Monkey Bar-Associated Pediatric Fractures: A National Epidemiologic Study of Emergency Department Visits.

INTRODUCTION: Emergency department (ED) visits because of pediatric fractures are not only burdensome for patients and their families but also result in an increased healthcare expenditure. Almost half of all children experience at least one fracture by the age of 15. Many fractures occur in playgrounds, with monkey bars and other climbing apparatuses noted as frequent mechanisms of injury. Our purpose was to identify the pattern of injury and the population sustaining monkey bar-associated fractures. METHODS: We queried the National Electronic Injury Surveillance System database for all monkey bar-associated injuries in patients aged 0 to 18 years from January 1, 2009, to December 31, 2019. We described demographic data, patient disposition from the ED, fracture pattern, and injury setting using unweighted and weighted estimates. Weighted results that more closely reflect national estimates were calculated. RESULTS: During the study period, 30,920 (862,595 weighted) monkey bar-associated injuries presented to EDs; 16,410 (53.1%) (weighted injuries: 408,722 [47.4%]) were fracture injuries. The average age of kids sustaining fractures was 6.5 years, with most injuries (66.4%) occurring in kids between 6 and 12 years. A higher percentage of male patients presented to the ED with fractures compared with female patients (53% versus 47%). Upper extremity fractures were most common, 382,672 (94%) with forearm fractures constituting the majority (156,691 [38%]). Most children were treated and released (354,323 [87%]), with only 35,227 children (9%) being admitted for treatment. Places of recreation/sports were the most common setting of fractures (148,039 [36%]), followed by schools (159,784 [39%]). A notable association was observed between year and ethnicity and between month period and injury setting. CONCLUSION: Monkey bar-associated injuries are a major cause of upper extremity fractures in children, with most injuries occurring in recreational areas or schools. Young elementary school children are at the highest risk of injury. ED visits because of monkey bar-associated fractures have increased over the study period, and these injuries continue to be a major cause of fractures in children. Additional measures should be installed to decrease these preventable fractures among children, with schools as a potential starting point.

Self-administered mindfulness interventions reduce stress in a large, randomized controlled multi-site study.

Mindfulness witnessed a substantial popularity surge in the past decade, especially as digitally self-administered interventions became available at relatively low costs. Yet, it is uncertain whether they effectively help reduce stress. In a preregistered (OSF https://doi.org/10.17605/OSF.IO/UF4JZ ; retrospective registration at ClinicalTrials.gov NCT06308744 ) multi-site study (nsites = 37, nparticipants = 2,239, 70.4% women, Mage = 22.4, s.d.age = 10.1, all fluent English speakers), we experimentally tested whether four single, standalone mindfulness exercises effectively reduced stress, using Bayesian mixed-effects models. All exercises proved to be more efficacious than the active control. We observed a mean difference of 0.27 (d = -0.56; 95% confidence interval, -0.43 to -0.69) between the control condition (M = 1.95, s.d. = 0.50) and the condition with the largest stress reduction (body scan: M = 1.68, s.d. = 0.46). Our findings suggest that mindfulness may be beneficial for reducing self-reported short-term stress for English speakers from higher-income countries.

Identifying and Reducing Insulin Errors in the Simulated Military Critical Care Air Transport Environment: A Human Factors Approach.

