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Abstract The quick Sequential Organ Failure Assessment (qSOFA) system identifies an individual’s risk to progress to poor sepsis-related outcomes using minimal variables. We used Support Vector Machine, Learning Using Concave and Convex Kernels, and Random Forest to predict an increase in qSOFA score using electronic health record (EHR) data, electrocardiograms (ECG), and arterial line signals. We structured physiological signals data in a tensor format and used Canonical Polyadic/Parallel Factors (CP) decomposition for feature reduction. Random Forests trained on ECG data show improved performance after tensor decomposition for predictions in a 6-h time frame (AUROC 0.67 ± 0.06 compared to 0.57 ± 0.08, $$p = 0.01$$ p = 0.01 ). Adding arterial line features can also improve performance (AUROC 0.69 ± 0.07, $$p < 0.01$$ p < 0.01 ), and benefit from tensor decomposition (AUROC 0.71 ± 0.07, $$p = 0.01$$ p = 0.01 ). Adding EHR data features to a tensor-reduced signal model further improves performance (AUROC 0.77 ± 0.06, $$p < 0.01$$ p < 0.01 ). Despite reduction in performance going from an EHR data-informed model to a tensor-reduced waveform data model, the signals-informed model offers distinct advantages. The first is that predictions can be made on a continuous basis in real-time, and second is that these predictions are not limited by the availability of EHR data. Additionally, structuring the waveform features as a tensor conserves structural and temporal information that would otherwise be lost if the data were presented as flat vectors.

Few studies examining the patient outcomes of concurrent neurological manifestations during acute COVID-19 leveraged multinational cohorts of adults and children or distinguished between central and peripheral nervous system (CNS vs. PNS) involvement. Using a federated multinational network in which local clinicians and informatics experts curated the electronic health records data, we evaluated the risk of prolonged hospitalization and mortality in hospitalized COVID-19 patients from 21 healthcare systems across 7 countries. For adults, we used a federated learning approach whereby we ran Cox proportional hazard models locally at each healthcare system and performed a meta-analysis on the aggregated results to estimate the overall risk of adverse outcomes across our geographically diverse populations. For children, we reported descriptive statistics separately due to their low frequency of neurological involvement and poor outcomes. Among the 106,229 hospitalized COVID-19 patients (104,031 patients ≥18 years; 2,198 patients

The quick Sequential Organ Failure Assessment (qSOFA) system identifies an individual's risk to progress to poor sepsis-related outcomes using minimal variables. We used Support Vector Machine, Learning Using Concave and Convex Kernels, and Random Forest to predict an increase in qSOFA score using electronic health record (EHR) data, electrocardiograms (ECG), and arterial line signals. We structured physiological signals data in a tensor format and used Canonical Polyadic/Parallel Factors (CP) decomposition for feature reduction. Random Forests trained on ECG data show improved performance after tensor decomposition for predictions in a 6-h time frame (AUROC 0.67 ± 0.06 compared to 0.57 ± 0.08, p = 0.01 ). Adding arterial line features can also improve performance (AUROC 0.69 ± 0.07, p < 0.01 ), and benefit from tensor decomposition (AUROC 0.71 ± 0.07, p = 0.01 ). Adding EHR data features to a tensor-reduced signal model further improves performance (AUROC 0.77 ± 0.06, p < 0.01 ). Despite reduction in performance going from an EHR data-informed model to a tensor-reduced waveform data model, the signals-informed model offers distinct advantages. The first is that predictions can be made on a continuous basis in real-time, and second is that these predictions are not limited by the availability of EHR data. Additionally, structuring the waveform features as a tensor conserves structural and temporal information that would otherwise be lost if the data were presented as flat vectors. [ABSTRACT FROM AUTHOR]

