What impacts the acceptability of wearable devices that detect opioid overdose in people who use opioids? A qualitative study.

INTRODUCTION: Drug-related deaths involving an opioid are at all-time highs across the United Kingdom. Current overdose antidotes (naloxone) require events to be witnessed and recognised for reversal. Wearable technologies have potential for remote overdose detection or response but their acceptability among people who use opioids (PWUO) is not well understood. This study explored facilitators and barriers to wearable technology acceptability to PWUO. METHODS: Twenty-four participants (79% male, average age 46 years) with current (n = 15) and past (n = 9) illicit heroin use and 54% (n = 13) who were engaged in opioid substitution therapy participated in semi-structured interviews (n = 7) and three focus groups (n = 17) in London and Nottingham from March to June 2022. Participants evaluated real devices, discussing characteristics, engagement factors, target populations, implementation strategies and preferences. Conversations were recorded, transcribed and thematically analysed. RESULTS: Three themes emerged: device-, person- and environment-specific factors impacting acceptability. Facilitators included inconspicuousness under the device theme and targeting subpopulations of PWUO at the individual theme. Barriers included affordability of devices and limited technology access within the environment theme. Trust in device accuracy for high and overdose differentiation was a crucial facilitator, while trust between technology and PWUO was a significant environmental barrier. DISCUSSION AND CONCLUSIONS: Determinants of acceptability can be categorised into device, person and environmental factors. PWUO, on the whole, require devices that are inconspicuous, comfortable, accessible, easy to use, controlled by trustworthy organisations and highly accurate. Device developers must consider how the type of end-user and their environment moderate acceptability of the device.

A scoping review of mHealth technologies for opioid overdose prevention, detection and response.

ISSUES: Opioid overdose kills over 100,000 people each year globally. Mobile health (mHealth) technologies and devices, including wearables, with the capacity to prevent, detect or respond to opioid overdose exist in early form, or could be re-purposed or designed. These technologies may particularly help those who use alone. For technologies to be successful, they must be effective and acceptable to the at-risk population. The aim of this scoping review is to identify published studies on mHealth technologies that attempt to prevent, detect or respond to opioid overdose. APPROACH: A systematic scoping review of literature was conducted up to October 2022. APA PsychInfo, Embase, Web of Science and Medline databases were searched. INCLUSION CRITERIA: articles had to report on (i) mHealth technologies that deal with (ii) opioid (iii) overdose. KEY FINDINGS: A total of 348 records were identified, with 14 studies eligible for this review across four domains: (i) technologies that require intervention/response from others (four); (ii) devices that use biometric data to detect overdose (five); (iii) devices that automatically respond to an overdose with administration of an antidote (three); (iv) acceptability/willingness to use overdose-related technologies/devices (five). IMPLICATIONS: There are multiple routes in which these technologies may be deployed, but several factors impact acceptability (e.g., discretion or size) and accuracy of detection (e.g., sensitive parameter/threshold with low false positive rate). CONCLUSION: mHealth technologies for opioid overdose may play a crucial role in responding to the ongoing global opioid crises. This scoping review identifies vital research that will determine the future success of these technologies.

Noninvasive Assessment of Neuromechanical and Neuroventilatory Coupling in COPD.

