RESUMEN
Nonpairwise multiqubit interactions present a useful resource for quantum information processors. Their implementation would facilitate more efficient quantum simulations of molecules and combinatorial optimization problems, and they could simplify error suppression and error correction schemes. Here, we present a superconducting circuit architecture in which a coupling module mediates two-local and three-local interactions between three flux qubits by design. The system Hamiltonian is estimated via multiqubit pulse sequences that implement Ramsey-type interferometry between all neighboring excitation manifolds in the system. The three-local interaction is coherently tunable over several MHz via the coupler flux biases and can be turned off, which is important for applications in quantum annealing, analog quantum simulation, and gate-model quantum computation.
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Interferometría , Simulación por ComputadorRESUMEN
OBJECTIVES: Previous research has demonstrated that accidental unsupervised ingestions (AUIs) were responsible for the majority of cough and cold medication (CCM) ingestions leading to significant adverse events (AEs) in children. The objective of this analysis was to characterize the role of AUIs in the morbidity associated with CCM exposure in children. METHODS: This surveillance study collected data from 5 United States data sources from 2009 to 2016, in children younger than 6 years with an AE from an AUI involving at least 1 CCM over-the-counter pharmaceutical ingredient. An expert panel reviewed each case to determine causality. RESULTS: From 4756 total cases reviewed, 3134 (65.9%) had an AE from an AUI determined to be at least potentially related to a CCM ingredient. The majority (61.3%) of cases occurred in children aged 2 to younger than 4 years. Most exposures occurred in the child's own residence (94.9%), and 43.8% were admitted to a health care facility (22.0% to a critical care unit). Dextromethorphan and diphenhydramine, when packaged alone or in combination products, contributed to 96.0% of AUIs. The most common specific products involved were single-ingredient pediatric liquid diphenhydramine (30.1%) and single-ingredient pediatric liquid dextromethorphan (21.4%). There were 3 deaths from solid diphenhydramine formulations. CONCLUSIONS: There continues to be opportunities for the implementation of interventions to prevent AUIs of CCM in children. Additional emphasis on engineering controls, such as flow restrictors for liquid formulations targeting diphenhydramine and dextromethorphan products, represent additional opportunities to further reduce AEs from AUIs of CCM.
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Tos , Medicamentos sin Prescripción , Niño , Tos/inducido químicamente , Tos/epidemiología , Difenhidramina , Ingestión de Alimentos , Hospitalización , Humanos , Lactante , Medicamentos sin Prescripción/efectos adversos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: The purpose of this report is to evaluate the quality of data sources used to study cough and cold medication (CCM) safety in children via the Pediatric Cough and Cold Safety Surveillance System. METHODS: The System utilized the National Poison Data System (NPDS), FDA Adverse Event Reporting System (FAERS), English-language medical literature, manufacturer postmarket safety databases, and news/media reports to identify cases from January 2008 through September 2016. Each data source was evaluated by the proportion of detected cases determined to be eligible (met case criteria) and the proportion determined to be evaluable (able to determine causal relationship between adverse event and exposure). RESULTS: A total of 7184 unique cases were identified from 27,597 detected reports. Of these, 6447 (89.7%) were evaluable. The data source with the highest volume of detected cases was news/media; however, only 0.3% of those cases were eligible for panel review and only 0.2% (24 out of 13,450 cases) were evaluable. The data source with the highest proportion of eligible and evaluable cases was NPDS with 7691 detected cases, 6113 (79.5%) eligible cases, and 5587 (72.6%) evaluable cases. CONCLUSIONS: The data sources utilized to evaluate the safety profile of pediatric CCMs yielded variable detection and evaluation rates, but overall provided a comprehensive look at exposures that otherwise cannot be studied in clinical trials. While this study suggests that each source made a valuable contribution and that evaluable cases are generalizable, improvements are needed in case completeness and accuracy to enhance the quality of postmarket safety evaluations.
