Research (Articles)

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Urine toxicology screening reduces misdiagnosis of cocaine-induced ANCA-positive disease as idiopathic granulomatosis with polyangiitis
(Oxford University Press, 2025-02-11) Bateman, James; Nadeem, Mir; Barraclough, James; Adizie, Tochukwu; Pucci, Mark; Sheeran, Tom; University of Birmingham; Royal Wolverhampton NHS Trust; Sandwell and West Birmingham NHS Trust; University of Wolverhampton; West Midlands Poisons Unit; Medical and Dental; Pucci, Mark
Objectives: Study aims were to assess the impact of urine cocaine screening in distinguishing cocaine-induced midline destruction lesions (CIMDLs) from idiopathic ANCA-associated systemic vasculitis (AASV), to evaluate the adoption and effectiveness of screening and to explore its clinical implications. Methods: We conducted a retrospective single-centre case series, reviewing rheumatology patients with suspected new or relapsing AASV, ages 18-55 years, from April 2021 to July 2024. Patients were in two groups: an active screening group offering urinary cocaine testing for all patients and a standard care group, with ad hoc testing based on clinical suspicion. Demographics, clinical presentations and diagnostic pathways were analysed. Results: Of 11 cases in the active screening group, all denied cocaine use, 7 were diagnosed with CIMDL from urine screening and 4 patients were treated for vasculitis. In the standard care group of 15 patients, 2 patients had CIMDLs (admitted cocaine use), no patients had urine screening and 13 were treated for AASV. In total, there were nine CIMDL cases [mean age 38.2 years (interquartile range 11; six females), most [7/9 (78%)] were from active screening. CIMDL presentations were heterogeneous, including vocal cord palsy, lymphadenopathy and cutaneous vasculitis. CIMDL cases were positive for perinuclear ANCA (6/9) and PR3 (7/9), with no MPO positivity, and 5/9 (71%) failed to provide an adequate initial urine sample. There were no formal complaints or concerns from screening. Conclusion: These data support the effectiveness and acceptability of systematic screening for cocaine to improve the identification of CIMDLs, reducing misdiagnosis and unnecessary treatment. A protocol for systematic screening is proposed to improve the care for these patients.
Comment on "Naloxone dosing and hospitalization for Nitazene overdose : a scoping review"
(Springer, 2025-04-15) Pucci, Mark; Jutley, Gurpreet Singh; Sandwell and West Birmingham NHS Trust; West Midlands Poisons Unit; Medical and Dental; Pucci, Mark; Jutley, Gurpreet Singh
No abstract available.
Poisoning in adolescents in the UK : a review of enquiries to the National Poisons Information Service
(BMJ Publishing Group, 2025-03-22) Watt, Annie; Caparrotta, Thomas; Bradberry, Sally; Gray, Laurence; Thanacoody, Ruben; Jackson, Gill; Sandilands, Euan A; Royal Infirmary of Edinburgh; Sandwell and West Birmingham NHS Trust; University Hospital Llandough; Regional Drug & Therapeutics Centre; National Poisons Information Service; Medical and Dental; Bradberry, Sally
Objective: The objective of this study is to analyse enquiries received by the UK National Poisons Information Service (NPIS) regarding poisoning in adolescent patients. Design: A retrospective analysis of telephone enquiries regarding patients aged 10-18 years inclusive to the UK NPIS between 1 January 2015 and 31 December 2022. Data analysed included patient demographics, nature of the poisoning, agent(s) involved and poisoning severity. Results: A total of 29 750 enquiries were received, of which 66% were regarding female patients. The largest proportion overall involved intentional self-poisoning. These enquiries have significantly increased since 2019, particularly in patients aged 10-12 (2019: 71 (2.2%) vs 2022: 181 (4.3%); p<0.0001) and 13-15 (796 (24.3%) (2019) vs 1429 (33.9%) (2022); p<0.0001). Pharmaceutical agents were most often implicated, with paracetamol and non-steroidal anti-inflammatory drugs being most common. Enquiries involving these agents have significantly increased since 2019. Recreational drugs were only involved in 4.3% of enquiries. Most cases (87.6%) were of low toxicity, but 44 deaths were recorded during the study. Conclusions: Self-poisoning in adolescent patients is an important issue in the UK. NPIS enquiries regarding intentional self-poisoning have risen significantly since 2019 and the COVID-19 pandemic and increasingly involve younger patients aged 10-12 and 13-15 years. Easily accessible medicines are most often involved. With improved recognition and understanding of this problem, initiatives can be targeted to those most at risk.
