Evaluation and comparison of pharmacokinetic profiles and safety of two extended-release buprenorphine formulations in common marmosets (Callithrix jacchus).

While sustained-release buprenorphine (BSR) is used as a long-lasting opioid analgesic in common marmosets (Callithrix jacchus), there are no published studies on pharmaceutical-grade extended-release buprenorphine options such as Ethiqa XR (EXR) for this species. However, BSR is a compounded product and has been reported to cause injection site reactions in multiple species, including marmosets. Additionally, now with the availability of EXR, a pharmaceutical-grade veterinary product, the use of BSR in laboratory animals is not compliant with the Guide for the Care and Use of Laboratory Animals (Guide) unless scientifically justified and approved by the IACUC. We compared pharmacokinetic and safety profiles of BSR (0.15 mg/kg) and EXR (0.1-0.2 mg/kg) administered subcutaneously to adult marmosets. Blood was collected by venipuncture of the saphenous vein at multiple time points (0.25-72 h) and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). EXR between 0.1 and 0.2 mg/kg resulted in a dose-dependent increase in Cmax (1.43-2.51 ng/mL) and were not statistically different from BSR (1.82 ng/mL). Tmax, lambdaz, and t1/2 were not statistically different between formulations. Mean plasma buprenorphine concentrations for BSR and EXR exceeded the therapeutic threshold (0.1 ng/mL) within 0.25 h and lasted for > 72 h. Mild sedation, but neither respiratory depression nor ataxia, was observed for both formulations. BSR injection sites had significantly higher histopathological scores compared to EXR. Video recordings for monitoring drug-induced behavioral changes showed increased animal activity levels after BSR and EXR versus saline controls. Norbuprenorphine, a buprenorphine metabolite associated with respiratory depression, was detected in the plasma after BSR and EXR administration as well as by in vitro liver microsome assays. In conclusion, we recommend using EXR over BSR as a long-lasting buprenorphine analgesic in marmosets because EXR is a pharmaceutical-grade formulation that is compliant with FDA guidelines and the Guide as well as exhibits comparable PK and safety profiles as BSR.

Smart dental materials for antimicrobial applications.

Smart biomaterials can sense and react to physiological or external environmental stimuli (e.g., mechanical, chemical, electrical, or magnetic signals). The last decades have seen exponential growth in the use and development of smart dental biomaterials for antimicrobial applications in dentistry. These biomaterial systems offer improved efficacy and controllable bio-functionalities to prevent infections and extend the longevity of dental devices. This review article presents the current state-of-the-art of design, evaluation, advantages, and limitations of bioactive and stimuli-responsive and autonomous dental materials for antimicrobial applications. First, the importance and classification of smart biomaterials are discussed. Second, the categories of bioresponsive antibacterial dental materials are systematically itemized based on different stimuli, including pH, enzymes, light, magnetic field, and vibrations. For each category, their antimicrobial mechanism, applications, and examples are discussed. Finally, we examined the limitations and obstacles required to develop clinically relevant applications of these appealing technologies.

Experimental and computational understanding of pulsatile release mechanism from biodegradable core-shell microparticles.

Next-generation therapeutics require advanced drug delivery platforms with precise control over morphology and release kinetics. A recently developed microfabrication technique enables fabrication of a new class of injectable microparticles with a hollow core-shell structure that displays pulsatile release kinetics, providing such capabilities. Here, we study this technology and the resulting core-shell microstructures. We demonstrated that pulsatile release is governed by a sudden increase in porosity of the polymeric matrix, leading to the formation of a porous path connecting the core to the environment. Moreover, the release kinetics within the range studied remained primarily independent of the particle geometry but highly dependent on its composition. A qualitative technique was developed to study the pattern of pH evolution in the particles. A computational model successfully modeled deformations, indicating sudden expansion of the particle before onset of release. Results of this study contribute to the understanding and design of advanced drug delivery systems.

Impact of the Affordable Care Act on trauma and emergency general surgery: An Eastern Association for the Surgery of Trauma systematic review and meta-analysis.

BACKGROUND: Trauma and emergency general surgery (EGS) patients who are uninsured have worse outcomes as compared with insured patients. Partially modeled after the 2006 Massachusetts Healthcare Reform (MHR), the Patient Protection and Affordable Care Act was passed in 2010 with the goal of expanding health insurance coverage, primarily through state-based Medicaid expansion (ME). We evaluated the impact of ME and MHR on outcomes for trauma patients, EGS patients, and trauma systems. METHODS: This study was approved by the Eastern Association for the Surgery of Trauma Guidelines Committee. Using Grading of Recommendations Assessment, Development and Evaluation methodology, we defined three populations of interest (trauma patients, EGS patients, and trauma systems) and identified the critical outcomes (mortality, access to care, change in insurance status, reimbursement, funding). We performed a systematic review of the literature. Random effect meta-analyses and meta-regression analyses were calculated for outcomes with sufficient data. RESULTS: From 4,593 citations, we found 18 studies addressing all seven predefined outcomes of interest for trauma patients, three studies addressing six of seven outcomes for EGS patients, and three studies addressing three of eight outcomes for trauma systems. On meta-analysis, trauma patients were less likely to be uninsured after ME or MHR (odds ratio, 0.49; 95% confidence interval, 0.37-0.66). These coverage expansion policies were not associated with a change in the odds of inpatient mortality for trauma (odds ratio, 0.96; 95% confidence interval, 0.88-1.05). Emergency general surgery patients also experienced a significant insurance coverage gains and no change in inpatient mortality. Insurance expansion was often associated with increased access to postacute care at discharge. The evidence for trauma systems was heterogeneous. CONCLUSION: Given the evidence quality, we conditionally recommend ME/MHR to improve insurance coverage and access to postacute care for trauma and EGS patients. We have no specific recommendation with respect to the impact of ME/MHR on trauma systems. Additional research into these questions is needed. LEVEL OF EVIDENCE: Review, Economic/Decision, level III.