Introduction: Emotional awareness and emotion regulation are crucial for cognitive and socio-emotional development in children. School-based interventions on socio-emotional skills have the potential to prevent these problems and promote well-being of children. The Japanese schoolbased program, Universal Unified Prevention Program for Diverse Disorders (Up2-D2), has shown preventive effects on mental health of children in Japan. The aims of this protocol paper are to describe the unique process of adapting the Up2-D2 from Eastern to Western context, and to present a feasibility study of the intervention, conducted in Finland. Methods: The cultural adaptation process started with the linguistic translation of materials, followed by the modification of language to fit the Finnish context. While the Japanese ideology was saved, some content was adapted to fit Finnish school children. Further modifications were made based on feedback from pupils and teachers. The Finnish version of the program was named "Let's learn about emotions" and consisted of 12 sessions and targeted 8- to 12-year-old pupils. A teacher education plan was established to assist Finnish teachers with the intervention, including a workshop, teachers' manual, brief introductory videos, and online support sessions. A feasibility study involving 512 4th graders in the City of Hyvinkää, South of Finland, was conducted. It assessed emotional and behavioral problems, classroom climate, bullying, loneliness, perception of school environment, knowledge of emotional awareness, and program acceptability. Discussion: The originality of this study underlies in the East-West adaptation of a cognitive behavioral therapy-based program. If promising feasibility findings are replicated in Finland, it could pave the way for further research on implementing such programs in diverse contexts and cultures, promoting coping skills, awareness, social skills and early prevention of child mental health problems. Ethics: The ethical board of the University of Turku gave ethics approval for this research. The educational board of the City of Hyvinkää accepted this study. [ABSTRACT FROM AUTHOR]

Refractory multi-principal element alloys constitute a novel category of metallic materials, and they have good properties, particularly at elevated temperatures. Currently, casting and powder metallurgy stand as the two predominant manufacturing routes. This study focuses on the production of the W19.8Mo19.8Nb19.8Ti19.8Cr19.8Al1 (At. %) alloy via the mechanical alloying process. Analyses of morphology and particle size distribution at intervals of 12, 24, 36, and 48 hours of milling showed a gradual decrease in particle size according to increase in milling time. The XRD showed the presence of the BCC phase after 48 hours of milling, and the application of the Williamson-Hall methods indicated that after 12, 24, and 36 hours of milling, the crystallite size decreased and the microstrain increased gradually. However, after 48 hours of milling, there was an increase in these values, suggesting the reordering of the structure of this alloy. In addition, Fe contamination increases significantly for higher milling time.

Objectives: In this literature review, we describe the progress of Indonesia's NBS program (which is heavily centered on CH screening), its current pilot projects, and what lies ahead for this program. Setting: Since its conception began with congenital hypothyroidism (CH) screening, Indonesia has experienced plodding progress in NBS. There is a shortage of literature discussing the history, or the lack of, and journey of NBS in Indonesia. Methods: We searched for literature in Pubmed and Google Scholar with keywords such as “Newborn Screening, “Neonatal Screening,'' “Indonesia,'' “Asia Pacific,'' “Congenital Hypothyroidism,'' “Congenital Adrenal Hyperplasia,””Critical Congenital Heart Disease,” “Hearing Loss,” and “Inborn Error of Metabolism.” Results: The only mandatory and regulated NBS program in Indonesia is congenital hypothyroid (CH) screening, with some pilot projects being conducted on screening for congenital adrenal hyperplasia (CAH), critical congenital heart disease (CCHD), hearing loss, and to a lesser extent, inborn error of metabolisms (IEMs). Conclusion: Despite the evidence and benefits, the government does not mandate or regulate newborn diseases such as CHD, CAH, hearing loss, and IEMs. The lack of regulation exists despite multiple pilot projects and studies showing a benefit in at least trying to screen newborns for those conditions.

