Prescription medicine misuse in the Asia-Pacific region: An evolving issue?

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.

Significant Misuse of Sildenafil in London Nightclubs.

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.

Misuse of prescription medicines is as prevalent as the use of recreational drugs and novel psychoactive substances in Singapore: an unrecognised public health issue?

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.

Benefits and safety of transdermal glyceryl trinitrate in acute stroke: A systematic review and meta-analysis of randomized trials.

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).

Benefits and safety of transdermal glyceryl trinitrate in acute stroke: a systematic review and meta-analysis of randomised trials (protocol).

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.

Systematic review on the use of activated charcoal for gastrointestinal decontamination following acute oral overdose.

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.

Performance of an emergency department observation unit protocol in reducing length of stay for acetaminophen overdose: a retrospective study.

INTRODUCTION: 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. RESULTS: Medical records of patients admitted from the emergency department from 2012 to 2016 for acetaminophen overdose were reviewed. One hundred ninety-five patients presenting with acetaminophen overdose were admitted to the EDOU while 184 were admitted to the general ward. Of these, 27 patients admitted to EDOU did not meet the admission criteria for it while 71 patients who met EDOU criteria were admitted to the ward instead. For patients who fulfilled EDOU admission criteria, median length of stay for EDOU patients was 23 h (IQR 19-24) while that for those admitted to the ward was 66 h (IQR 62.5-88.3). CONCLUSION: The EDOU is a safe alternative to hospitalisation for patients presenting with acetaminophen poisoning. It is also associated with a shorter length of stay for such patients. Further studies need to be done to assess the cost-effectiveness of EDOU for management of patients presenting with acetaminophen overdose.

The Little India riot: experience of an emergency department in Singapore.

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.

Using drug-intoxicated deaths as potential organ donors: impression of attendees at the American college of medical toxicology 2014 annual scientific meeting.

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.

Development of a 'patient information leaflet' for use following assessment of patients with reported or suspected paracetamol overdose in the UK.

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.

Acute psychosis associated with recreational use of benzofuran 6-(2-aminopropyl)benzofuran (6-APB) and cannabis.

INTRODUCTION: There is evidence from around Europe of the availability and use of 6-(2-aminopropyl)benzofuran (6-APB) as a recreational drug. However, there is currently limited information on the acute toxicity of this compound. We describe here a case of acute toxicity associated with recreational use of legal high (6-APB) and cannabis, in which the comprehensive toxicological analysis confirmed the presence of a significant amount of 6-APB together with metabolites of both tetrahydrocannabinol and the synthetic cannabinoid receptor agonist (JWH-122). CASE REPORT: A 21-year-old gentleman with no previous medical and psychiatric history was brought to the emergency department (ED) after he had developed agitation and paranoid behaviour following the use of 6-APB purchased over the Internet. There was no obvious medical cause for his acute psychosis. He required diazepam to control his agitation and was subsequently transferred to a psychiatric hospital for ongoing management of his psychosis. Toxicological screening of a urine sample collected after presentation to the ED detected 6-APB, with an estimated urinary concentration of 2,000 ng/ml; other drugs were also detected, but at lower concentrations including metabolites of the synthetic cannabinoid receptor agonist JWH-122 and tetrahydrocannabinol. CONCLUSION: This is the first case of analytically confirmed acute toxicity associated with the detection of 6-APB which will provide some information on acute toxicity of this drug to help clinicians with the management of such patients and legislative authorities in their consideration for the need of its control.