Methodological approach to sleep state misperception in insomnia disorder: Comparison between multiple nights of actigraphy recordings and a single night of polysomnography recording.

STUDY OBJECTIVE: To provide a comprehensive assessment of sleep state misperception in insomnia disorder (INS) and good sleepers (GS) by comparing recordings performed for one night in-lab (PSG and night review) and during several nights at-home (actigraphy and sleep diaries). METHODS: Fifty-seven INS and 29 GS wore an actigraphy device and filled a sleep diary for two weeks at-home. They subsequently completed a PSG recording and filled a night review in-lab. Sleep perception index (subjective/objective × 100) of sleep onset latency (SOL), sleep duration (TST) and wake duration (TST) were computed and compared between methods and groups. RESULTS: GS displayed a tendency to overestimate TST and WASO but correctly perceived SOL. The degree of misperception was similar across methods within the GS group. In contrast, INS underestimated their TST and overestimated their SOL both in-lab and at-home, yet the severity of misperception of SOL was larger at-home than in-lab. Finally, INS overestimated WASO only in-lab while correctly perceiving it at-home. While only the degree of TST misperception was stable across methods in INS, misperception of SOL and WASO were dependent on the method used. CONCLUSIONS: We found that GS and INS exhibit opposite patterns and severity of sleep misperception. While the degree of misperception in GS was similar across methods, only sleep duration misperception was reliably detected by both in-lab and at-home methods in INS. Our results highlight that, when assessing sleep misperception in insomnia disorder, the environment and method of data collection should be carefully considered.

Proteomic, Metabolomic, and Fatty Acid Profiling of Small Extracellular Vesicles from Glioblastoma Stem-Like Cells and Their Role in Tumor Heterogeneity.

Glioblastoma is a deadly brain tumor for which there is no cure. The presence of glioblastoma stem-like cells (GSCs) contributes to the heterogeneous nature of the disease and makes developing effective therapies challenging. Glioblastoma cells have been shown to influence their environment by releasing biological nanostructures known as extracellular vesicles (EVs). Here, we investigated the role of GSC-derived nanosized EVs (<200 nm) in glioblastoma heterogeneity, plasticity, and aggressiveness, with a particular focus on their protein, metabolite, and fatty acid content. We showed that conditioned medium and small extracellular vesicles (sEVs) derived from cells of one glioblastoma subtype induced transcriptomic and proteomic changes in cells of another subtype. We found that GSC-derived sEVs are enriched in proteins playing a role in the transmembrane transport of amino acids, carboxylic acids, and organic acids, growth factor binding, and metabolites associated with amino acid, carboxylic acid, and sugar metabolism. This suggests a dual role of GSC-derived sEVs in supplying neighboring GSCs with valuable metabolites and proteins responsible for their transport. Moreover, GSC-derived sEVs were enriched in saturated fatty acids, while their respective cells were high in unsaturated fatty acids, supporting that the loading of biological cargos into sEVs is a highly regulated process and that GSC-derived sEVs could be sources of saturated fatty acids for the maintenance of glioblastoma cell metabolism. Interestingly, sEVs isolated from GSCs of the proneural and mesenchymal subtypes are enriched in specific sets of proteins, metabolites, and fatty acids, suggesting a molecular collaboration between transcriptionally different glioblastoma cells. In summary, this study revealed the complexity of GSC-derived sEVs and unveiled their potential contribution to tumor heterogeneity and critical cellular processes commonly deregulated in glioblastoma.

Systematic review of clinical debriefing tools: attributes and evidence for use.

BACKGROUND AND OBJECTIVES: Clinical debriefing (CD) following a clinical event has been found to confer benefits for staff and has potential to improve patient outcomes. Use of a structured tool to facilitate CD may provide a more standardised approach and help overcome barriers to CD; however, we presently know little about the tools available. This systematic review aimed to identify tools for CD in order to explore their attributes and evidence for use. METHODS: A systematic review was conducted in line with PRISMA standards. Five databases were searched. Data were extracted using an electronic form and analysed using critical qualitative synthesis. This was guided by two frameworks: the '5 Es' (defining attributes of CD: educated/experienced facilitator, environment, education, evaluation and emotions) and the modified Kirkpatrick's levels. Tool utility was determined by a scoring system based on these frameworks. RESULTS: Twenty-one studies were included in the systematic review. All the tools were designed for use in an acute care setting. Criteria for debriefing were related to major or adverse clinical events or on staff request. Most tools contained guidance on facilitator role, physical environment and made suggestions relating to psychological safety. All tools addressed points for education and evaluation, although few described a process for implementing change. Staff emotions were variably addressed. Many tools reported evidence for use; however, this was generally low-level, with only one tool demonstrating improved patient outcomes. CONCLUSION: Recommendations for practice based on the findings are made. Future research should aim to further examine outcomes evidence of these tools in order to optimise the potential of CD tools for individuals, teams, healthcare systems and patients.

Videolaryngoscopy use before and after the initial phases of the COVID-19 pandemic: The report of the VL-iCUE survey with responses from 96 countries.