Objective: Laparoscopic cholecystectomy is currently the gold standard for treating symptomatic gallstone disease. Despite its success, approximately 10% of patients may experience persistent biliary symptoms, leading to the post-cholecystectomy syndrome. A remnant gallbladder with cystic duct or bile duct stones is one of the causes of this syndrome. The objective of this study was to shed light on the clinical manifestations, evaluation, therapeutic strategies, and outcomes associated with laparoscopic management of symptomatic remnant gallbladders. Methods: This was a retrospective study, conducted over a five-year period (January 2017 to December 2022) at Apollo Hospitals in South India. All patients who underwent laparoscopic completion cholecystectomy for a remnant gall bladder were included. The following data were collected: patient demographics, symptoms, preoperative investigations, intraoperative details and post operative outcomes. Results: In total, 36 patients were included and analysed. The majority of patients were male (25, 69.4%), with a mean age of 50.7 ± 12.1 years. The most common presentation was pain in the upper abdomen or right upper quadrant region (24, 66.7%). The laparoscopic approach was attempted in all patients, with a success rate of 94.4%. Two patients required conversion to open surgery. Cholecystoenteric fistula to the colon was observed in one patient. Choledocholithiasis was observed in 7 patients (19.4%), and stone clearance was successfully achieved using endoscopic retrograde cholangiopancreatography in all patients preoperatively. Conclusion: Incomplete gall bladder removal either intentionally or unintentionally leaves a remnant gall bladder that is at risk for stone formation and infection. Patients who have this clinical entity with symptoms require a redo or complete cholecystectomy, a complex procedure associated with certain risks. This study highlights the feasibility and safety of laparoscopic completion cholecystectomy for the management of remnant gallbladder with cystic duct or bile duct stones.

Abstract When processed conventionally, aluminum-bronze alloys with high mechanical strength require machining after the raw state of fusion, and the waste (chips), if not reused, can cause problems for the environment and costs for the company. Therefore, this article proposes an alternative for recycling aluminum bronze through the new route via Powder Metallurgy (PM), analyzing the resulting microstructure. This study compares the microstructures of the aluminum bronze derived from extraction (the samples received - SR) and the state after the powder metallurgy (PM) process with the addition of vanadium carbides (VC). The study also analyzes the distribution of VC in the microstructure of the PM composite as well as the influence of the TQ30 heat treatment on this composite. For the PM process, aluminum alloy and bronze chips were ground together with vanadium carbide (VC) in a high-energy mill for 50 hours. The powders obtained were pressed uniaxially (400 MPa) to achieve good compaction. The samples were then sintered (900°C/lh), water quenched (900°C/2h), and subjected to treatment according to the TQ30 standard, which, in addition to the previous treatments, also includes tempering at 500°C for 2 hours (ASTM B150/B150M-12 standard). The microstructure observed in the SR samples was martensitic (in needles), with secondary phases dispersed in the matrix. On the other hand, the microstructure of the PM samples showed equiaxed grains of the alpha phase (a), as well as the secondary phases kapa (k) and beta line (β1), in contrast to the needle-shaped microstructure of the conventional melting process.

Graduate students consider research as the most challenging task in their studies. Aside from the researches that they do in their course work, they are also required to conduct, write, and defend their thesis or dissertation which is the terminal output of the graduate program. In spite of the challenges in research work, there are graduate students who did researches that were published in local and international journals. Though publication is not yet a requirement, they decided to do research and had them published. However, the Commission on Higher Education issued CMO 15 s. 2019 “Policies, Standards and Guidelines for Graduate Programs” requiring publication of a research work in an internationally or nationally refereed and indexed journal or have a juried creative work outlet before a graduate student earns the degree. In consideration of this policy, the study looked into the motivations, experiences and needs of selected graduate students who have engaged in research and publication. The findings revealed that their motivations are professors’ encouragement, course requirements, new learning experience, collaboration, and promotion. In describing their experiences, they found it enriching, collaborative, fulfilling, and challenging. Their needs are mentoring, research capability building, having a research community, financial support and incentives, and providing relevant information. From the findings, it can be concluded that graduate students will be able to do research with the right motivation and support from the faculty. Research and publication are fulfilling and enriching but challenging. The experiences and needs of the selected graduate students can be used as inputs in the development of a research and publication program for graduate students.

