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To detect the presence of unsuspected and/or undeclared cathinone and piperazine-type designer drugs in methamphetamine (METH) and amphetamine users treated in emergency departments, and to compare clinical and toxicologic profiles.Retrospective observational study of emergency department patients treated for confirmed acute intoxication by recreational drugs (METH and amphetamines) between March 2019 and December 2020. We ordered high-performance liquid chromatography with tandem mass spectrometry to detect cathinones (methylone, fluoromethcathinone, mexedrone, fluoromethamphetamine, mephedrone, methylenedioxypyrovalerone) and synthetic piperazines (meta-chlorophenylpiperazine and trifluoromethylphenylpiperazine). Demographic, clinical, and toxicologic variables were analyzed with SPSS software (version 23).Thirty-nine patients were included: 24 (61.5%) had used METH and 15 (38.5%) an amphetamine. Synthetic cathinones were detected in samples from 11 patients (28.2%), 10 (90.9%) in the METH group and 1 (9.1%) in the amphetamine group (P = .028). The METH users had taken mephedrone (8 patients) or methylone (2 patients); the amphetamine user had taken mephedrone. None of the patients had declared use of a cathinone; nor was use suspected. The mean (SD) number of substances involved was higher among users of cathinones (3.5 [1.13] vs 2.5 [1.40] in those who took no cathinones; P = .036). Among the cathinone users, 90.9% were men, 90.9% had used METH, and 45.5% had practiced chemsex. HIV positivity was significantly associated with cathinone use (in 45.5% vs 10.7% of those not using cathinones; P = .028). All 5 of the patients who had taken cathinones and also practiced chemsex were HIV positive. Significantly more patients who had taken cathinones presented with anxiety (72.7% vs 21.43%; P = .007). No differences in clinical management were found.Detection of METH in intoxicated patients should raise suspicion of probable use of a synthetic cathinone. Patients in whom new psychoactive substances are detected should be kept under observation, and clinical protocols should include referring them to addiction treatment centers.Determinar la incidencia de catinonas y piperazinas, no sospechadas y/o declaradas en consumidores de metanfetamina (MANF) y anfetamina (ANF) atendidos en servicios de urgencias hospitalarios (SUH) y comparar los perfiles clínicos y toxicológicos.Estudio retrospectivo de pacientes con intoxicación aguda por drogas recreativas con MANF y ANF confirmadas analíticamente atendidos en 3 SUH entre marzo de 2019 y diciembre de 2020. Se detectaron por HPLC-MS/MS las catinonas [metilona, fluorometcatinona, mecedrona, fluorometanfetamina, mefedrona, metilendioxipirovalerona (MDPV)] y las piperazinas sintéticas [meta-clorofenilpiperazina (mCPP), trifluorometilfenilpiperazina (TFMPP)].Se incluyeron 39 pacientes: 24 (61,5%) en el grupo MANF y 15 (38,5%) en el ANF. En 11 (28,2%), se detectaron catinonas sintéticas (grupo CAT), 10 en el grupo MANF (8 mefedrona, 2 metilona) y 1 en el grupo ANF (1 mefedrona) (90,9% vs 9,1%; p = 0,028). Ninguno de los pacientes declaró consumo de catinonas. El número de drogas implicadas en la intoxicación fue superior en el grupo CAT (3,5 [1,13] vs 2,5 [1,40]; p = 0,036). El perfil clínico del grupo CAT fue: varón (90,9%), consumidor de MANF (90,9%) y usuario de chemsex (45,5%). El diagnóstico de VIH se asoció significativamente al grupo CAT (45,5% vs 10,7%; p = 0,028). Los pacientes del grupo CAT presentaron mayor ansiedad (72,7% vs 21,4%; p = 0,007). No se hallaron diferencias en su manejo clínico.La detección de MANF debería considerarse un dato de sospecha de consumo de catinonas sintéticas, y en esos casos debería contemplarse la detección de nuevas sustancias psicoactivas de abuso.

