Broad evidence of xylazine in the UK illicit drug market beyond heroin supplies: Triangulating from toxicology, drug-testing and law enforcement.

BACKGROUND AND AIMS: Xylazine is a non-opioid sedative which has spread rapidly throughout the US illicit drug supply. This study aimed to describe the spread of xylazine throughout the UK illicit drug supply. METHODS: Xylazine detections in human biological samples were collated from toxicology laboratories operating in the United Kingdom with the date, location, case type, xylazine concentration and co-detected drugs (with quantifications where performed) detailed, where permitted, by the corresponding coroner. Drug-testing cases positive for xylazine were collated from the Welsh Emerging Drugs and Identification of Novel Substances (WEDINOS) drug-testing postal service with the date, location, purchase intent and co-detected drugs detailed. Drug seizures made by UK law enforcement were communicated by the Office for Health Improvement and Disparities with the date and location detailed. RESULTS: By the end of August 2023, xylazine was detected in 35 cases from throughout toxicology, drug-testing and drug seizure sources covering England, Scotland and Wales. There were no cases reported from Northern Ireland. Xylazine was detected in biological samples from 16 people. In most cases where full toxicology results were provided, xylazine was detected with heroin and/or a strong opioid (n = nine of 11), but this polydrug use pattern was not evident in all cases (n = two of 11), suggesting a wider circulation of xylazine in the UK illicit drug market beyond heroin supplies. Evidence from WEDINOS supports this claim, as all 14 drug samples (100%) submitted from across the UK contained xylazine; however, in none of these cases was heroin the purchase intent but rather counterfeit prescription medication tablets (n = 11 of 14), tetrahydrocannabinol (THC) vapes (n = two of 14) or white powder (n = one of 14). Additional evidence for the spread of illicit xylazine comes from five drug seizures made by law enforcement. CONCLUSIONS: Xylazine has penetrated the UK illicit drug market and is not limited to heroin supplies.

Navigating Chemical Toxicity in Coca Production in the Colombian Borderlands of Putumayo.

In Putumayo, a jungle borderland in southern Colombia, thousands of farmers derive their livelihood from the cultivation and processing of coca leaf, exposing themselves to fertilizers, pesticides, and other toxic chemicals on a daily basis. In this article, we show how the coca growers' relationship with chemicals and the health risks to which they are exposed, are politically and institutionally structured. We discuss the specific impact of anti-narcotics policy in a broader context of deep inequalities and document the emergent and adaptive day-to-day attempts of the farmers to navigate the structural risk environment.

Caring for coca, living with chemicals: Towards ecological harm reduction.

In this paper, we show how the materialisation of chemical harms linked to the cultivation of coca and its processing into coca paste reside in a wider politics of structural violence which is also situated ecologically. Drawing on the qualitative interview accounts of coca farmers in Putumayo, Colombia, we attend to practices of care in the field and in the laboratory. We look first at chemicals used in coca's cultivation (herbicides, fertilizers, pesticides), and second at chemicals (such as sulphuric acid, sodium carbonate, magnesium permanganate) used in the processing of coca leaf into paste (before the paste is sold on for refinement into cocaine). Our analysis highlights the tensions which inevitably arise in the balance and multiplicities of care - for crops, livelihood, and environment. We trace how farmers' narratives of the neutralisation of chemical risks habituate chemical harms as mundane, even uneventful, in an economic imperative to 'carry on as normal' in the coca economy. We emphasise health and harm as matters of care which not only affect humans but living environments. Accounts of 'risk environment' can give insufficient attention to Nature, and this leads us to consider 'ecological harm reduction'.

