Iloperidone, asenapine, and lurasidone: a brief overview of 3 new second-generation antipsychotics

Three new second-generation antipsychotics were approved by the US Food and Drug Administration in 2009 and 2010: iloperidone, asenapine, and lurasidone. All 3 agents are approved for the treatment of acute schizophrenia in adults, and asenapine is also approved for the maintenance treatment of schizophrenia and as a monotherapy or as an adjunct to lithium or valproate for the treatment of bipolar manic or mixed episodes. The expectation is that these new agents will be less problematic regarding treatment-emergent weight gain and metabolic disturbances, which unfortunately can occur with several other second-generation antipsychotics. Asenapine is a sublingual preparation, in contrast to iloperidone and lurasidone, which are swallowed. Iloperidone and asenapine are dosed twice daily, in contrast to lurasidone, which is dosed once daily with food. Both asenapine and lurasidone can be initiated at a dose that is possibly therapeutic, but iloperidone requires 4 days of titration to reach its recommended target dose range. Although both asenapine and lurasidone can be associated with dose-related treatment-emergent akathisia, iloperidone is essentially free of extrapyramidal adverse effects or akathisia throughout its recommended dose range. Sedation and/or somnolence have been reported with each medication. They are the most common adverse events associated with asenapine treatment, and are clearly dose-related for lurasidone. In contrast, no therapeutic dose response for iloperidone, asenapine, or lurasidone is clearly evident from short-term clinical trials. Longer-term and naturalistic studies will be helpful in evaluating these agents and their role in the psychiatric armamentarium.     

Trends in types of calls managed by U.S. poison centers 2000–2015

Aim: The number of cases reported to poison centers has decreased since 2008 but there is evidence that the complexity of calls is increasing.

Objectives: The objectives are to evaluate national poison center data for trends in reason and how these changes effect management site, medical outcomes, and poison center workload.

Methods: Data regarding reason, age, management site, and medical outcome were extracted from annual reports of the National Poison Data System from 2000 to 2015. The proportion of cases by year were determined for unintentional and intentional exposures. Analysis of data from a single poison center from 2005 to 2015 compared the number of interactions between poison center staff and callers for unintentional versus intentional reasons.

Results: Trend analyses found that from 2000 to 2015 the percent of unintentional cases decreased (from 85.9 to 78.4%, p?p?p?Discussion: Poison centers are managing more intentional exposures and fewer unintentional exposures. Intentional exposures require more poison center staff expertise and time.

Conclusion: Looking only at poison center total call volume may not be an adequate method to gauge productivity.     

2011 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 29th Annual Report

Abstract

Background: This is the 29th Annual Report of the American Association of Poison Control Centers’ (AAPCC) National Poison Data System (NPDS). As of 1 July 2011, 57 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 8.43 [6.29, 13.7] (median [25%, 75%]) minutes, creating a near real-time national exposure and information database and surveillance system.

Methodology: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of 38 medical and clinical toxicologist reviewers using an ordinal scale of 1–6 to assess the Relative Contribution to Fatality (RCF) of the exposure to the death.

Results: In 2011, 3,624,063 closed encounters were logged by NPDS: 2,334,004 human exposures, 80,266 animal exposures, 1,203,282 information calls, 6,243 human confirmed nonexposures, and 268 animal confirmed nonexposures. Total encounters showed an 8.3% decline from 2010, while health care facility exposure calls increased by 4.8%. Human exposures with less serious outcomes decreased by 3.4% while those with more serious outcomes (moderate, major or death) increased by 6.8%. All information calls decreased by 17.9% and health care facility (HCF) information calls decreased by 2.9%, Medication identification requests (Drug ID) decreased by 24.1%, and human exposures reported to US poison centers decreased by 2.2%.

The top 5 substance classes most frequently involved in all human exposures were analgesics (11.7%), cosmetics/personal care products (8.0%), household cleaning substances (7.0%), sedatives/hypnotics/antipsychotics (6.1%), and foreign bodies/toys/miscellaneous (4.1%). Analgesic exposures as a class increased most rapidly (10,134 calls/year) over the last 11 years. The top 5 most common exposures in children aged 5 years or less were cosmetics/personal care products (14.0%), analgesics (9.9%), household cleaning substances (9.2%), foreign bodies/toys/miscellaneous (6.9%), and topical preparations (6.6%). Drug identification requests comprised 59.5% of all information calls. NPDS documented 2,765 human exposures resulting in death with 1,995 human fatalities judged related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory).

