Proportion and conditions of use of intranasal take-home naloxone kits: A retrospective study in two French outpatient addiction centers, 2016–2020

  • CHU de Lyon - Centre Hospitalier le Vinatier
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Background: Take-home naloxone (THN) helps to revert the medical consequences of an opioid overdose among people who use drugs (PWUD). In France, an intranasal THN was available from July 2016 to Dec 2020, which was directly dispensed in addiction centers, after a specific education program. However, this intranasal THN was subsequently removed from the market. Objective: To retrospectively explore the post-dispensing proportion and conditions of use of intranasal THN kits, as well as the preferences for intranasal or intramuscular THN among French PWUD. Methods: Based on medical records, all PWUD who benefit from a dispensation of at least one intranasal THN kit in two French outpatient addiction centers, between July 2016 and Dec 2020, were recontacted by phone in April-May 2021, and asked if they used their kits, and, if yes, how. An additional question also explores whether French PWUD preferred being provided with intranasal or intramuscular THN kits. Results: Five hundred thirty-four (534) PWUD were provided a THN kits, but only 188 (35.2%) could be joined by phone. Of them, 26 (13.8%) did not remember being trained for and dispensed with a THN kit. Of the 160 PWUD interviewed, only six (3.7%) reported having used their kits because of an overdose, in three cases for themselves, and in three cases for someone else. In all the six situations, the victim of the overdose survived. One hundred and eleven (111; 59.0%) PWUD declared preferring intranasal THN form, while 30 (16.0%) preferred intramuscular kits, and 47 (25.0%) had no preference. Conclusions: Compared to what was found in other countries, the proportion of use of THN was low among treatment-seeking French PWUD. This might be due to a reduced likelihood of overdose in this population, or more possibly to an insufficient interest in THN benefits by French PWUD.

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Backgrounds: Between 2009 and 2018, the number of opioid-related deaths (ORDs) in Scotland showed a dramatic increase, whereas in England and Wales, a much lower increase in ORD was seen. This regional difference is remarkable, and the situation in Scotland is worrisome. Therefore, it is important to identify the drivers of ORD in Scotland. Methods: A systematic literature review according to PRISMA guidelines was conducted to identify peer-reviewed studies about key drivers for the observed differences in ORDs between Scotland and England/Wales. In addition, non-peer-reviewed reports on nationwide statistical data were retrieved via Google and Google Scholar and analysed to quantify differences in ORD drivers between Scotland and England/Wales. Results: The systematic review identified some important drivers of ORD, but none of these studies provided direct or indirect comparisons of ORD drivers in Scotland and England/Wales. However, the reports with nationwide statistical data showed important differences in ORD drivers between Scotland and England/Wales, including a higher prevalence of people using opioids in a problematic way (PUOP), more polydrug use in people using drugs in a problematic way (PUDP), a higher age of PUDP, and lower treatment coverage and efficacy of PUDP in Scotland compared to England/Wales, but no regional differences in injecting drug use, incarceration/prison release without treatment, and social deprivation in PUDP. Conclusion: It is concluded that the opioid crisis in Scotland is best explained by a combination of drivers, consisting of a higher population involvement in (problematic) opioid use (notably methadone), relatively more polydrug use (notably benzodiazepines and gabapentinoids), a steeper ageing of the PUOP population in the past 2 decades, and lower treatment coverage and efficacy in Scotland compared to England/Wales. The findings have important consequences for strategies to handle the opioid crisis in Scotland.
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Introduction: Improving the knowledge and attitudes of people facing an opioid overdose is one of the key prevention measures for reducing overdose occurrence and severity. In this respect, the Opioid Overdose Knowledge (OOKS) and Attitudes (OOAS) Scales have been developed and validated in English to assess and improve knowledge and attitudes of opioid users and their families and care providers, in case of an overdose. Here the OOKS and OOAS scales have been translated into French, Spanish, and German, respectively, and the different versions of the two scales have been assessed regarding their psychometric properties. Methods: The translation procedure of the scales was based on the international recommendations, including a back-translation by a native English speaker. Subsequently, 80 (Spain: 29, France: 27, Germany: 23) former or current heroin users, aged from 20 to 61 years (M = 39.4 ± 9.23), completed the OOKS and OOAS versions of their native language, in test-retest, without specific between-assessment training. Internal consistency was assessed using Cronbach’s α, while test-retest reliability was assessed using interclass correlation coefficient (ICC). The correlation between the OOKS and OOAS scores of a same language was assessed using the Spearman’s () coefficient. Results: Internal consistency of the OOKS was found good to very good, with Cronbach’s α ranging from 0.62 to 0.87. Test-retest reliability was also very good, with ICCs ranging from 0.71 to 0.82. However, results were less reliable for the OOAS, as internal consistency was questionable to acceptable, with Cronbach’s α ranging from 0.12 to 0.63, while test-retest ICCs were very good for the French (0.91) and Spanish (0.99) versions, and barely acceptable for the German version (0.41). No significant correlation was found between the OOKS and OOAS scores, irrespective of the version concerned. Conclusion: While satisfactory results were found for the three versions of the OOKS, results on the OOAS were relatively inconsistent, suggesting a possible gap between knowledge and attitudes on overdose among opioid users.