Agreement between self-reported illicit drug use and biological samples: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Studies often rely upon self-report and biological testing methods for measuring illicit drug use, although evidence for their agreement is limited to specific populations and self-report instruments. We aimed to examine comprehensively the evidence for agreement between self-reported and biologically measured illicit drug use among all major illicit drug classes, biological indicators, populations and settings. METHODS: We systematically searched peer-reviewed databases (Medline, Embase and PsycINFO) and grey literature. Included studies reported 2 × 2 table counts or agreement estimates comparing self-reported and biologically measured use published up to March 2022. With biological results considered to be the reference standard and use of random-effect regression models, we evaluated pooled estimates for overall agreement (primary outcome), sensitivity, specificity, false omission rates (proportion reporting no use that test positive) and false discovery rates (proportion reporting use that test negative) by drug class, potential consequences attached to self-report (i.e. work, legal or treatment impacts) and time-frame of use. Heterogeneity was assessed by inspecting forest plots. RESULTS: From 7924 studies, we extracted data from 207 eligible studies. Overall agreement ranged from good to excellent (> 0.79). False omission rates were generally low, while false discovery rates varied by setting. Specificity was generally high but sensitivity varied by drug, sample type and setting. Self-report in clinical trials and situations of no consequences was generally reliable. For urine, recent (i.e. past 1-4 days) self-report produced lower sensitivity and false discovery rates than past month. Agreement was higher in studies that informed participants biological testing would occur (diagnostic odds ratio = 2.91, 95% confidence interval = 1.25-6.78). The main source of bias was biological assessments (51% studies). CONCLUSIONS: While there are limitations associated with self-report and biological testing to measure illicit drug use, overall agreement between the two methods is high, suggesting both provide good measures of illicit drug use. Recommended methods of biological testing are more likely to provide reliable measures of recent use if there are problems with self-disclosure.

Analysis of the UK Government's 10-Year Drugs Strategy-a resource for practitioners and policymakers.

In 2021, during a drug-related death crisis in the UK, the Government published its ten-year drugs strategy. This article, written in collaboration with the Faculty of Public Health and the Association of Directors of Public Health, assesses whether this Strategy is evidence-based and consistent with international calls to promote public health approaches to drugs, which put 'people, health and human rights at the centre'. Elements of the Strategy are welcome, including the promise of significant funding for drug treatment services, the effects of which will depend on how it is utilized by services and local commissioners and whether it is sustained. However, unevidenced and harmful measures to deter drug use by means of punishment continue to be promoted, which will have deleterious impacts on people who use drugs. An effective public health approach to drugs should tackle population-level risk factors, which may predispose to harmful patterns of drug use, including adverse childhood experiences and socioeconomic deprivation, and institute evidence-based measures to mitigate drug-related harm. This would likely be more effective, and just, than the continuation of policies rooted in enforcement. A more dramatic re-orientation of UK drug policy than that offered by the Strategy is overdue.

Hospital policies can create barriers to good management of opioid withdrawal.

The studyHarris M, Holland A, Lewer D, et al. Barriers to management of opioid withdrawal in hospitals in England: a document analysis of hospital policies on the management of substance dependence. BMC Med 2022;20:151.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/many-hospital-policies-create-barriers-to-good-management-of-opioid-withdrawal/.

Temperature as a key parameter for graphene sono-exfoliation in water.

Graphene dispersions in water are highly desirable for a range of applications such as biomedicines, separation membranes, coatings, inkjet printing and more. Recent novel research has been focussed on developing a green approach for scalable production of graphene. However, one important parameter, which is often neglected is the bulk temperature of the processing liquid. This paper follows our earlier work where optimal sono-exfoliation parameters of graphite in aqueous solutions were determined based on the measured acoustic pressure fields at various temperatures and input powers. Here, we take the next step forward and demonstrate using systematic characterisation techniques and acoustic pressure measurements that sonication-assisted liquid phase exfoliation (LPE) of graphite powder can indeed produce high quality few layer graphene flakes in pure water at a specific temperature, i.e. 40 °C, and at an optimised input generator power of 50%, within 2-h of processing. UV-vis analysis also revealed that the exfoliation, stability and uniformity of dispersions were improved with increasing temperature. We further confirmed the successful exfoliation of graphene sheets with minimal level of defects in the optimized sample with the help of Raman microscopy and transmission electron microscopy. This study demonstrated that understanding and controlling processing temperature is one of the key parameters for graphene exfoliation in water which offers a potential pathway for its large-scale production.

Barriers to management of opioid withdrawal in hospitals in England: a document analysis of hospital policies on the management of substance dependence.

