A comparison of cognitive behavioral therapy for insomnia to standard of care in an outpatient substance use disorder clinic embedded within a therapeutic community: a RE-AIM framework evaluation.

BACKGROUND: Rates of substance use disorders (SUDs) continue to rise in the USA with parallel rises in admissions to outpatient SUD treatment programs. Insomnia symptoms reduce treatment adherence, trigger relapse, and generally undermine SUD recovery efforts. Cognitive-behavioral therapy for insomnia (CBT-I) is the first-line treatment recommended for chronic insomnia. No study has examined the effectiveness of CBT-I for individuals who recently entered an outpatient SUD treatment program embedded within a therapeutic community (i.e., long-term drug-free residential setting). METHODS: A randomized controlled trial conducted at a SUD program embedded in a therapeutic community aimed to compare group-based CBT-I (gCBT-I) (N = 10) with the standard of care (SOC) (N = 11) among individuals who have SUDs and comorbid insomnia. We present a RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework evaluation to provide empirical data on gCBT-I feasibility and facilitators and barriers of conducting an insomnia-focused clinical effectiveness study within a therapeutic community. RESULTS: Participants in both study arms reported moderately severe insomnia symptoms at admission and reductions in insomnia symptoms over time. Among participants who completed the Insomnia Severity Index (ISI) beyond admission, ISI decreased to ≤ 8 (the clinical cutoff for mild insomnia) in 80% of individuals in the gCBT-I group compared with 25% of individuals in the SOC group. A RE-AIM framework evaluation showed initial success with Reach and Adoption while Implementation, and Maintenance were limited. Effectiveness was inconclusive because of challenges with recruitment, intervention integrity, and missing data that precluded meeting the planned recruitment and study aims and led to study termination. Coordination and communication with staff and leadership facilitated gCBT-I implementation, yet well-known CBT-I barriers including time- and resource-intensive sleep medicine training for interventionalists and maintenance of treatment integrity during an 8-week intervention limited gCBT-I sustainability. CONCLUSIONS: This analysis supports the feasibility of conducting behavioral sleep medicine research in outpatient SUD treatment programs embedded within therapeutic communities. Implementation of an insomnia-focused intervention was widely accepted by patients and providers and has potential to address insomnia symptoms in early SUD recovery. Addressing patient- and organizational-level implementation barriers may enhance the sustainability and scalability of sleep interventions and provide new hope to effectively treat insomnia among people living with SUDs. TRIAL REGISTRATION: Clinicaltrials.gov : NCT03208855. Registered July 6, 2017https://clinicaltrials.gov/ct2/show/NCT03208855?term=NCT03208855&draw=2&rank=1.

Effects of Early Life Trauma on Risks for Adult Opioid Use Disorder Are Mediated by Stress and Occur Independent of Depression and Anxiety.

OBJECTIVES: Adverse childhood experiences, or early life trauma (ELT), may be a potential risk factor for opioid use disorders (OUDs) that could be further influenced by depression, anxiety, and stress. The prevalence and strength of these associations are largely unknown. METHODS: This study examined the association between current OUD severity and lifetime history of ELT, and the degree to which current depression, anxiety, and stress influenced this association, in persons (n = 310) with at least 1 lifetime exposure to opioids using an online survey. RESULTS: Ninety-three percent of respondents experienced at least 1 trauma in their lifetime, and 65% met the criteria for OUD. Early life trauma was largely unassociated with demographics but demonstrated an almost "dose-dependent" association among all forms of ELT (total, general, physical, emotional, sexual), whereby more ELT was associated with more severe current OUD. A multivariate mediation model found perceived stress to be a robust mediator of this association. Current psychiatric functioning did not significantly moderate the relationship between ELT and OUD, suggesting that ELT may impact OUD severity at varying levels of psychiatric functioning. CONCLUSIONS: These data support existing evidence that greater ELT may influence adult OUD severity and identify perceived stress as a potential mechanistic contributor to this association. Results are preliminary in nature but support continued research into mechanisms underlying the association between ELT and OUD, particularly conformational changes in the stress system resultant from ELT, and interventions to mitigate the impact of ELT on OUD development and/or develop trauma-informed OUD treatment approaches.

Treatment Disruption and Childcare Responsibility as Risk Factors for Drug and Alcohol Use in Persons in Treatment for Substance Use Disorders During the COVID-19 Crisis.

