Depot buprenorphine as an opioid agonist therapy in New South Wales correctional centres: a costing model.

BACKGROUND: In 2019 daily liquid methadone and sublingual buprenorphine-naloxone were primary opioid agonist treatments for correctional centres in New South Wales, Australia. However, both had significant potential for diversion to other patients, and their daily administration was resource intensive. An alternative treatment in the form of subcutaneous depot buprenorphine became a viable option following a safety trial in 2020 - the UNLOC-T study. Depot preparation demonstrated advantages over current treatments as more difficult to divert and requiring fewer administrations. This paper reports the results of economic modelling of staffing costs in medication administration comparing depot buprenorphine, methadone, and sublingual buprenorphine provision in UNLOC-T trial facilities. METHODS: The costing study adopted a micro-costing approach involving the synthesis of cost data from the UNLOC-T clinical trial as well as data collected from Justice Health and Forensic Mental Health Network records. Labour and materials data were collected during site observations and interviews. Costs were calculated from two payer perspectives: a) the New South Wales (state) government which funds custodial and health services; and b) the Australian Commonwealth government, which pays for medications. The analysis compared the monthly-per-patient cost for each of the three medications in trial-site facilities during July 2019. This was followed by simulation of depot buprenorphine implementation across the study population. Costs associated with medical assessment and reviews were excluded. RESULTS: The monthly-per-patient New South Wales government service costs of depot buprenorphine, methadone and sublingual buprenorphine were: $151, $379 and $1,529 respectively while Commonwealth government medication costs were $434, $80 and $525. The implementation simulation found that service costs of depot buprenorphine declined as patients transitioned from weekly to monthly administration. Costs of treatment using the other medications increased as patient numbers decreased alongside fixed costs. At 12 months, monthly-per-patient service costs for depot buprenorphine, methadone and sublingual buprenorphine-which would be completely phased out by month 13-were $92, $530 and $2,162 respectively. CONCLUSIONS: Depot buprenorphine was consistently the least costly of the treatment options. Future modelling could allow for dynamic patient populations and downstream impacts for participants and the state health system. TRIAL REGISTRATION: ACTRN12618000942257 . Registered 4 June 2018.

Alcohol Text Messages: A Developmental Study.

Risky paternal alcohol use is associated with maternal alcohol use during pregnancy, poor fetal and infant outcomes, domestic violence and depression. This study developed 30 SMS text messages about alcohol for fathers who drink at risky levels. The text messages were developed using two motivational styles: messages presented in a second person voice and the same messages presented in a child's voice. Fifty-one fathers were recruited through social media to complete an online survey rating the SMS text messages for message importance and likelihood of seeking further information and measuring risky alcohol use and psychosocial distress. Seventeen participants then participated in a semi-structured qualitative interview. Fathers rated the text messages presented in the child's voice as more important than messages presented in the second person. Qualitative data supported survey results that motivational SMS text messages could provide an acceptable way to raise awareness of risky alcohol consumption for future fathers.

Effect of treatment willingness on specialist assessment and treatment uptake for hepatitis C virus infection among people who use drugs: the ETHOS study.

Among people who inject drugs (PWID) with chronic HCV, the association between HCV treatment willingness and intent, and HCV specialist assessment and treatment were evaluated. The Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) is a prospective observational cohort. Recruitment was through six opioid substitution treatment clinics, two community health centres and one Aboriginal community controlled health organisation in Australia. Analyses were performed using logistic regression. Among 415 participants (mean age 41 years, 71% male), 67% were 'definitely willing' to receive HCV treatment and 70% reported plans to initiate therapy 12 months postenrolment. Those definitely willing to receive HCV treatment were more likely to undergo specialist assessment (64% vs 32%, P < 0.001) and initiate therapy (36% vs 9%, P < 0.001), compared to those with lower treatment willingness. Those with early HCV treatment plans were more likely to undergo specialist assessment (65% vs 27%, P < 0.001) and initiate therapy (36% vs 5%, P < 0.001), compared to those without early plans. In adjusted analyses, HCV treatment willingness independently predicted specialist assessment (aOR 3.06, 95% CI 1.90, 4.94) and treatment uptake (aOR 4.33, 95% CI 2.14, 8.76). In adjusted analysis, having early HCV treatment plans independently predicted specialist assessment (aOR 4.38, 95% CI 2.63, 7.29) and treatment uptake (aOR 9.79, 95% CI 3.70, 25.93). HCV treatment willingness was high and predicted specialist assessment and treatment. Strategies for enhanced HCV care should be developed with an initial focus on people willing to receive treatment and to increase treatment willingness among those less willing.