INTRODUCTION: During high-fidelity simulations in the Critical Care Air Transport (CCAT) Advanced course, we identified a high frequency of insulin medication errors and sought strategies to reduce them using a human factors approach. MATERIALS AND METHODS: Of 169 eligible CCAT simulations, 22 were randomly selected for retrospective audio-video review to establish a baseline frequency of insulin medication errors. Using the Human Factors Analysis Classification System, dosing errors, defined as a physician ordering an inappropriate dose, were categorized as decision-based; administration errors, defined as a clinician preparing and administering a dose different than ordered, were categorized as skill-based. Next, 3 a priori interventions were developed to decrease the frequency of insulin medication errors, and these were grouped into 2 study arms. Arm 1 included a didactic session reviewing a sliding-scale insulin (SSI) dosing protocol and a hands-on exercise requiring all CCAT teams to practice preparing 10 units of insulin including a 2-person check. Arm 2 contained arm 1 interventions and added an SSI cognitive aid available to students during simulation. Frequency and type of insulin medication errors were collected for both arms with 93 simulations for arm 1 (January-August 2021) and 139 for arm 2 (August 2021-July 2022). The frequency of decision-based and skill-based errors was compared across control and intervention arms. RESULTS: Baseline insulin medication error rates were as follows: decision-based error occurred in 6/22 (27.3%) simulations and skill-based error occurred in 6/22 (27.3%). Five of the 6 skill-based errors resulted in administration of a 10-fold higher dose than ordered. The post-intervention decision-based error rates were 9/93 (9.7%) and 23/139 (2.2%), respectively, for arms 1 and 2. Compared to baseline error rates, both arm 1 (P = .04) and arm 2 (P < .001) had a significantly lower rate of decision-based errors. Additionally, arm 2 had a significantly lower decision-based error rate compared to arm 1 (P = .015). For skill-based preparation errors, 1/93 (1.1%) occurred in arm 1 and 4/139 (2.9%) occurred in arm 2. Compared to baseline, this represents a significant decrease in skill-based error in both arm 1 (P < .001) and arm 2 (P < .001). There were no significant differences in skill-based error between arms 1 and 2. CONCLUSIONS: This study demonstrates the value of descriptive error analysis during high-fidelity simulation using audio-video review and effective risk mitigation using training and cognitive aids to reduce medication errors in CCAT. As demonstrated by post-intervention observations, a human factors approach successfully reduced decision-based error by using didactic training and cognitive aids and reduced skill-based error using hands-on training. We recommend the development of a Clinical Practice Guideline including an SSI protocol, guidelines for a 2-person check, and a cognitive aid for implementation with deployed CCAT teams. Furthermore, hands-on training for insulin preparation and administration should be incorporated into home station sustainment training to reduced medication errors in the operational environment.

An update on the development of a bottlenose dolphin, Tursiops truncatus, immune reagent toolkit.

There are extensive immunological reagents available for laboratory rodents and humans. However, for veterinary species there is a need for expansion of immunological toolkits, with this especially evident for marine mammals, such as cetaceans. In addition to their use in a research setting, immune assays could be employed to monitor the health status of cetaceans and serve as an adjunct to available diagnostic tests. Such development of specific and sensitive immune assays will enhance the proper care and stewardship of wild and managed cetacean populations. Our goal is to provide immune reagents and immune assays for the research community, clinicians, and others involved in care of bottlenose dolphins. This review will provide an update on our development of a bottlenose dolphin immunological toolkit. The future availability and continued development of these reagents is critical for improving wild and managed bottlenose dolphin population health through enhanced assessment of their responses to alterations in the marine environment, including pathogens, and improve our ability to monitor their status following vaccination.

Variation of terpene alkaloids in Daphniphyllum macropodum across plants and tissues.

Daphniphyllum macropodum produces alkaloids that are structurally complex with polycyclic, stereochemically rich carbon skeletons. Understanding how these compounds are formed by the plant may enable exploration of their biological function and bioactivities. We employed multiple metabolomics techniques, including a workflow to annotate compounds in the absence of standards, to compare alkaloid content across plants and tissues. Different alkaloid structural types were found to have distinct distributions between genotypes, between tissues and within tissues. Alkaloid structural types also showed different isotope labelling enrichments that matched their biosynthetic relationships. The work suggests that mevalonate derived 30-carbon alkaloids are formed in the phloem region before their conversion to 22-carbon alkaloids which accumulate in the epidermis. This sets the stage for further investigation into the biosynthetic pathway.

Revolutionizing Combat Casualty Care: The Power of Digital Twins in Optimizing Casualty Care Through Passive Data Collection.