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AimsTo assess the effectiveness for Scotland's National Naloxone Programme (NNP) by comparison between 2006-10 (before) and 2011-13 (after NNP started in January 2011) and to assess cost-effectiveness. DesignThis was a pre-post evaluation of a national policy. Cost-effectiveness was assessed by prescription costs against life-years gained per opioid-related death (ORD) averted. SettingScotland, in community settings and all prisons. InterventionBrief training and standardized naloxone supply became available to individuals at risk of opioid overdose. MeasurementsORDs as identified by National Records of Scotland. Look-back determined the proportion of ORDs who, in the 4weeks before ORD, had been (i) released from prison (primary outcome) and (ii) released from prison or discharged from hospital (secondary). We report 95% confidence intervals for effectiveness in reducing the primary (and secondary) outcome in 2011-13 versus 2006-10. Prescription costs were assessed against 1 or 10 life-years gained per averted ORD. FindingsIn 2006-10, 9.8% of ORDs (193 of 1970) were in people released from prison within 4weeks of death, whereas only 6.3% of ORDs in 2011-13 followed prison release (76 of 1212, P<0.001; this represented a difference of 3.5% [95% confidence interval (CI)=1.6-5.4%)]. This reduction in the proportion of prison release ORDs translates into 42 fewer prison release ORDs (95% CI=19-65) during 2011-13, when 12000 naloxone kits were issued at current prescription cost of 225000. Scotland's secondary outcome reduced from 19.0 to 14.9%, a difference of 4.1% (95% CI=1.4-6.7%). Conclusions Scotland's National Naloxone Programme, which started in 2011, was associated with a 36% reduction in the proportion of opioid-related deaths that occurred in the 4weeks following release from prison.
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In most European countries, methadone treatment is provided to only 20– 30% of opiate abusers who need treatment due to regulations and concerns about safety. To address this need in France, all registered medical doctors since 1995 have been allowed to prescribe buprenorphine (BUP) without any special education or licensing. This led to treating approximately 65,000 patients per year with BUP, about ten times more than with more restrictive methadone policies. French physician compensation mechanisms, pharmacy services, and medical insurance funding all minimized barriers to BUP treatment. About 20% of all physicians in France are using BUP to treat about half of the estimated 150,000 problem heroin users. Daily supervised dosing by a phamacist for the first six months resulted in significantly better treatment retention (80% vs 46%) and lower heroin use. Intravenous diversion of BUP may occur in up to 20% of BUP patients and has led to various infections and relatively rare overdoses in combination with sedatives. Opiate overdose deaths have declined substantially (by 79%) since BUP was introduced in 1995. Newborn opiate withdrawal in mothers treated with buprenorphine compared to methadone was reported to be less frequent, less severe, and of shorter duration. Although some of the public health benefits seen during the time of buprenorphine expansion in France might be contingent upon characteristics of the French health and social services system, the French model raises questions about the value of tight regulations on prescribing BUP imposed by many countries throughout the world.
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Doctors routinely give naloxone during emergency resuscitation after opiate overdose. The distribution of naloxone to opiate addicts has recently been addressed,1–4 and a survey of drug users shows extensive support for the provision of supplies to take away.4 We present the preliminary results of two pilot schemes to provide take home naloxone to opiate users. ### The Berlin project In January 1999 drug users in Berlin were given naloxone to take home. Opiate misusers attending a healthcare project (operating from a mobile van or ambulance) were offered training in emergency resuscitation after overdose, provided with naloxone (two 400 μg ampoules), needles, syringes, an emergency handbook, and information on naloxone. They were asked to report on any use of the drug. After 16 months, 124 opiate misusers had received training in resuscitation and were provided with supplies of naloxone to take away; 40 reported back, with 22 having given emergency naloxone (two on two occasions, one on three, and one on four). #### Case 1 (Berlin) “Three days ago, I was walking along the canal with a friend of mine. We saw a guy lying on the ground, with two people trying to help him—they were trying to help him breathe by mouth to mouth. When …
Background: Opioid-related overdose has increased 137% in the past decade. Training nonmedical bystanders to administer naloxone (Narcan™) is a widely-researched intervention that has been associated with decreases in overdose rates in the communities in which it has been implemented. A recent review advocated for noninjectable formulations of naloxone, however patient preference for naloxone formulations has not yet been examined (Strang et al., 2016). Methods: Two cohorts of respondents (N1 = 501, N2 = 172) who reported currently being prescribed an opioid for pain management were recruited through the crowd-sourcing program Amazon Mechanical Turk (MTurk) to assess their preference for naloxone formulations. All respondents were provided a description of different formulations and asked to indicate all formulations they would be willing to administer for overdose reversal and to then rank formulations in order of preference. Results: Results were remarkably similar across both cohorts. Specifically, respondents preferred noninjectable formulations (intranasal, sublingual, buccal) over injectable (intravenous, intramuscular) formulations. A small percent (8.9%-9.8%) said they would never be willing to administer naloxone. An identical percent of respondents in both cohorts (44.9%) rated intranasal as their most preferred formulation. Conclusions: Two independent cohorts of respondents who were receiving opioid medications for pain management reported a preference for noninjectable over injectable formulations of naloxone to reverse an opioid overdose. Though initial preference is only one of many factors that impacts ultimate public acceptance and uptake of a new product, these results support the additional research and development of noninjectable naloxone formulations.
