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Mast cell activation syndrome (MCAS) is a term applied to several clinical entities that have gained increased attention from patients and medical providers. Although several descriptive publications about MCAS exist, there are many gaps in knowledge, resulting in confusion about this clinical syndrome. Whether MCAS is a primary syndrome or exists as a constellation of symptoms in the context of known inflammatory, allergic, or clonal disorders associated with systemic mast cell activation is not well understood. More importantly, the underlying mechanisms and pathways that lead to mast cell activation in MCAS patients remain to be elucidated. Here we summarize the known literature, identify gaps in knowledge, and highlight research needs. Covered topics include contextualization of MCAS and MCAS-like endotypes and related diagnostic evaluations; mechanistic research; management of typical and refractory symptoms; and MCAS-specific education for patients and health care providers., Competing Interests: Disclosure statement M.C.C. and D.D.M. were supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not represent the official views of the NIH. Disclosure of potential conflict of interest: M. Castells has received research funding and consulting fees from Blueprint Medicines and consulting fees from Cogent Biosciences. M. P. Giannetti has received research funding and consulting fees from Blueprint Medicines and consulting fees from Cogent Biosciences. M. J. Hamilton has received consulting fees from Blueprint Medicines. P. Novak has received funding from Mona Taliaferro/Bay Shore Recycling, the National Heart, Lung, and Blood Institute (NHLNI; 1OT2HL156812-01), and FBRI (2022A018462); is current or previous shareholder of Moderna, Edidas Medicine, Novavax, and Pfizer; and has received royalties from Oxford University Press. J. Nicoloro-SantaBarbara has received consulting fees from Cogent Biosciences and Blueprint Medicines. S. C. Glover received consulting fees from Blueprint Medicine, Janssen, BMS, AbbVie, and Takeda. S. J. Galli has received research funding from and is scientific advisor to Evommune; and is on the scientific advisory board of Jasper Therapeutics. A. White is on the speakers bureau at Blueprint Medicines; and received consulting fees from Cogent Biosciences and Blueprint Medicines. P. Valent received funding from BMS/Celgene and AOP Orphan; and consultancy fees from Novartis, BMS/Celgene, Blueprint, Pfizer, Cogent, and Stemline. J. H. Butterfield has received a fee for the licensing of HMC-1 cell lines. D. D. Metcalfe has received consulting fees from Visterra. J. D. Milner has received consulting fees from Blueprint Medicines. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Experiencing gender-based violence (GBV) is associated with health conditions that are common indications for referral to exercise physiologists, physiotherapists and other allied health professionals (AHPs). The readiness of AHPs to identify and respond to GBV is currently unknown. This study aimed to determine the readiness of AHPs to respond to a person who had experienced GBV. Participants completed the modified Physician Readiness to Manage Intimate Partner Violence Survey (PREMIS) and/or an interview. The AHPs felt underprepared, had low perceived knowledge and lacked confidence to respond to and support people who have experienced GBV, despite recognition of the importance and agreement of the relevance to AHPs' practice., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Studies of asthma and allergy are generating increasing volumes of omics data for analysis and interpretation. The National Institute of Allergy and Infectious Diseases (NIAID) assembled a workshop comprising investigators studying asthma and allergic diseases using omics approaches, omics investigators from outside the field, and NIAID medical and scientific officers to discuss the following areas in asthma and allergy research: genomics, epigenomics, transcriptomics, microbiomics, metabolomics, proteomics, lipidomics, integrative omics, systems biology, and causal inference. Current states of the art, present challenges, novel and emerging strategies, and priorities for progress were presented and discussed for each area. This workshop report summarizes the major points and conclusions from this NIAID workshop. As a group, the investigators underscored the imperatives for rigorous analytic frameworks, integration of different omics data types, cross-disciplinary interaction, strategies for overcoming current limitations, and the overarching goal to improve scientific understanding and care of asthma and allergic diseases., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Introduction: Patients with major burns can undergo temporary coverage while skin graft donor sites heal, where dermal templates have an emerging role. The aim of this study was to evaluate the clinical outcomes and resource