Research Spotlight

Bissonnette, R., M. Luchi, R. Fidelus-Gort, S. Jackson, H. Zhang, R. Flores, R. Newton, P. Scherle, S. Yeleswaram, X. Chen and A. Menter (2016). “A randomized, double-blind, placebo-controlled, dose-escalation study of the safety and efficacy of INCB039110, an oral janus kinase 1 inhibitor, in patients with stable, chronic plaque psoriasis.” J Dermatolog Treat: 1-7.

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BACKGROUND: Chronic plaque psoriasis is partially mediated by elevation of proinflammatory cytokines, including several within the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. OBJECTIVE: To evaluate the safety and efficacy of the oral selective JAK1 inhibitor INCB039110 in stable, chronic plaque psoriasis. METHODS: This was a phase 2, randomized, double-blind, placebo-controlled, dose-escalation study of INCB039110 (100 mg once daily, 200 mg once daily, 200 mg twice daily and 600 mg once daily) for 28 days. The primary endpoint was mean percent change from baseline in the static Physician Global Assessment (sPGA) at day 28. The protocol was institutional review board approved. RESULTS: Of 50 patients, 48 completed the study. At day 28, mean percent reduction from baseline in sPGA was 22.2% for INCB039110 100 mg once daily (p = 0.270 vs. placebo), 29.4% for 200 mg once daily (p = 0.118), 35.2% for 200 mg twice daily (p = 0.053), 42.4% for 600 mg once daily (p = 0.003) and 12.5% for placebo. Across groups, 11.1% to 45.5% achieved an sPGA score of 1 versus 0% for placebo. INCB039110 was generally well tolerated; the most common treatment-emergent adverse event was nasopharyngitis (18.4%). CONCLUSION: INCB039110 produced significant improvements in sPGA, demonstrating proof of concept in chronic plaque psoriasis.

Carpenter, J. P., R. Cuff, C. Buckley, C. Healey, S. Hussain, M. M. Reijnen, J. Trani and D. Bockler (2016). “Results of the Nellix system investigational device exemption pivotal trial for endovascular aneurysm sealing.” J Vasc Surg 63(1): 23-31.e21.

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OBJECTIVE: The Nellix EndoVascular Aneurysm Sealing system (Endologix, Inc, Irvine, Calif) is a novel approach to abdominal aortic aneurysm (AAA) endovascular repair whereby biocompatible polymer is employed to exclude and to seal the AAA sac. We report 30-day results of the U.S. pivotal trial. METHODS: Consecutive, eligible, consenting patients were enrolled at 29 sites in the United States and Europe.  Inclusion criteria required an asymptomatic infrarenal AAA, with aortic neck length >/=10 mm and angle to the sac </=60 degrees, aortic neck diameter of 18 to 32 mm, aneurysm blood lumen diameter </=6 cm, common iliac artery lumen diameter of 9 to 35 mm, access artery diameter >/=6 mm, and serum creatinine level </=2 mg/dL. Follow-up at 30 days included clinical assessment and computed tomography angiography evaluation of endoleaks and device integrity as assessed by a core laboratory. The primary safety end point is the incidence of independently adjudicated 30-day major adverse events (MAEs), with success defined as superiority with reference to the Society for Vascular Surgery open repair control group (56%). RESULTS: Between January and November 2014, 150 trial patients having a mean AAA diameter of 5.8 cm were enrolled and treated with the Nellix system with 100% procedural success. One early death (0.7%) occurred secondary to multisystem organ failure. All 149 surviving patients completed 30-day follow-up. There were no aneurysm ruptures, conversions, limb thromboses, stent fractures, or stent kinking. Five early MAEs occurred in four patients (2.7%) and included one death, bowel ischemia (1), renal failure (2), and respiratory failure (1). One (0.7%) secondary intervention to treat inadvertent coverage of a renal artery was performed. The core laboratory identified nine (6%) endoleaks (one type I, eight type II) on 30-day computed tomography angiography. Freedom from MAE was 97.3% (95% confidence interval, 93.3%-99.0%). CONCLUSIONS: In selected patients, perioperative outcomes with the Nellix system for endovascular aneurysm sealing are encouraging, with very low 30-day morbidity and mortality and high procedural success. The primary safety end point has been achieved. Longer term follow-up is in progress.

Collinsworth, A. W., E. L. Priest, C. R. Campbell, E. E. Vasilevskis and A. L. Masica (2016). “A Review of Multifaceted Care Approaches for the Prevention and Mitigation of Delirium in Intensive Care Units.” J Intensive Care Med 31(2): 127-141.

