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

Course of serum amyloid A (SAA) plasma concentrations in horses undergoing surgery for injuries penetrating synovial structures, an observational clinical study

Abstract Background Injuries penetrating synovial structures are common in equine practice and often result in septic synovitis. Significantly increased plasma levels of serum amyloid A (SAA) have been found in various infectious conditions in horses including wounds and septic arthritis. Plasma SAA levels were found to decrease rapidly once the infectious stimulus was eliminated. The purpose of the current study was to investigate the usefulness of serial measurements of plasma SAA as a monitoring tool for the response to treatment of horses presented with injuries penetrating synovial structures. In the current study plasma SAA concentrations were measured every 48 hours (h) during the course of treatment. Results A total of 19 horses with a wound penetrating a synovial structure were included in the current study. Horses in Group 1 (n = 12) (injuries older than 24 h) only needed one surgical intervention. Patients in this group had significantly lower median plasma SAA levels (P = 0.001) between 48 h (median 776 mg/L) and 96 h (median 202 mg/L) after surgery. A significant decrease (P = 0.004) in plasma SAA levels was also observed between 96 h after surgery (median 270 mg/L) and 6 days (d) after surgery (median 3 mg/L). Four horses (Group 2) required more than one surgical intervention. In contrast to Group 1 patients in Group 2 had either very high initial plasma concentrations (3378 mg/L), an increase or persistently high concentrations of plasma SAA after the first surgery (median 2525 mg/L). A small group of patients (n = 3) (Group 3) were admitted less than 24 h after sustaining a wound. In this group low SAA values at admission (median 23 mg/L) and peak concentrations at 48 h after surgery (median 1016 mg/L) were observed followed by a decrease in plasma SAA concentration over time. Conclusions A decrease in plasma SAA concentrations between two consecutive time points could be associated with positive response to treatment in the current study. Therefore, serial measurements of plasma SAA could potentially be used as an additional inexpensive, quick and easy tool for monitoring the treatment response in otherwise healthy horses presented with injuries penetrating synovial structures. However further studies will be necessary to ascertain its clinical utility

Druckmessungen an den Kontaktflächen zwischen Pferd und Reiter – eine Literaturübersicht