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Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Resfriado Común/tratamiento farmacológico , Tos/tratamiento farmacológico , Almacenamiento y Recuperación de la Información/estadística & datos numéricos , Vigilancia de Productos Comercializados/estadística & datos numéricos , Sistemas de Registro de Reacción Adversa a Medicamentos/normas , Niño , Preescolar , Exactitud de los Datos , Femenino , Humanos , Lactante , Recién Nacido , Almacenamiento y Recuperación de la Información/normas , Masculino , Centros de Control de Intoxicaciones/normas , Centros de Control de Intoxicaciones/estadística & datos numéricos , Vigilancia de Productos Comercializados/métodos , Vigilancia de Productos Comercializados/normasRESUMEN
We provide recommendations for stocking of antidotes used in emergency departments (EDs). An expert panel representing diverse perspectives (clinical pharmacology, medical toxicology, critical care medicine, hematology/oncology, hospital pharmacy, emergency medicine, emergency medical services, pediatric emergency medicine, pediatric critical care medicine, poison centers, hospital administration, and public health) was formed to create recommendations for antidote stocking. Using a standardized summary of the medical literature, the primary reviewer for each antidote proposed guidelines for antidote stocking to the full panel. The panel used a formal iterative process to reach their recommendation for both the quantity of antidote that should be stocked and the acceptable timeframe for its delivery. The panel recommended consideration of 45 antidotes; 44 were recommended for stocking, of which 23 should be immediately available. In most hospitals, this timeframe requires that the antidote be stocked in a location that allows immediate availability. Another 14 antidotes were recommended for availability within 1 hour of the decision to administer, allowing the antidote to be stocked in the hospital pharmacy if the hospital has a mechanism for prompt delivery of antidotes. The panel recommended that each hospital perform a formal antidote hazard vulnerability assessment to determine its specific need for antidote stocking. Antidote administration is an important part of emergency care. These expert recommendations provide a tool for hospitals that offer emergency care to provide appropriate care of poisoned patients.
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Antídotos/provisión & distribución , Consenso , Servicios Médicos de Urgencia/organización & administración , Guías como Asunto , Hospitales/normas , Servicio de Farmacia en Hospital/normas , Intoxicación/tratamiento farmacológico , Humanos , Encuestas y CuestionariosAsunto(s)
Intoxicación por Plomo , Plomo/análisis , Niño , Humanos , Michigan , Abastecimiento de AguaRESUMEN
OBJECTIVE: To characterize the rates, root causes, and clinical effects of unintentional exposures to buprenorphine sublingual formulations among young children and to determine whether exposure characteristics differ between formulations. STUDY DESIGN: Unintentional exposures to buprenorphine-containing products among children 28 days to less than 6 years old were collected from the Researched Abuse, Diversion, and Addiction-Related Surveillance System Poison Center Program and Reckitt Benckiser Pharmaceuticals' pharmacovigilance system from October 2009-March 2012. After adjustment for drug availability, negative binomial regression was used to estimate average exposure rates. Root cause assessment was conducted, and an expert clinician panel adjudicated causality and severity of moderate to severe adverse events (AEs). RESULTS: A total of 2380 cases were reviewed, including 4 deaths. Exposures to buprenorphine-naloxone combination film were significantly less frequent than exposures to buprenorphine tablets (rate ratio 3.5 [95% CI, 2.7-4.5]) and buprenorphine-naloxone combination tablets (rate ratio 8.8 [7.2-10.6]). The most commonly identified root causes were medication stored in sight, accessed from a bag or purse, and not stored in the original packaging. Among 536 panel review cases, the most common AEs reported for all formulations were lethargy, respiratory depression, miosis, and vomiting. The highest level AE severity did not differ significantly by formulation. CONCLUSIONS: Unintentional exposure to buprenorphine can cause central nervous system depression, respiratory depression, and death in young children. Exposure rates to film formulations are significantly less than to tablet formulations. Package and storage deficiencies contribute to unintentional exposures in young children.