A case series of ibogaine toxicity reported to the United Kingdom National Poisons Information Service (NPIS) over a 10-year period
(Taylor and Francis Group, 2025-01-30) Edwards, Ella P; Gray, Laurence A; Elamin, Muhammad; Veiraiah, Aravindan; Thanacoody, Ruben H K; Coulson, James M; University Hospital Llandough; Sandwell and West Birmingham NHS Trust; Royal Infirmary of Edinburgh; Newcastle-upon-Tyne Hospitals; National Poisons Information Service; Medical and Dental; Elamin, Muhammad EMO
Introduction: Ibogaine is a psychoactive alkaloid derived from the root bark of the West African shrub Tabernanthe iboga. It is not licensed in the United Kingdom but is used by individuals to alleviate drug or alcohol use. Methods: A retrospective analysis of telephone enquiries involving ibogaine between 1 January 2012 and 31 December 2022 to the United Kingdom National Poisons Information Service was performed. Case series: Eleven enquiries relating to seven patients were made to the United Kingdom National Poisons Information Service in this period. Five of these patients were male (71%) with the majority in the age category 31-40 years (57%). All patients presented symptomatically. The circumstances for all seven cases were recorded as "recreational abuse." The exact indication was not specified in three cases but in two cases it was being used to alleviate diacetylmorphine (heroin) use and in another two cases it was being used for relief from insomnia. Three sources of ibogaine were reported - in one case it was bought online, in one case by a dealer and in two cases it was bought from a shaman. When reported, the dose ingested ranged from 5g to 34g. Two patients took it in tablet form and four patients ingested the root bark. The time since exposure, when reported, ranged from 16 h to 1 month. Seven patients experienced neurological symptoms and six displayed features of cardiotoxicity. The most frequently reported features included cardiac arrest, hypoxia, torsade de pointes, QT interval prolongation, coma, convulsions, stupor, bradycardia, vomiting and anxiety. Conclusions: Individuals using ibogaine in variable doses to self-treat for drug use are at risk of developing severe cardiotoxicity and neurological symptoms. Further studies to quantify dose-response relationship and to further improve knowledge of its pharmacokinetics are required.
Treatment of chloramine-induced chemical pneumonitis with extracorporeal membrane oxygenation (ECMO) following bleach and disinfectant inhalation
(Taylor and Francis Group, 2023-01-19) Moyns, Emma; Welby-Everard, Peter; Karim, N A; Thanacoody, R H K; Sandwell and West Birmingham NHS Trust; Hairmyres Hospital; National Poisons Information Service (Newcastle Unit); West Midlands Poisons Unit; Medical and Dental; Moyns, Emma J.; Welby-Everard, Peter
No abstract available.
Fatal lead encephalopathy following the ingestion of fishing weights ("sinkers").
(Taylor and Francis Group, 2021-11-03) Vale, Allister; Barlow, Nicola; Bradberry, Sally M; Sandwell and West Birmingham NHS Trust; Black Country Pathology Service; Poison Unit; Medical and Dental; Vale, Allister; Bradberry, Sally
No abstract available
Moderate-to-severe envenoming requiring ViperaTAb antivenom therapy in the UK.
(Taylor and Francis Group, 2021-03-15) Lamb, Thomas; Stewart, David; Warrell, David A; Lalloo, David G; Jagpal, Pardeep; Jones, Dacia; Thanacoody, Ruben; Gray, Laurence A; Eddleston, Michael; Royal Infirmary of Edinburgh; University of Oxford; Liverpool School of Tropical Medicine; Sandwell and West Birmingham NHS Trust; Sandwell West Birmingham NHS Trust; Medical and Dental; Jagpal, Pardeep
Bites by the European adder (Vipera berus) in the UK are uncommon but potentially life threatening, and can be associated with marked limb swelling and disability. Following an interruption in Zagreb Imunološki zavod antivenom supply around 2012, the UK changed its national choice of antivenom for Vipera berus to ViperaTAb, an ovine Fab monospecific antivenom. In the absence of randomised controlled trials, we established an audit to review its use in clinical practice.