Introduction and objectives Sudden cardiac death (SCD) in young people often has a genetic cause. Consequently, the results of “molecular autopsy” may have important implications for their relatives. Our objective was to evaluate the diagnostic yield of a molecular autopsy program using next-generation sequencing. Methods We performed a prospective study of a cohort of consecutive patients who died from nonviolent SCD, aged ≤ 50 years, and who underwent molecular autopsy using large panels of next-generation sequencing, with subsequent clinical and genetic family screening. We analyzed demographic, clinical, toxicological, and genetic data. Results We studied 123 consecutive cases of SCD in persons aged ≤ 50 years. The incidence of SCD was 5.8 cases/100 000 individuals/y, mean age was 36.15 ± 12.7 years, and 95 were men (77%). The cause was cardiac in 53%, unexplained SCD in 24%, toxic in 10.6%, and infant SCD in 4%. Among cardiac causes, ischemic heart disease accounted for 38% of deaths, arrhythmogenic cardiomyopathy for 7%, hypertrophic cardiomyopathy for 5%, and idiopathic left ventricular hypertrophy for 11%. Genetic analysis was performed in 62 cases (50.4%). Genetic variants were found in 42 cases (67.7%), with a mean of 3.4 ± 4 genetic variants/patient, and the variant found was considered to be pathogenic or probably pathogenic in 30.6%. In unexplained SCD, 70% showed some genetic variant. Family screening diagnosed 21 carriers or affected individuals, 5 of whom were at risk, indicating an implantable cardiac defibrillator. Conclusions Protocol-based and exhaustive study of SCD from cardiac causes in persons aged ≤ 50 years is feasible and necessary. In a high percentage of cases, the cause is genetic, indicating the existence of relatives at risk who could benefit from early diagnosis and treatment to avoid complications.

Resumen Introduccion y objetivos La muerte subita (MS) de personas jovenes suele tener una causa genetica, por lo cual la «autopsia molecular» puede tener implicaciones importantes para los familiares. El objetivo del estudio es evaluar el rendimiento diagnostico de un programa de autopsia molecular mediante secuenciacion masiva. Metodos Estudio prospectivo de una cohorte de pacientes consecutivos de edad ≤ 50 anos y fallecidos por MS no violenta, a los que se realizo autopsia molecular mediante paneles amplios por secuenciacion masiva, con posterior cribado familiar clinico y genetico. Se analizan datos demograficos, clinicos, toxicologicos y geneticos. Resultados Se estudiaron 123 casos consecutivos de MS a edades ≤ 50 anos. La incidencia de MS fue de 5,8 casos/100.000 individuos/ano, a una media de edad de 36,15 ± 12,7 anos; 95 (77%) eran varones. La causa fue cardiaca en el 53%; MS inexplicada en el 24%, toxicos en el 10,6% y MS del lactante en el 4%. De las cardiacas, el 38% por cardiopatia isquemica, el 7% por miocardiopatia arritmogenica, el 5% por miocardiopatia hipertrofica y el 11% por hipertrofia ventricular izquierda idiopatica. Se indico analisis genetico en 62 casos (50,4%). Se hallaron variantes geneticas en 42 (67,7%), con una media de 3,4 ± 4 variantes/paciente, que se consideraron patogenicas o probablemente patogenicas en el 30,6%. De las MS inexplicadas, hasta el 70% presento alguna variante genetica. El estudio familiar permitio detectar a 21 portadores o afectos, 5 de ellos estaban en riesgo, por lo que se indico implante de desfibrilador. Conclusiones El estudio protocolizado y exhaustivo de la MS cardiaca de personas jovenes es factible y necesario. En un alto porcentaje la causa es genetica y, por lo tanto, existen familiares en riesgo que pueden beneficiarse de un diagnostico y un tratamiento precoces para evitar complicaciones.