BACKGROUND: The potential benefit of videolaryngoscopy use in facilitating tracheal intubation has already been established, however its use was actively encouraged during the COVID-19 pandemic as it was likely to improve intubation success and increase the patient-operator distance. OBJECTIVES: We sought to establish videolaryngoscopy use before and after the early phases of the pandemic, whether institutions had acquired new devices during the COVID-19 pandemic, and whether there had been teaching on the devices acquired. DESIGN: We designed a survey with 27 questions made available via the Joint Information Scientific Committee JISC online survey platform in English, French, Spanish, Chinese, Japanese and Portuguese. This was distributed through 18 anaesthetic and airway management societies. SETTING: The survey was open for 54 to 90 days in various countries. The first responses were logged on the databases on 28 October 2021, with all databases closed on 26 January 2022. Reminders to participate were sent at the discretion of the administering organisations. PARTICIPANTS: All anaesthetists and airway managers who received the study were eligible to participate. MAIN OUTCOME MEASURES: Videolaryngoscopy use before the COVID-19 pandemic and at the time of the survey. RESULTS: We received 4392 responses from 96 countries: 944/4336 (21.7%) were from trainees. Of the 3394 consultants, 70.8% (2402/3394) indicated no change in videolaryngoscopy use, 19.9% (675/3394) increased use and 9.3% (315/3393) reduced use. Among trainees 65.5% (618/943) reported no change in videolaryngoscopy use, 27.7% (261/943) increased use and 6.8% (64/943) reduced use. Overall, videolaryngoscope use increased by 10 absolute percentage points following the pandemic. CONCLUSIONS: Videolaryngoscopy use increased following the early phase of the COVID-19 pandemic but this was less than might have been expected.

The Rubik's cube of doing and being: Factors influencing professional identity transition to the medical registrar.

BACKGROUND: Professional identity transitions, such as the transition to medical registrar, are challenging. How minoritised identities influence transitions during medical training requires further study. This study aimed to explore the factors influencing the transition to the medical registrar in Scotland to guide support during training. METHODS: Interviews exploring this transition with internal medicine trainees were audio recorded, transcribed verbatim and double-coded using template analysis. We applied an initial coding template informed by multiple and multidimensional transition theory of individual, interpersonal, systemic and macro-level factors. Using a critical theory lens, a further template analysis specifically sought to understand how trainees' social identities interacted with the various levels. FINDINGS: Nineteen IM trainees were interviewed between January 2021 and February 2022. Influential factors reflected a parallel process of competence (doing) and identity (being) development. The interaction of social identities, such as gender (being a woman) and country of origin (being an international medical graduate), occurred across levels. This can be conceptualised as a Rubik's cube with the interplay between doing and being from an individual to a macro level with trainees' social identities interacting at all levels. CONCLUSION: The transition to the medical registrar is multifaceted; with a challenging balance between support and independence in providing opportunities to perform (doing) whilst identity develops (being). Identity transitions involve multiple Rubik's-cube-like rotations between the facets of 'doing' and 'being,' until these align. Taking heed of influential factors and the interaction of minoritised social identities could guide a trainee-centred and smoother transition.

The Design and Evolution of an Adaptable CME Programme to Suit the Changing Educational Needs of the Clinical Community.

Continuing medical education (CME) plays a critical role in healthcare, helping to ensure patients receive the best possible care and optimal disease management. Considering the obstacles to engaging in CME activities faced by the clinical community, as well as employing learning theory, Liberum IME developed Classroom to Clinic™ - a bespoke, accredited learning format that can be tailored to individuals' educational needs and time constraints. Through monitoring use, and incorporating qualitative and quantitative feedback, we continuously evaluate the usability, value and accessibility of this programme and adapt subsequent iterations accordingly. An example of this is the way we adapted our engagement of facilitators. Originally this was accomplished by targeting individuals for train-the-trainer events, but it was clear this was more effective in some countries than in others. To address this variability, we piloted launching a new module at a relevant large international congress. This aimed to instigate a cascade in education sharing, from congress attendees to peers at their clinics and across departments and hospitals. So far, the programme has reported encouraging improvements in uptake, as well as knowledge, competence and clinical practice, while qualitative feedback has allowed for the identification of further educational needs and continued evolution of the programme.

Screening for Osteoporosis Risk Among Community-Dwelling Older Adults: A Scoping Review.