Conclusions: These data support the continued value of poison center expertise and need for specialized medical toxicology information to manage the more severe exposures, despite a decrease in calls involving less severe exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national public health resource to collect and monitor US exposure cases and information calls. The continuing mission of NPDS is to provide a nationwide infrastructure for public health surveillance for all types of exposures, public health event identification, resilience response and situational awareness tracking. NPDS is a model system for the nation and global public health.     

Comparison of pediatric atypical antipsychotic exposures reported to U.S. poison centers

Context: The rise in atypical antipsychotic prescribing increases the risk of pediatric exposures. Published studies in children are limited.

Objective: The objectives are to evaluate national poison center data on atypical antipsychotic exposures in young children and compare toxicity amongst selected agents.

Materials and methods: A retrospective study of U.S. National Poison Data System single substance exposures, from 2005 to 2013, of five atypical antipsychotics in children <6 years old, followed to known outcome was performed. Data were evaluated for reason, clinical effects, management site and outcome.

Results: There were 16,935 exposures included: 5018 aripiprazole, 1735 olanzapine, 3904 quetiapine, 4778 risperidone and 1500 ziprasidone. Median age was two years. Most common reason was unintentional-general (90.6%). Therapeutic error occurred more often with risperidone (19.9%). Clinical effects occurred in 59.4% of aripiprazole, 57.9% of olanzapine, 56.6% of ziprasidone, 40.1% of risperidone, and 29.3% of quetiapine. The most frequent were drowsiness/lethargy (35.6%), tachycardia (6.9%), agitation (4.0%), and ataxia (3.3%). Drowsiness/lethargy occurred most with aripiprazole (47.6%), ziprasidone (46.5%) and olanzapine (45.1%) and least with quetiapine (20.5%) and risperidone (28.6%). Tachycardia and agitation both occurred most often with olanzapine (11.4% and 12.7%, respectively). Management sites were non-health care facility (28.0%), treated/discharged from emergency department (48.9%), admitted – noncritical care (11.4%), critical care (9.5%), and other/unknown (2.2%). Admission was lowest for risperidone (13.9%) and quetiapine (11.9%) and highest for olanzapine (32.9%). Coded outcomes were no effect (53.3%), minor (33.7%), moderate (12.1%), major (0.9%) and no deaths. Moderate/major outcomes occurred most often with ziprasidone (20.5%) and olanzapine (19.0%) and least often with quetiapine (5.3%) and risperidone (10.9%).

Discussion and conclusion: Overall outcomes were favorable, with major toxicity in <1% of exposures. Risperidone and quetiapine exposures resulted in less toxicity. This finding may be attributed to higher frequency of therapeutic errors for risperidone but the reason for less toxicity with quetiapine is unclear.     

Toxicity and clinical outcomes of paliperidone exposures reported to U.S. Poison Centers

Context. Paliperidone is an atypical antipsychotic that was approved in the U.S. in 2006, and is also available in Canada, Australia, New Zealand, Europe, and Asia. Information regarding paliperidone overdoses is limited to case reports. Serious toxicity has yet to be reported. Objective. To evaluate the toxicity of paliperidone exposures using a national poison center database. Methods. A retrospective, observational case series of single-substance paliperidone cases reported to the National Poison Data System from 2007 to 2012 was conducted. Cases were evaluated for demographics, reason for exposure, clinical effects, treatments, disposition, and coded medical outcomes. For cases with major effects the text fields in poison center charts were evaluated to verify accuracy of coded outcome. The relationship between dose and severity of medical outcome was analyzed for acute exposure cases. Results. There were 801 paliperidone cases that met inclusion criteria that included 592 persons of 13 years or greater, 67 children of 6–12 years, 140 children of less than 6 years, and 2 unknown ages. Most common reasons for exposure included: suicide attempt (39.6%), unintentional general (21.1%), therapeutic error (15.7%), and adverse drug reaction (11.9%). The most commonly observed clinical effects were drowsiness/lethargy (28.7%), tachycardia (23.3%), and dystonia (14.2%). Most patients were managed in the emergency department (40.3%) or were admitted to a health care facility (HCF) (42.7%). In 564 cases treated in a HCF, treatments included activated charcoal (25.7%), antihistamines (21.1%), and benzodiazepines (9.4%). Medical outcomes were no effect (35.0%), minor (30.8%), moderate (33.7%), and major effect (0.5%). There were no deaths. Of 491 acute exposures, dose was coded for 74.3% of exposures. There was a significant difference in the reported median dose between those with no effect (6 mg) and either minor effect (12 mg; p = 0.047) or moderate effect cases (12 mg; p = 0.020) in 91 children less than 6 years. Conclusions. The majority of patients experienced no or minor toxicity and were not admitted for medical care. Although a higher dose was associated with a more serious outcome in children less than 6 years, the data do not provide clear-cut triage guidelines.     