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Buprenorfina/efectos adversos , Buprenorfina/envenenamiento , Administración Sublingual , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/envenenamiento , Sistema Nervioso Central/efectos de los fármacos , Preescolar , Estudios Transversales , Embalaje de Medicamentos , Femenino , Humanos , Lactante , Masculino , Farmacovigilancia , Centros de Control de Intoxicaciones , Sistema de Registros , Análisis de Regresión , Estudios Retrospectivos , Comprimidos , Estados UnidosRESUMEN
Importance: The US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of acetaminophen poisoning, resulting in significant variability in management. Objective: To develop consensus guidelines for the management of acetaminophen poisoning in the US and Canada. Evidence Review: Four clinical toxicology societies (America's Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) selected participants (n = 21). Led by a nonvoting chairperson using a modified Delphi method, the panel created a decision framework and determined the appropriate clinical management of a patient with acetaminophen poisoning. Unique to this effort was the collection of guidelines from most poison centers in addition to systematic collection and review of the medical literature. Comments from review by external organizations were incorporated before the guideline was finalized. The project began in March 2021 and ended in March 2023. Findings: The search retrieved 84 guidelines and 278 publications. The panel developed guidelines for emergency department management of single or repeated ingestion of acetaminophen. In addition, the panel addressed extended-release formulation, high-risk ingestion, coingestion of anticholinergics or opioids, age younger than 6 years, pregnancy, weight greater than 100 kg, and intravenous acetaminophen use. Differences from current US practice include defining acute ingestion as an ingestion presentation from 4 to 24 hours after overdose was initiated. A revised form of the Rumack-Matthew nomogram was developed. The term massive ingestion was replaced with the term high-risk ingestion and denoted by a specific nomogram line. Other recommendations include specific criteria for emergency department triage, laboratory evaluation and monitoring parameters, defining the role of gastrointestinal decontamination, detailed management of acetylcysteine treatment, associated adverse effects, and stopping criteria for acetylcysteine treatment, as well as criteria for consultation with a clinical toxicologist. Finally, specific treatment considerations, including acetylcysteine dosing, fomepizole administration, and considerations for extracorporeal elimination and transplant evaluation, were addressed. Conclusions and Relevance: This qualitative study provides a consensus statement on consistent evidence-based recommendations for medical, pharmacy, and nursing education and practice to optimize care of patients with acetaminophen poisoning.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Venenos , Humanos , Niño , Acetaminofén , Acetilcisteína , Atención Ambulatoria/métodos , Medicina Basada en la Evidencia , Canadá/epidemiologíaRESUMEN
BACKGROUND: Envenomation by crotaline snakes (rattlesnake, cottonmouth, copperhead) is a complex, potentially lethal condition affecting thousands of people in the United States each year. Treatment of crotaline envenomation is not standardized, and significant variation in practice exists. METHODS: A geographically diverse panel of experts was convened for the purpose of deriving an evidence-informed unified treatment algorithm. Research staff analyzed the extant medical literature and performed targeted analyses of existing databases to inform specific clinical decisions. A trained external facilitator used modified Delphi and structured consensus methodology to achieve consensus on the final treatment algorithm. RESULTS: A unified treatment algorithm was produced and endorsed by all nine expert panel members. This algorithm provides guidance about clinical and laboratory observations, indications for and dosing of antivenom, adjunctive therapies, post-stabilization care, and management of complications from envenomation and therapy. CONCLUSIONS: Clinical manifestations and ideal treatment of crotaline snakebite differ greatly, and can result in severe complications. Using a modified Delphi method, we provide evidence-informed treatment guidelines in an attempt to reduce variation in care and possibly improve clinical outcomes.
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Algoritmos , Técnicas de Apoyo para la Decisión , Mordeduras de Serpientes/terapia , Viperidae , Animales , Antivenenos/administración & dosificación , Antivenenos/efectos adversos , Venenos de Crotálidos/toxicidad , Técnica Delphi , Medicina de Emergencia Basada en la Evidencia , Humanos , Mordeduras de Serpientes/diagnóstico , Mordeduras de Serpientes/fisiopatología , Estados UnidosRESUMEN
INTRODUCTION: Initial research following regulatory changes addressing the pediatric safety of cough and cold medications (CCMs) demonstrated decreases in adverse events (AEs). Using a national multi-source surveillance system, we studied subsequent CCM-related AE case rate trends and associated health-care facility (HCF) evaluation in children. METHODS: Data were collected from 2009 to 2016. Case eligibility included: age <12 years; exposure to an over-the-counter product containing ≥1 CCM pharmaceutical ingredient; ≥1 significant AE that occurred in the United States. RESULTS: About 4756 (72.6%) cases were determined at least potentially related to an index ingredient. Accidental unsupervised ingestions (AUIs; 3134; 65.9%) were the most common case type. Nearly half of AE cases involved children 2 to <4 years old (2,159; 45.4%). The AE case rate did not change significantly over time (p = 0.22). The proportion of AE cases resulting in HCF admission increased from 32.4% (207) in 2009 to 43.4% (238) in 2016 (p < 0.01). Exposures to diphenhydramine (1,305; 67.3%) and/or dextromethorphan (591; 30.5%) were involved in the majority of HCF admissions. CONCLUSIONS: The proportion of AE cases resulting in HCF admission increased from 2009 to 2016. Efforts to prevent AUIs such as packaging innovation and engineering controls, particularly for diphenhydramine and dextromethorphan-containing products, should be pursued.
