Highlighting the hidden dangers of a ‘weak’ opioid:Deaths following use of dihydrocodeine in England (2001–2020)

BackgroundDihydrocodeine (DHC) is considered a ‘weak’ opioid, but there is evidence of its increasing misuse in overdose deaths. This research aims to analyse trends in DHC-related deaths in England relevant to source and dose of DHC, and decedent demographics.MethodsCases from England reported to the National Programme on Substance Abuse Deaths (NPSAD) where DHC was identified at post-mortem and/or implicated in death between 2001 and 2020 were extracted for analysis.Results2071 DHC-related deaths were identified. The greatest number of deaths involved illicitly obtained DHC and a significant increase in these deaths was recorded over time (r = 0.5, p = 0.03). However, there was a concurrent decline in the implication rate of DHC in causing death (r = −0.6, p &lt; 0.01). Fatalities were primarily due to accidental overdose (64.8%) and misuse was highly prevalent in combination with additional central nervous system depressants (95.3%), namely illicit heroin/morphine and diazepam. In contrast, when DHC was obtained over-the-counter (OTC) suicide mortality accounted for almost half of the deaths (42.5%). Differences in polysubstance use were also identified, with less heroin/morphine and benzodiazepine co-detection, but increased OTC codeine co-detection.ConclusionsDHC misuse in England is increasing. The pharmacological consideration of DHC as a ‘weak’ opioid may be misinterpreted by users, leading to accidental overdosing. There is an urgent need to understand increasing polypharmacy in overdose deaths. Additionally, suicides involving DHC is a potential cause for concern and a review of OTC opioid-paracetamol preparations is necessary to determine whether the benefits of these medications continue to outweigh the risks of intentional overdose.</p

Trends in deaths following drug use in England before, during, and after the COVID-19 lockdowns

AimThis research aimed to describe how the characteristics of deaths following drug use changed during the COVID-19 pandemic in England, and how this can inform future strategy to support the health and social care of people who use drugs in future emergency scenarios.MethodAll deaths reported to the National Programme on Substance Abuse Deaths which occurred between January 2018 and December 2021 inclusive were extracted for analysis. Exponential smoothing models were constructed to determine any differences between forecasted vs. actual trends.Key resultsFollowing the first lockdown period in England there were significant increases in the proportion of people who died at home beyond the 95% confidence bounds of the exponential smoothing model and concurrent decreases in the proportion of people who died in hospital. Whilst the overall proportion of deaths attributable to opioids did not significantly deviate from the forecasted trend, there were significant increases in methadone-related deaths and decreases in heroin/morphine-related death beyond the 95% confidence bounds. The proportion of deaths concluded as suicide increased, as did those implicating antidepressant use. There were no changes in the proportion of deaths following use of other drug classes, alcohol use in combination with psychoactive drugs, or on decedent demographics (gender, age, and drug user status). A small number of deaths due to drug use had COVID-19 infection itself listed as a cause of death (n = 23).ConclusionFor people who use drugs, the impact of the restrictions due to the COVID-19 pandemic was greater than that of infection from the virus itself. The health and social care strategy for these people needs to be pre-emptively adapted to mitigate against the specific risk factors for fatal drug overdose associated with future emergency scenarios

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Opioid-related deaths during hospital admissions or shortly after discharge in the United Kingdom: A thematic framework analysis of coroner reports.