utilisation in patients with major burns treated with a bilayer biodegradable synthetic matrix (NovoSorb BTM)., Method: This retrospective cohort study included patients admitted to the Royal Brisbane and Women's Hospital Adult Burn Unit with burns to at least 40 % TBSA who survived their acute admission. Patients treated from July 2017 to June 2022 with BTM were compared with patients with similar injuries treated using cadaveric allograft as temporising full thickness wound coverage between January 2013 and June 2017. Outcomes measures included number of operations, total operative time, hospital and intensive care unit (ICU) length of stay (LOS), cadaveric allograft and BTM use, and blood product use. Unadjusted comparisons were made with Wilcoxon Rank-Sum tests and Fisher's exact tests. Multivariate linear regression was used to adjust for the effect of TBSA on each outcome., Results: Fifty-five patients were included (78 % male), 22 of whom were treated with BTM. We found no significant differences in age, sex, or TBSA between groups. One patient had half of the BTM removed due to infection and replaced with allograft. Patients treated with BTM had significantly less operative theatre time (median 1361.5 min [BTM] vs 1768 min [no BTM], P = 0.044). Number of operations, allograft use, hospital and ICU LOS, and blood product use were similar between groups. Adjusted models accounting for TBSA supported unadjusted models., Conclusion: Resource utilisation and clinical outcomes were similar in patients with at least 40 % TBSA treated with BTM and those who were treated with allograft before the introduction of BTM. Patients treated with BTM had significantly less total operative time and no difference in number of operations, allograft use and ICU LOS., Competing Interests: Declarations of interest Timothy Barker is an employee of PolyNovo Biomaterials Pty Ltd., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Developmental studies have revealed the importance of the transcription factor Hand2 in cardiac development. Hand2 promotes cardiac progenitor differentiation and epithelial maturation, while repressing other tissue types. The mechanisms underlying the promotion of cardiac fates are far better understood than those underlying the repression of alternative fates. Here, we assess Hand2-dependent changes in gene expression and chromatin remodeling in cardiac progenitors of zebrafish embryos. Cell-type specific transcriptome analysis shows a dual function for Hand2 in activation of cardiac differentiation genes and repression of pronephric pathways. We identify functional cis- regulatory elements whose chromatin accessibility are increased in hand2 mutant cells. These regulatory elements associate with non-cardiac gene expression, and drive reporter gene expression in tissues associated with Hand2-repressed genes. We find that functional Hand2 is sufficient to reduce non-cardiac reporter expression in cardiac lineages. Taken together, our data support a model of Hand2-dependent coordination of transcriptional programs, not only through transcriptional activation of cardiac and epithelial maturation genes, but also through repressive chromatin remodeling at the DNA regulatory elements of non-cardiac genes.

Objective: Lung function testing is used in diagnosing asthma and assessing asthma control. Spirometry is most commonly used, but younger children can find performing this test challenging. Non-volitional tests such as airwave oscillometry (AOS) may be helpful in that population. We compared the success of spirometry and AOS in assessing bronchodilator responsiveness in children., Methods: AOS was conducted alongside routine lung function testing. Resistance at 5 Hz (R5), the difference between the resistance at 5 and 20 Hz (R5-20) and the area under the reactance curve (AX) were assessed. Patients between 5 and 16 years old attending clinic with wheeze or asthma were assessed. Patients performed AOS, followed by spirometry and were then given 400 µg salbutamol; the tests were repeated 15 minutes later., Results: Lung function testing was performed in 47 children of whom 46 (98%) and 32 (68%) performed acceptable baseline oscillometry and spirometry, respectively ( p  < 0.001). Children unable to perform acceptable spirometry were younger (7.35, range: 5.4-10.3 years) than those who could (10.4, range: 5.5-16.9 years), p  < 0.001. The baseline z-scores of AOS R5 correlated with FEV 1 ( r  = 0.499, p  = 0.004), FEF 75 ( r  = 0.617, p  < 0.001), and FEV 1 /FVC ( r  = 0.618, p  < 0.001). There was a positive bronchodilator response assessed by spirometry (change in FEV 1 ≥ 12%) in eight children which corresponded to a change in R5 of 36% (range: 30%-50%) and a change in X5 of 39% (range: 15%-54%)., Conclusions: Oscillometry is a useful adjunct to spirometry in assessing young asthmatic children's lung function. The degree of airway obstruction, however, might affect the comparability of the results of the two techniques.

