Novel tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris in a preadolescent population.

BackgroundAcne vulgaris (acne) is a common skin condition in children and adolescents. Efficacy of tretinoin is well documented in studies that included pediatric patients (12-18 years of age). With acne routinely presenting in younger patients, data are needed in this important group. Lotion formulations are commonly used across dermatology and are well liked by patients.ObjectiveTo evaluate the safety and efficacy of a novel once-daily tretinoin 0.05% lotion in preadolescent subjects (≤ 13 years) with moderate-to-severe acne.MethodsPost hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies in moderate-to-severe acne. Preadolescent subjects (N = 154) randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory/noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator's Global Severity Score [EGSS] and clear/almost clear). Safety, adverse events (AEs), and cutaneous tolerability evaluated throughout.ResultsAt Week 12, mean percent reduction in inflammatory and noninflammatory lesion counts were 49.5% and 44.0% compared with 31.4% and 18.8% with vehicle (both P = 0.001). Treatment success was achieved by 23.7% of subjects by Week 12, compared with 7.2% (P = 0.009). The majority of AEs were mild and transient: most frequently were application site pain (5.6%) and application site dryness (2.8%). Local cutaneous safety and tolerability assessments were generally mild-to-moderate and improved by Week 12.ConclusionsTretinoin 0.05% lotion was significantly more effective than vehicle in achieving treatment success and reducing inflammatory and noninflammatory lesions in preadolescent acne. It was well tolerated, with all treatment-related AEs deemed mild or moderate

Abdominal aortic aneurysm rupture presenting with focal weakness and altered mental status: a case report.

BACKGROUND: Abdominal aortic aneurysms (AAA) can present asymptomatically and may be found through routine screening or seen incidentally on imaging. Rupture due to weaking of the aortic wall is the main complication of an AAA and leads to approximately 200,000 deaths annually worldwide. Clinically, AAA rupture most frequently presents with abdominal and/or back pain, pulsatile abdominal mass, and hypotension. Here, we present an unusual presentation of embolic cerebrovascular accident associated with an AAA rupture. CASE PRESENTATION: A 58-year-old African American man transported to the emergency department via ambulance presents with altered mental status and unilateral extremity weakness. The initial presentation was concerning for acute cerebrovascular accident, acute kidney injury, severe sepsis, and urinary tract infection. Several hours after the initial presentation, the patient\u27s abdomen began to appear distended and he became hypotensive. An abdominal CT was ordered which showed a large AAA rupture with a retroperitoneal bleed. The patient was transferred to a higher-level medical center for surgical repair. CONCLUSION: Abdominal aortic aneurysm rupture can rarely present due to an acute cerebrovascular accident with altered mental status and focal neurologic deficits

Improving the Graphical User Interface (GUI) for the Dynamic Feedback Signal Set (DyFSS): Increasing Accessibility for the Neurodiverse

Peripheral biofeedback is an explicit learning tool that allows for real-time evaluation and control of physiological proxies by means of computerized signals. Its integration into health practice allows users to calibrate self-awareness and self regulation then apply these skills to everyday life. People with neurodevelopmental differences encounter limitations when using commercially available clinical biofeedback due to variation in their autonomic response. Principles of Universal Design dictate that biofeedback inputs and displays allow effective access and benefit for as many individuals as possible. Our Dynamic Feedback Signal Set (DyFSS, nonprovisional patent-in-process) algorithm adjusts signal processing by dynamically weighting feedback signals to the best abilities of the user, increasing the efficacy of biofeedback for the neurodiverse. The software includes an interactive graphical tutorial and quiz, a variety of graphical user interfaces to honor individual preferences and abilities, and a game that can be played by blind and hard of hearing individuals alike

Research Ethics Recommendations for Whole-Genome Research: Consensus Statement

Interest in whole-genome research has grown substantially over the past few months. This article explores the challenging ethics issues associated with this work

Pragmatic clinical trials embedded in healthcare systems: generalizable lessons from the NIH Collaboratory

Background: The clinical research enterprise is not producing the evidence decision makers arguably need in a timely and cost effective manner; research currently involves the use of labor-intensive parallel systems that are separate from clinical care. The emergence of pragmatic clinical trials (PCTs) poses a possible solution: these large-scale trials are embedded within routine clinical care and often involve cluster randomization of hospitals, clinics, primary care providers, etc. Interventions can be implemented by health system personnel through usual communication channels and quality improvement infrastructure, and data collected as part of routine clinical care. However, experience with these trials is nascent and best practices regarding design operational, analytic, and reporting methodologies are undeveloped. Methods: To strengthen the national capacity to implement cost-effective, large-scale PCTs, the Common Fund of the National Institutes of Health created the Health Care Systems Research Collaboratory (Collaboratory) to support the design, execution, and dissemination of a series of demonstration projects using a pragmatic research design. Results: In this article, we will describe the Collaboratory, highlight some of the challenges encountered and solutions developed thus far, and discuss remaining barriers and opportunities for large-scale evidence generation using PCTs. Conclusion: A planning phase is critical, and even with careful planning, new challenges arise during execution; comparisons between arms can be complicated by unanticipated changes. Early and ongoing engagement with both health care system leaders and front-line clinicians is critical for success. There is also marked uncertainty when applying existing ethical and regulatory frameworks to PCTS, and using existing electronic health records for data capture adds complexity

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer