ABSTRACT:By examining key milestones, challenges and future directions, this review chronicles the evolution of clinical toxicology in Singapore into a recognised subspeciality and thriving community of practice. Poisoning trends have transitioned alongside socioeconomic changes from agricultural toxins to pharmaceuticals, substance misuse and prescription drugs. Currently, toxicology services have expanded across public hospitals, offering 24/7 consultations and managing selected cases in short-stay observation units to optimise resources. Singapore's hazardous material (HazMat) preparedness includes specialised HazMat Medical Life Support training, antidote and personal protective equipment (PPE) stockpiling, and deployment of semi-automated decontamination facilities. Research has focused on case reports and description of local poisoning epidemiology. Toxicology has also been integrated into nursing, undergraduate medical and residency curricula, with a national fellowship programme in the pipeline. Challenges include the latent HazMat threat, rising burden of poisoning cases, continual evolution of synthetic drugs and occupational hazards from emerging industries. Future directions should emphasise interdisciplinary collaboration, regional partnerships and leveraging artificial intelligence and toxicogenomics to enhance care.

INTRODUCTION:The Clinical Toxicology Recommendations Collaborative was established by three international clinical toxicology societies and tasked to produce recommendations on the management of poisonings. The Activated Charcoal in Clinical Toxicology Workgroup (the Workgroup) was formed to provide recommendations on the administration of activated charcoal for gastrointestinal decontamination and enhanced elimination in poisoning. METHODS:Based on a systematic review of the literature, 43 poisons or poison categories were selected for appraisal. Voting statements were drafted using a predetermined format. Strength of consensus was measured using the Disagreement Index as defined by the RAND/University of California at Los Angeles Appropriateness Method. A two-round modified Delphi method was used to reach expert consensus. RESULTS:The Workgroup concluded that there is no role for activated charcoal in poisoning from arsenic, caesium, copper, ethanol, methanol, ethylene glycol, iron, lead, lithium, and metformin. Activated charcoal is appropriate after ingestion of antidysrhythmics (types I and III not discussed specifically), beta-adrenergic antagonists, bupropion, calcium-channel blockers, carbamazepine, cardiac glycosides, chloroquine, cocaine, colchicine, cyanide, dapsone, diphenhydramine, disopyramide, factor Xa inhibitors, ibuprofen, isoniazid, lamotrigine, methotrexate, moclobemide, opioids, organophosphorus insecticides, paracetamol (acetaminophen), paraquat, phenobarbital, phenytoin, quinidine and quinine, salicylates, selective serotonin reuptake inhibitors, sulfonylureas, thallium, theophylline, tricyclic antidepressants, valproic acid, venlafaxine, and warfarin. An additional dose of activated charcoal to complete gastrointestinal decontamination is appropriate after ingestion of carbamazepine, paracetamol, paraquat, phenobarbital, salicylates, thallium, theophylline, valproic acid and verapamil. The maximum time post-ingestion for which activated charcoal administration is recommended differs for each poison and different formulations. According to an individualized risk assessment, activated charcoal is appropriate up to 6 h post-ingestion for many poisons. If ongoing absorption is suspected, which may occur, for example, with pharmacobezoar formation, certain modified-release preparations, or when drug burden exceeds the limits of solubility, then activated charcoal can be administered beyond 6 h post-ingestion for gastrointestinal decontamination. Multiple-dose activated charcoal for enhanced elimination is appropriate in poisoning with carbamazepine, cardiac glycosides, colchicine, dapsone, phenobarbital, phenytoin, thallium and theophylline. Before deciding to perform endotracheal intubation to assist with the administration of activated charcoal, every clinician needs to weigh the potential complications and adverse effects of this procedure against the toxicity expected to be prevented by the administration of activated charcoal. This is a challenging decision, and a local poison centre and/or a bedside toxicology consultation can assist with this decision. Endotracheal intubation is not a benign procedure and is associated with a high rate of various adverse events, such as new haemodynamic instability, severe hypoxaemia, and cardiac arrest, which seem more common in children. In three studies that evaluated the risks of endotracheal intubation in over 2,200 poisoned patients, the rates of hypotension were between 1.5% and 11.8%, desaturation between 3.4% and 7.1%, and cardiac arrest in 0.4%. The risk of aspiration following administration of activated charcoal after endotracheal intubation is reported to be low (1-4%). Therefore, the decision to endotracheally intubate a patient to administer activated charcoal needs to carefully assess the patient's other comorbidities and the expected toxicity of the ingestion, which needs to be clinically significant to outweigh the risk of endotracheal intubation. Endotracheal intubation may also be considered if another treatment, such as haemodialysis or extracorporeal circulation, might be required or for transportation to another institution for ongoing clinical care. In these situations, for which endotracheal intubation has been performed for another indication, the risk-benefit will change in favour of activated charcoal administration. The following good practice statements were adopted to address the use of endotracheal intubation to facilitate the administration of activated charcoal. Endotracheal intubation should not be performed solely for the purpose of administration of activated charcoal in patients not anticipated to develop clinically significant complications of poisoning.In patients in whom endotracheal intubation is clinically indicated (e.g., compromised or unprotected airway, respiratory failure, significantly diminished level of consciousness, refractory seizures, hemodynamic instability), insertion of a nasogastric or orogastric tube is reasonable to facilitate gastrointestinal decontamination with activated charcoal.In patients with a clinically significant risk of developing life-threatening toxicity, endotracheal intubation is reasonable to safely facilitate gastrointestinal decontamination, especially if other treatment options are nonexistent or unavailable.Use of nasogastric or orogastric tube insertion without endotracheal intubation to facilitate the administration of activated charcoal: The following good practice statement was adopted: Nasogastric or orogastric tube insertion without endotracheal intubation should not be performed solely for the purpose of administration of AC. DISCUSSION:The decision to use activated charcoal is complex and depends primarily on the nature of the poison(s), the time since ingestion, the severity of the symptoms present at the time of decision or expected based on the dose ingested or patient comorbidities, and the availability of antidotes or other treatments. Although the existing level of evidence is primarily of low or very low quality, clinical decisions are still necessary. CONCLUSIONS:The Workgroup recommends the administration of a single-dose of activated charcoal beyond the traditional 1 h post-ingestion time point in selected poisons and introduces the concept of an additional dose of activated charcoal to prevent further absorption of poisons that may remain in the gastrointestinal tract for prolonged periods of time. Multiple-dose activated charcoal is also recommended to enhance elimination in selected clinical scenarios.