This study explored the use of parasternal second intercostal space and lower intercostal space surface electromyogram (sEMG) and surface mechanomyogram (sMMG) recordings (sEMGpara and sMMGpara, and sEMGlic and sMMGlic, respectively) to assess neural respiratory drive (NRD), neuromechanical (NMC) and neuroventilatory (NVC) coupling, and mechanical efficiency (MEff) noninvasively in healthy subjects and chronic obstructive pulmonary disease (COPD) patients. sEMGpara, sMMGpara, sEMGlic, sMMGlic, mouth pressure (Pmo), and volume (Vi) were measured at rest, and during an inspiratory loading protocol, in 16 COPD patients (8 moderate and 8 severe) and 9 healthy subjects. Myographic signals were analyzed using fixed sample entropy and normalized to their largest values (fSEsEMGpara%max, fSEsMMGpara%max, fSEsEMGlic%max, and fSEsMMGlic%max). fSEsMMGpara%max, fSEsEMGpara%max, and fSEsEMGlic%max were significantly higher in COPD than in healthy participants at rest. Parasternal intercostal muscle NMC was significantly higher in healthy than in COPD participants at rest, but not during threshold loading. Pmo-derived NMC and MEff ratios were lower in severe patients than in mild patients or healthy subjects during threshold loading, but differences were not consistently significant. During resting breathing and threshold loading, Vi-derived NVC and MEff ratios were significantly lower in severe patients than in mild patients or healthy subjects. sMMG is a potential noninvasive alternative to sEMG for assessing NRD in COPD. The ratios of Pmo and Vi to sMMG and sEMG measurements provide wholly noninvasive NMC, NVC, and MEff indices that are sensitive to impaired respiratory mechanics in COPD and are therefore of potential value to assess disease severity in clinical practice.

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.

COVID-19 pandemic and methanol poisoning outbreak in Iranian children and adolescents: A data linkage study.

BACKGROUND: During the first wave of COVID-19, many Iranians were poisoned by ingesting hand sanitizers and/or alcoholic beverages to avoid viral infection. To assess whether the COVID-19 pandemic resulted in an increased prevalence of accidental hand sanitizer/alcoholic beverage exposure in children and adolescents, we compared pediatric hospitalization rates during COVID-19 and the previous year. For poisoning admissions during COVID-19, we also evaluated the cause by age and clinical outcomes. METHODS: This retrospective data linkage study evaluated data from the Legal Medicine Organization (reporting mortalities) and hospitalization data from nine toxicology referral centers for alcohol-poisoned patients (age 0 to 18 years) for the study period (February 23 to June 22, 2020) and the pre-COVID-19 reference period (same dates in 2019). RESULTS: Hospitalization rates due to ethanol and methanol exposure were significantly higher in 2020 (n = 375) than 2019 (n = 202; OR [95% CI] 1.9 [1.6, 2.2], p < 0.001). During COVID-19, in patients ≤15 years, the odds of intoxication from hand sanitizers were significantly higher than from alcoholic beverages, while in 15- to 18-year-olds, alcoholic beverage exposure was 6.7 times more common (95% CI 2.8, 16.1, p < 0.001). Of 375 children/adolescents hospitalized for alcoholic beverage and hand sanitizer exposure in 2020, six did not survive. The odds of fatal outcome were seven times higher in 15- to 18-year-olds (OR (95% CI) 7.0 (2.4, 20.1); p < 0.001). CONCLUSION: The Iranian methanol poisoning outbreak during the first wave of COVID-19 was associated with significantly increased hospitalization rates among children and adolescents-including at least six pediatric in-hospital deaths from poisoning. Public awareness needs to be raised of the risks associated with ingesting alcoholic hand sanitizers.

Heroin-induced respiratory depression and the influence of dose variation: within-subject between-session changes following dose reduction.

BACKGROUND AND AIMS: Globally, more than 100 000 people die annually from opioid overdose. Opportunities to study physiological events in at-risk individuals are limited. This study examined variation of opioid dose and impact on respiratory depression in a chronic injecting heroin user at separate time-points during his long-term diamorphine maintenance treatment. DESIGN: A single-subject study over 5 years during which participant underwent experimental studies on diamorphine-induced respiratory depression, at changing maintenance doses. SETTING: A clinical research facility. Participant Male subject on long-term injectable diamorphine (pharmaceutical heroin) maintenance treatment for heroin addiction. MEASUREMENTS: Physiological measures of oxygen saturation (SpO2 ), end-tidal carbon dioxide (ETCO2 ) and respiratory rate (RR) were used to indicate severity of respiratory depression. FINDINGS: (1) After diamorphine injection, respiratory regulation became abnormal, with prolonged apnoea exceeding 20 sec (maximum 56 sec), elevated ETCO2 (maximum 6.9%) and hypoxaemia (minimum SpO2 80%). (2) Abnormalities were greater with highest diamorphine dose: average SpO2 was 89.3% after 100 mg diamorphine versus 93.6% and 92.8% for the two 30-mg doses. (3) However, long apnoeic pauses and high levels of ETCO2 % were also present after lower doses. CONCLUSIONS: With marked inter-session variability, these findings corroborate observations of inconsistent relationships between opioid dose and overdose risk.

