Stop the Bleed® in medical schools: Early advocacy and promising results.

OBJECTIVE: We hypothesized that medical students would be empowered by hemorrhage-control training and would support efforts to include Stop the Bleed® (STB) in medical education. DESIGN: This is a multi-institution survey study. Surveys were administered immediately following and 6 months after the course. SETTING: This study took place at the Association of American Medical Colleges-accredited medical schools in the United States. PARTICIPANTS: Participants were first-year medical students at participating institutions. A total of 442 students completed post-course surveys, and 213 students (48.2 percent) also completed 6-month follow-up surveys. INTERVENTION: An 1-hour, in-person STB course. MAIN OUTCOMES MEASURES: Student empowerment was measured by Likert-scale scoring, 1 (Strongly Disagree) to 5 (Strongly Agree). The usage of hemorrhage-control skills was also measured. RESULTS: A total of 419 students (95.9 percent) affirmed that the course taught the basics of bleeding control, and 169 (79.3 percent) responded positively at follow-up, with a significant decrease in Likert response (4.65, 3.87, p < 0.001). Four hundred and twenty-three students (97.0 percent) affirmed that they would apply bleeding control skills to a patient, and 192 (90.1 percent) responded positively at follow-up (4.61, 4.19, p < 0.001). Three hundred and sixty-one students (82.8 percent) believed that they were able to save a life, and 109 (51.2 percent) responded positively at follow-up (4.14, 3.56, p < 0.001). Four hundred and twenty-five students (97.0 percent) would recommend the course to another medical student, and 196 (92.0 percent) responded positively at follow-up (4.68, 4.31, p < 0.001). Six students (2.8 percent) used skills on live patients, with success in five of the six instances. CONCLUSIONS: Medical students were empowered by STB and have used hemorrhage-control skills on live victims. Medical students support efforts to include STB in medical education.

Tolerance development in cow's milk-allergic children receiving amino acid-based formula with synbiotics: 36-Months follow-up of a randomized controlled trial (PRESTO Study).

The objective of the present study is to assess the rates of acquired tolerance to cow's milk (CM) after 36 months in subjects who consumed amino acid-based formula with synbiotics (AAF-S) or amino acid-based formula without synbiotics (AAF) during a 1-year intervention period in early life as part of the PRESTO study (Netherlands Trial Register number NTR3725). Differences in CM tolerance development between groups were analysed using a logistic regression model. Results show that the proportion of subjects (mean [±SD] age, 3.8 ± 0.27 years) who developed CM tolerance after 36 months was similar in the group receiving AAF-S (47/60 [78%]) and in the group receiving AAF (49/66 [74%]) (p = 0.253), that is, figures comparable to natural outgrowth of CM allergy. Our data suggest that the consumption of AAF and absence of exposure to CM peptides do not slow down CM tolerance acquisition.

Adrenaline auto injectors pharmacokinetic/pharmacodynamic studies and potential consequences for clinical practice.

BACKGROUND: Anaphylaxis is a sudden multisystem allergic reaction which may result in a fatal outcome if not treated promptly. Guidelines worldwide suggest intramuscular adrenaline as the first-line treatment for anaphylaxis outside a perioperative reaction. Adrenaline autoinjectors (AAIs) are widely used self-administrable devices, especially in community settings. Different commercial AAIs have been authorized to be marketed in Europe. For an AAI to be efficacious, a rapid adrenaline delivery in patients, including those who are overweight or obese, resulting in an optimal cardiovascular (CV) response, is a key feature. AAIs are designed to achieve this requirement, which is reflected in their differing functional properties such as primary container selection, drug delivery mechanism (cartridge-or syringe-based), needle length, needle gauge, and adrenaline dose (150 µg, 300 µg, or 500 µg). However, the differences in functional properties across these devices may play a critical role in achieving these requirements as well as the differences in ergonomics in the handling of these devices. THE PURPOSE OF THIS REVIEW: Considering the dynamic pharmacokinetic/pharmacodynamic (PK/PD) profiles of different AAIs marketed in Europe and their effect on adrenaline delivery, the expert panel, also serving as author for this paper have carried out a detailed analysis of the PK/PD profiles of four AAIs, namely, Anapen, Emerade, EpiPen, and Jext, to delineate the adrenaline delivery and their subsequent physiological effects on the backdrop of device characteristics, dose strength, and the skin-to-muscle distances of the participants.