Introduction The use of activated charcoal in poisoning remains both a pillar of modern toxicology and a source of debate. Following the publication of the joint position statements on the use of single-dose and multiple-dose activated charcoal by the American Academy of Clinical Toxicology and the European Association of Poison Centres and Clinical Toxicologists, the routine use of activated charcoal declined. Over subsequent years, many new pharmaceuticals became available in modified or alternative-release formulations and additional data on gastric emptying time in poisoning was published, challenging previous assumptions about absorption kinetics. The American Academy of Clinical Toxicology, the European Association of Poison Centres and Clinical Toxicologists and the Asia Pacific Association of Medical Toxicology founded the Clinical Toxicology Recommendations Collaborative to create a framework for evidence-based recommendations for the management of poisoned patients. The activated charcoal workgroup of the Clinical Toxicology Recommendations Collaborative was tasked with reviewing systematically the evidence pertaining to the use of activated charcoal in poisoning in order to update the previous recommendations. Objectives The main objective was: Does oral activated charcoal given to adults or children prevent toxicity or improve clinical outcome and survival of poisoned patients compared to those who do not receive charcoal? Secondary objectives were to evaluate pharmacokinetic outcomes, the role of cathartics, and adverse events to charcoal administration. This systematic review summarizes the available evidence on the efficacy of activated charcoal. Methods A medical librarian created a systematic search strategy for Medline (Ovid), subsequently translated for Embase (via Ovid), CINAHL (via EBSCO), BIOSIS Previews (via Ovid), Web of Science, Scopus, and the Cochrane Library/DARE. All databases were searched from inception to December 31, 2019. There were no language limitations. One author screened all citations identified in the search based on predefined inclusion/exclusion criteria. Excluded citations were confirmed by an additional author and remaining articles were obtained in full text and evaluated by at least two authors for inclusion. All authors cross-referenced full-text articles to identify articles missed in the searches. Data from included articles were extracted by the authors on a standardized spreadsheet and two authors used the GRADE methodology to independently assess the quality and risk of bias of each included study. Results From 22,950 titles originally identified, the final data set consisted of 296 human studies, 118 animal studies, and 145 in vitro studies. Also included were 71 human and two animal studies that reported adverse events. The quality was judged to have a Low or Very Low GRADE in 469 (83%) of the studies. Ninety studies were judged to be of Moderate or High GRADE. The higher GRADE studies reported on the following drugs: paracetamol (acetaminophen), phenobarbital, carbamazepine, cardiac glycosides (digoxin and oleander), ethanol, iron, salicylates, theophylline, tricyclic antidepressants, and valproate. Data on newer pharmaceuticals not reviewed in the previous American Academy of Clinical Toxicology/European Association of Poison Centres and Clinical Toxicologists statements such as quetiapine, olanzapine, citalopram, and Factor Xa inhibitors were included. No studies on the optimal dosing for either single-dose or multiple-dose activated charcoal were found. In the reviewed clinical data, the time of administration of the first dose of charcoal was beyond one hour in 97% (n = 1006 individuals), beyond two hours in 36% (n = 491 individuals), and beyond 12 h in 4% (n = 43 individuals) whereas the timing of the first dose in controlled studies was within one hour of ingestion in 48% (n = 2359 individuals) and beyond two hours in 36% (n = 484) of individuals. Conclusions This systematic review found heterogenous data. The higher GRADE data was focused on a few select poisonings, while studies that addressed patients with unknown and or mixed ingestions were hampered by low rates of clinically meaningful toxicity or death. Despite these limitations, they reported a benefit of activated charcoal beyond one hour in many clinical scenarios.

