Concordance of antibiotic prescribing with the American Dental Association acute oral infection guidelines within Veterans' Affairs (VA) dentistry.

OBJECTIVE: United States dentists prescribe 10% of all outpatient antibiotics. Assessing appropriateness of antibiotic prescribing has been challenging due to a lack of guidelines for oral infections. In 2019, the American Dental Association (ADA) published clinical practice guidelines (CPG) on the management of acute oral infections. Our objective was to describe baseline national antibiotic prescribing for acute oral infections prior to the release of the ADA CPG and to identify patient-level variables associated with an antibiotic prescription. DESIGN: Cross-sectional analysis. METHODS: We performed an analysis of national VA data from January 1, 2017, to December 31, 2017. We identified cases of acute oral infections using International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Antibiotics prescribed by a dentist within ±7 days of a visit were included. Multivariable logistic regression identified patient-level variables associated with an antibiotic prescription. RESULTS: Of the 470,039 VA dental visits with oral infections coded, 12% of patient visits with irreversible pulpitis, 17% with apical periodontitis, and 28% with acute apical abscess received antibiotics. Although the median days' supply was 7, prolonged use of antibiotics was frequent (≥8 days, 42%-49%). Patients with high-risk cardiac conditions, prosthetic joints, and endodontic, implant, and oral and maxillofacial surgery dental procedures were more likely to receive antibiotics. CONCLUSIONS: Most treatments of irreversible pulpitis and apical periodontitis cases were concordant with new ADA guidelines. However, in cases where antibiotics were prescribed, prolonged antibiotic courses >7 days were frequent. These findings demonstrate opportunities for the new ADA guidelines to standardize and improve dental prescribing practices.

Sustained Release of Hydrogen Sulfide (H2S) from Poly(Lactic Acid) Functionalized 4-Hydroxythiobenzamide Microparticles to Protect Against Oxidative Damage.

Hydrogen sulfide (H2S) has emerged as a gaseous mediator capable of exhibiting many beneficial properties including cytoprotection, anti-inflammation, and vasodilation. The study presented here provides characterization of a poly(lactic acid) polymer with a functionalized 4-hydroxythiobenzamide (PLA-4HTB) capable of extended H2S release. The polymer was used to fabricate microparticles that can be potentially loaded with a drug allowing for co-release of the drug and H2S. Microparticles with the average diameter of 500 ± 207 nm were fabricated and shown to release 77.0 ± 1.76 µM of H2S over 4 weeks (release of H2S from 1 mg of particles). To test for the antioxidant properties of the PLA-4HTB microparticles, human embryonic kidney 293 cells were first incubated with PLA-4HTB microparticles and then oxidative stress was induced using CoCl2. Particle suspensions of 1 mg/mL were shown to protect cells resulting in reactive oxygen species (ROS) levels of superoxide that were similar to that of the control group. The microparticles fabricated from the PLA-4HTB released H2S over a sustained period of weeks to months, while providing protection from ROS. The microparticles described in this article represent a new platform technology that could be used to prevent and treat diseases caused by oxidative damage.

Combining ultrasound and intratumoral administration of doxorubicin-loaded microspheres to enhance tumor cell killing.

Melanoma is an incurable disease for which alternative treatments to chemotherapy alone are sought. Here, using a melanoma model, we investigated the antitumor potential of combining ultrasound (US) with poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with doxorubicin (DOX). The aim was to achieve synergistic tumoricidal activity through direct and indirect US-mediated damage of tumor cells combined with sustained and potentially controllable release (when combined with US) of DOX from microspheres. An in vitro release assay demonstrated an ability of US to affect the release kinetics of DOX from DOX-loaded PLGA microspheres by inducing a 12% increase in the rate of release. In vitro viability assays demonstrated that combining US with DOX-loaded PLGA microspheres resulted in synergistic tumor cell (B16-F10 melanoma cells) killing. Melanoma-bearing mice were treated intratumorally with DOX (8 µg)-loaded microspheres and subjected to US treatment at the tumor site. This treatment could significantly extend survival (mean survival (MS) = 22.1 days) compared to untreated mice (MS = 10.4 days) and most other treatments, such as blank microspheres plus US (MS = 11.5 days) and DOX (8 µg)-loaded microspheres alone (MS = 13 days). The findings that immune checkpoint blockade did not significantly extend survival of mice treated with DOX (8 µg)-loaded microspheres plus US, and that tumor-free ("cured") mice were not protected from subsequent tumor rechallenge suggests minimal involvement of the adaptive immune response in the observed antitumor activity. Nevertheless, the synergistic increase in survival of melanoma-challenged mice treated with the combination of US and DOX-loaded microspheres implicates such a treatment methodology as a promising additional tool for combatting otherwise currently incurable cancers.