Disaster planning for a surgical surge: when mass trauma threatens to overwhelm your operating rooms.

Mass casualty events particularly those requiring multiple simultaneous operating rooms are of increasing concern. Existing literature predominantly focuses on mass casualty care in the emergency department. Hospital disaster plans should include a component focused on preparing for multiple simultaneous operations. When developing this plan, representatives from all segments of the perioperative team should be included. The plan needs to address activation, communication, physical space, staffing, equipment, blood and medications, disposition offloading, special populations, and rehearsal.

Are trauma surgeons prepared? A survey of trauma surgeons' disaster preparedness before and during the COVID-19 pandemic.

Objective: US trauma centers (TCs) must remain prepared for mass casualty incidents (MCIs). However, trauma surgeons may lack formal MCI training. The recent COVID-19 pandemic drove multiple patient surges, overloaded Emergency Medical Services (EMS) agencies, and stressed TCs. This survey assessed trauma surgeons' MCI training, experience, and system and personal preparedness before the pandemic compared with the pandemic's third year. Methods: Survey invitations were emailed to all 1544 members of the American Association for the Surgery of Trauma in 2019, and then resent in 2022 to 1575 members with additional questions regarding the pandemic. Questions assessed practice type, TC characteristics, training, experience, beliefs about personal and hospital preparedness, likelihood of MCI scenarios, interventions desired from membership organizations, and pandemic experiences. Results: The response rate was 16.7% in 2019 and 12% in 2022. In 2022, surgeons felt better prepared than their hospitals for pandemic care, mass shootings, and active shooters, but remained feeling less well prepared for cyberattack and hazardous material events, compared with 2019. Only 35% of the respondents had unintentional MCI response experience in 2019 or 2022, and even fewer had experience with intentional MCI. 78% had completed a Stop the Bleed (STB) course and 63% own an STB kit. 57% had engaged in family preparedness activities; less than 40% had a family action plan if they could not come home during an MCI. 100% of the respondents witnessed pandemic-related adverse events, including colleague and coworker illness, patient surges, and resource limitations, and 17% faced colleague or coworker death. Conclusions: Trauma surgeons thought that they became better at pandemic care and rated themselves as better prepared than their hospitals for MCI care, which is an opportunity for them to take greater leadership roles. Opportunities remain to improve surgeons' family and personal MCI preparedness. Surgeons' most desired professional organization interventions include advocacy, national standards for TC preparedness, and online training. Level of evidence: VII, survey of expert opinion.

Transcranial histotripsy parameter study in primary and metastatic murine brain tumor models.

OBJECTIVE: This study investigated the effect of various histotripsy dosages on tumor cell kill and associated bleeding in two murine brain tumor models (glioma [Gl261] and lung metastasis [LL/2-Luc2]). METHODS AND MATERIALS: GL261 or LL/2-Luc2 cells were cultured and implanted into the brains of C57BL/6 mice. Histotripsy (1-cycle pulses, 5 Hz PRF, 30 MPa-P) was performed using a 1 MHz transducer for five different dosages for each cell line: 5, 20 or 200 pulses per location (PPL) at a single treatment point, or 5 or 10-20 PPL at multiple treatment points. MRI, bioluminescence imaging and histology were used to assess tumor ablation and treatment effects within 4-6 h post-treatment. RESULTS: All treatment groups resulted in a reduction of BLI intensity for the LL/2-Luc2 tumors, with significant signal reductions for the multi-point groups. The average pre-/post-treatment BLI flux (photons/s, ×108) for the different treatment groups were: 4.39/2.19 (5 PPL single-point), 5.49/1.80 (20 PPL single-point), 3.86/1.73 (200 PPL single-point), 2.44/1.11 (5 PPL multi-point) and 5.85/0.80 (10 PPL multi-point). MRI and H&E staining showed increased tumor damage and hemorrhagic effects with increasing histotripsy dose for both GL261 and LL/2-Luc2 tumors, but the increase in tumor damage was diminished beyond 10-20 PPL for single-point treatments and outweighed by increased hemorrhage. In general, hemorrhage was confined to be within 1 mm of the treatment boundary for all groups. CONCLUSIONS: Our results suggest that a lower number of histotripsy pulses at fewer focal locations can achieve substantial tumor kill while minimizing hemorrhage.