To determine whether clinical and toxicologic findings differed between cases of amphetamine (AMP) and methamphetamine (mAMP) poisoning attended in 2 Balearic Island hospital emergency departments.Retrospective observational study of AMP and mAMP cases with laboratory confirmation between 2013 and 2018. We compared clinical and toxicologic variables as well as clinical management between groups.1) A total of 120 cases were found: 86 (71.7%) with AMP poisoning and 34 (28.3%) with mAMP poisoning. 2) Drug poisoning was confirmed by gas chromatography associated with mass spectrometry (GC-MS) in 787 urine samples found to be positive during screening. One hundred fifty-four (19.6%) were confirmed by GC-MS. Thirtyfour of them did not meet the inclusion criteria. 3) Significant differences between AMP and mAMP cases were found for age (32.3 vs 28.4 y, respectively); sex (72.1% vs 94.1% men); and Spanish nationality (64.0% vs 29.4%). Reasons for admission and clinical features also differed: the reasons were aberrant behavior (15.1% in the AMP group vs 0% in the mAMP group) and palpitations (1.2% vs 20.6%); agitation was observed in 27.9% and 8.8%, respectively. Clinical management was similar in the 2 groups. Multiple drug poisoning was detected in 76.6% patients and was more common in patients in the AMP group (82.6% vs 61.8%). The additional drugs in these cases were mainly cocaine (63.0%), cannabis (48.9%), 3,4-methylenedioxy-N-methamphetamine (MDMA) (38.0%), and alcohol (35.9%). Cannabis was detected in a significantly higher proportion in the AMP group (45.3%) than in the mAMP group (17.6%). False positives were found in 78.7% of the samples. The culprit drug was most often MDMA (71.2%).AMP poisonings were associated with age over 30 years, Spanish nationality, aberrant behavior, agitation, multiple drug findings, and the use of cannabis. Poisonings caused by mAMP abuse were associated with age under 30 years, non-Spanish nationality, palpitations, and single-drug use.Investigar si existen diferencias clínicas y toxicológicas en pacientes intoxicados por anfetamina (ANF) y metanfetamina (MANF) atendidos en servicios de urgencias.Estudio observacional retrospectivo de intoxicaciones por ANF y MANF con confirmación analítica en Baleares (2013-2018). Se compararon variables clínicas, toxicológicas y de manejo clínico entre grupos.1) Se incluyeron 120 pacientes, 86 (71,7%) grupo ANF y 34 (28,3%) grupo MANF. 2) La confirmación de derivados anfetamínicos se realizó por cromatografía de gases-espectrometría de masas en 787 muestras de orina previamente positivas mediante un método de cribado cualitativo. Se confirmaron 154 (19,6%) muestras. De ellas, 34 fueron excluidas. 3) Se encontraron diferencias significativas entre ANF y MANF en: edad (32,3 vs 28,4 años); sexo (72,1 vs 94,1% hombres); nacionalidad española (64,0 vs 29,4%); en motivos de admisión: alteración de conducta (15,1 vs 0%) y palpitaciones (1,2 vs 20,6%); y en características clínicas: agitación (27,9 vs 8,8%). No hubo diferencias de manejo clínico. El 76,6% de casos fueron polintoxicaciones, más comunes en ANF (82,6 vs 61,8%). En estos casos se detectó principalmente cocaína (63,0%), cannabis (48,9%), MDMA (38,0%) y alcohol (35,9%). La mayor asociación del cannabis con el grupo de ANF fue estadísticamente significativa (45,3 vs 17,6%). La causa de los falsos positivos se identificó en el 78,7% de muestras, siendo el MDMA (71,2%) la principal.Se observaron diferencias entre ANF y MANF en cuanto a variables demográficas y motivo de asistencia; no obstante en esta serie hubo un alto porcentaje de polintoxicaciones.

The beneficial effects of fish consumption in both children and adults are well known. However, the intake of methylmercury, mainly from contaminated fish and shellfish, can have adverse health effects. The study group on the prevention of exposure to methylmercury (GEPREM-Hg), made up of representatives from different Spanish scientific societies, has prepared a consensus document in a question and answer format, containing the group's main conclusions, recommendations and proposals. The objective of the document is to provide broader knowledge of factors associated with methylmercury exposure, its possible effects on health amongst the Spanish population, methods of analysis, interpretation of the results and economic costs, and to then set recommendations for fish and shellfish consumption. The group sees the merit of all initiatives aimed at reducing or prohibiting the use of mercury as well as the need to be aware of the results of contaminant analyses performed on fish and shellfish marketed in Spain. In addition, the group believes that biomonitoring systems should be set up in order to follow the evolution of methylmercury exposure in children and adults and perform studies designed to learn more about the possible health effects of concentrations found in the Spanish population, taking into account the lifestyle, eating patterns and the Mediterranean diet.