Assessment of Patient-Centered Approaches to Collect Sexual Orientation and Gender Identity Information in the Emergency Department: The EQUALITY Study.

Importance: Health care and government organizations call for routine collection of sexual orientation and gender identity (SOGI) information in the clinical setting, yet patient preferences for collection methods remain unknown. Objective: To assess of the optimal patient-centered approach for SOGI collection in the emergency department (ED) setting. Design, Setting, and Participants: This matched cohort study (Emergency Department Query for Patient-Centered Approaches to Sexual Orientation and Gender Identity [EQUALITY] Study) of 4 EDs on the east coast of the United States sequentially tested 2 different SOGI collection approaches between February 2016 and March 2017. Multivariable ordered logistic regression was used to assess whether either SOGI collection method was associated with higher patient satisfaction with their ED experience. Eligible adults older than 18 years who identified as a sexual or gender minority (SGM) were enrolled and then matched 1 to 1 by age (aged ≥5 years) and illness severity (Emergency Severity Index score ±1) to patients who identified as heterosexual and cisgender (non-SGM), and to patients whose SOGI information was missing (blank field). Patients who identified as SGM, non-SGM, or had a blank field were invited to complete surveys about their ED visit. Data analysis was conducted from April 2017 to November 2017. Interventions: Two SOGI collection approaches were tested: nurse verbal collection during the clinical encounter vs nonverbal collection during patient registration. The ED physicians, physician assistants, nurses, and registrars received education and training on sexual or gender minority health disparities and terminology prior to and throughout the intervention period. Main Outcomes and Measures: A detailed survey, developed with input of a stakeholder advisory board, which included a modified Communication Climate Assessment Toolkit score and additional patient satisfaction measures. Results: A total of 540 enrolled patients were analyzed; the mean age was 36.4 years and 66.5% of those who identified their gender were female. Sexual or gender minority patients had significantly better Communication Climate Assessment Toolkit scores with nonverbal registrar form collection compared with nurse verbal collection (mean [SD], 95.6 [11.9] vs 89.5 [20.5]; P = .03). No significant differences between the 2 approaches were found among non-SGM patients (mean [SD], 91.8 [18.9] vs 93.2 [13.6]; P = .59) or those with a blank field (92.7 [15.9] vs 93.6 [14.7]; P = .70). After adjusting for age, race, illness severity, and site, SGM patients had 2.57 (95% CI, 1.13-5.82) increased odds of a better Communication Climate Assessment Toolkit score category during form collection compared with verbal collection. Conclusions and Relevance: Sexual or gender minority patients reported greater comfort and improved communication when SOGI was collected via nonverbal self-report. Registrar form collection was the optimal patient-centered method for collecting SOGI information in the ED.

Closed reduction and fluoroscopic-assisted percutaneous pinning of 42 physeal fractures in 37 dogs and 4 cats.

OBJECTIVE: To report complications and clinical outcome of dogs and cats that underwent fluoroscopic-assisted percutaneous pinning (FAPP) of physeal fractures. STUDY DESIGN: Retrospective study. ANIMALS: Client-owned dogs (n = 37) and cats (n = 4). MATERIALS AND METHODS: Records (August 2007-August 2014) of physeal fractures treated with FAPP in 3 hospitals were evaluated. Data collected included signalment, fracture characteristics (etiology, location, duration, Salter-Harris classification, preoperative and postoperative displacement), surgical information (implant size, surgical duration), and outcome assessment information (functional outcome, radiographic outcome, and complications). RESULTS: The majority of animals (92%) were classified as full functional outcome. No significant predictors of functional outcome were identified. The overall complication rate was 15% (n = 6). Elective pin removal rate was 41% (n = 17). Goniometry and limb circumference measurements of the affected and contralateral limbs were not significantly different in dogs for which measurements were obtained. Seventeen of 18 animals (16 dogs, 2 cats) measured had bone length changes on follow-up radiographs. CONCLUSION: FAPP is associated with an excellent functional outcome in a narrow selection of fracture configurations, specifically those with minimal displacement and for which anatomical alignment can be achieved with closed reduction.