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Antitusígenos/efectos adversos , Medicamentos Compuestos contra Resfriado, Gripe y Alergia/efectos adversos , Niño , Preescolar , Dextrometorfano/efectos adversos , Difenhidramina/efectos adversos , Humanos , Medicamentos sin Prescripción/efectos adversos , Aceptación de la Atención de Salud/estadística & datos numéricos , Centros de Control de Intoxicaciones/estadística & datos numéricos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND AND OBJECTIVES: In 2008, over-the-counter cough and cold medications (CCMs) underwent labeling changes in response to safety concerns, including fatalities, reported in children exposed to CCMs. The objective of this study is to describe fatalities associated with exposures to CCMs in children <12 years old that were detected by a safety surveillance system from 2008 to 2016. METHODS: Fatalities in children <12 years old that occurred between 2008 and 2016 associated with oral exposure to one or more CCMs were identified by the Pediatric Cough and Cold Safety Surveillance System. An expert panel reviewed all cases to determine the causal relationship between the exposure and death, if the intent of exposure was therapeutic, and if the dose was supratherapeutic. Other contributing factors related to the child's death were also identified as part of a root cause analysis. RESULTS: Of the 180 eligible fatalities captured during the study period, 40 were judged by the expert panel to be either related or potentially related to the CCM. Of these, the majority (n = 24; 60.0%) occurred in children <2 years old and involved nontherapeutic intent (n = 22; 55.0%). The most frequently involved index ingredient was diphenhydramine (n = 28; 70.0%). In 6 cases (n = 6; 15.0%), the CCM was administered to murder the child. In another 7 cases (n = 7; 17.5%), death followed the intentional use of the CCM to sedate the child. CONCLUSIONS: Pediatric fatalities associated with CCMs occurred primarily in young children after deliberate medication administration with nontherapeutic intent by a caregiver.
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Antitusígenos/envenenamiento , Medicamentos sin Prescripción/envenenamiento , Antitusígenos/administración & dosificación , Bromofeniramina/envenenamiento , Niño , Preescolar , Clorfeniramina/envenenamiento , Dextrometorfano/envenenamiento , Difenhidramina/administración & dosificación , Difenhidramina/envenenamiento , Doxilamina/envenenamiento , Etiquetado de Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/mortalidad , Femenino , Guaifenesina/envenenamiento , Homicidio/estadística & datos numéricos , Humanos , Lactante , Masculino , Medicamentos sin Prescripción/administración & dosificación , Fenilefrina/envenenamiento , Seudoefedrina/envenenamientoRESUMEN
Introduction: Cardiovascular collapse due to large ingestions of isopropanol is rare. We report a case of a pediatric patient who had severe CNS and respiratory depression and cardiovascular collapse and was not hemodynamically stable enough to undergo hemodialysis.Case report: A 14-year-old 50 kg male was initially reported to have ingested an unknown amount of HEET® gas line antifreeze about 1 h prior to emergency department (ED) arrival. Despite severe CNS and respiratory depression and cardiovascular collapse, the patient was not initially acidotic. The patient did have an elevated osmolar gap. Approximately 6 h post-ingestion relatives updated the history to reflect that the product was in fact called ISO-HEET® which contains 99% isopropanol. Based on these concerns, a serum isopropanol and acetone levels were obtained that resulted at 475 and 75 mg/dL, respectively. Nephrology was consulted and it was decided to start the patient on sustained low-efficiency dialysis (SLED) which commenced 11 h post-ingestion. Serum and ultrafiltrate concentrations for isopropanol and acetone decreased to normal range over the course of SLED therapy.Discussion: SLED was instituted in this patient primarily for the treatment of elevated serum lactate, isopropanol, and acetone concentrations. The patient's systemic clearance was calculated as 26.9 mL/min. During SLED therapy, the patient was able to clear isopropanol and acetone at 41.21 mL/min and 29.74 mL/min, respectively. SLED therapy is a viable treatment option when a patient is hemodynamically unstable and hemodialysis is not an option.
