Exploring Patients' Perceptions on Injectable Opioid Agonist Treatment: Influences on Treatment Initiation and Implications for Practice.

INTRODUCTION: Injectable opioid agonist treatment (iOAT) with diacetylmorphine is an effective option for individuals previously considered non-responsive to opioid substitution treatment. Despite implementation in Canada and several European countries, relatively few eligible people choose to initiate iOAT. To better understand what encourages or deters prospective patients from initiating iOAT, the current study explores patients' perceptions on iOAT and how these influence therapy initiation in practice. METHODS: We conducted 34 semi-structured interviews with individuals currently in or eligible for iOAT in two German outpatient iOAT clinics. Transcripts were analysed following qualitative content analysis, with development of inductive categories and use of consensual coding. For member checking, we consulted individuals with lived experiences prior to data collection and publication. RESULTS: Participants based their choice to initiate iOAT on the perceived implications of the treatment on one's daily life and individual recovery. Participants were encouraged to initiate iOAT due to the therapy's perceived potential in reducing cravings and substance use, its positive health consequences, and due to the image of iOAT as a path towards abstinence. Regarding deterring perceptions, participants feared a profound impairment of daily life due to factors such as the daily visits to the clinic, were concerned about whether iOAT would sufficiently promote or even impede one's recovery, and described negative health effects. CONCLUSION: Perceptions found in this study profoundly influenced participants' decisions on iOAT enrolment and contextualize the previous literature. The study reveals the dynamic coexistence of different perceptions about iOAT and sheds light on the inner-group stigmatization of iOAT. Practitioners and future research should acknowledge the complexities found in the current study in order to exploit the full potential of effective treatment modalities such as iOAT.

Supervised on-site dosing in injectable opioid agonist treatment-considering the patient perspective. Findings from a cross-sectional interview study in two German cities.

BACKGROUND: Injectable opioid agonist treatment (iOAT) is an effective option to support people living with opioid use disorder (OUD) who have not sufficiently benefitted from oral OAT. However, iOAT has been criticised based on theoretical and practical grounds for its dosing policies: Current regulations demand supervised, on-site application and require patients to frequently visit their treatment facility. The current study aims to investigate how patients experience on-site application and derive strategies to enhance the acceptability and effectiveness of iOAT-delivery. METHODS: This article is based on semi-structured interviews with 27 individuals currently or previously in iOAT in two German outpatient iOAT-clinics. We undertook an inductive qualitative content analysis, which included blinded, independent coding and the analysis of individual cases. RESULTS: Comments regarding on-site application and daily visits to the clinic were grouped into positive and negative aspects, iOAT as the best alternative option, facilitators of daily visits, and suggestions for improvement. Positive aspects took the factors stability and social support in regard. Negative aspects ranged from general inconveniences to major impediments to individuals' daily lives and towards achieving psychosocial goals. Participants reported rigorous adherence to iOAT's treatment regime, often due to a perceived lack of alternative options. Meeting iOAT's demands was eased by the patients' coping-strategies and through facilitating measures implemented by iOAT-clinics. Despite acknowledgement of the potential detriments from easing regulations, take-home arrangements were frequently suggested by participants to improve iOAT. CONCLUSIONS: Being required to attend the clinic for supervised iOAT-application is not experienced uniformly. While clinics can support their patients to cope with strict regulations, alternative approaches to iOAT-application should be considered to accommodate patients' individual needs. Examples from other treatment modalities (e.g., remote supervision and delivery services) might aid to reconcile individualisation while providing adequate safety measures and improve iOAT in the long term.

Shaping and shifting schemas on supervised injectable opioid treatment: findings from a cross-sectional qualitative study in two German treatment facilities.

BACKGROUND: Supervised injectable opioid treatment (SIOT) is a promising alternative for people living with opioid use disorder (OUD) who have not sufficiently benefitted from oral opioid substitution treatment. Yet, SIOT utilization remains limited in Germany. We propose that this is due to beliefs, or schemas, on SIOT among people living with OUD. Drawing from medical sociology and social psychology, this study explores the emergence and evolution of such schemas on SIOT. METHODS: We conducted semi-structured interviews with 34 individuals currently in or eligible for SIOT in two German outpatient treatment facilities and paralleled an inductive qualitative content analysis with the exploration of individual cases. RESULTS: The analysis revealed that peer-to-peer interaction and individuals' practical experiences in therapy are crucial in constructing and changing idiosyncratic and shared schemas of SIOT. When facing ambiguous information, cognitive strategies like subtyping served to mitigate uncertainty. CONCLUSION: This research has important practical implications for integrating experiential knowledge into clinical care and improve information sharing among people living with OUD. A nuanced understanding of the complex network of informal advice-seeking and -giving among people living with OUD is indispensable to adequately expand treatment modalities of proven effectiveness.

