Using wearable technology to detect prescription opioid self-administration.

ABSTRACT: Appropriate monitoring of opioid use in patients with pain conditions is paramount, yet it remains a very challenging task. The current work examined the use of a wearable sensor to detect self-administration of opioids after dental surgery using machine learning. Participants were recruited from an oral and maxillofacial surgery clinic. Participants were 46 adult patients (26 female) receiving opioids after dental surgery. Participants wore Empatica E4 sensors during the period they self-administered opioids. The E4 collected physiological parameters including accelerometer x-, y-, and z-axes, heart rate, and electrodermal activity. Four machine learning models provided validation accuracies greater than 80%, but the bagged-tree model provided the highest combination of validation accuracy (83.7%) and area under the receiver operating characteristic curve (0.92). The trained model had a validation sensitivity of 82%, a specificity of 85%, a positive predictive value of 85%, and a negative predictive value of 83%. A subsequent test of the trained model on withheld data had a sensitivity of 81%, a specificity of 88%, a positive predictive value of 87%, and a negative predictive value of 82%. Results from training and testing model of machine learning indicated that opioid self-administration could be identified with reasonable accuracy, leading to considerable possibilities of the use of wearable technology to advance prevention and treatment.

Effect of short-term prescription opioids on DNA methylation of the OPRM1 promoter.

BACKGROUND: A long-term opioid use has been associated with hypermethylation of the opioid receptor mu 1 (OPRM1) promoter. Very little is currently known about the early epigenetic response to therapeutic opioids. Here, we examine whether we can detect DNA methylation changes associated with a few days' use of prescribed opioids. Genome-wide DNA methylation was assayed in a cohort of 33 opioid-naïve participants who underwent standard dental surgery followed by opioid self-administration. Saliva samples were collected before surgery (visit 1), and at two postsurgery visits at 2.7 ± 1.5 days (visit 2), and 39 ± 10 days (visit 3) after the discontinuation of opioid analgesics. RESULTS: The perioperative methylome underwent significant changes over the three visits that were primarily due to postoperative inflammatory response and cell heterogeneity. To specifically examine the effect of opioids, we started with a candidate gene approach and evaluated 10 CpGs located in the OPRM1 promoter. There was a significant cross-sectional variability in opioid use, and for participants who self-administered the prescribed drugs, the total dosage ranged from 5-210 morphine milligram equivalent (MME). Participants were categorized by cumulative dosage into three groups: < 25 MME, 25-90 MME, and ≥ 90 MME. Using mixed-effects modeling, 4 CpGs had significant positive associations with opioid dose at two-tailed p value < 0.05, and overall, 9 of the 10 OPRM1 promoter CpGs showed the predicted higher methylation in the higher dose groups relative to the lowest dose group. After adjustment for age, cellular heterogeneity, and past tobacco use, the promoter mean methylation also had positive associations with cumulative MME (regression coefficient = 0.0002, one-tailed p value = 0.02) and duration of opioid use (regression coefficient = 0.003, one-tailed p value = 0.001), but this effect was significant only for visit 3. A preliminary epigenome-wide association study identified a significant CpG in the promoter of the RAS-related signaling gene, RASL10A, that may be predictive of opioid dosage. CONCLUSION: The present study provides evidence that the hypermethylation of the OPRM1 promoter is in response to opioid use and that epigenetic differences in OPRM1 and other sites are associated with a short-term use of therapeutic opioids.

A randomized pilot program to reduce opioid use following dental surgery and increase safe medication return.

Research indicates that increased cumulative exposure (duration of administration and strength of dose) is associated with long-term opioid use. Because dentists represent some of the highest opioid prescribing medical professionals in the US, dental practices offer a critical site for intervention. The current study used a randomized clinical trial design to examine the efficacy of an opioid misuse prevention program (OMPP), presented as a brief intervention immediately prior to dental extraction surgery. The OMPP provided educational counseling about risks and appropriate use of opioid medication, as well as 28 tablets of ibuprofen (200 mg) and 28 tablets of acetaminophen (500 mg) for weaning off opioid medication. This was compared with a Treatment as Usual (TAU) control condition. Participants were individuals presenting for surgery who were eligible for opioid medication (N = 76). Follow up assessment was conducted at 1 week following surgery, with 4 individuals refusing follow up or not prescribed opioid. Intent to treat analysis indicated a non-significant treatment group effect (N = 72, Beta = 0.16, p = .0835), such that the OMPP group self-reported less opioid use (in morphine milligram equivalents, MMEs) than the TAU group (37.94 vs. 47.79, effect size d = 0.42). Sensitivity analysis, excluding individuals with complications following surgery (n = 6) indicated a significant treatment group effect (N = 66, Beta = 0.24, p = .0259), such that the OMPP group self-reported significantly less MMEs than the TAU group (29.74 vs. 43.59, effect size d = 0.56). Results indicate that a 10-minute intervention and provision of non-narcotic pain medications may reduce the amount of self-administered opioid medication following dental surgery.

Treatment for Recurrent Odontogenic Keratocysts.

Controversy remains in understanding both the development and treatment for the odontogenic keratocyst (OKC). With recent changes in nomenclature recognizing the odontogenic keratocyst as a benign tumor, the debate over the proper course of treatment to limit recurrence and morbidity will continue. This study presents two cases where conservative treatment failed to prevent recurrence and each patient underwent resection of aggressive, multicystic OKCs to provide the best chance for definitive care without recurrence and limited morbidity.