The potential impact of large-scale combat operations and multidomain operations against peer adversaries poses significant challenges to the Military Health System including large volumes of critically ill and injured casualties, prolonged care times in austere care contexts, limited movement, contested logistics, and denied communications. These challenges contribute to the probability of higher casualty mortality and risk that casualty care hinders commanders' forward momentum or opportunities for overmatch on the battlefield. Novel technical solutions and associated concepts of operation that fundamentally change the delivery of casualty care are necessary to achieve desired medical outcomes that include maximizing Warfighter battle-readiness, minimizing return-to-duty time, optimizing medical evacuation that clears casualties from the battlefield while minimizing casualty morbidity and mortality, and minimizing resource consumption across the care continuum. These novel solutions promise to "automate" certain aspects of casualty care at the level of the individual caregiver and the system level, to unburden our limited number of providers to do more and make better (data-driven) decisions. In this commentary, we describe concepts of casualty digital twins-virtual representations of a casualty's physical journey through the roles of care-and how they, combined with passive data collection about casualty status, caregiver actions, and real-time resource use, can lead to human-machine teaming and increasing automation of casualty care across the care continuum while maintaining or improving outcomes. Our path to combat casualty care automation starts with mapping and modeling the context of casualty care in realistic environments through passive data collection of large amounts of unstructured data to inform machine learning models. These context-aware models will be matched with patient physiology models to create casualty digital twins that better predict casualty needs and resources required and ultimately inform and accelerate decision-making across the continuum of care. We will draw from the experience of the automotive industry as an exemplar for achieving automation in health care and inculcate automation as a mechanism for optimizing the casualty care survival chain.

Efficacy of a Single Day Extracorporeal Membrane Oxygenation Training Course for Critical Care Air Transport Team Eligible Personnel.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an advanced medical technology that is used to treat respiratory and heart failure. The U.S. military has used ECMO in the care of combat casualties during Operation Enduring Freedom and Operation Iraqi Freedom as well as in the treatment of patients during the recent Coronavirus Disease 2019 pandemic. However, few Military Health System personnel have training and experience in the use of ECMO therapy. To address this dearth of expertise, we developed and evaluated an accelerated ECMO course for military medical personnel. OBJECTIVES: To compare the efficacy of an accelerated ECMO course for Military Health System critical care teams. METHODS: Seventeen teams, each consisting of a physician and nurse, underwent a 5-h accelerated ECMO course. Similar to our previous live-tissue ECMO training program (phases I and II), each team watched prerecorded ECMO training lectures. Subjects then practiced priming the ECMO circuit, cannulating ECMO, initiating ECMO, and correcting common complications on an ECMO simulation model. An added component to this phase III project included transportation and telemedicine consultation availability. Training success was evaluated via knowledge and confidence assessments, and observation of each team attempting to initiate ECMO on a Yorkshire swine patient model, transport the patient model, and troubleshoot complications with the support of telemedicine consultation when desired. RESULTS: Seventeen teams successfully completed the course. All seventeen teams (100%) successfully placed the swine on veno-arterial ECMO. Of those, 15 teams successfully transitioned to veno-arterial-venous ECMO. The knowledge assessments of physicians and nurses increased by 12.2% from pretest (mean of 62.1%, SD 10.4%) to posttest (mean of 74.4%, SD 8.2%), P < .0001; their confidence assessments increased by 41.1% from pretest (mean of 20.1%, SD 11.8%) to posttest (mean of 61.2%, SD 18.6%). CONCLUSIONS: An abbreviated 1-day lecture and hands-on task-trainer-based ECMO course resulted in a high rate of successful skill demonstration and improvement of physicians' and nurses' knowledge assessments and confidence levels, similar to our previous live-tissue training program. When compared to our previous studies, the addition of telemedicine and patient transportation to this study did not affect the duration or performance of procedures.

A prospective, pragmatic non-inferiority study of emergency intubation success with the single-use i-view versus standard reusable video laryngoscope.

INTRODUCTION: Video laryngoscope (VL) technology improves first-pass success. The novel i-view VL device is inexpensive and disposable. We sought to determine the first-pass intubation success with the i-view VL device versus the standard reusable VL systems in routine use at each site. METHODS: We performed a prospective, pragmatic study at two major emergency departments (EDs) when VL was used. We rotated i-view versus reusable VL as the preferred device of the month based on an a priori schedule. An investigator-initiated interim analysis was performed. Our primary outcome was a first-pass success with a non-inferiority margin of 10% based on the per-protocol analysis. RESULTS: There were 93 intubations using the reusable VL devices and 81 intubations using the i-view. Our study was stopped early due to futility in reaching our predetermined non-inferiority margin. Operator and patient characteristics were similar between the two groups. The first-pass success rate for the i-view group was 69.1% compared to 84.3% for the reusable VL group. A non-inferiority analysis indicated that the difference (-15.1%) and corresponding 90% confidence limits (-25.3% to -5.0%) did not fall within the predetermined 10% non-inferiority margin. CONCLUSIONS: The i-view device failed to meet our predetermined non-inferiority margin when compared to the reusable VL systems with the study stopping early due to futility. Significant crossover occurred at the discretion of the intubating operator during the i-view month.

Growth Mindset Messages from Instructors Improve Academic Performance Among First-Generation College Students.

First-generation (FG) college students (i.e., those for whom neither parent/guardian obtained a bachelor's degree) experience more barriers in college, compared with continuing-generation students. These barriers are compounded by subtle messages from instructors that convey the idea that natural talent is necessary for success in scientific fields. In contrast, growth mindset messages communicate that ability can improve with effort, help-seeking, and using productive study strategies. In a large enrollment introductory biology course, students were randomly assigned to receive email messages from their instructor after the first two exams containing either a growth mindset or control message. The intervention improved grades in the course for everyone, on average, compared with control messages, and were especially beneficial for FG students. This increase in performance was partially mediated by increased activity accessing course materials on the course website. This study provides preliminary evidence that instructors communicating growth mindset messages can support FG students' performance.

Interventions associated with survival after prehospital intubation in the deployed combat setting.

INTRODUCTION: Airway compromise is the second leading cause of potentially preventable death on the battlefield. Prehospital airway management is often unavoidable in a kinetic combat environment and expected to increase in future wars where timely evacuation will be unreliable and air superiority not guaranteed. We compared characteristics of survivors to non-survivors among combat casualties undergoing prehospital airway intubation. MATERIALS AND METHODS: We requested all Department of Defense Trauma Registry (DODTR) encounters during 2007-2023 with documentation of any airway intervention or assessment within the first 72-h after injury. We conducted a retrospective cohort study of all casualties with intubation documented in the prehospital setting. We used descriptive and inferential statistical analysis to compare survivors through 7 days post injury versus non-survivors. We constructed 3 multivariable logistic regression models to test for associations between interventions and 7-day survival after adjusting for injury severity score, mechanism of injury, and receipt of sedatives, paralytics, and blood products. RESULTS: There were 1377 of 48,301 patients with documentation of prehospital intubation in a combat setting. Of these, 1028 (75%) survived through 7 days post injury. Higher proportions of survivors received ketamine, paralytic agents, parenteral opioids, and parenteral benzodiazepines; there was no difference in the proportions of survivors versus non-survivors receiving etomidate. The multivariable models consistently demonstrated positive associations between 7-day survival and receipt of non-depolarizing paralytics and opioid analgesics. CONCLUSIONS: We found an association between non-depolarizing paralytic and opioid receipt with 7-day survival among patients undergoing prehospital intubation. The literature would benefit from future multi-center randomized controlled trials to establish optimal pharmacologic strategies for trauma patients undergoing prehospital intubation.

Progress in the development and use of monoclonal antibodies to study the evolution and function of the immune systems in the extant lineages of ungulates.