To identify analytical factors associated with mortality in patients with type-2 diabetes under long-term treatment with metformin who come to the emergency department with acute symptoms of lactic acidosis. Retrospective observational analysis of patient records in a referral hospital. We collected clinical data and laboratory results for a series of metformin-treated patients with type-2 diabetes who developed lactic acidosis, stratified by severity. Factors related to the episode were analyzed for associations with mortality or survival. Of 16 patients studied (mean age 70 years; range, 60-77 years), 75% had gastrointestinal symptoms in the 5 days before they came to the emergency department. Mortality (19%) was associated with sepsis on arrival; elevated white blood cell counts, particularly neutrophil counts; low platelet counts; high C-reactive protein (CRP) and procalcitonin levels; and 1 or more chronic concomitant diseases. Metformin concentration was not significantly associated with mortality. Signs of sepsis, high neutrophil counts with low platelet counts, elevated CRP and procalcitonin levels, and the presence of 1 or more concomitant diseases may be risk factors for death in metformin-treated patients with lactic acidosis.El objetivo de este estudio es la detección de parámetros analíticos asociados a la mortalidad en los pacientes con diabetes mellitus tipo 2 (DM2) con tratamiento crónico con metformina que acuden a urgencias por un cuadro clínico agudo con presencia de acidosis láctica. Se trata de un estudio observacional-analítico retrospectivo realizado en un hospital de tercer nivel. Se recogieron datos clínicos y analíticos en una serie de pacientes con acidosis láctica, estratificada por gravedad, y tratamiento con metformina para DM2. Se compararon los resultados en función de la mortalidad o supervivencia del episodio. De 16 pacientes estudiados, con una edad media de 70 años (rango de 60 a 77), el 75% presentó sintomatología gastrointestinal los 5 días previos a su ingreso. La mortalidad total observada fue del 19%, que se asoció a la presencia de sepsis al ingreso, leucocitosis con neutrofilia, plaquetopenia, elevación de proteína C reactiva (PCR), valores altos de procalcitonina y la comorbilidad con una o más patologías crónicas. Las cifras séricas de metformina no se correlacionaron significativamente con la mortalidad. Se concluye que en pacientes con acidosis láctica y tratamiento con metformina pueden ser factores asociados a la mortalidad la presencia de criterios de sepsis, neutrofilia con plaquetopenia, elevación de PCR y de procalcitonina y la existencia de una o más patologías comórbidas.

To analyze the diagnostic yield of a cut-point of 3 μg/mL for paracetamol in urine to screen for poisoning in children.Prospective case-control observational study in a pediatric intensive care unit (PICU). All enrolled patients had been admitted to the PICU. Cases were children receiving a therapeutic dose of intravenous paracetamol. Controls were not receiving paracetamol. Urine samples were collected early in the morning and 4 hours after a dose of paracetamol was received by case patients. Paracetamol concentration was measured in all samples. We compared the percentages of cases and controls who had a concentration of 3 μg/mL or more. The sensitivity, specificity, and predictive values of the cut-point were calculated.Forty children aged between 1 month and 19 years (20 per matched group) were enrolled. Paracetamol was not detected in any of the control samples. The sensitivity of the test in early morning urine was 95% (95% CI, 85.5%-100%); specificity was 100%. The positive predictive value was 100%; the negative predictive value was 95.2% (95% CI, 86.1%-100%). Paracetamol was detected in all of the second samples collected from cases.Measuring the paracetamol concentration in urine within 4 hours of dosing is useful to rule out prior intake of paracetamol and overdosing in PICU patients. Studies to validate the new cut-point of 3 μg/mL for paracetamol in urine are required with a view to possibly including it in a diagnostic protocol for suspected acute poisoning.Analizar el rendimiento de un punto de corte de 3 μg/mL en la determinación de paracetamol urinario (PCTo) como método de cribado para detectar paracetamol en posibles sobreingestas en población pediátrica.Estudio de caso-control, observacional, analítico y prospectivo realizado en una unidad de cuidados intensivos pediátricos (UCIP). Se seleccionó una muestra compuesta por aquellos pacientes ingresados en UCIP, considerando el grupo de casos aquellos con administración pautada de una dosis terapéutica endovenosa de paracetamol y un grupo control sin administración del fármaco. Se recogió una muestra de orina dentro de la primera hora y una segunda muestra pasadas 4 horas de la dosis del fármaco. En todos se determinó PCTo cuantitativamente. Se comparó la proporción de pacientes con PCTo STX 3 μg/mL. Se calcularon sensibilidad, especificidad y valores predictivos.Se incluyeron 40 niños de edades entre 1 mes y 19 años (20 en cada grupo). No se obtuvo ningún paciente de control con PCTo positiva. La sensibilidad de la prueba en la primera orina recogida fue del 95% (IC 95%: 85,5-100%) y su especificidad del 100%. El valor predictivo positivo fue 100%, y el negativo del 95,2% (IC 95%: 86,1-100%). En las segundas orinas recogidas todos los valores de rendimiento del test fueron del 100%.La detección de PCTo antes de las 4 horas es útil para descartar la ingesta de paracetamol en población pediátrica. Se requieren estudios que permitan validar el nuevo punto de corte de 3 μg/mL para su posible inclusión en el algoritmo de sospecha de intoxicación aguda.