Background: Occult fractures may cause multiple morbidities. If occult fractures were detected earlier, complications may be preventable. This umbrella review and updated meta-analysis will aim to evaluate the use of imaging modalities in detecting occult scaphoid and hip fractures. Methods: The protocol for this study is available in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42024525388). The literature search started and ended on 17 March 2024. We searched seven academic databases: MEDLINE, Cochrane Library, Pubmed, Science Direct, Google Scholar, WHO International Clinical Trials Registry Platform, and The Joanna Briggs Institute (JBI) database. The meta-analysis was conducted with the STATA program using the “midas” command. Results: There are four systematic reviews evaluating occult hip and femoral fractures with 6174 patients and two reviews evaluating occult scaphoid fractures with 1355 patients. The prevalence of occult scaphoid fracture and occult hip and femoral fractures is 23.87% (95% CI 18.25–29.49) and 44.8% (95% CI 39.38–51.4), respectively. Magnetic resonance imaging (MRI) had the best posterior probability of positive likelihood ratio (LR+) with 95% and 96% and negative likelihood ratio (LR-) with 0.15% and 1% for both occult scaphoid and hip fractures, respectively, assuming a 25% baseline. MRI could both confirm and exclude occult hip fractures while it can only confirm occult scaphoid fractures. Bone scans are inappropriate for either type of occult fractures The level of evidence for occult scaphoid fracture is weak while it is suggestive for occult hip fractures. Conclusion: The findings strengthen the use of MRI after an initially negative radiograph fracture for occult hip and femoral fractures, with a CT scan as a viable second option.

In the frame of the H2020 MORE&LESS project co-funded by European Commission, a test campaign for a hypersonic vehicle demonstrator took place at the INCAS Trisonic Facility. CFD analysis was used to quantify the effects of the wind tunnel model support, the closed engine nacelle, and to perform the Reynolds number extrapolation. Three sets of simulations were used in order to generate the corrections. The wind tunnel configuration with sting, sting cavity, and closed nacelle was used as the baseline, with the aim of matching the experimental results as precisely as possible. A configuration with a flow-through nacelle and the shock cone in the appropriate position for each Mach number and no sting or cavity was used to determine the effect of the sting and the closed nacelle. For the Reynolds extrapolation, a 1:1 model was used, with the boundary conditions deriving from the theoretical trajectory of the vehicle. The CFD results for the wind tunnel configuration closely align with the experimental data. Significant differences between the three configurations can be observed just for the pitching moment, and those are caused by the presence of the sting and the open nacelle. The difference in Reynolds number does not seem to have a significant effect on the aerodynamic coefficients.

Background and Objectives: Myocardial bridging (MB) is still not yet considered a significant finding in Indonesia both radiographically and clinically. Hence, this article aims to assess the prevalence of MB using multi-detector computed tomography (MDCT) and look at factors contributing to stenosis amongst patients with MB. Materials and Methods: This study is cross-sectional in a single centre, with consecutive sampling, looking at all patients who underwent a multi-detector computed tomography (MDCT) scan from February 2021 until February 2023. GraphPad Prism version 9.0.0 for Windows (GraphPad Software, Boston, MA, USA) was used to analyse the results. Results: There are 1029 patients with an MB, yielding a prevalence of 44.3% (95%CI 42.3–46.4). The left anterior descending vessel is the most commonly implicated, with 99.6%. Among those with stenosis, the middle portion of the bridging vessel is the most common site of stenosis (n = 269), followed by the proximal portion (n = 237). The severity of stenosis is more often moderate, with 30–50% (n = 238). Females (odds ratio [OR] of 1.8, 95%CI 1.4–2.3; p-value < 0.0001), older age (t-value 5.6, p-value < 0.0001), symptomatic patients (OR 1.4, 95% CI 1.1–1.9; p-value = 0.013), and higher mean coronary artery calcium score (t-value 11.3, p-value < 0.0001) are more likely to have stenosis. The degree of stenosis is significantly higher in the proximal stenosis group than in the middle stenosis group (t-value 27, p-value < 0.0001). Conclusions: Our research demonstrates that MB may prevent atheromatosis of the coronary segment distal to the MB and predispose the development of atherosclerosis in the section proximal to the bridge.

