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Tracheal intubation is a fundamental facet of airway management, for which the importance of achieving success at the first attempt is well recognized. Failure to do so can lead to significant morbidity and mortality if there is inadequate patient oxygenation by alternate means. The evidence supporting the benefits of a videolaryngoscope in attaining this objective is now overwhelming (in adults). This has led to its increasing recognition in international airway management guidelines and its promotion from an occasional airway rescue tool to the first-choice device during routine airway management. However, usage in clinical practice does not currently reflect the increased worldwide availability that followed the upsurge in videolaryngoscope purchasing during the coronavirus disease 2019 pandemic. There are a number of obstacles to widespread adoption, including lack of adequate training, fears over de-skilling at direct laryngoscopy, equipment and cleaning costs, and concerns over the environmental impact, among others. It is now clear that in order for patients to benefit maximally from the technology and for airway managers to fully appreciate its role in everyday practice, proper training and education are necessary. Recent research evidence has addressed some existing barriers to default usage, and the emergence of techniques such as awake videolaryngoscopy and video-assisted flexible (bronchoscopic) intubation has also increased the scope of clinical application. Future studies will likely further confirm the superiority of videolaryngoscopy over direct laryngoscopy, therefore, it is incumbent upon all airway managers (and their teams) to gain expertise in videolaryngoscopy and to use it routinely in their everyday practice..

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Background: Athlete injury risk assessment and management is an important, yet challenging task for sport and exercise medicine professionals. A common approach to injury risk screening is to stratify athletes into risk groups based on their performance on a test relative to a cut-off threshold. However, one potential reason for ineffective injury prevention efforts is the over-reliance on identifying these 'at-risk' groups using arbitrary cut-offs for these tests and measures. The purpose of this commentary is to discuss the conceptual and technical issues related to the use of a cut-off in both research and clinical practice. Clinical Question: How can we better assess and interpret clinical tests or measures to enable a more effective injury risk assessment in athletes? Key Results: Cut-offs typically lack strong biologic plausibility to support them; and are typically derived in a data-driven manner and thus not generalizable to other samples. When a cut-off is used in analyses, information is lost, leading to potentially misleading results and less accurate injury risk prediction. Dichotomizing a continuous variable using a cut-off should be avoided. Using continuous variables on its original scale is advantageous because information is not discarded, outcome prediction accuracy is not lost, and personalized medicine can be facilitated. Clinical Application: Researchers and clinicians are encouraged to analyze and interpret the results of tests and measures using continuous variables and avoid relying on singular cut-offs to guide decisions. Injury risk can be predicted more accurately when using continuous variables in their natural form. A more accurate risk prediction will facilitate personalized approaches to injury risk mitigation and may lead to a decline in injury rates. Level of Evidence: 5.

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BACKGROUND: The optimization of athlete training load is not a new concept; however in recent years, the concept of "load management" is one of the most widely studied and divisive topics in sports science and medicine. PURPOSE: Discuss the challenges faced by sports when utilizing training load monitoring and management, with a specific focus on the use of data to inform load management guidelines and policies/mandates, their consequences, and how we move this field forward. CHALLENGES: While guidelines can theoretically help protect athletes, overzealous and overcautious guidelines may restrict an athlete's preparedness, negatively influence performance, and increase injury risk. Poor methods, wrong interpretation of study findings, and faulty logic do not allow for systematic scientific evaluations to inform guidelines. Practical Solutions: Guidelines and mandates should be developed through a systematic research process with stronger research designs and clear research questions. Collaborating with statistical and epidemiological experts is essential. Implementing open science principles and sharing all sports training load data increase transparency and allow for more rapid and valid advancements in knowledge. Practitioners should incorporate multiple data streams and consider individual athlete responses, rather than applying broad guidelines based on average data. CONCLUSION: Many current training load guidelines and mandates in sports come from good intentions; however, they are arbitrary without sound knowledge of the underlying scientific principles or methods. Common sense guidelines are helpful when there is sparse literature, but they should be careful to avoid arbitrarily choosing findings from weak research. Without precise scientific inquiries, implementing training load interventions or guidelines can have negative implications.

