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    Pharmacogenetic, pharmacokinetic and epigenetic profiles in children who experience vomiting or recovery agitation during sedation with ketamine

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    Background: Ketamine is one of the sedatives most used in North America for procedural sedation outside the operating room in children. Vomiting and recovery agitation are the adverse events most frequently reported after ketamine administration in children. The aim of this study was to identify genetic variants associated with the development of vomiting or recovery administration after intravenous ketamine administration. Material and methods: This was a single-center prospective pharmacogenetic study performed at the tertiary level children’s hospital Institute for Maternal and Child Health IRCCS Burlo Garofolo of Trieste, Italy. Children, between 1 and 17yrs of age, performing procedural sedation with intravenous ketamine as the sole sedative agent were enrolled. Pharmacogenetic, pharmacokinetic and epigenetic analysis were predisposed. The genotyping was performed through Illumina Omni 2.5+ exome array. The search for biomarkers was performed through the analysis of the variants of 10 candidate genes, codifying for proteins responsible for the metabolism and pharmacodynamics of ketamine. A target sequencing genome-wide analysis was carried out to identify the presence of genetic variants associated with the development of adverse events but not related to the candidate genes. The plasma concentration of ketamine and norketamine were determined and pharmacokinetic parameters were determined. A pharmacogenomic approach provided neural-derived exosomal miRNA profiles for patients. The miRNA contained in neural-derived exosomes were quantified and related to the occurrence of ketamine adverse events, through a next-generation sequencing technique. Results: From September 2019 to October 2021, 106 patients were enrolled in the study. Among them, 87 patients were analyzed. The mean age was 8yrs (+/- 4.3). 55% were females, 37% were affected by chronic diseases. Arthrocentesis and bone fracture reduction were the procedures most frequently performed. A mean dose of 1.7mg/kg of intravenous ketamine was employed to perform the procedures. Thirty-one patients (35%) experienced vomiting or recovery agitation and were compared to the 56 patients (65%) without these events. Polymorphisms on GRIN2A, GRIN2B, and CYP2A6 were associated with the development of vomiting or recovery agitation. A stronger association was found with polymorphisms related to the pharmacodynamic of ketamine. Conclusion: The development of vomiting and recovery agitation after ketamine administration seems associated with specific genetic variants. These findings should be confirmed in a greater population.Background: Ketamine is one of the sedatives most used in North America for procedural sedation outside the operating room in children. Vomiting and recovery agitation are the adverse events most frequently reported after ketamine administration in children. The aim of this study was to identify genetic variants associated with the development of vomiting or recovery administration after intravenous ketamine administration. Material and methods: This was a single-center prospective pharmacogenetic study performed at the tertiary level children’s hospital Institute for Maternal and Child Health IRCCS Burlo Garofolo of Trieste, Italy. Children, between 1 and 17yrs of age, performing procedural sedation with intravenous ketamine as the sole sedative agent were enrolled. Pharmacogenetic, pharmacokinetic and epigenetic analysis were predisposed. The genotyping was performed through Illumina Omni 2.5+ exome array. The search for biomarkers was performed through the analysis of the variants of 10 candidate genes, codifying for proteins responsible for the metabolism and pharmacodynamics of ketamine. A target sequencing genome-wide analysis was carried out to identify the presence of genetic variants associated with the development of adverse events but not related to the candidate genes. The plasma concentration of ketamine and norketamine were determined and pharmacokinetic parameters were determined. A pharmacogenomic approach provided neural-derived exosomal miRNA profiles for patients. The miRNA contained in neural-derived exosomes were quantified and related to the occurrence of ketamine adverse events, through a next-generation sequencing technique. Results: From September 2019 to October 2021, 106 patients were enrolled in the study. Among them, 87 patients were analyzed. The mean age was 8yrs (+/- 4.3). 55% were females, 37% were affected by chronic diseases. Arthrocentesis and bone fracture reduction were the procedures most frequently performed. A mean dose of 1.7mg/kg of intravenous ketamine was employed to perform the procedures. Thirty-one patients (35%) experienced vomiting or recovery agitation and were compared to the 56 patients (65%) without these events. Polymorphisms on GRIN2A, GRIN2B, and CYP2A6 were associated with the development of vomiting or recovery agitation. A stronger association was found with polymorphisms related to the pharmacodynamic of ketamine. Conclusion: The development of vomiting and recovery agitation after ketamine administration seems associated with specific genetic variants. These findings should be confirmed in a greater population