Medicines and murder.
(SAGE Publications, 2021-03-14) Ferner, Robin; Sandwell and West Birmingham NHS Trust; Sandwell and West Birmingham NHS Trust; Healthcare Scientists; Ferner, Robin
Medicines and murder
Outbreak of lead poisoning from a civilian indoor firing range in the UK
(BMJ Publishing Group, 2024-03-08) Warsi, Aamna; Pucci, Mark Richard; Bradberry, Sally Marie; Khan, Aleha; Elamin, Muhammad Elamin Muhammad Osman; Royal Air Force Medical Services; Sandwell and West Birmingham NHS Trust; Black Country Pathology Services; West Midlands Poisons Unit; Medical and Dental; Pucci, Mark R.; Bradberry, Sally M.; Elamin, Muhammad EMO.
Introduction: Lead exposure from discharged lead dust is a recognised risk at firing ranges. We report a lead poisoning outbreak among staff and their close contacts at a UK civilian indoor 24 m firing range. Methods: A retrospective review was undertaken of data collected on all patients at risk of lead poisoning identified either by direct referral to the Clinical Toxicology clinicians at the West Midlands Poisons Unit, or via the Trace Elements Supra-Regional Assay Service Laboratory at Sandwell hospital. Results: Eighty-seven patients were identified as having possible lead exposure, either at the firing range or via close contacts. Of these, 63 patients aged between 6 months and 78 years attended for blood lead concentration (BLC) testing. The highest BLC at presentation was 11.7 µmol/L (242 µg/dL). Only nine patients reported any symptoms at presentation. Fifteen patients received lead chelation therapy with oral dimercaptosuccinic acid (or succimer) 30 mg/kg/day or intravenous sodium calcium edetate (EDTA) 75 mg/kg/day, dependent on stock availability. Discussion: This report highlights the need for vigilance of lead poisoning as an occupational hazard in the UK, including at recreational facilities such as indoor firing ranges. It emphasises the importance of regulation of lead exposure in the workplace, particularly given the vague symptoms of lead poisoning, and proposes re-appraisal of UK legislation. This report also highlights potential issues surrounding stock availability of rarely used antidotes for uncommon presentations in the event of an outbreak of poisoning.
N-desethyl isotonitazene detected in polydrug users admitted to hospital in Birmingham, United Kingdom
(Taylor and Francis Group, 2024-02-14) Pucci, Mark; Singh Jutley, Gurpreet; Looms, Jonathan; Ford, Loretta; Sandwell and West Birmingham NHS Trust; West Midlands Poisons Unit; Toxicology; Medical and Dental; Pucci, Mark; Singh Jutley, Gurpreet; Looms, Jonathan; Ford, Loretta
Introduction: Nitazenes are potent synthetic opioids and N-desethyl isotonitazene, a metabolite of isotonitazene, has emerged as a drug in its own right. Methods: This is an observational case series of patients with suspected or declared substance use who were admitted to hospitals in the Sandwell and West Birmingham National Health Service Trust between July and October 2023. All patients were found on toxicological screening to have been exposed to N-desethyl isotonitazene. Results: Twenty presentations involving 19 patients who tested positive for N-desethyl isotonitazene were included in the study. In 19 presentations, multiple substances were detected on toxicological screening. The number of patients testing positive for other substances were: 19 for cocaine and its main metabolite benzoylecgonine, 13 for morphine, 11 for the heroin-specific metabolite 6-monoacetylmorphine, ten for xylazine, eight for gabapentinoids (pregabalin and/or gabapentin), seven for methadone and/or the metabolite, 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine, six for benzodiazepines and five for the synthetic cannabinoid MDMB-4en-PINACA. Only one patient had no other substances detected apart from N-desethyl isotonitazene. This patient presented with coma, miosis, bradypnoea and hypercapnia and responded to naloxone. In this cohort, the median concentration of N-desethyl isotonitazene was 1.53 µg/L (n = 14; range 0.59-5.48) in whole blood and 27.75 µg/L (n = 16; range 0.51-91.53) in urine. Discussion: The majority of the patients in this cohort presented with features typical of an opioid overdose, which is unsurprising as they were all experienced users of diamorphine. Although these features are also consistent with the known effects of N-desethyl isotonitazene, in only one case is it possible to attribute the patient's features to N-desethyl isotonitazene toxicity alone. Conclusions: This case series highlights the need for toxicovigilance in the illicit drug market as patterns of substance misuse evolve and novel psychoactive substances continue to emerge.