The use of systems for pressure measurement between the rider ’s body and the back of the horse is a relatively new procedure. The size and transfer of the load inside the horse-pad-saddle -rider system can be assessed in various ways. This paper provides a review of literature published from 1994 to 2010 that discusses using pressure mapping systems for measuring the contact load between the horse and its rider. Literature was obtained using common scientific databases such as Web of Science, SCOPUS and PubMed entering the key words: “horse”, “pressure”, and “back ”. The first published studies aimed to verify sensor parameters and to minimize animal- and operator-induced errors. In order to obtain valid and reliable data, it is important to perform pressure measurements under highly standardized conditions. Moreover using properly established guidelines for calibrating and placing sensors is crucial for receiving valid data. Subsequent studies focused on the influence of various types of saddles, pads, blankets and adjustments of saddle fit on the loading of the horse’s back. Results of these studies showed that using pressure mapping systems provide a useful evaluation of the load applied to the area of contact between the horse and rider. A properly fitted saddle with a pad can serve as a shock absorber. Literature findings suggest that improving the fit of a saddle by using a saddle pad needs to be individually adapted for each horse and rider. Considering the current status of literature on the use of pressure mapping systems in horseback riding future research should concentrate on using data obtained by biomechanical modelling of contact surfaces, including their interactions; on determining a “normal pattern” of pressure distribution on the equine back; and on finding a way to include individual parameters of the horse and its rider into the overall assessment.Die Größe und die Einwirkung der Belastung im System Pferd - Unterlage - Sattel - Reiter muss aus verschiedenen Blickwinkeln betrachtet werden. Diese Arbeit präsentiert eine Übersicht die Anwendung von Drucksystemen zur Messung der Kontaktbelastungen zwischen Pferd und Reiter. Die Auswahl der Studien erfolgte unter Verwendung der Suchbegriffe „horse“, „pressure“ und „back“ in den Datenbanken Web of Science, Scopus und PubMed. Im ersten Teil dieses Artikels werden Studien präsentiert, die sich mit der die Entwicklung von Druckmesssystemen für den Reitsattel beschäftigen. Der erste, notwendige Schritt vor der Anwendung dieser Druckmesssysteme ist die Überprüfung der Parameter, um etwaige Fehlerquelle festzustellen und so Bedienungsfehler ausschließen zu können. Um zuverlässige und gültige Daten zu erhalten, müssen methodische Regeln (wie z. B.: korrekte Kalibrierung und korrekte Sensor-Platzierung) eingehalten werden. Im nächsten Teil dieses Artikels wird Betonung auf die Beurteilung der biologischen Systeme (Reiter, Pferd) und deren Interaktion mit dem Sattel als rigide Struktur gelegt. Es werden erste wissenschaftliche Studien, die Druckmessungen beim Reiten, bei unterschiedlichen Sätteln, Sattelkissen, Satteldecken und Änderungen, die durch verschiedene Sattelpolsterungen verursacht werden, untersuchen, diskutiert. Ein schlecht aufliegender Sattel ist ein Grund für Rückenschmerzen, die zur Senkung der Lebensqualität und der Rittigkeit des Pferdes führen. Die Stabilität des Reitersitzes kann mit Hilfe des Druckmesssystem quantifiziert werden. Sie ist für die Kommunikation zwischen Reiter und Pferd wichtig. Von gleicher Bedeutung ist auch Einfluss des Reiters auf die Belastung. Um das Verständnis verschiedener Einflüsse auf Ätiologie und Pathogenese des Pferderückens zu erhöhen, können biomechanische Modelle zur dynamischen Simulation verwendet warden. Auch zur Dokumentation von Hippotherapie ist der Einsatz des Druckmesssystems vorteilhaft. Eine Zunahme der Gesamtkraft zwischen Patient und Pferderücken drückt erhöhtes Selbstvertrauen (Sicherheit) des Reiters aus. Dies ist eine der positiven Wirkungen der Therapie. Aus den Ergebnissen der im Review diskutierten Studien geht hervor, dass die Anwendung der Druckmesssysteme zur Bewertung der Belastung des Pferderückens und des Reiters Bedeutung hat. Zukünftige Forschung sollte sich auf die Einbindung der gesammelten Daten in biomechanische Modelle konzentrieren, umso individuelle Interaktionsmuster besser abgrenzen zu können.Web of Science28559358

Co-culture of osteochondral explants and synovial membrane as in vitro model for osteoarthritis.

The purpose of the current study was to establish an in vitro model for osteoarthritis (OA) by co-culture of osteochondral and synovial membrane explants. Osteochondral explants were cultured alone (control-1) or in co-culture with synovial membrane explants (control-2) in standard culture medium or with interleukin-1β (IL1β) and tumor necrosis factor (TNFα) added to the culture medium (OA-model-1 = osteochondral explant; OA-model-2 = osteochondroal-synovial explant). In addition, in OA-model groups a 2-mm partial-thickness defect was created in the centre of the cartilage explant. Changes in the expression of extracellular matrix (ECM) genes (collagen type-1 (Col1), Col2, Col10 and aggrecan) as well as presence and quantity of inflammatory marker genes (IL6, matrix metalloproteinase-1 (MMP1), MMP3, MMP13, a disintegrin and metalloproteinase with-thrombospondin-motif-5 (ADAMTS5) were analysed by immunohistochemistry, qPCR and ELISA. To monitor the activity of classically-activated pro-inflammatory (M1) versus alternatively-activated anti-inflammatory/repair (M2) synovial macrophages, the nitric oxide/urea ratio in the supernatant of osteochondral-synovial explant co-cultures was determined. In both OA-model groups immunohistochemistry and qPCR showed a significantly increased expression of MMPs and IL6 compared to their respective control group. ELISA results confirmed a statistically significant increase in MMP1and MMP3 production over the culturing period. In the osteochondral-synovial explant co-culture OA-model the nitric oxide/urea ratio was increased compared to the control group, indicating a shift toward M1 synovial macrophages. In summary, chemical damage (TNFα, IL1β) in combination with a partial-thickness cartilage defect elicits an inflammatory response similar to naturally occurring OA in osteochondral explants with and without osteochondral-synovial explant co-cultures and OA-model-2 showing a closer approximation of OA due to the additional shift of synovial macrophages toward the pro-inflammatory M1 phenotype