Background Opioid overdose is a major cause of mortality, but injury and fatal outcomes can be prevented by timely administration of the opioid antagonist naloxone. Pre-provision of naloxone to opioid users and family members (take-home naloxone, THN) was first proposed in 1996, and WHO Guidelines were issued in 2014. While widespread in some countries, THN is minimally available or absent elsewhere. This review traces the development of THN over twenty years, from speculative harm reduction proposal to public health strategy. Method Medline and PsycINFO were searched for peer-reviewed literature (1990-2016) using Boolean queries: 1) “naloxone OR Narcan”; 2) “(opioid OR opiate) AND overdose AND prevention”. Grey literature and specialist websites were also searched. Data were extracted and synthesized as narrative review, with key events presented as chronological timeline. Results Results are presented in 5-year intervals, starting with the original proposal and THN pilots from 1996-2001. Lack of familiarity with THN challenged early distribution schemes (2001-2006), leading to further testing, evaluation, and assessment of challenges and perceived medicolegal barriers. From 2006-2011, response to social and legal concerns led to the expansion of THN programs; followed by high-impact research and efforts to widen THN availability from 2011-2016. Conclusions Framed as a public health tool for harm reduction, THN has overcome social, clinical, and legal barriers in many jurisdictions. Nonetheless, the rising death toll of opioid overdose illustrates that current THN coverage is insufficient, and greater public investment in overdose prevention will be required if THN is to achieve its full potential impact.
Background: The epidemic of drug-related mortality continues to endure. The most common cause of death associated with drugs is overdose and opioids are consistently the substances most prominently involved. As well as efforts to control the availability of illicit drugs and increase engagement in treatment services, the use of naloxone for peer administration has increasingly been championed as a mechanism for addressing the DRD epidemic. Despite increasing adoption and use of take-home naloxone (THN) as a primary response to DRD internationally the evidence base remains limited. Methods: A systematic review and descriptive meta-analysis of the international THN literature was undertaken to determine an effect size for THN programmes. For each study, a proportion of use (PoU) was calculated using the number of 'peer administered uses' and the 'total number of participant/clients' trained and supplied with naloxone with a specific focus on people who use drugs (PWUD). This was constrained to a three month period as the lowest common denominator. As a percentage this gives the three month rate of use (per 100 participants). Results: From twenty-five identified THN evaluations, nine studies allowed a PoU to be determined. Overall, the model shows a range of 5.2-13.1 (point estimate 9.2) naloxone uses every three months for every 100 PWUD trained. Conclusion: Our model estimates that around 9% of naloxone kits distributed are likely to be used for peer administration within the first three months of supply for every 100 PWUD trained. Future evaluations should directly compare different training structures to test relative effectiveness and use a series of fixed time periods (3, 6 and 12 months) to determine whether time since training affects rate of naloxone use.
Feedback from two French addiction centers and national survey on the intranasal naloxone (Nalscue®) in the prevention of opioid overdoses
  • Lenglard
Exploring the life-saving potential of naloxone: A systematic review and descriptive meta-analysis of take home naloxone (THN) programmes for opioid users
  • A Mcauley
  • L Aucott
  • C Maethseon
McAuley A, Aucott L, Maethseon C. Exploring the life-saving potential of naloxone: A systematic review and descriptive meta-analysis of take home naloxone (THN) programmes for opioid users. Int J Drug Policy 2015;26:1183-8.
Feedback from two French addiction centers and national survey on the intranasal naloxone (Nalscue ® ) in the prevention of opioid overdoses
  • F Lenglard
  • A Berger-Vergiat
  • D Ragonnet
  • N Duvernay
  • P Lack
  • E Poulet
Lenglard F, Berger-Vergiat A, Ragonnet D, Duvernay N, Lack P, Poulet E, et al. Feedback from two French addiction centers and national survey on the intranasal naloxone (Nalscue ® ) in the prevention of opioid overdoses. Therapie 2019;74:477-86.