Broad-scale overdose education and naloxone distribution – 5-year follow-up of a regional program in Skåne County, Sweden

Broad-scale overdose education and naloxone distribution – 5-year follow-up of a regional program in Skåne County, Sweden | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Broad-scale overdose education and naloxone distribution – 5-year follow-up of a regional program in Skåne County, Sweden Katja Troberg, Pernilla Isendahl, Disa Dahlman, Anders Håkansson This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5281562/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Jun, 2025 Read the published version in Harm Reduction Journal → Version 1 posted 9 You are reading this latest preprint version Abstract Background Opioid use disorder is a chronic disorder with a high risk of overdose related morbidity and mortality where a large proportion of these can be averted by timely administration of the antidote naloxone. For naloxone to be present when and where overdoses occur, broad-scale overdose education and naloxone distribution (OEND) must be established. A regional naloxone program was implemented in 2018, in Skåne County, Sweden. This five-year follow-up aims to describe all naloxone-related lay-person events and whether recommendations previously described in the literature were met and to further investigate events conducted by individuals reporting overdose reversals with naloxone on three or more occasions (‘Supersavers’). Methods Between June 2018 and June 2023, data was collected in six-month intervals from participating units (n = 52), containing information on trained individuals, gender, year of birth and distributed naloxone kits. Upon naloxone replenishment, patients were asked whether previous naloxone had been used for overdose reversals on someone else, or themselves, had been lost, stolen, or given to someone else. Results Training and initial kits had been provided to 2685 individuals at risk of own opioid overdose. Each of the 5900 naloxone kits distributed, contained two naloxone doses. Upon refill (n = 2364), naloxone had been used for overdose reversal in 39% (n = 926) situations. The minimum distribution target of 20 kits per annual opioid overdose death was met annually, while the target of enrolling > 100 individuals at-risk individuals per 100,000 population was first met during the second year. The core group of Supersavers represent 9% (n = 50) of those returning for refill and while reporting 54.5% (n = 292) of all overdose reversals. Conclusions Broad-scale naloxone training and distribution reaches a large proportion of individuals at risk of opioid overdose. A continuous focus and priority in supporting units with a high prevalence of individuals witnessing overdose events is of great importance as these individuals report a large proportion of overdose reversals. Likewise, it is of great importance to provide these individuals, i.e. Supersavers, with needed and sufficient support for their continued essential work intervening in overdose situations. Trial Registration: Naloxone Treatment in Skåne County – Effect on Drug-related Mortality and Overdose-related Complications, NCT03570099, registered 26 June 2018. Take-home naloxone Overdose Education and Naloxone Distribution People who use opioids harm reduction Figures Figure 1 Figure 2 1. Introduction With the World Health Organization’s estimate of approximately 125,000 people dying in 2019 from opioid overdose worldwide ( 1 ) overdose mortality and morbidity persist to present a pressing public health crisis. The harms of predominantly heroin, with increasing use of other illicit opioids such as methadone, oxycodone, buprenorphine, tramadol, fentanyl derivatives and lately also nitazenes (benzimidazole opioids), is continuously an urgent matter as these are linked to a majority (74%) of drug-related deaths in Europe ( 2 ). International research shows a prevalence of 17–68% self-reported experience of an own non-fatal overdose among people who use drugs, while 50–96% have witnessed someone else’s overdose ( 3 ). In many cases these overdoses are preventable. For decades, naloxone has been used for overdose reversals, both in prehospital healthcare and by training and by providing laypersons with naloxone through overdose education and naloxone distribution (OEND) programs. With few adverse events, naloxone may effectively reverse opioid overdose if administered timely ( 4 ). Large-scale programs are often effective in reaching individuals at-risk of own, or those witnessing overdose and have been significantly associated with reduced opioid overdose deaths ( 5 – 7 ). For naloxone to be present when and where overdoses occur, it has been estimated that naloxone programs should aim to distribute 20 times the annual opiate overdose mortality rate, with a minimum of 9 times as many ( 8 ). Research by Walley and colleagues (2013) ( 5 ) showed significant reductions in overdose deaths in communities where OEND had been implemented, with a 46% reduction of overdose deaths in communities where enrolment rates exceeded 100 per 100,000 inhabitants. In congruence with our previous findings ( 9 ), international research found overdose reversals predominantly being performed by individuals who themselves are at risk of overdose ( 10 – 12 ). Broad-scale provision of naloxone in Sweden is imperative as drug-related deaths are approximately four times higher than the European average ( 13 ), and where 88% of drug induced deaths involve opioids ( 14 ). Therefore, by targeting a large proportion of at-risk individuals who are prepared to act in overdose situations would be a self-evident step trying to reduce overdose morbidity and mortality. This study aims to contribute to the growing, but yet scarce, body of literature on long-term follow-ups of systematic broad-scale OEND by 1) describing all naloxone-related events during the first five years of the naloxone program in Skåne county, 2) studying the naloxone distribution in relation to annual opioid overdose mortality rate ( 8 ), and evaluate whether the program reaches targeted recommendations of enrolment on a population level ( 5 ), 3) studying the core group of individuals who reported three or more overdose reversals, i.e. “Supersavers”. Success of the program is largely dependent on these individuals as they perform a large part of overdose reversals. Investigation into their situation and specific needs is imperative to assure provision and support to maintain sustainable conditions, thus, enabling them to continue their important work. 2. Methods 2.1. Study Design This study is based on data from all participants who received OEND in Skåne county between June 2018 and June 2023. Upon completion of training and having received take-home naloxone (THN), containing two doses of intranasal naloxone (IN), year of birth, gender facility and date of training have been registered continuously over time by key-trainers at each participating unit. For trained individuals who returned for naloxone replenishment, initial training unit was noted, and participants were asked what had happened to previous dose/-s (used on one-self, used on someone else, lost, given to other, stolen, or not known). All kits were replenished, regardless of reason for refill of previous kit. Participating units reported data every six months to coordinators for Skåne Naloxone program. 2.2. Setting Skåne Naloxone program was implemented in June 2018 and is situated in southernmost Sweden, in Skåne, a county with 1.4 million inhabitants. The program includes all opioid agonist treatment (OAT) facilities, needle and syringe programs (NSPs), in-patient addiction facilities and non-OAT outpatient facilities. The naloxone kit contains two doses of naloxone and is given to the patients directly after training, free of charge (described in detail previously in Troberg et al. (2020) ( 15 ). NSPs in Skåne are run by the departments for infectious disease with physicians specialized in infections disease, nurses, assistant nurses, social workers, and midwives offering comprehensive free of charge healthcare including tests for blood borne viruses, vaccination for hepatitis A and B, and hepatitis C treatment besides providing visitors with clean needles and syringes. Only facilities specialized in psychiatry may provide OAT. On a national level, a survey referred to by The National Board of Health and Welfare showed that approximately 65 per 100,000 inhabitants were enrolled in OAT in 2022 ( 16 ), with low availability in rural areas. All regions are self-governing and in Skåne the situation is unique compared to the rest of Sweden as OATs are run by both public and privately owned healthcare providers, through a “choice of healthcare” system, rendering a much higher availability at 158/100,000[1] . Swedish healthcare and medication are heavily subsidised by governmental fundings. Naloxone is provided free of charge at all facilities included in the program. During the study period, naloxone could be prescribed by any physician. As of November 1 st, 2018, naloxone could also be prescribed by registered nurses. As with the majority of all prescribed medication, naloxone included in the high-cost protection scheme, a subsidy that sets an upper limit of individual costs for medication and medical care ( 17 ). 2.3. Study participants All individuals (n = 2685) took part of the theoretical and practical overdose prevention training and were provided with a naloxone-kit from one of the OEND facilities (n = 52) in Skåne county. The study included the following facilities in the region: NSPs (n = 4), OATs (n = 30), emergency ward (n = 1), in-patient addiction units, non-OAT out-patient addiction units and psychiatric facilities (n = 17). Three of the OAT facilities closed during the study period, though they provided data for the study. An additional map shows the location of units in more detail [see Supplementary Fig. 1, Additional File 1]. Throughout this study we refer to participants having reported naloxone use for overdose reversals on three occasions or more as “Supersavers”, a definition previously applied in similar research settings in our neighboring country Norway ( 18 ). While preventive training has been provided to the broader community, this study only presents data concerning individuals at risk of own overdose who received naloxone through the regional program, as to this date, naloxone has not been available to others. 2.4. Procedures and data management Data regarding all individuals participating in OEND were collected on a regular basis (every six months) from key instructors at all participating units. Program coordinators (KT and PI) provided a template (pen-and-paper or digital) for each unit to use when reporting all collected data on naloxone events. Program coordinators then transferred all new events to an Excel file unique to every unit. This was returned to the key instructors for control whereafter reported data accuracy was confirmed by telephone. Data collected from all the units during the five-year period was compiled into an Excel file and transferred to SPSS for analysis. Variables included unit providing initial training and naloxone, type of unit, city/town, date of inclusion, year of birth, gender and numbers of kits issued for replenishment, and what had happened to the previous kit (lost/stolen/given to someone else/used on someone else/ used on oneself/not known). Additional variables were constructed: Returned for refill, used naloxone (used on someone else or oneself), supersaver (previously described in the literature as having used naloxone for overdose reversal on three or more occasions ( 18 ), or having used naloxone 0–2 times. While a total number of 3215 refills were reported during the study period, refills due to previous naloxone having expired (n = 815) were excluded from the analysis since a large batch with short expiry date had been distributed and had to be replaced within 6 months. Although most were replaced, some were simply given additional doses. As expired doses per definition are traded in for new naloxone, they do not make an additional contribution to the market. To certify that the numbers of kits out in the public are not exaggerated, these were excluded from the analysis. 2.5. Outcome measures The measures examined a) participant characteristics, number of trained individuals, distribution, replenishment and use of naloxone for overdose reversal, b) reason for refill and differences in reports by participants trained at different types of units, c) annual enrolment and distribution in relation to previous recommendations of > 100 enrolments per 100,000 inhabitants ( 5 ) and distribution in relation to annual overdose death rates, where the recommended target of naloxone distribution is set to 20 times the annual opioid overdose death rates in the county ( 8 ) and finally, d) Supersaver characteristics and reports of overdose reversals in relation to non-Supersavers. 2.6. Statistical analysis Descriptive statistics were used to describe baseline demographic characteristics (gender, year of birth, training facility). Numbers of previous kits used for overdose reversal on self, someone else, had been lost, given to someone else, stolen and or kits that could not be accounted for (i.e., the person returning for refill did not know what had happened to the previous kit) were described for all participating units, and respectively for NSPs, OATs and in-patient facilities. Students’ t-test was employed to analyze whether differences between the types of units were significant. In analyzing naloxone replenishment, use and type of facility, data from in-patient facilities were excluded due to low numbers of refills. This study covers all events attached to naloxone in the region, regardless of acceptance of inclusion in the original study ( 9 ). Unlike that study, a 30-month follow-up based on personal ID-numbers, this study focusses on the distribution (and refill) of naloxone kits at each unit of initial training. The analysis included all reports of what had become of the previously distributed kit (used on self, used on other, lost, stolen or had been given to someone else) thus accounting for regional use and coverage. In the analysis of enrolment and naloxone distribution in relation to suggested targeted rates, opioid related deaths among individuals in Skåne County, aged 15 and older at the time of death, with X42 or Y12 diagnoses were in 2018 36 individuals, respectively 37 and 31 in 2019 and 2020. In 2021, 28 fatalities were registered. With no available statistics for 2022, an average of 33 deaths were used (National causes of death register). The analysis employed the targets previously suggested by Bird et al. (2015) ( 8 ) as 20 times the number of annual opiate-related fatalities, and a minimum of 9 times annual fatalities, and by Walley et al. (2013) ( 5 ) suggesting enrolment to be 100 or more per 100 000 population. Reports of Supersavers were described for all participating units, and for NSPs and OATs respectively. Participant characteristics (age, gender, type of facility returned to for refill) of Supersavers were compared to that of individuals returning for refill reported less than three overdose reversals where naloxone had been used. Differences between groups were analyzed using Chi-Square-test, with the exception for age where Mann-Whitney U-test was applied. P-values < 0.05 with 95% CI was found to be statistically significant. The collected data was analyzed using SPSS Statistics Version 29.0 ( 19 ) and analyzed through descriptive statistics, chi-2-test and Students’ t-test. 3. Results 3.1. Participants characteristics The majority (66%) of all participants (n = 2685) received training and an initial kit with two naloxone doses at one of the OAT facilities, while patients recruited at NSPs, or in-patient facilities, represented 17% respectively [Table 1 ]. Table 1 Baseline characteristics of individuals receiving initial overdose education and take-home naloxone (n = 2685) Training unit and initial kit N (%) Needle and syringe program 459 (17.1) Opioid agonist treatment 1782 (66.4) In-patient 444 (16.5) Gender a Male 1858 (70.6) Female 773 (29.4) Age b Mean age (years/SD) 39.5 (11.5) Median age (years/range) 38.0 (56; 18–74) 18–29 years 587 (22.5) 30–39 years 857 (32.9) 40–49 years 615 (23.6) > 50 years 549 (21.1) Year of inclusion 2018 519 (19.7) 2019 718 (27.2) 2020 435 (16.5) 2021 435 (16.5) 2022 374 (14.2) 2023 160 (6.1) *Patients in outpatient addiction treatment facilities included in this group (non-OAT) n = 54 a missing n = 23, b missing n = 77 The cohort represented individuals between 18 and 74 years with a mean age of 39.5 years and 71% were male. Thirty-three percentages of all participants were allocated in the age group 30–39 years, while between 21 to 24% were represented in the other age groups [Table 1 ]. The highest mean age was found among male participants included at OATs (41 years), whereas the lowest mean age was seen among women trained at in-patient facilities (34 years). In general, a younger cohort appeared to have been reached through in-patient facilities. An additional table shows this in more detail [see Supplementary Table A, Additional file 2]. 