Investigating brain dynamics and their association with cognitive control in opioid use disorder using naturalistic and drug cue paradigms.

Objectives: Opioid use disorder (OUD) impacts millions of people worldwide. The prevalence and debilitating effects of OUD present a pressing need to understand its neural mechanisms to provide more targeted interventions. Prior studies have linked altered functioning in large-scale brain networks with clinical symptoms and outcomes in OUD. However, these investigations often do not consider how brain responses change over time. Time-varying brain network engagement can convey clinically relevant information not captured by static brain measures. Methods: We investigated brain dynamic alterations in individuals with OUD by applying a new multivariate computational framework to movie-watching (i.e., naturalistic; N=76) and task-based (N=70) fMRI. We further probed the associations between cognitive control and brain dynamics during a separate drug cue paradigm in individuals with OUD. Results: Compared to healthy controls (N=97), individuals with OUD showed decreased variability in the engagement of recurring brain states during movie-watching. We also found that worse cognitive control was linked to decreased variability during the rest period when no opioid-related stimuli were present. Conclusions: These findings suggest that individuals with OUD may experience greater difficulty in effectively engaging brain networks in response to evolving internal or external demands. Such inflexibility may contribute to aberrant response inhibition and biased attention toward opioid-related stimuli, two hallmark characteristics of OUD. By incorporating temporal information, the current study introduces novel information about how brain dynamics are altered in individuals with OUD and their behavioral implications.

Centers for Medicare and Medicaid Services Positive Airway Pressure Adherence Criteria May Limit Treatment to Many Medicare Beneficiaries.

STUDY OBJECTIVES: Centers for Medicare and Medicaid Services (CMS) reimbursement for positive airway pressure (PAP) devices for obstructive sleep apnea treatment is dependent on patients meeting adherence expectations within the first 3 months on therapy. Adherence is defined as usage of the device for at least 4 hours per night on 70% of nights during a consecutive 30-day period. We hypothesize that the adherence pattern may be established beyond this initial period, which may limit the opportunity to treat many patients. METHODS: Treatment and adherence data from PAP devices were monitored via wireless modems for 42 consecutive PAP-naïve military veterans who completed 1 year of nightly monitoring. Their baseline characteristics were as follows: age (mean ± standard deviation) 58.5 ± 12.5 years; body mass index 33.7 ± 5.7 kg/m2; diagnostic apnea-hypopnea index (pretreatment) 28.1 ± 18.5 events/h; apnea-hypopnea index on PAP: 4.3 ± 3.3 events/h. We examined daily, monthly, quarterly, semiannual, and annual reports, and the best 30-day adherence report for each quarter. RESULTS: In the first 3 months, 19 of 42 participants were adherent by CMS criteria, and 23 of 42 participants were not. Of the 19 adherent participants, 13 remained adherent and 6 became nonadherent or stopped PAP treatment for the remainder of the year. In the 23 initially nonadherent participants, 16 stopped PAP treatment, and 7 participants (30.4%) became adherent (using CMS criteria) during the rest of the year. Thus, PAP adherence during the first 3 months was predictive for the rest of the year in only 68.4%. PAP nonadherence during the first 3 months was predictive for further nonadherence in only 69.6% of the cases. Overall, this led to a 65% sensitivity and 72% specificity of using adherence at 3 months in predicting adherence at 1 year. CONCLUSIONS: CMS adherence criteria affecting PAP coverage are restrictive and can result in the withholding of therapy in many patients who otherwise might become adherent. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov, Title: Remote Monitoring in Obstructive Sleep Apnea, Identifier: NCT01678560, URL: https:// clinicaltrials.gov/ct2/show/NCT01678560.

Neutrophil-to-lymphocyte ratio decreases in obstructive sleep apnea treated with mandibular advancement devices.

PURPOSE: Obstructive sleep apnea has been associated with chronic inflammation triggered by nocturnal hypoxemia. The neutrophil-to-lymphocyte ratio (NLR) is a measure of subclinical systemic inflammation. We hypothesize that NLR levels would improve as chronic inflammation diminishes in obstructive sleep apnea (OSA) patients treated with mandibular advancement devices (MADs). METHODS: We studied patients with OSA who were treated with MAD as a first-line treatment or because they could not tolerate CPAP. We obtained pre-treatment and post-treatment complete blood counts. NLR was calculated by dividing the number of neutrophils by the number of lymphocytes obtained from the CBCs. Patients with other conditions known to affect NLR were excluded from the study. RESULTS: We compared the values of NLR and oxygen desaturation index (ODI) before and after treatment with MAD in 22 patients who met inclusion criteria and completed the study protocol. There was a significant difference in NLR before and after treatment (p = 0.01). There was also a significant difference in the 3% ODI and 4% ODI before and after treatment with MAD (p = 0.014, 0.007), respectively. A subgroup analysis compared NLR in two groups of patients, the optimally treated and suboptimally treated. There was a significant decrease in the NLR in the optimally treated group (n = 10) (p < 0.01), whereas it did not change in the suboptimally treated group (n = 12) (p = 0.349). CONCLUSION: The neutrophil-to-lymphocyte ratio may be useful in documenting improvement in inflammation for OSA patients treated with mandibular advancement devices. Our results specifically suggest that the NLR values are associated with the decrease in the ODI.