Introduction: Osteogenesis imperfecta (OI) is a heritable skeletal disorder and comprises various subtypes that differ in clinical presentation, with Type I considered the least severe and Types III/IV the most severe forms. The study aim was to understand the OI patient diagnostic and treatment journey across Europe., Methods: We conducted a qualitative, descriptive study to understand the OI patient journey. A selection of people with OI/their caregivers and clinicians involved in OI-patient care from across Europe were interviewed using a specially developed questionnaire., Results: Between May 2022 and July 2022, 22 people with OI/caregivers and 22 clinicians (endocrinologists, orthopaedic surgeons, geneticists and metabolic specialists) from across Europe were interviewed. Our study showed various areas of concerns for the OI community. Timely diagnosis of OI is essential; misdiagnoses and a delay to treatment initiation are all too common. There are a lack of consensus guidelines regarding optimal treatments (including when bisphosphonate therapy should be initiated and the route of administration) and patient management throughout the duration of the patient's life. Adult OI patients do not have a medical home and are often managed by endocrinologists and rheumatologists. Adult care is often reactive based on the development of new symptoms. The psychosocial burden of OI impacts on the patient's quality of life., Conclusions: There is an urgent need for increased awareness about OI and its wide range of symptoms. In particular, there is a need for consensus guidelines outlining the optimum care throughout the duration of the OI patient's life., (© 2024. The Author(s).)

Smartphone applications are one of the main delivery modalities in digital health. Many of these mHealth apps use gamification to engage users, improve user experience, and achieve better health outcomes. Yet, it remains unclear whether gamified approaches help to deliver effective, safe, and clinically beneficial products to users. This study examines the compliance of 69 gamified mHealth apps with the EU Medical Device Regulation and assesses the specific risks arising from the gamified nature of these apps. Of the identified apps, 32 (46.4%) were considered non-medical devices; seven (10.1%) were already cleared/approved by the regulatory authorities, and 31 (44.9%) apps were assessed as likely non-compliant or potentially non-compliant with regulatory requirements. These applications and one approved application were assessed as on the market without the required regulatory approvals. According to our analysis, a higher proportion of these apps would be classified as medical devices in the US. The level of risk posed by gamification remains ambiguous. While most apps showed only a weak link between the degree of gamification and potential risks, this link was stronger for those apps with a high degree of gamification or an immersive game experience., (© 2024. The Author(s).)

Background Recent advancements, including image processing capabilities, present new potential applications of large language models such as ChatGPT (OpenAI), a generative pretrained transformer, in radiology. However, baseline performance of ChatGPT in radiology-related tasks is understudied. Purpose To evaluate the performance of GPT-4 with vision (GPT-4V) on radiology in-training examination questions, including those with images, to gauge the model's baseline knowledge in radiology. Materials and Methods In this prospective study, conducted between September 2023 and March 2024, the September 2023 release of GPT-4V was assessed using 386 retired questions (189 image-based and 197 text-only questions) from the American College of Radiology Diagnostic Radiology In-Training Examinations. Nine question pairs were identified as duplicates; only the first instance of each duplicate was considered in ChatGPT's assessment. A subanalysis assessed the impact of different zero-shot prompts on performance. Statistical analysis included χ 2 tests of independence to ascertain whether the performance of GPT-4V varied between question types or subspecialty. The McNemar test was used to evaluate performance differences between the prompts, with Benjamin-Hochberg adjustment of the P values conducted to control the false discovery rate (FDR). A P value threshold of less than.05 denoted statistical significance. Results GPT-4V correctly answered 246 (65.3%) of the 377 unique questions, with significantly higher accuracy on text-only questions (81.5%, 159 of 195) than on image-based questions (47.8%, 87 of 182) (χ 2 test, P < .001). Subanalysis revealed differences between prompts on text-based questions, where chain-of-thought prompting outperformed long instruction by 6.1% (McNemar, P = .02; FDR = 0.063), basic prompting by 6.8% ( P = .009, FDR = 0.044), and the original prompting style by 8.9% ( P = .001, FDR = 0.014). No differences were observed between prompts on image-based questions with P values of .27 to >.99. Conclusion While GPT-4V demonstrated a level of competence in text-based questions, it showed deficits interpreting radiologic images. © RSNA, 2024 See also the editorial by Deng in this issue.

