Is extended release naltrexone superior to buprenorphine-naloxone to reduce drinking among outpatients receiving treatment for opioid use disorder? A secondary analysis of the CTN X:BOT trial.

BACKGROUND: The comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT) trial showed that following induction, treatment with the sublingual agonist (buprenorphine-naloxone, BUP-NX) or injected antagonist (extended release naltrexone, XR-NTX) produced similar reductions in opioid relapse in injection users with opioid use disorder (OUD). Because XR-NTX reduces drinking in alcohol use disorder (AUD), we conducted a secondary analysis of the X:BOT sample of patients successfully inducted onto treatment to determine whether XR-NTX (n = 204) was superior to BUP-NX (n = 270) in reducing drinking or heavy drinking in patients with OUD. METHODS: Standard drink units consumed were measured using the Timeline Follow-back method. Mixed-models regression was used to examine the monthly frequency of any drinking and heavy drinking over 6 months of treatment. We used a proportional hazard survival analysis to examine the time to first drink. RESULTS: Both treatment groups reduced drinking from baseline to posttreatment (small to medium effect), but no differences between groups were detected. However, only 29% (n = 136) of the sample had AUD and 19% (n = 26/136) of those were abstinent before treatment. Analysis of a subsample enriched for possible drinking included 136 individuals with an AUD diagnosis plus 43 who did not have AUD, but reported at least one day of heavy drinking prior to the study. However, this subsample reported only 32% of days of any drinking with a median of only 13% of days designated as "heavy." Within this subsample, at baseline, the BUP-NX group reported more mean drinks per drinking day than the XR-NTX group (p = 0.03); however, there were no other significant group differences on drinking observed before, during, or at the end of treatment. CONCLUSIONS: There was an overall reduction in drinking during treatment of OUD using both agonist and antagonist medications, so that the hypothesis that XR-NTX would be superior to BUP-NX was not supported. The study is limited by low levels of comorbid AUD or heavy drinking observed in X:BOT trial participants seeking treatment for OUD.

Extended-release vs. oral naltrexone for alcohol dependence treatment in primary care (XON).

BACKGROUND: Extended-release naltrexone (XR-NTX, Vivitrol®) and daily oral naltrexone tablets (O-NTX) are FDA-approved mu opioid receptor antagonist medications for alcohol dependence treatment. Despite the efficacy of O-NTX, non-adherence and poor treatment retention have limited its adoption into primary care. XR-NTX is a once-a-month injectable formulation that offers a potentially more effective treatment option in reducing alcohol consumption and heavy drinking episodes among persons with alcohol use disorders. METHODS: This pragmatic, open-label, randomized controlled trial examines the effectiveness of XR-NTX vs. O-NTX in producing a Good Clinical Outcome, defined as abstinence or moderate drinking (<2 drinks/day, men; <1 drink/day, women; and < 2 heavy drinking occasions/month) during the final 20 of 24 weeks of primary care-based Medical Management treatment for alcohol dependence. Secondary aims will estimate the cost effectiveness of XR-NTX vs. O-NTX, in conjunction with primary-care based Medical Management for both groups, and patient-level characteristics associated with effectiveness in both arms. Alcohol dependent persons are recruited from the community into treatment in a New York City public hospital primary care setting (Bellevue Hospital Center) for 24 weeks of either XR-NTX (n = 117) or O-NTX (n = 120). RESULTS: We describe the rationale, specific aims, design, and recruitment results to date. Alternative design considerations and secondary aims and outcomes are reported. CONCLUSIONS: XR-NTX treatment in a primary care setting is potentially more efficacious, feasible, and cost-effective than oral naltrexone when treating community-dwelling persons with alcohol use disorders. This study will estimate XR-NTX's treatment and cost effectiveness relative to oral naltrexone.

Respiratory-swallowing interactions during sleep in premature infants at term.

Non-nutritive swallowing occurs frequently during sleep in infants and is vital for fluid clearance and airway protection. Swallowing has also been shown to be associated with prolonged apnea in some clinical populations. What is not known is whether swallowing contributes to apnea or may instead help resolve these clinically significant events. We studied the temporal relationships between swallowing, respiratory pauses and arousal in six preterm infants at term using multi-channel polysomnography and a pharyngeal pressure transducer. Results revealed that swallows occurred more frequently during respiratory pauses and arousal than during control periods. They did not trigger the respiratory pause, however, as most swallows (66%) occurred after respiratory pause onset and were often tightly linked to arousal from sleep. Swallows not associated with respiratory pauses (other than the respiratory inhibition to accommodate swallowing) and arousal occurred consistently during the expiratory phase of the breathing cycle. Results suggest that swallowing and associated arousal serve an airway protective role during sleep and medically stable preterm infants exhibit the mature pattern of respiratory-swallowing coordination by the time they reach term.

Adenotonsillectomy improves sleep, breathing, and quality of life but not behavior.