Updated guidance regarding the risk of allergic reactions to COVID-19 vaccines and recommended evaluation and management: A GRADE assessment and international consensus approach.

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history.

Timing and delay discounting in attention-deficit/hyperactivity disorder: A translational approach.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that often presents with abnormal time perception and increased impulsive choice behavior. The spontaneously hypertensive rat (SHR) is the most widely used preclinical model of the ADHD-Combined and ADHD-Hyperactive/Impulsive subtypes of the disorder. However, when testing the spontaneously hypertensive rat from Charles River (SHR/NCrl) on timing and impulsive choice tasks, the appropriate control strain is not clear, and it is possible that one of the possible control strains, the Wistar Kyoto from Charles River (WKY/NCrl), is an appropriate model for ADHD-Predominately Inattentive. Our goals were to test the SHR/NCrl, WKY/NCrl, and Wistar (WI; the progenitor strain for the SHR/NCrl and WKY/NCrl) strains on time perception and impulsive choice tasks to assess the validity of SHR/NCrl and WKY/NCrl as models of ADHD, and the validity of the WI strain as a control. We also sought to assess impulsive choice behavior in humans diagnosed with the three subtypes of ADHD and compare them with our findings from the preclinical models. We found SHR/NCrl rats timed faster and were more impulsive than WKY/NCrl and WI rats, and human participants diagnosed with ADHD were more impulsive compared to controls, but there were no differences between the three ADHD subtypes.

The role of online symptom questionnaires to support the diagnosis of cow's milk allergy in children for healthcare professionals - A Delphi consensus study.

BACKGROUND: Cow's milk allergy (CMA) is one of the most common food allergies world-wide. The emergence of online CMA symptom questionnaires, aimed at parents and/or healthcare professionals (HCP), may raise awareness about the possible diagnosis of CMA, but also increases the risk for overdiagnosis leading to unnecessary dietary restriction impacting on growth and nutrition. This publication sets out to establish the availability of these CMA symptom questionnaires and critically assesses the development and validity. METHODS: Thirteen HCP working in the field of CMA, from different countries, were recruited to participate. A combination of a Pubmed and CINAHL literature and online review using the Google search engine in English language was used. Symptoms in the questionnaires were assessed, using the European Academy for Allergy and Clinical Immunology guidelines for food allergy. Following the assessment of both the questionnaires and literature, the authors followed the modified Delphi approach to generate consensus statements. RESULTS: Six hundred and fifty-one publications were identified, of which 29 were suitable for inclusion, with 26 being associated with the Cow's Milk-Related Symptoms Score. The online search yielded 10 available questionnaires: 7/10 were sponsored by formula milk companies and 7/10 were aimed at parents and three at HCP. Following the assessment of data, 19 statements were generated in two rounds of anonymous voting reaching 100% agreement. CONCLUSIONS: Online CMA questionnaires, available to parents and HCP's, are varied in symptoms, and most were not validated. The overarching consensus generated from authors is that these questionnaires should not be used without the involvement of HCP.

Acquiring tissue for advanced lung cancer diagnosis and comprehensive biomarker testing: A National Lung Cancer Roundtable best-practice guide.

