Anti-nerve growth factor antibodies for the treatment of low back pain.

INTRODUCTION: The treatment of chronic low back pain (cLBP) often involves multimodal pharmacologic and non-pharmacologic strategies. There remain shortcomings with these tools with regards to both effect size and side effects. AREAS COVERED: In an effort to better address cLBP, anti-nerve growth factor (NGF) monoclonal antibodies (mAbs) are nearing marketing approval. This class of medications has been primarily evaluated for osteoarthritis, but are being examined at higher doses for use in cLBP. We review the efficacy of this class in treating LBP as well as their potential side effects based on nine phase II or III published clinical trials. Five trials evaluated Tanezumab and four trials evaluated Fasinumab, with seven trials evaluating nonspecific LBP, one evaluating sciatica related cLBP, and one evaluating vertebral fracture related cLBP. EXPERT OPINION: The results of available clinical trials indicate modest effectiveness with regard to reduction of pain in the low back, and improved functionality, compared to placebo in keeping with the effect size of other pharmacologic treatment modalities. Rapidly progressive osteoarthritis was infrequently reported. However, the continued observation of this serious side effects warrants careful patient selection and balancing the risks and benefits of anti-NGF mAbs in treating cLBP.

Evaluation of Knowledge Acquisition with a Practice Management Course for Anesthesiology Residents: A Pilot Study.

Physicians routinely rely on nontechnical skills-including leadership ability, managerial skills and financial considerations-when delivering patient care. Efficient practice management is a commonplace expectation of attending anesthesiologists, but there is no uniform residency training to foster the expertise required to succeed in this endeavor. The purpose of this study is to evaluate a novel practice management course for anesthesiology residents. METHODS: Senior anesthesiology residents (Clinical Anesthesia-3) at The George Washington University were eligible to participate in a 1-month Ambulatory Anesthesiology-Practice Management Rotation focusing on the acquisition of nontechnical skills and knowledge applicable to becoming an effective clinical leader. The rotation included 1-week service as operating room manager, completion of an online module, assigned readings with follow-up discussions, and completion of a billing and reimbursement exercise. The interventions, in aggregate, were measured with a preknowledge and a postknowledge test. RESULTS: Twelve residents out of 14 (86%) completed the preknowledge and postknowledge tests. Residents scored significantly higher on the postcourse exam (61.49%, SD 18.65%) than the pretest (42.7%, SD 12.7%) (P < .004). CONCLUSION: A curriculum designed to develop the practice management skills required of a physician anesthesiologist is feasible and effective at improving knowledge within a 1-month, senior resident rotation.

Pathophysiology of Autoimmune Bullous Diseases: Nature Versus Nurture.

Pemphigus and pemphigoid are the prototypical immunobullous diseases. Although it has been well established that they are caused by deposition of autoreactive antibodies directed against adherence proteins within the skin, the specific genetic and environmental factors leading to development of these diseases continue to be an area of investigation. Herein, we discuss several of the potential environmental triggers that may induce patients to develop immunobullous diseases including medications, viral infections, UV exposure or other radiation injury and dietary factors. In addition, the potential genetic and immunologic mechanisms contributing to the pathogenesis of pemphigus and pemphigoid will be reviewed. The multifactorial nature of these diseases contributes to their complexity and highlights the importance of a detailed personal and family history when caring for these patients.

Topical clobetasol for the treatment of toxic epidermal necrolysis: study protocol for a randomized controlled trial.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a rare systemic allergic drug eruption with high patient mortality. Currently, no established treatments have been shown to be effective for TEN beyond supportive care. Prior studies of systemic corticosteroids have yielded conflicting data, with some showing a possible benefit and others reporting in increased mortality. However, topical steroids have shown promise for treatment of ocular sequelae of TEN, such as scarring and vision loss. We have designed a randomized controlled trial to evaluate topical clobetasol for treatment of the epidermal manifestations of TEN. In addition, we propose genetic studies to characterize the TEN transcriptome and alterations in cutaneous gene expression that might occur following topical steroid treatment. METHODS/DESIGN: This split-body randomized, double-blind, placebo-controlled Phase IIa proof-of-concept trial will evaluate the safety and efficacy of once-daily topical clobetasol applied to the skin of patients with TEN. This multicenter trial will recruit a total of 15 patients between the ages of 12 and 85 from the University of California Davis Medical Center and Shriners Hospital for Children inpatient burn units. Designated treatment areas on opposite sides of the body will be treated with blinded clobetasol 0.05% ointment or control petrolatum ointment daily for 14 days. On day 3 of therapy, a biopsy will be taken from the treated area for genetic studies. The primary study aims will be to establish the safety of topical clobetasol treatment and determine the time to cessation of skin detachment for the control and clobetasol-treated areas. Secondary endpoints will evaluate efficacy using parameters such as time to 90% re-epithelialization and percentage of affected skin at 0, 3, 6, 9, 12 and 15 days. Genomic DNA and RNA will be obtained from biopsy samples, to characterize the TEN transcriptome and identify changes in gene expression after topical steroid treatment. DISCUSSION: Topical steroids have shown promise for treating ocular complications of TEN, but to date have not been evaluated for cutaneous manifestations of the disease. This trial will investigate clinical and molecular outcomes of topical clobetasol application and hopefully provide insight into the disease pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov NCT02319616. https://clinicaltrials.gov/ct2/show/NCT02351037.

Metastatic melanoma - a review of current and future treatment options.

Despite advances in treatment and surveillance, melanoma continues to claim approximately 9,000 lives in the US annually (SEER 2013). The National Comprehensive Cancer Network currently recommends ipilumumab, vemurafenib, dabrafenib, and high-dose IL-2 as first line agents for Stage IV melanoma. Little data exists to guide management of cutaneous and subcutaneous metastases despite the fact that they are relatively common. Existing options include intralesional Bacillus Calmette-Guérin, isolated limb perfusion/infusion, interferon-α, topical imiquimod, cryotherapy, radiation therapy, interferon therapy, and intratumoral interleukin-2 injections. Newly emerging treatments include the anti-programmed cell death 1 receptor agents (nivolumab and pembrolizumab), anti-programmed death-ligand 1 agents, and oncolytic vaccines (talimogene laherparepevec). Available treatments for select sites include adoptive T cell therapies and dendritic cell vaccines. In addition to reviewing the above agents and their mechanisms of action, this review will also focus on combination therapy as these strategies have shown promising results in clinical trials for metastatic melanoma treatment.