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. TRIAL REGISTRATION: ISRCTN58958179 (retrospectively registered).

Clinical provision of improvised nasal naloxone without experimental testing and without regulatory approval: imaginative shortcut or dangerous bypass of essential safety procedures?

CONTEXT: Take-home naloxone is increasingly provided to prevent heroin overdose deaths. Naloxone 0.4-2.0 mg is licensed for use by injection. Some clinicians supply improvised nasal naloxone kits (outside licensed approval). Is this acceptable? AIMS: (1) To consider provision of improvised nasal naloxone in clinical practice and (2) to search for evidence for pharmacokinetics and effectiveness (versus injection). METHODS: (1) To document existing nasal naloxone schemes and published evidence of pharmacokinetics (systematic search of the CINAHL, Cochrane, EMBASE and MEDLINE databases and 18 records included in narrative synthesis). (2) To analyse ongoing studies investigating nasal naloxone (WHO International Clinical Trials Registry Platform and US NIH RePORT databases). FINDINGS: (1) Multiple studies report overdose reversals following administration of improvised intranasal naloxone. (2) Overdose reversal after nasal naloxone is frequent but may not always occur. (3) Until late 2015, the only commercially available naloxone concentrations were 0.4 mg/ml and 2 mg/2 ml. Nasal medications are typically 0.05-0.25 ml of fluid per nostril. The only published study of pharmacokinetics and bioavailability finds that nasal naloxone has poor bioavailability. QUESTIONS FOR DEBATE: (1) Why are pharmacokinetics and bioavailability data for nasal naloxone not available before incorporation into standard clinical practice? (2) Does nasal naloxone have the potential to become a reliable clinical formulation? (3) What pre-clinical and clinical studies should precede utilization of novel naloxone formulations as standard emergency medications? CONCLUSIONS: The addictions treatment field has rushed prematurely into the use of improvised nasal naloxone kits. Evidence of adequate bioavailability and acceptable pharmacokinetic curves are vital preliminary steps, especially when effective approved formulations exist.

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.

The TRPM8 channel forms a complex with the 5-HT(1B) receptor and phospholipase D that amplifies its reversal of pain hypersensitivity.

Effective relief from chronic hypersensitive pain states remains an unmet need. Here we report the discovery that the TRPM8 ion channel, co-operating with the 5-HT(1B) receptor (5-HT(1B)R) in a subset of sensory afferents, exerts an influence at the spinal cord level to suppress central hypersensitivity in pain processing throughout the central nervous system. Using cell line models, ex vivo rat neural tissue and in vivo pain models, we assessed functional Ca(2+) fluorometric responses, protein:protein interactions, immuno-localisation and reflex pain behaviours, with pharmacological and molecular interventions. We report 5-HT(1B)R expression in many TRPM8-containing afferents and direct interaction of these proteins in a novel multi-protein signalling complex, which includes phospholipase D1 (PLD1). We provide evidence that the 5-HT(1B)R activates PLD1 to subsequently activate PIP 5-kinase and generate PIP2, an allosteric enhancer of TRPM8, achieving a several-fold increase in potency of TRPM8 activation. The enhanced activation responses of synaptoneurosomes prepared from spinal cord and cortical regions of animals with a chronic inflammatory pain state are inhibited by TRPM8 activators that were applied in vivo topically to the skin, an effect potentiated by co-administered 5-HT(1B)R agonists and attenuated by 5-HT(1B)R antagonists, while 5-HT(1B)R agents alone had no detectable effect. Corresponding results are seen when assessing reflex behaviours in inflammatory and neuropathic pain models. Control experiments with alternative receptor/TRP channel combinations reveal no such synergy. Identification of this novel receptor/effector/channel complex and its impact on nociceptive processing give new insights into possible strategies for enhanced analgesia in chronic pain.