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OBJECTIVE: The objective of this review is to examine the effectiveness, implementation, and costs of multifaceted care approaches, including care bundles, for the prevention and mitigation of delirium in patients hospitalized in intensive care units (ICUs). DATA SOURCES: A systematic search using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted utilizing PubMed, EMBASE, and CINAHL. Searches were limited to studies published in English from January 1, 1988, to March 31, 2014. Randomized controlled trials and comparative studies of multifaceted care approaches with the reduction of delirium in ICU patients as an outcome and evaluations of the implementation or cost-effectiveness of these interventions were included. DATA EXTRACTION: Data on study methods including design, cohort size, interventions, and outcomes were abstracted, reviewed, and summarized. Given the variability in study design, populations, and interventions, a qualitative review of findings was conducted. DATA SYNTHESIS: In all, 14 studies met our inclusion criteria: 6 examined outcomes, 5 examined implementation, 2 examined outcomes and implementation, and 1 examined cost-effectiveness. The majority of studies indicated that multifaceted care approaches were associated with improved patient outcomes including reduced incidence and duration of delirium. Additionally, improvements in functional status and reductions in coma and ventilator days, hospital length of stay, and/or mortality rates were observed. Implementation strategies included structured quality improvement approaches with ongoing audit and feedback, multidisciplinary care teams, intensive training, electronic reporting systems, and local support teams. The cost-effectiveness analysis indicated an average reduction of $1000 in hospital costs for patients treated with a multifaceted care approach. CONCLUSION: Although multifaceted care approaches may reduce delirium and improve patient outcomes, greater improvements may be achieved by deploying a comprehensive bundle of care practices including awakening and breathing trials, delirium monitoring and treatment, and early mobility. Further research to address this knowledge gap is essential to providing best care for ICU patients.

Crouse, S. F., S. White, J. P. Erwin, T. H. Meade, S. E. Martin, J. M. Oliver, D. P. Joubert, B. S. Lambert, J. P. Bramhall, K. Gill and D. Weir (2016). “Echocardiographic and Blood Pressure Characteristics of First-Year Collegiate American-Style Football Players.” Am J Cardiol 117(1): 131-134.

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Echocardiographic (echo) and blood pressure (BP) reference values may help identify athletes at cardiovascular risk, yet benchmarks are inadequate for collegiate American-style football (ASF) players. Our purpose was to describe echo characteristics and BP values in collegiate ASF athletes compared with normal. First-year players (n = 80, age = 18 +/- 1 years, height = 186 +/- 7 cm, weight = 100.1 +/- 22.0 kg, body mass index = 28.7 +/- 5.0), body surface area [BSA] = 2.24 +/- 0.25; percentage fat = 16.5 +/- 9.7%) were measured for systolic and diastolic BP, and underwent echo procedures by a certified sonographer. Data analyses included simple statistics, Pearson r, frequencies in normal ranges, and t test; alpha = 0.05. Selected echo measurements (and indexed by BSA) were: left ventricular (LV) internal diameter diastole = 5.3 +/- 0.5 cm (2.4 +/- 0.3); left atrial diameter = 3.9 +/- 0.5 cm (1.8 +/- 0.2): LV end-diastolic volume = 138 +/- 30 ml (62 +/- 11); septal wall thickness = 1.0 +/- 0.2 cm (0.5 +/- 0.1); LV posterior wall thickness = 1.0 +/- 0.1 cm (0.5 +/- 0.1), LV mass = 212 +/- 46 g (95 +/- 18); and relative wall thickness = 0.39 +/- 0.07. Correlations between BSA and echo variables were significant (r = 0.26 to 0.50). Indexing by BSA reduced percentages above reference ranges from 36% to 7%. Septal wall thickness index was significantly greater in black (0.5 +/- 0.1) than nonblack (0.4 +/- 0.1) athletes. Fifty-nine athletes were hypertensive or prehypertensive, and diastolic BP was significantly greater in black (76 +/- 10 mm Hg) compared with nonblack athletes (71 +/- 8 mm Hg). ASF athletes demonstrated LV wall thicknesses and cavity sizes consistent with sport-training hypertrophy but which were unremarkable when indexed by BSA. Ethnicity generally did not influence echo variables. No ASF players were identified with cardiac dysfunction or disease.

Dehmer, G. J., J. Jennings, R. A. Madden, D. J. Malenka, F. A. Masoudi, C. R. McKay, D. L. Ness, S. V. Rao, F. S. Resnic, M. E. Ring, J. S. Rumsfeld, M. E. Shelton, M. C. Simanowith, L. E. Slattery, W. S. Weintraub, A. Lovett and S. L. Normand (2016). “The National Cardiovascular Data Registry Voluntary Public Reporting Program: An Interim Report From the NCDR Public Reporting Advisory Group.” J Am Coll Cardiol 67(2): 205-215.

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Public reporting of health care data continues to proliferate as consumers and other stakeholders seek information on the quality and outcomes of care. Medicare’s Hospital Compare website, the U.S. News & World Report hospital rankings, and several state-level programs are well known. Many rely heavily on administrative data as a surrogate to reflect clinical reality. Clinical data are traditionally more difficult and costly to collect, but more accurately reflect patients’ clinical status, thus enhancing the validity of quality metrics. We describe the public reporting effort being launched by the American College of Cardiology and partnering professional organizations using clinical data from the National Cardiovascular Data Registry (NCDR) programs. This hospital-level voluntary effort will initially report process of care measures from the percutaneous coronary intervention (CathPCI) and implantable cardioverter-defibrillator (ICD) registries of the NCDR. Over time, additional process, outcomes, and composite performance metrics will be reported.