BACKGROUND: People who use illicit opioids are more likely to be admitted to hospital than people of the same age in the general population. Many admissions end in discharge against medical advice, which is associated with readmission and all-cause mortality. Opioid withdrawal contributes to premature discharge. We sought to understand the barriers to timely provision of opioid substitution therapy (OST), which helps to prevent opioid withdrawal, in acute hospitals in England. METHODS: We requested policies on substance dependence management from 135 National Health Service trusts, which manage acute hospitals in England, and conducted a document content analysis. Additionally, we reviewed an Omitted and Delayed Medicines Tool (ODMT), one resource used to inform critical medicine categorisation in England. We worked closely with people with lived experience of OST and/or illicit opioid use, informed by principles of community-based participatory research. RESULTS: Eighty-six (64%) trusts provided 101 relevant policies. An additional 44 (33%) responded but could not provide relevant policies, and five (4%) did not send a definitive response. Policies illustrate procedural barriers to OST provision, including inconsistent application of national guidelines across trusts. Continuing community OST prescriptions for people admitted in the evening, night-time, or weekend was often precluded by requirements to confirm doses with organisations that were closed during these hours. 42/101 trusts (42%) required or recommended a urine drug test positive for OST medications or opioids prior to OST prescription. The language used in many policies was stigmatising and characterised people who use drugs as untrustworthy. OST was not specifically mentioned in the reviewed ODMT, with 'drugs used in substance dependence' collectively categorised as posing low risk if delayed and moderate risk if omitted. CONCLUSIONS: Many hospitals in England have policies that likely prevent timely and effective OST. This was underpinned by the 'low-risk' categorisation of OST delay in the ODMT. Delays to continuity of OST between community and hospital settings may contribute to inpatient opioid withdrawal and increase the risk of discharge against medical advice. Acute hospitals in England require standardised best practice policies that account for the needs of this patient group.

Causes of death among people who used illicit opioids in England, 2001-18: a matched cohort study.

BACKGROUND: In many countries, the average age of people who use illicit opioids, such as heroin, is increasing. This has been suggested to be a reason for increasing numbers of opioid-related deaths seen in surveillance data. We aimed to describe causes of death among people who use illicit opioids in England, how causes of death have changed over time, and how they change with age. METHODS: In this matched cohort study, we studied patients in the Clinical Practice Research Datalink with recorded illicit opioid use (defined as aged 18-64 years, with prescriptions or clinical observations that indicate use of illicit opioids) in England between Jan 1, 2001, and Oct 30, 2018. We also included a comparison group, matched (1:3) for age, sex, and general practice with no records of illicit opioid use before cohort entry. Dates and causes of death were obtained from the UK Office for National Statistics. The cohort exit date was the earliest of date of death or Oct 30, 2018. We described rates of death and calculated cause-specific standardised mortality ratios. We used Poisson regression to estimate associations between age, calendar year, and cause-specific death. FINDINGS: We collected data for 106 789 participants with a history of illicit opioid use, with a median follow-up of 8·7 years (IQR 4·3-13·5), and 320 367 matched controls with a median follow-up of 9·5 years (5·0-14·4). 13 209 (12·4%) of 106 789 participants in the exposed cohort had died, with a standardised mortality ratio of 7·72 (95% CI 7·47-7·97). The most common causes of death were drug poisoning (4375 [33·1%] of 13 209), liver disease (1272 [9·6%]), chronic obstructive pulmonary disease (COPD; 681 [5·2%]), and suicide (645 [4·9%]). Participants with a history of illicit opioid use had higher mortality rates than the comparison group for all causes of death analysed, with highest standardised mortality ratios being seen for viral hepatitis (103·5 [95% CI 61·7-242·6]), HIV (16·7 [9·5-34·9]), and COPD (14·8 [12·6-17·6]). In the exposed cohort, at age 20 years, the rate of fatal drug poisonings was 271 (95% CI 230-313) per 100 000 person-years, accounting for 59·9% of deaths at this age, whereas the mortality rate due to non-communicable diseases was 31 (16-45) per 100 000 person-years, accounting for 6·8% of deaths at this age. Deaths due to non-communicable diseases increased more rapidly with age (1155 [95% CI 880-1431] deaths per 100 000 person-years at age 50 years; accounting for 52·0% of deaths at this age) than did deaths due to drug poisoning (507 (95% CI 452-562) per 100 000 person-years at age 50 years; accounting for 22·8% of deaths at this age). Mirroring national surveillance data, the rate of fatal drug poisonings in the exposed cohort increased from 345 (95% CI 299-391) deaths per 100 000 person-years in 2010-12 to 534 (468-600) per 100 000 person-years in 2016-18; an increase of 55%, a trend that was not explained by ageing of participants. INTERPRETATION: People who use illicit opioids have excess risk of death across all major causes of death we analysed. Our findings suggest that population ageing is unlikely to explain the increasing number of fatal drug poisonings seen in surveillance data, but is associated with many more deaths due to non-communicable diseases. FUNDING: National Institute for Health Research.