Advances in biomarker-driven therapies for patients with nonsmall cell lung cancer (NSCLC) both provide opportunities to improve the treatment (and thus outcomes) for patients and pose new challenges for equitable care delivery. Over the last decade, the continuing development of new biomarker-driven therapies and evolving indications for their use have intensified the importance of interdisciplinary communication and coordination for patients with or suspected to have lung cancer. Multidisciplinary teams are challenged with completing comprehensive and timely biomarker testing and navigating the constantly evolving evidence base for a complex and time-sensitive disease. This guide provides context for the current state of comprehensive biomarker testing for NSCLC, reviews how biomarker testing integrates within the diagnostic continuum for patients, and illustrates best practices and common pitfalls that influence the success and timeliness of biomarker testing using a series of case scenarios.

Provision of Food Allergy Care in the United Kingdom and United States: Current Issues and Future Directions.

Food allergy (FA) is a growing issue worldwide. The United Kingdom and United States are high-income, industrialized countries with reported increases in FA prevalence over the past few decades. This review compares delivery of FA care in the United Kingdom and United States and each country's response to the heightened demand and disparities for FA services. In the United Kingdom, allergy specialists are scarce and general practitioners (GPs) provide most allergy care. Whereas the United States has more allergists per capita than the United Kingdom, there is still a shortage of allergy services owing to the greater reliance on specialist care for FA in America and wide geographic variation in access to allergist services. Currently, generalists in these countries lack the specialty training and equipment to diagnose and manage FA optimally. Moving forward, the United Kingdom aims to enhance training for GPs so they may provide better quality frontline allergy care. In addition, the United Kingdom is implementing a new tier of semi-specialized GPs and increasing cross-center collaboration through clinical networks. The United Kingdom and United States aim to increase the number of FA specialists, which is critical at a time of rapidly expanding management options for allergic and immunologic diseases requiring clinical expertise and shared decision-making to select appropriate therapies. While these countries aim to grow their supply of quality FA services actively, further efforts to build clinical networks and perhaps recruit international medical graduates and expand telehealth services are necessary to reduce disparities in access to care. For the United Kingdom in particular, increasing quality services will require additional support from the leadership of the centralized National Health Service, which remains challenging.

Preventing food allergy fatalities.

Fatal anaphylaxis to food is thankfully rare, but every death is a potentially avoidable tragedy. Usually, there will be a coronial inquest to establish the 'how and why' for each death. Reviewing these food allergy-related deaths identifies a number of common themes and risk factors. While some are non-modifiable (such as age, gender and ethnicity), others are and include delayed epinephrine administration and communication difficulties in allergen avoidance. This review highlights the key messages in food allergy-related fatality prevention for healthcare professionals and patients alike, and where available, we explain the evidence behind such recommendations. We describe the data behind the good practice points to facilitate their adoption in routine practice without generating additional anxiety for what is a comparatively rare event. We also propose an information leaflet for patients and carers, developed with patients and endorsed by two major allergy charities, to facilitate dissemination of the recommendations in this review.

International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature.

BACKGROUND & AIMS: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature. METHODS: This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement. RESULTS: Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas. CONCLUSIONS: This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science.

Tolerance development in cow's milk-allergic infants receiving amino acid-based formula: A randomized controlled trial.