In anamniote embryos, the major wave of zygotic genome activation starts during the mid-blastula transition. However, some genes escape global genome repression, are activated substantially earlier, and contribute to the minor wave of genome activation. The mechanisms underlying the minor wave of genome activation are little understood. We explored the genomic organization and cis-regulatory mechanisms of a transcription body, in which the minor wave of genome activation is first detected in zebrafish. We identified the miR-430 cluster as having excessive copy number and the highest density of Pol-II-transcribed promoters in the genome, and this is required for forming the transcription body. However, this transcription body is not essential for, nor does it encompasse, minor wave transcription globally. Instead, distinct minor-wave-specific promoter architecture suggests that promoter-autonomous mechanisms regulate the minor wave of genome activation. The minor-wave-specific features also suggest distinct transcription initiation mechanisms between the minor and major waves of genome activation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Antigen-specific immunoglobulin responses have yet to be studied at the oral mucosal surface during peanut oral immunotherapy (PnOIT)., Objective: We aimed to quantify salivary peanut-specific IgG4 (PNsIgG4) and IgA (PNsIgA) and total IgG4 and IgA in participants from the Immune Tolerance Network's IMPACT study, a phase 2 PnOIT trial., Methods: Peanut-allergic children, aged 12 months to younger than 48 months at screening, were enrolled and randomized to PnOIT or placebo oral immunotherapy (OIT) for 134 weeks. Per-protocol analysis included 69 PnOIT and 23 placebo participants. Double-blind, placebo-controlled food challenges were conducted at weeks 134 and 160 to assess desensitization and remission, respectively. Saliva samples were collected at baseline and 30, 82, 134, and 160 weeks to quantify PNsIgG4, PNsIgA, and total IgG4 and IgA., Results: Participants who received PnOIT experienced significant increases in PNsIgG4 in saliva, whereas participants on placebo did not (P < .01 at all time points). The PNsIgA/total IgA ratio was also significantly increased in participants treated with PnOIT when compared with those receiving placebo at 30 and 82 weeks (P < .05). During PnOIT, desensitized participants had increased PNsIgA that plateaued, whereas the not desensitized/no remission group did not change over time. Interestingly, when the PnOIT group was evaluated by clinical outcome, PNsIgA was higher at baseline in the not desensitized/no remission group than in the desensitized/remission group (P < .05)., Conclusions: PnOIT induces substantial increases in allergen-specific IgG4 and IgA in saliva. These data provide insight into OIT-induced mucosal responses and suggest the utility of these easily obtained samples for biomarker development., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Genome sequencing is a powerful tool for identifying SARS-CoV-2 variant lineages; however, there can be limitations due to sequence dropout when used to identify specific key mutations. Recently, ThermoFisher Scientific has developed genotyping assays to help bridge the gap between testing capacity and sequencing capability to generate real-time genotyping results based on specific variants. Over a 6-week period during the months of April and May 2021, we set out to assess the ThermoFisher TaqMan mutation panel genotyping assay, initially for three mutations of concern and then for an additional two mutations of concern, against SARS-CoV-2-positive clinical samples and the corresponding COVID-19 Genomics UK Consortium (COG-UK) sequencing data. We demonstrate that genotyping is a powerful in-depth technique for identifying specific mutations, is an excellent complement to genome sequencing, and has real clinical health value potential, allowing laboratories to report and take action on variants of concern much more quickly.