Living Under Coronavirus and Injecting Drugs in Bristol (LUCID-B): A qualitative study of experiences of COVID-19 among people who inject drugs.

BACKGROUND: People who inject drugs (PWID) are a high-risk group for COVID-19 transmission and serious health consequences. Restrictions imposed in the UK in response to the pandemic led to rapid health and housing service alterations. We aimed to examine PWID experiences of: 1) challenges relating to the COVID-19 public health measures; 2) changes to opioid substitution therapy (OST) and harm reduction services; and 3) perceived effects of COVID-19 on drug use patterns and risk behaviour. METHODS: Telephone semi-structured interviews were conducted with 28 PWID in Bristol, Southwest of England. Analysis followed a reflexive thematic analysis. RESULTS: Concern about COVID-19 and adherence to public health guidance varied. Efforts made by services to continue providing support during the pandemic were appreciated and some changes were preferred, such as less frequent OST collection, relaxation of supervised consumption and needle and syringe programmes (NSP) home delivery. However, remote forms of contact were highlighted as less beneficial and more difficult to engage with than in-person contact. Public health guidance advising people to 'stay home' led to increased isolation, boredom, and time to ruminate which impacted negatively on mental health. Lockdown restrictions directly impacted on sources of income and routine. Changes in drug use were explained as a consequence of isolation and fewer interactions with peers, problems accessing drugs, reduced drug purity and reduced financial resources. CONCLUSION: This study captures the significant impacts and challenges of the COVID-19 pandemic on the lives of PWID. While rapid adaptations to service delivery to help mitigate the risks of COVID-19 were appreciated and some changes such as relaxation of supervised daily OST consumption were viewed positively, barriers to access need further attention. Going forwards there may be opportunities to harness the positive aspects of some changes to services.

Rapid (FLASH-FLIM) imaging of protoporphyrin IX in a lipid mixture using a CMOS based widefield fluorescence lifetime imaging camera in real time for margin demarcation applications.

The fluorescence from protoporphyrin IX (PpIX) has been employed to characterise cellular activity and assist in the visualisation of tumour cells. Its formation can be induced by 5-aminolevulonic acid (5-ALA) which is metabolised by tumour cells to form PpIX. The PpIX is localised within the cells, rather than spreading into the vascular system. This, plus its photophysics, exhibits potential in photodynamic therapy. Hence its study and the ability to rapidly image its localisation is of importance, especially in the field of fluorescence guided surgery. This has led to investigations using tissue phantoms and widefield intensity imaging. Aggregation or the presence of photoproducts can alter PpIX emission, which has implications using widefield imaging and a broad wavelength range detection. The use of the fluorescence lifetime imaging (FLIM) is therefore advantageous as it can distinguish between the emissive species as they exhibit different fluorescence lifetimes. Here we use PpIX in a construct consisting of lipid mixture (Intralipid), employed to simulate fat content and optical scattering, in a gellan gum matrix. PpIX in intralipid in aqueous solution was injected into the gellan host to form inclusions. The samples are imaged using commercial widefield TCSPC camera based on a sensor chip with 192 × 128 pixels. Each pixel contains both detection and photon timing enabling the Fluorescence Lifetime Acquisition by Simultaneous Histogramming (FLASH). This 'FLASH-FLIM' approach enables widefield fluorescence lifetime images, displayed in real time to be acquired, which has potential for use in visualising tumour boundaries.