BACKGROUND: Tolerance development is an important clinical outcome for infants with cow's milk allergy. OBJECTIVE: This multicenter, prospective, randomized, double-blind, controlled clinical study (NTR3725) evaluated tolerance development to cow's milk (CM) and safety of an amino acid-based formula (AAF) including synbiotics (AAF-S) comprising prebiotic oligosaccharides (oligofructose, inulin) and probiotic Bifidobacterium breve M-16V in infants with confirmed IgE-mediated CM allergy. METHODS: Subjects aged ≤13 months with IgE-mediated CM allergy were randomized to receive AAF-S (n = 80) or AAF (n = 89) for 12 months. Stratification was based on CM skin prick test wheal size and study site. After 12 and 24 months, CM tolerance was evaluated by double-blind, placebo-controlled food challenge. A logistic regression model used the all-subjects randomized data set. RESULTS: At baseline, mean ± SD age was 9.36 ± 2.53 months. At 12 and 24 months, respectively, 49% and 62% of subjects were CM tolerant (AAF-S 45% and 64%; AAF 52% and 59%), and not differ significantly between groups. During the 12-month intervention, the number of subjects reporting at least 1 adverse event did not significantly differ between groups; however, fewer subjects required hospitalization due to serious adverse events categorized as infections in the AAF-S versus AAF group (9% vs 20%; P = .036). CONCLUSIONS: After 12 and 24 months, CM tolerance was not different between groups and was in line with natural outgrowth. Results suggest that during the intervention, fewer subjects receiving AAF-S required hospitalization due to infections.

Timing and Intertemporal Choice Behavior in the Valproic Acid Rat Model of Autism Spectrum Disorder.

Recently it has been proposed that impairments related to autism spectrum disorder (ASD) may reflect a more fundamental disruption in time perception. Here, we examined whether in utero exposure to valproic acid (VPA) can generate specific behavioral deficits related to ASD and time perception. Pups from control and VPA groups were tested using fixed-interval (FI) temporal bisection, peak interval, and intertemporal choice tasks. In addition, the rats were assessed on motor function, perseverative and exploratory behavior, anxiety, and memory. The VPA group displayed a leftward shift in timing functions. VPA rats displayed no deficits on the motor and memory tasks, but were significantly different from controls on measures of perseveration and anxiety.

Effects of immediate-reinforcement training on delay discounting behavior in rats.

Chronic exposure to delayed reinforcement has been shown to increase choice for larger, later reinforcement in a subsequent delay discounting task. In the three experiments presented in this paper, the opposite was tested: effects of chronic exposure to immediate reinforcement on choice in a subsequent delay discounting task. In Experiment 1, larger, later reinforcement choice was significantly reduced as a result of exposure to immediate reinforcement, compared to a maturation/handle control group, in experienced, male Lewis rats. In Experiment 2, with naive male and female Wistar rats, and Experiment 3, with naïve male Long Evans rats, the impact of exposure to immediate reinforcement was less robust, but directionally consistent with results from Experiment 1. These results align with some previous work reporting that exposure to immediate reinforcement may decrease choice for larger, later reinforcement in a delay discounting task, and/or blunt maturational increases in choice for larger, later reinforcement. These findings have implications for future research investigating experience-based interventions to manipulate delay discounting behavior. They also have clinical implications for understanding and treating disorders involving maladaptive choice.

Transcranial Magnetic Resonance-Guided Histotripsy for Brain Surgery: Pre-clinical Investigation.

Histotripsy has been previously applied to target various cranial locations in vitro through an excised human skull. Recently, a transcranial magnetic resonance (MR)-guided histotripsy (tcMRgHt) system was developed, enabling pre-clinical investigations of tcMRgHt for brain surgery. To determine the feasibility of in vivo transcranial histotripsy, tcMRgHt treatment was delivered to eight pigs using a 700-kHz, 128-element, MR-compatible phased-array transducer inside a 3-T magnetic resonance imaging (MRI) scanner. After craniotomy to open an acoustic window to the brain, histotripsy was applied through an excised human calvarium to target the inside of the pig brain based on pre-treatment MRI and fiducial markers. MR images were acquired pre-treatment, immediately post-treatment and 2-4 h post-treatment to evaluate the acute treatment outcome. Successful histotripsy ablation was observed in all pigs. The MR-evident lesions were well confined within the targeted volume, without evidence of excessive brain edema or hemorrhage outside of the target zone. Histology revealed tissue homogenization in the ablation zones with a sharp demarcation between destroyed and unaffected tissue, which correlated well with the radiographic treatment zones on MRI. These results are the first to support the in vivo feasibility of tcMRgHt in the pig brain, enabling further investigation of the use of tcMRgHt for brain surgery.