    Facing somatic symptom disorder in the emergency department

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    Somatic symptom disorder is a condition in which a patient's subjective report of physical symptoms is associated with distress; disruption of day-to-day functioning; or disproportionate thoughts, feelings and behaviours regarding the symptoms, whether or not they are associated with an identified medical condition. While somatic symptom disorder affects a considerable proportion of children and adolescents presenting to the emergency department (ED), it has not been well investigated in the ED literature, nor is there much formal training in, or guidelines for, how to care for affected patients in the ED. The aim of this paper is to highlight the historical clues commonly reported by these patients in order to try to help the emergency physicians recognise patients affected by a somatic symptom disorder. Adolescent age, the presence of daily subjective symptoms presenting daily for weeks or months, a long medical history record, an extensive diagnostic workup and, most of all, disproportionate functional impairment related to the symptoms are all features strongly suggestive of this disorder. Emergency physicians should become used to taking advantage of these clues to formulate a positive diagnosis of somatic symptom disorder according to the most recent diagnostic criteria. Emergency physicians have the unique opportunity to contribute to the correct diagnosis and treatment of these patients and to have a positive impact on their prognosis

    Controllo del dolore da venipuntura e accesso venoso periferico: tecniche farmacologiche e non

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    Venipuncture and peripheral intravenous access are the painful procedures more commonly performed in children. This article aims to present the techniques that are available and usually employed to decrease pain and distress during these procedures. Evidence shows that pharmacological techniques, such as the application of anaesthetic creams or topical anaesthesia, have the best pain-relieving effect. Nevertheless, considering that the painful experience during venipuncture and vascular access is related both to perceived pain and procedural anxiety, the integrated use of pharmacological and non-pharmacological techniques is warranted. In this sense, the appropriate preparation is a cornerstone of the procedure. The article presents brief management strategies with easily implemented techniques that help improve daily practice

    Un mal di schiena fastidioso

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    A 7-year-old boy was admitted to the Emergency Unit for a one-month history of low back pain, which got worse and resulted in a refusal to walk. On physical examination, the patient refused to stand, and palpation of the spinous processes of the lumbosacral spine evoked pain. Blood tests were normal, except for raised erythrocyte sedimentation rate (51 mm/h, ULN 20 mm/h). An X-ray showed fecaloma and MRI of the spine was performed. Different diagnostic hypotheses and diagnostic exams are discussed

    A girl with gastric distension and hyperamylasemia

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    A 3-year-old girl was admitted with abrupt onset of acute severe abdominal pain and drowsiness, without vomiting or diarrhoea. No history of abdominal trauma was reported. On admission, she was moaning, her heart rate was 161 bpm, blood pressure was 108/72 mm Hg, capillary refill time was <2 s and she was apyrexial. On physical examination, there was marked abdominal distension, with generalised abdominal tenderness without peritoneal signs. Blood tests showed hyperamylasemia (780 IU/L), neutrophilia (white cell count 14×10^9/L; neutrophil 11.9×10^9/L) and hyperglycaemia (155 mg/dL–8.6 mmol/L). A supine plain abdominal X-ray showed a huge gastric bubble (figure 1). A nasogastric tube was inserted, and 500 mL of non-bilious fluid and 150 mL of gas were suctioned, with prompt improvement of symptoms
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