Emergency department management of mild traumatic brain injury in the USA

Objective: To describe the emergency department (ED) management of isolated mild traumatic brain injury (TBI) in the USA and to examine variation in care across age and insurance types.

Methods: A secondary analysis of ED visits for isolated mild TBI in the National Hospital Ambulatory Medical Care Survey 1998–2000 was performed. Mild TBI was defined by International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9) codes for skull fracture, concussion, intracranial injury (unspecified), and head injury (unspecified). Available ED care variables were analysed by patient age and insurance categories using multivariate logistic regression.

Results: The incidence of isolated mild TBI cases attending ED was 153 296 per year, or 56.4/100 000 people. Of the patients with isolated mild TBI, 44.3% underwent computed tomography, 23.9% underwent other non-extremity, non-chest x rays, 17.1% received wound care and 14.1% received intravenous fluids. However, only 43.8% had an assessment of pain. Of those with documented pain, only 45.5% received analgesics in the ED. Nearly 38% were discharged without recommendations for specific follow up. Several aspects of ED care varied by age but not by insurance type.

Conclusion: Substantial ED resources are devoted to the care of isolated mild TBI. The present study identified deficiencies in and variation around several important aspects of ED care. The development of guidelines specific for mild TBI could reduce variation and improve emergency care for this injury.

     

2014 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 32nd Annual Report

ABSTRACT

Background: This is the 32nd Annual Report of the American Association of Poison Control Centers’ (AAPCC) National Poison Data System (NPDS). As of 1 January 2014, 56 of the nation’s poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 7.82 [7.02, 11.17] (median [25%, 75%]) minutes, creating a near real-time national exposure and information database and surveillance system.

Methodology: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1–6 to assess the Relative Contribution to Fatality (RCF) of the exposure to the death.

Results: In 2014, 2,890,909 closed encounters were logged by NPDS: 2,165,142 human exposures, 56,265 animal exposures, 663,305 information calls, 6,085 human confirmed nonexposures, and 112 animal confirmed nonexposures. US poison centers (PCs) also made 2,617,346 follow-up calls in 2014. Total encounters showed a 5.5% decline from 2013, while health care facility human exposure cases increased by 3.3% from 2013. All information calls decreased by 17.7% and health care facility (HCF) information calls were essentially flat, decreasing by 0.04%, medication identification requests (Drug ID) decreased 29.8%, and human exposures reported to US PCs decreased 1.1%. Human exposures with less serious outcomes have decreased 3.40% per year since 2008 while those with more serious outcomes (moderate, major or death) have increased by 4.29% per year since 2000.

The top 5 substance classes most frequently involved in all human exposures were analgesics (11.3%), cosmetics/personal care products (7.7%), household cleaning substances (7.7%), sedatives/hypnotics/antipsychotics (5.9%), and antidepressants (4.4%). Sedative/Hypnotics/Antipsychotics exposures as a class increased the most rapidly (2,368 calls (12.2%)/year) over the last 13 years for cases showing more serious outcomes. The top 5 most common exposures in children age 5 years or less were cosmetics/personal care products (14.0%), household cleaning substances (11.0%), analgesics (9.3%), foreign bodies/toys/miscellaneous (6.7%), and topical preparations (5.8%). Drug identification requests comprised 43.3% of all information calls. NPDS documented 1,835 human exposures resulting in death with 1,408 human fatalities judged related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory).

Conclusions: These data support the continued value of PC expertise and need for specialized medical toxicology information to manage more serious exposures, despite a decrease in calls involving less serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national public health resource to collect and monitor US exposure cases and information calls. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, viral, bacterial, venomous, chemical agent, or commercial product), the identification of events of public health significance, resilience, response and situational awareness tracking. NPDS is a model system for the real-time surveillance of national and global public health.

