Research Spotlight

Nery-Hurwit, M., L. Kincl, S. Driver and B. Heller (2017). “Stakeholder evaluation of an online program to promote physical activity and workplace safety for individuals with disability.” Eval Program Plann 63: 39-44.

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Individuals with disabilities face increasing health and employment disparities, including increased risk of morbidity and mortality and decreased earnings, occupational roles, and greater risk of injury at work. Thus, there is a need to improve workplace safety and health promotion efforts for people with disability. The purpose of this study was to obtain stakeholder feedback about an online program, Be Active, Work Safe, which was developed to increase the physical activity and workplace safety practices of individuals with disability. Eight stakeholders (content experts and individuals with disability) evaluated the 8-week online program and provided feedback on accessibility, usability, and content using quantitative and qualitative approaches. Stakeholders suggested changes to the organization, layout and accessibility, and content. This included making a stronger connection between the physical activity and workplace safety components of the program, broadening content to apply to individuals in different vocational fields, and reducing the number of participant assessments. Engaging stakeholders in the development of health promotion programs is critical to ensure the unique issues of the population are addressed and facilitate engagement in the program. Feedback provided by stakeholders improved the program and provided insight on barriers for adoption of the program.

Mumtaz, M., H. Gada, M. J. Mack and M. J. Reardon (2017). “Who’s afraid of the big bad wolf?” J Thorac Cardiovasc Surg: 2017 Mar [Epub ahead of print].

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Cardiac surgeons traditionally have been leaders in the development of innovative therapy for the treatment of cardiovascular diseases. We hold deep convictions and strong opinions on discovering and delivering the best treatment for our patients. We have led the way in all of medicine in data collection and rigorous outcomes analysis to improve the care of our patients. Our passion for rigorous self-examination is unparalleled. Simply put, we are staunch patient advocates who do not run from the challenges of finding and delivering the best care to our patients. Surgical aortic valve replacement (SAVR) for the treatment of symptomatic severe aortic stenosis is arguably one of the most successful cardiac procedures ever developed. Since the introduction of SAVR in 1960, millions of lives have been saved and improved. Although never tested against the previous standard of care, medical therapy, we as surgeons knew it was the right choice because without SAVR these patients were resigned to heart failure and death. We did track our outcomes both individually and nationally by the creation of the Society of Thoracic Surgery Adult Cardiac Surgery database, which now encompasses more than 6.1 million patients contributed by more than 95% of cardiac surgeons in the United States.

Menter, A., R. B. Warren, R. G. Langley, J. F. Merola, L. N. Kerr, E. B. Dennehy, D. Shrom, D. Amato, Y. Okubo and K. Reich (2017). “Efficacy of ixekizumab compared to etanercept and placebo in patients with moderate to severe plaque psoriasis and non-pustular palmoplantar involvement: results from three phase 3 trials (UNCOVER-1, -2, and -3).” J Eur Acad Dermatol Venereol: 2017 Mar [Epub ahead of print].

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BACKGROUND: Palmoplantar psoriasis has significant physical and emotional impact on patients and can be difficult to treat. OBJECTIVE: To evaluate the efficacy of ixekizumab in the treatment of patients with moderate-to-severe non-pustular palmoplantar involvement and moderate-to-severe plaque psoriasis. METHODS: In three phase 3, double-blind, placebo-controlled trials, patients with moderate-to-severe non-pustular plaque psoriasis (UNCOVER-1 (N=1296), UNCOVER-2 (N=1224), UNCOVER-3 (N=1346)) were randomised to subcutaneous 80 mg ixekizumab every 2 or 4 weeks (Q2W, Q4W), after a 160 mg starting dose, or placebo through week 12. Additional UNCOVER-2 and -3 cohorts were randomised to 50 mg etanercept bi-weekly. Patients entering the open-label long-term extension (UNCOVER-3) received ixekizumab Q4W weeks 12-60. Moderate-to-severe palmoplantar involvement was defined as Palmoplantar Psoriasis Area and Severity Index (PPASI) >/=8. RESULTS: Twenty-eight percent of UNCOVER-1,-2,-3 patients had baseline palmoplantar involvement (PPASI>/=0, n=1092) and 9.1% (n=350) had moderate-to-severe involvement, with mean baseline PPASI ~20, PASI ~24, and most (>60%) had static Physician’s Global Assessment >/=4. Higher percentages of patients treated with ixekizumab versus placebo or etanercept achieved PPASI 50 (approximately 80% versus 32.9%, 67.8%; ixekizumab, placebo, etanercept, respectively) and PPASI 75 (approximately 70% versus 18.8%, 44.1%; ixekizumab, placebo, etanercept, respectively) at week 12 (all P<0.05). PPASI 100 was achieved by higher percentages of ixekizumab-treated patients versus placebo (approximately 50% versus 8.2%, P<0.001) and ixekizumab Q2W-treated patients versus etanercept (51.8% versus 32.2%, P<0.05). Outcomes were maintained or improved in patients continuing on ixekizumab Q4W through week 60. Differences between ixekizumab and placebo or etanercept were statistically significant as early as week 1. CONCLUSION: In a subpopulation analysis of patients from phase 3 trials with moderate-to-severe non-pustular palmoplantar involvement and moderate-to-severe plaque psoriasis, ixekizumab treatment resulted in greater and more rapid improvements than placebo and etanercept at week 12; improvements were sustained with continued treatment.