Recognition of Coroners' concerns to prevent future deaths from medicines : a systematic review
(Springer, 2023-07-08) Ferner, Robin; Brittain, Richard; Cox, Anthony R; Heneghan, Carl; Richards, Georgia C; Aronson, Jeffrey K; University of Birmingham; Sandwell and West Birmingham NHS Trust; St Pancras Coroner's Court; University of Oxford; West Midlands Centre for Adverse Drug Reactions; Medical and Dental; Ferner, Robin
Background: Coroners, who hold inquests to determine the causes of unnatural deaths in England and Wales, having recognised factors that could cause other deaths, are legally obliged to signal concerns by sending 'Reports to Prevent Future Deaths' (PFDs) to interested persons. We aimed to establish whether Coroners' concerns about medications are widely recognised. Methods: We searched MEDLINE, Embase and Web of Science up to 30 November, 2022 for publications linking PFDs and medications using a combination of search terms "coroner*", "inquest*", "medicine*", "medication*" and "prevent*". We also searched the BMJ, a UK journal that carries news items; and the databases Nexis Advance and News On the Web for reports in national newspapers between 2013 and 2022, using the search terms ("regulation 28" OR "prevent future deaths" OR "prevention of future deaths") AND "coroner". We recorded the number of publications, as well as their citations in Google Scholar at 23 May, 2023. Results: Only 11 published papers on medicines referenced UK PFDs, nine of which were from our group. The BMJ carried 23 articles mentioning PFDs, five related to medicines. Of 139 PFDs (out of over 4000) mentioned in national newspapers, only nine related to medicines. Conclusions: The PFDs related to medicines are not widely referred to in medical journals or UK national newspapers. By contrast, the Australian and New Zealand National Coronial Information System has contributed cases to 206 publications cited in PubMed, of which 139 are related to medicines. Our search suggests that information from English and Welsh Coroners' PFDs is under-recognised, even though it should inform public health. The results of inquiries by Coroners and medical examiners worldwide into potentially preventable deaths involving medicines should be used to strengthen the safety of medicines.
The prescribing safety assessment : protecting patients from poor prescribing
(Taylor and Francis Group, 2023-06-28) McGettigan, Patricia; Ferner, Robin; Queen Mary University of London; Sandwell and West Birmingham NHS Trust; University of Birmingham; West Midlands Centre for Adverse Drug Reactions; Medical and Dental; Ferner, Robin
No abstract available.
Metformin-associated lactic acidosis reported to the United Kingdom National Poisons Information Service (NPIS) between 2010 and 2019 : a ten-year retrospective analysis
(Taylor and Francis Group, 2023-06-15) Hughes, Bethan W; Gray, Laurence A; Bradberry, Sally M; Sandilands, Euan A; Thanacoody, Ruben H; Coulson, James M; University Hospital Llandough; Sandwell and West Birmingham NHS Trust; Royal Infirmary of Edinburgh; Newcastle upon Tyne Hospitals; et al.; National Poisons Information Service; Medical and Dental; Bradberry, Sally M.