NOTE: Comparison of exposure or outcome data from previous AAPCC Annual Reports is problematic. In particular, the identification of fatalities (attribution of a death to the exposure) differed from pre-2006 Annual Reports (see Fatality Case Review – Methods). Poison center death cases are described as all cases resulting in death and those determined to be exposure-related fatalities. Likewise, Table 22 (Exposure Cases by Generic Category) since year 2006 restricts the breakdown of included deaths to single-substance cases to improve precision and avoid misinterpretation.     

2010 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 28th Annual Report

Abstract

Background: This is the 28th Annual Report of the American Association of Poison Control Centers’ (AAPCC) National Poison Data System (NPDS). All US poison centers upload case data automatically with a median time interval of 19.0 [11.9, 40.6] (median [25%, 75%]) minutes, creating a near real-time national exposure and information database and surveillance system.

Methodology: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of 33 medical and clinical toxicologist reviewers using an ordinal scale of 1 (Undoubtedly responsible) – 6 (Unknown) to determine Relative Contribution to Fatality (RCF) of the exposure to the death.

Results: In 2010, 3,952,772 closed encounters were logged by NPDS: 2,384,825, human exposures, 94,823 animal exposures, 1,466,253 information calls, 6537 human confirmed nonexposures, and 334 animal confirmed nonexposures. Total encounters showed a 7.7% decline from 2009 while health care facility calls increased by 2.7%. Human exposures with more serious outcomes (minor, moderate, major or death) increased 4.5% while those with less serious outcomes (all other medical outcome categories) decreased 5.9%. All information calls decreased 12.6% and health care facility (HCF) information calls decreased 13.6%, Drug ID calls decreased 10.9%, and human exposures decreased 3.8%. The top 5 substance classes most frequently involved in all human exposures were analgesics (11.5%), cosmetics/personal care products (7.7%), household cleaning substances (7.3%), sedatives/hypnotics/ antipsychotics (6.0%), and foreign bodies/toys/miscellaneous (4.2%). Analgesic exposures as a class increased the most rapidly by 32.8% over the last decade. The top f ve most common exposures in children age 5 years or less were cosmetics/personal care products (13.2%), analgesics (9.4%), household cleaning substances (9.2%), foreign bodies/toys/miscellaneous (7.2%), and topical preparations (6.8%). THC homolog and designer amphetamine (“Bath Salts”) exposures were identified as emerging public health threats. Drug identification requests comprised 64.3% of all information calls. NPDS documented 1730 human exposures resulting in death with 1146 human fatalities judged related with an RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory.

Conclusions: These data support the continued value of poison center expertise and need for specialized medical toxicology information to manage the more severe exposures, despite a decrease in calls involving less severe exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national public health resource to collect and monitor US exposure cases and information calls. The continuing mission of NPDS is to provide a nationwide infrastructure for public health surveillance for all types of exposures, public health event identification, resilience response and situational awareness tracking. NPDS is a model system for the nation and global public health.     

Characterization of edible marijuana product exposures reported to United States poison centers

Context: Edible marijuana products are sold as brownies, cookies, and candies, which may be indistinguishable from counterparts without marijuana and are palatable to children and adults. The consumption of an entire product containing multiple dose-units may result in overdose.

Objective: To characterize edible marijuana exposures reported to US poison centers with subgroup analysis by age.

Methods: We analyzed single substance, human exposure calls coded to marijuana brownies, candies, cookies, beverages, or other foods reported to the National Poison Data System from January 2013 to December 2015. Calls were analyzed by state, age, gender, exposure route, clinical effect, therapies, and level of healthcare facility utilization.

Results: Four-hundred and thirty calls were reported: Colorado (N?=?166, 1.05/100,000 population/year) and Washington (96, 0.46) yielded the highest number of exposures. Three hundred and eighty-one (91%) calls occurred in states with decriminalized medical/recreational marijuana. The number of calls increased every year of the study. The most common age groups were: ≤5 years (N?=?109, 0.15/100,000 population/year) and 13–19 (78, 0.09). The most frequent clinical effects were drowsiness/lethargy (N?=?118, percentage?=?43%), tachycardia (84, 31%), agitated/irritable (37, 14%), and confusion (37, 14%). Children ≤5 years have more drowsiness/lethargy, ataxia, and red eye/conjunctivitis. No deaths were reported. The most common therapies administered were intravenous fluids (85, 20%), dilute/irrigate/wash (48, 11 %), and benzodiazepines (47, 11%). Three patients (ages 4, 10, and 57 years) received intubation. 97 (23%), 217 (50%), and 12 (3%) calls were managed at home, treated/released, admitted to a critical care unit, respectively.