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The Cochrane systematic review and meta-analysis published in 2022 that compared videolaryngoscopy (VL) with direct laryngoscopy (DL) for facilitating tracheal intubation in adults found that all three types of VL device (Macintosh-style, hyper-angulated and channeled) reduced the risk of failed intubation and increased the likelihood of first-pass success. We report the findings of a subgroup re-analysis of the 2022 Cochrane meta-analysis data focusing on the Macintosh-style VL group. This was undertaken to establish whether sufficient evidence exists to guide airway managers in making purchasing decisions for their local institutions based upon individual device-specific performance. This re-analysis confirmed the superiority of Macintosh-style VL over Macintosh DL in elective surgical patients, with similar efficacy demonstrated between the Macintosh-style VL devices examined. Thus, when selecting which VL device(s) to purchase for their hospital, airway managers decisions are likely to remain focused upon issues such as financial costs, portability, cleaning schedules and previous device experience.

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With varying hydrofluoric acid (HF) concentrations under three etching conditions, we presented a comparative study of the effects of both the ordered and randomly ternary mixed terminated Ti3C2Tx surfaces with a wide variation of O/OH/F stoichiometry on the thermodynamic stability and electronic properties. Regardless of the HF concentration, an OH-rich surface is found to be thermodynamically stable and the electrical conductivity of Ti3C2Tx is substantially affected by the OH concentration. The charge density difference and electron localization function demonstrated a significant electron localization at the hydroxyl group on the O/OH/F mixed terminated surface, which could yield a locally induced dipole on the surface that renders favorable reaction sites on the functionalized surface. In addition, a large tunability in the work function (ΔΦ âˆ¼ 3.5 eV) is predicted for Ti3C2Tx. These findings provide a pathway for strategically tuning the electronic and structural properties of Ti3C2 MXenes etched with HF.

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Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing cancer cells, such as those in advanced prostate cancer. This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant prostate cancer (mCRPC), primarily taxane pretreated. Ninety-seven patients received ≥1 intravenous dose ranging from 0.001 to 2.0 mg weekly or every 2 weeks. MTD was identified as 1.5 mg i.v. weekly via a 3-step dose. The most common treatment-related adverse events were cytokine release syndrome (CRS; 72%), fatigue (45%), and myalgia (34%). CRS occurred primarily during cycle 1 and improved with premedication and step dosing. Prostate-specific antigen (PSA) and RECIST responses across cohorts were encouraging [49% PSA50; 24% objective response rate (ORR)], with greater frequency at target doses ≥0.75 mg (59% PSA50; 41% ORR). Xaluritamig is a novel immunotherapy for prostate cancer that has shown encouraging results supporting further development. SIGNIFICANCE: Xaluritamig demonstrated encouraging responses (PSA and RECIST) compared with historical established treatments for patients with late-line mCRPC. This study provides proof of concept for T-cell engagers as a potential treatment for prostate cancer, validates STEAP1 as a target, and supports further clinical investigation of xaluritamig in prostate cancer. See related commentary by Hage Chehade et al., p. 20. See related article by Nolan-Stevaux et al., p. 90. This article is featured in Selected Articles from This Issue, p. 5.