BACKGROUND Benzofurans and benzodifurans are two groups of psychoactive substances that had originally been synthesized for research purpose. Benzofurans' structure is quite similar to the known recreational drug 3,4-methylenedioxymethamphetamine together with its active metabolite 3,4-methylenedioxyamphetamine. Benzodifurans are closely related to phenethylamines, but have more hallucinogens effects and much longer duration of action. This study aims to review the accessible evidence-based literature on benzofurans and benzodifurans pharmacology and toxicology. METHODS A literature search on benzofurans and benzodifurans has been conducted using PubMed. We reviewed articles up to February 2017 and also included data from various governmental websites and discussion groups. RESULTS This review describes the emergent literature that illustrates the chemical composition of these drugs, patterns of use, pharmacology, toxicology, desired and clinical effects, and treatments of patients. It also provides a compilation of case reports. CONCLUSION The knowledge regarding usage prevalence, pharmacokinetic and pharmacodynamic profiles, acute toxic effects, the effects desired on patients and drug related mortality attributed to these drugs is still limited. Nowadays, there are no specific guidelines available to treat benzofurans or dibenzofurans intoxications. For that reason, clinical effects should be the base of treatment. Backing exposures analytically confirmed in clinical and forensic cases and reported clinical effects need to be combined with these compounds while monitoring its prevalence.

Heroin-related myelopathy is an uncommon but often devastating complication of heroin intake. It is usually reported in individuals exposed to intravenous heroin after a variable drug-free period, leading to acute and complete spinal cord injury with poor long-term outcome. We describe an original case of acute longitudinally extensive transverse myelopathy following single heroin and cocaine intravenous exposure after a long period of abstinence confirmed by toxicological hair and retrospective urine drug analysis. This case could provide new insights in the understanding of this rare neurological complication.

Resumen Introduccion El uso del laboratorio es inadecuado (excesivo o innecesario) y es preciso controlarlo. Material y metodos Elaborar una estrategia para gestionar, segun criterios de medicina basada en la evidencia, la derivacion de pruebas subcontratadas y comparar los resultados entre dos anos consecutivos. Resultados La demanda se ha reducido un 6,56% y los costes un 26,9%. Es de destacar que solo el 1,9 % de los peticionarios a los que se les ha denegado alguna prueba contacta con el laboratorio para reclamar o mostrar su disconformidad. Conclusiones El profesional del laboratorio clinico debe implicarse como consultor clinico para mejorar la eficiencia de las pruebas de laboratorio.

The beneficial effects of fish consumption in both children and adults are well known. However, the intake of methylmercury, mainly from contaminated fish and shellfish, can have adverse health effects. The study group on the prevention of exposure to methylmercury (GEPREM-Hg), made up of representatives from different Spanish scientific societies, has prepared a consensus document in a question and answer format, containing the group's main conclusions, recommendations and proposals. The objective of the document is to provide broader knowledge of factors associated with methylmercury exposure, its possible effects on health amongst the Spanish population, methods of analysis, interpretation of the results and economic costs, and to then set recommendations for fish and shellfish consumption. The group sees the merit of all initiatives aimed at reducing or prohibiting the use of mercury as well as the need to be aware of the results of contaminant analyses performed on fish and shellfish marketed in Spain. In addition, the group believes that biomonitoring systems should be set up in order to follow the evolution of methylmercury exposure in children and adults and perform studies designed to learn more about the possible health effects of concentrations found in the Spanish population, taking into account the lifestyle, eating patterns and the Mediterranean diet.