In recent years there has been an increasing effort in improving the performance of Nb 3 Sn for high-field applications, in particular for the fabrication of conductors suitable for the realization of the Future Circular Collider (FCC) at CERN. This challenging task has led to the investigation of new routes to advance the high-field pinning properties, the irreversibility and the upper critical fields (H Irr and H c2 , respectively). The effect of hafnium addition to the standard Nb-4Ta alloy has been recently demonstrated to be particularly promising and, in this paper, we investigate the origins of the observed improvements of the superconducting properties. Electron microscopy, Extended X-ray Absorption Fine Structure Spectroscopy (EXAFS) and Atom Probe Tomography (APT) characterization clearly show that, in presence of oxygen, both fine Nb 3 Sn grains and HfO 2 nanoparticles form. Although EXAFS is unable to detect significant amounts of Hf in the A15 structure, APT does indeed reveal some residual intragrain metallic Hf. To investigate the layer properties in more detail, we created a microbridge from a thin lamella extracted by Focused Ion Beam (FIB) and measured the transport properties of Ta-Hf-doped Nb 3 Sn. H c2 (0) is enhanced to 30.8 T by the introduction of Hf, ~ 1 T higher than those of only Ta-doped Nb 3 Sn, and, even more importantly the position of the pinning force maximum exceeds 6 T, against the typical ~ 4.5-4.7 T of the only Ta-doped material. These results show that the improvements generated by Hf addition can significantly enhance the high-field performance, bringing Nb 3 Sn closer to the requirements necessary for FCC realization., (© 2021. The Author(s).)

Aim: Parents and carers of children with developmental and epileptic encephalopathies (DEEs) experience high rates of mental health disorders including depression and posttraumatic stress disorder. Physical activity is an evidence-based strategy which may help to improve the wellbeing of this population., Method: We delivered a 4-week physical activity group program via a private Facebook group for carers of children with DEEs and their nominated support person. The facilitators provided education and motivation on different weekly topics (e.g. goal setting, overcoming barriers to exercise) and encouraged social support between participants. All participants were provided with a physical activity tracker (Fitbit). The primary outcome was feasibility and secondary outcomes included psychological distress, quality of life, physical activity levels, and PTSD symptoms., Results: N=20 (parents and support partners) were recruited. All participants remained in the program for the full duration and 85% completed the post assessment questionnaires. High acceptability was observed in the qualitative interviews and exploratory analysis of pre-post outcomes found significant improvements in psychological distress and quality of life (ps < 0.01), while changes in physical activity levels and PTSD symptoms were non-significant., Conclusion: A mental health informed physical activity program delivered via Facebook is feasible for carers of children with DEEs and may help improve wellbeing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In many animal models, primordial germ cell (PGC) development depends on maternally deposited germ plasm, which prevents somatic cell fate. Here, we show that PGCs respond to regulatory information from the germ plasm in two distinct phases using two distinct mechanisms in zebrafish. We demonstrate that PGCs commence zygotic genome activation together with the somatic blastocysts with no demonstrable differences in transcriptional and chromatin opening. Unexpectedly, both PGC and somatic blastocysts activate germ-cell-specific genes, which are only stabilized in PGCs by cytoplasmic germ plasm determinants. Disaggregated perinuclear relocalization of germ plasm during PGC migration is regulated by the germ plasm determinant Tdrd7 and is coupled to dramatic divergence between PGC and somatic transcriptomes. This transcriptional divergence relies on PGC-specific cis-regulatory elements characterized by promoter-proximal distribution. We show that Tdrd7-dependent reconfiguration of chromatin accessibility is required for elaboration of PGC fate but not for PGC migration., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Real-time sensing of nitric oxide (NO) in physiological environments is critically important in monitoring neurotransmission, inflammatory responses, cardiovascular systems, etc. Conventional approaches for NO detection relying on indirect colorimetric measurement or built with rigid and permanent materials cannot provide continuous monitoring and/or require additional surgical retrieval of the implants, which comes with increased risks and hospital cost. Herein, we report a flexible, biologically degradable and wirelessly operated electrochemical sensor for real-time NO detection with a low detection limit (3.97 nmol), a wide sensing range (0.01-100 μM), and desirable anti-interference characteristics. The device successfully captures NO evolution in cultured cells and organs, with results comparable to those obtained from the standard Griess assay. Incorporated with a wireless circuit, the sensor platform achieves continuous sensing of NO levels in living mammals for several days. The work may provide essential diagnostic and therapeutic information for health assessment, treatment optimization and postsurgical monitoring.