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ABSTRACT: McNeill, C, Beaven, CM, McMaster, DT, Ward, P, and Gill, N. Eccentric force-velocity-load relationship in trained rugby union athletes. J Strength Cond Res 38(3): 549-555, 2024-The force-velocity relationship is traditionally believed to resemble a hyperbolic shape, known as the "force-velocity curve." However, there is less evidence regarding this relationship during eccentric muscle action in multijoint isotonic exercise, especially in applied settings. The purpose of this study was to investigate the force-velocity-load relationship in an incremental eccentric back squat test. In addition, 37 professional male rugby union athletes were recruited to participate. Separate generalized linear mixed models were used to analyze the effect of barbell load on relative eccentric peak force (REPF), relative eccentric mean force (REMF), eccentric peak velocity (EPV), and eccentric mean velocity (EMV). A significant effect of load ( p < 0.05) was observed for each of the eccentric variables tested. Each increase in barbell load tended to result in a linear increase in REMF and a decrease in EMV and EPV; however, we observed a plateauing effect for REPF as load increased. These results show that for "peak" variables lighter loads produced similar magnitudes of force, but generally moved at higher velocities than heavier loads. These observations suggest that the eccentric force-velocity-load relationship may vary depending on the parameters used. Quantifying rapid, multijoint eccentric performance is justified as it seems to provide valuable insight into individual athletic capability and training program design. Further research may investigate the responsiveness of the qualities to training and the causal nature of eccentric characteristics and athletic performance.

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PURPOSE: Despite data-driven consensus recommendations, there remains significant nonadherence to genetic screening and testing. More than 300,000 patients are diagnosed with breast cancer annually, with one third of these estimated to be eligible for homologous recombination deficiency (HRD)/BRCA testing following National Comprehensive Cancer Network (NCCN) guidelines. Only 35% of eligible patients are referred for genetic counseling. METHODS: The goal of this project was to apply NCCN guidelines for germline genetic testing to all new patients with breast cancer within a large community oncology practice to improve HRD/BRCA testing. Plan-Do-Study-Act methodology was used, and cycles were built on a proven teaching infrastructure. In cycle 1, providers were educated and directed to use electronic health record (EHR) templates in the setting of an initial diagnosis visit and treatment planning. Discreet data fields were created in the EHR during cycle 2 to streamline and automate the process. Appropriate patients were referred to the genetics team for further evaluation, counseling, and testing. Adherence to the plan was maintained and measured using data analytic reports and chart audits. RESULTS: Of the 1,203 patients with breast cancer eligible for inclusion, 1,200 (99%) were screened according to NCCN guidelines. Of the screened patients, 631 (52.5%) met the referral/testing criteria. In total, 585 (92.7%) of the 631 were referred to a genetic specialist. Seven percent had previous referrals. A total of 449 (71%) patients were acceptable to genetics referral while 136 (21.5%) patients refused. CONCLUSION: The implemented methods of education, NCCN guidelines imbedded within provider notes, and discreet data fields in the EHR have proven to be highly effective in screening appropriate patients and ordering subsequent genetic referrals.

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OBJECTIVE: To investigate open science practices in research published in the top 5 sports medicine journals from May 1, 2022, and October 1, 2022. DESIGN: A meta-research systematic review. LITERATURE SEARCH: Open science practices were searched in MEDLINE. STUDY SELECTION CRITERIA: We included original scientific research published in one of the identified top 5 sports medicine journals in 2022 as ranked by Clarivate: (1) British Journal of Sports Medicine, (2) Journal of Sport and Health Science, (3) American Journal of Sports Medicine, (4) Medicine and Science in Sports and Exercise, and (5) Sports Medicine-Open. Studies were excluded if they were systematic reviews, qualitative research, gray literature, or animal or cadaver models. DATA SYNTHESIS: Open science practices were extracted in accordance with the Transparency and Openness Promotion guidelines and patient and public involvement. RESULTS: Two hundred forty-three studies were included. The median number of open science practices in each study was 2, out of a maximum of 12 (range: 0-8; interquartile range: 2). Two hundred thirty-four studies (96%, 95% confidence interval [CI]: 94%-99%) provided an author conflict-of-interest statement and 163 (67%, 95% CI: 62%-73%) reported funding. Twenty-one studies (9%, 95% CI: 5%-12%) provided open-access data. Fifty-four studies (22%, 95% CI: 17%-27%) included a data availability statement and 3 (1%, 95% CI: 0%-3%) made code available. Seventy-six studies (32%, 95% CI: 25%-37%) had transparent materials and 30 (12%, 95% CI: 8%-16%) used a reporting guideline. Twenty-eight studies (12%, 95% CI: 8%-16%) were preregistered. Six studies (3%, 95% CI: 1%-4%) published a protocol. Four studies (2%, 95% CI: 0%-3%) reported an analysis plan a priori. Seven studies (3%, 95% CI: 1%-5%) reported patient and public involvement. CONCLUSION: Open science practices in the sports medicine field are extremely limited. The least followed practices were sharing code, data, and analysis plans. J Orthop Sports Phys Ther 2023;53(12):1-13. Epub 20 October 2023. doi:10.2519/jospt.2023.12016.