Among the rapid integration of artificial intelligence in clinical settings, large language models (LLMs), such as Generative Pre-trained Transformer-4, have emerged as multifaceted tools that have potential for health-care delivery, diagnosis, and patient care. However, deployment of LLMs raises substantial regulatory and safety concerns. Due to their high output variability, poor inherent explainability, and the risk of so-called AI hallucinations, LLM-based health-care applications that serve a medical purpose face regulatory challenges for approval as medical devices under US and EU laws, including the recently passed EU Artificial Intelligence Act. Despite unaddressed risks for patients, including misdiagnosis and unverified medical advice, such applications are available on the market. The regulatory ambiguity surrounding these tools creates an urgent need for frameworks that accommodate their unique capabilities and limitations. Alongside the development of these frameworks, existing regulations should be enforced. If regulators fear enforcing the regulations in a market dominated by supply or development by large technology companies, the consequences of layperson harm will force belated action, damaging the potentiality of LLM-based applications for layperson medical advice., Competing Interests: Declaration of interests SG is an advisory group member of the EY-coordinated study on regulatory governance and innovation in the field of medical devices conducted on behalf of the Directorate General for Health and Food Safety of the European Commission. SG has or has had consulting relationships with Una Health, Lindus Health, Flo, Thymia, FORUM Institut für Management, High-Tech Gründerfonds Management, and Ada Health, and holds share options in Ada Health. JNK received funding from GlaxoSmithKline; has or has had consulting relationships with Owkin, DoMore Diagnostics, Histofy, and Panakeia; received honoraria for lectures and events from Bayer, Eisai, Merck Sharp & Dohme, Bristol Myers Squibb, Roche, Pfizer, and Fresenius; participated on boards of Bayer, Eisai, Merck Sharp & Dohme, Bristol Myers Squibb, Roche, and Pfizer; and has a leadership role and holds stock in StratifAI. OF has worked as a freelance doctor for Clinical Research Services Berlin, and has a leadership role and holds stock in WhalesDontFly. ICW declares no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Older adults are at risk of adverse drug events during transition of care from hospital to community, thus optimal communication about medications at discharge is essential. Standardization of medication discharge plan (MDP) is lacking. This study aimed to (1) create a standardized MDP for older adults using consensus-based principles, (2) create a short-version MDP and (3) generate a practical guide. Modified Delphi was used to establish consensus on guiding principles for the MDP. Additionally, participants were asked about guiding principles deemed most essential, patient prioritization, the format and mode of transmission of the MDP. Twenty-six guiding principles reached consensus, with 17 prioritized for a short-version MDP. The practical guide includes explanations of the guiding principles, criteria for patient selection and recommendations on the format and mode of transmission. The results of this study will assist implementation of MDPs when older adults are discharged from hospital., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Purpose: Patients with advanced renal cell carcinoma (RCC) face significant challenges, stemming both from the complexities of the disease itself and the adverse effects of treatments. This study evaluated the feasibility and acceptability of a mobile health (mHealth) application tailored for education and symptom management of patients with advanced RCC receiving combined immune checkpoint inhibitor and tyrosine kinase inhibitor (ICI-TKI) therapy., Methods: The primary end points were acceptability and feasibility. Acceptability was defined as the proportion of patients approached who consented to participate, setting a benchmark of at least 50% for this metric. Feasibility was gauged by the completion rate of the intervention among the participants; it required at least 50% of participants to fully complete the intervention and at least 70% to finish half of the administered questionnaires. The secondary end points included knowledge assessment and patient-reported outcomes (PROs). PROs were evaluated using validated instruments. To discern the changes between pre- and post-educational module quiz scores, we used the Wilcoxon signed-rank test. Time-course data of PROs were visualized using line plots and then compared using paired t-tests., Results: From November 2022 to July 2023, 20 of 22 (90%) patients approached for the study consented and enrolled. Of the enrolled patients, 60% completed all questionnaires and knowledge assessments at every time point and 75% completed at least half of the surveys and questionnaires. Significant pre/post differences were noted in two of six quizzes in the knowledge assessment. This study population did not experience a significant change in PRO scores after starting therapy., Conclusion: The mHealth application designed for education and symptom management in patients with advanced RCC undergoing combination ICI-TKI has proven to be both acceptable and feasible, meeting previous research benchmarks.