A randomised controlled trial of sublingual buprenorphine-naloxone film versus tablets in the management of opioid dependence.

BACKGROUND: Buprenorphine-naloxone sublingual film was introduced in 2011 in Australia as an alternative to tablets. This study compared the two formulations on subjective dose effects and equivalence, trough plasma levels, adverse events, patient satisfaction, supervised dosing time, and impact upon treatment outcomes (substance use, psychosocial function). METHODS: 92 buprenorphine-naloxone tablet patients were recruited to this outpatient multi-site double-blind double-dummy parallel group trial. Patients were randomised to either tablets or film, without dose changes, over a 31 day period. RESULTS: No significant group differences were observed for subjective dose effects, trough plasma buprenorphine or norbuprenorphine levels, adverse events and treatment outcomes. Buprenorphine-naloxone film took significantly less time to dissolve than tablets (173±71 versus 242±141s, p=0.007, F=7.67). CONCLUSIONS: The study demonstrated dose equivalence and comparable clinical outcomes between the buprenorphine-naloxone film and tablet preparations, whilst showing improved dispensing times and patient ratings of satisfaction with the film.

Disruption of the cyclic AMP phosphodiesterase-4 (PDE4)-HSP20 complex attenuates the ß-agonist induced hypertrophic response in cardiac myocytes.

The small heat shock protein HSP20 is known to be cardioprotective during times of stress and the mechanism underlying its protective abilities depends on its phosphorylation on Ser16 by PKA (protein kinase A). Although the external stimuli that trigger Ser16 phosphorylation have been well studied, the events that modulate spatial and temporal control of this modification remain to be clarified. Here, we report that inhibition of cAMP phosphodiesterase-4 (PDE4) induces the phosphorylation of HSP20 in resting cardiac myocytes and augments its phosphorylation by PKA following ß-adrenergic stimulation. Moreover, using peptide array technology, in vitro binding studies, co-immunoprecipitation techniques and immunocytochemistry, we show that HSP20 binds directly to PDE4 within a region of the conserved catalytic domain. We also show that FRET-based, genetically-encoded cAMP reporters anchored to HSP20 exhibit a larger response to PDE4 inhibition compared to free cytosolic cAMP reporters, suggesting that the interaction with PDE4 is crucial in modulating the highly localised pool of cAMP to which HSP20 is exposed. Using information gleaned from peptide array analyses, we developed a cell-permeable peptide that serves to inhibit the interaction of PDE4 with HSP20. Disruption of the HSP20-PDE4 complex, using this peptide, suffices to induce phosphorylation of HSP20 by PKA and to protect against the hypertrophic response measured in neonatal cardiac myocytes following chronic ß-adrenergic stimulation.

The psychiatric disease risk factors DISC1 and TNIK interact to regulate synapse composition and function.

Disrupted in schizophrenia 1 (DISC1), a genetic risk factor for multiple serious psychiatric diseases including schizophrenia, bipolar disorder and autism, is a key regulator of multiple neuronal functions linked to both normal development and disease processes. As these diseases are thought to share a common deficit in synaptic function and architecture, we have analyzed the role of DISC1 using an approach that focuses on understanding the protein-protein interactions of DISC1 specifically at synapses. We identify the Traf2 and Nck-interacting kinase (TNIK), an emerging risk factor itself for disease, as a key synaptic partner for DISC1, and provide evidence that the DISC1-TNIK interaction regulates synaptic composition and activity by stabilizing the levels of key postsynaptic density proteins. Understanding the novel DISC1-TNIK interaction is likely to provide insights into the etiology and underlying synaptic deficits found in major psychiatric diseases.