3.2. Naloxone distribution rate, replenishment, and use – an overview of 6-month intervals After exclusion of all refills due previous naloxone having expired (n = 851), a total number of 5049 kits each containing two doses of IN naloxone had been distributed to 2685 trained individuals, between June 2018 – June 2023. Figure 2 , below, illustrates an overview of patients trained, naloxone distributed, and reports of naloxone used for overdose reversal during 6-month intervals. This five-year follow-up indicates certain trends; a decrease in recruitment of new participants, and a slight increase in both distribution and of naloxone having been reported as used for overdose reversal. The most recent 6-month period shows the highest number of distributed kits [Figure 2 ]. 3.3. Reason for naloxone refill, use and type of unit During the five-year period, 2364 refills were reported of which a total number of 926 overdose reversals were performed. The majority (93%) had been used for overdose reversal on someone else than of the person who naloxone had been prescribed to. Although most patients had been provided training and THN at an OAT facility, significantly more reversals on others were reported by participants trained at, and returning to, NSP for refill ( p < 0.01), compared to reversals by those trained at, and returning to, OATs. No significant difference between patients trained and returning to OATs versus NSPs was found regarding reversals that had been made on the person reporting the incident. Significant differences between groups were found regarding reports on naloxone lost or given to other ( p < 0.01 and p = 0.04, respectively) [Table 2 ]. Mean number of refills per trained individual were 2.8 at NSPs while 0.6 at OATs. Mean number of overdose reversals per trained individual were 1.4 among participants trained at NSPs, while 0.2 for those trained at OAT. Naloxone reported as lost or given to someone else ( p < 0.01 respectively p = 0.04) was significantly more frequently reported by participants at NSP, while no significant differences were shown as for when naloxone had been stolen or when what happened to previous naloxone was reported as unknown [Table 2 ]. Table 2 Naloxone replenishment, use of previous naloxone and type of facility providing refill (N = 2364) All refills N (%) NSP refills N (%) OAT refills N (%) 95% CI Mean diff (Lower/Upper) t-test (2-sided) p -value Refills 2364 1294 983 1.416 (1.217—1.614) < 0.01* Overdose (OD) reversal 926 (39.2) 621 (48.0) 281 (28.6) 1.008 (0.706—1.311) < 0.01* Reversal of OD other 857 (36.3) 571 (44.0) 262 (26.7) 0.967 (0.660—1.275) < 0.01* Reversal OD on self 69 (2.9) 50 (3.9) 19 (1.9) 0.164 (-0.220—0.548) 0.396 Lost 741 (31.3) 431 (33.3) 289 (29.4) 0.579 (0.374—0.783) < 0.01* Given to other 328 (13.9) 143 (11.1) 179 (18.2) 0.270 (0.014—0.525) 0.04* Other (incl. stolen) 77 (3.3) 58 (4.5) 18 (1.8) 0.101 (-0.115—0.317) 0.353 Not known 292 (12.4) 41 (3.2) 216 (22.0) 0.020 (-0.107—0.147) 0.760 Expired doses were excluded (n = 851 in relation to all refills, of which n = 92 and n = 749 at NSPs and OATs respectively) In-patient refills (n = 87) have been excluded from this analysis due to its low numbers *p = < 0.05 3.4. Annual OEND enrolment and THN distribution in relation to recommendations Although annual distribution exceeded the recommended target of twenty times the annual opioid overdose deaths ( 8 ), the cumulative enrolment target on training and distribution did not exceed 100 per 100,000 inhabitants ( 5 ) until the second year [Table 3 ]. Table 3 Annual overdose education enrolment and naloxone distribution in relation to previously suggested targets a, c 1st year June 2018 –June 2019 2nd year June 2019 –June 2020 3rd year June 2020 – June 2021 4th year June 2021 – June 2022 5th year June 2022 – June 2023 Distribution Annual distribution, Skåne county 1045 1060 730 961 1253 Suggested annual distribution in relation to overdose deaths a, b 324–720 333–740 279–620 252–560 297–660 Cumulative distribution 1045 2105 2835 3796 5049 Annual distribution in per 100,000 inhabitants d 76 77 52 68 88 Cumulative distribution per 100,000 inhabitants d 76 152 203 270 356 Enrolment Annual enrolment, Skåne county 892 663 313 376 441 Annual enrolment per 100,000 inhabitants in Skåne county c, d 65 48 22 27 31 Cumulative enrolment 892 1555 1868 2244 2685 Cumulative enrolment rates per 100,000 inhabitants in Skåne county c, d 65 113 135 162 193 Refills due to previous naloxone expired have been excluded, n = 851 a Targeting to distribute 20 times the number of annual opiate-related fatalities, and a minimum of 9 times annual fatalities, rates suggested by Bird et al. (2015) ( 8 ) as crucial for naloxone to be present when overdoses occur. b Opioid related deaths among individuals in Skåne County, aged 15 and older at the time of death, with X42 or Y12 diagnoses were in 2018 36 individuals, respectively 37 and 31 in 2019 and 2020. In 2021, 28 fatalities were registered. With no available statistics for 2022, an average of 33 deaths were used (National causes of death register). c Walley et al. (2013) ( 5 ) Targeting enrolment of 100, or more, individuals in OEND per 100 000 population. d Population in Skåne https://www.statistikdatabasen.scb.se/ 2018–2019: 1369996, 2019–2020: 1383582, 2020–2021:1395881, 2021–2022: 1408375, 2022–2023: 1418053 3.5. Supersavers A first analysis of the material identified 74 cases where individuals had used naloxone on three or more occasions for overdose reversal, of which 50 could be traced throughout the entire period, eliminating cases for those who may have reported three or more overdose reversals at multiple units. The percentage of women among Supersavers was not significantly higher (38%) than among individuals who had used naloxone 0–2 times (31%, p = 0.33), nor were there any significant differences in age between groups. Accessing training and refill through NSPs were a significant predictor of being a supersaver ( p < 0.01). Supersavers more often reported previously having administered naloxone on someone else ( p < 0.01), having been administered on them by someone else ( p < 0.01), or previous naloxone having been lost ( p < 0.01). For the alternatives of previous naloxone having been given to someone else, stolen/other, or not knowing what had happened, or of the naloxone having expired, there were no significant differences between the groups [Table 4 ]. Among men in the supersaver group, the mean number of overdose reversals was 5.1, while women had reported an average of 6.2. Table 4 Participants returning for refill – Zero to two overdose reversals compared to Supersavers (three or more reversals) Return for refill (all) (n = 559) Naloxone used 0–2 times (n = 517) Supersavers (Naloxone used ≥ 3 times) (n = 50) p -value Male n (%) 377 (67.4) a 351 (67.9) a 31 (62.0) 0.333 Female n (%) 176 (31.5) a 160 (30.9) a 19 (38.0) Mean age (SD) 39.8 (10.5) a 39.9 (10.5) b 39.6 (11.4) 0.836 Median age (range) 38 (53; 20–73) a 38 (47; 20–67) b 36.5 (51; 22–73) Initial training NSP n (%) 230 (41.1) 188 (36.4) 44 (88.0) < 0.001* Initial training OAT n (%) 318 (56.9) 318 (61.5) 6 (12.0) Initial training In-patient n (%) 11 (2.0) 11 (2.1) 0 Refills (n) 1207 819 388 < 0.001* Mean number of refills (range) 2.16 (21; 1–22) 1.58 (10; 1–11) 7.76 (19; 3–22) Naloxone used for overdose reversal n (%) 536 (44.4) 244 (29.8) 292 (75.3) < 0.001* Naloxone use on others n (%) 490 (40.6) 215 (26.3) 275 (70.9) < 0.001* Mean OD reversals on others 0.88 0.42 5.50 Naloxone used on one-self n (%) 46 (3.8) 29 (3.5) 17 (4.4) 0.007* Mean OD reversals on one-self 0.08 0.07 0.34 Lost n (%) 339 (28.1) 276 (33.7) 63 (16.2) < 0.001* Given n (%) 169 (14.0) 146 (28.2) 23 (5.9) 0.064 Stolen/other n (%) 39 (3.2) 31 (3.8) 8 (2.1) 0.334 Not known n (%) 124 (10.3) 122 (14.9) 2 (0.0) 0.847 Participants who reported at another unit than those which provided initial training were excluded (loss to follow-up). Refills due to previous naloxone having expired have been excluded. *p = < 0.05 Pearson Chi-2-test for all analyzes except for age, for which Student’s t-test was applied. a Missing n = 6 4. Discussion To this date, there have been few studies covering long-term follow-up on broad-scale preventive training and distribution and what it takes to achieve a significant reduction in overdose mortality. The results show that annual naloxone distribution exceeded the target of 20 times annual opioid overdose deaths recommended by Bird et al., ( 8 ), though neither the annual target exceeding 100 enrolments or distributed kits per 100,000 inhabitants was met, whereas the cumulative enrolment and distribution exceeded 100 per 100,000 inhabitants ( 5 ) during the second year. Although these numbers may be seen at somewhat disappointing, they do still show an effect on overdose related deaths in relation to the population in Skåne ( 7 ). If resources are limited, the recommendation is for naloxone programs to prioritize individuals with own risk for overdose ( 20 ). In our case, the naloxone program was implemented in an already existing infrastructure of needle and syringe programs and addiction facilities and although naloxone and additional material was covered by the region, there was no addition to the workforce when it came to training and distribution of naloxone for patients. This meant that there was a natural limitation as the additional work was added to an already heavy workload generally which is why it was of great importance to initially focus on individuals with the most pressing needs, at risk of own overdose, and to give them instructions and training materials enabling them to inform individuals in their near proximity on how to identify an overdose, what to do when witnessing an overdose and where naloxone was kept. Additionally, by giving their kit to someone else in need, they could return to pick up a new kit for themselves. The sub-analysis of when in time Supersavers versus those returning for refill reporting to have used naloxone on zero to two occasions indicated that at-risk individuals were prioritized throughout the five-year period. An additional table shows this more in detail [see Supplementary Table B, Additional file 3]. As with data from the National Naloxone Programme in Scotland, our regional data was not bound to any information on the individual level. The Swedish Ethical Review Authority confirmed that acceptance to partake in the study was not needed, which enabled this study to analyze all events in connection to the naloxone program during a longer time span (5 years) and serve as a control to whether study participants and events presented in our previous study covering the 30-month follow-up ( 9 ) were representative in relation to all trained individuals. This data is also important from the perspective that our recent study showed a significant difference in mortality after implementation in relation to a historical period, before naloxon became available ( 7 ). This study will also provide insight into the infrastructure and program development that led to these results. A decision was made to exclude refills due to naloxone having expired as these merely were replacements to be returned to the pharmacy. Although, in some cases a new kit was simply given without the actual return, this interpretation seemed to be more reasonable. After having excluded the 851 refills due to passed expiry date, the remaining 5049 events included 2364 (46%) refills, of which previous naloxone reportedly had been used for overdose reversal in 39% (n = 926) cases. This is a somewhat lower percentage than that of 60% reported in our previous 30-month follow-up. To some extent, the difference could be explained by the expansion of the program, initially targeting individuals with a higher risk of overdose involvement. Also, as this data includes not only participants who were interested in participating in the study, but individuals in this broader cohort may be less inclined to report back. In relation to international research, the proportion of refills that had been used for overdose reversals varied between 39–69% ( 21 – 25 ), leaving our results at the lower end of this span. Fear of negative consequences related to OAT may result in underreporting naloxone used in OD reversals, as being suspected of illicit drug use is enough to lose privileges of take-home medications and instead being obliged to daily visits to the clinic for supervised medical intake. Fear of social welfare being contacted if suspected of drug use while caring for minors, a matter of which international research has described being a barrier especially for women when it comes to seeking treatment and/or harm reduction services ( 26 , 27 ). Employing a more naturalistic comparison, examining the ratio of naloxone use for overdose reversals in relation to refills (expired excluded) on a community level of the National Naloxone Programme in Scotland, the 5-year follow-up demonstrates a ratio of 38% ( 28 ) which is more in congruence with our results at 39%. A systematic review by McDonald and Strang ( 29 ) showed a broad variation of used naloxone in relation to total distribution (4–67%), in which studies with more than 1500 distributed kits showed a variation between 9 and 28%. Here, Skåne is placed somewhere in the middle, reaching 18%. In spite of initial scepticism of naloxone related to stigma, high staff turnover, negative effects of the pandemic, and a steady increase of OAT patients in Skåne, from 1579 to 2226, during the study period, OEND enrolment within this population has been highly effective. Due to patients having to visit their clinic regularly according to the Swedish treatment regimen and to mandatory naloxone training at OATs in Skåne, there has been a steady increase of patients receiving OEND, where 79% had been included in June 2023. Although a majority had received training through OATs, overdose reversals were more frequently reported among participants returning to NSPs for refill. This is not surprising as individuals who actively use drugs are more likely to witness more overdoses ( 5 , 9 , 10 , 18 , 20 ). Compared to the 30-month follow-up, an increase in overdose reversals were reported at NSPs (67.1% vs. 53.7%) and an increase in participants trained at in-patient facilities from 11–17%, respectively from 15–17% at NSPs, while patients trained at OAT are reduced from 74–66%, implying a continuously high engagement by NSP visitors. These numbers imply the importance of a constant need for NSPs to be prioritized as main hubs for overdose prevention training and naloxone distribution ( 9 ). As NSPs and OATs serve as a continuum rather than two separate entities, it emphasizes the importance of continued work to stimulate training and distribution to patients at OATs as the risk of overdose continue to exist even though, for most, on a lower scale ( 30 ). While the continuum of care between OAT and NSP with its high regional availability has offered patients high access to training and take-home naloxone, in-patient facilities provide the opportunity of reaching individuals who for some reason cannot be reached at NSPs and OATs. As previously described by Bennett et al., ( 31 ), people who use drugs and their peers turn to “nodes” or “hubs” of individuals recognized to possess increased experience and knowledge, and that naloxone programs should reach out to these peer public health workers whereby they may serve as an effective link from mainstream healthcare to hard-to-reach individuals ( 31 ). More recent data from Norway suggest Supersavers, having reported overdose reversal with naloxone on three or more occasions, to be younger, more commonly use opioids actively and have witnessed more overdoses at baseline than participants who reported between zero and two reversals upon refill. Neither our nor the Norwegian Supersavers ( 18 ) showed any significant differences in gender, although a larger percentage of women were represented in both the Swedish and the Norwegian supersaver-cohorts. In our data, fifty individuals could be traced throughout the five-year timeframe having reported three or more reversals on others, with no evidence of Supersavers generally being younger. The lack of significant results may at least partly be explained by a large percentage being loss to follow up (33%). Approximately 50% of Supersavers had been trained during 2018, compared to less than 20% of all trained individuals [See Supplementary Table B, Additional file 2], indicating that this was a highly prioritized group from the start. The Norwegian findings concerning opioid use and having witnessed overdoses ( 18 ) could not be studied among our participants, though as having received initial training and naloxone kit through NSPs was significantly more common among Supersavers ( p < 0.01), this could serve as a proxy for being more actively involved in substance use. Supersavers represented less than 2% of all trained individuals, and less than 9% of those returning for refill however reported more than half (54%) of all reversals registered at initial training unit. This calls for a need to secure adequate and requested support for these individuals´ energy and motivation to continue their important efforts to keep peers, family members and acquaintances alive. No major differences between age and gender distribution were found when comparing the current data to that of the 30-month follow-up and age and gender distribution was also found to be representative to the whole population[2] . The 6-month interval report from all participating units depicts an increase in distribution and naloxone used for overdose reversal, while the number of trained individuals has been reduced over time. An interpretation of this data could be that the need for naloxone has not yet been saturated as an increase of naloxone distribution also increases the number of reports of naloxone used for overdose reversals, while the need for initial training has been reduced due to most at-risk individuals having received initial training and kit. Although Sweden was not subjected to any lock-down during the Covid-19 pandemic, it did put a substantial strain on healthcare in general. With high numbers of staff themselves being on sick-leave and parts of remaining staff being allocated to care for the growing number of in-patients, the core of everyday work had to be prioritized leaving less opportunity for preventive training and naloxone distribution ( 32 ). This is likely to have caused a drop in naloxone distribution, registered in the period covering data between December 2019 and June 2020 with a further reduction in distribution the following period, while the trend for the whole period indicates an increase. Skåne Naloxone program has shown that effective multi-site implementation of THN is possible, even in Sweden, a country traditionally identified as a high-threshold nation with respect to harm reduction interventions. This model can easily be implemented in other settings and the program continues to expand. Between the 30-month and the 5-year follow-up the program was implemented at an additional seven units. Allowing for future rapid upscaling an educational film on overdose prevention and practical training has been launched. In an effort to further broaden access to naloxone The Swedish Medicines Agency announced for Naloxone to be made available at pharmacies over the counter during 2024 ( 33 ). There are several limitations to this study. The study is based on self-reported data and may be subject to recall and social desirability bias. Fear of stigma, or fear of losing benefits of take-home OAT-medication, may also lead to individuals preferring to report previous doses as lost, not known or given to someone else rather than being used in reversals on oneself. Data was only available for those returning for refill, therefore overdose events may have been missed as there was no other active follow-up. As data initially was collected primarily for clinical follow-up purposes, there was no identification number which could be traced. This meant that a rather high proportion of events had to be counted as “lost to follow-up” as only those returning to the unit where they had received their initial training could be followed. Also, the definition of a supersaver was based on reports from the initial training unit whereby data of additional refills made at other units was lost on an individual level. The actual number of Supersavers may therefore be higher than reported here. Despite these limitations, through this data we were able to follow a large proportion of the events reported over the first five years of these regional program with 2685 participants having received take-home naloxone, theoretical and practical overdose prevention training. Conclusions Large scale implementation of overdose education and naloxone distribution using the existing infrastructure of low-threshold facilities is effective in reaching individuals at risk of own overdose. With this data, all events involving take-home naloxone distributed to lay persons in the region could be studied. The distribution target, in relation to annual overdose deaths, were met while, on a population level, cumulative enrolment and distribution targets were met during the second year. Compared to the 30-month follow-up, OAT facilities continued to be the major provider of training to at-risk individuals, though reversals are still primarily reported through patients returning to NSPs implying the importance of a continuous need for NSPs to be prioritized when it comes to overdose prevention training and naloxone distribution. As a small proportion of enrolees represent a large proportion of reversals, their actions are of great importance to their community and to their peers. Measures need to be taken to assure sustainable conditions and sufficient support for them to continue in their efforts to save lives. Abbreviations IN Intranasal Naloxone NSP Needle and Syringe Program OAT Opioid Agonist Treatment OEND Overdose Education and Naloxone Distribution THN Take-Home Naloxone Declarations Ethics approval and consent to participate The study was conducted in accordance with the World Medical Association Declaration of Helsinki (2013) (34). Both the original application (no. 2018/300) and changes thereof (no. 2020-05176) was approved by the Swedish Ethical Review authority, and by its predecessor Lund Regional Ethics Committee, Lund, Sweden. As this study did not collect any data containing personal information The Swedish Ethical Review authority concluded that there was no need for a consent to participate, nor for publication. Consent for publication As this study did not collect any data containing personal information The Swedish Ethical Review authority concluded that there was no need for a consent to participate, nor for publication. Availability of data and materials The SPSS data used to support the findings of this study are restricted by the Regional Ethics Board, Lund, Sweden, to protect people’s privacy. The data are not publicly available due to the sensitivity of substance use and due to participant privacy concerns. Though, data is available from the corresponding author on request, for researchers who meet the criteria for access to confidential data. Competing interest AH’s researcher position at Lund University is sponsored by the state-owned gambling operator of Sweden, AB Svenska Spel. He also has funding from the research council of the same state-owned gambling operator and from the research council of the Swedish alcohol monopoly. None of these organizations have any role in the present research. Authors KT, PI, and DD declare that they have no conflict of interest regarding the publication of this article. Funding This work was financially supported by grants from Region Skåne for Katja Troberg, and by regional health care research funding (‘Young researcher ALF’ and ‘ALF project’ grants, Region Skåne, Sweden) to Disa Dahlman and to Anders Håkansson, respectively. Authors’ contributions AH is the principal investigator of the Naloxone project in Skåne. The original approach to the manuscript was developed by AH, KT, DD and PI. During the five-year study period, data was collected and organized on a six-month interval by KT and PI. KT performed the statistical analysis and was the major contributor in writing the manuscript, while PI, DD and AH all contributed to the manuscript. All have read and approved the final manuscript. Acknowledgements The authors would like to thank the staff at all NSPs, OATs and addiction facilities in Skåne for their help with training, distribution and monitoring of the program and for collecting and submitting data. The authors are also grateful to all the participating individuals for engaging in this program, participating in training and of carrying naloxone, without you there would be no program. References World Health Organization (WHO). Opioid overdose. https://www.who.int/news-room/fact-sheets/detail/opioid-overdose#:~:text=Worldwide%2C%20about%20600%20000%20deaths,of%20opioid%20overdose%20in%202019 (2023). Accessed 17 June 2024. European Monitoring Centre for Drugs and Drug Addiction and Europol. EU Drug Market: Heroin and other opioids — In-depth analysis. https://www.euda.europa.eu/publications/eu-drug-markets/heroin-and-other-opioids_en. (2024). Accessed 2 October 2024. Martins SS, Sampson L, Cerdá M, Galea S. Worldwide Prevalence and Trends in Unintentional Drug Overdose: A Systematic Review of the Literature. Am J Public Health. 2015;105(11):e29-49. Baca CT, Grant KJ. Take-home naloxone to reduce heroin death. Addiction. 2005;100(12):1823-31. 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Troberg K, Isendahl P, Blomé MA, Dahlman D, Håkansson A. Characteristics of and Experience Among People Who Use Take-Home Naloxone in Skåne County, Sweden. Frontiers in Public Health. 2022;10. Rowe C, Santos GM, Vittinghoff E, Wheeler E, Davidson P, Coffin PO. Predictors of participant engagement and naloxone utilization in a community-based naloxone distribution program. Addiction. 2015;110(8):1301-10. Clark AK, Wilder CM, Winstanley EL. A systematic review of community opioid overdose prevention and naloxone distribution programs. J Addict Med. 2014;8(3):153-63. Ericson Ø B, Eide D, Lobmaier P, Clausen T. Risks and overdose responses: Participant characteristics from the first seven years of a national take-home naloxone program. Drug Alcohol Depend. 2022;240:109645. European Union Drugs Agency (EUDA). Frequently asked questions (FAQ): drug overdose deaths in Europe. https://www.euda.europa.eu/publications/topic-overviews/drug-induced-deaths-faq_en (2024). Accessed 2 September 2024. 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Drug Alcohol Depend. 2017;173:17-23. Moustaqim-Barrette A, Papamihali K, Williams S, Ferguson M, Moe J, Purssell R, et al. Adverse events related to bystander naloxone administration in cases of suspected opioid overdose in British Columbia: An observational study. PloS one. 2021;16(10):e0259126. Lee N, Boeri M. Managing Stigma: Women Drug Users and Recovery Services. Fusio : the Bentley undergraduate research journal. 2017;1(2):65-94. Scheidell JD, Hoff L, Khan MR, Bennett AS, Elliott L. Parenting and childcare responsibilities, harm reduction service engagement, and opioid overdose among women and men who use illicit opioids in New York City. Drug Alcohol Depend Rep. 2022;3. National Naloxone Programme Scotland Monitoring Report 2015/16. National Health Services Scotland. Publication date 25 October 2016. McDonald R, Strang J. Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria. Addiction. 2016;111(7):1177-87. Sordo L, Barrio G, Bravo MJ, Indave BI, Degenhardt L, Wiessing L, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. Bmj. 2017;357:j1550. Bennett AS, Bell A, Tomedi L, Hulsey EG, Kral AH. Characteristics of an overdose prevention, response, and naloxone distribution program in Pittsburgh and Allegheny County, Pennsylvania. J Urban Health. 2011;88(6):1020-30. Ludvigsson JF. How Sweden approached the COVID-19 pandemic: Summary and commentary on the National Commission Inquiry. Acta Paediatr. 