Details on the origin and function of the immune system are beginning to emerge from genomic studies tracing the origin of B and T cells and the major histocompatibility complex. This is being accomplished through identification of DNA sequences of ancestral genes present in the genomes of lineages of vertebrates that have evolved from a common primordial ancestor. Information on the evolution of the composition and function of the immune system is being obtained through development of monoclonal antibodies (mAbs) specific for the MHC class I and II molecules and differentially expressed on leukocytes differentiation molecules (LDM). The mAbs have provided the tools needed to compare the similarities and differences in the phenotype and function of immune systems that have evolved during speciation. The majority of information currently available on evolution of the composition and function of the immune system is derived from study of the immune systems in humans and mice. As described in the present review, further information is beginning to emerge from comparative studies of the immune systems in the extant lineages of species present in the two orders of ungulates, Perissodactyla and Artiodactyla. Methods have been developed to facilitate comparative research across species on pathogens affecting animal and human health.

Perceptions and Attitudes Related to Driving after Cannabis Use in Canadian and US Adults.

BACKGROUND: This study examined the risk perceptions related to driving after cannabis use (DACU) among Canadian and US adults who used cannabis in the past six months. METHODS: Perceptions of danger, normative beliefs, perceived likelihood of negative consequences, and other driving-related variables were collected via online surveys in Canadian (n = 158; 50.0% female, 84.8% White, mean age = 32.73 years [SD = 10.61]) and US participants (n = 678; 50.9% female, 73.6% White, mean age = 33.85 years [SD = 10.12]). Driving cognitions and DACU quantity/frequency were compared between samples using univariate analyses of variance, and Spearman's (ρ) correlations were performed to examine associations between driving cognitions and DACU quantity/frequency. RESULTS: The two samples did not significantly differ in self-reported level of cannabis use, lifetime quantity of DACU, or the number of times they drove within two hours of cannabis use in the past three months (Ps > .12). Compared to US participants, Canadians perceived driving within two hours of cannabis use as more dangerous (P < 0.001, ηp2 = 0.013) and reported more of their friends would disapprove of DACU (P = 0.03, ηp2 = 0.006). There were no differences in the number of friends who would refuse to ride with a driver who had used cannabis (P = 0.15) or the perceived likelihood of negative consequences (Ps > 0.07). More favorable perceptions were significantly correlated with greater lifetime DACU and driving within two hours of use (ρ = 0.25-0.53, Ps < 0.01). CONCLUSIONS: These findings reveal differences in distal risk factors for DACU between Canada and the US and may inform prevention efforts focusing on perceptions of risk and social acceptance of DACU.

Quantified impacts of non-pharmaceutical interventions on influenza circulation during the COVID-19 pandemic in 13 African countries, 2020-2022.

Nonpharmaceutical interventions (NPIs) for SARS-CoV-2 disrupted circulation of influenza. We used data from 13 African countries and generalized linear models to identify associations between levels of NPIs, using the Oxford Stringency Index, and seasonal influenza activity, using parameters derived from 2020-2022 seasonal influenza surveillance. We found that for each step increase in school closings, the average percentage of respiratory specimens testing positive for influenza across the influenza season dropped by 20% (95% CI: 1-38%); no other NPI was significant. These findings may inform interventions to slow influenza circulation in pandemics and possibly during seasonal epidemics.

Use of RNA-seq to identify genes encoding cytokines and chemokines activated following uptake and processing a candidate peptide vaccine developed against Mycobacterium avium subsp. paratuberculosis.

