in the planning, development, evaluation, and dissemination of VRET applications, including the need for more high-quality research. We conclude by discussing how new technology (e.g. eye-tracking) can be incorporated into future VRETs and how widespread use of VRET self-help applications will enable collection of naturalistic “Big Data” that promises to inform learning theory and behavioral therapy in general.

O’Leary, J. G., C. Smith, J. Cai, B. Hart, L. W. Jennings, M. Everly, G. B. Klintmalm and A. J. Demetris (2017). “Chronic amr in liver transplant: Validation of the 1-year camr score’s ability to determine long-term outcome.” Transplantation 101(9): 2062-2070.

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BACKGROUND: A proposed chronic antibody-mediated rejection (AMR) score has recently predicted 50%10-year death-censored allograft loss in patients with donor-specific alloantibodies (DSA) mean florescence intensity (MFI) greater than 10 000 and requires confirmation in patients with lower MFI (1000-10 000). METHODS: All patients who underwent liver transplantation from January 2000 to April 2009, had DSA (MFI >/=1000) in serum 10 to 14 months postliver transplantation, and had a protocolized liver biopsy were evaluated (n = 230). The previously proposed chronic AMR (cAMR) score was used to risk-stratify putative chronic AMR in DSA+ patients with MFI from 1000 to 10 000. RESULTS: The MFI distribution of DSA+ recipients were as follows: 66% had MFI 1000 to 4999, 14% had MFI 5000 to 10 000, and 20% had MFI greater than 10 000. The cAMR score distribution on 1-year protocol liver biopsy found that 41% had a score less than 13; 27% a score of 13 to 27.5, and 32% a score greater than 27.5. MFI correlated with 1-year cAMR category (<13, 46% vs 21% and >27.5, 29% vs 42% when MFI was 1000-10 000 vs MFI >10 000; P = 0.047). In patients with a cAMR score less than 13, 10-year death-censored allograft survival was 96% to 100% regardless of MFI (P = NS). The risk of allograft loss increased in patients with a cAMR score greater than 13 (P = 0.004) in DSA+ patients with MFI 1000 to 10 000. DSA MFI greater than 10 000 versus MFI 1000 to 10 000 at 1 year was also more likely to persist at 5 years (95% vs 68%; P < 0.0001). CONCLUSIONS: Validation of the previously proposed cAMR score in a separate cohort predicts death-censored long-term allograft failure in DSA+ patients regardless of MFI, and higher MFI at 1 year predicts DSA persistence at 5 years.

Zurita, A. J., R. C. Gagnon, Y. Liu, H. T. Tran, R. A. Figlin, T. E. Hutson, A. M. D’Amelio, Jr., C. N. Sternberg, L. N. Pandite and J. V. Heymach (2017). “Integrating cytokines and angiogenic factors and tumour bulk with selected clinical criteria improves determination of prognosis in advanced renal cell carcinoma.” Br J Cancer 117(4): 478-484.

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BACKGROUND: In two clinical trials of the vascular endothelial growth factor (VEGF) receptor inhibitor pazopanib in advanced renal cell carcinoma (mRCC), we found interleukin-6 as predictive of pazopanib benefit. We evaluated the prognostic significance of candidate cytokines and angiogenic factors (CAFs) identified in that work relative to accepted clinical parameters. METHODS: Seven preselected plasma CAFs (interleukin-6, interleukin-8, osteopontin, VEGF, hepatocyte growth factor, tissue inhibitor of metalloproteinases (TIMP-1), and E-selectin) were measured using multiplex ELISA in plasma collected pretreatment from 343 mRCC patients participating in the phase 3 registration trial of pazopanib vs placebo (NCT00334282). Tumour burden (per sum of longest diameters (SLD)) and 10 other clinical factors were also analysed for association with overall survival (OS; based on initial treatment assignment). RESULTS: Osteopontin, interleukin-6, and TIMP-1 were independently associated with OS in multivariable analysis. A model combining the three CAFs and five clinical variables (including SLD) had higher prognostic accuracy than the International Metastatic Renal Cell Carcinoma Database Consortium criteria (concordance-index 0.75 vs 0.67, respectively), and distinguished two groups of patients within the original intermediate risk category. CONCLUSIONS: A prognostic model incorporating osteopontin, interleukin-6, TIMP-1, tumour burden, and selected clinical criteria increased prognostic accuracy for OS determination in mRCC patients.