2023;112(1):19-33. Naloxon blir receptfritt [Naloxone available without prescription]. The Swedish Medicines Agency. https://www.lakemedelsverket.se/sv/nyheter/naloxon-blir-receptfritt. (2023). Accessed 3 September 2024. World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Jama.2013;310(20):2191-4. Footnotes Data collected July 2023 from all OAT units in Skåne by the regional Naloxone program coordinators. In comparison with data retrieved from the Region Skåne Head Office, Data Analysis and Register center and from the regional annual reports from NSPs, based on data from InfCare database. Additional Declarations Competing interest reported. AH’s researcher position at Lund University is sponsored by the state-owned gambling operator of Sweden, AB Svenska Spel. He also has funding from the research council of the same state-owned gambling operator and from the research council of the Swedish alcohol monopoly. None of these organizations have any role in the present research. Authors KT, PI, and DD declare that they have no conflict of interest regarding the publication of this article. Supplementary Files Additionalfile1SupplementaryFigure1UnitsincludedinSkneNaloxoneprogram.docx Additional file 1. Supplementary Figure 1. Units included in Skåne Naloxone program, June 2018 – June 2023. Additionalfile2SupplementaryTableABaselinecharacteristicsofindividualsreceivingtrainingandnaloxone.docx Additional file 2 - Supplementary Table A. Baseline characteristics of individuals receiving training and naloxone. Additionalfile3SupplementaryTableBYearofinitialtrainingandnaloxonedistribution.docx Additional file 3 - Supplementary Table B. Year of initial training and naloxone distribution. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5281562","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":367612422,"identity":"2c193388-45fb-473b-bb4e-f72f185f98d5","order_by":0,"name":"Katja Troberg","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCElEQVRIiWNgGAWjYBACCSA2gLMYKoD4AHMDAS3MIC0GUC1nQFoYCWthgGthbCNCi2T7+QMFPxj+5PNLNx/7+HXeNjm+A4xtEgx/bHBqkeZJZjDsYTCwnDnnWPJs2W23jSVBWhjb0nBqkWNIZjDgYTAwMLiRY8wsue124gawlobDuLXwP2Yw/APWkv+ZWXLO7foNEIf9x+0wiWQGY6gtzIwfG24nGIC1sB3A7f0Zjw2MZQyMDSTnHDNmZjh223DmYcZmi8S2ZJxaJM4nPjN8UyFnAAyxx4w/am7L8x1vPnjjwx87nFqAgM0AGv8MzDxgEogT8GkAKnkAYzH+wK9yFIyCUTAKRigAAA7tUKiWJh8xAAAAAElFTkSuQmCC","orcid":"","institution":"Faculty of Medicine, Department of Clinical Sciences Lund, Lund University, Lund","correspondingAuthor":true,"prefix":"","firstName":"Katja","middleName":"","lastName":"Troberg","suffix":""},{"id":367612423,"identity":"6c04ff0c-7bd2-4f4c-b0d9-a61892e5c402","order_by":1,"name":"Pernilla Isendahl","email":"","orcid":"","institution":"Department of Infectious Disease, University Hospital Skåne, Malmö","correspondingAuthor":false,"prefix":"","firstName":"Pernilla","middleName":"","lastName":"Isendahl","suffix":""},{"id":367612424,"identity":"f1b4b076-34ff-448e-8e88-bdf0f2355d52","order_by":2,"name":"Disa Dahlman","email":"","orcid":"","institution":"Center for Primary Health Care Research, Department of Clinical Sciences, Lund University/Region Skåne, Malmö","correspondingAuthor":false,"prefix":"","firstName":"Disa","middleName":"","lastName":"Dahlman","suffix":""},{"id":367612425,"identity":"da797203-b6bf-4c44-bac8-10a2c33a28bb","order_by":3,"name":"Anders Håkansson","email":"","orcid":"","institution":"Faculty of Medicine, Department of Clinical Sciences Lund, Lund University, Lund","correspondingAuthor":false,"prefix":"","firstName":"Anders","middleName":"","lastName":"Håkansson","suffix":""}],"badges":[],"createdAt":"2024-10-17 09:38:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5281562/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5281562/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12954-025-01255-3","type":"published","date":"2025-06-05T15:57:52+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":67290084,"identity":"610170d9-c10d-4fcd-9482-9d035ada9cca","added_by":"auto","created_at":"2024-10-23 09:59:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":4493,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"fig.png","url":"https://assets-eu.researchsquare.com/files/rs-5281562/v1/c65a29ec0689efeee0671a8a.png"},{"id":67290086,"identity":"44e19a2e-0af8-451d-9b9e-a3ec484ac91f","added_by":"auto","created_at":"2024-10-23 09:59:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":204629,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOEND Training, distributed kits and reports of previous naloxone used for overdose reversals, June 2018 - June 2023, 6-month intervals (refills due to expiry date have been excluded).\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5281562/v1/28be2f6cc5ee9f610fa005ec.png"},{"id":84242936,"identity":"23a610a0-84a4-4440-add6-95d050e2a608","added_by":"auto","created_at":"2025-06-09 16:12:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1355496,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5281562/v1/6fc9dcf5-d4d7-4415-9a3f-fd0ffa3c649e.pdf"},{"id":67290089,"identity":"ce2b9551-3a4a-4cf5-b303-20c3e9751ff8","added_by":"auto","created_at":"2024-10-23 09:59:07","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":539221,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 1. Supplementary Figure 1. Units included in Skåne Naloxone program, June 2018 – June 2023.\u003c/p\u003e","description":"","filename":"Additionalfile1SupplementaryFigure1UnitsincludedinSkneNaloxoneprogram.docx","url":"https://assets-eu.researchsquare.com/files/rs-5281562/v1/db6ce867ec08aa97902a2368.docx"},{"id":67290407,"identity":"0a3a003f-3e64-41b8-ad65-69a47041b424","added_by":"auto","created_at":"2024-10-23 10:07:07","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":16119,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 2 - Supplementary Table A. Baseline characteristics of individuals receiving training and naloxone.\u003c/p\u003e","description":"","filename":"Additionalfile2SupplementaryTableABaselinecharacteristicsofindividualsreceivingtrainingandnaloxone.docx","url":"https://assets-eu.researchsquare.com/files/rs-5281562/v1/5a2e012c5932ec9b21ae8bb1.docx"},{"id":67290405,"identity":"9c3af43b-75e7-40e4-b4de-3d415dbfa4e8","added_by":"auto","created_at":"2024-10-23 10:07:07","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":17894,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 3 - Supplementary Table B. Year of initial training and naloxone distribution.\u003c/p\u003e","description":"","filename":"Additionalfile3SupplementaryTableBYearofinitialtrainingandnaloxonedistribution.docx","url":"https://assets-eu.researchsquare.com/files/rs-5281562/v1/533742a3c34b60ac019793df.docx"}],"financialInterests":"Competing interest reported. AH’s researcher position at Lund University is sponsored by the state-owned gambling operator of Sweden, AB Svenska Spel. He also has funding from the research council of the same state-owned gambling operator and from the research council of the Swedish alcohol monopoly. None of these organizations have any role in the present research. Authors KT, PI, and DD declare that they have no conflict of interest regarding the publication of this article.","formattedTitle":"Broad-scale overdose education and naloxone distribution – 5-year follow-up of a regional program in Skåne County, Sweden","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eWith the World Health Organization\u0026rsquo;s estimate of approximately 125,000 people dying in 2019 from opioid overdose worldwide (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) overdose mortality and morbidity persist to present a pressing public health crisis. The harms of predominantly heroin, with increasing use of other illicit opioids such as methadone, oxycodone, buprenorphine, tramadol, fentanyl derivatives and lately also nitazenes (benzimidazole opioids), is continuously an urgent matter as these are linked to a majority (74%) of drug-related deaths in Europe (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). International research shows a prevalence of 17\u0026ndash;68% self-reported experience of an own non-fatal overdose among people who use drugs, while 50\u0026ndash;96% have witnessed someone else\u0026rsquo;s overdose (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In many cases these overdoses are preventable. For decades, naloxone has been used for overdose reversals, both in prehospital healthcare and by training and by providing laypersons with naloxone through overdose education and naloxone distribution (OEND) programs. With few adverse events, naloxone may effectively reverse opioid overdose if administered timely (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eLarge-scale programs are often effective in reaching individuals at-risk of own, or those witnessing overdose and have been significantly associated with reduced opioid overdose deaths (\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). For naloxone to be present when and where overdoses occur, it has been estimated that naloxone programs should aim to distribute 20 times the annual opiate overdose mortality rate, with a minimum of 9 times as many (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Research by Walley and colleagues (2013) (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) showed significant reductions in overdose deaths in communities where OEND had been implemented, with a 46% reduction of overdose deaths in communities where enrolment rates exceeded 100 per 100,000 inhabitants.\u003c/p\u003e \u003cp\u003eIn congruence with our previous findings (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), international research found overdose reversals predominantly being performed by individuals who themselves are at risk of overdose (\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Broad-scale provision of naloxone in Sweden is imperative as drug-related deaths are approximately four times higher than the European average (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), and where 88% of drug induced deaths involve opioids (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Therefore, by targeting a large proportion of at-risk individuals who are prepared to act in overdose situations would be a self-evident step trying to reduce overdose morbidity and mortality.\u003c/p\u003e \u003cp\u003eThis study aims to contribute to the growing, but yet scarce, body of literature on long-term follow-ups of systematic broad-scale OEND by 1) describing all naloxone-related events during the first five years of the naloxone program in Sk\u0026aring;ne county, 2) studying the naloxone distribution in relation to annual opioid overdose mortality rate (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), and evaluate whether the program reaches targeted recommendations of enrolment on a population level (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), 3) studying the core group of individuals who reported three or more overdose reversals, i.e. \u0026ldquo;Supersavers\u0026rdquo;. Success of the program is largely dependent on these individuals as they perform a large part of overdose reversals. Investigation into their situation and specific needs is imperative to assure provision and support to maintain sustainable conditions, thus, enabling them to continue their important work.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Study Design\u003c/h2\u003e \u003cp\u003eThis study is based on data from all participants who received OEND in Sk\u0026aring;ne county between June 2018 and June 2023. Upon completion of training and having received take-home naloxone (THN), containing two doses of intranasal naloxone (IN), year of birth, gender facility and date of training have been registered continuously over time by key-trainers at each participating unit. For trained individuals who returned for naloxone replenishment, initial training unit was noted, and participants were asked what had happened to previous dose/-s (used on one-self, used on someone else, lost, given to other, stolen, or not known). All kits were replenished, regardless of reason for refill of previous kit. Participating units reported data every six months to coordinators for Sk\u0026aring;ne Naloxone program.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Setting\u003c/h2\u003e \u003cp\u003eSk\u0026aring;ne Naloxone program was implemented in June 2018 and is situated in southernmost Sweden, in Sk\u0026aring;ne, a county with 1.4\u0026nbsp;million inhabitants. The program includes all opioid agonist treatment (OAT) facilities, needle and syringe programs (NSPs), in-patient addiction facilities and non-OAT outpatient facilities. The naloxone kit contains two doses of naloxone and is given to the patients directly after training, free of charge (described in detail previously in Troberg et al. (2020) (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNSPs in Sk\u0026aring;ne are run by the departments for infectious disease with physicians specialized in infections disease, nurses, assistant nurses, social workers, and midwives offering comprehensive free of charge healthcare including tests for blood borne viruses, vaccination for hepatitis A and B, and hepatitis C treatment besides providing visitors with clean needles and syringes.\u003c/p\u003e \u003cp\u003eOnly facilities specialized in psychiatry may provide OAT. On a national level, a survey referred to by The National Board of Health and Welfare showed that approximately 65 per 100,000 inhabitants were enrolled in OAT in 2022 (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), with low availability in rural areas. All regions are self-governing and in Sk\u0026aring;ne the situation is unique compared to the rest of Sweden as OATs are run by both public and privately owned healthcare providers, through a \u0026ldquo;choice of healthcare\u0026rdquo; system, rendering a much higher availability at 158/100,000[1]\u003ca class=\"FNLink\" href=\"#Fn1\" id=\"#FNLinkFn1\"\u003e\u003c/a\u003e. Swedish healthcare and medication are heavily subsidised by governmental fundings.\u003c/p\u003e \u003cp\u003eNaloxone is provided free of charge at all facilities included in the program. During the study period, naloxone could be prescribed by any physician. As of November 1\u003csup\u003est,\u003c/sup\u003e 2018, naloxone could also be prescribed by registered nurses. As with the majority of all prescribed medication, naloxone included in the high-cost protection scheme, a subsidy that sets an upper limit of individual costs for medication and medical care (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Study participants\u003c/h2\u003e \u003cp\u003eAll individuals (n\u0026thinsp;=\u0026thinsp;2685) took part of the theoretical and practical overdose prevention training and were provided with a naloxone-kit from one of the OEND facilities (n\u0026thinsp;=\u0026thinsp;52) in Sk\u0026aring;ne county. The study included the following facilities in the region: NSPs (n\u0026thinsp;=\u0026thinsp;4), OATs (n\u0026thinsp;=\u0026thinsp;30), emergency ward (n\u0026thinsp;=\u0026thinsp;1), in-patient addiction units, non-OAT out-patient addiction units and psychiatric facilities (n\u0026thinsp;=\u0026thinsp;17). Three of the OAT facilities closed during the study period, though they provided data for the study. An additional map shows the location of units in more detail [see Supplementary Fig.