An ethical analysis of UK drug policy as an example of a criminal justice approach to drugs: a commentary on the short film Putting UK Drug Policy into Focus.

BACKGROUND: Drug-related deaths in the UK are at the highest level on record-the war on drugs has failed. A short film has been produced intended for public and professional audiences featuring academics, representatives of advocacy organisations, police and policymakers outlining the problems with, and highlighting alternative approaches to, UK drug policy. A range of ethical arguments are alluded to, which are distilled here in greater depth for interested viewers and a wider professional and academic readership. MAIN BODY: The war on drugs is seemingly driven by the idea that the consumption of illegal drugs is immoral. However, the meaning ascribed to 'drug' in the illicit sense encompasses a vast range of substances with different properties that have as much in common with legal drugs as they do with each other. The only property that distinguishes illegal from legal drugs is their legal status, which rather than being based on an assessment of how dangerous they are has been defined by centuries of socio-political idiosyncrasies. The consequences of criminalising people who use drugs often outweigh the risks they face from drug use, and there is not convincing evidence that this prevents wider drug use or drug-related harm. Additionally, punishing someone as a means, to the end of deterring others from drug use, is ethically problematic. Although criminalising the production of harmful drugs may seem more ethically tenable, it has not reduced the supply of drugs and it precludes effective regulation of the market. Other potential policy approaches are highlighted, which would be ethically preferable to existing punitive policy. CONCLUSION: It is not possible to eliminate all drug use and associated harms. The current approach is not only ineffective in preventing drug-related harm but itself directly and indirectly causes incalculable harm to those who use drugs and to wider society. For policymakers to gain the mandate to rationalise drug policy, or to be held accountable if they do not, wider engagement with the electorate is required. It is hoped that this film will encourage at least a few to give pause and reflect on how drug policy might be improved.

Rapid evidence review of harm reduction interventions and messaging for people who inject drugs during pandemic events: implications for the ongoing COVID-19 response.

BACKGROUND: People who inject drugs are at increased health risk in a pandemic due to their greater susceptibility to severe disease and as a consequence of the restrictions put in place to halt the spread of infection. Harm reduction (HR) services, which aim to reduce the negative effects of drug use on health, are likely to be diminished in a pandemic. However, innovative HR interventions and messaging may also develop in response to such a crisis. It is vital to understand the most effective ways to deliver HR in pandemic situations so that guidance can be provided for current and future disruptions to service provision. METHODS: A rapid evidence review was conducted with the aim of exploring what HR interventions and messaging are most effective during a pandemic-type situation. Ten health databases were systematically searched using terms relevant to the research aim. A search was also made of grey literature, including a targeted search of HR messaging from key national and service provider websites. RESULTS: In the initial search, 121 pieces of evidence were identified which, after screening and de-duplication, resulted in 60 for inclusion. The included evidence consists mainly of non-peer reviewed, pre-publication or expert opinion pieces. The rapid findings suggest that HR services should be deemed essential during a pandemic, with staff supported to work safely and social distancing adaptations implemented. Services should be encouraged to operate more flexibly; for instance, in deciding the amounts of take-home supplies of injecting equipment and medications. The evidence on HR communication was very limited but key messages on infection control, uncertain drug supply and accessing services were identified. CONCLUSIONS: This rapid evidence review identifies implications for national policy makers, commissioners and HR service providers. A person-centred rather than disease-centred approach to HR delivered by collaborating partners, as well as prioritizing tailored HR messaging, is recommended. Further research evaluating the delivery of HR services and messaging, particularly focusing on health inequalities, is urgently needed.

Absolute measurements of photoluminescence quantum yields of solutions using an integrating sphere.

We demonstrate that absolute measurements of the photoluminescence quantum yield of solutions can be made using an integrating sphere and a conventional fluorimeter. With this method the need for measurements against a luminescence standard is overcome. The sphere is mounted inside a commercial fluorimeter, which gives flexibility in excitation and emission wavelength ranges. A number of compounds have been investigated and the results are compared to literature values and data obtained using a comparative method.