Hyperoxia impairs intraflagellar transport and causes dysregulated metabolism with resultant decreased cilia length.

Supplemental oxygen is a lifesaving measure in infants born premature to facilitate oxygenation. Unfortunately, it may lead to alveolar simplification and loss of proximal airway epithelial cilia. Little is known about the mechanism by which hyperoxia causes ciliary dysfunction in the proximal respiratory tract. We hypothesized that hyperoxia causes intraflagellar transport (IFT) dysfunction with resultant decreased cilia length. Differentiated basal human airway epithelial cells (HAEC) were exposed to hyperoxia or air for up to 48 h. Neonatal mice (<12 h old) were exposed to hyperoxia for 72 h and recovered in room air until postnatal day (PND) 60. Cilia length was measured from scanning electron microscopy images using a MATLAB-derived program. Proteomics and metabolomics were carried out in cells after hyperoxia. After hyperoxia, there was a significant time-dependent reduction in cilia length after hyperoxia in HAEC. Proteomic analysis showed decreased abundance of multiple proteins related to IFT including dynein motor proteins. In neonatal mice exposed to hyperoxia, there was a significant decrease in acetylated α tubulin at PND10 followed by recovery to normal levels at PND60. In HAEC, hyperoxia decreased the abundance of multiple proteins associated with complex I of the electron transport chain. In HAEC, hyperoxia increased levels of malate, fumarate, and citrate, and reduced the ATP/ADP ratio at 24 h with a subsequent increase at 36 h. Exposure to hyperoxia reduced cilia length, and this was associated with aberrant IFT protein expression and dysregulated metabolism. This suggests that hyperoxic exposure leads to aberrant IFT protein expression in the respiratory epithelium resulting in shortened cilia.

Virtual Training Is More Cost-Effective Than In-Person Training for Preparing Staff to Implement Contingency Management.

Behavior therapy implementation relies in part on training to foster counselor skills in preparation for delivery with fidelity. Amidst Covid-19, the professional education arena witnessed a rapid shift from in-person to virtual training, yet these modalities' relative utility and expense is unknown. In the context of a cluster-randomized hybrid type 3 trial of contingency management (CM) implementation in opioid treatment programs (OTPs), a multi-cohort design presented rare opportunity to compare cost-effectiveness of virtual vs. in-person training. An initial counselor cohort (n = 26) from eight OTPs attended in-person training, and a subsequent cohort (n = 31) from ten OTPs attended virtual training. Common training elements were the facilitator, learning objectives, and educational strategies/activities. All clinicians submitted a post-training role-play, independently scored with a validated fidelity instrument for which performances were compared against benchmarks representing initial readiness and advanced proficiency. To examine the utility and expense of in-person and virtual trainings, cohort-specific rates for benchmark attainment were computed, and per-clinician expenses were estimated. Adjusted between-cohort differences were estimated via ordinary least squares, and an incremental cost effectiveness ratio (ICER) was calculated. Readiness and proficiency benchmarks were attained at rates 12-14% higher among clinicians attending virtual training, for which aggregated costs indicated a $399 per-clinician savings relative to in-person training. Accordingly, the ICER identified virtual training as the dominant strategy, reflecting greater cost-effectiveness across willingness-to-pay values. Study findings document greater utility, lesser expense, and cost-effectiveness of virtual training, which may inform post-pandemic dissemination of CM and other therapies.

From parenting skills to adolescent treatment needs: Questions elicited by parents of adolescents discharged from residential treatment.

Background: Despite the utility of parent involvement in continuing care following adolescent residential treatment, parent engagement in traditional office-based treatment is low. In our prior work, we found that parents who had access to a continuing care forum directed questions to a clinical expert and to other parents around five topics: parenting skills; parent support; managing the post-discharge transition; adolescent substance use; family functioning. The current qualitative study elicited questions from parents without access to a continuing care support forum to explore overlapping and new themes. Methods: This study was embedded within the pilot trial of a technology-assisted intervention for parents of adolescents in residential treatment for substance use. Thirty-one parents randomized to residential treatment as usual were asked two prompts at follow-up assessments: what questions they would like to ask a clinical expert and what questions they would like to ask other parents of adolescents discharged from residential care. Thematic analysis identified major themes and subthemes. Results: Twenty-nine parents generated 208 questions. Analyses revealed three themes identified in prior work: parenting skills; parent support; adolescent substance use. Three new themes emerged: adolescent mental health; treatment needs; socialization. Conclusions: The current study identified several distinct needs among parents who did not receive access to a continuing care support forum. Needs identified in this study can inform resources to support parents of adolescents during the post-discharge period. Parents may benefit from convenient access to an experienced clinician for advice on skills and adolescent symptoms, paired with access to parental peer support.

Sustainment of Contingency Management within Opioid Treatment Programs: COVID-Related Barriers and Innovative Workflow Adaptations.

Introduction: Contingency Management (CM) is one of the most effective interventions for persons with opioid use disorder, but one of the least available interventions in community settings, including opioid treatment programs. Project MIMIC is a NIDA-funded cluster randomized trial that is measuring CM implementation and sustainment across 30 opioid treatment programs in the New England region of the United States. The advent of the COVID-19 pandemic occurred in the midst of Project MIMIC's first cohort of eight opioid treatment programs, presenting a natural opportunity to document and analyze novel challenges to CM sustainment. Utilizing both quantitative and qualitative data collection, we aimed to identify both COVID-related barriers to CM sustainment and innovative workflow strategies to mitigate these barriers. Methods: Quantitative analysis was conducted using data collected from a study-specific CM tracker tool on various CM implementation metrics over three distinct, successive time intervals: prior to COVID-19 social distancing orders with active support; during COVID-19 social distancing orders with active support; and during COVID-19 social distancing orders after removal of support. Semi-structured qualitative interviews were conducted with a representative from each of the eight opioid treatment programs. Using a reflexive team approach, transcripts were coded by independent raters to identify both COVID-related barriers to sustainment and innovative workflow adaptations. Results: Quantitative data revealed a substantial decrease in the number of CM encounters following social distancing orders from 31.8 encounters weekly across eight programs to 6.9 encounters weekly across five programs. A further decline to 1.8 weekly encounters across three programs was observed after implementation support was removed. Four COVID-related barriers were identified via thematic analysis: fear of contagion; difficulty engaging patients remotely; challenges re-defining the CM attendance target due to changing regulations; and staff shortages. Potential adjustments discussed to help address one or more of these barriers included an electronic prize generator; use of technology to promote engagement; brief individual remote check-ins; and expansion of training to non-counseling staff. Conclusion: Although CM implementation challenges emerged during the pandemic, associated workflow adaptations also emerged. The feedback solicited in this study will inform multi-level strategies to aid with CM sustainment post-pandemic.