\u0026nbsp;1, Additional File 1].\u003c/p\u003e \u003cp\u003eThroughout this study we refer to participants having reported naloxone use for overdose reversals on three occasions or more as \u0026ldquo;Supersavers\u0026rdquo;, a definition previously applied in similar research settings in our neighboring country Norway (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhile preventive training has been provided to the broader community, this study only presents data concerning individuals at risk of own overdose who received naloxone through the regional program, as to this date, naloxone has not been available to others.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Procedures and data management\u003c/h2\u003e \u003cp\u003eData regarding all individuals participating in OEND were collected on a regular basis (every six months) from key instructors at all participating units. Program coordinators (KT and PI) provided a template (pen-and-paper or digital) for each unit to use when reporting all collected data on naloxone events. Program coordinators then transferred all new events to an Excel file unique to every unit. This was returned to the key instructors for control whereafter reported data accuracy was confirmed by telephone. Data collected from all the units during the five-year period was compiled into an Excel file and transferred to SPSS for analysis. Variables included unit providing initial training and naloxone, type of unit, city/town, date of inclusion, year of birth, gender and numbers of kits issued for replenishment, and what had happened to the previous kit (lost/stolen/given to someone else/used on someone else/ used on oneself/not known). Additional variables were constructed: Returned for refill, used naloxone (used on someone else or oneself), supersaver (previously described in the literature as having used naloxone for overdose reversal on three or more occasions (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), or having used naloxone 0\u0026ndash;2 times.\u003c/p\u003e \u003cp\u003eWhile a total number of 3215 refills were reported during the study period, refills due to previous naloxone having expired (n\u0026thinsp;=\u0026thinsp;815) were excluded from the analysis since a large batch with short expiry date had been distributed and had to be replaced within 6 months. Although most were replaced, some were simply given additional doses. As expired doses per definition are traded in for new naloxone, they do not make an additional contribution to the market. To certify that the numbers of kits out in the public are not exaggerated, these were excluded from the analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Outcome measures\u003c/h2\u003e \u003cp\u003eThe measures examined a) participant characteristics, number of trained individuals, distribution, replenishment and use of naloxone for overdose reversal, b) reason for refill and differences in reports by participants trained at different types of units, c) annual enrolment and distribution in relation to previous recommendations of \u0026gt;\u0026thinsp;100 enrolments per 100,000 inhabitants (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) and distribution in relation to annual overdose death rates, where the recommended target of naloxone distribution is set to 20 times the annual opioid overdose death rates in the county (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) and finally, d) Supersaver characteristics and reports of overdose reversals in relation to non-Supersavers.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6. Statistical analysis\u003c/h2\u003e \u003cp\u003eDescriptive statistics were used to describe baseline demographic characteristics (gender, year of birth, training facility). Numbers of previous kits used for overdose reversal on self, someone else, had been lost, given to someone else, stolen and or kits that could not be accounted for (i.e., the person returning for refill did not know what had happened to the previous kit) were described for all participating units, and respectively for NSPs, OATs and in-patient facilities. Students\u0026rsquo; t-test was employed to analyze whether differences between the types of units were significant.\u003c/p\u003e \u003cp\u003eIn analyzing naloxone replenishment, use and type of facility, data from in-patient facilities were excluded due to low numbers of refills.\u003c/p\u003e \u003cp\u003eThis study covers all events attached to naloxone in the region, regardless of acceptance of inclusion in the original study (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Unlike that study, a 30-month follow-up based on personal ID-numbers, this study focusses on the distribution (and refill) of naloxone kits at each unit of initial training. The analysis included all reports of what had become of the previously distributed kit (used on self, used on other, lost, stolen or had been given to someone else) thus accounting for regional use and coverage.\u003c/p\u003e \u003cp\u003eIn the analysis of enrolment and naloxone distribution in relation to suggested targeted rates, opioid related deaths among individuals in Sk\u0026aring;ne County, aged 15 and older at the time of death, with X42 or Y12 diagnoses were in 2018 36 individuals, respectively 37 and 31 in 2019 and 2020. In 2021, 28 fatalities were registered. With no available statistics for 2022, an average of 33 deaths were used (National causes of death register). The analysis employed the targets previously suggested by Bird et al. (2015) (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) as 20 times the number of annual opiate-related fatalities, and a minimum of 9 times annual fatalities, and by Walley et al. (2013) (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) suggesting enrolment to be 100 or more per 100 000 population.\u003c/p\u003e \u003cp\u003eReports of Supersavers were described for all participating units, and for NSPs and OATs respectively. Participant characteristics (age, gender, type of facility returned to for refill) of Supersavers were compared to that of individuals returning for refill reported less than three overdose reversals where naloxone had been used. Differences between groups were analyzed using Chi-Square-test, with the exception for age where Mann-Whitney U-test was applied.\u003c/p\u003e \u003cp\u003eP-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 with 95% CI was found to be statistically significant. The collected data was analyzed using SPSS Statistics Version 29.0 (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) and analyzed through descriptive statistics, chi-2-test and Students\u0026rsquo; t-test.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Participants characteristics\u003c/h2\u003e \u003cp\u003eThe majority (66%) of all participants (n\u0026thinsp;=\u0026thinsp;2685) received training and an initial kit with two naloxone doses at one of the OAT facilities, while patients recruited at NSPs, or in-patient facilities, represented 17% respectively [Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of individuals receiving initial overdose education and take-home naloxone (n\u0026thinsp;=\u0026thinsp;2685)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTraining unit and initial kit\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeedle and syringe program\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e459 (17.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpioid agonist treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1782 (66.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIn-patient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e444 (16.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1858 (70.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e773 (29.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean age (years/SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.5 (11.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian age (years/range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.0 (56; 18\u0026ndash;74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u0026ndash;29 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e587 (22.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30\u0026ndash;39 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e857 (32.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40\u0026ndash;49 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e615 (23.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e549 (21.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eYear of inclusion\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e519 (19.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e718 (27.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e435 (16.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e435 (16.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e374 (14.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e160 (6.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e*Patients in outpatient addiction treatment facilities included in this group (non-OAT) n\u0026thinsp;=\u0026thinsp;54\u003c/p\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e missing n\u0026thinsp;=\u0026thinsp;23, \u003csup\u003eb\u003c/sup\u003e missing n\u0026thinsp;=\u0026thinsp;77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe cohort represented individuals between 18 and 74 years with a mean age of 39.5 years and 71% were male. Thirty-three percentages of all participants were allocated in the age group 30\u0026ndash;39 years, while between 21 to 24% were represented in the other age groups [Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e]. The highest mean age was found among male participants included at OATs (41 years), whereas the lowest mean age was seen among women trained at in-patient facilities (34 years). In general, a younger cohort appeared to have been reached through in-patient facilities. An additional table shows this in more detail [see Supplementary Table A, Additional file 2].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Naloxone distribution rate, replenishment, and use \u0026ndash; an overview of 6-month intervals\u003c/h2\u003e \u003cp\u003eAfter exclusion of all refills due previous naloxone having expired (n\u0026thinsp;=\u0026thinsp;851), a total number of 5049 kits each containing two doses of IN naloxone had been distributed to 2685 trained individuals, between June 2018 \u0026ndash; June 2023. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e, below, illustrates an overview of patients trained, naloxone distributed, and reports of naloxone used for overdose reversal during 6-month intervals. This five-year follow-up indicates certain trends; a decrease in recruitment of new participants, and a slight increase in both distribution and of naloxone having been reported as used for overdose reversal. The most recent 6-month period shows the highest number of distributed kits [Figure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Reason for naloxone refill, use and type of unit\u003c/h2\u003e \u003cp\u003eDuring the five-year period, 2364 refills were reported of which a total number of 926 overdose reversals were performed. The majority (93%) had been used for overdose reversal on someone else than of the person who naloxone had been prescribed to. Although most patients had been provided training and THN at an OAT facility, significantly more reversals on others were reported by participants trained at, and returning to, NSP for refill (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01), compared to reversals by those trained at, and returning to, OATs. No significant difference between patients trained and returning to OATs versus NSPs was found regarding reversals that had been made on the person reporting the incident. Significant differences between groups were found regarding reports on naloxone lost or given to other (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01 and \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04, respectively) [Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e]. Mean number of refills per trained individual were 2.8 at NSPs while 0.6 at OATs. Mean number of overdose reversals per trained individual were 1.4 among participants trained at NSPs, while 0.2 for those trained at OAT.\u003c/p\u003e \u003cp\u003eNaloxone reported as lost or given to someone else (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01 respectively \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04) was significantly more frequently reported by participants at NSP, while no significant differences were shown as for when naloxone had been stolen or when what happened to previous naloxone was reported as unknown [Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNaloxone replenishment, use of previous naloxone and type of facility providing refill (N\u0026thinsp;=\u0026thinsp;2364)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll refills\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNSP refills\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOAT refills\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003cp\u003eMean diff (Lower/Upper)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003et-test\u003c/p\u003e \u003cp\u003e(2-sided)\u003c/p\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRefills\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2364\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1294\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e983\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.416 (1.217\u0026mdash;1.614)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverdose (OD) reversal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e926 (39.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e621 (48.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e281 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.008 (0.706\u0026mdash;1.311)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReversal of OD other\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e857 (36.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e571 (44.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e262 (26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.967 (0.660\u0026mdash;1.275)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReversal OD on self\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.164 (-0.220\u0026mdash;0.548)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.396\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e741 (31.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e431 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e289 (29.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.579 (0.374\u0026mdash;0.783)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGiven to other\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e328 (13.