Why are drug-related deaths among women increasing in Scotland? A mixed-methods analysis of possible explanations.

Drug-related deaths have increased significantly in Scotland in recent years, with a much greater percentage increase in deaths among women than among men. We undertook a mixed-methods project to identify explanations for this trend, comprising three parallel methodological strands: (i) an analysis of available routine data, including drug treatment data, death registrations, and surveys of people using needle exchanges; (ii) thematic analysis of interviews and focus groups with professional stakeholders and (iii) secondary analysis of interviews with women who use drugs. Results indicated that the observed trend is likely to reflect multiple, interacting causes. Potential contributors identified were: ageing; changing patterns of substance use; increasing prevalence of physical and mental health co-morbidities; changing relationships and parenting roles; changes to treatment services and wider health and social care provision; unintended consequences or poor implementation of recovery-oriented practice; and changes in the social security system. Policy responses to rising drug-related death rates require a gender-informed approach, recognising the commonalities and differences between men and women who use drugs; the diversity of experiences within each gender; and the intersections between gender and other forms of inequality, such as poverty.

SARS-CoV-2 vaccine uptake and risks of severe COVID-19 disease among people prescribed opioid agonist therapy in Scotland.

BACKGROUND: There is limited evidence quantifying the risk of severe COVID-19 disease among people with opioid dependence. We examined vaccine uptake and severe disease (admission to critical care or death with COVID-19) among individuals prescribed opioid agonist therapy (OAT). METHOD: A case-control design was used to examine vaccine uptake in those prescribed OAT compared with the general population, and the association between severe disease and OAT. In both analyses, 10 controls from the general population were matched (to each OAT recipient and COVID-19 case, respectively) according to socio-demographic factors. Conditional logistic regression was used to estimate rate ratios (RR) for severe disease. RESULTS: Vaccine uptake was markedly lower in the OAT cohort (dose 1: 67%, dose 2: 53% and dose 3: 31%) compared with matched controls (76%, 72% and 57%, respectively). Those prescribed OAT within the last 5 years, compared with those not prescribed, had increased risk of severe COVID-19 (RR 3.38, 95% CI 2.75 to 4.15), particularly in the fourth wave (RR 6.58, 95% CI 4.20 to 10.32); adjustment for comorbidity and vaccine status attenuated this risk (adjusted RR (aRR) 2.43, 95% CI 1.95 to 3.02; wave 4 aRR 3.78, 95% CI 2.30 to 6.20). Increased risk was also observed for those prescribed OAT previously (>3 months ago) compared with recently (aRR 1.74, 95% CI 1.11 to 2.71). CONCLUSIONS: The widening gap in vaccine coverage for those prescribed OAT, compared with the general population, is likely to have exacerbated the risk of severe COVID-19 in this population over the pandemic. However, continued OAT use may have provided protection from severe COVID-19 among those with opioid dependence.

Factors associated with SARS-CoV-2 testing, diagnosis and COVID-19 disease among individuals prescribed opioid-agonist treatment: a nationwide retrospective cohort study.

OBJECTIVES: Among people receiving opioid-agonist treatment (OAT), the risk of COVID-19 infection and disease may be higher owing to underlying health problems and vulnerable social circumstances. We aimed to determine whether recent OAT, when compared with past exposure, affected the risk of (i) testing for SARS-CoV-2, (ii) testing positive for SARS-CoV-2, and (iii) being hospitalized or dying with COVID-19 disease. METHODS: We included individuals prescribed OAT in Scotland from 2015 to 2020. We performed record linkage to SARS-CoV-2 PCR testing, vaccination, hospitalization, and mortality data, and followed up from March 2020 to December 2021. We used proportional hazards analysis and multivariate logistic regression to estimate associations between recent OAT prescription (in the previous 2 months), compared with past exposure (off treatment for over a year), and COVID-19 outcomes. Models were adjusted for confounders. RESULTS: Among 36 093 individuals prescribed OAT, 19 071 (52.9%) were tested for SARS-CoV-2; 2896 (8.3%) tested positive; and 552 (1.5%) were hospitalized or died with COVID-19. Recent OAT, compared with past exposure, was associated with lower odds of testing positive among those tested (aOR, 0.63; 95% CI, 0.57-0.69). However, among those testing positive, recent OAT was associated with two-fold higher odds of hospitalization or death (aOR, 2.04; 95% CI, 1.60-2.59). DISCUSSION: We found that recent OAT was associated with lower odds of SARS-CoV-2 infection, but with higher odds of disease once diagnosed. Clinical studies are needed to unravel the role of OAT in these associations. An enhanced effort is warranted to increase vaccine coverage among OAT patients to mitigate the severe consequences of COVID-19.

