Treatment approaches and outcome trajectories for youth with high-risk opioid use: A narrative review.

AIM: First use of opioids often happens in adolescence and an increasing number of opioid overdoses are being reported among youth. The purpose of this narrative review was to present the treatment approaches for youth with high-risk opioid use, determine whether the literature supports the use of opioid agonist treatment among youth and identify evidence for better treatment outcomes in the younger population. METHODS: A search of the literature on PubMed using MeSH terms specific to youth, opioid use and treatment approaches generated 1436 references. Following a screening process, 137 papers were found to be relevant to the treatment of high-risk opioid use among youth. After full-text review, 19 eligible studies were included: four randomized controlled trials, nine observational studies and six reviews. RESULTS: Research for the different treatment options among youth is limited. The available evidence shows better outcomes in terms of retention in care and cost-effectiveness for opioid agonist treatment than abstinence-based comparisons. Integrating psychosocial interventions into the continuum of care for youth can be an effective way of addressing comorbid psychiatric conditions and emotional drivers of substance use, leading to improved treatment trajectories. CONCLUSIONS: From the limited findings, there is no evidence to deny youth with high-risk opioid use the same treatment options available to adults. A combination of pharmacological and youth-specific psychosocial interventions is required to maximize retention and survival. There is an urgent need for more research to inform clinical strategies toward appropriate treatment goals for such vulnerable individuals.

Cell-Free Prototyping of AND-Logic Gates Based on Heterogeneous RNA Activators.

RNA-based devices controlling gene expression bear great promise for synthetic biology, as they offer many advantages such as short response times and light metabolic burden compared to protein-circuits. However, little work has been done regarding their integration to multilevel regulated circuits. In this work, we combined a variety of small transcriptional activator RNAs (STARs) and toehold switches to build highly effective AND-gates. To characterize the components and their dynamic range, we used an Escherichia coli (E. coli) cell-free transcription-translation (TX-TL) system dispensed via nanoliter droplets. We analyzed a prototype gate in vitro as well as in silico, employing parametrized ordinary differential equations (ODEs), for which parameters were inferred via parallel tempering, a Markov chain Monte Carlo (MCMC) method. On the basis of this analysis, we created nine additional AND-gates and tested them in vitro. The functionality of the gates was found to be highly dependent on the concentration of the activating RNA for either the STAR or the toehold switch. All gates were successfully implemented in vivo, offering a dynamic range comparable to the level of protein circuits. This study shows the potential of a rapid prototyping approach for RNA circuit design, using cell-free systems in combination with a model prediction.

One size does not fit all-evolution of opioid agonist treatments in a naturalistic setting over 23 years.

BACKGROUND AND AIMS: Opioid agonist treatment (OAT) is currently the most effective treatment for people with opioid dependence. In most countries, however, access to the whole range of effective medications is restricted. This study aims to model the distribution of different OAT medications within a naturalistic and relatively unrestricted treatment setting (Zurich, Switzerland) over time, and to identify patient characteristics associated with each medication. METHODS: We used generalized estimating equation analysis with data from the OAT register of Zurich and the Swiss register for heroin-assisted treatment (HAT) to model and forecast the annual proportion of opioids applying exponential distributions until 2018 and patient characteristics between 1992 and 2015. RESULTS: Data from 11 895 patients were included in the analysis. Methadone remains the mainstay of OAT, being prescribed to two-thirds of patients. Following its approval, the proportion of HAT increased rapidly and is now constant at 12.16% [95% confidence interval (CI) = 11.15-13.17]. The initial increase of proportions of buprenorphine or slow-release oral morphine (SROM) following their approval for OAT was slower. While in 2014 both medications had a proportion of 10.2% and 10.3%, respectively, our model predicts a further increase of SROM to 19.9% in 2018, with a ceiling level of 25.19% (21.40-28.98%) thereafter. SROM patients display characteristics similar to those treated with methadone; buprenorphine patients show the highest social integration; and HAT patients are the most homogeneous group, with highest mean age, most widespread injecting experience and lowest social integration. CONCLUSIONS: Based on data from Zurich, Switzerland from 1992 to 2015, there is no evidence for an excessive demand for a single medication in a naturalistic and liberal opioid agonist treatment setting. Rather, the specific patient characteristics associated with each medication underline the need for diversified treatment options for opioid dependence.

Novel remote electronic medication supply model for opioid-dependent outpatients with polypharmacy--first long-term case study.

BACKGROUND: Patients with substance use disorders grow older thanks to effective treatments. Together with a high prevalence of comorbidities, psychological problems, and low social support, these patients are at high risk for medication non-adherence. Established treatment facilities face challenges to accommodate these complex patients within their setting. Electronic medication management aids (e-MMAs) might be appropriate to simultaneously monitor and improve adherence for these patients. CASE PRESENTATION: We report the first long-term experiences with a novel remote electronic medication supply model for two opioid-dependent patients with HIV. John (beginning dementia, 52 years, 6 tablets daily at 12 am) and Mary (frequent drug holidays, 48 years, 5-6 tablets daily at 8 pm) suffered from disease progression due to non-adherence. We electronically monitored adherence and clinical outcomes during 659 (John) and 953 (Mary) days between July 2013 and April 2016. Both patients retrieved over 90% of the pouches within 75 min of the scheduled time. Technical problems occurred in 4% (John) and 7.2% (Mary) of retrievals, but on-site support was seldom required. Viral loads fell below detection limits during the entire observation period. CONCLUSIONS: Continuous medication supply and persistence with treatment of over 1.7 years, timing adherence of more than 90%, and suppressed HIV viral load are first results supporting the feasibility of the novel supply model for patients on opioid-assisted treatment and polypharmacy.

