Rising Kawasaki disease incidence in New Zealand: analysis of national population incidence and outcomes 2000-2017.

OBJECTIVE: The recent epidemiology of Kawasaki disease (KD) in New Zealand (NZ) is unknown. Our aim was to describe the incidence, seasonal variation, long-term outcomes and mortality for KD in NZ. DESIGN: Retrospective national database analysis. SETTING: New Zealand. PATIENTS: First hospitalisation and deaths diagnosed with KD. MAIN OUTCOME MEASURES: Data were extracted for all hospital admissions in NZ coded as KD (International Classification of Diseases (ICD)-9 and ICD-10) from the National Minimum Dataset 1 January 2000 to 31 December 2017. Age, sex, ethnicity and associated diagnoses were available to review. Intervention rates for immunoglobulin administration were also analysed. RESULTS: Over the study period, there were 1008 children with initial hospitalisation for KD. The mean age was 39.8 months (SD 37) and 592 (59%) were boys. The annual incidence rate of KD has increased from 12.2 to 19.5 per 100 000 children <5 years old (0.46 case increase per year; 95% CI 0.09 to 0.83). Children of Asian and Pacific Island ethnicities had the highest incidence (51.2 and 26.1/100 000, respectively). The highest growth in incidence was among East Asian children. The case mortality rate was low (12 of 1008, 1.2%); however, Maori were over-represented (6 of 12 deaths). CONCLUSIONS: There is evidence of increasing KD hospitalisation in NZ, similar to recent studies from Northeast Asia and Australia. KD incidence data were available for retrospective review from a national database, but data on complications and outcomes were incomplete. Notification for KD and an active national surveillance system are recommended to improve care. Future work should focus on factors contributing to poorer outcomes in Maori.

The clinical toxicology of ketamine.

INTRODUCTION: Ketamine is a pharmaceutical drug possessing both analgesic and anaesthetic properties. As an anaesthetic, it induces anaesthesia by producing analgesia with a state of altered consciousness while maintaining airway tone, respiratory drive, and hemodynamic stability. At lower doses, it has psychoactive properties and has gained popularity as a recreational drug. OBJECTIVES: To review the epidemiology, mechanisms of toxicity, pharmacokinetics, clinical features, diagnosis and management of ketamine toxicity. METHODS: Both OVID MEDLINE (January 1950-April 2023) and Web of Science (1900-April 2023) databases were searched using the term "ketamine" in combination with the keywords "pharmacokinetics", "kinetics", "poisoning", "poison", "toxicity", "ingestion", "adverse effects", "overdose", and "intoxication". Furthermore, bibliographies of identified articles were screened for additional relevant studies. These searches produced 5,268 non-duplicate citations; 185 articles (case reports, case series, pharmacokinetic studies, animal studies pertinent to pharmacology, and reviews) were considered relevant. Those excluded were other animal investigations, therapeutic human clinical investigations, commentaries, editorials, cases with no clinical relevance and post-mortem investigations. EPIDEMIOLOGY: Following its introduction into medical practice in the early 1970s, ketamine has become a popular recreational drug. Its use has become associated with the dance culture, electronic and dubstep dance events. MECHANISM OF ACTION: Ketamine acts primarily as a non-competitive antagonist on the glutamate N-methyl-D-aspartate receptor, causing the loss of responsiveness that is associated with clinical ketamine dissociative anaesthesia. PHARMACOKINETICS: Absorption of ketamine is rapid though the rate of uptake and bioavailability is determined by the route of exposure. Ketamine is metabolized extensively in the liver. Initially, both isomers are metabolized to their major active metabolite, norketamine, by CYP2B6, CYP3A4 and CYP2C9 isoforms. The hydroxylation of the cyclohexan-1-one ring of norketamine to the three positional isomers of hydroxynorketamine occurs by CYP2B6 and CYP2A6. The dehydronorketamine metabolite occurs either by direct dehydrogenation from norketamine via CYP2B6 metabolism or non-enzymatic dehydration of hydroxynorketamine. Norketamine, the dehydronorketamine isomers, and hydroxynorketamine have pharmacological activity. The elimination of ketamine is primarily by the kidneys, though unchanged ketamine accounts for only a small percentage in the urine. The half-life of ketamine in humans is between 1.5 and 5 h. CLINICAL FEATURES: Acute adverse effects following recreational use are diverse and can include impaired consciousness, dizziness, irrational behaviour, hallucinations, abdominal pain and vomiting. Chronic use can result in impaired verbal information processing, cystitis and cholangiopathy. DIAGNOSIS: The diagnosis of acute ketamine intoxication is typically made on the basis of the patient's history, clinical features, such as vomiting, sialorrhea, or laryngospasm, along with neuropsychiatric features. Chronic effects of ketamine toxicity can result in cholangiopathy and cystitis, which can be confirmed by endoscopic retrograde cholangiopancreatography and cystoscopy, respectively. MANAGEMENT: Treatment of acute clinical toxicity is predominantly supportive with empiric management of specific adverse effects. Benzodiazepines are recommended as initial treatment to reduce agitation, excess neuromuscular activity and blood pressure. Management of cystitis is multidisciplinary and multi-tiered, following a stepwise approach of pharmacotherapy and surgery. Management of cholangiopathy may require pain management and, where necessary, biliary stenting to alleviate obstructions. Chronic effects of ketamine toxicity are typically reversible, with management focusing on abstinence. CONCLUSIONS: Ketamine is a dissociative drug employed predominantly in emergency medicine; it has also become popular as a recreational drug. Its recreational use can result in acute neuropsychiatric effects, whereas chronic use can result in cystitis and cholangiopathy.