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2-Propanol/envenenamiento , Sobredosis de Droga/terapia , Terapia de Reemplazo Renal Híbrido , Solventes/envenenamiento , 2-Propanol/sangre , Acetona/sangre , Adolescente , Sobredosis de Droga/etiología , Humanos , Terapia de Reemplazo Renal Híbrido/métodos , MasculinoRESUMEN
Introduction: Diphenhydramine (DPH) exposures in children may be the result of accidental unsupervised ingestions, caregiver error, and intentional misuse of DPH-containing cough and cold medications (CCM). We sought to understand the nature of pediatric ingestions of DPH, particularly the toxicity and outcome of a single product, single ingredient DPH (DPH-only) exposures, in order to derive ingredient-specific information about the clinical effects and course of such cases.Methods: As part of a U.S. multi-year safety surveillance program to assess the safety of over-the-counter (OTC) medications used in cough and cold preparations in children <12 years of age, an expert panel reviewed cases involving symptomatic adverse events potentially related to oral exposures to these medications. After individual review, the cases were categorized by causal relationship of the reported ingredients to the adverse event, exposure intent (therapeutic, non-therapeutic, unknown intent), and dose (therapeutic, supratherapeutic, or unknown). Following panel review, any disagreement on classification was discussed until a consensus was reached. The data were then analyzed with respect to descriptive findings.Results: The panel reviewed 6618 eligible cases and determined 2802 were at least potentially related to oral exposure to DPH. Of these, 2028 were DPH-only cases (39.1% of all cases judged at least potentially related to a cough and cold medication). The majority (79.5%) of DPH-only cases occurred in children 2 to <4 years of age and involved accidental unsupervised ingestions (74.7%). Liquid pediatric formulations were the most common (51.7%) products reported followed by solid pediatric formulations (24.0%). The most common adverse events were tachycardia (53.4%), hallucinations (46.5%), somnolence (34.7%), agitation (33.9%), and mydriasis (26.3%). Seizures occurred in only 5.5% of cases. Five (0.2%) deaths were reported; in the death cases, the DPH dose was judged supratherapeutic in one and unknown in the other four. Child abuse was reported in four of the five death cases and three of the five deaths were homicides.Conclusions: Exposures to DPH-only products were the most common type of exposure detected in our study of adverse events associated with CCM in children. The majority of the DPH-only cases were the result of accidental unsupervised ingestions. Most adverse events were relatively mild self-limited anticholinergic effects and few deaths occurred. Deaths involving DPH were often associated with child abuse or homicide. Interventions targeting the prevention of accidental unsupervised are likely to be impactful in preventing morbidity associated with DPH-only exposure.
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Antitusígenos/efectos adversos , Difenhidramina/efectos adversos , Medicamentos sin Prescripción/efectos adversos , Sistemas de Registro de Reacción Adversa a Medicamentos , Antitusígenos/administración & dosificación , Antitusígenos/uso terapéutico , Niño , Tos/tratamiento farmacológico , Difenhidramina/administración & dosificación , Difenhidramina/uso terapéutico , Humanos , Medicamentos sin Prescripción/administración & dosificación , Medicamentos sin Prescripción/uso terapéuticoRESUMEN
OBJECTIVE: Out of hospital medication-related adverse events (AEs) from cough and cold medications (CCMs) can have significant public health impact. The objective of this study was to characterize pediatric medication error AEs involving over-the-counter (OTC) CCMs to identify preventable factors. METHODS: Multisource national data surveillance system study using an expert panel evaluating CCM AEs related to medication errors. INCLUSION CRITERIA: age <12 years, and at least 1 significant AE from at least 1 index ingredient from a CCM OTC product. RESULTS: From 2009 through 2016, 4756 cases were determined to have a significant AE related to an OTC CCM ingredient and 513 (10.8%) cases were due to a medication error. Nearly half of medication errors involved children 2 to <6 years old (nâ¯=â¯235; 45.8%). Many involved administration by a parent (nâ¯=â¯231; 45.0%) or alternative caregiver (nâ¯=â¯148; 28.8%). In nearly all cases (93.2%), the medication error involved the wrong dose of the medication. Health care facility evaluation occurred in 381 (74.3%) cases. Diphenhydramine and dextromethorphan were responsible for most medication errors and medication errors involving health care facility evaluation. There were no deaths from medication errors. CONCLUSION: In this multiyear surveillance study, medication errors most commonly occurred in children <6 years old who received the wrong volume of a liquid product. Diphenhydramine and dextromethorphan dosing errors were the most common cause of medication errors resulting from CCM use. Continued standardization of measuring devices, concentrations, and units of measure along with consumer education are needed to further decrease medication errors from CCMs.