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e143 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e179 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.270 (0.014\u0026mdash;0.525)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.04*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther (incl. stolen)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.101 (-0.115\u0026mdash;0.317)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.353\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot known\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e292 (12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e216 (22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.020 (-0.107\u0026mdash;0.147)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.760\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eExpired doses were excluded (n\u0026thinsp;=\u0026thinsp;851 in relation to all refills, of which n\u0026thinsp;=\u0026thinsp;92 and n\u0026thinsp;=\u0026thinsp;749 at NSPs and OATs respectively)\u003c/p\u003e \u003cp\u003eIn-patient refills (n\u0026thinsp;=\u0026thinsp;87) have been excluded from this analysis due to its low numbers\u003c/p\u003e \u003cp\u003e*p\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.4. Annual OEND enrolment and THN distribution in relation to recommendations\u003c/h2\u003e \u003cp\u003eAlthough annual distribution exceeded the recommended target of twenty times the annual opioid overdose deaths (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), the cumulative enrolment target on training and distribution did not exceed 100 per 100,000 inhabitants (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) until the second year [Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAnnual overdose education enrolment and naloxone distribution in relation to previously suggested targets a, c\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1st year\u003c/p\u003e \u003cp\u003eJune 2018 \u0026ndash;June 2019\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2nd year\u003c/p\u003e \u003cp\u003eJune 2019 \u0026ndash;June 2020\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3rd year\u003c/p\u003e \u003cp\u003eJune 2020 \u0026ndash; June 2021\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4th year\u003c/p\u003e \u003cp\u003eJune 2021 \u0026ndash; June 2022\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5th year\u003c/p\u003e \u003cp\u003eJune 2022 \u0026ndash; June 2023\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDistribution\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnnual distribution, Sk\u0026aring;ne county\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1060\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e730\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e961\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1253\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuggested annual distribution in relation to overdose deaths \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e324\u0026ndash;720\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e333\u0026ndash;740\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e279\u0026ndash;620\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e252\u0026ndash;560\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e297\u0026ndash;660\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCumulative distribution\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2835\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3796\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5049\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnnual distribution in per 100,000 inhabitants \u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCumulative distribution per 100,000 inhabitants \u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e270\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e356\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEnrolment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnnual enrolment, Sk\u0026aring;ne county\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e892\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e663\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e313\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e376\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e441\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnnual enrolment per 100,000 inhabitants in Sk\u0026aring;ne county \u003csup\u003ec, d\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCumulative enrolment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e892\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1555\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1868\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2244\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2685\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCumulative enrolment rates per 100,000 inhabitants in Sk\u0026aring;ne county \u003csup\u003ec, d\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e135\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e193\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eRefills due to previous naloxone expired have been excluded, n\u0026thinsp;=\u0026thinsp;851\u003c/p\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e Targeting to distribute 20 times the number of annual opiate-related fatalities, and a minimum of 9 times annual fatalities, rates suggested by Bird et al. (2015) (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) as crucial for naloxone to be present when overdoses occur.\u003c/p\u003e \u003cp\u003e\u003csup\u003eb\u003c/sup\u003e Opioid related deaths among individuals in Sk\u0026aring;ne County, aged 15 and older at the time of death, with X42 or Y12 diagnoses were in 2018 36 individuals, respectively 37 and 31 in 2019 and 2020. In 2021, 28 fatalities were registered. With no available statistics for 2022, an average of 33 deaths were used (National causes of death register).\u003c/p\u003e \u003cp\u003e\u003csup\u003ec\u003c/sup\u003e Walley et al. (2013) (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) Targeting enrolment of 100, or more, individuals in OEND per 100\u0026nbsp;000 population.\u003c/p\u003e \u003cp\u003e\u003csup\u003ed\u003c/sup\u003e Population in Sk\u0026aring;ne \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.statistikdatabasen.scb.se/\u003c/span\u003e\u003cspan address=\"https://www.statistikdatabasen.scb.se/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e 2018\u0026ndash;2019: 1369996, 2019\u0026ndash;2020: 1383582, 2020\u0026ndash;2021:1395881, 2021\u0026ndash;2022: 1408375, 2022\u0026ndash;2023: 1418053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.5. Supersavers\u003c/h2\u003e \u003cp\u003eA first analysis of the material identified 74 cases where individuals had used naloxone on three or more occasions for overdose reversal, of which 50 could be traced throughout the entire period, eliminating cases for those who may have reported three or more overdose reversals at multiple units.\u003c/p\u003e \u003cp\u003eThe percentage of women among Supersavers was not significantly higher (38%) than among individuals who had used naloxone 0\u0026ndash;2 times (31%, p\u0026thinsp;=\u0026thinsp;0.33), nor were there any significant differences in age between groups. Accessing training and refill through NSPs were a significant predictor of being a supersaver (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e \u003cp\u003eSupersavers more often reported previously having administered naloxone on someone else (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01), having been administered on them by someone else (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01), or previous naloxone having been lost (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). For the alternatives of previous naloxone having been given to someone else, stolen/other, or not knowing what had happened, or of the naloxone having expired, there were no significant differences between the groups [Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAmong men in the supersaver group, the mean number of overdose reversals was 5.1, while women had reported an average of 6.2.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eParticipants returning for refill \u0026ndash; Zero to two overdose reversals compared to Supersavers (three or more reversals)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReturn for refill (all)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;559)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNaloxone used 0\u0026ndash;2 times\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;517)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSupersavers (Naloxone used\u0026thinsp;\u0026ge;\u0026thinsp;3 times)\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMale n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e377 (67.4) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e351 (67.9) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31 (62.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.333\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFemale n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e176 (31.5) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e160 (30.9) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19 (38.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMean age (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39.8 (10.5) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39.9 (10.5) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39.6 (11.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.836\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMedian age (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (53; 20\u0026ndash;73) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38 (47; 20\u0026ndash;67) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36.5 (51; 22\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eInitial training NSP n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e230 (41.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e188 (36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e44 (88.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eInitial training OAT n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e318 (56.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e318 (61.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (12.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eInitial training In-patient n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eRefills (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e819\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e388\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMean number of refills (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.16 (21; 1\u0026ndash;22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.58 (10; 1\u0026ndash;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.76 (19; 3\u0026ndash;22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNaloxone used for overdose reversal n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e536 (44.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e244 (29.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e292 (75.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNaloxone use on others n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e490 (40.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e215 (26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e275 (70.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean OD reversals on others\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNaloxone used on one-self n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17 (4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.007*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean OD reversals on one-self\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLost n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e339 (28.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e276 (33.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e63 (16.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGiven n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e169 (14.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e146 (28.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.064\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eStolen/other n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.334\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNot known n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e124 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e122 (14.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.847\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eParticipants who reported at another unit than those which provided initial training were excluded (loss to follow-up).\u003c/p\u003e \u003cp\u003eRefills due to previous naloxone having expired have been excluded.\u003c/p\u003e \u003cp\u003e*p\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.05 Pearson Chi-2-test for all analyzes except for age, for which Student\u0026rsquo;s t-test was applied.\u003c/p\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e Missing n\u0026thinsp;=\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eTo this date, there have been few studies covering long-term follow-up on broad-scale preventive training and distribution and what it takes to achieve a significant reduction in overdose mortality.\u003c/p\u003e \u003cp\u003eThe results show that annual naloxone distribution exceeded the target of 20 times annual opioid overdose deaths recommended by Bird et al., (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), though neither the annual target exceeding 100 enrolments or distributed kits per 100,000 inhabitants was met, whereas the cumulative enrolment and distribution exceeded 100 per 100,000 inhabitants (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) during the second year. Although these numbers may be seen at somewhat disappointing, they do still show an effect on overdose related deaths in relation to the population in Skåne (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). If resources are limited, the recommendation is for naloxone programs to prioritize individuals with own risk for overdose (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). In our case, the naloxone program was implemented in an already existing infrastructure of needle and syringe programs and addiction facilities and although naloxone and additional material was covered by the region, there was no addition to the workforce when it came to training and distribution of naloxone for patients. This meant that there was a natural limitation as the additional work was added to an already heavy workload generally which is why it was of great importance to initially focus on individuals with the most pressing needs, at risk of own overdose, and to give them instructions and training materials enabling them to inform individuals in their near proximity on how to identify an overdose, what to do when witnessing an overdose and where naloxone was kept. Additionally, by giving their kit to someone else in need, they could return to pick up a new kit for themselves. The sub-analysis of when in time Supersavers versus those returning for refill reporting to have used naloxone on zero to two occasions indicated that at-risk individuals were prioritized throughout the five-year period. An additional table shows this more in detail [see Supplementary Table B, Additional file 3].