Introduction: Metformin toxicity following therapeutic use or overdose may result in metabolic acidosis with hyperlactatemia. This study aims to assess the relationship between serum lactate concentration, arterial pH, and ingested dose with severity of poisoning, and to identify if serum lactate concentration is a useful marker of severity in metformin toxicity. Methods: A retrospective study of telephone enquiries relating to metformin exposures to the National Poisons Information Service between 2010 and 2019 from hospitals in the United Kingdom. Results: Six-hundred and thirty-seven cases were identified; 117 involved metformin only and 520 involved metformin with other drugs. The majority of cases involved acute (87%) and intentional (69%) exposures. There was a statistically significant difference in doses between the Poisoning Severity Scores, as well as between intentional and unintentional or therapeutic error doses (P < 0.0001). The distribution of cases for each Poisoning Severity Score differed between the metformin only and metformin with other drugs cases (P < 0.0001). Lactic acidosis was reported in 232 cases. Serum lactate concentration and arterial pH differed across Poisoning Severity Scores. Arterial pH inversely correlated with ingested dose (r=-0.3, P = 0.003), and serum lactate concentration positively correlated with ingested dose (r = 0.37, P < 0.0001). Serum lactate concentration and arterial pH did not correlate with each other. Twenty-five deaths were recorded, all following intentional overdoses. Discussion: The dataset focuses mostly on acute, intentional overdoses. Increasing ingested metformin dose, a higher serum lactate concentration and worsening arterial pH were all associated with an unfavourable Poisoning Severity Score in patients in both metformin only and metformin with other drugs groups. As serum lactate concentration did not correlate with arterial pH, it represents an independent marker of poisoning severity. Conclusions: Data from the present study suggest that serum lactate concentration can be used to assess severity of poisoning in patients who have reportedly ingested metformin.
Communicating for the safe use of medicines : progress and directions for the 2020s promoted by the special interest group of the International Society of Pharmacovigilance
(Springer, 2023-05-23) Bahri, Priya; Bowring, Geoffrey; Edwards, Brian D; Anton, Christopher; Aronson, Jeffrey K; Caro-Rojas, Angela; Hugman, Bruce P J; Mol, Peter G; Trifirò, Gianluca; Ilic, Katarina; Daghfous, Riadh; Fermont, Irene; Furlan, Giovanni; Gaissmaier, Wolfgang; Geer, Mohammad Ishaq; Hartigan-Go, Kenneth Y; Houÿez, François; Neth, Hansjörg; Norgela, Gediminas; Oppamayun, Yaowares; Raynor, D K Theo; Bouhlel, Mehdi; Santoro, Federica; Sultana, Janet; International Society of Pharmacovigilance; European Medicines Agency; Uppsala Monitoring Centre; Sandwell and West Birmingham NHS Trust; et al.; West Midlands Centre for Adverse Drug Reactions; Admin and Clerical; Anton, Christopher
No abstract available.
Spontaneous Reporting to Regulatory Authorities of Suspected Adverse Drug Reactions to COVID-19 Vaccines Over Time: The Effect of Publicity.
(Adis, 2022-01-22) Ferner, Robin E; Stevens, Richard J; Anton, Christopher; Aronson, Jeffrey K; Sandwell and West Birmingham NHS Trust; University of Birmingham; University of Oxford; Sandwell and West Birmingham NHS Trust; Medical and Dental; Ferner, Robin E; Anton, Christopher
Introduction: The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published frequent summaries of spontaneous reports of suspected adverse drug reactions (ADRs) (Yellow Cards) to vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The EudraVigilance database has provided similar data for the European Economic Area. Objective: Our objective was to characterize the evolution over time of spontaneous reports of suspected ADRs to coronavirus disease 2019 (COVID-19) vaccines and to observe the effect of a publicized reaction (cerebral venous and sinus thrombosis [CVST]) on reporting rates. Methods: We used publicly available data on reports of suspected ADRs and doses of vaccine administered, published by the MHRA, EudraVigilance, and the European Centre for Disease Prevention and Control to calculate reporting rates. Results: Approximately 4814 Yellow Card reports (23 fatal) per million doses of ChAdOx1 nCoV-19 (AstraZeneca) and 2890 (13 fatal) per million doses of tozinameran (Pfizer/BioNTech) have been lodged. Between 15 March and 31 October 2021, cumulative European reports of CVST rose from 0 to 443 (183 with thrombocytopenia, 72 fatal) with ChAdOx1 nCoV-19 and from 2 to 315 (9 with thrombocytopenia, 28 fatal) with tozinameran. European cases of retinal vein occlusion and thrombosis rose from 0 to 168 with ChAdOx1 nCoV-19 and from 1 to 220 with tozinameran; four of the ChAdOx1 nCoV-19 cases were associated with thrombocytopenia. Conclusion: Reports of fatal adverse reactions to coronavirus vaccines are very rare. Reports of CVST have been made in relation to both vaccines. Most were submitted after the reaction had been publicized. Thrombocytopenia occurred in a minority of cases. Reports linked both vaccines to cases of retinal vein thrombosis, just four cases with thrombocytopenia. This suggests two different mechanisms of thrombosis associated with the vaccines.