Evaluation of medication-assisted treatment of opioid dependence-The physicians' perspective.

BACKGROUND: There is controversy about which outcome parameters should be employed to assess substance use treatment. Subjective measures of medication-assisted treatment (MAT) of opioid dependence are increasingly important. However, while patients' perspectives have been examined, the caregivers' views remain largely unknown. Here, we explore how physicians evaluate MAT, and which predictors are most relevant. METHODS: We conducted a retrospective cohort study of all MAT episodes with oral opioid agonists in the canton of Zurich between 1998 and 2013 using a case register. Termination forms of the register include a physician-completed assessment on the course of the treatment episode. Mixed model analysis was applied to determine relevant predictors. RESULTS: The analysis was based on 17,234 episodes from 7432 patients. Mean global assessment of the course of MAT was 'moderate'. The most important predictors for treatment evaluation by physicians were treatment break off as reason for termination (p<0.0001), psychological improvement throughout treatment (p<0.0001), wish for abstinence from the substitute (p<0.0001), social integration index at termination (p<0.0001), and social (p<0.0001) as well as medical (p<0.0001) improvement. The negative association of treatment break off with MAT assessment was more pronounced in semi-rural than urban areas (p<0.0001). CONCLUSION: Predictors relating to the well-being and functioning of the patient as well as the reasons underlying treatment termination appear to be more important for the treating physician's evaluation of medication-assisted treatment episodes than on-going substance use. Coming off the opioid medication plays a central role, independent of ongoing illicit substance use.

Cost of attempted suicide: a retrospective study of extent and associated factors.

QUESTIONS UNDER STUDY: Suicidal behaviour is a major source of burden of disease. While most studies focus on cost associated with completed suicides, data on costs of, non-lethal, suicide attempts are lacking. The aim of this study was to assess direct annual cost of suicide attempts in Basel in 2003 from a health services perspective. METHODS: Retrospective cost-of-illness-study of the Basel cohort of the 2003 WHO/EURO-Multicentre Study on Parasuicide. We extracted cost information from the two major hospitals involved in treatment of these patients. We determined overall cost, compared cost medians and identified variables associated with higher cost by means of logistic regression. RESULTS: For 2003, treatment of suicide attempters in Basel's main hospitals amounted to 3,373,025 Swiss Francs (CHF), mainly attributable to psychiatric care. Mean and median cost per case were 19,165 CHF and 6,108 CHF, respectively. Based on these findings, the extrapolated direct medical costs for medical treatment of suicide attempts in Switzerland per year amount to 191 million CHF. Parameters associated with high costs were age above 65 (p<0.01), using a hard method (p<0.05), receiving intensive care (p<.05), and lethal intention (p<0.05). The ICD-10 diagnostic category F3 was associated with significantly higher costs than F1 (p<0.05) and F4 (p<0.05). CONCLUSIONS: Attempted suicide produces substantial direct medical costs, which are only a part of the financial burden. Prevention targeting mood disorders, the elderly and the use of hard methods may be most cost-effective. Further research should aim at identifying additional indirect costs and the cost-effectiveness of prevention measures.

There is no age limit for methadone: a retrospective cohort study.

BACKGROUND: Data from the US indicates that methadone-maintained populations are aging, with an increase of patients aged 50 or older. Data from European methadone populations is sparse. This retrospective cohort study sought to evaluate the age trends and related developments in the methadone population of Basel-City, Switzerland. METHODS: The study included methadone patients between April 1, 1995 and March 31, 2003. Anonymized data was taken from the methadone register of Basel-City. For analysis of age distributions, patient samples were split into four age categories from '20-29 years' to '50 years and over'. Cross-sectional comparisons were performed using patient samples of 1996 and 2003. RESULTS: Analysis showed a significant increase in older patients between 1996 and 2003 (p < 0.001). During that period, the percentage of patients aged 50 and over rose almost tenfold, while the proportion of patients aged under 30 dropped significantly from 52.8% to 12.3%. The average methadone dose (p < 0.001) and the 1-year retention rate (p < 0.001) also increased significantly. CONCLUSIONS: Findings point to clear trends in aging of methadone patients in Basel-City which are comparable, although less pronounced, to developments among US methadone populations. Many unanswered questions on medical, psychosocial and health economic consequences remain as the needs of older patients have not yet been evaluated extensively. However, older methadone patients, just as any other patients, should be accorded treatment appropriate to their medical condition and needs. Particular attention should be paid to adequate solutions for persons in need of care.