OBJECTIVES: The novel 2019 coronavirus (COVID-19) crisis has caused considerable upheaval in the U.S. healthcare system. The current study examined patient-reported experiences in substance use disorder (SUD) treatment during the early stages of the COVID-19 crisis. METHODS: Participants in SUD treatment were recruited via online crowdsourcing from April 14, 2020 to May 26, 2020, during the early stages of the COVID-19 crisis. Participants reported disruptions in SUD treatment, stress and anxiety caused by these disruptions on a 0-100 point visual analogue scale (VAS), stress associated with childcare responsibilities on a 0-100 VAS, current stress on the Perceived Stress Scale (PSS), anxiety symptoms on the Beck Anxiety Inventory (BAI), sleep disturbances on the Insomnia Severity Index (ISI), and whether they used drugs or alcohol during the COVID-19 crisis. RESULTS: Participants (N = 240) endorsed that at least 1 SUD treatment was switched to telemedicine (63.7%), had some appointments cancelled (37.5%), or was discontinued due to COVID-19 (29.6%). Participants who did versus did not endorse drug/alcohol use reported difficulty obtaining medications to treat their SUD (OR = 2.47, 95% CI, 1.17-5.22, χ2 = 5.98, P = .016), greater scores on VAS treatment-related stress (F1,197 = 5.70, P = .018) and anxiety (F1,197 = 4.07, P = .045), greater VAS stress related to childcare (F1,107 = 10.24, P = .002), and greater scores on the PSS (F1,235 = 19.27, P < .001), BAI (F1,235 = 28.59, P < .001), and ISI (F1,235 = 14.41, P < .001). CONCLUSIONS: Providers and public health officials should work to improve continuity and quality of care during the COVID-19 crisis, with special attention on addressing childcare difficulties and providing remote methods to improve stress, anxiety, and sleep for persons in SUD treatment.

Method for Successfully Inducting Individuals Who Use Illicit Fentanyl Onto Buprenorphine/Naloxone.

BACKGROUND AND OBJECTIVES: Individuals exposed to fentanyl are at risk of precipitated withdrawal using typical buprenorphine/naloxone induction procedures. METHODS: This case series describes buprenorphine/naloxone inductions of four individuals who tested positive for fentanyl. RESULTS: Buprenorphine-precipitated withdrawal was observed in two individuals who completed a conventional buprenorphine/naloxone induction strategy. Two more individuals completed a revised buprenorphine/naloxone induction strategy that did not precipitate withdrawal. DISCUSSION AND CONCLUSION: Using multiple 2 mg doses of buprenorphine/naloxone in patients already in mild/moderate withdrawal improved outcomes. SCIENTIFIC SIGNIFICANCE: Persons who use illicit fentanyl might be less likely to experience precipitated withdrawal from this revised buprenorphine/naloxone induction strategy. (Am J Addict 2021;30:83-87).

Far-red light allophycocyanin subunits play a role in chlorophyll d accumulation in far-red light.

Some terrestrial cyanobacteria acclimate to and utilize far-red light (FRL; λ = 700-800 nm) for oxygenic photosynthesis, a process known as far-red light photoacclimation (FaRLiP). A conserved, 20-gene FaRLiP cluster encodes core subunits of Photosystem I (PSI) and Photosystem II (PSII), five phycobiliprotein subunits of FRL-bicylindrical cores, and enzymes for synthesis of chlorophyll (Chl) f and possibly Chl d. Deletion mutants for each of the five apc genes of the FaRLiP cluster were constructed in Synechococcus sp. PCC 7335, and all had similar phenotypes. When the mutants were grown in white (WL) or red (RL) light, the cells closely resembled the wild-type (WT) strain grown under the same conditions. However, the WT and mutant strains were very different when grown under FRL. Mutants grown in FRL were unable to assemble FRL-bicylindrical cores, were essentially devoid of FRL-specific phycobiliproteins, but retained RL-type phycobilisomes and WL-PSII. The transcript levels for genes of the FaRLiP cluster in the mutants were similar to those in WT. Surprisingly, the Chl d contents of the mutant strains were greatly reduced (~ 60-99%) compared to WT and so were the levels of FRL-PSII. We infer that Chl d may be essential for the assembly of FRL-PSII, which does not accumulate to normal levels in the mutants. We further infer that the cysteine-rich subunits of FRL allophycocyanin may either directly participate in the synthesis of Chl d or that FRL bicylindrical cores stabilize FRL-PSII to prevent loss of Chl d.

Potentiating toxicological interaction of single-walled carbon nanotubes with dissolved metals.

The present study explored the ecotoxicology of single-walled carbon nanotubes (SWCNTs) and their likely interaction with dissolved metals, with a focus on the effect of in vivo exposure in marine mussels. Any nano-scale effects were negated by the tendency of uncoated SWCNTs to agglomerate in water, particularly with high ionic strength as is the case in estuarine and full-strength seawater. However, SWCNTs, in combination with natural organic matter, remained suspended in seawater for long enough to become available to filter-feeding mussels, leading to their concentration on and increased contact with gill epithelia during exposure. For the first time, the authors describe a potentiating toxicological effect, expressed as DNA strand breaks obtained using the comet assay, on divalent metals afforded by negatively charged SWCNT agglomerates in seawater at concentrations as low as 5 µg L⁻¹. This is supported by the observation that SWCNTs alone were only toxic at concentrations ≥100 µg L⁻¹ and that the SWCNT-induced DNA damage was correlated with oxidative stress only in the absence of metals. If these laboratory experiments are confirmed in the natural environment, the present results will have implications for the understanding of the role of carbon nanotubes in environmental metal dynamics, toxicology, and consequently, regulatory requirements.