OBJECTIVE: To obtain parental perspectives on changes in sleep, breathing, quality of life (QOL), and neurobehavioral measures after adenotonsillectomy. STUDY DESIGN: This retrospective cohort study comprised otherwise healthy children evaluated for obstructive sleep apnea syndrome (OSAS) from 1993 to 2001. We compared those children who underwent adenotonsillectomy with those children who did not. The parents of 473 children (292 boys) 2 years of age and older were sent questionnaires to evaluate QOL and clinical and behavioral changes. For 94 children 3 years of age and older, behavioral changes were evaluated using the Conners' Parent Rating Scale-Revised (CPRS-R) for three different periods: pre-operatively/pre-polysomnography, postoperatively/postpolysomnography, and recently. RESULTS: One hundred and sixty-six questionnaires were returned (35%), 138 of which were complete with written consent provided. Compared with parents of unoperated children, parents of children who had adenotonsillectomy were more likely to report improvements in sleep, breathing, and QOL but not improvements in concentration, school performance, and intellectual or developmental progress. Both short and long term, there were no significant effects of adenotonsillectomy on any of the CPRS-R behavior subscales. CONCLUSION: From a parental perspective, adenotonsillectomy frequently improves sleep, breathing, and QOL but does not often improve neurobehavioral outcomes.

Buprenorphine prescribing practice trends and attitudes among New York providers.

Buprenorphine office-based opioid maintenance is an increasingly common form of treatment for opioid use disorders. However, total prescribing has not kept pace with the current opioid and overdose epidemic and access remains scarce among the underserved. This study sought to assess current provider attitudes and clinical practices among a targeted sample of primarily New York City public sector buprenorphine prescribers. A cross-sectional online survey purposefully sampled buprenorphine prescribers in NYC with a focus on those serving Medicaid and uninsured patient populations. Expert review of local provider networks, snowball referrals, and in-person networking generated an email list, which received a survey link. A brief 25-question instrument queried provider and practice demographics, prescribing practices including induction approaches and attitudes regarding common hot topics (e.g., buprenorphine diversion, prescriber patient limits, insurance issues, ancillary treatments). Of 132 email invitations, N=72 respondents completed (n=64) or partially completed (n=8) the survey between January and April 2016. Most (79%) were Medicaid providers in non-psychiatric specialties (72%), working in a hospital-based or community general practice (51%), and board-certified in addiction medicine or psychiatry (58%). Practice sizes were generally 100 patients or fewer (71%); many providers (64%) individually prescribed buprenorphine <25% of total practice time to a median 23 patients (mean 31, range 0-102). Unobserved (home) induction for new patients was a common practice: 49% predominantly prescribed unobserved induction; 16% mixed unobserved and observed inductions. Adjunctive psychosocial counseling was routinely recommended (46%) or considered on a case-by-case basis (17%) versus mandated (37%). Medication prior authorization requirements were the highest rated barriers to practice, followed by inadequate clinic space, limited clinic time and/or support staff, and inadequate psychiatric services for dual diagnoses. Buprenorphine diversion was not rated as an important practice barrier. In conclusion, this targeted survey of buprenorphine prescribers in NYC treating primarily underserved populations showed a consistent pattern of part-time prescribing to modest volumes of patients, routine use of unobserved buprenorphine induction, and primarily elective referrals to psychosocial counseling. Barriers to prescribing included prior authorization requirements, lack of clinical resources (space, staff) and psychiatric services. Federal and local efforts to reduce such barriers may improve buprenorphine access among the underserved.

Planning adenotonsillectomy in children with obstructive sleep apnea: the role of overnight oximetry.

OBJECTIVE: Obstructive sleep apnea (OSA) in children is usually effectively treated by adenotonsillectomy (T&A). However, there may be a waiting list for T&A, and the procedure is associated with an increased risk of postoperative complications in children with OSA. Needed is a simple test that will facilitate logical prioritization of the T&A surgical list and help to predict children who are at highest risk of postoperative complications. The objective of this study was to develop and validate a severity scoring system for overnight oximetry and to evaluate the score as a tool to prioritize the T&A surgical list. METHODS: This study comprised 3 phases. In phase 1, a severity score was developed by review of preoperative overnight oximetry in children who had urgent T&A in 1999-2000. In phase 2, the score was validated retrospectively in 155 children who had polysomnography (PSG) before T&A in 1992-1998. In a phase 3, a 12-month prospective evaluation of a protocol based on the score was conducted. RESULTS: In phase 1, a 4-level severity score was developed on the basis of the number and the depth of desaturation events (normal to severely abnormal, categories 1-4). In phase 2, the McGill oximetry score correlated with severity of OSA by PSG criteria. In phase 3, a clinical management protocol was developed based on the score. Of 230 children tested, 179 (78%) had a normal/inconclusive oximetry (category 1) and went on to have PSG. Those with a positive oximetry (categories 2-4; 22%) had no additional sleep studies before T&A. Timing of T&A was based on oximetry score, leading to a significant reduction in waiting time for surgery for those with higher oximetry scores. Postoperative respiratory complications were more common with increasing oximetry score. CONCLUSIONS: Overnight pulse oximetry can be used to estimate the severity of OSA, to shorten the diagnostic and treatment process for those with more severe disease, and to aid clinicians in prioritization of T&A and planning perioperative care.