Discussion: Although most clinical effects are minor, ventilatory support may be necessary for children and adults. We speculate the increasing exposures may be related to a combination of delayed absorption kinetics of Δ9-tetrahydrocannablnol, lagging packaging regulations, increased accessibility in decriminalized states, and increased familiarity of poison center specialists with edible product codes.

Conclusions: Edible marijuana exposures are increasing and may lead to severe respiratory depression.     

Discharge from triage: modelling the potential in different types of emergency department

Objective: To assess the potential for patients to be assessed and discharged directly from triage in an emergency department (ED).

Methods: Modelling was undertaken by collection of retrospective electronic data from four different EDs. Serial removal of groups was undertaken using data from coding systems related to patients details of admission/treatment/investigations and procedure undertaken. The final group left were analysed for ambulance usage, prior primary care consultation, and age group.

Results: 29.4% patients were discharged after clinical assessment but without any specific treatment or investigation. It was seen that of the patients who can be considered for discharge from triage, 15.5% were brought to the ED by ambulance, 3.5% were patients who had already consulted primary care, and 11% were children.

Conclusions: This study suggests that a large percentage of patients seen in EDs may not require the extra facilities of that department. There is potential for a large number to be discharged within a few minutes of arrival if appropriate assessment skills are available at first contact. This may require more senior assessment than is currently used. This study has not assessed safety of such a system or the times of day when it is best deployed.

     

Safety and effectiveness of physostigmine: a 10-year retrospective review*

Background: Physostigmine has long been recognized as an antidote to reverse anticholinergic delirium. However, its effectiveness, safety profile, and dosing have been disputed.

Objectives: To describe effectiveness, adverse events, and dosing associated with the use of physostigmine to reverse anticholinergic delirium.

Methods: A retrospective cohort study of hospitalized patients reported to a regional poison center system between 2003 and 2012 who received physostigmine to reverse an anticholinergic toxidrome. Data extraction of a priori defined variables were recorded with concurrence of investigators. The cases were stratified by the primary ingestant as the presumed causative agent and associations for response were performed using odds ratios (ORs), 95% confidence intervals (CI’s), and p values.

Results: Of the 1422 cases identified, 191 met the inclusion criteria. Patients exposed to non-diphenhydramine antihistamines (n?=?14), antipsychotics (n?=?4), and tricyclic antidepressants (n?=?3) had 100% response to physostigmine, whereas anticholinergic plants (n?=?46/67; 68.7%, OR: 0.70; CI: 0.36–1.35), diphenhydramine (n?=?43/56; 64.2%, OR: 1.30; CI: 0.63–2.68), and combination products (n?=?8/10; 80%, OR: 1.48; CI: 0.30–7.24) had partial response rates. Of the included patients, 142 (74.3%) were treated with physostigmine alone, and 16 (8.4%) of these patients were discharged directly from the emergency department (ED).

Discussion: Most patients, 182 (95.3%), had no documented adverse effects. Four patients (2.1%) experienced emesis, two experienced QTc prolongation (1.0%), and two experienced seizures (1.0%). There was a single fatality 6?h after physostigmine administration. Average initial total doses of physostigmine ranged from 1.0 to 1.75?mg. Most patients were admitted to the ICU (n?=?110; 57.6%), however, 36 (18.8%) patients were discharged directly from the ED.

Conclusions: In this retrospective cohort study, physostigmine administration to reverse anticholinergic delirium had a good safety profile, and often improved or resolved anticholinergic delirium when administered in doses less than 2?mg.     

Interfacility transports by emergency medical services in the United States: Estimates from the National Hospital Ambulatory Medical Care Survey

ObjectiveTo describe characteristics of encounters in U.S. emergency departments (EDs) brought by interfacility transport by emergency medical services (EMS) from other EDs or urgent care settings.MethodsWe performed a cross-sectional study of the National Hospital Ambulatory Medical Care Survey, a multistage probability survey of nonfederal of visits to U.S. EDS. We evaluated patients who were brought to the ED as an interfacility transport by EMS from another ED or urgent care setting between 2014 and 2017. We report demographics, clinical characteristics and treatment factors of ED encounters brought interfacility transport and assessed factors associated with discharge from the receiving ED.ResultsOf 562.9 million ED encounters during the assessed period, 4.5 million were brought by interfacility transport by EMS (1.1 million per year). This represented 0.8% (95% CI 0.6–1.0%) of all ED encounters and 5.3% (95% CI 4.4–6.3%) of ED encounters transported by EMS. Most encounters brought by interfacility transport were adults (85%) who were publicly insured (62%). 39% had at least one abnormal vital sign. Most encounters received diagnostic testing (84%) and were seen within 30 min of presentation (61%). 54% were admitted, and 36% were discharged from the ED. Encounters without chronic complex conditions and with normal triage vital signs were associated with ED discharge (p < 0.01).DiscussionInterfacility transports between EDs transported by EMS account for <1% of ED encounters in the U.S. Nearly 40% of such encounters are ultimately discharged. Further research is needed to identify a low-risk cohort among patients in need of secondary transport.     

