Botensilimab and Balstilimab Optimization in Colorectal Cancer

Preventable deaths involving opioids in England and Wales, 2013-2022: a systematic case series of coroners’ reports (preprint)

Background Deaths from opioids have increased in England and Wales, despite recognition of their harms. Coroners’ Prevention of Future Death reports (PFDs) provide important insights that may enable safer use and avert harms, yet these reports involving opioids have not been synthesised. We therefore aimed to identify opioid-related PFDs and explore concerns expressed by coroners to prevent future deaths. Methods In this systematic case series, we screened 3897 coronial PFDs dated between 01 July 2013 and 23 February 2022. These were obtained by web scraping the UK’s Courts and Tribunals Judiciary website to create an openly available database: https://preventabledeathstracker.net/ . PFDs were included when an opioid was implicated in the death. Included PFDs were descriptively analysed, and content analysis was used to assess concerns reported by coroners and responses to such concerns. Findings Opioids were involved in 219 deaths reported by coroners in PFDs (5·6% of all PFDs), equating to 4418 years of life lost (median 33 years/person). Morphine (29%), methadone (23%), and diamorphine (16%) were the most common implicated opioids. Coroners most frequently raised concerns regarding systems and protocols (52%) or safety issues (15%). These concerns were most often addressed to NHS organisations (51%), but response rates were low overall (47%). Interpretation Opioids could be used more safely and appropriately if coroners’ concerns in PFDs were addressed by national organisations such as NHS bodies, government agencies, and policymakers, as well as individual prescribing clinicians. Funding No funding was obtained for this study. The National Institute for Health Research (NIHR) School for Primary Care Research (SCPR) provided funding to establish the Preventable Deaths Tracker website: https://preventabledeathstracker.net/ Research in context Evidence before this study We conducted a systematic search of PubMed and Google Scholar to identify studies of deaths involving opioids in England and Wales and analyses of coroners’ Prevention of Future Death reports (PFDs). We found that deaths from opioids had increased in England and Wales. We also identified studies that have used PFDs to assess preventable deaths during the COVID-19 pandemic and deaths involving anticoagulants, medicines purchased online, medication errors and adverse drug reactions. However, no study to date has examined opioid-related PFDs. Added value of this study We analysed coroners’ concerns in opioid-related deaths for which they issued PFDs and found that on average three decades of life are lost per individual. We found that most opioid-related PFDs involved males (64%) and were caused by prescribed opioids (52%). Deaths involving illicit opioids (24%) were more likely to occur in younger males than deaths from prescribed opioids. Failures in systems and processes were most commonly found to have contributed to preventable opioid-related deaths, but more than half of such concerns remain unaddressed. Implications of all the available evidence Coroners’ PFDs offer important real-world insights into opioid-related deaths and can inform public health strategies that aim to improve the safe use of opioids. Future work should focus on disseminating these findings more widely and engaging with key stakeholders such as NHS organisations and government agencies, so that findings from PFDs can inform guidelines and be implemented in clinical practice.

Trends, regional variation and clinical characteristics of recipients of antivirals and neutralising monoclonal antibodies for non-hospitalised COVID-19: a descriptive cohort study of 23.4 million people in OpenSAFELY (preprint)

ObjectivesAscertain patient eligibility status and describe coverage of antivirals and neutralising monoclonal antibodies (nMAB) as treatment for COVID-19 in community settings in England. DesignCohort study, approved by NHS England. SettingRoutine clinical data from 23.4m people linked to data on COVID-19 infection and treatment, within the OpenSAFELY-TPP database. ParticipantsNon-hospitalised COVID-19 patients at high-risk of severe outcomes. InterventionsNirmatrelvir/ritonavir (Paxlovid), sotrovimab, molnupiravir, casirivimab or remdesivir, administered in the community by COVID-19 Medicine Delivery Units. ResultsWe identified 102,170 non-hospitalised patients with COVID-19 between 11th December 2021 and 28th April 2022 at high-risk of severe outcomes and therefore potentially eligible for antiviral and/or nMAB treatment. Of these patients, 18,210 (18%) received treatment; sotrovimab, 9,340 (51%); molnupiravir, 4,500 (25%); Paxlovid, 4,290 (24%); casirivimab, 50 (<1%); and remdesivir, 20 (<1%). The proportion of patients treated increased from 8% (180/2,380) in the first week of treatment availability to 22% (420/1870) in the latest week. The proportion treated varied by high risk group, lowest in those with Liver disease (12%; 95% CI 11 to 13); by treatment type, with sotrovimab favoured over molnupiravir/Paxlovid in all but three high risk groups: Down syndrome (36%; 95% CI 31 to 40), Rare neurological conditions (46%; 95% CI 44 to 48), and Primary immune deficiencies (49%; 95% CI 48 to 51); by ethnicity, from Black (10%; 95% CI 9 to 11) to White (18%; 95% CI 18 to 19); by NHS Region, from 11% (95% CI 10 to 12) in Yorkshire and the Humber to 23% (95% CI 22 to 24) in the East of England); and by deprivation level, from 12% (95% CI 12 to 13) in the most deprived areas to 21% (95% CI 21 to 22) in the least deprived areas. There was also lower coverage among unvaccinated patients (5%; 95% CI 4 to 7), those with dementia (5%; 95% CI 4 to 6) and care home residents (6%; 95% CI 5 to 6). ConclusionsUsing the OpenSAFELY platform we were able to identify patients who were potentially eligible to receive treatment and assess the coverage of these new treatments amongst these patients. Targeted activity may be needed to address apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, socioeconomically deprived areas, and care homes. What is already known about this topicSince the emergence of COVID-19, a number of approaches to treatment have been tried and evaluated. These have mainly consisted of treatments such as dexamethasone, which were used in UK hospitals,from early on in the pandemic to prevent progression to severe disease. Until recently (December 2021), no treatments have been widely used in community settings across England. What this study addsFollowing the rollout of antiviral medicines and neutralising monoclonal antibodies (nMABs) as treatment for patients with COVID-19, we were able to identify patients who were potentially eligible to receive antivirals or nMABs and assess the coverage of these new treatments amongst these patients, in as close to real-time as the available data flows would support. While the proportion of the potentially eligible patients receiving treatment increased over time, rising from 8% (180/2,380) in the first week of the roll out to 22% (420/1870) in the last week of April 2022, there were variations in coverage between key clinical, geographic, and demographic subgroup. How this study might affect research, practice, or policyTargeted activity may therefore be needed to address lower treatment rates observed among certain geographic areas and key groups including ethnic minorities, people living in areas of higher deprivation, and in care homes.