Outcomes of Prehospital Chemical Sedation With Ketamine Versus Haloperidol and Benzodiazepine or Physical Restraint Only

Objective: The goal of this study is to describe complications and outcomes of prehospital ketamine use for agitation as compared to other methods of physical or chemical restraint such as haloperidol plus benzodiazepine or physical restraint only. Methods: We conducted a single-center retrospective review of patient encounters in which restraint was administered in the prehospital setting. At the beginning of our study window, only physical restraint was available to paramedics managing agitated patients but subsequently, haloperidol and benzodiazepines were introduced, followed by ketamine 2 years later. By comparing patients before and after each transition, we divided subjects into 3 cohorts based on restraint type: physical restraint, haloperidol plus benzodiazepine, and ketamine. Demographic data were collected, and outcome measures included intubation rate, need for additional physical or chemical restraint, emergency department (ED) length of stay, need for hospital admission, and employee injury. Results: Of 214 subjects included in the study, 95 patients were administered ketamine, 68 received haloperidol and benzodiazepine, and 51 were physically restrained. Eleven of the patients (11.6%) who received ketamine were intubated. Compared to patients who received haloperidol plus benzodiazepine, patients who received ketamine were more likely to be intubated (odds ratio [OR]?=?8.77, 95% confidence interval [CI], 1.10–69.68) and were more likely to require additional chemical restraint when compared to haloperidol/benzodiazepine or physical restraint only (OR =2.94, 95% CI, 1.49–5.80, and OR =2.15, 95% CI, 1.07–4.31, respectively). There were no differences between the 2 chemical sedation groups in terms of ED length of stay or hospital admission rate. Conclusions: This study demonstrates a lower intubation rate in patients administered ketamine than prior literature in association with a lower weight-based dosing regimen. Ketamine use was correlated with a higher frequency of intubation and a greater need for additional chemical restraint when compared with other restraint modalities, though exogenous factors such as provider preference may have impacted this result. There was no difference in ED length of stay or admission rate between the ketamine and haloperidol plus benzodiazepine groups. Further prospective study is needed to determine whether there is a subset of patients for whom ketamine would be beneficial compared to other therapies.     

Expanding the phenotype associated to KMT2A variants: overlapping clinical signs between Wiedemann–Steiner and Rubinstein–Taybi syndromes

Lysine-specific methyltransferase 2A (KMT2A) is responsible for methylation of histone H3 (K4H3me) and contributes to chromatin remodeling, acting as “writer” of the epigenetic machinery. Mutations in KMT2A were first reported in Wiedemann–Steiner syndrome (WDSTS). More recently, KMT2A variants have been described in probands with a specific clinical diagnosis comprised in the so-called chromatinopathies. Such conditions, including WDSTS, are a group of overlapping disorders caused by mutations in genes coding for the epigenetic machinery. Among them, Rubinstein–Taybi syndrome (RSTS) is mainly caused by heterozygous pathogenic variants in CREBBP or EP300. In this work, we used next generation sequencing (either by custom-made panel or by whole exome) to identify alternative causative genes in individuals with a RSTS-like phenotype negative to CREBBP and EP300 mutational screening. In six patients we identified different novel unreported variants in KMT2A gene. The identified variants are de novo in at least four out of six tested individuals and all of them display some typical RSTS phenotypic features but also WDSTS specific signs. This study reinforces the concept that germline variants affecting the epigenetic machinery lead to a shared molecular effect (alteration of the chromatin state) determining superimposable clinical conditions.Subject terms: Epigenetics, Mutation     

Pulmonary alveolar microlithiasis: clinical features,evolution of the phenotype,and review of the literature

Pulmonary alveolar microlithiasis (PAM) (MIM 265100) is a rare, autosomal recessive pneumopathy characterized by intra-alveolar formation and accumulation of tiny, roundish corpuscles called "microliths". The name "alveolar microlithiasis" was first used by Puhr in 1933; since then, several reports have appeared, and over 300 individuals with this condition have been reported. We have reviewed the PAM cases in the literature in light of personal experience, focusing on medical implications, disease diagnosis and progression over time, familial predisposition, and geographical and sex distribution. This study confirms autosomal recessive inheritance and does not support the role of other, non-genetic, factors in the pathogenesis of PAM.     

Non-Celiac Gluten/Wheat Sensitivity: Clinical Characteristics and Microbiota and Mycobiota Composition by Response to the Gluten Challenge Test

The aims of this observational “proof-of-concept” study were to analyze the clinical/psychological characteristics and gut microbiota/mycobiota composition of individuals with suspected non-celiac gluten/wheat sensitivity (NCGS/WS) according to responses to the double-blind-placebo-controlled (DBPC) crossover gluten challenge test. Fifty individuals with suspected NCGS/WS were subjected to the DBPC challenge test; anthropometric measurements, psychometric questionnaires, and fecal samples were collected. Twenty-seven (54%) participants were gluten responsive (NCGS), and 23 were placebo responsive, with an order effect. NCGS individuals displayed a significantly lower risk of eating disorders and a higher mental health score when compared to placebo-responsive participants, confirmed by multiple logistic regression analyses (OR = 0.87; 95% CI 0.76–0.98, p = 0.021, and OR = 1.30; 95% CI 1.06–1.59, p = 0.009, respectively). Principal coordinate analyses based on microbiota composition showed a separation by the DBPC response (p = 0.039). For Bacteroides (p = 0.05) and Parabacteroides (p = 0.007), the frequency of amplicon sequence variants was lower, and that for Blautia (p = 0.009) and Streptococcus (p = 0.004) was higher in NCGS individuals at multiple regression analyses. No difference in the mycobiota composition was detected between the groups. In conclusion, almost half of the individuals with suspected gluten sensitivity reported symptoms with placebo; they showed lower mental health scores, increased risk for eating disorders, and a different gut microbiota composition.     

Sudden cardiac death in J wave syndrome with short QT associated to a novel mutation in Nav 1.8 coding gene SCN10A: First case report for a possible pharmacogenomic role

Introduction

Sudden cardiac death is an important cause of mortality in the general population. It represents an important challenge for clinicians, often being the only symptom of a broad spectrum of cardiac pathologies and inherited heart conditions. Early repolarization syndrome and Brugada syndrome are part of the wider “J-wave” syndrome, which may also include the short QT syndrome as a third factor of an ionic channel imbalance in the arrhythmogenic landscape.

Personality traits and violent behavior: A comparison between psychopathic and non-psychopathic male murderers

The relationship between psychopathy and traits of temperament and character in a specific population of criminals, such as murderers, has not been sufficiently investigated. This study assesses the relationship between psychopathy and temperament and character traits in murderers. The sample consisted of 118 men divided into three groups: psychopathic murderers (N=40), non-psychopathic murderers (N=40) and 38 non-psychopathic non-criminals (controls). All individuals were evaluated by Psychopathy Checklist Revised (PCL-R) and The Temperament and Character Inventory (TCI). Psychopathic murderers presented higher scores than the other two groups in PCL-R; both criminal groups presented higher scores than non-psychopathic non-criminals. Psychopathic murderers showed lower scores than non-psychopathic murderers on Harm Avoidance, Reward Dependence, Persistence, Self-Directness and Cooperativeness. There was no difference between murderers groups regarding Novelty Seeking and Self-transcendence. In all TCI personality traits psychopathic and non-psychopathic murderers showed scores lower than controls, except Harm Avoidance for non-psychopathic murderers. In conclusion, most personality traits assessed by TCI were associated with psychopathy, while Novelty Seeking and Self-transcendence were associated with homicidal behavior independently of the psychopathy.