Miyoshi, J., S. Toden, K. Yoshida, Y. Toiyama, S. R. Alberts, M. Kusunoki, F. A. Sinicrope and A. Goel (2017). “MiR-139-5p as a novel serum biomarker for recurrence and metastasis in colorectal cancer.” Sci Rep 7: 43393.

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Approximately 30-50% of colorectal cancer (CRC) patients who undergo curative resection subsequently experience tumor recurrence or metastasis. Although microRNAs (miRNAs) are a class of small noncoding RNAs frequently deregulated in various human malignancies, it remains unknown if these can help predict recurrence and metastasis in CRC patients. MiRNAs were initially screened using miRNA-microarray and miRNA-seq datasets with or without recurrence. Candidate miRNAs were then tested in two independent cohorts of 111 stage II/III and 139 stage I-III CRC patients, as well as serum samples and matched primary and metastatic liver tissues. An animal model of peritoneal dissemination was used to assess the oncogenic role of the target miRNA. Four candidate miRNAs were identified during the initial screening, and we subsequently validated upregulation of miR-139-5p in two independent clinical cohorts, wherein it associated with poor recurrence-free survival. Moreover, miR-139-5p were also upregulated in the serum of recurrence-positive CRC patients and yielded significantly shorter recurrence-free survival. Intriguingly, miR-139-5p was upregulated in metastatic liver tissues and negatively correlated with genes associated with epithelial-mesenchymal transition. Lastly, we showed that miR-139-5p overexpression enhanced peritoneal dissemination in a mouse model. In conclusion, we identified miR-139-5p as a novel biomarker for tumor recurrence and metastasis in CRC.

Moore, L., C. J. Kramer, S. Delcoix-Lopes and A. M. Modrykamien (2017). “Comparison of Cisatracurium Versus Atracurium in Early ARDS.” Respir Care: 2017 Mar [Epub ahead of print].

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BACKGROUND: Administration of cisatracurium in severe ARDS decreases in-hospital mortality. Whether clinical outcomes are cisatracurium-specific or related with all neuromuscular blockers is unknown. This study aimed to compare outcomes in severe ARDS patients treated with cisatracurium versus atracurium. METHODS: Patients admitted in ICUs with a diagnosis of severe ARDS and treated with neuromuscular blocking agents within 72 h of diagnosis were included. Subjects treated with cisatracurium versus atracurium were compared. The primary outcome was improvement in oxygenation, defined as the difference of PaO2 /FIO2 at 72 h post-initiation of neuromuscular blocking agents. Secondary outcomes were ventilator-free days at day 28, ICU and hospital lengths of stay, and hospital mortality. RESULTS: Seventy-six subjects with ARDS were included in the study. Eighteen subjects (24%) were treated with atracurium, whereas 58 (76%) were treated with cisatracurium. Equivalent dosages of sedation and analgesia as well as use of brain function monitoring technology were similar between both groups. There were no differences in clinical outcomes. Specifically, improvement of PaO2 /FIO2 was a median (interquartile range [IQR]) of 65 (25-162) in the atracurium group and 66 (IQR 16-147) in the cisatracurium group (P = .65). Ventilator-free days at day 28 were 13 d (IQR 0-22 d) and 15 d (IQR 8-21 d) in the atracurium and cisatracurium groups, respectively (P = .72). ICU length or stay was 18 d (IQR 8-34 d) in the atracurium group and 15 d (IQR 9-22 d) in the cisatracurium group (P = .34). In-hospital mortality was 50% for the atracurium population and 62% for the cisatracurium group (P = .42) CONCLUSIONS: Among subjects with early severe ARDS, the utilization of atracurium versus cisatracurium within 72 h of admission was not associated with significant differences in clinical outcomes.