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.

Assessing the links between childhood trauma, C-reactive protein and response to antidepressant treatment in patients with affective disorders.

Adverse Childhood Experiences (ACE) are a well-known risk-factor for depression. Additionally, (high-sensitive) C-reactive Protein (hsCRP) is elevated in subgroups of depressed patients and high following ACE. In this context the literature considers hsCRP and ACE to be associated with treatment resistant depression. With the data being heterogenous, this study aimed to explore the associations of ACE, hsCRP levels and response to antidepressant treatment in uni- and bipolar depression. N = 76 patients diagnosed with uni- or bipolar depression and N = 53 healthy controls were included. Treatment was over 6 weeks in an inpatient psychiatric setting within an observatory study design. Depressive symptoms were assessed by the Montgomery-Asberg Depression Rating Scale (MADRS), ACE were assessed by the Childhood Trauma Questionnaire (CTQ); the body-mass-index (BMI) and hsCRP were measured. HsCRP levels did not differ between the study population and the healthy controls. While the depressive symptoms decreased, the hsCRP levels increased. Sexual abuse was associated with significant higher and emotional abuse with lower levels of hsCRP after 6 weeks. The baseline hsCRP levels and the ACE subgroups did not show significant associations with the treatment response in unipolar depressed patients. The long-lasting effects of specific forms of ACE may have relevant impact on inflammation, supporting hsCRP to be a suitable biomarker. With ACE and hsCRP not showing any significant associations with treatment response in the unipolar depressed subgroup, a more differentiate research concerning biomarkers and treatment regimens is needed when talking about treatment response.

The OX40 Axis is Associated with Both Systemic and Local Involvement in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic, or chronically relapsing, inflammatory skin disease associated with asthma and allergic rhinitis, and is dominated by Th2 cells. The co-stimulatory T-cell receptor OX40 and its ligand, OX40L, play a central role in the pathogenesis of AD, as their interactions are crucial for the generation of TH2 memory cells. Using enzyme-linked immunoassay (ELISA) and flow cytometry on blood samples from patients with AD and healthy volunteers, this study shows that the serum level of soluble (s) OX40 is decreased in patients with AD, and the expression of OX40 by activated skin-homing CD4+ T cells is increased. This study further shows, using immunofluorescence on skin biopsies, that OX40+ and OX40L+ cells are co-located within the dermis, indicating local activity of OX40/OX40L. Serum levels of sOX40 were associated with atopic diseases and, together, these results support that the OX40 system is important for chronic inflammation in AD skin.

Co-occurring Mental Disorders in Transitional Aged Youth With Substance Use Disorders - A Narrative Review.

Adolescence and emerging adulthood are often referred to as youth. Transitional psychiatry addresses this target group, which considers patients between 15 and 25 years of age. Substance use usually begins and peaks at this stage of life. Psychiatric disorders, foremost attention-deficit/hyperactivity disorder, and affective disorders, conduct disorders, and first-episodes psychosis frequently appear in early life stages. This review aims to provide a broad overview of transitional-aged youth's most common psychiatric comorbidities with substance use disorders. A literature search was conducted in Embase and Pubmed, and the main findings are described narratively. We present main findings for the following comorbidities: attention-deficit/hyperactivity disorder, conduct disorder, personality disorders, affective disorders, psychotic disorders, and the phenomena of overdose and suicidality. In conclusion, co-occurring mental health disorders are common and appear to facilitate the development of substance use disorders and exacerbate their overall course. Substance use also affects the severity and course of comorbid psychiatric disorders. Overall, data on transition-age youth with substance use disorders are highly inconsistent. Universal screening and treatment guidelines do not yet exist but should be aimed for in the future.

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.