Fetal articular cartilage regeneration versus adult fibrocartilaginous repair: secretome proteomics unravels molecular mechanisms in an ovine model

Osteoarthritis (OA), a degenerative joint disease characterized by progressive cartilage degeneration, is one of the leading causes of disability worldwide owing to the limited regenerative capacity of adult articular cartilage. Currently, there are no disease-modifying pharmacological or surgical therapies for OA. Fetal mammals, in contrast to adults, are capable of regenerating injured cartilage in the first two trimesters of gestation. A deeper understanding of the properties intrinsic to the response of fetal tissue to injury would allow us to modulate the way in which adult tissue responds to injury. In this study, we employed secretome proteomics to compare fetal and adult protein regulation in response to cartilage injury using an ovine cartilage defect model. The most relevant events comprised proteins associated with the immune response and inflammation, proteins specific for cartilage tissue and cartilage development, and proteins involved in cell growth and proliferation. Alarmins S100A8, S100A9 and S100A12 and coiled-coil domain containing 88A (CCDC88A), which are associated with inflammatory processes, were found to be significantly upregulated following injury in adult, but not in fetal animals. By contrast, cartilage-specific proteins like proteoglycan 4 were upregulated in response to injury only in fetal sheep postinjury. Our results demonstrate the power and relevance of the ovine fetal cartilage regeneration model presented here for the first time. The identification of previously unrecognized modulatory proteins that plausibly affect the healing process holds great promise for potential therapeutic interventions

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.Medicine, Faculty ofNon UBCEmergency Medicine, Department ofPediatrics, Department ofPsychiatry, Department ofReviewedFacultyResearcherOthe

Fetal articular cartilage regeneration versus adult fibrocartilaginous repair: secretome proteomics unravels molecular mechanisms in an ovine model

Osteoarthritis (OA), a degenerative joint disease characterized by progressive cartilage degeneration, is one of the leading causes of disability worldwide owing to the limited regenerative capacity of adult articular cartilage. Currently, there are no disease-modifying pharmacological or surgical therapies for OA. Fetal mammals, in contrast to adults, are capable of regenerating injured cartilage in the first two trimesters of gestation. A deeper understanding of the properties intrinsic to the response of fetal tissue to injury would allow us to modulate the way in which adult tissue responds to injury. In this study, we employed secretome proteomics to compare fetal and adult protein regulation in response to cartilage injury using an ovine cartilage defect model. The most relevant events comprised proteins associated with the immune response and inflammation, proteins specific for cartilage tissue and cartilage development, and proteins involved in cell growth and proliferation. Alarmins S100A8, S100A9 and S100A12 and coiled-coil domain containing 88A (CCDC88A), which are associated with inflammatory processes, were found to be significantly upregulated following injury in adult, but not in fetal animals. By contrast, cartilage-specific proteins like proteoglycan 4 were upregulated in response to injury only in fetal sheep postinjury. Our results demonstrate the power and relevance of the ovine fetal cartilage regeneration model presented here for the first time. The identification of previously unrecognized modulatory proteins that plausibly affect the healing process holds great promise for potential therapeutic interventions.© 201