BACKGROUND:Transdermal glyceryl trinitrate (GTN) has potential beneficial properties in acute stroke including intracerebral hemorrhage (ICH) and possible clinical benefits suggested in ultra-early stroke (≤6 h). Our meta-analysis updated the evidence on its safety and benefits in acute stroke. METHODS:We searched major electronic databases for randomized trials comparing transdermal GTN versus placebo/control in acute stroke. Primary outcomes were mortality, 90-day modified Rankin Scale (mRS), and blood pressure (BP) effects. Secondary outcomes included early, late, resource utilization, and surrogate outcomes. Safety outcomes were adverse events. Reviewers identified studies, extracted data, and assessed risk of bias (RoB) using a modified Cochrane RoB instrument and quality of evidence (QoE) using GRADE. We also performed a priori subgroup and trial sequential analyses (TSA) on primary outcomes. These subgroup analyses were ICH versus ischemic stroke, minor (NIHSS ≤5) versus major (NIHSS >5) ischemic stroke, ischemic stroke with versus without thrombolysis, prehospital versus non prehospital settings, time from stroke to randomization ≤6 h versus >6 h, and high versus low overall RoB studies. RESULTS:Seven eligible primary trials enrolled 5363 patients. GTN reduced BP (mean difference [MD] = -4.74 mm Hg, 95% confidence interval [CI] = -6.03 to -3.45 mm Hg] and diastolic BP (MD = -2.94 mm Hg, 95% CI = -3.74 to -2.13 mm Hg) 24 h posttreatment but did not affect 4- to 10-day mortality (relative risk [RR] = 1.11, 95% CI = 0.82 to 1.49), 90-day mortality (RR = 0.96, 95% CI = 0.77 to 1.19), and 90-day mRS >2 (RR = 0.98, 95% CI = 0.93 to 1.03) compared to control/placebo. The QoE was high for primary outcomes with no subgroup effects detected. GTN did not affect secondary outcomes and increased risk of headache and hypotension. TSA generally supported our conclusions regarding primary outcomes. CONCLUSIONS:Transdermal GTN reduces BP in acute stroke but does not alter clinical outcomes even in ultra-early stroke (≤6 h).

INTRODUCTION:High blood pressure (BP) in acute stroke has adverse outcomes. Transdermal glyceryl trinitrate (GTN) has beneficial properties in controlling BP. The 2016 meta-analysis and 2017 Cochrane review showed that transdermal GTN was beneficial in a small patient subgroup with stroke onset ≤6 hours. Larger studies focusing on this patient subgroup have since been conducted. We report the protocol for an updated systematic review and meta-analysis on the safety and benefits of transdermal GTN in acute stroke.METHODS AND ANALYSIS:We will search Medline, Pubmed, Embase, CINAHL and Cochrane Library from inception until June 2020 for randomised trials that report the efficacy and safety of transdermal GTN versus placebo/control therapy among adult patients with acute stroke. Primary outcomes include in-hospital mortality, BP lowering and late functional status. Secondary outcomes include early, late, resource utilisation and surrogate outcomes. Safety outcomes include reported adverse events. Reviewers will first screen titles and abstracts, and then full texts, to identify eligible studies. Independently and in duplicate, they will extract data, assess risk of bias (RoB) using a modified Cochrane RoB tool and quality of evidence using Grading of Recommendations, Assessment, Development and Evaluation. Disagreement will be resolved by discussion and consultation with an external reviewer if necessary. Using a random-effects model, we will report effect sizes using relative risks and 95% CIs. We will perform predefined subgroup analyses: intracerebral haemorrhage versus ischaemic stroke; minor (NIHSS (National Institutes of Health Stroke Scale) ≤five) versus major (NIHSS >five) ischaemic stroke; ischaemic stroke with versus without thrombolysis; prehospital versus non-prehospital settings; time from stroke to randomisation ≤6 versus >6 hours and high versus low overall RoB studies. We will also perform trial sequential analysis for the primary outcomes.ETHICS AND DISSEMINATION:Ethics board approval is unnecessary. PROSPERO registration has been obtained. The results will be disseminated through publication in a peer-reviewed journal.PROSPERO REGISTRATION NUMBER:CRD42020173093.