Risk of drug-related death associated with co-prescribing of gabapentinoids and Z-drugs among people receiving opioid-agonist treatment: A national retrospective cohort study.

BACKGROUND: Prescribing of gabapentinoids and Z-drug-hypnotics has increased in the population and among people receiving opioid-agonist treatment (OAT) for opioid dependence. Evidence is mixed on whether co-prescribing of sedatives such as gabapentinoids and Z-drugs during OAT increases risk of drug-related death (DRD). METHODS: We conducted a retrospective cohort study of individuals prescribed OAT between 2011 and 2020 in Scotland. Prescribing records were linked to mortality data and other healthcare datasets (sociodemographic, comorbidity). We identified episodes of treatment with gabapentinoids/Z-drugs and used multivariable quasi-Poisson regression to model associations between co-prescription and DRD risk. RESULTS: Among 46,602 individuals with 304,783 person-years of follow-up, we found that co-prescription was common, with 25 % and 34 % ever being co-prescribed gabapentinoids and Z-drugs, respectively. Gabapentinoid exposure was strongly associated (adjusted hazard ratio (aHR)=2·18, 95 % CI=1·92, 2·46) and Z-drug exposure moderately associated (aHR=1·39, 95 % CI=1·15, 1·66) with elevated risk of DRD. Gabapentinoid exposure was associated with DRD risk on and off OAT; Z-drug exposure was less strongly associated with DRD risk when on OAT. CONCLUSIONS: Co-prescription of gabapentinoids and Z-drugs is common among OAT patients. However, co-prescription is associated with increased risk of DRD. Alternatives to prescribing sedative medications to OAT patients and/or greater monitoring - if prescribed - are needed.

Prevalence of opioid dependence in Scotland 2015-2020: A multi-parameter estimation of prevalence (MPEP) study.

BACKGROUND AND AIMS: Drug-related deaths in Scotland more than doubled between 2011 and 2020. To inform policymakers and understand drivers of this increase, we estimated the number of people with opioid dependence aged 15-64 from 2014/15 to 2019/20. DESIGN: We fitted a Bayesian multi-parameter estimation of prevalence (MPEP) model, using adverse event rates to estimate prevalence of opioid dependence jointly from Opioid Agonist Therapy (OAT), opioid-related mortality and hospital admissions data. Estimates are stratified by age group, sex and year. SETTING: Scotland, 2014/15 to 2019/20. PARTICIPANTS: People with opioid dependence and potential to benefit from OAT, whether ever treated or not. Using data from the Scottish Public Health Drug Linkage Programme, we identified a baseline cohort of individuals who had received OAT within the last 5 years, and all opioid-related deaths and hospital admissions (whether among or outside of this cohort). MEASUREMENTS: Rates of each adverse event type and (unobserved) prevalence were jointly modelled. FINDINGS: The estimated number and prevalence of people with opioid dependence in Scotland in 2019/20 was 47 100 (95% Credible Interval [CrI] 45 700 to 48 600) and 1.32% (95% CrI 1.28% to 1.37%). Of these, 61% received OAT during 2019/20. Prevalence in Greater Glasgow and Clyde was estimated as 1.77% (95% CrI 1.69% to 1.85%). There was weak evidence that overall prevalence fell slightly from 2014/15 (change -0.07%, 95% CrI -0.14% to 0.00%). The population of people with opioid dependence is ageing, with the estimated number of people aged 15-34 reducing by 5100 (95% CrI 3800 to 6400) and number aged 50-64 increasing by 2800 (95% CrI 2100 to 3500) between 2014/15 and 2019/20. CONCLUSIONS: The prevalence of opioid dependence in Scotland remained high but was relatively stable, with only weak evidence of a small reduction, between 2014/15 and 2019/20. Increased numbers of opioid-related deaths can be attributed to increased risk among people with opioid dependence, rather than increasing prevalence.

Mortality among individuals prescribed opioid-agonist therapy in Scotland, UK, 2011-20: a national retrospective cohort study.