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Airway management is usually an uncomplicated and safe intervention; however, when problems arise with the primary airway technique, the clinical situation can rapidly deteriorate, resulting in significant patient harm. Videolaryngoscopy has been shown to improve patient outcomes when compared with direct laryngoscopy, including improved first-pass success at tracheal intubation, reduced difficult laryngeal views, reduced oxygen desaturation, reduced airway trauma, and improved recognition of oesophageal intubation. The shared view that videolaryngoscopy affords may also facilitate superior teaching, training, and multidisciplinary team performance. As such, its recommended role in airway management has evolved from occasional use as a rescue device (when direct laryngoscopy fails) to a first-intention technique that should be incorporated into routine clinical practice, and this is reflected in recently updated guidelines from a number of international airway societies. However, currently, overall videolaryngoscopy usage is not commensurate with its now widespread availability. A number of factors exist that may be preventing its full adoption, including perceived financial costs, inadequacy of education and training, challenges in achieving deliverable decontamination processes, concerns over sustainability, fears over "de-skilling" at direct laryngoscopy, and perceived limitations of videolaryngoscopes. This article reviews the most up-to-date evidence supporting videolaryngoscopy, explores its current scope of utilisation (including specialist techniques), the potential barriers preventing its full adoption, and areas for future advancement and research.

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PURPOSE: Biosimilars are clinically equivalent to branded products yet cost significantly less. Interchangeability is a US Food and Drug Administration (FDA) designation that allows generic drugs to be substituted for reference drugs at the pharmacy, without a physician's consent. Currently, no oncologic biosimilar has FDA approval for interchangeability. METHODS: Building on pharmacy auto-substitution processes with therapeutic interchange, Plan-Do-Study-Act methodology was used to automate conversions from reference biological products to Pharmacy and Therapeutics-/Physician-approved biosimilars. After establishing the baseline metrics, cycle 1 focused on full staff education (completed July 2020) with systematic pharmacy-driven biosimilar conversion initiated in September 2020 for rituximab, trastuzumab, and bevacizumab. Physician-initiated conversion of Neulasta biosimilar products was encouraged but not mandated. During cycle 2 (May 1, 2021-November 30, 2021), pharmacy-driven Neulasta biosimilar conversion was mandated. In cycle 3 (December 1, 2021-April 30, 2023), stakeholder education was reinforced and the sustainability of conversions was confirmed. RESULTS: Systematic pharmacy-driven conversion to biosimilar products improved over cycles 1 and 2 from baseline: 1.8% to 90.3% for rituximab, 9.2% to 89.7% for trastuzumab, and 20.5% to 96.1% for bevacizumab. Physician-driven biosimilar conversion for Neulasta was lower at 12.7% through April 2021. Pharmacy-driven Neulasta biosimilar conversion was initiated during cycle 2, resulting in a conversion rate of 39.7%. The conversion rates remained sustainable through April 2023. CONCLUSION: Pharmacy-driven auto-substitution of biosimilar products results in rapid and statistically significant biosimilar adoption. The pharmacy-based substitution approach was found to be far more effective than physician-driven substitution. Rapid conversion from branded products to FDA-approved biosimilar is feasible, measurable, and sustainable and can be scaled. Barriers to Neulasta conversion warrant further investigation.