Accidental pharmacological poisonings in young children: population-based study in three settings

Introduction: Pharmacological poisonings in young children are avoidable. Previous studies report calls to poisons centres, presentations to emergency departments (ED) or hospital admissions. There are limited data assessing concurrent management of poisonings across all three settings. We aimed to describe accidental pharmacological poisonings in young children across our Poisons Information Centre (PIC), EDs and hospitals.

Methods: A population-based study in New South Wales, Australia, of PIC calls, ED presentations and hospital admissions for accidental pharmacological poisoning in children aged <5 years, 2007–2013. We examined trends, medicines responsible and subsequent management. Medicines were coded using ICD10-AM diagnosis codes (T36-50).

Results: Over 2007–2013, pharmacological poisonings accounted for 67,816 PIC calls, 7739 ED presentations and 2082 admissions. Rates (per 10,000 children) of PIC calls declined from 220 to 178; ED presentations were stable (～22–24), with a decrease in emergency cases offset by an increase in semi- or non-urgent presentations; hospital admissions declined (8–5). Most PIC calls related to “non-opioid analgesics” (25%), and “topical agents” (18%). Nearly every day, one child aged <5 years was admitted to hospital for poisoning. “Benzodiazepines”, “other and unspecified antidepressants”, “uncategorised antihypertensives”, and “4-aminophenol derivatives” accounted for over one-third of all admissions. Most PIC calls (90%) were advised to stay home, 6% referred to hospital. One-quarter of ED presentations resulted in admission.

Conclusions: Poisonings reported to PIC and hospitals declined, however, non-urgent ED presentations increased. Strategies to reduce therapeutic errors and access to medicines, and education campaigns to improve Poisons Centre call rates to prevent unnecessary ED presentations are needed.     

Is it Appropriate for Patients to be Discharged at the Scene by Paramedics?

Background: Outcomes of patients who are discharged at the scene by paramedics are not fully understood. Objective: We aimed to describe the risk of re-presentation and/or death in prehospital patients discharged at the scene. Methods: We conducted a retrospective cohort study using linked ambulance, emergency department (ED), and death data. We compared outcomes in patients who were discharged at the scene by paramedics with those who were transported to ED by paramedics and then discharged from ED between January 1 and December 31, 2013 in metropolitan Perth, Western Australia. Occurrences of subsequent ambulance requests, ED attendance, hospital admission and death were compared between those discharged at the scene and those discharged from ED. Results: There were 47,330 patients during the study period, of whom 19,732 and 27,598 patients were discharged at the scene and from ED, respectively. Compared to those discharged from ED, those discharged at the scene were more likely to subsequently: request an ambulance (6.1% vs. 1.8%, adjusted odds ratio [adj OR] 3.4; 95% confidence interval [CI] 3.0–3.9), attend ED (4.6% vs. 1.4%, adj OR 3.3; 95% CI 2.8–3.8), be admitted to hospital (3.3% vs. 0.8%, adj OR 4.2; 95% CI 3.4–5.1). Those discharged at the scene tended towards an increased likelihood of death (0.2% vs. 0.1%, adj OR 1.8; 95% CI 0.99–3.2) within 24 hours of discharge compared to those discharged from ED. Conclusion: Patients attended by paramedics who were discharged at the scene had more subsequent events than those who were transported to and discharged from ED. Further consideration needs to be given to who is suitable to be discharged at the scene by paramedics.     

Unusual human poisoning with Delphinium peregrinum

Abstract

Background: This is the 30^th Annual Report of the American Association of Poison Control Centers’ (AAPCC) National Poison Data System (NPDS). As of July 1, 2012, 57 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 7.58 [6.30, 11.22] (median [25%, 75%]) min, creating a near real-time national exposure and information database and surveillance system.