BACKGROUND: Drug-related death (DRD) rate in Scotland, UK, has increased rapidly to one of the highest in the world. Our aim was to examine the extent to which opioid-agonist therapy (OAT) in Scotland is protective against drug-related mortality and how this effect has varied over time. METHODS: We included individuals in Scotland with opioid use disorder who received at least one OAT prescription between Jan 1, 2011, and Dec 31, 2020. We calculated drug-related mortality rates and used Quasi-Poisson regression models to estimate trends over time and by OAT exposure, adjusting for potential confounding. FINDINGS: In a cohort of 46 453 individuals prescribed OAT with a total of 304 000 person-years of follow-up, DRD rates more than trebled from 6·36 per 1000 person-years (95% CI 5·73-7·01) in 2011-12 to 21·45 (20·31-22·63) in 2019-20. DRD rates were almost three and a half times higher (hazard ratio 3·37; 95% CI 1·74-6·53) for those off OAT compared with those on OAT after adjustment for confounders. However, confounder adjusted DRD risk increased over time for both people off and on OAT. INTERPRETATION: Drug-related mortality rates among people with opioid use disorders in Scotland increased between 2011 and 2020. OAT remains protective but is insufficient on its own to slow the increase in DRD risk for people who are opioid dependent in Scotland. FUNDING: Scottish Government Drug Deaths Taskforce, Public Health Scotland, and National Institute for Health and Care Research.

Examining the impact of the first wave of COVID-19 and associated control measures on interventions to prevent blood-borne viruses among people who inject drugs in Scotland: an interrupted time series study.

BACKGROUND: COVID-19 has likely affected the delivery of interventions to prevent blood-borne viruses (BBVs) among people who inject drugs (PWID). We examined the impact of the first wave of COVID-19 in Scotland on: 1) needle and syringe provision (NSP), 2) opioid agonist therapy (OAT) and 3) BBV testing. METHODS: An interrupted time series study design; 23rd March 2020 (date of the first 'lockdown') was chosen as the key date. RESULTS: The number of HIV tests and HCV tests in drug services/prisons, and the number of needles/syringes (N/S) distributed decreased by 94% (RR=0.062, 95% CI 0.041-0.094, p < 0.001), 95% (RR=0.049, 95% CI 0.034-0.069, p < 0.001) and 18% (RR = 0.816, 95% CI 0.750-0.887, p < 0.001), respectively, immediately after lockdown. Post-lockdown, an increasing trend was observed relating to the number of N/S distributed (0.6%; RR = 1.006, 95% CI 1.001-1.012, p = 0.015), HIV tests (12.1%; RR = 1.121, 95% CI 1.092-1.152, p < 0.001) and HCV tests (13.2%; RR = 1.132, 95 CI 1.106-1.158, p < 0.001). Trends relating to the total amount of methadone prescribed remained stable, but a decreasing trend in the number of prescriptions (2.4%; RR = 0.976, 95% CI 0.959-0.993, p = 0.006) and an increasing trend in the quantity prescribed per prescription (2.8%; RR = 1.028, 95% CI 1.013-1.042, p < 0.001) was observed post-lockdown. CONCLUSIONS: COVID-19 impacted the delivery of BBV prevention services for PWID in Scotland. While there is evidence of service recovery; further effort is likely required to return some intervention coverage to pre-pandemic levels in the context of subsequent waves of COVID-19.

A rapid assessment of take-home naloxone provision during COVID-19 in Europe.

BACKGROUND: In March 2020, the World Health Organization declared COVID-19 a global pandemic. In the following weeks, most European countries implemented national lockdowns to mitigate viral spread. Services for people who use drugs had to quickly revise their operating procedures to rearrange service provision while adhering to lockdown requirements. Given the scarcity of literature published on overdose prevention during COVID-19 in Europe, we aimed to examine how these changes to service provision affected take-home naloxone (THN) programmes and naloxone availability across Europe. METHODS: Between November 2020 and January 2021, we conducted a rapid assessment with country experts from European countries that provide THN. We sent country experts a template to report monthly THN distribution data (January 1, 2019-October 31, 2020) and a structured 6-item survey for completion. RESULTS: Responses were received from 14 of the 15 European countries with THN provision of which 11 participated in the rapid assessment: Austria, Denmark, England, Estonia, Lithuania, Northern Ireland, Norway, Scotland, Spain (Catalonia only), Sweden, and Wales. All reported reduced organisational capacity during COVID-19, and some put into place a range of novel approaches to manage the restrictions on face-to-face service provision. In six countries, the introduction of programme innovation occurred alongside the publication of government guidelines recommending increased THN provision during COVID-19. Eight of the eleven participating countries managed to maintain 2019-level monthly THN distribution rates or even increase provision during the pandemic. CONCLUSION: Through programme innovation supported by public guidelines, many European THN programmes managed to ensure stable or even increased THN provision during the pandemic, despite social distancing and stay-at-home orders affecting client mobility.