Prescription medicine misuse, especially misuse of opioids has become a major public healthcare issue in many developed countries such as the USA and Australia where this is associated with significant morbidity (Emergency Department visits due to acute toxicity) and mortality. In this review, we looked at the available data obtained from peer-reviewed articles and population surveys to gain an insight into the current situation in the Asia-Pacific region. There is currently limited information available, but data from subpopulation surveys in a number of countries suggests that prescription medicine misuse is likely to be an issue of concern from a public health perspective in the Asia-Pacific region. The available data suggest that misuse prevalence rates and the medicines that are commonly misused are similar to countries such as the USA and UK. Further studies are required to determine the overall prevalence of misuse, the harms associated with this and the sources of drugs being misused so that appropriate interventions can be implemented to tackle issues related to prescription medicine misuse in this region.

Introduction: Misuse of prescription medicines and the harms associated with such use are growing threats across the world. There is currently, however, limited data on the extent of prescription medicine misuse in Singapore and whether this is a current threat in the country. Methods: An online survey, limited to 1,000 individuals (aged 21 years and over) who were residents in Singapore, was administered through a survey panel company in September 2015. The survey collected information on participant demographics, and their awareness, self-reported lifetime and past-year misuse of commonly available prescription medicines in Singapore as well as the use of a range of recreational drugs and novel psychoactive substances (NPS). Results: Lifetime (6.7%) and past-year (4.8%) misuse of any prescription medicine was comparable to lifetime (6.0%) and past-year (3.0%) use of any recreational drugs/NPS. The top five prescription medicines for lifetime misuse were: diazepam (2.7%); codeine (2.3%); dhasedyl (promethazine, codeine and ephedrine; 1.6%); panadeine (paracetamol and codeine; 1.5%); and methylphenidate (1.2%). The top five drugs for past-year misuse were: diazepam (1.6%); codeine (0.9%); panadeine (0.7%); alprazolam (0.6%); baclofen (0.6%); and gabapentin (0.6%). Conclusion: Misuse of prescription medicine in Singapore was common, with prevalence comparable to the use of recreational drugs/NPS. A common source for misused drugs was physicians. Further studies are required to determine whether this is more widespread in Singapore and establish the different forms of drug diversion, so that appropriate prevention strategies can be implemented.

Acetaminophen is one of the most common causes of poisoning among developed countries. The emergency department observation unit (EDOU) has been increasingly used in the management of various conditions to reduce hospitalisation but its efficacy in not well studied in management of poisoned patients. In this study, we aim to study the effectiveness of our EDOU in the management of acetaminophen overdosed patients.

Objectives. There is currently little research on the extent of prescription and over-the-counter (OTC) medicines misuse in the United Kingdom. The objectives of this study were to determine the prevalence of OTC/prescription medicine misuse in the South London nightclub community and to look at the sources of supply. Methods. Individuals attending nightclubs in South London catering for, but not exclusively for, men who have sex with men (MSM) were surveyed about their use of recreational drugs, prescription, and OTC medicines and where they obtained these medications. Results. In total, 313 individuals were surveyed: 282 (90.1%) were male and 248 (79.2%) were MSM; 113 (36.1%) had misused at least one medicine in their lifetime and were more likely to have lifetime use of a recreational drug (OR 9.74, 95% CI 1.27-74.44). Diazepam (25.2%) and Z-drugs (zolpidem, zopiclone, zaleplon) (16.3%) were the most commonly misused medicines. The sources were friends (32.9%), dealers (15.7%), primary care doctors (13.7%), Internet purchases (10.9%), and overseas (7.3%). Conclusion. OTC and prescription medicines misuse is common among nightclub attendees in South London with these medicines coming from numerous sources. Further work is needed to determine the extent of this problem and the various forms of drug diversion.