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BACKGROUND: Guidelines from the Obstetric Anaesthetists' Association and Difficult Airway Society state that 'a videolaryngoscope should be immediately available for all obstetric general anaesthetics'. OBJECTIVE: To report the incidence of videolaryngoscopy use, and other airway management safety interventions, in an obstetric population before and after various quality improvement interventions. DESIGN: Prospective data collection was undertaken over 18 months, divided into three separate 6-month periods: June to November 2019; March to August 2021; January to June 2022. These periods relate to evaluation of specific quality improvement interventions. SETTING: The project was carried out in a large tertiary referral obstetric unit. PATIENTS: We identified 401 pregnant women (> 20 weeks' gestation) and postnatal women (up to 48 h post delivery) undergoing an obstetric surgical procedure under general anaesthesia. INTERVENTIONS: To standardise practice, an intubation checklist was introduced in December 2020 and multidisciplinary staff training in August 2021. MAIN OUTCOME MEASURES: Primary outcome measures were use of a Macintosh-style videolaryngoscope and tracheal intubation success. Secondary outcome measures were use of an intubation checklist; low flow nasal oxygen; and ramped patient positioning. RESULTS: Data from 334 tracheal intubations (83.3% of cases) were recorded. Videolaryngoscope use increased from 60% in 2019, to 88% in 2021, to 94% in 2022. Tracheal intubation was successful in all patients, with 94% first pass success overall and only 0.9% requiring three attempts. Use of secondary outcome measures also increased: low flow nasal oxygen from 48% in 2019 to 90% in 2022; ramped positioning from 95% in 2021 to 97% in 2022; and checklist use from 63% in 2021 to 92% in 2022. CONCLUSIONS: We describe the successful adoption of simple safety measures introduced into routine practice. These comprised videolaryngoscopy, ramped positioning and low flow nasal oxygen. Their introduction was supported by the implementation of an intubation checklist and multidisciplinary team training.

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Samuraciclib is a selective oral CDK7-inhibitor. A multi-modular, open-label Phase I study to evaluate safety and tolerability of samuraciclib in patients with advanced malignancies was designed (ClinicalTrials.gov: NCT03363893). Here we report results from dose escalation and 2 expansion cohorts: Module 1A dose escalation with paired biopsy cohort in advanced solid tumor patients, Module 1B-1 triple negative breast cancer (TNBC) monotherapy expansion, and Module 2A fulvestrant combination in HR+/HER2- breast cancer patients post-CDK4/6-inhibitor. Core study primary endpoints are safety and tolerability, and secondary endpoints are pharmacokinetics (PK), pharmacodynamic (PD) activity, and anti-tumor activity. Common adverse events are low grade nausea, vomiting, and diarrhea. Maximum tolerated dose is 360 mg once daily. PK demonstrates dose proportionality (120 mg-480 mg), a half-life of approximately 75 hours, and no fulvestrant interaction. In dose escalation, one partial response (PR) is identified with disease control rate of 53% (19/36) and reduction of phosphorylated RNA polymerase II, a substrate of CDK7, in circulating lymphocytes and tumor tissue. In TNBC expansion, one PR (duration 337 days) and clinical benefit rate at 24 weeks (CBR) of 20.0% (4/20) is achieved. In combination with fulvestrant, 3 patients achieve PR with CBR 36.0% (9/25); in patients without detectable TP53-mutation CBR is 47.4% (9/19). In this study, samuraciclib exhibits tolerable safety and PK is supportive of once-daily oral administration. Clinical activity in TNBC and HR+/HER2-breast cancer post-CDK4/6-inhibitor settings warrants further evaluation.

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