Background: Prolonged use of opioids initiated for surgical or trauma-related pain management has become a global problem. While several factors have been reported to increase the risk of prolonged opioid use, there is considerable inconsistency regarding their significance or effect size. Therefore, we aimed to pool the effects of risk factors for prolonged opioid use following trauma or surgery and to assess the rate and temporal trend of prolonged opioid use in different settings. Methods: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched Embase, PubMed, Web of Science, EBM (Evidence-Based Medicine) Reviews - Cochrane Database of Systematic Reviews, and ClinicalTrials.gov from inception to August 28, 2017, without language restriction. Observational studies reporting risk factors for, or the rate of, prolonged opioid use among adult patients following surgery or trauma with a minimum of 1 month of follow-up were included. Study and patient characteristics, risk factors, and the rate of prolonged opioid use were synthesized. Results: Thirty-seven studies with 1,969,953 patients were included; 4.3% (95% confidence interval [CI] = 2.3% to 8.2%) of patients continued opioid use after trauma or surgery. Prior opioid use (number needed to harm [NNH] = 3, odds ratio [OR] = 11.04 [95% CI = 9.39 to 12.97]), history of back pain (NNH = 23, OR = 2.10 [95% CI = 2.00 to 2.20]), longer hospital stay (NNH = 25, OR = 2.03 [95% CI = 1.03 to 4.02]), and depression (NNH = 40, OR = 1.62 [95% CI = 1.49 to 1.77]) showed some of the largest effects on prolonged opioid use (p < 0.001 for all but hospital stay [p = 0.042]). The rate of prolonged opioid use was higher in trauma (16.3% [95% CI = 13.6% to 22.5%]; p < 0.001) and in the Workers’ Compensation setting (24.6% [95% CI = 2.0% to 84.5%]; p = 0.003) than in other subject enrollment settings. The temporal trend was not significant for studies performed in the U.S. (p = 0.07) while a significant temporal trend was observed for studies performed outside of the U.S. (p = 0.014). Conclusions: To our knowledge, this is the first meta-analysis reporting the pooled effect of risk factors that place patients at an increased chance for prolonged opioid use. Understanding the pooled effect of risk factors and their respective NNH values can aid patients and physicians in developing effective and individualized pain-management strategies with a lower risk of prolonged opioid use. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Burn wounds result from exposure to hot liquids, chemicals, fire, electric discharge or radiation. Wound severity ranges from first-degree injury, which is superficial, to fourth-degree injury, which exposes bone, tendons and muscles. Rapid assessment of burn depth and accurate wound management in the outpatient setting is critical to prevent injury progression into deeper layers of the dermis. Injury progression is of particular pertinence to second-degree burns, which are the most common form of thermal burn. As our understanding of wound healing advances, treatment options and technologies for second-degree burn management also evolve. Polymeric hydrogels are a class of burn wound dressings that adhere to tissue, absorb wound exudate, protect from the environment, can be transparent facilitating serial wound evaluation and, in some cases, enable facile removal for dressing changes. This review briefly describes the burn level classification and common, commercially available dressings used to treat second-degree burns, and then focuses on new polymeric hydrogel burn dressings under preclinical development analyzing their design, structure and performance. The review presents the follow key learning points: (1) introduction to the integument system and the wound-healing process; (2) classification of burns according to severity and clinical appearance; (3) available dressings currently used for second-degree burns; (4) introduction to hydrogels and their preparation and characterization techniques; and (5) pre-clinical hydrogel burn wound dressings currently being developed.

Arthrofibrosis is a prevalent condition affecting greater than 5% of the general population and leads to a painful decrease in joint range of motion (ROM) and loss of independence due to pathologic accumulation of periarticular scar tissue. Current treatment options are limited in effectiveness and do not address the underlying cause of the condition: accumulation of fibrotic collagenous tissue. Herein, the naturally occurring peptide hormone relaxin-2 is administered for the treatment of adhesive capsulitis (frozen shoulder) and to restore glenohumeral ROM in shoulder arthrofibrosis. Recombinant human relaxin-2 down-regulates type I collagen and α smooth muscle actin production and increases intracellular cAMP concentration in human fibroblast-like synoviocytes, consistent with a mechanism of extracellular matrix degradation and remodeling. Pharmacokinetic profiling of a bolus administration into the glenohumeral joint space reveals the brief systemic and intraarticular (IA) half-lives of relaxin-2: 0.96 h and 0.62 h, respectively. Furthermore, using an established, immobilization murine model of shoulder arthrofibrosis, multiple IA injections of human relaxin-2 significantly improve ROM, returning it to baseline measurements collected before limb immobilization. This is in contrast to single IA (sIA) or multiple i.v. (mIV) injections of relaxin-2 with which the ROM remains constrained. The histological hallmarks of contracture (e.g., fibrotic adhesions and reduced joint space) are absent in the animals treated with multiple IA injections of relaxin-2 compared with the untreated control and the sIA- and mIV-treated animals. As these findings show, local delivery of relaxin-2 is an innovative treatment of shoulder arthrofibrosis.