Telephone delivered incentives for encouraging adherence to supervised methadone consumption (TIES): study protocol for a feasibility study for an RCT of clinical and cost effectiveness

The majority of people receiving treatment for their heroin addiction, are prescribed methadone; for which there is an extensive evidence base. When treatment starts, people take their daily dose of methadone under supervision at a community pharmacy. Supervision guarantees methadone is taken as directed by the individual for whom it has been prescribed, helps to ensure individuals take their correct dose every day, and safeguards against diversion and overdose. However, individuals often fail to attend the pharmacy to take their methadone. Each missed dose is of concern. If a patient misses their daily dose of methadone, they will start to experience opiate withdrawal and cravings and are more likely to use heroin. If they miss three days dose, there are concerns that they may lose tolerance to the drug and may be at risk of overdose when the next dose is taken. Hence there is an urgent need to develop effective interventions for medication adherence. Research suggests that incentive-based medication adherence interventions may be very effective, but there are few controlled trials and the provision of incentives requires time and organisational systems which can be challenging in pharmacies. The investigators have developed the technology to deliver incentives by mobile telephone. This cluster randomised trial will test the feasibility of conducting a future trial evaluating the clinical and cost effectiveness of using telephone delivered incentives (praise and modest financial rewards via text messaging) to encourage adherence with supervised consumption of methadone in community pharmacies. Three drug services (each with two or three community pharmacies supervising methadone consumption that will enrol 20 individuals, a total of 60 participants) will be recruited and randomly allocated to deliver either i) telephone delivered incentives, ii) telephone delivered reminders or iii) no telephone system. Acceptability, recruitment, follow-up, and suitable measures of clinical and cost effectiveness will be assessed. Findings from this feasibility study will be assessed against stated progression criteria and used to inform a future confirmatory trial of the clinical and cost effectiveness of telephone delivered incentives to encourage medication adherence. ISRCTN58958179 (retrospectively registered). [Abstract copyright: © 2019 Published by Elsevier Inc.

What will B will B: identifying molecular determinants of diverse B-cell fate decisions through systems biology

B-cells are the poster child for cellular diversity and heterogeneity. The diverse repertoire of B lymphocytes, each expressing unique antigen receptors, provides broad protection against pathogens. However, B-cell diversity goes beyond unique antigen receptors. Side-stepping B-cell receptor (BCR) diversity through BCR-independent stimuli or engineered organisms with monoclonal BCRs still results in seemingly identical B-cells reaching a wide variety of fates in response to the same challenge. Identifying to what extent the molecular state of a B-cell determines its fate is key to gaining a predictive understanding of B-cells and consequently the ability to control them with targeted therapies. Signals received by B-cells through transmembrane receptors converge on intracellular molecular signaling networks, which control whether each B-cell divides, dies, or differentiates into a number of antibody-secreting distinct B-cell subtypes. The signaling networks that interpret these signals are well known to be susceptible to molecular variability and noise, providing a potential source of diversity in cell fate decisions. Iterative mathematical modeling and experimental studies have provided quantitative insight into how B-cells achieve distinct fates in response to pathogenic stimuli. Here, we review how systems biology modeling of B-cells, and the molecular signaling networks controlling their fates, is revealing the key determinants of cell-to-cell variability in B-cell destiny

Heroin overdose resuscitation with naloxone:Patient uses own prescribed supply to save the life of a peer

Opiate overdose is the primary cause of death among injection-drug users, representing a major public health concern worldwide. Opiate overdose can be reversed through timely administration of naloxone, and users have expressed willingness to carry the antidote for emergency use (take-home naloxone). In November 2014, new WHO guidelines identified that naloxone should be made available to anyone at risk of witnessing an overdose. We present the case of a 46-year-old man in opioid-maintenance treatment who used take-home naloxone to rescue an overdose victim. This is the first- ever account of a patient using dose titration of naloxone to restore respiratory function while minimising the risk of adverse effects. To improve the safety of take-home naloxone, the authors call for clinicians involved in the treatment of opiate users to: prescribe take-home naloxone to all patients; forewarn patients of potential side effects; and instruct patients in naloxone dose titration

Could COVID expand the future of addiction research? Long-term implications in the pandemic era

BACKGROUND/AIMS: The COVID‐19 pandemic has significantly impacted face‐to‐face research. This has propelled ideas and plans for more remote styles of research and provided new perspectives on conducting research. This paper aimed to identify challenges specific to conducting remote forms of experimental addiction research, although some of these challenges apply to all types of addiction research. ARGUMENT: The impact of the COVID‐19 pandemic has led to important lessons for future addiction research. Although remote research has been conducted for decades, little experimental research has been performed remotely. To do so require a new perspective on what research questions we can ask and could also enable preferential capture of those who may be more reluctant to engage in research based in clinical settings. There may, however, be crucial factors that will compromise this process. We illustrate our argument with three real‐world, ongoing case studies centred on gambling behaviour, opioid overdose, and cannabinoid psychopharmacology. We highlight the obstacles to overcome to enable more remote methods of study. CONCLUSIONS: The future of experimental research and, more generally, addiction research, will be shaped by the pandemic and may result in advantages, such as reaching different populations and conducting addiction research in more naturalistic settings