BackgroundPeople who use heroin and other illicit opioids are at high risk of fatal overdose in the days after hospital discharge, but the reasons for this risk have not been studied.MethodsWe used the National Programme on Substance Abuse Deaths, a database of coroner reports for deaths following psychoactive drug use in England, Wales, and Northern Ireland. We selected reports where the death occurred between 2010 and 2021, an opioid was detected in toxicology testing, the death was related to nonmedical opioid use, and death was either during an acute medical or psychiatric hospital admission or within 14 days after discharge. We used thematic framework analysis of factors that may contribute to the risk of death during hospital admission or after discharge.ResultsWe identified 121 coroners' reports; 42 where a patient died after using drugs during hospital admission, and 79 where death occurred shortly after discharge. The median age at death was 40 (IQR 34-46); 88 (73%) were male; and sedatives additional to opioids were detected at postmortem in 88 cases (73%), most commonly benzodiazepines. In thematic framework analysis, we categorised potential causes of fatal opioid overdose into three areas: (a) hospital policies and actions. Zero-tolerance policies mean that patients conceal drug use and use drugs in unsafe places such as locked bathrooms. Patients may be discharged to locations such as temporary hostels or the street while recovering. Some patients bring their own medicines or illicit opioids due to expectations of low-quality care, including undertreated withdrawal or pain; (b) high-risk use of sedatives. People may increase sedative use to manage symptoms of acute illness or a mental health crisis, and some may lose tolerance to opioids during a hospital admission; (c) declining health. Physical health and mobility problems posed barriers to post-discharge treatment for substance use, and some patients had sudden deteriorations in health that may have contributed to respiratory depression.ConclusionHospital admissions are associated with acute health crises that increase the risk of fatal overdose for patients who use illicit opioids. Hospitals need guidance to help them care for this patient group, particularly in relation to withdrawal management, harm reduction interventions such as take-home naloxone, discharge planning including continuation of opioid agonist therapy during recovery, management of poly-sedative use, and access to palliative care

Opioid-related deaths during hospital admissions or shortly after discharge in the United Kingdom: A thematic framework analysis of coroner reports

Background People who use heroin and other illicit opioids are at high risk of fatal overdose in the days after hospital discharge, but the reasons for this risk have not been studied. Methods We used the National Programme on Substance Abuse Deaths, a database of coroner reports for deaths following psychoactive drug use in England, Wales, and Northern Ireland. We selected reports where the death occurred between 2010 and 2021, an opioid was detected in toxicology testing, the death was related to nonmedical opioid use, and death was either during an acute medical or psychiatric hospital admission or within 14 days after discharge. We used thematic framework analysis of factors that may contribute to the risk of death during hospital admission or after discharge. Results We identified 121 coroners’ reports; 42 where a patient died after using drugs during hospital admission, and 79 where death occurred shortly after discharge. The median age at death was 40 (IQR 34–46); 88 (73%) were male; and sedatives additional to opioids were detected at postmortem in 88 cases (73%), most commonly benzodiazepines. In thematic framework analysis, we categorised potential causes of fatal opioid overdose into three areas: (a) hospital policies and actions. Zero-tolerance policies mean that patients conceal drug use and use drugs in unsafe places such as locked bathrooms. Patients may be discharged to locations such as temporary hostels or the street while recovering. Some patients bring their own medicines or illicit opioids due to expectations of low-quality care, including undertreated withdrawal or pain; (b) high-risk use of sedatives. People may increase sedative use to manage symptoms of acute illness or a mental health crisis, and some may lose tolerance to opioids during a hospital admission; (c) declining health. Physical health and mobility problems posed barriers to post-discharge treatment for substance use, and some patients had sudden deteriorations in health that may have contributed to respiratory depression. Conclusion Hospital admissions are associated with acute health crises that increase the risk of fatal overdose for patients who use illicit opioids. Hospitals need guidance to help them care for this patient group, particularly in relation to withdrawal management, harm reduction interventions such as take-home naloxone, discharge planning including continuation of opioid agonist therapy during recovery, management of poly-sedative use, and access to palliative care

Themes relating to the risk of opioid-related deaths during hospital admissions or shortly after hospital discharge.

Themes relating to the risk of opioid-related deaths during hospital admissions or shortly after hospital discharge.</p

Flow chart of the process of selecting coroner reports for analysis.

NPSAD = National Programme on Substance Abuse Deaths.</p

Characteristics of study participants; data from NPSAD 2010–2021.

Characteristics of study participants; data from NPSAD 2010–2021.</p

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.</p