Viral haemorrhagic fevers (VHF) pose a significant threat to human health. In recent years, VHF outbreaks caused by Ebola, Marburg and Lassa viruses have caused substantial morbidity and mortality in West and Central Africa. In 2022, an Ebola disease outbreak in Uganda caused by Sudan virus resulted in 164 cases with 55 deaths. In 2023, a Marburg disease outbreak was confirmed in Equatorial Guinea and Tanzania resulting in over 49 confirmed or suspected cases; 41 of which were fatal. There are no clearly defined correlates of protection against these VHF, impeding targeted vaccine development. Any vaccine developed should therefore induce strong and preferably long-lasting humoral and cellular immunity against these viruses. Ideally this immunity should also cross-protect against viral variants, which are known to circulate in animal reservoirs and cause human disease. We have utilized two viral vectored vaccine platforms, an adenovirus (ChAdOx1) and Modified Vaccinia Ankara (MVA), to develop a multi-pathogen vaccine regime against three filoviruses (Ebola virus, Sudan virus, Marburg virus) and an arenavirus (Lassa virus). These platform technologies have consistently demonstrated the capability to induce robust cellular and humoral antigen-specific immunity in humans, most recently in the rollout of the licensed ChAdOx1-nCoV19/AZD1222. Here, we show that our multi-pathogen vaccines elicit strong cellular and humoral immunity, induce a diverse range of chemokines and cytokines, and most importantly, confers protection after lethal Ebola virus, Sudan virus and Marburg virus challenges in a small animal model., Competing Interests: TL reports consulting fees from Vaccitech on an unrelated project, an honorarium from Seqirus, grant support from the DHSC for this work, and is named as an inventor on a patent application for a vaccine against SARS-CoV-2. SG is named as an inventor on patents covering use of ChAdOx1-vectored vaccines and a vaccine against SARS-CoV-2., (Copyright: © 2024 Flaxman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Although licensed vaccines against influenza virus have been successful in reducing pathogen-mediated disease, they have been less effective at preventing viral infection of the airways and current seasonal updates to influenza vaccines do not always successfully accommodate viral drift. Most licensed influenza and recently licensed RSV vaccines are administered via the intramuscular route. Alternative immunisation strategies, such as intranasal vaccinations, and "prime-pull" regimens, may deliver a more sterilising form of protection against respiratory viruses. A bivalent ChAdOx1-based vaccine (ChAdOx1-NP + M1-RSVF) encoding conserved nucleoprotein and matrix 1 proteins from influenza A virus and a modified pre-fusion stabilised RSV A F protein, was designed, developed and tested in preclinical animal models. The aim was to induce broad, cross-protective tissue-resident T cells against heterotypic influenza viruses and neutralising antibodies against RSV in the respiratory mucosa and systemically. When administered via an intramuscular prime-intranasal boost (IM-IN) regimen in mice, superior protection was generated against challenge with either RSV A, Influenza A H3N2 or H1N1. These results support further clinical development of a pan influenza & RSV vaccine administered in a prime-pull regimen., (© 2024. The Author(s).)