Specialist medical toxicologist consultations provided by the New Zealand National Poisons Centre, 2018-2020.

AIMS: The National Poisons Centre (NPC) provides 24/7 specialist medical toxicologist consultations to healthcare professionals regarding the clinical management of poisoning cases. The use of toxicologist services was investigated to characterise the extent and content of consults to inform further development of this service. METHODS: A retrospective analysis of 2018-2020 medical toxicologist consultations summarised contact numbers, professional backgrounds and district health boards (DHBs) of the people contacting the NPC, and the patient(s) and substance(s) involved. RESULTS: There were 3,451 medical toxicologist consultations with 2,400 (67%) provided directly to healthcare professionals. Crude rates of consults increased across all DHBs. Of all 2,603 therapeutic substances that were consulted about during the study period, 1,492 (57.3%) were drugs affecting the nervous system, and paracetamol was the most common individual drug (528; 20.3%). Of all 1,185 non-therapeutic substance exposures that were advised on, 66 (5.6%) were unidentified mushrooms, 51 (4.3%) unidentified substances, and 47 (4.0%) lead exposures. CONCLUSIONS: There was increasing utilisation of the NPC service by healthcare professionals from all 24 areas of the country, covering a wide range of substance exposures and scenarios. The growing utilisation suggests healthcare professionals derive value from this consultation service for the care of their patients.

Prevalence of psychoactive drugs in injured patients presenting to an emergency department.

OBJECTIVE: The aim of the present study was to obtain an unbiased understanding of the prevalence of psychoactive drugs in trauma patients presenting to a large ED. METHODS: Consecutive adult patients presenting to the ED with an injury resulting in a trauma call had an anonymised, additional blood test taken for detection of over 2000 drugs. Laboratory testing was to judicial standards. Drugs given by ambulance pre-hospital were detected but excluded from the analysis. RESULTS: Over 6 months 276 (74.7%) of 371 patients were tested. Of the 276 patients tested, 158 (57.2%) had one or more psychoactive drug present. Recreational drugs were detected in 101 (36.6%) patients and medicinal drugs in 88 (31.8%) patients, with a combination of both detected in 31 (11.2%) patients. The most common drugs detected were cannabis (22.1%), antidepressants (18.4%), alcohol (15.5%), opioids (10.1%), benzodiazepine/z-drugs (9.4%) and methamphetamine (7.2%). The prevalence of psychoactive drugs differed by age group, sex and cause of injury. CONCLUSIONS: The prevalence of psychoactive drugs in injury presentations to an ED is high, and provides an opportunity to reduce harm. The present study demonstrates the feasibility of an approach which limits bias and obtains results that accurately reflect the drug prevalence in injured cohorts. Systematic testing of injured patients is an important contribution to the epidemiology of injury.

Temporal clustering of Kawasaki disease cases around the world.

In a single-site study (San Diego, CA, USA), we previously showed that Kawasaki Disease (KD) cases cluster temporally in bursts of approximately 7 days. These clusters occurred more often than would be expected at random even after accounting for long-term trends and seasonality. This finding raised the question of whether other locations around the world experience similar temporal clusters of KD that might offer clues to disease etiology. Here we combine data from San Diego and nine additional sites around the world with hospitals that care for large numbers of KD patients, as well as two multi-hospital catchment regions. We found that across these sites, KD cases clustered at short time scales and there were anomalously long quiet periods with no cases. Both of these phenomena occurred more often than would be expected given local trends and seasonality. Additionally, we found unusually frequent temporal overlaps of KD clusters and quiet periods between pairs of sites. These findings suggest that regional and planetary range environmental influences create periods of higher or lower exposure to KD triggers that may offer clues to the etiology of KD.

