University of Manchester



Prevalence of recent fentanyl use among treated users of illicit opioids in England: based on piloted urine drug screensPrun Bijral a*, Karen P. Hayhurst b, Sheila M. Bird c,d, Tim Millar ba Medical Director, CGL, London. UK; b Centre for Mental Health and Safety, University of Manchester, UK; c Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK; d MRC Biostatistics Unit, University of Cambridge, School of Clinical Medicine, Institute for Public Health, Cambridge, UK.* Corresponding authorPrevalence of recent fentanyl use among treated users of illicit opioids in England: based on piloted urine drug screensAbstractObjective: To use a pilot of national fentanyl screening to establish the current prevalence of recent fentanyl use among treated users of illicit opioids in the English treatment system and inform the design of a full study.Design: Cross-sectional fentanyl metabolite urine screening in randomly-selected study sites, stratified to cover all 9 geographical regions of England, supplemented with self-report subsequent to a positive fentanyl test. Patients: 468 adult (18 years of age and above) patients receiving treatment for opioid use disorder, screened December 2017 to May 2018.Results: The fentanyl-positive rate in patients receiving treatment for opioid use disorder in the English treatment system was 3% (15/468, 95% CI 1.8% to 5.2%) with a per-site range (for the 10 sites in 9 regions where fentanyl was detected) of between 2% (1/57) and 15% (4/27). Self-report data indicated that the majority of fentanyl-positives (12/15, 80%) was unaware of having purchased fentanyl. Conclusion: Despite alerts already in place, patients receiving treatment for opioid use disorder, who were fentanyl-positive, were unwittingly purchasing and consuming fentanyl. IntroductionTorjesen [1] points out that the determinants of the US fentanyl crisis, where poorer quality illicit heroin is increasingly adulterated with synthetic fentanyl, may not translate to the UK, where illicit heroin is purer and cheaper [2]. Reports to date, point to a spike in fentanyl-related deaths occurring predominantly in the Yorkshire and Humber regions of the UK [3] although the extent and availability of fentanyl across other UK regions, and hence the potential for future fentanyl-related deaths elsewhere, is unknown.Recent post-mortem toxicology of UK fentanyl-related deaths concluded that the presence of fentanyl together with heroin in the majority of cases points to adulteration of UK heroin supplies [4]. Twenty-five of a subset selected from 297 heroin-related deaths were positive for fentanyl, a contamination rate of 9%.People who use illicit opioids and test urine-positive for fentanyl may not knowingly have ingested fentanyl, however [5]. If so, national public health alerts [6] could have limited benefit. Conversely, the current intense publicity around fentanyl, coupled with its availability online, may lead less risk-averse UK users of opiates purposely to seek it out.An essential element to mitigate potential harm from a UK fentanyl outbreak is robustly to estimate the prevalence of fentanyl use among users of illicit opioids. We report recently collected data from a pilot study which help clarify the current situation among patients receiving treatment for opioid use disorder in English treatment services.Patients and methodsPatientsAdults receiving treatment for opioid use disorder, whose routine urine drug screen was due December 2017 to May 2018, were approached (469, out of 11,956 site-listed patients). In the UK treatment system, urine drug screening is used: during the initial assessment stage; to confirm treatment compliance; and to monitor illicit drug use [7]. Study-specific consent was not required as urine drug screening is part of routine clinical management, to which patients give their consent on treatment entry. SettingSixteen study sites were randomly-selected and stratified to cover all nine geographical regions of England. Two sites were chosen at random from each of seven regions (Eastern, London, North East, North West, South East, South West, West Midlands), with just one site each being available for two regions (East Midlands, Yorkshire & Humber). The lottery method was used to randomly select study sites from the seven regions listed above. The service provider was Change, Grow, Live (CGL), one of the main UK providers of substance use disorder treatment services. MethodCross-sectional fentanyl metabolite urine screening was carried out using the Alere Drug Screen Test Strip, viable within a 3-day window of use (sensitivity 99%, specificity 90%) [8]. The test targets the main urinary metabolite (norfentanyl) and is able to detect norfentanyl at a cut-off concentration of 20ng/mL; the 99th percentile sensitivity for norfentanyl is 30ng/mL.Patient-attributable data were collected as participants wanted to know their test results, but personal details were not disclosed beyond the clinical team. Self-report data were collected from individuals testing positive for fentanyl: ‘were you aware that you had bought heroin containing fentanyl?’ Data analysisFor 95% confidence that recent-use rate was less than 5%, 60 individuals would need to be tested per site without finding any positive. Recent prevalence of fentanyl use was simply calculated as the proportion testing positive in the sample as a whole and per site. The 95% confidence interval (CI) was estimated using the exact (Clopper-Pearson) 95% CI for a binomial proportion. ResultsSampleWe report data from 14 sites (covering all 9 regions), pertaining to 468 patients (out of 469 approached). Key characteristics of the sample are set out in Table 1. The screened cohort was comparable on gender (71% male) and age-group (mean age 40 years) to the national cohort of patients currently receiving treatment for opioid use disorder (established via the National Drug Treatment Monitoring System: NDTMS). Some differences on key markers of risk, e.g. on-top stimulant use, appear to discriminate fentanyl positives from fentanyl negatives (see Table 1) although numbers of fentanyl-positive tests were too low for a robust analysis. Full national screening to follow on from this pilot will have sufficient numbers to explore such patterns further. PrevalenceThe fentanyl-positive rate was 3% (15/468, 95% CI 1.8% to 5.2%) with a per-site range (for the 10 sites in 9 regions where fentanyl was detected) of between 2% (1/57) and 15% (4/27). In the remaining 4 sites, the numbers screened were 29, 32, 40 and 40. Other drug use and self-report dataTo approximate the rate at which heroin is contaminated by fentanyl we also assessed patients’ urine samples for co-presence of opiates. Over a half (55%) were opiate-positive, meaning that the rate at which heroin was potentially contaminated by fentanyl could have been as high as 15/257 or 6%.The majority of those testing positive for fentanyl (11/15, 73%) also tested positive for cocaine. Two-thirds of the fentanyl test positive individuals had previously self-reported stimulant use (see Table 1); this use referred to crack, rather than powder, cocaine. Self-report data collected subsequent to a positive fentanyl test indicated that the majority (12/15, 80%) was unaware of having purchased fentanyl. DiscussionThree per cent (15/468, 95% CI 1.8% to 5.2%) of patients receiving treatment for opioid use disorder in the English treatment system tested positive for fentanyl in a pilot screening study. The majority (12/15, 80%) was unaware of having purchased fentanyl. Recent research also indicates high levels of unwitting fentanyl use; 55% of 30 US individuals attending emergency care subsequent to a heroin overdose were able to accurately self-identify their fentanyl exposure [9]. Conversely, this sample had a fentanyl positive test rate of 97%, albeit in a high-risk sample; this discrepancy serves to highlight the differing context and determinants of US and UK fentanyl use [1,2]. Strengths and limitationsThe test used is capable of detecting the major fentanyl metabolite (norfentanyl). The test may detect other fentanyls (including sulfentanyl and alfentanyl, as well as the parent drug fentanyl) although it has not been specifically designed to do so. Confirmatory testing using a more accurate technique, such as gas, or liquid, mass spectrometry is recommended for positive results. We acknowledge that the test may not have detected some fentanyl analogues, meaning that our estimate is conservative and should be considered a minimum. Our objective was to estimate the fentanyl prevalence rate with a maximally high volunteer rate among eligible participants in a pilot study ahead of national screening; minimally-intrusive questions were therefore used. Sites where fentanyl use was believed to be more likely were not specifically targeted and random selection (for routine drug testing) aimed to eliminate any systematic differences in behaviour. To mitigate selection bias, all eligible patients were screened, i.e. screening was not targeted at those thought most likely to use ‘on-top’ and screening did not exclude those who tested negative for other opiates. Currently, we do not have sufficient information about the ‘on-top’ use of patients who ingest fentanyl in England to exclude negative opiate testers from fentanyl