Gene expression studies and gene therapy require efficient gene delivery into cells. Different technologies by viral and non-viral mechanisms have been used for gene delivery into cells. Small gene vectors transfer across the cell membrane with a relatively high efficiency, but not large genes or entire loci spanning several kilobases, which do not remain intact following introduction. Previously, we developed an efficient delivery system based on herpes virus simplex type 1 (HSV-1) amplicons to transfer large fragments of DNA incorporated in human artificial chromosome (HAC) vectors into the nucleus of human cells. The HSV-1 amplicon lacks the signals for cleavage and replication of its own genome, yet each amplicon has the capacity to incorporate up to 150 kb of exogenous DNA. In this study, we investigated whether the capacity of gene delivery could be increased by simultaneously introducing multiple HSV-1 modified amplicons carrying a gene expressing HAC vector into cells with the aim of generating a single artificial chromosome containing the desired genes. Following co-transduction of two HSV-1 HAC amplicons, artificial chromosomes were successfully generated containing the introduced genes, which were appropriately expressed in different human cell types., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Most metazoan embryos commence development with rapid, transcriptionally silent cell divisions, with genome activation delayed until the mid-blastula transition (MBT). However, a set of genes escapes global repression and gets activated before MBT. Here we describe the formation and the spatio-temporal dynamics of a pair of distinct transcription compartments, which encompasses the earliest gene expression in zebrafish. 4D imaging of pri-miR430 and zinc-finger-gene activities by a novel, native transcription imaging approach reveals transcriptional sharing of nuclear compartments, which are regulated by homologous chromosome organisation. These compartments carry the majority of nascent-RNAs and active Polymerase II, are chromatin-depleted and represent the main sites of detectable transcription before MBT. Transcription occurs during the S-phase of increasingly permissive cleavage cycles. It is proposed, that the transcription compartment is part of the regulatory architecture of embryonic nuclei and offers a transcriptionally competent environment to facilitate early escape from repression before global genome activation.

Increasing evidence shows that maternal touch may promote emotion regulation in infants, however less is known about how parental higher-order social cognition abilities are translated into tactile, affect-regulatory behaviours towards their infants. During 10 min book-reading, mother-infant sessions when infants were 12 months old (N = 45), we investigated maternal mind-mindedness (MM), the social cognitive ability to understand an infant's mental state, by coding the contingency of maternal verbal statements towards the infants' needs and desires. We also rated spontaneous tactile interactions in terms of their emotional contingency. We found that frequent non-attuned mind-related comments were associated with touch behaviours that were not contingent with the infant's emotions; ultimately discouraging affective tactile responses from the infant. However, comments that were more appropriate to infant's mental states did not necessarily predict more emotionally-contingent tactile behaviours. These findings suggest that when parental high-order social cognitive abilities are compromised, they are also likely to translate into inappropriate, tactile attempts to regulate infant's emotions., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Overweight asthmatic children report greater symptoms than normal weight asthmatics, despite comparable airflow obstruction. This has been widely assumed to be due to heightened perception of respiratory effort. Three groups of children (healthy weight controls, healthy weight asthmatics, overweight asthmatics) rated perceived respiratory effort throughout an inspiratory resistive loading protocol. Parasternal intercostal electromyogram was used as an objective marker of respiratory load; this was expressed relative to tidal volume and reported as a ratio of the baseline value (neuroventilatory activity ratio (NVEAR)). Significant increases in perception scores (p<0.0001), and decreases in NVEAR (p<0.0001) were observed from lowest to highest resistive load. Higher BMI increased overall perception scores, with no influence of asthma or BMI-for-age percentile on the resistance-perception relationships. These data, indicating elevated overall respiratory effort in overweight asthmatic children but comparable responses to dynamic changes in load, suggest that the greater disease burden in overweight asthmatic children may be due to altered respiratory mechanics associated with increased body mass., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Calls for transformational change of our healthcare system are increasingly clear, persuasive and insistent. They resonate at all levels, with those who fund, deliver, provide and receive care, and they are rooted in a deep understanding that the system, as currently rigidly structured, most often lacks the necessary flexibility to comprehensively meet the needs of patients across the continuum of care. The St. Joseph's Health System (SJHS) Integrated Comprehensive Care (ICC) Program, which bundles care and funding across the hospital to home continuum, has reduced fragmentation of care, and it has delivered improved outcomes for patients, providers and the system. This case study explores the essential contribution of nursing leadership to this successful transformation of healthcare service delivery.