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Resfriado Común/tratamiento farmacológico , Tos/tratamiento farmacológico , Dextrometorfano/efectos adversos , Difenhidramina/efectos adversos , Errores de Medicación/estadística & datos numéricos , Medicamentos sin Prescripción/efectos adversos , Niño , Preescolar , Dextrometorfano/administración & dosificación , Difenhidramina/administración & dosificación , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Humanos , Lactante , Masculino , Medicamentos sin Prescripción/administración & dosificación , Padres , Vigilancia en Salud Pública , Estados UnidosRESUMEN
STUDY OBJECTIVE: The use of nonprescription cough and cold medicines is widespread, but their use has been sporadically associated with severe toxicity and death. We evaluate the role of these medications in pediatric fatalities and identified factors that contributed to the death. METHODS: Fatalities that involved a child younger than 12 years and mentioned a cough and cold ingredient were obtained from 5 sources. An independent panel of 8 experts (pediatrics, pediatric critical care, pediatric toxicology, clinical toxicology, forensic toxicology, forensic pathology) used explicit definitions to assess the causal relationship between medication ingestion and death. Contributing factors were identified. RESULTS: Of 189 cases included, 118 were judged possibly, likely, or definitely related to a cough and cold ingredient. Of these 118 cases, 103 involved a nonprescription drug, whereas 15 cases involved a prescription medication alone. Of 103 cases associated with nonprescription drugs, the evidence indicated that 88 involved an overdosage. A dosage could not be assessed in the remaining 15 cases. Several contributing factors were identified: age younger than 2 years, use of the medication for sedation, use in a daycare setting, use of 2 medicines with the same ingredient, failure to use a measuring device, product misidentification, and use of a nonprescription product intended for adult use. All cases that occurred in a daycare setting involved a child younger than 2 years. CONCLUSION: In our sample, pediatric fatalities caused by nonprescription cough and cold medications were uncommon, involved overdose, and primarily affected children younger than 2 years. The intent of caregivers appears to be therapeutic to relieve symptoms in some cases and nontherapeutic to induce sedation or to facilitate child maltreatment in other cases.
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Antitusígenos/envenenamiento , Resfriado Común/tratamiento farmacológico , Tos/tratamiento farmacológico , Descongestionantes Nasales/envenenamiento , Medicamentos sin Prescripción/envenenamiento , Intoxicación/mortalidad , Sistemas de Registro de Reacción Adversa a Medicamentos , Niño , Preescolar , Sobredosis de Droga , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
INTRODUCTION: This is the 35th Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 January 2017, 55 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 8.07 [7.32, 12.65] (median [25%, 75%]) minutes, creating a near real-time national exposure and information database and surveillance system. METHODS: 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. 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. RESULTS: In 2017, 2,607,413 closed encounters were logged by NPDS: 2,115,186 human exposures, 51,164 animal exposures, 435,540 information contacts, 5,424 human confirmed nonexposures, and 99 animal confirmed nonexposures. US PCs also made 2,680,625 follow-up calls in 2017. Total encounters showed a 3.79% decline from 2016, while health care facility (HCF) human exposure cases increased by 3.06%. All information contacts decreased by 11.5%, medication identification (Drug ID) requests decreased by 30.2%, and human exposure cases decreased by 2.03%. Human exposures with less serious outcomes have decreased 2.48% per year since 2008, while those with more serious outcomes (moderate, major or death) have increased 4.44% per year since 2000. Consistent with the previous year, the top 5 substance classes most frequently involved in all human exposures were analgesics (11.08%), household cleaning substances (7.43%), cosmetics/personal care products (6.76%), sedatives/hypnotics/antipsychotics (5.74%), and antidepressants (5.02%). As a class, sedative/hypnotics/antipsychotics exposures increased most rapidly, by 1962 cases/year (4.91%/year), over the last 17 years for cases with more serious outcomes. The top 5 most common exposures in children age 5 years or less were cosmetics/personal care products (12.59%), household cleaning substances (10.96%), analgesics (9.18%), foreign bodies/toys/miscellaneous (6.39%), and topical preparations (4.84%). Drug identification requests comprised 22.1% of all information contacts. NPDS documented 3,208 human exposures resulting in death; 2,682 (83.6%) of these were judged as 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 cases 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 status of NPDS represents a national public health resource to collect and monitor US exposure cases and information contacts. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, infectious, venomous, chemical agent, or commercial product), and the identification and tracking of significant public health events. NPDS is a model system for the near real-time surveillance of national and global public health.
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Bases de Datos Factuales , Centros de Control de Intoxicaciones , Intoxicación/epidemiología , Intoxicación/terapia , Estados UnidosRESUMEN
A 13-year-old female was presented to the emergency department following an intentional ingestion. The patient developed significant toxicity including multiple, discreet tonic-clonic seizures. Despite appropriate resuscitation and antidotal management, the patient's symptoms persisted for more than 36 hours post-ingestion. An upright abdominal radiograph was performed revealing a radiopacity suggesting a pharmacobezoar. An esophagogastroduodenoscopy was performed with successful removal of a tennis ball-sized pharmacobezoar. The patient's symptoms subsequently subsided and she recovered fully with no neurologic deficits. Diphenhydramine has not been previously identified as a medication likely to form a pharmacobezoar and has not been shown to be radiopaque. Though bezoar formation is a rare clinical scenario, it is one that toxicologists must consider in patients with clinical courses that persist far beyond expected based on known toxicokinetic principles.
