Use of the online poisons information database TOXBASE and admissions rates for poisoned patients from emergency departments in England and Wales during 2008 to 2015

Background The impact of poison information services on patient care in hospital, particularly decisions on whether to admit patients after initial attendance at an emergency department (ED), is unclear. In the United Kingdom, the vast majority of poisons information is provided by use of the online poisons information database, TOXBASE. We investigated the relationship between rates of hospital access to TOXBASE and rates of poisoning admissions from EDs in England and Wales to begin to address the interactions between use of poisons information and patient management as reflected by hospital activity. Methods Data were obtained on attendances and admissions due to poisoning for individual National Health Service (NHS) Trusts in both England and Wales, together with data on the overall number of accesses to TOXBASE for drugs (pharmaceuticals and drugs of abuse), from 2008 to 2015. Rates of TOXBASE access and admissions per poisoning attendance in London were clearly different to the rest of England and Wales; London was therefore analyzed separately. Negative binomial generalized additive models were fit, incorporating an interaction effect, for accesses, attendances and admissions to check for variability according to hospital size. Additional models were then fit to assess whether there was any variation in association of overall TOXBASE use with rates of admission for 6 key drug subgroups: antidepressants, paracetamol, antipsychotics, opioids (including all medicines, but excluding heroin), heroin and non‐opioid drugs of abuse. Results Rates of TOXBASE use per Trust increased across the study period by 39.3% (95% confidence interval [CI] = 34.1%, 44.8%) in England and 76.9% (24.7%, 151.0%) in Wales, showing an increase in TOXBASE use which was substantially greater than the increase in poisoning attendances. Admission rates exhibited seasonality, with lower rates in January and February, increasing by 2.0% (1.0%, 3.1%) in England and 5.8% (5.5%, 5.9%) in Wales toward the middle of the year. The initial model fit indicated that the average proportion of poisoning patients admitted increased with both increasing attendances and increasing TOXBASE use (England and Wales overall, P < 0.0001; England and Wales excluding London, P < 0.0001; London, P < 0.0001). In England and Wales overall, and in London alone, increased TOXBASE access to non‐opioid drugs of abuse advice was associated with a significant decrease in admissions (England and Wales, −0.15% [−0.29%, −0.01%] [P = 0.032]; London, −1.02% [−1.53%, −0.50%] [P < 0.0001]). In contrast, increased access to heroin advice was associated with a significant increase in admissions in London (+2.03% [+0.11%, +3.99%] [P = 0.034]). Increasing access to TOXBASE for paracetamol advice was associated with lower admissions in England and Wales (England and Wales, −0.11% [−0.23%, −0.01%] [P = 0.036]; England and Wales excluding London, −0.18% [−0.30%, −0.06%] [P = 0.001]) but higher admissions in London (+0.52% [+0.03%, +1.01%] [P = 0.035]). Conclusions We have shown that greater overall use of TOXBASE by hospitals is associated with a higher proportion of poisoning attendances being admitted. Interestingly, looking at particular drug groups, we found significant associations in both directions between overall TOXBASE use and rates of admission for some drug groups. The current methodology is unable to determine whether such decisions might be appropriate or not. Mixed‐methods research is now required to gain a better understanding of how provision of poisons information affects decisions within the ED

Bites by exotic snakes reported to the UK National Poisons Information Service 2009-2020

Introduction: Snakebite is recognised as a neglected tropical disease and a cause of substantial morbidity and mortality. Whilst the most medically important snakes are typically native of Asia, Africa, Latin America and Oceania, the possibility of encountering these snakes is no longer limited by geography due to an increasing number of exotic (non-native) snakes being held in captivity. Methods: A retrospective review of snakebite enquiries to the UK National Poisons Information Service (NPIS) between 2009 and 2020. Enquiries about the European adder (Vipera berus) or where the identity of the snake was unknown were excluded. Results: There were 321 exotic snakebites in 300 patients involving 68 different species during this period. Ten patients were bitten on more than one occasion. The majority of patients (64.5%) were male. Most bites were inflicted by snakes of the family Colubridae (184/321, 57.3%); seventeen bites resulted in moderate symptoms (predominantly swelling of the bitten limb). There were 30 (9.3%) bites by Viperidae and 14 (4.3%) bites by Elapidae. All severe cases (n = 15) resulted from bites by either Viperidae (n = 10) or Elapidae (n = 5). Antivenom was given in 17 cases. One fatality was recorded. Conclusions: Despite their low incidence, exotic snakebites present a substantial challenge for UK healthcare professionals. Although rare, these bites typically occur in individuals (usually male) who keep snakes as part of their occupation or hobby and are therefore at risk of multiple bites. Bites can result in venom hypersensitisation and the risk of venom-induced anaphylaxis. Rapid access to expert clinical advice is available in the UK on a 24-hour basis through the National Poisons Information Service and is strongly recommended in all cases of exotic snakebite