Analysis of the primary and recall responses to a membrane molecule (MMP), encoded by MAP2121c demonstrated that tri-directional signaling between the antigen-presenting cell (APC), CD4 and CD8 is essential for eliciting a CD8 cytotoxic T cell (CTL) response against Mycobacterium avium subsp. paratuberculosis. As reported here, RNA-sequencing was used to initiate the characterization of the signaling pathways involved in eliciting the development of CD8 CTL, starting with the characterization of the activation status of genes in monocyte-derived macrophages (MoMΦ) following uptake and processing MMP for the presentation of antigenic epitopes to CD4 and CD8 T cells. Activation status was compared with the uptake and processing of LPS, a nonspecific stimulator of macrophages. 1609 genes were identified that were upregulated, and 1277 were downregulated three hours after uptake and processing MMP. No significant difference was observed in the cytokine genes selected for analysis of the signaling that must occur between APC, CD4, and CD8 for the development of CTL. The initial observations indicate screening of the transcriptome should include genes involved in signaling between APC and CD4, and CD8 regardless of their activation status. Four genes of interest in this study, IL12A, IL12B, IL15, and IL23A, were not significantly different from control values. The initial studies also indicate MoMΦ can be included with dendritic cells and monocyte-derived dendritic cells for further analysis of the tri-directional signaling required for the development of CTL.

A análise das respostas primárias e de recall a uma molécula de membrana (MMP), codificada por MAP2121c demonstrou que a sinalização tridirecional entre a célula apresentadora de antígeno (APC), CD4 e CD8 é essencial para provocar uma resposta de células T citotóxicas CD8 (CTL) contra Mycobacterium avium subsp. paratuberculose. Conforme relatado aqui, o sequenciamento de RNA foi usado para iniciar a caracterização das vias de sinalização envolvidas na indução do desenvolvimento de CTL CD8, começando com a caracterização do status de ativação de genes em macrófagos derivados de monócitos (MoMΦ) após captação e processamento de MMP para a apresentação de epítopos antigênicos às células T CD4 e CD8. O status de ativação foi comparado com a captação e processamento de LPS, um estimulador inespecífico de macrófagos. Foram identificados 1.609 genes que foram regulados positivamente e 1.277 foram regulados negativamente três horas após a captação e processamento de MMP. Nenhuma diferença significativa foi observada nos genes de citocinas selecionados para análise da sinalização que deve ocorrer entre APC, CD4 e CD8 para o desenvolvimento de CTL. As observações iniciais indicam que o rastreio do transcriptoma deve incluir genes envolvidos na sinalização entre APC e CD4 e CD8, independentemente do seu estado de activação. Quatro genes de interesse neste estudo, IL12A, IL12B, IL15 e IL23A, não foram significativamente diferentes dos valores de controle. Os estudos iniciais também indicam que o MoMΦ pode ser incluído com células dendríticas e células dendríticas derivadas de monócitos para análise adicional da sinalização tridirecional necessária para o desenvolvimento de CTL.

Differential interferon responses to influenza A and B viruses in primary ferret respiratory epithelial cells.

Influenza B viruses (IBV) cocirculate with influenza A viruses (IAV) and cause periodic epidemics of disease, yet antibody and cellular responses following IBV infection are less well understood. Using the ferret model for antisera generation for influenza surveillance purposes, IAV resulted in robust antibody responses following infection, whereas IBV required an additional booster dose, over 85% of the time, to generate equivalent antibody titers. In this study, we utilized primary differentiated ferret nasal epithelial cells (FNECs) which were inoculated with IAV and IBV to study differences in innate immune responses which may result in differences in adaptive immune responses in the host. FNECs were inoculated with IAV (H1N1pdm09 and H3N2 subtypes) or IBV (B/Victoria and B/Yamagata lineages) and assessed for 72 h. Cells were analyzed for gene expression by quantitative real-time PCR, and apical and basolateral supernatants were assessed for virus kinetics and interferon (IFN), respectively. Similar virus kinetics were observed with IAV and IBV in FNECs. A comparison of gene expression and protein secretion profiles demonstrated that IBV-inoculated FNEC expressed delayed type-I/II IFN responses and reduced type-III IFN secretion compared to IAV-inoculated cells. Concurrently, gene expression of Thymic Stromal Lymphopoietin (TSLP), a type-III IFN-induced gene that enhances adaptive immune responses, was significantly downregulated in IBV-inoculated FNECs. Significant differences in other proinflammatory and adaptive genes were suppressed and delayed following IBV inoculation. Following IBV infection, ex vivo cell cultures derived from the ferret upper respiratory tract exhibited reduced and delayed innate responses which may contribute to reduced antibody responses in vivo.IMPORTANCEInfluenza B viruses (IBV) represent nearly one-quarter of all human influenza cases and are responsible for significant clinical and socioeconomic impacts but do not pose the same pandemic risks as influenza A viruses (IAV) and have thus received much less attention. IBV accounts for greater severity and deaths in children, and vaccine efficacy remains low. The ferret can be readily infected with human clinical isolates and demonstrates a similar course of disease and immune responses. IBV, however, generates lower antibodies in ferrets than IAV following the challenge. To determine whether differences in initial innate responses following infection may affect the development of robust adaptive immune responses, ferret respiratory tract cells were isolated, infected with IAV/IBV, and compared. Understanding the differences in the initial innate immune responses to IAV and IBV may be important in the development of more effective vaccines and interventions to generate more robust protective immune responses.