Positive inotropic effects of epigallocatechin-3-gallate (EGCG) involve activation of Na+/H+ and Na+/Ca2+ exchangers.

BACKGROUND: There is evidence that the tea catechin epigallocatechin-3-gallate (EGCG) modulates myocardial contractility. However, the underlying mechanisms remain to be determined. AIMS: To study potential signalling pathways involved in EGCG-induced contractile parameters. METHODS AND RESULTS: EGCG increased fractional shortening in rat cardiac myocytes and enhanced intracellular systolic Ca2+ concentrations. In isolated rat hearts, perfusion with EGCG resulted in significant, dose-dependent increase in peak systolic left ventricular pressure, as well as in contraction and relaxation velocities. Heart rate did not change. Inhibition of the beta1-receptor with metoprolol had no influence on the contractile effects of EGCG. Furthermore, levels of cAMP and phosphorylation of phospholamban did not change with EGCG, indicating that the beta-receptor pathway is not involved. The L-type Ca2+ channel inhibitors, nifedipine and gallopamil, failed to modulate EGCG-induced increase in contractility. However, the myocardial effects and intracellular calcium transients stimulated by EGCG were significantly reduced by the antagonist of the Na+/H+ exchanger (NHE) methyl-N-isobutyl amiloride (MIA), and by blocking of the reverse mode of the Na+/Ca2+ exchanger (NCX) by KB-R7943. CONCLUSION: These results indicate that Ca2+-dependent positive inotropic and lusitropic effects of EGCG are mediated in part via activation of the Na+/H+ exchanger and the reverse mode of the Na+/Ca2+ exchanger in the rat myocardium.

Long-term up-regulation of eNOS and improvement of endothelial function by inhibition of the ubiquitin-proteasome pathway.

The ubiquitin-proteasome system is the major pathway for intracellular protein degradation in eukaryotic cells. Endothelial nitric oxide synthase (eNOS) is the key enzyme of vascular homeostasis involved in the pathophysiology of several cardiovascular diseases. The aim of our study was to investigate whether eNOS expression and activity are regulated by the proteasome. Bovine pulmonary artery endothelial cells (CPAE cells) were treated with the proteasome inhibitor MG132. MG132 (50-250 nmol/L) dose-dependently increased mRNA and protein levels of eNOS. Comparable results were obtained with other specific proteasome inhibitors, whereas the nonproteasomal calpain and cathepsin inhibitor ALLM had no effect. Efficacy of proteasome inhibition was evidenced by accumulation of poly-ubiquitinylated proteins and by measuring proteasomal activity in cell extracts. Cycloheximide prevented up-regulation of eNOS protein, indicating that post-translational stabilization of eNOS is not involved. eNOS activity was increased up to 2.8-fold (MG132 100 nmol/L, 48 h). Incubation of rat aortic rings with MG132 significantly enhanced endothelial-dependent vasorelaxation. Single MG132 treatment (100 nmol/L) induced long-term effects in CPAE cells, with increases of eNOS protein and activity for up to 10 days. Our results indicate that low-dose proteasome inhibition enhances eNOS expression and activity, and improves endothelial function.

Prevalence of HIV, Hepatitis B and C Infections and an Assessment of HCV-Genotypes and Two IL28B SNPs among People Who Inject Drugs in Three Regions of Nepal.

As part of a comprehensive health care programme for people who use drugs in Nepal, HIV and viral hepatitis B and C status--including risk factors, HCV-genotypes and co-infections--as well as two IL28B Single-nucleotide polymorphisms (SNPs) were assessed for a random sample of 401 people who inject drugs in three regions of Nepal: mid-western Terrai (Nepalgunj), the eastern region (Dharan, Biratnagar) and the central region (Kathmandu, Lalitpur and Chitwan). Individuals were included who showed at least a minimum of health care seeking behaviour. This latter criterion was defined by being registered with any organisation offering health services. The average age of the participants was 30.5 yrs, and the average length of intravenous drug use was 8.5 yrs. The prevalence rates of HBsAg, anti-HIV antibodies and HCV-RNA were 3.5%, 13.8% and 41.9%, respectively. Spontaneous HCV clearance was evident in 16% of all of those who tested positive for anti-HCV antibodies. Independent risk factors for HCV-RNA positivity were age, gender, geographical region, duration of injecting drug use, history of imprisonment and HIV co-infection. In the age group ≤24 yrs, the rate of spontaneous HCV clearance was 43.5%. Overall, 59.8% of HCV infections were caused by HCV genotype 3 and 40.2% by HCV genotype 1. No other HCV genotypes were identified in this study. The IL28B SNP rs12979860 and rs8099917 were identified in 122 patients, and 75.4% of all participants had both favourable genotypes rs12979860 C/C and rs8099917 T/T.