INTRODUCTION:Singapore experienced its second riot in 40 years on 8 December 2013, in the area known as Little India. A retrospective review of 36 casualties treated at the emergency department was conducted to evaluate injury patterns.METHODS:Characteristics including the rate of arrival, injury severity, type and location, and disposition of the casualties were analysed.RESULTS:The injuries were predominantly mild (97.2%), with the most common injuries involving the head (50.0%) and limbs (38.9%). 97.2% of the casualties were managed as outpatient cases.CONCLUSION:The majority of the injuries in this incident were mild and could be managed as outpatient cases. Important lessons were learnt from the incident about the utilisation of manpower and safety of staff in the emergency department.

Background: There is anecdotal evidence of misuse of erectile dysfunction medication, particularly to counteract some of the unwanted effects of recreational drugs on erectile function. However, there is little data from the United Kingdom (UK). Aim: To evaluate the prevalence of sildenafil misuse in a UK population that has previously been shown to have high recreational drug use. Design: Questionnaire survey. Methods: Individuals attending nightclubs catering for the men who have sex with men (MSM) community in South London were asked about lifetime and last year use of recreational drugs and sildenafil. Results: 313 individuals were surveyed over four nights in 2013: 282 (90.1%) were males and 248 (79.2%) were MSM. Last year use of recreational drugs was high: mephedrone (74.1%), cocaine (61.3%), MDMA/Ecstasy (59.2%), GHB/GBL (52.8%), cannabis (51.8%), and ketamine (50%). 136 (49.1%) MSM versus 6 (18.8%) non-MSM clubbers had misused sildenafil in the last year (p < .001). Amongst the MSM clubbers, 232 (93.5%) had heard of sildenafil, 161 (64.9%) reported misuse of sildenafil in their lifetime and 133 (53.6%) had misused sildenafil in the last year. Conclusion: This study demonstrates a high prevalence of sildenafil misuse in a population who are heavy users of recreational drugs; it is not likely that this young population have underlying erectile dysfunction as a reason for legitimate sildenafil use. There is the potential for interaction with other recreational drugs used including cocaine and volatile nitrites. Further work is required in to determine the extent and reason for the misuse.

Introduction Over the last decade, there has been a reduction of organ donation from intracranial haemorrhage-, stroke- and blunt trauma-related deaths in the USA. There has been a corresponding increase in the use of drug-intoxicated patients as organ donors from 2.1 % in 2003 to 6.8 % in 2013.Methods Questionnaire survey of attendees at the American College of Medical Toxicology 2014 Annual Scientific Meeting breakout session on transplantation from deaths related to poisoning was performed. Participants were asked whether they would recommend the use of solid organs from cocaine- or carbon monoxide-related death before and after the breakout session.Results Forty-eight US participants (attending 23, fellow 15, resident 3 and other (including non-medical) 7) completed the survey, and 97.8 and 89.1 % of participants would consider cocaine- and carbon monoxide-related deaths for potential organ donation pre-breakout session, respectively; this increased to 100 % for both post-breakout sessions. There was variability in the consideration of different solid organs (the heart, lungs, liver, pancreas and kidneys)-76.2-95.2 and 76.2-85.7 % for individual solid organs for cocaine- and carbon monoxide-related deaths, respectively. For both scenarios, participants were least likely to consider potential heart donation (76.2 % of participants for both), which increased to 100 % following the breakout session.Conclusions Medical toxicologists have some reservation in recommending solid organs for transplantation from deaths from cocaine and carbon monoxide. Given the decrease in potential organ donors from typical methods of death, further work is needed to promote organ donation in deaths related to acute poisoning.

The aim of this study was to design an information leaflet for patients with paracetamol overdose based on Medicines and Healthcare products Regulatory Agency guidance and to assess its readability. A two-sided one page information leaflet was designed for patients being discharged from hospital after a paracetamol overdose. Patients presenting with an acute paracetamol overdose, irrespective of whether they were treated or not, were recruited to read the leaflet and then answer a brief structured questionnaire based on the leaflet. The readability of the information leaflet was assessed using the Flesch reading ease score. Thirty patients (15 male, 12 female, 3 not recorded; mean age 38 ± 13.0 years) were recruited, wherein 100% of patients reported the language used was understandable, 96.6% knew which symptoms would require urgent medical review after discharge and 100% of patients knew the liver was affected by paracetamol. The Flesch reading ease score was 67.6 (out of a maximum of 100), equivalent to a UK reading age of 10-11years old. Our information leaflet for all patients being discharged after paracetamol overdose was well received by patients, provided them with the required knowledge and had an appropriate reading age based on UK literacy rates. We would recommend that this leaflet could be used as a template on a national level, localized to individual hospitals, to improve patient knowledge of paracetamol toxicity, and facilitate early medical review in the event of deterioration following discharge from the hospital.