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Bezoares/diagnóstico por imagen , Bezoares/terapia , Antagonistas Colinérgicos/envenenamiento , Difenhidramina/envenenamiento , Adolescente , Sobredosis de Droga/terapia , Servicio de Urgencia en Hospital , Endoscopía del Sistema Digestivo , Femenino , Humanos , Convulsiones/diagnóstico por imagen , Convulsiones/terapia , Resultado del TratamientoRESUMEN
INTRODUCTION: This is the 34th Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 January 2016, 55 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 9.50 [7.33, 14.6] (median [25%, 75%]) min, facilitating a near real-time national exposure and information database and surveillance system. METHODS: 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. 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. RESULTS: In 2016, 2,710,042 closed encounters were logged by NPDS: 2,159,032 human exposures, 54,019 animal exposures, 490,215 information cases, 6687 human confirmed non-exposures, and 89 animal confirmed non-exposures. US PCs also made 2,718,022 follow-up calls in 2016. Total encounters showed a 2.94% decline from 2015, while health care facility (HCF) human exposure cases increased by 3.63% from 2015. All information calls decreased by 12.5% but HCF information calls increased 0.454%, and while medication identification requests (Drug ID) decreased 29.6%, human exposure cases were essentially flat, decreasing by 0.431%. Human exposures with less serious outcomes have decreased 2.59% per year since 2008 while those with more serious outcomes (moderate, major or death) have increased by 4.39% per year since 2000. The top five substance classes most frequently involved in all human exposures were analgesics (11.2%), household cleaning substances (7.54%), cosmetics/personal care products (7.20%), sedatives/hypnotics/antipsychotics (5.84%), and antidepressants (4.74%). As a class, sedative/hypnotics/antipsychotics exposures increased most rapidly, by 10.7% per year (2088 cases/year), over the last 15 years for cases showing more serious outcomes. The top five most common exposures in children age 5 years or less were cosmetics/personal care products (13.3%), household cleaning substances (11.1%), analgesics (9.21%), foreign bodies/toys/miscellaneous (6.48%), and topical preparations (5.07%). Drug identification requests comprised 28.1% of all information calls. NPDS documented 1977 human exposures resulting in death; 1492 (75.5%) of these were judged as 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 cases 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 for collecting and monitoring 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, infectious, venomous, chemical agent, or commercial product), and the identification and tracking of significant public health events. NPDS is a model system for the real-time surveillance of national and global public health.
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Informes Anuales como Asunto , Preparaciones Farmacéuticas , Centros de Control de Intoxicaciones/estadística & datos numéricos , Intoxicación/epidemiología , Animales , Bases de Datos Factuales , Humanos , Preparaciones Farmacéuticas/clasificación , Intoxicación/etiología , Intoxicación/terapia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Western Pygmy Rattlesnake (WPR) envenomation reportedly causes refractory and persistent coagulopathy when treated with CroFab® (Crotalidae Polyvalent Immune Fab). We report two cases where polyvalent equine anti-viper serum (AntivipmynTRI®) was used to treat recurrent coagulopathy in children. CASE DETAILS: The first patient was a 16-month-old male who was bitten by a confirmed WPR. The patient received a total of 18 vials of CroFab®. His labs normalized, swelling gradually improved, and the child was discharged to home. On day 5, the child returned to the emergency department with a great deal of inguinal tenderness. Labs were obtained and the child's INR was >13.1, while the fibrinogen was <60 mg/dL and the d-dimer was 11.72 mg/L. A decision was made to administer Antivipmyn TRI®, and the child received a total of 10 vials. Lab values significantly improved: INR 1.2, fibrinogen 93 mg/dL, and d-dimer 4.21 mg/L. The second patient was a 20-month-old male who presented following snake envenomation. The child was administered a total of 22 vials of CroFab® over approximately 70 h following envenomation. Physical exam continued to improve, however, lab results showed an increasing INR 1.98, decreasing platelet count 124 × 103 per µL, fibrinogen <60 mg/dL, and d-dimer >20 ug/mL. A total of 15 vials of Antivipmyn TRI® were administered to this patient. Following this administration, labs and clinical exam both significantly improved. Labs revealed INR 1.16, fibrinogen 110 mg/dL, d-dimer 3.2 mg/L and platelet count 215 × 103/µL. DISCUSSION: CroFab® is still the first-line treatment for children bitten by a WPR, but in some cases patients develop a recurrent coagulopathy. The rapid response demonstrated by Antivipmyn TRI® leads us to conclude that this is a potential therapy for this clinical situation.