Background: St. Joseph's Health System has implemented an integrated comprehensive care bundle care (ICC) program with the hopes that it would improve patients' care while reducing overall costs. The aim of this analysis was to evaluate the performance of the ICC program within patients admitted with chronic pulmonary obstructive disease (COPD)., Methods: We conducted a retrospective observational cohort study comparing ICC patients to non-ICC patients admitted to St. Joseph's Healthcare Hamilton for COPD being discharged with support services between June 2012 and March 2015, using administrative data. Confounding adjustment was achieved through the use of propensity score matching. Medical resource utilizations during the initial hospitalization and within the 60 days following discharge were compared using regression models., Results: All 76 patients who entered the ICC program (100.0%) were matched 1 : 1 to 76 eligible non-ICC patients (28.4%). Length of stay (6.47 [7.29] versus 9.55 [10.21] days) and resource intensity weights (1.16 [0.80] versus 1.64 [1.69]) were lower in the ICC group within the initial hospitalization but, while favoring the ICC program, healthcare resource use tended not to differ statistically following discharge., Interpretation: The ICC program was able to reduce initial medical resource utilization without increasing subsequent medical resource use.

Data are presented from a longitudinal investigation examining the relationship between maternal mind-mindedness (MM) in infancy and socio-cognitive development in childhood. We revisited children (n = 18) who had taken part in a longitudinal study as infants. MM had been assessed at 10, 12, 16, and 20 months of age. We followed up these children at 5-6 years of age to test their higher order theory of mind (ToM) (using the strange stories task). The convergent validity, temporal stability, and predictive validity of the construct of MM were examined in a longitudinal data set. The five measures of MM were not significantly correlated. Mother's production of appropriate mind-related comments (but no other measures) showed evidence of temporal stability throughout infancy. Thus, MM (as measured by appropriate mind-related comments) was confirmed as a stable construct. Children's ToM at 5-6 years of age was significantly predicted by their mother's MM up to 4 years earlier, with MM accounting for 40% of the variance of the strange stories task scores. These findings identify a relationship between MM across a protracted period of infancy and socio-cognitive development at 5-6 years of age., (© 2015 The British Psychological Society.)

Study Objective: We investigate the safety and effectiveness of droperidol for sedation of acute behavioral disturbance in the emergency department (ED)., Methods: This was a prospective observational study in 6 EDs (August 2009 to April 2013). Adult patients requiring parenteral sedation for acute behavioral disturbance received droperidol 10 mg. If this did not sedate the patient within 15 minutes, further sedation was allowed but droperidol 10 mg was recommended as part of a sedation protocol. The primary outcome was the proportion of patients with an abnormal QT interval, defined by the at-risk line on the QT nomogram. Secondary outcomes were effectiveness determined by the time to sedation measured on the Sedation Assessment Tool, use of additional sedation, adverse events, and injury to staff or patients., Results: There were 1,009 patients with an ECG performed within 2 hours of droperidol administration, with a median dose of 10 mg (interquartile range [IQR]10 to 17.5 mg). Thirteen of the 1,009 patients had an abnormal QT (1.3%; 95% confidence interval 0.7% to 2.3%), but 7 of these had another cause attributed for prolonged QT (methadone, escitalopram, amiodarone, or preexisting). In 1,403 patients sedated with a median total dose of droperidol of 10 mg (IQR 10 to 20 mg), the median time to sedation was 20 minutes (IQR 10 to 30 minutes) and 97% were sedated within 120 minutes. Additional sedation was required for 435 patients (31.0%; 95% confidence interval 28.6% to 33.5%). Adverse events occurred in 70 patients (5%) and oversedation without complications in 109 (8%), the latter more common for patients receiving benzodiazepines as additional sedation (16/109 [15%]). There were no cases of torsades de pointes. Injuries occurred in 34 staff members and 4 patients., Conclusion: The study supports the use of high-dose droperidol as a safe sedating agent for patients with acute behavioral disturbance in the ED. There is no evidence of increased risk for QT prolongation with the doses used in this study., (Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)