Perinatal mental health in medical school curricula: a national scoping survey of British universities and student psychiatry societies.

AIMS AND METHOD: With increasing recognition of the prevalence and impact of perinatal mental health (PMH) disorders comes a responsibility to ensure that tomorrow's doctors can support families during the perinatal period. Online surveys seeking information about the inclusion of PMH education in undergraduate curricula were sent to psychiatry curriculum leads and student psychiatry societies from each university medical school in the UK between April and September 2021. RESULTS: Responses were received from 32/35 (91.4%) medical schools. Two-thirds reported specific inclusion of PMH content in the core curriculum, typically integrated into general adult psychiatry or obstetric teaching. Students at the remaining schools were all likely to be examined on the topic or see perinatal cases during at least one clinical attachment. CLINICAL IMPLICATIONS: PMH education offers an opportunity for collaboration between psychiatry and other disciplines. Future work looking at educational case examples with objective outcomes would be valuable.

Safety and immunogenicity of locally produced trivalent inactivated influenza vaccine (Tri Fluvac) in healthy Thai adults aged 18-64 years in Nakhon Phanom: A Phase III double blinded, three-arm, randomized, controlled trial.

BACKGROUND: Domestic influenza vaccine production facilitates a sustainable supply for mitigating seasonal influenza and improves national health security by providing infrastructure and experience for pandemic vaccine production, if needed. METHODS: A Phase III, double blind, randomized controlled trial was conducted from Sep 2019-Oct 2020 in healthy adults 18-64 years in Nakhon Phanom, Thailand. Randomization (3:3:1) compared study vaccine (Tri Fluvac), saline placebo, and an active comparator (licensed vaccine). Primary outcomes were superior efficacy compared to placebo based on RT-PCR-confirmed influenza virus infection within 12 months and non-inferiority compared to active comparator based on immunogenicity (HAI assay) at 28 days. Safety was also assessed. RESULTS: The trial enrolled 4,284 participants (Tri Fluvac = 1,836; placebo = 1,836; active comparator = 612). There were 29 RT-PCR positive influenza infections (10 Tri Fluvac, 5.5/1,000 PY; 19 placebo, 10.4/1,000PY; 0 comparator) for an absolute protective efficacy of 46.4 (95 % CI = -22.0-76.5) compared with placebo, but the power was 43.7 %. Seroconversion difference rates between Tri Fluvac and comparator at Day 28 were 1.74 (95 % CI: -2.77, 6.25), 2.22 (-2.40, 6.84), and -0.57 (-5.41, 4.27) for A(H1N1), A(H3N2), and B strains, respectively. Adverse and severe adverse events occurred in 175 (9.5 %) Tri Fluvac, 177 (10.8 %) placebo, and 66 (10.8 %) comparator arms (p-value = 0.437, Tri Fluvac vs. comparator) CONCLUSIONS: Tri Fluvac was well tolerated, and immunogenicity was non-inferior to the active comparator, meeting U.S. Food and Drug Administration (FDA) criteria for adult vaccine licensure. Few acute respiratory infections were reported during intense COVID-19 pandemic restrictions, resulting in insufficient power to evaluate clinical efficacy.