Evaluating the impact of a national naloxone programme on ambulance attendance at overdose incidents: a controlled time-series analysis.

BACKGROUND AND AIMS: It has been suggested that distributing naloxone to people who inject drugs (PWID) will lead to fewer attendances by emergency medical services at opioid-related overdose incidents if peer administration of naloxone was perceived to have resuscitated the overdose victim successfully. This study evaluated the impact of a national naloxone programme (NNP) on ambulance attendance at opioid-related overdose incidents throughout Scotland. Specifically, we aimed to answer the following research questions: is there evidence of an association between ambulance call-outs to opioid-related overdose incidents and the cumulative number of 'take-home naloxone' (THN) kits in issue; and is there evidence of an association between ambulance call-outs to opioid-related overdose incidents in early adopter (pilot) or later adopting (non-pilot) regions and the cumulative number of THN kits issued in those areas? DESIGN: Controlled time-series analysis. SETTING: Scotland, UK, 2008-15. PARTICIPANTS: Pre-NNP implementation period for the evaluation was defined as 1 April 2008 to 31 March 2011 and the post-implementation period as 1 April 2011 to 31 March 2015. In total, 3721 ambulance attendances at opioid-related overdose were recorded for the pre-NNP implementation period across 158 weeks (mean 23.6 attendances per week) and 5258 attendances across 212 weeks in the post-implementation period (mean 24.8 attendances per week). INTERVENTION: Scotland's NNP; formally implemented on 1 April 2011. MEASUREMENTS: Primary outcome measure was weekly incidence (counts) of call-outs to opioid-related overdoses at national and regional Health Board level. Data were acquired from the Scottish Ambulance Service (SAS). Models were adjusted for opioid replacement therapy using data acquired from the Information Services Division on monthly sums of all dispensed methadone and buprenorphine in the study period. Models were adjusted further for a control group: weekly incidence (counts) of call-outs to heroin-related overdose in the London Borough area acquired from the London Ambulance Service. FINDINGS: There was no significant association between SAS call-outs to opioid-related overdose incidents and THN kits in issue for Scotland as a whole (coefficient 0.009, 95% confidence intervals = -0.01, 0.03, P = 0.39). In addition, the magnitude of association between THN kits and SAS call-outs did not differ significantly between pilot and non-pilot regions (interaction test, P = 0.62). CONCLUSIONS: The supply of take-home naloxone kits through a National Naloxone Programme in Scotland was not associated clearly with a decrease in ambulance attendance at opioid-related overdose incidents in the 4-year period after it was implemented in April 2011.

Mortality related to novel psychoactive substances in Scotland, 2012: an exploratory study.

BACKGROUND: The growth of novel psychoactive substances (NPS) over the last decade, both in terms of availability and consumption, is of increasing public health concern. Despite recent increases in related mortality, the circumstances surrounding and characteristics of individuals involved in NPS deaths at a population level remain relatively unknown. METHODS: The Scottish National Drug Related Death Database (NDRDD) collects a wide-range of data relating to the nature and circumstances of individuals who have died a drug-related death (DRD). We conducted exploratory descriptive analysis of DRDs involving NPS recorded by the NDRDD in 2012. Statistical testing of differences between sub-groups was also conducted where appropriate. RESULTS: In 2012, we found 36 DRDs in Scotland to have NPS recorded within post-mortem toxicology. However, in only 23 of these cases were NPS deemed by the reporting pathologist to be implicated in the actual cause of death. The majority of NPS-implicated DRDs involved Benzodiazepine-type drugs (13), mainly Phenazepam (12). The remaining 10 NPS-implicated deaths featured a range of different Stimulant-type drugs. The majority of these NPS-implicated deaths involved males and consumption of more than one drug was recorded by toxicology in all except one case. NPS-implicated deaths involving Benzodiazepine-type NPS drugs appeared to involve older individuals known to be using drugs for a considerable period of time, many of whom had been in prison at some point in their lives. They also typically involved combinations of opioids and benzodiazepines; no stimulant drugs were co-implicated. Deaths where stimulant-type NPS drugs were implicated appeared to be a younger group in comparison, all consuming two or more Stimulant-type drugs in combination. CONCLUSION: This exploratory study provides an important insight into the circumstances surrounding and characteristics of individuals involved in NPS deaths at a population level. It identifies important issues for policy and practice, not least the prominent role of unlicensed benzodiazepines in drug-related mortality, but also the need for a range of harm reduction strategies to prevent future deaths.