Towards an International Consensus on the Prevention, Treatment, and Management of High-Risk Substance Use and Overdose among Youth.

Background and Objectives: Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods: A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system's response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform.

Time to act: Early experience suggests stabilization care offers a feasible approach for adolescents after acute life-threatening opioid toxicity.

British Columbia is the epicentre of the opioid crisis in North America. Illicit drug toxicity is now one of the top 3 causes of death for adolescents in British Columbia. Evidence informed treatment is available but adolescents rarely receive it. Non-fatal toxicity can provide an opportunity to intervene. Since 2018, paediatricians in British Columbia have been offering admission, involuntary if necessary, to adolescents presenting to hospital after a life-threatening illicit drug toxicity. This brief stay, termed "stabilization care," offers medical and psychiatric assessments, withdrawal management and initiation of opioid agonist therapy and discharge planning. Hospital policies, procedures and protocols were revised to support the unique needs of this population. Early experience with 17 adolescents shows relatively high attachment to treatment services and opioid agonist treatment, suggesting that paediatric interdisciplinary teams, working strategically, can improve care for adolescents in the face of the opioid epidemic.

A Case Report: Rapid Micro-Induction of Buprenorphine/Naloxone to Administer Buprenorphine Extended-Release in an Adolescent With Severe Opioid Use Disorder.

BACKGROUND AND OBJECTIVES: Buprenorphine extended-release (BUP-XR) is a monthly injectable form of opioid agonist therapy. Before its administration, a minimum 7-day induction period with a transmucosal buprenorphine-containing product is recommended. METHODS: Case report (n = 1). RESULTS: A 16-year-old female with active, severe opioid use disorder (OUD) and stimulant use disorder, hepatitis C virus, co-occurring mental health disorders, and complex social stressors had five recent overdoses requiring naloxone. She had previously been treated with methadone and several trials of sublingual buprenorphine/naloxone, but would quickly discontinue the treatment. Using a rapid micro-induction protocol, buprenorphine/naloxone was administered for 3 days. On day 4, 300 mg BUP-XR was administered subcutaneously. Minimal withdrawal symptoms occurred, despite recent fentanyl use. DISCUSSION AND CONCLUSIONS: A rapid sublingual buprenorphine/naloxone micro-induction was successfully used to initiate BUP-XR, thereby eliminating the abstinence period prior to buprenorphine/naloxone administration, shortening the induction period, and minimizing withdrawal. SCIENTIFIC SIGNIFICANCE: This is the first reported case of using rapid micro-induction as a bridge to initiate BUP-XR. By reducing the length of induction to 4 days and minimizing withdrawal, this induction method can make BUP-XR more accessible to patients who would otherwise refuse the medication due to concerns of enduring withdrawal. (Am J Addict 2020;29:531-535).

Contraception and clean needles: feasibility of combining mobile reproductive health and needle exchange services for female exotic dancers.

Young women engaged in exotic dancing have a higher need for reproductive health services than women not in this profession, and many also use drugs or exchange sex for money or drugs. Few report receiving reproductive health services. We describe a public health, academic, and community partnership that provided reproductive health services on needle exchange mobile vans in the "red light district" in downtown Baltimore, Maryland. Women made 220 visits to the vans in the first 21 months of the program's operation, and 65% of these visits involved provision of contraception. Programmatic costs were feasible. Joint provision of needle exchange and reproductive health services targeting exotic dancers has the potential to reduce unintended pregnancies and link pregnant, substance-abusing women to reproductive care, and such programs should be implemented more widely.

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.

Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects.

Cross-sex hormone treatment is an important component in medical treatment of transsexual people. Endocrinologists are often faced with designing treatment recommendations. Although guidelines from organizations, such as the Harry Benjamin International Gender Dysphoria Association, have been helpful, management remains complex and experience guided. We discuss the range of treatment used by transsexual people, the rationale behind these, and the expectation from such treatment. Recommendations from seven clinical research centers treating transsexual people are discussed. In addition, self-reported hormonal regimens from 25 male-to-female transsexual people and five female-to-male transsexual people are reported. Finally, the potential adverse effects of cross-sex hormone treatment of transsexual people are reviewed. In light of the complexity of managing treatment goals and adverse effects, the active involvement of a medical doctor experienced in cross-sex hormonal therapy is vital to ensure the safety of transsexual people.

Redox reactions of the pyranopterin system of the molybdenum cofactor.

This work provides the first extensive study of the redox reactivity of the pyranopterin system that is a component of the catalytic site of all molybdenum and tungsten enzymes possessing molybdopterin. The pyranopterin system possesses certain characteristics typical of tetrahydropterins, such as a reduced pyrazine ring; however, it behaves as a dihydropterin in redox reactions with oxidants. Titrations using ferricyanide and dichloroindophenol (DCIP) prove a 2e(-)/2H(+) stoichiometry for pyranopterin oxidations. Oxidations of pyranopterin by Fe(CN)(6)(3-) or DCIP are slower than tetrahydropterin oxidation under a variety of conditions, but are considerably faster than observed for oxidations of dihydropterin. The rate of pyranopterin oxidation by DCIP was studied in a variety of media. In aqueous buffered solution the pyranopterin oxidation rate has minimal pH dependence, whereas the rate of tetrahydropterin oxidation decreases 100-fold over the pH range 7.4-8.5. Although pyranopterin reacts as a dihydropterin with oxidants, it resists further reduction to a tetrahydropterin. No reduction was achieved by catalytic hydrogenation, even after several days. The reducing ability of the commonly used biological reductants dithionite and methyl viologen radical cation was investigated, but experiments showed no evidence of pyranopterin reduction by any of these reducing agents. This study illustrates the dual personalities of pyranopterin and underscores the unique place that the pyranopterin system holds in the spectrum of pterin redox reactions. The work presented here has important implications for understanding the biosynthesis and reaction chemistry of the pyranopterin cofactor in molybdenum and tungsten enzymes.