\u003c/p\u003e \u003cp\u003eAs with data from the National Naloxone Programme in Scotland, our regional data was not bound to any information on the individual level. The Swedish Ethical Review Authority confirmed that acceptance to partake in the study was not needed, which enabled this study to analyze all events in connection to the naloxone program during a longer time span (5 years) and serve as a control to whether study participants and events presented in our previous study covering the 30-month follow-up (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) were representative in relation to all trained individuals. This data is also important from the perspective that our recent study showed a significant difference in mortality after implementation in relation to a historical period, before naloxon became available (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). This study will also provide insight into the infrastructure and program development that led to these results.\u003c/p\u003e \u003cp\u003eA decision was made to exclude refills due to naloxone having expired as these merely were replacements to be returned to the pharmacy. Although, in some cases a new kit was simply given without the actual return, this interpretation seemed to be more reasonable. After having excluded the 851 refills due to passed expiry date, the remaining 5049 events included 2364 (46%) refills, of which previous naloxone reportedly had been used for overdose reversal in 39% (n = 926) cases. This is a somewhat lower percentage than that of 60% reported in our previous 30-month follow-up. To some extent, the difference could be explained by the expansion of the program, initially targeting individuals with a higher risk of overdose involvement. Also, as this data includes not only participants who were interested in participating in the study, but individuals in this broader cohort may be less inclined to report back. In relation to international research, the proportion of refills that had been used for overdose reversals varied between 39–69% (\u003cspan additionalcitationids=\"CR22 CR23 CR24\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e–\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), leaving our results at the lower end of this span. Fear of negative consequences related to OAT may result in underreporting naloxone used in OD reversals, as being suspected of illicit drug use is enough to lose privileges of take-home medications and instead being obliged to daily visits to the clinic for supervised medical intake. Fear of social welfare being contacted if suspected of drug use while caring for minors, a matter of which international research has described being a barrier especially for women when it comes to seeking treatment and/or harm reduction services (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEmploying a more naturalistic comparison, examining the ratio of naloxone use for overdose reversals in relation to refills (expired excluded) on a community level of the National Naloxone Programme in Scotland, the 5-year follow-up demonstrates a ratio of 38% (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e) which is more in congruence with our results at 39%. A systematic review by McDonald and Strang (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e) showed a broad variation of used naloxone in relation to total distribution (4–67%), in which studies with more than 1500 distributed kits showed a variation between 9 and 28%. Here, Skåne is placed somewhere in the middle, reaching 18%.\u003c/p\u003e \u003cp\u003eIn spite of initial scepticism of naloxone related to stigma, high staff turnover, negative effects of the pandemic, and a steady increase of OAT patients in Skåne, from 1579 to 2226, during the study period, OEND enrolment within this population has been highly effective. Due to patients having to visit their clinic regularly according to the Swedish treatment regimen and to mandatory naloxone training at OATs in Skåne, there has been a steady increase of patients receiving OEND, where 79% had been included in June 2023. Although a majority had received training through OATs, overdose reversals were more frequently reported among participants returning to NSPs for refill. This is not surprising as individuals who actively use drugs are more likely to witness more overdoses (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Compared to the 30-month follow-up, an increase in overdose reversals were reported at NSPs (67.1% vs. 53.7%) and an increase in participants trained at in-patient facilities from 11–17%, respectively from 15–17% at NSPs, while patients trained at OAT are reduced from 74–66%, implying a continuously high engagement by NSP visitors. These numbers imply the importance of a constant need for NSPs to be prioritized as main hubs for overdose prevention training and naloxone distribution (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). As NSPs and OATs serve as a continuum rather than two separate entities, it emphasizes the importance of continued work to stimulate training and distribution to patients at OATs as the risk of overdose continue to exist even though, for most, on a lower scale (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). While the continuum of care between OAT and NSP with its high regional availability has offered patients high access to training and take-home naloxone, in-patient facilities provide the opportunity of reaching individuals who for some reason cannot be reached at NSPs and OATs.\u003c/p\u003e \u003cp\u003eAs previously described by Bennett et al., (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), people who use drugs and their peers turn to “nodes” or “hubs” of individuals recognized to possess increased experience and knowledge, and that naloxone programs should reach out to these peer public health workers whereby they may serve as an effective link from mainstream healthcare to hard-to-reach individuals (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). More recent data from Norway suggest Supersavers, having reported overdose reversal with naloxone on three or more occasions, to be younger, more commonly use opioids actively and have witnessed more overdoses at baseline than participants who reported between zero and two reversals upon refill. Neither our nor the Norwegian Supersavers (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) showed any significant differences in gender, although a larger percentage of women were represented in both the Swedish and the Norwegian supersaver-cohorts. In our data, fifty individuals could be traced throughout the five-year timeframe having reported three or more reversals on others, with no evidence of Supersavers generally being younger. The lack of significant results may at least partly be explained by a large percentage being loss to follow up (33%). Approximately 50% of Supersavers had been trained during 2018, compared to less than 20% of all trained individuals [See Supplementary Table B, Additional file 2], indicating that this was a highly prioritized group from the start. The Norwegian findings concerning opioid use and having witnessed overdoses (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) could not be studied among our participants, though as having received initial training and naloxone kit through NSPs was significantly more common among Supersavers (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.01), this could serve as a proxy for being more actively involved in substance use. Supersavers represented less than 2% of all trained individuals, and less than 9% of those returning for refill however reported more than half (54%) of all reversals registered at initial training unit. This calls for a need to secure adequate and requested support for these individuals´ energy and motivation to continue their important efforts to keep peers, family members and acquaintances alive.\u003c/p\u003e \u003cp\u003eNo major differences between age and gender distribution were found when comparing the current data to that of the 30-month follow-up and age and gender distribution was also found to be representative to the whole population[2]\u003ca class=\"FNLink\" href=\"#Fn2\" id=\"#FNLinkFn2\"\u003e\u003c/a\u003e.\u003c/p\u003e \u003cp\u003eThe 6-month interval report from all participating units depicts an increase in distribution and naloxone used for overdose reversal, while the number of trained individuals has been reduced over time. An interpretation of this data could be that the need for naloxone has not yet been saturated as an increase of naloxone distribution also increases the number of reports of naloxone used for overdose reversals, while the need for initial training has been reduced due to most at-risk individuals having received initial training and kit. Although Sweden was not subjected to any lock-down during the Covid-19 pandemic, it did put a substantial strain on healthcare in general. With high numbers of staff themselves being on sick-leave and parts of remaining staff being allocated to care for the growing number of in-patients, the core of everyday work had to be prioritized leaving less opportunity for preventive training and naloxone distribution (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). This is likely to have caused a drop in naloxone distribution, registered in the period covering data between December 2019 and June 2020 with a further reduction in distribution the following period, while the trend for the whole period indicates an increase.\u003c/p\u003e \u003cp\u003eSkåne Naloxone program has shown that effective multi-site implementation of THN is possible, even in Sweden, a country traditionally identified as a high-threshold nation with respect to harm reduction interventions. This model can easily be implemented in other settings and the program continues to expand. Between the 30-month and the 5-year follow-up the program was implemented at an additional seven units. Allowing for future rapid upscaling an educational film on overdose prevention and practical training has been launched. In an effort to further broaden access to naloxone The Swedish Medicines Agency announced for Naloxone to be made available at pharmacies over the counter during 2024 (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere are several limitations to this study. The study is based on self-reported data and may be subject to recall and social desirability bias. Fear of stigma, or fear of losing benefits of take-home OAT-medication, may also lead to individuals preferring to report previous doses as lost, not known or given to someone else rather than being used in reversals on oneself. Data was only available for those returning for refill, therefore overdose events may have been missed as there was no other active follow-up.\u003c/p\u003e \u003cp\u003eAs data initially was collected primarily for clinical follow-up purposes, there was no identification number which could be traced. This meant that a rather high proportion of events had to be counted as “lost to follow-up” as only those returning to the unit where they had received their initial training could be followed. Also, the definition of a supersaver was based on reports from the initial training unit whereby data of additional refills made at other units was lost on an individual level. The actual number of Supersavers may therefore be higher than reported here.\u003c/p\u003e \u003cp\u003eDespite these limitations, through this data we were able to follow a large proportion of the events reported over the first five years of these regional program with 2685 participants having received take-home naloxone, theoretical and practical overdose prevention training.\u003c/p\u003e "},{"header":"Conclusions","content":"\u003cp\u003eLarge scale implementation of overdose education and naloxone distribution using the existing infrastructure of low-threshold facilities is effective in reaching individuals at risk of own overdose. With this data, all events involving take-home naloxone distributed to lay persons in the region could be studied. The distribution target, in relation to annual overdose deaths, were met while, on a population level, cumulative enrolment and distribution targets were met during the second year. Compared to the 30-month follow-up, OAT facilities continued to be the major provider of training to at-risk individuals, though reversals are still primarily reported through patients returning to NSPs implying the importance of a continuous need for NSPs to be prioritized when it comes to overdose prevention training and naloxone distribution. As a small proportion of enrolees represent a large proportion of reversals, their actions are of great importance to their community and to their peers. Measures need to be taken to assure sustainable conditions and sufficient support for them to continue in their efforts to save lives.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIN\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Intranasal Naloxone\u003c/p\u003e\n\u003cp\u003eNSP\u0026nbsp; \u0026nbsp; \u0026nbsp;Needle and Syringe Program\u003c/p\u003e\n\u003cp\u003eOAT \u0026nbsp; \u0026nbsp;Opioid Agonist Treatment\u003c/p\u003e\n\u003cp\u003eOEND\u0026nbsp;Overdose Education and Naloxone Distribution\u003c/p\u003e\n\u003cp\u003eTHN \u0026nbsp; \u0026nbsp;Take-Home Naloxone\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the World Medical Association Declaration of Helsinki (2013) (34). Both the original application (no. 2018/300) and changes thereof (no. 2020-05176) was approved by the Swedish Ethical Review authority, and by its predecessor Lund Regional Ethics Committee, Lund, Sweden. As this study did not collect any data containing personal information The Swedish Ethical Review authority concluded that there was no need for a consent to participate, nor for publication.