screening. It would be necessary to repeat the screening design reported here at least six-monthly to provide early warning of further escalation or of a potential epidemic. We also note users’ strong interest in their fentanyl-test result being reported back to them. ConclusionsDespite assurances from policy makers that fentanyl’s emergence was among “limited networks of drug users in specific areas” [10], the availability of fentanyl to UK patients who use illicit opioids appears not to be a short-lived phenomenon. Since not all patients will have accessed heroin pre-screening, the rate at which their heroin was contaminated by fentanyl could be considerably greater than 3%.Despite alerts being in place, people who use illicit opioids in treatment who were fentanyl-positive were unwittingly purchasing and consuming fentanyl. Effective methods of communicating evidence-based messages of risk and harm reduction to people who use illicit opioids require further development and evaluation. Disclosure statementPB: Member of the Royal College of Psychiatrists, Executive on Addiction Faculty. Technical Committee Member, Advisory Council on the Misuse of Drugs.KPH: has received research grant funding from Change, Grow, Live (CGL), a third-sector provider of substance misuse services. SMB: Served on Scotland’s National Naloxone Advisory Group.TM: has received research funding from Change, Grow Live, the UK National?Treatment Agency for Substance Misuse/Public Health England, and the Home Office; has been a member of the?organising committee for conferences?supported by unrestricted educational grants from Reckitt?Benckiser, Lundbeck, Martindale Pharma,?and Britannia Pharmaceuticals Ltd, for which he received no personal remuneration;?is a member of the Advisory Council on the Misuse?of Drugs.AcknowledgementsThis study was funded by Change, Grow, Live (CGL), one of the main UK providers of substance use disorder treatment services. The Medical Director of CGL (PB) is lead author on the manuscript and contributed to the design of the study and to the final writing of the paper. We would like to thank those individuals who made the study possible, specifically Donal Cairns, Stefan Jahr, Andrew Jones and Elin Williams at The University of Manchester; Harry Wallace of CGL; CGL treatment service personnel in study sites and CGL patients, in particular. ORCID IDsKPH: : [1] Torjesen I. Fentanyl misuse in the UK: will we see a surge in deaths? BMJ;361:doi: [2] UK Drug Focal Point on Drugs. United Kingdom Drug Situation: Focal Point Annual Report. London: Public Health England; 2017. [3] National Crime Agency (NCA). Recent deaths possibly linked to fentanyl. London: NCA; 2017. [4] Hikin L, Smith PR, Ringland E, et al. Multiple fatalities in the North of England associated with synthetic fentanyl exposure: detection and quantitation a case series from early 2017. Forensic Sci Int. 2018;282:179-183. [5] Amlani A, McKee G, Khamis N, et al. Why the FUSS (Fentanyl Urine Screen Study)? A cross-sectional survey to characterize an emerging threat to people who use drugs in British Columbia, Canada. Harm Reduction J. 2015;12:54. [6] Public Health England (PHE). Evidence of harm from fentanyl-contaminated heroin. London: PHE; 2017. Available at: [7] Department of Health (DH). Drug misuse and dependence: UK guidelines on clinical management. London: Department of Health; 2017. [8] Industry data [Internet]. Available from: [9] Griswold MK, Chai PR, Krotulski AJ, et al. Self-identification of nonpharmaceutical fentanyl exposure following heroin overdose. Clin Toxicol. 2018;56:37-42. [10] O’Connor R. Fentanyl: what’s being done to mitigate future problems. Gov.UK Public Health Matters blog 18th September 2017. Available at: 1. Key demographic and clinical characteristicsKey characteristicsMarkers of riskUse of non-opiates last 4 weeksNAge, years (Mean, 95% CI)Gender (% male)Ethnicity (% white)Length of current treatment episode, days (Mean, 95% CI)Injecting last 4 weeks (%)3 On-top opiate use last 4 weeks (%)3 Stimulants (%)1,3Cannabis (%)3Alcohol (%)3Unstable/ unsuitable accommodation last 4 weeks (%)3Total sample 468240.3 (39.5 to 41.1)71.389.8727 (645 to 808)20.561.250.621.733.910.4Positive fentanyl testers 1539.3 (33.4 to 45.2)73.393.3650 (365 to 935)20.066.766.720.013.06.7Negative fentanyl testers 45240.4 (39.6 to 41.2)71.289.7731 (647 to 815)20.660.950.121.834.710.5Notes: 1 Crack cocaine, powder cocaine, amphetamines. 2 Refusals N=1 (details not listed). 3 Risk markers taken from TOP (Treatment Outcomes Profile) data, completed at treatment start and then 3-monthly. ................
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