Methodology: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of 34 medical and clinical toxicologist reviewers using an ordinal scale of 1–6 to assess the Relative Contribution to Fatality (RCF) of the exposure to the death.

Results: In 2012, 3,373,025 closed encounters were logged by NPDS: 2,275,141 human exposures, 66,440 animal exposures, 1,025,547 information calls, 5,679 human confirmed nonexposures, and 218 animal confirmed nonexposures. Total encounters showed a 6.9% decline from 2011, while healthcare facility (HCF) exposure calls increased by 1.2%. All information calls decreased by 14.8% and HCF information calls decreased by 1.7%, medication identification requests (Drug ID) decreased by 22.0%, and human exposures reported to US PCs decreased by 2.5%. Human exposures with less serious outcomes have decreased by 3.7% per year since 2008, while those with more serious outcomes (moderate, major, or death) have increased by 4.6% per year since 2000.

The top five substance classes most frequently involved in all human exposures were analgesics (11.6%), cosmetics/personal care products (7.9%), household cleaning substances (7.2%), sedatives/hypnotics/antipsychotics (6.1%), and foreign bodies/toys/miscellaneous (4.1%). Analgesic exposures as a class increased the most rapidly (8,780 calls/year) over the last 12 years. The top five most common exposures in children aged 5 years or less were cosmetics/ personal care products (13.9%), analgesics (9.9%), household cleaning substances (9.7%), foreign bodies/toys/ miscellaneous (7.0%), and topical preparations (6.3%). Drug identification requests comprised 54.4% of all information calls. NPDS documented 2,937 human exposures resulting in death with 2,576 human fatalities judged related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory).

Conclusions: These data support the continued value of PC expertise and need for specialized medical toxicology information to manage the more severe exposures, despite a decrease in calls involving less severe exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national public health resource to collect and monitor US exposure cases and information calls. The continuing mission of NPDS is to provide a nationwide infrastructure for public health surveillance for all types of exposures, public health event identification, resilience response, and situational awareness tracking. NPDS is a model system for the nation and global public health.     

Analytical confirmation of synthetic cannabinoids in a cohort of 179 presentations with acute recreational drug toxicity to an Emergency Department in London,UK in the first half of 2015

Context: Synthetic cannabinoid receptor agonists are the largest group of new psychoactive substances reported in the last decade; in this study we investigated how commonly these drugs are found in patients presenting to the Emergency Department with acute recreational drug toxicity.

Methods: We conducted an observational cohort study enrolling consecutive adult patients presenting to an Emergency Department (ED) in London (UK) January–July 2015 (6 months) with acute recreational drug toxicity. Residual serum obtained from a serum sample taken as part of routine clinical care was analyzed using high-resolution accurate mass-spectrometry with liquid-chromatography (HRAM-LCMSMS). Minimum clinical data were obtained from ED medical records.

Results: 18 (10%) of the 179 patient samples were positive for synthetic cannabinoid receptor agonists. The most common was 5F AKB-48 (13 samples, concentration 50–7600?pg/ml), followed by 5F PB-22 (7, 30–400?pg/mL), MDMB-CHMICA (7, 80–8000?pg/mL), AB-CHMINACA (3, 50–1800?pg/mL), Cumyl 5F-PINACA (1, 800?pg/mL) and BB-22 (1, 60?pg/mL). Only 9/18 (50%) in whom synthetic cannabinoid receptor agonists were detected self-reported synthetic cannabinoid receptor agonist use. The most common clinical features were seizures and agitation, both recorded in four (22%) individuals. Fourteen patients (78%) were discharged from the ED, one of the four admitted to hospital was admitted to critical care.

Conclusions: Synthetic cannabinoid receptor agonists were found in 10% of this cohort with acute recreational drug toxicity but self-reported in only half of these. This suggests that presentations to the ED with acute synthetic cannabinoid receptor agonist toxicity may be more common than reported.     

An epidemiologic and clinical description of e-cigarette toxicity

Introduction: E-cigarettes are battery-powered electronic nicotine delivery systems that simulate smoking by vaporizing nicotine-containing solutions. Systematic published data on e-liquid toxicity and exposures are limited to case reports and retrospective studies. Prospectively-collected data on the type of exposure, symptomatology, duration of symptoms, and concentration/flavor of e-fluids has not been published.