Paediatric exploratory ingestion presentations to Christchurch Hospital emergency department during 2019.

AIM: To quantify and describe presentations to a New Zealand tertiary hospital emergency department (ED) associated with paediatric exploratory ingestions (PEIs) during 2019 in comparison to 1999. METHODS: A retrospective descriptive study was conducted of PEI presentations by children under 7 years of age to Christchurch Hospital ED between 1 January and 31 December 2019. Data were studied for demographic and management details and compared to data from 1999. RESULTS: There were 111 PEI presentations in children under 7 years during 2019, out of 9,445 presentations for this age group (1.2%). The estimated incidence of PEIs was 223.8 per 100,000. PEI presentations relative to total paediatric presentations had reduced compared to 1999 (X2=94.7, p<0.001). Two year olds were most likely to have PEIs (odds ratio (OR)=15.01, 95% confidence interval (CI)=6.78, 33.22). Children of Asian (OR=0.50, 95% CI=0.26, 0.95) and Pacific (OR=0.34, 95% CI=0.12, 0.93) ethnicity were less likely to present with PEIs. Paracetamol was the most commonly ingested substance (15.3%), followed by opioids (11.7%). CONCLUSION: Paediatric presentations due to exploratory ingestions reduced between 1999 and 2019. However, there was a concerning increase in ingestions of medications like opioids that have a significant risk of toxicity at low doses.

The clinical toxicology of cannabis.

Cannabis is one of the most widely used recreational drugs in the world. Tetrahydrocannabinol (THC) is the psychoactive principal constituent of the cannabis plant (Cannabis sativa). It is taken either orally or by inhalation, resulting in sedation, euphoria, relaxation and loss of social inhibition. Adverse effects from higher doses can include fear, distrust and a profound state of unease, hallucinations, ataxia, stupor and seizures. Long-term use can result in respiratory and cardiovascular toxicity and has been associated with a range of psychiatric conditions. Cannabinoid hyperemesis syndrome can occur with chronic use. Driving under the influence of THC is associated with approximately double the risk of motor vehicle crashes. The intensity and duration of symptoms is proportional to the concentration of THC in the blood. Following acute use, THC only remains in the blood for several hours before it is converted into a carboxylic derivative of THC and this partitions into the fat, from where it leaches out and can be detected in urine for weeks after use. Treatment of acute intoxication mainly consists of appropriate symptom-directed supportive care. Children are more susceptible to cannabis toxicity, particularly seizures and coma, and therefore may require additional supportive care for these potential symptoms. The aim of this narrative review is to provide a brief overview of the acute and chronic effects of cannabis, its pharmacokinetics, toxicity and the medical management of intoxication.

Case series: toxicity from 25B-NBOMe--a cluster of N-bomb cases.

Background A new class of hallucinogens called NBOMes has emerged. This class includes analogues 25I-NBOMe, 25C-NBOMe and 25B-NBOMe. Case reports and judicial seizures indicate that 25I-NBOMe and 25C-NBOMe are more prevalently abused. There have been a few confirmed reports of 25B-NBOMe use or toxicity. Report Observational case series. This report describes a series of 10 patients who suffered adverse effects from 25B-NBOMe. Hallucinations and violent agitation predominate along with serotonergic/stimulant signs such as mydriasis, tachycardia, hypertension and hyperthermia. The majority (7/10) required sedation with benzodiazepines. Analytical method 25B-NBOMe concentrations in plasma and urine were quantified in all patients using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Peak plasma levels were measured between 0.7-10.1 ng/ml. Discussion The NBOMes are desired by users because of their hallucinogenic and stimulant effects. They are often sold as LSD or synthetic LSD. Reported cases of 25B- NBOMe toxicity are reviewed and compared to our series. Seizures and one pharmacological death have been described but neither were observed in our series. Based on our experience with cases of mild to moderate toxicity, we suggest that management should be supportive and focused on preventing further (self) harm. High doses of benzodiazepines may be required to control agitation. Patients who develop significant hyperthermia need to be actively managed. Conclusions Effects from 25B-NBOMe in our series were similar to previous individual case reports. The clinical features were also similar to effects from other analogues in the class (25I-NBOMe, 25C-NBOMe). Violent agitation frequently present along with signs of serotonergic stimulation. Hyperthermia, rhabdomyolysis and kidney injury were also observed.