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Antivenenos/uso terapéutico , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Mordeduras de Serpientes/tratamiento farmacológico , Venenos de Víboras/toxicidad , Animales , Trastornos de la Coagulación Sanguínea/etiología , Crotalus , Edema/tratamiento farmacológico , Edema/etiología , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Fibrinógeno/metabolismo , Humanos , Lactante , Masculino , Dolor/tratamiento farmacológico , Dolor/etiología , Recuento de PlaquetasRESUMEN
STUDY OBJECTIVE: Dextromethorphan is the most common over-the-counter (OTC) antitussive medication. We sought to characterize adverse events associated with dextromethorphan in children <12 years old from a surveillance program of OTC cough/cold medication exposures. METHODS: This is a retrospective case series of oral exposures to dextromethorphan with ≥1 adverse event from multiple U.S. sources (National Poison Data System, FDA Adverse Event Reporting System, manufacturer safety reports, news/media, medical literature) reported between 2008 and 2014. An expert panel determined the relationship between exposure and adverse events, estimated dose ingested, intent of exposure, and identified contributing factors to exposure. RESULTS: 1716 cases contained ≥1 adverse event deemed at least potentially related to dextromethorphan; 1417 were single product exposures. 773/1417 (55%) involved only one single-ingredient dextromethorphan product (dextromethorphan-only). Among dextromethorphan-only cases, 3% followed ingestion of a therapeutic dose; 78% followed an overdose. 69% involved unsupervised self-administration and 60% occurred in children <4 years old. No deaths or pathologic dysrhythmias occurred. Central nervous system [e.g., ataxia (N = 420)] and autonomic symptoms [e.g., tachycardia (N = 224)] were the most common adverse events. Flushing and/or urticarial rash occurred in 18.1% of patients. Dystonia occurred in 5.4%. CONCLUSIONS: No fatalities were identified in this multifaceted surveillance program following a dextromethorphan-only ingestion. Adverse events were predominantly associated with overdose, most commonly affecting the central nervous and autonomic systems.
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Antitusígenos/envenenamiento , Enfermedades del Sistema Nervioso Autónomo/inducido químicamente , Enfermedades del Sistema Nervioso Central/inducido químicamente , Dextrometorfano/envenenamiento , Medicamentos sin Prescripción/envenenamiento , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Enfermedades del Sistema Nervioso Central/epidemiología , Niño , Preescolar , Sobredosis de Droga , Femenino , Humanos , Lactante , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND AND OBJECTIVES: The safety of cough and cold medication (CCM) use in children has been questioned. We describe the safety profile of CCMs in children <12 years of age from a multisystem surveillance program. METHODS: Cases with adverse events (AEs) after ingestion of at least 1 index CCM ingredient (brompheniramine, chlorpheniramine, dextromethorphan, diphenhydramine, doxylamine, guaifenesin, phenylephrine, and pseudoephedrine) in children <12 years of age were collected from 5 data sources. An expert panel determined relatedness, dose, intent, and risk factors. Case characteristics and AEs are described. RESULTS: Of the 4202 cases reviewed, 3251 (77.4%) were determined to be at least potentially related to a CCM, with accidental unsupervised ingestions (67.1%) and medication errors (13.0%) the most common exposure types. Liquid (67.3%), pediatric (75.5%), and single-ingredient (77.5%) formulations were most commonly involved. AEs occurring in >20% of all cases included tachycardia, somnolence, hallucinations, ataxia, mydriasis, and agitation. Twenty cases (0.6%) resulted in death; most were in children <2 years of age (70.0%) and none involved a therapeutic dose. The overall reported AE rate was 0.573 cases per 1 million units (ie, tablets, gelatin capsules, or liquid equivalent) sold (95% confidence interval, 0.553-0.593) or 1 case per 1.75 million units. CONCLUSIONS: The rate of AEs associated with CCMs in children was low. Fatalities occurred even less frequently. No fatality involved a therapeutic dose. Accidental unsupervised ingestions were the most common exposure types and single-ingredient, pediatric liquid formulations were the most commonly reported products. These characteristics present an opportunity for targeted prevention efforts.