Methods: This was a prospective observational study over a 42-month period (07/01/2014–12/31/2017). For all calls to a single poison center that involved e-cigarette devices or refill fluid, a data collection instrument was filled out by the specialist in poison information (SPI).

Results: Two hundred sixty-five total cases were identified, including 193 children and 72 adults. The majority of both pediatric (72%; 139/193) and adult (61%; n?=?44/72) exposures involved e-liquid refill containers or fluid. Fifty-six percent (n?=?108/193) of pediatric exposures involved ingestion of refill liquid. Though children who ingested e-liquid received only a small amount, initial symptoms were evident in 32% (n?=?35/108) of cases. Children who did not ingest or inhale the products were less likely to develop toxicity. Only 2 children who were asymptomatic on initial call became symptomatic on follow-up. Most patients symptoms resolved within 4?hours. Seventy-one specific products/brands were identified with nicotine concentrations ranging from 0?mg/mL to 60?mg/mL with one product containing 3000?mg in a single bottle. A variety of flavors were identified, including several with names that may be attractive to toddlers or adolescents.

Discussion: E-cig exposures tend to produce irritant effects from topical exposures and nicotine toxicity from ingestions, as well as some dermal and “sucking” toddler exposures.

Conclusion: Exposure to e-cig fluid or device frequently causes mild symptoms and rarely may produce systemic nicotine toxicity.     

Acute disseminated encephalomyelitis in children - clinical and MRI decision making in the emergency department

BackgroundAcute disseminated encephalomyelitis (ADEM) is an uncommon, treatable, primarily pediatric, immune-mediated disease. Diagnosis of ADEM requires two essential elements: typical clinical presentation and magnetic resonance imaging (MRI) findings. The aim of this study was to evaluate how clinical findings in the initial emergency department (ED) presentation influenced the timing of MRI.MethodsA retrospective chart review was conducted of children diagnosed with ADEM, over a 12-year period, in a tertiary care pediatric center. Clinical presentation at ED admission was recorded and patients who underwent an MRI as part of their ED evaluation (early MRI) with those who had MRI performed during ward hospitalization (late MRI) were compared.Results30 patients were diagnosed with ADEM during the study period. Encephalopathy and polyfocal neurological signs were described in 80% and 50% of patients ED charts, respectively. Seven patients underwent early MRI and polyfocal neurological signs were more common in this group (p = 0.006). Fever was more common in the late MRI group (p = 0.02). Following diagnosis, all patients were treated with immune-modulation therapy, improved clinically, and were discharged.Conclusion20% of ADEM patients were not encephalopathic at ED presentation. Polyfocal neurological signs and absence of fever at ED presentation were related to earlier MRI utilization and thus earlier diagnosis and treatment. Familiarity with the ADEM constellation of signs, and a high index of suspicion, may help the ED clinician in early diagnosis and treatment of this rare disease.     

2009 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 27th Annual Report

Background:?This is the 27th Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 July 2009, 60 of the nation's 60 US poison centers (PCs) uploaded case data automatically. The upload time was 19.9 [9.7, 58.7] (median [25%, 75%]) minutes, creating a near real-time national exposure and information database and surveillance system.

? Methodology:?We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of 29 medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to determine Relative Contribution to Fatality (RCF) of the exposure to the death.

? Results:?In 2009, 4,280,391 calls were captured by NPDS: 2,479,355 closed human exposures, 116,408 animal exposures, 1,677,403 information calls, 6,882 human confirmed nonexposures, and 343 animal confirmed nonexposures. The top 5 substance classes most frequently involved in all human exposures were analgesics (11.7%), cosmetics/personal care products (7.7%), household cleaning substances (7.4%), sedatives/hypnotics/antipsychotics (5.8%), and foreign bodies/toys/miscellaneous (4.3%). Analgesic exposures as a class increased the most rapidly (12,494 calls per year) over the last decade. The top 5 most common exposures in children age 5 or less were cosmetics/personal care products (13.0%), analgesics (9.7%), household cleaning substances (9.3%), foreign bodies/toys/miscellaneous (7.0%), and topical preparations (6.8%). Drug identification requests comprised 63.0% of all information calls. NPDS documented 1,544 human exposures resulting in death with 1,158 human fatalities judged related with an RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory.

? Conclusions:?Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national public health resource to collect and monitor US exposure cases and information calls. The continuing mission of NPDS is to provide a nationwide infrastructure for public health surveillance for all types of exposures, public health event identification, resilience response and situational awareness tracking. NPDS is a model system for the nation and global public health.