Measuring Treatment Attrition at Various Stages of Engagement in Opioid Agonist Treatment in Ontario Canada Using a Cascade of Care Framework

Background The cascade of care framework is an effective way to measure attrition at various stages of engagement in Opioid Agonist Treatment (OAT). The primary objective of the study was to describe the cascade of care for individuals who have accessed OAT from a network of specialized addiction clinics in Ontario, Canada. The secondary objectives were to evaluate correlates associated with retention in OAT at various stages and the impact of patients' location of the residence on retention in OAT. Design: A multi-clinic retrospective cohort study was conducted using electronic medical record (EMR) data from the largest network of OAT clinics in Canada (70 clinics) from 2014-2020. Study participants included all individuals who received OAT from the network of clinics during the study period. Measurements: In this study, four stages of the cascade of care framework were operationalized to identify treatment engagement patterns, including patients retained within 90 days, 90 to 365 days, one to two years, and more than two years. Correlates associated with OAT retention for 90 days, 90 to 365 days, one to two years, and more than two years were also evaluated and compared across rural and urban areas in northern and southern Ontario. Results A total of 32,487 individuals were included in the study. Compared to individuals who were retained in OAT for 90 days, individuals who were retained for 90 to 365 days, one to two years, or more than two years were more likely to have a higher number of treatment attempts, a higher number of average monthly urine drug screening and a lower proportion of positive urine drug screening results for other drug use. Conclusion Distinct sociodemographic and clinical factors are likely to influence treatment retention at various stages of engagement along the OAT continuum. Research is required to determine if tailored strategies specific to people at different stages of engagement have the potential to improve outcomes of OAT.

Prevalence and clinical implication of adverse childhood experiences and their association with substance use disorder among patients with schizophrenia

Background Adverse childhood experiences (ACEs) and substance use disorder (SUD) are well-known risk factors for psychosis and dramatically affect schizophrenia. In this research, we aimed to measure the prevalence of adverse childhood experiences and substance use disorder in patients with schizophrenia and assess the effect of ACEs on the clinical presentation and overall functioning and the association between them and SUD in patients with schizophrenia. A cross-sectional study included a random sample of 165 schizophrenic patients who were examined by doing drug screen in urine, structured questionnaire to collect Socioeconomic characteristics, history of schizophrenia, structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders-fifth edition, Positive and Negative Syndrome Scale (PANSS), Adverse Childhood Experiences International Questionnaire (ACE-IQ), World Health Organization Disability Assessment Schedule 2.0, compliance rating scale, addiction severity index fifth edition (ASI) for individuals with positive urine drug screen. Results Only 14.4% of the studied patients had no adverse childhood experiences. The prevalence of positive substance abuse screening was 18.2%. There were statistically significant negative correlations between total ACE score and educational level, socioeconomic level, and the onset of schizophrenia. On the other hand, statistically significant positive correlations were found between the total ACE score and PANSS score and ASI score. The first most frequent ACE was significantly associated with female gender, lower education levels, low and middle socioeconomic classes, lifetime substance use, smokers, and positive drug screening. Emotional neglect and contact sexual abuse were significantly associated with positive drug screening. At the same time, Physical abuse was significantly associated with both lifetime substance use and positive drug screening. Conclusion The current study’s findings indicate that childhood adverse experiences and substance abuse are prevalent problems in patients with schizophrenia. Given that there is an association between both issues, they may affect the symptomatology of the disorder, the prognosis, and the therapeutic plan. It is advised that a greater emphasis on and identification of childhood trauma and drug use disorder may be a necessary step in assessing patients with schizophrenia.

Mesenchymal tumor organoid models recapitulate rhabdomyosarcoma subtypes

Rhabdomyosarcomas (RMS) are mesenchyme-derived tumors and the most common childhood soft tissue sarcomas. Treatment is intense, with a nevertheless poor prognosis for high-risk patients. Discovery of new therapies would benefit from additional preclinical models. Here we describe the generation of a collection of pediatric RMS tumor organoid (tumoroid) models comprising all major subtypes. For aggressive tumors, tumoroid models can often be established within four to eight weeks, indicating the feasibility of personalized drug screening. Molecular, genetic and histological characterization show that the models closely resemble the original tumors, with genetic stability over extended culture periods of up to six months. Importantly, drug screening reflects established sensitivities and the models can be modified by CRISPR/Cas9 with TP53 knockout in an embryonal RMS model resulting in replicative stress drug sensitivity. Tumors of mesenchymal origin can therefore be used to generate organoid models, relevant for a variety of preclinical and clinical research questions.