Oral Appliances for OSA Treatment: Meeting the Quadruple Aim.

INTRODUCTION: In order to better treat obstructive sleep apnea (OSA) in a more efficient and cost-effective way, a joint program between dental clinics and the sleep medicine clinic was piloted at Fort Hood, Texas. Obstructive sleep apnea negatively affects soldier readiness and deployability, leading to the need to establish a successful and proven workflow to treat these patients with oral appliance therapy (OAT). MATERIALS AND METHODS: We performed a retrospective review of a de-identified data set which included 288 patients from July 2016 to July 2020. Projected cost data were obtained from routinely collected sleep clinic positive airway pressure (PAP) data. Data were analyzed to determine treatment success and potential cost savings using OAT versus continuous positive airway pressure (CPAP). Patient workflow including successes and challenges with the program is summarized. RESULTS: About 85.5% of patients met criteria for successful control of their OSA using OAT as treatment. Five patients did not tolerate OAT and switched back to CPAP. A higher (less severe) O2 nadir on diagnostic polysomnography is moderately correlated with OAT success. Diagnostic Apnea-Hypopnea Index was inversely and weakly correlated with success. Two of the major challenges noted in the program were (1) loss of follow-up and (2) the length of time from oral appliance referral to fitting the oral appliance. If this program was successfully implemented at other Defense Health Agency (DHA) medical treatment facility (MTF) markets nationwide, a potential cost savings of over $500,000/year/MTF could be achieved. CONCLUSIONS: Oral appliance therapy has the potential to increase both readiness and deployability for active duty soldiers. Using baseline O2 nadir can help predict success with OAT patients, determining which patients will benefit from this joint program between the dental and medical sleep clinics. Future studies can aim to establish an evidence-based pathway for clinic testing and follow-up. If this patient workflow is implemented properly, there can be significant cost savings army-wide. This all helps The United States Medical Command (MEDCOM) align with the DHA's Quadruple Aim of increased readiness, better health, better care, and lower cost.

Mechanistic Studies of the N-formylation of Edivoxetine, a Secondary Amine-Containing Drug, in a Solid Oral Dosage Form.

Edivoxetine (LY2216684 HCl), although a chemically stable drug substance, has shown the tendency to degrade in the presence of carbohydrates that are commonly used tablet excipients, especially at high excipient:drug ratios. The major degradation product has been identified as N-formyl edivoxetine. Experimental evidence including solution and solid-state investigations, is consistent with the N-formylation degradation pathway resulting from a direct reaction of edivoxetine with (1) formic acid (generated from decomposition of microcrystalline cellulose or residual glucose) and (2) the reducing sugar ends (aldehydic carbons) of either residual glucose or the microcrystalline cellulose polymer. Results of labeling experiments indicate that the primary source of the formyl group is the C1 position from reducing sugars. Presence of water or moisture accelerates this degradation pathway. Investigations in solid and solution states support that the glucose Amadori Rearrangement Product does not appear to be a direct intermediate leading to N-formyl degradation of edivoxetine, and oxygen does not appear to play a significant role. Solution-phase studies, developed to rapidly assess propensity of amines toward Maillard reactivity and formylation, were extended to show comparative behavior with example systems. The cyclic amine systems, such as edivoxetine, showed the highest propensity toward these side reactions.

Probability of foliar injury for Acer sp. based on foliar fluoride concentrations.

Fluoride is considered one of the most phytotoxic elements to plants, and indicative fluoride injury has been associated over a wide range of foliar fluoride concentrations. The aim of this study was to determine the probability of indicative foliar fluoride injury based on Acer sp. foliar fluoride concentrations using a logistic regression model. Foliage from Acer nedundo, Acer saccharinum, Acer saccharum and Acer platanoides was collected along a distance gradient from three separate brick manufacturing facilities in southern Ontario as part of a long-term monitoring programme between 1995 and 2014. Hydrogen fluoride is the major emission source associated with the manufacturing facilities resulting with highly elevated foliar fluoride close to the facilities and decreasing with distance. Consistent with other studies, indicative fluoride injury was observed over a wide range of foliar concentrations (9.9-480.0 µg F- g-1). The logistic regression model was statistically significant for the Acer sp. group, A. negundo and A. saccharinum; consequently, A. negundo being the most sensitive species among the group. In addition, A. saccharum and A. platanoides were not statistically significant within the model. We are unaware of published foliar fluoride values for Acer sp. within Canada, and this research provides policy maker and scientist with probabilities of indicative foliar injury for common urban Acer sp. trees that can help guide decisions about emissions controls. Further research should focus on mechanisms driving indicative fluoride injury over wide ranging foliar fluoride concentrations and help determine foliar fluoride thresholds for damage.