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time., Purpose:  The tele-intensive care unit (tele-ICU) pharmacist facilitates patient-specific diabetic ketoacidosis (DKA) treatment utilizing guideline-directed therapy. This study was designed to determine how patient-specific interventions by a tele-ICU pharmacist affected patients with DKA compared to the standard of care., Methods: This retrospective cohort study utilized custom reports and manual chart review to evaluate the electronic health records of patients 18 years or older who received continuous intravenous insulin and were admitted for DKA between January 2019 and December 2020. The primary endpoint was time to DKA resolution, defined by the patient meeting at least 2 of the following criteria: a serum bicarbonate concentration of at least 18 mEq/L, an arterial pH of greater than 7.3, and closure of the anion gap (less than or equal to 12 mEq/L)., Results: Patients treated with tele-ICU pharmacist patient-specific interventions reached DKA resolution 7.32 hours earlier than patients treated with the standard of care (22.16 vs 29.48 hours; P = 0.0019). There was no statistically significant difference between the groups for ICU length of stay, time until subcutaneous insulin administration, incidence of hypoglycemia, incidence of severe hypoglycemia, and sodium bicarbonate use. In patients who received a tele-ICU pharmacist intervention, there was a statistically significant increase in the volume for fluid resuscitation and the amount of total continuous insulin infused after ICU admission and a statistically significant reduction in the time between laboratory draws., Conclusion: Treatment of patients with tele-ICU pharmacist patient-specific interventions was associated with faster DKA resolution, more frequent laboratory monitoring, and a higher volume of insulin and fluids infused than in patients treated with protocol-driven therapy., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: The increase in gabapentinoid prescribing is paralleling the increase in serious harms. To describe the low back pain workers compensation population whose management included a gabapentinoid between 2010 and 2017, and determine secular trends in, and factors associated with gabapentinoid use., Methods: We analysed claim-level and service-level data from the Victorian workers' compensation programme between 1 January 2010 and 31 December 2017 for workers with an accepted claim for a low back pain injury and who had programme-funded gabapentinoid dispensing. Secular trends were calculated as a proportion of gabapentinoid dispensings per year. Poisson, negative binomial and Cox hazards models were used to examine changes over time in incidence and time to first dispensing., Results: Of the 17 689 low back pain claimants, one in seven (14.7%) were dispensed at least one gabapentinoid during the first 2 years (n=2608). The proportion of workers who were dispensed a gabapentinoid significantly increased over time (7.9% in 2010 to 18.7% in 2017), despite a reduction in the number of claimants dispensed pain-related medicines. Gabapentinoid dispensing was significantly associated with an opioid analgesic or anti-depressant dispensing claim, but not claimant-level characteristics. The time to first gabapentinoid dispensing significantly decreased over time from 311.9 days (SD 200.7) in 2010 to 148.2 days (SD 183.1) in 2017., Conclusions: The proportion of claimants dispensed a gabapentinoid more than doubled in the period 2010-2017; and the time to first dispensing halved during this period., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Dogs are exposed to increasing environmental risk for developing heat-related illness (HRI), with 2022 recorded as the hottest year to date in the UK and most of Europe., Methods: This study used VetCompass data to report the incidence risk, event fatality rate and canine risk factors for HRI in dogs presenting to Vets Now emergency care practices in the UK during 2022., Results: From the clinical records of 167,751 dogs under care at Vets Now emergency clinics in 2022, 384 HRI events were identified. The 2022 incidence risk of HRI within the Vets Now caseload was 0.23% (95% confidence interval [CI]: 0.21%‒0.25%), with an event fatality rate of 26.56% (95% CI: 21.66%-32.25%). Multivariable analysis identified breed, age and sex/neuter status as risk factors for HRI. Brachycephalic dogs had 4.21 times the odds of HRI compared to mesocephalic dogs (95% CI: 3.22‒5.49, p < 0.001)., Limitations: The clinical data used in this study were not primarily recorded for research and had some substantial levels of missing data (especially patient bodyweight)., Conclusion: In order to protect canine welfare, improved long-term mitigation strategies are urgently needed to minimise HRI risk and associated fatality in UK dogs., (© 2024 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)