Acetylcysteine has No Mechanistic Effect in Patients at Risk of Contrast-Induced Nephropathy - A Failure of Academic Clinical Science

Contrast‐induced nephropathy (CIN) is a major complication of imaging in patients with chronic kidney disease (CKD). The publication of an academic randomized controlled trial (RCT; n = 83) reporting oral (N)‐acetylcysteine (NAC) to reduce CIN led to > 70 clinical trials, 23 systematic reviews, and 2 large RCTs showing no benefit. However, no mechanistic studies were conducted to determine how NAC might work; proposed mechanisms included renal artery vasodilatation and antioxidant boosting. We evaluated the proposed mechanisms of NAC action in participants with healthy and diseased kidneys. Four substudies were performed. Two randomized, double‐blind, placebo‐controlled, three‐period crossover studies (n = 8) assessed the effect of oral and intravenous (i.v.) NAC in healthy kidneys in the presence/absence of iso‐osmolar contrast (iodixanol). A third crossover study in patients with CKD stage III (CKD3) (n = 8) assessed the effect of oral and i.v. NAC without contrast. A three‐arm randomized, double‐blind, placebo‐controlled parallel‐group study, recruiting patients with CKD3 (n = 66) undergoing coronary angiography, assessed the effect of oral and i.v. NAC in the presence of contrast. We recorded systemic (blood pressure and heart rate) and renal (renal blood flow (RBF) and glomerular filtration rate (GFR)) hemodynamics, and antioxidant status, plus biomarkers of renal injury in patients with CKD3 undergoing angiography. Primary outcome for all studies was RBF over 8 hours after the start of i.v. NAC/placebo. NAC at doses used in previous trials of renal prophylaxis was essentially undetectable in plasma after oral administration. In healthy volunteers, i.v. NAC, but not oral NAC, increased blood pressure (mean area under the curve (AUC) mean arterial pressure (MAP): mean difference 29 h⋅mmHg, P = 0.019 vs. placebo), heart rate (28 h⋅bpm, P < 0.001), and RBF (714 h⋅mL/min, 8.0% increase, P = 0.006). Renal vasodilatation also occurred in the presence of contrast (RBF 917 h⋅mL/min, 12% increase, P = 0.005). In patients with CKD3 without contrast, only a rise in heart rate (34 h⋅bpm, P = 0.010) and RBF (288 h⋅mL/min, 6.0% increase, P = 0.001) occurred with i.v. NAC, with no significant effect on blood pressure (MAP rise 26 h⋅mmHg, P = 0.156). Oral NAC showed no effect. In patients with CKD3 receiving contrast, i.v. NAC increased blood pressure (MAP rise 52 h⋅mmHg, P = 0.008) but had no effect on RBF (151 h⋅mL/min, 3.0% increase, P = 0.470), GFR (29 h⋅mL/min/1.73m², P = 0.122), or markers of renal injury. Neither i.v. nor oral NAC affected plasma antioxidant status. We found oral NAC to be poorly absorbed and have no reno‐protective effects. Intravenous, not oral, NAC caused renal artery vasodilatation in healthy volunteers but offered no protection to patients with CKD3 at risk of CIN. These findings emphasize the importance of mechanistic clinical studies before progressing to RCTs for novel interventions. Thousands were recruited to academic clinical trials without the necessary mechanistic studies being performed to confirm the approach had any chance of working

Safety and efficacy of the SNAP 12 hour acetylcysteine regimen for the treatment of paracetamol overdose

© 2019 Background: Acetylcysteine (NAC) is effective at preventing liver injury after paracetamol overdose. The Scottish and Newcastle Anti-emetic Pre-treatment for Paracetamol Poisoning (SNAP) Study demonstrated that a 12 h NAC regimen was associated with fewer adverse drug reactions compared with the standard 21 h regimen. Here, we describe the clinical effectiveness of the SNAP NAC regimen. Methods: The SNAP regimen, consisting of intravenous NAC 100 mg/kg over 2 h then 200 mg/kg over 10 h, was introduced to treat all paracetamol overdose patients at the Royal Infirmary of Edinburgh, the Royal Victoria Infirmary, Newcastle and St Thomas' Hospital, London. Patient data were prospectively and systematically collected before and after the change in treatment (total patients N = 3340, 21 h N = 1488, SNAP N = 1852). Health record linkage was used to determine patient outcome after hospital discharge. Findings: There was no difference in liver injury or liver synthetic dysfunction between regimens. Hepatotoxicity (peak ALT > 1000 U/L) occurred in 64 (4.3%) and 67 (3.6%) patients, respectively, in the 21 h and SNAP groups (absolute difference − 0.7%, 95% CI − 2.1 to 0.6). Multivariable logistic regression did not identify treatment regimen as an outcome-associated factor. No patients were readmitted to hospital with, or died from, liver failure within 30 days of discharge. Anti-histamine treatment (for NAC anaphylactoid drug reactions) was prescribed for 163 (11.0%) patients with the 21 h regimen and 37 (2.0%) patients with the SNAP regimen (absolute difference 9.0% (95% CI 7.3 to 10.7)). Interpretation: In clinical use the SNAP regimen has similar efficacy as standard therapy for preventing liver injury and produces fewer adverse reactions

Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial:a randomised controlled trial

Copyright © 2014 Bateman et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved. The trial was funded by Chief Scientist Office, Scotland (award CZB/4/722).Peer reviewedPublisher PD

Effect of the UK's revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment

AIMS: In September 2012 the UK’s Commission on Human Medicines (CHM) recommended changes in the management of paracetamol poisoning: use of a single ‘100 mg l(−1)’ nomogram treatment line, ceasing risk assessment, treating all staggered/uncertain ingestions and increasing the duration of the initial acetylcysteine (NAC) infusion from 15 to 60 min. We evaluated the effect of this on presentation, admission, treatment, adverse reactions and costs of paracetamol poisoning. METHODS: Data were prospectively collected from adult patients presenting to three large UK hospitals from 3 September 2011 to 3 September 2013 (year before and after change). Infusion duration effect on vomiting and anaphylactoid reactions was examined in one centre. A cost analysis from an NHS perspective was performed for 90 000 patients/annum with paracetamol overdose. RESULTS: There were increases in the numbers presenting to hospital (before 1703, after 1854; increase 8.9% [95% CI 1.9, 16.2], P = 0.011); admitted (1060/1703 [62.2%] vs. 1285/1854 [69.3%]; increase 7.1% [4.0, 10.2], P < 0.001) and proportion treated (626/1703 [36.8%] vs. 926/1854 [50.0%]; increase: 13.2% [95% CI 10.0, 16.4], P < 0.001). Increasing initial NAC infusion did not change the proportion of treated patients developing adverse reactions (15 min 87/323 [26.9%], 60 min 145/514 [28.2%]; increase: 1.3% [95% CI –4.9, 7.5], P = 0.682). Across the UK the estimated cost impact is £8.3 million (6.4 million–10.2 million) annually, with a cost-per-life saved of £17.4 million (13.4 million–21.5 million). CONCLUSIONS: The changes introduced by the CHM in September 2012 have increased the numbers of patients admitted to hospital and treated with acetylcysteine without reducing adverse reactions. A safety and cost-benefit review of the CHM guidance is warranted, including novel treatment protocols and biomarkers in the assessment of poisoning

Reductions in emergency department visits after primary healthcare use of the UK National Poisons Information Service

<p><b>Background:</b> Suspected poisoning is a common cause of hospital admission internationally. In the United Kingdom, the National Poisons Information Service (NPIS), a network of four poisons units, provides specialist advice to health professionals on the management of poisoning by telephone and via its online poisoning information and management database, TOXBASE^®.</p> <p><b>Objective:</b> To demonstrate the impact of NPIS telephone advice and TOXBASE^® guidance on poisoning-related referrals to emergency departments (ED) from primary healthcare settings.</p> <p><b>Methods:</b> A telephone survey of primary healthcare providers calling the NPIS and an online survey of TOXBASE^® primary care users were conducted to evaluate the effect of these services on poisoning-related ED referrals. Enquirers were asked to indicate whether referral was needed before and after using these information sources.</p> <p><b>Results:</b> The number of cases considered by enquirers appropriate for ED referral was reduced from 1178 (58.1%) before to 819 (40.4%) after the provision of telephone advice for 2028 cases (absolute reduction 17.7%, 95% CI 14.6, 20.7%) and from 410 (48.2%) before to 341 (40.1%) after consideration of TOXBASE^® guidance for 851 cases (absolute reduction 8.1%, 95% CI 3.3, 12.9%). By extrapolating these figures over a full year, it is estimated that these services prevent approximately 41,000 ED referrals annually.</p> <p><b>Conclusions:</b> The use of NPIS services significantly reduced ED referrals from primary healthcare services with resulting avoided healthcare costs exceeding the current annual NPIS budget. Further studies are needed to evaluate other potential benefits of accessing NPIS services.</p