Sex- and Age-Related Differences in Post-Concussive Symptom Reporting Among Children and Their Parents.

Pediatric mild traumatic brain injury (pmTBI) has received increased public attention over the past decade, especially for children who experience persistent post-concussive symptoms (PCS). Common methods for obtaining pediatric PCS rely on both self- and parental report, exhibit moderate test-retest reliability, and variable child-parent agreement, and may yield high false positives. The current study investigated the impact of age and biological sex on PCS reporting (Post-Concussion Symptom Inventory) in patients with pmTBI (n = 286) at retrospective, 1 week, 4 months, and 1 year post-injury time points, as well as reported symptoms in healthy controls (HC; n = 218) at equivalent assessment times. HC and their parents reported higher PCS for their retrospective rating relative to the other three other study visits. Child-parent agreement was highest for female adolescents, but only approached acceptable ranges (≥ 0.75) immediately post-injury. Poor-to-fair child/parental agreement was observed for most other study visits for pmTBI and at all visits for HC. Parents rated female adolescents as being more symptomatic than their male counterparts in spite of small (pmTBI) or no (HC) sex-related differences in self-reported ratings, suggestive of a potential cultural bias in parental ratings. Test-retest reliability for self-report was typically below acceptable ranges for both pmTBI and HC groups, with reliability decreasing for HC and increasing for pmTBI as a function of time between visits. Parental test-retest reliability was higher for females. Although continued research is needed, current results support the use of child self-report over parental ratings for estimating PCS burden. Results also highlight the perils of relying on symptom self-report for diagnostic and prognostic purposes.

Examining the effect of cannabis cues on cannabis demand in sleep, driving, and typical drug-use contexts.

PURPOSE: Given the expanding legal cannabis market in the U.S., it is vital to understand how context impacts cannabis use. Therefore, we explored the effect of cannabis cues and cannabis-use context on cannabis demand in 79 adults who reported smoking cannabis at least weekly. METHODS: Participants completed a single laboratory session consisting of four hypothetical marijuana purchase tasks (MPTs) involving either a typical use situation or a driving or sleep context. The MPTs were alternated with exposure to cannabis or neutral picture cues based on block randomization by gender. RESULTS: Cannabis cues increased self-reported craving for cannabis (p =.044) but did not significantly alter demand (ps =0.093-0.845). In the driving context, participants demonstrated a significant reduction in cannabis demand, indicated by lower intensity (p <0.001), Omax (p <0.001), and Pmax (p <0.001), breakpoint (p =.003), and higher α (p <0.001). The sleep context was associated with significantly greater α (p <0.006) but nonsignificant effects for other indices (ps =0.123-0.707). Finally, cannabis cues increased Omax (p =.013) and breakpoint (p =.035) in the sleep context but not in the typical-use context. CONCLUSIONS: These findings suggest that cannabis-use behavior is sensitive to contingencies surrounding driving after cannabis use and may also be sensitive to sleep contexts in the presence of cannabis cues. Since this is the first study to examine driving and sleep contexts, we caution against drawing broad conclusions until future research is conducted to replicate these findings.

The role of asymptomatic infections in influenza transmission: what do we really know.

Before the COVID-19 pandemic, the role of asymptomatic influenza virus infections in influenza transmission was uncertain. However, the importance of asymptomatic infection with SARS-CoV-2 for onward transmission of COVID-19 has led experts to question whether the role of asymptomatic influenza virus infections in transmission had been underappreciated. We discuss the existing evidence on the frequency of asymptomatic influenza virus infections, the extent to which they contribute to infection transmission, and remaining knowledge gaps. We propose priority areas for further evaluation, study designs, and case definitions to address existing knowledge gaps.