Comment on Fomepizole as an adjunct in acetylcysteine treated acetaminophen overdose patients: a case series.
(Taylor and Francis Group, 2021-12-23) Bateman, D Nicholas; Dear, James W; Eddleston, Michael; Vale, Allister; University of Edinburgh; Sandwell and West Birmingham NHS Trust; University of Birmingham; Toxicology; Medical and Dental; Vale, J Allister
No abstract available
Treatment of insulin poisoning : a 100-year review
(Wiley, 2023-03-23) Moyns, Emma; Ferner, Robin; Sandwell and West Birmingham NHS Trust; National Poisons Information Service; Medical and Dental; Moyns, Emma J.; Ferner, Robin
Background: Insulin poisoning, as opposed to hypoglycaemia induced by therapeutic doses of insulin, is rare, and guidelines on management differ. We have reviewed the evidence on treatment of insulin poisoning. Methods: We searched PubMed, EMBASE and J-Stage with no restrictions of date or language for controlled studies on treatment of insulin poisoning, collected published cases of insulin poisoning from 1923, and used data from the UK National Poisons Information Service. Results: We identified no controlled trials of treatment in insulin poisoning and few relevant experimental studies. Case reports described 315 admissions (301 patients) with insulin poisoning between 1923 and 2022. The insulin with the longest duration of action was long-acting in 83 cases, medium-acting in 116, short-acting in 36 and a rapid-acting analogue in 16. Decontamination by surgical excision of the injection site was reported in six cases. To restore and maintain euglycaemia, almost all cases were treated with glucose, infused for a median 51 hours, interquartile range 16-96 h in 179 cases; 14 patients received glucagon and nine octreotide; adrenaline was tried occasionally. Both corticosteroids and mannitol were occasionally given to mitigate hypoglycaemic brain damage. There were 29 deaths reported, 22/156 (86% survival) up to 1999 and 7/159 (96% survival) between 2000 and 2022 (p = 0.003). Conclusions: There is no randomized controlled trial to guide treatment of insulin poisoning. Treatment with glucose infusion, sometimes supplemented with glucagon, is almost always effective in restoring euglycaemia, but optimum treatments to maintain euglycaemia and restore cerebral function remain uncertain.
Ferric chloride ingestion with corrosive gastritis.
(Informa Healthcare, 2022-09-26) Pucci, Mark; Theodorou, Pavlos; Patel, Neel; Sandwell and West Birmingham NHS Trust; Acute Medical Unit; Neurology; West Midlands Poisons Unit; Medical and Dental; Medical and Dental; Pucci, Mark; Theodorou, Pavlos; Patel, Neel
No abstract available
Successful treatment of potentially lethal dose thallium sulfate poisoning with sequential use of Prussian blue and multiple-dose activated charcoal
(Taylor and Francis Group, 2023-02-15) Wallbridge, Thomas; James, Sunil; Lee, Ryan; Khan, Aleha; Bradberry, Sally; Elamin, Muhammad; Sandwell and West Birmingham NHS Trust; National Poisons Information Service (Birmingham Unit); Black Country Pathology Services; West Midlands Poisons Unit; Medical and Dental; Wallbridge, Thomas; James, Sunil; Bradberry, Sally; Elamin, Muhammad EMO
No abstract available.
Medicines legislation and regulation in the United Kingdom 1500-2020.
(Wiley, 2022-09-23) Ferner, Robin; Aronson, Jeffrey K; University of Birmingham; Sandwell and West Birmingham NHS Trust; University of Oxford; West Midlands Centre for Adverse Drug Reactions; Medical and Dental; Ferner, Robin
The initial purposes of regulation of medicines in England, and latterly in the United Kingdom, were principally to raise government revenue, to discourage murder by poisoning and to regulate the activities of pharmacists. It was only much later that regulators sought to ensure that medicines were of good quality, reasonably safe, and at least somewhat effective, and to curtail misuse of drugs. Here we survey the history of the regulation of medicines and poisons in England from the perspective of clinicians with an interest in therapeutics.

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