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs this study did not collect any data containing personal information The Swedish Ethical Review authority concluded that there was no need for a consent to participate, nor for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe SPSS data used to support the findings of this study are restricted by the Regional Ethics Board, Lund, Sweden, to protect people\u0026rsquo;s privacy. The data are not publicly available due to the sensitivity of substance use and due to participant privacy concerns. Though, data is available from the corresponding author on request, for researchers who meet the criteria for access to confidential data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAH\u0026rsquo;s researcher position at Lund University is sponsored by the state-owned gambling operator of Sweden, AB Svenska Spel. He also has funding from the research council of the same state-owned gambling operator and from the research council of the Swedish alcohol monopoly. None of these organizations have any role in the present research. Authors KT, PI, and DD declare that they have no conflict of interest regarding the publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was financially supported by grants from Region Sk\u0026aring;ne for Katja Troberg, and by regional health care research funding (\u0026lsquo;Young researcher ALF\u0026rsquo; and \u0026lsquo;ALF project\u0026rsquo; grants, Region Sk\u0026aring;ne, Sweden) to Disa Dahlman and to Anders H\u0026aring;kansson, respectively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAH is the principal investigator of the Naloxone project in Sk\u0026aring;ne. The original approach to the manuscript was developed by AH, KT, DD and PI. During the five-year study period, data was collected and organized on a six-month interval by KT and PI. KT performed the statistical analysis and was the major contributor in writing the manuscript, while PI, DD and AH all contributed to the manuscript. All have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the staff at all NSPs, OATs and addiction facilities in Sk\u0026aring;ne for their help with training, distribution and monitoring of the program and for collecting and submitting data. The authors are also grateful to all the participating individuals for engaging in this program, participating in training and of carrying naloxone, without you there would be no program.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWorld Health Organization (WHO). Opioid overdose. https://www.who.int/news-room/fact-sheets/detail/opioid-overdose#:~:text=Worldwide%2C%20about%20600%20000%20deaths,of%20opioid%20overdose%20in%202019 (2023). Accessed 17 June 2024.\u003c/li\u003e\n\u003cli\u003eEuropean Monitoring Centre for Drugs and Drug Addiction and Europol. EU Drug Market: Heroin and other opioids \u0026mdash; In-depth analysis. https://www.euda.europa.eu/publications/eu-drug-markets/heroin-and-other-opioids_en. (2024). Accessed 2 October 2024.\u003c/li\u003e\n\u003cli\u003eMartins SS, Sampson L, Cerd\u0026aacute; M, Galea S. Worldwide Prevalence and Trends in Unintentional Drug Overdose: A Systematic Review of the Literature. Am J Public Health. 2015;105(11):e29-49. \u003c/li\u003e\n\u003cli\u003eBaca CT, Grant KJ. Take-home naloxone to reduce heroin death. Addiction. 2005;100(12):1823-31. \u003c/li\u003e\n\u003cli\u003eWalley AY, Xuan Z, Hackman HH, Quinn E, Doe-Simkins M, Sorensen-Alawad A, et al. Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. Bmj. 2013;346:f174. \u003c/li\u003e\n\u003cli\u003eBird SM, McAuley A, Perry S, Hunter C. Effectiveness of Scotland\u0026apos;s National Naloxone Programme for reducing opioid-related deaths: a before (2006-10) versus after (2011-13) comparison. Addiction. 2016;111(5):883-91. \u003c/li\u003e\n\u003cli\u003eH\u0026aring;kansson A, Alanko Blom\u0026eacute; M, Isendahl P, Landgren M, Malmqvist U, Troberg K. Distribution of intranasal naloxone to potential opioid overdose bystanders in Sweden: effects on overdose mortality in a full region-wide study. BMJ open. 2024;14(1):e074152. \u003c/li\u003e\n\u003cli\u003eBird SM, Parmar MK, Strang J. Take-home naloxone to prevent fatalities from opiate-overdose: Protocol for Scotland\u0026apos;s public health policy evaluation, and a new measure to assess impact. Drugs (Abingdon, England). 2015;22(1):66-76. \u003c/li\u003e\n\u003cli\u003eTroberg K, Isendahl P, Blom\u0026eacute; MA, Dahlman D, H\u0026aring;kansson A. Characteristics of and Experience Among People Who Use Take-Home Naloxone in Sk\u0026aring;ne County, Sweden. Frontiers in Public Health. 2022;10. \u003c/li\u003e\n\u003cli\u003eRowe C, Santos GM, Vittinghoff E, Wheeler E, Davidson P, Coffin PO. Predictors of participant engagement and naloxone utilization in a community-based naloxone distribution program. Addiction. 2015;110(8):1301-10. \u003c/li\u003e\n\u003cli\u003eClark AK, Wilder CM, Winstanley EL. A systematic review of community opioid overdose prevention and naloxone distribution programs. J Addict Med. 2014;8(3):153-63. \u003c/li\u003e\n\u003cli\u003eEricson \u0026Oslash; B, Eide D, Lobmaier P, Clausen T. Risks and overdose responses: Participant characteristics from the first seven years of a national take-home naloxone program. Drug Alcohol Depend. 2022;240:109645. \u003c/li\u003e\n\u003cli\u003eEuropean Union Drugs Agency (EUDA). Frequently asked questions (FAQ): drug overdose deaths in Europe. https://www.euda.europa.eu/publications/topic-overviews/drug-induced-deaths-faq_en (2024). Accessed 2 September 2024.\u003c/li\u003e\n\u003cli\u003eEuropean Monitoring Centre for Drugs and Drug Addiction (EMCDDA, now EUDA). European Drug Report 2023: Trends and Developments. https://www.euda.europa.eu/publications/european-drug-report/2023_en. (2023). Accessed 30 August 2023.\u003c/li\u003e\n\u003cli\u003eTroberg K, Isendahl P, Blom\u0026eacute; MA, Dahlman D, H\u0026aring;kansson A. Protocol for a multi-site study of the effects of overdose prevention education with naloxone distribution program in Sk\u0026aring;ne County, Sweden. BMC psychiatry. 2020;20(1):49. \u003c/li\u003e\n\u003cli\u003eReThink. Tillg\u0026auml;ngligheten till LARO-behandling i Sverige [OAT Availability in Sweden]. 2023. Contract No.: NP-GEN-SE-00056 Version 01 06-09-2023.\u003c/li\u003e\n\u003cli\u003eMedicines and high-cost protection in Sweden. Nordic Council. https://www.norden.org/en/info-norden/medicines-and-high-cost-protection-sweden (2023). Accessed 22 August 2024.\u003c/li\u003e\n\u003cli\u003eEide D, Lobmaier P, Clausen T. Who is using take-home naloxone? An examination of supersavers. Harm Reduct J. 2022;19(1):65. \u003c/li\u003e\n\u003cli\u003eIBM Corp. Released 2023. IBM SPSS Statistics for Windows, Version 29.0.2.0 Armonk, NY: IBM Corp.\u003c/li\u003e\n\u003cli\u003eBennett AS, Bell A, Doe-Simkins M, Elliott L, Pouget E, Davis C. From Peers to Lay Bystanders: Findings from a Decade of Naloxone Distribution in Pittsburgh, PA. J Psychoactive Drugs. 2018;50(3):240-6. \u003c/li\u003e\n\u003cli\u003eBanjo O, Tzemis D, Al-Qutub D, Amlani A, Kesselring S, Buxton JA. A quantitative and qualitative evaluation of the British Columbia Take Home Naloxone program. CMAJ open. 2014;2(3):E153-61. \u003c/li\u003e\n\u003cli\u003eEnteen L, Bauer J, McLean R, Wheeler E, Huriaux E, Kral AH, et al. Overdose prevention and naloxone prescription for opioid users in San Francisco. J Urban Health. 2010;87(6):931-41. \u003c/li\u003e\n\u003cli\u003eKatzman JG, Takeda MY, Greenberg N, Moya Balasch M, Alchbli A, Katzman WG, et al. Association of Take-Home Naloxone and Opioid Overdose Reversals Performed by Patients in an Opioid Treatment Program. JAMA Netw Open. 2020;3(2):e200117.\u003c/li\u003e\n\u003cli\u003eMadah-Amiri D, Clausen T, Lobmaier P. Rapid widespread distribution of intranasal naloxone for overdose prevention. Drug Alcohol Depend. 2017;173:17-23. \u003c/li\u003e\n\u003cli\u003eMoustaqim-Barrette A, Papamihali K, Williams S, Ferguson M, Moe J, Purssell R, et al. Adverse events related to bystander naloxone administration in cases of suspected opioid overdose in British Columbia: An observational study. PloS one. 2021;16(10):e0259126. \u003c/li\u003e\n\u003cli\u003eLee N, Boeri M. Managing Stigma: Women Drug Users and Recovery Services. Fusio : the Bentley undergraduate research journal. 2017;1(2):65-94.\u003c/li\u003e\n\u003cli\u003eScheidell JD, Hoff L, Khan MR, Bennett AS, Elliott L. Parenting and childcare responsibilities, harm reduction service engagement, and opioid overdose among women and men who use illicit opioids in New York City. Drug Alcohol Depend Rep. 2022;3.\u003c/li\u003e\n\u003cli\u003eNational Naloxone Programme Scotland Monitoring Report 2015/16. National Health Services Scotland. Publication date 25 October 2016. \u003c/li\u003e\n\u003cli\u003eMcDonald R, Strang J. Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria. Addiction. 2016;111(7):1177-87.\u003c/li\u003e\n\u003cli\u003eSordo L, Barrio G, Bravo MJ, Indave BI, Degenhardt L, Wiessing L, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. Bmj. 2017;357:j1550.\u003c/li\u003e\n\u003cli\u003eBennett AS, Bell A, Tomedi L, Hulsey EG, Kral AH. Characteristics of an overdose prevention, response, and naloxone distribution program in Pittsburgh and Allegheny County, Pennsylvania. J Urban Health. 2011;88(6):1020-30.\u003c/li\u003e\n\u003cli\u003eLudvigsson JF. How Sweden approached the COVID-19 pandemic: Summary and commentary on the National Commission Inquiry. Acta Paediatr. 2023;112(1):19-33.\u003c/li\u003e\n\u003cli\u003eNaloxon blir receptfritt [Naloxone available without prescription]. The Swedish Medicines Agency. https://www.lakemedelsverket.se/sv/nyheter/naloxon-blir-receptfritt. (2023). Accessed 3 September 2024.\u003c/li\u003e\n\u003cli\u003eWorld Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Jama.2013;310(20):2191-4.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Footnotes","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e Data collected July 2023 from all OAT units in Sk\u0026aring;ne by the regional Naloxone program coordinators.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e In comparison with data retrieved from the Region Sk\u0026aring;ne Head Office, Data Analysis and Register center and from the regional annual reports from NSPs, based on data from InfCare database.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"harm-reduction-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"harj","sideBox":"Learn more about [Harm Reduction Journal](http://harmreductionjournal.biomedcentral.com/)","snPcode":"12954","submissionUrl":"https://submission.nature.com/new-submission/12954/3","title":"Harm Reduction Journal","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Take-home naloxone, Overdose Education and Naloxone Distribution, People who use opioids, harm reduction","lastPublishedDoi":"10.21203/rs.3.rs-5281562/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5281562/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eOpioid use disorder is a chronic disorder with a high risk of overdose related morbidity and mortality where a large proportion of these can be averted by timely administration of the antidote naloxone. For naloxone to be present when and where overdoses occur, broad-scale overdose education and naloxone distribution (OEND) must be established. A regional naloxone program was implemented in 2018, in Sk\u0026aring;ne County, Sweden. This five-year follow-up aims to describe all naloxone-related lay-person events and whether recommendations previously described in the literature were met and to further investigate events conducted by individuals reporting overdose reversals with naloxone on three or more occasions (\u0026lsquo;Supersavers\u0026rsquo;).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eBetween June 2018 and June 2023, data was collected in six-month intervals from participating units (n\u0026thinsp;=\u0026thinsp;52), containing information on trained individuals, gender, year of birth and distributed naloxone kits. Upon naloxone replenishment, patients were asked whether previous naloxone had been used for overdose reversals on someone else, or themselves, had been lost, stolen, or given to someone else.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTraining and initial kits had been provided to 2685 individuals at risk of own opioid overdose. Each of the 5900 naloxone kits distributed, contained two naloxone doses. Upon refill (n\u0026thinsp;=\u0026thinsp;2364), naloxone had been used for overdose reversal in 39% (n\u0026thinsp;=\u0026thinsp;926) situations. The minimum distribution target of 20 kits per annual opioid overdose death was met annually, while the target of enrolling\u0026thinsp;\u0026gt;\u0026thinsp;100 individuals at-risk individuals per 100,000 population was first met during the second year. The core group of Supersavers represent 9% (n\u0026thinsp;=\u0026thinsp;50) of those returning for refill and while reporting 54.5% (n\u0026thinsp;=\u0026thinsp;292) of all overdose reversals.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eBroad-scale naloxone training and distribution reaches a large proportion of individuals at risk of opioid overdose. A continuous focus and priority in supporting units with a high prevalence of individuals witnessing overdose events is of great importance as these individuals report a large proportion of overdose reversals. Likewise, it is of great importance to provide these individuals, i.e. Supersavers, with needed and sufficient support for their continued essential work intervening in overdose situations.\u003c/p\u003e\u003ch2\u003eTrial Registration:\u003c/h2\u003e \u003cp\u003eNaloxone Treatment in Sk\u0026aring;ne County \u0026ndash; Effect on Drug-related Mortality and Overdose-related Complications, NCT03570099, registered 26 June 2018.\u003c/p\u003e","manuscriptTitle":"Broad-scale overdose education and naloxone distribution – 5-year follow-up of a regional program in Skåne County, Sweden","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-23 09:59:02","doi":"10.21203/rs.3.rs-5281562/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-24T14:08:58+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-24T00:20:17+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-09T15:58:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"115178420205923309485423836037299783574","date":"2025-03-25T13:44:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"261937427204013778126315827242294539546","date":"2025-03-22T01:38:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-10-21T15:27:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-18T09:49:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-18T09:49:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"Harm Reduction Journal","date":"2024-10-17T09:26:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"harm-reduction-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"harj","sideBox":"Learn more about [Harm Reduction Journal](http://harmreductionjournal.biomedcentral.com/)","snPcode":"12954","submissionUrl":"https://submission.nature.com/new-submission/12954/3","title":"Harm Reduction Journal","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"694544b2-a8e9-404b-b64b-88e06caacbaf","owner":[],"postedDate":"October 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-09T16:08:14+00:00","versionOfRecord":{"articleIdentity":"rs-5281562","link":"https://doi.org/10.1186/s12954-025-01255-3","journal":{"identity":"harm-reduction-journal","isVorOnly":false,"title":"Harm Reduction Journal"},"publishedOn":"2025-06-05 15:57:52","publishedOnDateReadable":"June 5th, 2025"},"versionCreatedAt":"2024-10-23 09:59:02","video":"","vorDoi":"10.1186/s12954-025-01255-3","vorDoiUrl":"https://doi.org/10.1186/s12954-025-01255-3","workflowStages":[]},"version":"v1","identity":"rs-5281562","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5281562","identity":"rs-5281562","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}