BACKGROUND AND PURPOSE: Due to potential health-related consequences of osteoporosis (OP), health care providers who do not order imaging, such as physical therapists, should be aware of OP screening tools that identify individuals who need medical and rehabilitation care. However, current knowledge and guidance on screening tools is limited. Therefore, we explored OP screening tools that are appropriate and feasible for physical therapy practice, and evaluated tools' effectiveness by examining their clinimetric properties. METHODS: A systematic search of the following databases was performed: PubMed, PEDro, PsycINFO, CINAHL, and Web of Science. Articles were included if the study population was 50 years and older, had a diagnosis of OP, if the screening tool was within the scope of physical therapy practice, and was compared to either a known diagnosis of OP or bone densitometry scan results. Included articles underwent multiple reviews for inclusion and exclusion, with each review round having a different randomly selected pair of reviewers. Data were extracted from included articles for participant demographics, outcome measures, cut-off values, and clinimetric properties. Results were categorized with positive and negative likelihood ratios (+LR/-LR) based on the magnitude of change in the probability of having or not having OP. RESULTS: +LRs ranged from 0.15 to 20.21, with the Fracture Risk Assessment Tool (FRAX) and Study of Osteoporotic Fractures (SOF) having a large shift in posttest probability. -LRs ranged from 0.03 to 1.00, with the FRAX, Male Osteoporosis Risk Estimation Scores, Osteoporosis Self-Assessment Tool (OST), and Simple Calculated Osteoporosis Risk Estimation having a large shift in posttest probability. CONCLUSION: Tools with moderate-large shift for both +LR and -LR recommended for use are: (1) OST; (2) FRAX; and (3) SOF. The variability in cut-off scores and clinimetric properties based on gender, age, and race/ethnicities made it impossible to provide one specific recommendation for an OP screening tool. Future research should focus on OP risk prediction among males and racial and ethnic groups.

Engaging Future Healthcare Professionals as Caregivers to Hospice Patients in Comfort Care Homes.

Most people wish to die at home yet significant barriers exist in accessing care in one's home, especially for individuals with caregiver and/or housing instability. Across the U.S., residential homes for the dying are opening to address gaps in end-of-life care by recruiting community members to serve as caregivers to hospice patients during their final days. This paper describes a blended-experiential training program, informed by both an evidence-based educational framework and transformative learning theory, that trains undergraduate students to serve as surrogate family members to hospice patients in residential care homes. This study analyzed data from a sample of undergraduate students (n = 35) who participated in an 8-week program. Applying Kirkpatrick's evaluation model, study results indicate the program provided essential knowledge and skills in end-of-life care, benefiting both student learning outcomes and resident care.

Online non-technical skills faculty training.

BACKGROUND: The Medical Students Non-Technical Skills (Medi-StuNTS) system is a behavioural marker system (BMS) designed to identify and debrief non-technical skills (NTS) for medical students during immersive simulation. Educators must be adequately trained in using the BMS. This study aimed to design and implement an online platform to deliver a faculty development course on using Medi-StuNTS and evaluate the feasibility of this platform in training faculty to identify and debrief NTS. APPROACH: The online platform was developed by faculty with expertise in NTS, based on guidance for faculty training programme requirements and the multimodal model for online education. Content was arranged in modules, using presentations, videos of simulation scenarios and interactive discussion boards. EVALUATION: Fifteen participants completed the course and feedback over a two-month period. A feedback form was completed to assess feasibility, based on a feasibility framework. The areas of focus were acceptability, demand, implementation, practicality, adaptation, integration, expansion and limited efficacy. Feedback indicated that the course shows promise in improving the ability of faculty to identify and debrief NTS. IMPLICATIONS: The platform was successfully developed and implemented and was able to reach a national audience due to its online nature. Specific strengths include increased flexibility and accessibility compared to in-person training. Feasibility assessment suggests that this newly developed online platform can work as an effective method for faculty development in order to increase skills in identifying and debriefing NTS using Medi-StuNTS. Future work will focus on expansion of the online platform and dissemination to an international audience.

Examining physical activity participation barriers among adults 50 years and older: a scoping review.

Background: Addressing physical activity (PA) barriers is essential for increasing PA levels in middle-aged and older adults. However, there are no recommendations on selecting PA barrier assessment tools. Objectives: Thus, we aimed to identify and provide clinimetric properties on PA barrier assessment tools that healthcare providers, exercise experts, and public health officials can use to examine potential barriers faced by community-dwelling adults 50 years and older. Methods: We performed a systematic search of the following databases: PubMed, PsycINFO, CINAHL, and Web of Science. Articles were included if they presented clinimetric data on a PA participation barrier assessment tool for community-dwelling participants with a mean age of 50 years and older. The 561 identified articles underwent multiple rounds of blinded reviews. Included articles underwent data extraction for participant characteristics, scoring, constructs, reference tests, and clinimetric properties. Results: The 35 included articles reported on 33 different PA participation barrier assessment tools. Eighteen articles reported on participants with cardiovascular, musculoskeletal, or neurological diagnoses, diabetes, hemodialysis, history of cancer, or mobility limitations. Tools with two or more supporting publications included the Exercise Benefits/Barrier Scale (EBBS), Episode-Specific Interpretations of Exercise Inventory (ESIE), and Inventory of Physical Activity and Barriers (IPAB). Due to differences in methodologies, across-tool comparison was not possible. Conclusion: The EBBS, ESIE, and IPAB are promising tools for community-dwelling adults 50 years and older. However, additional research is warranted to identify the best PA barrier assessment tool among adults 50 years and older.

PFKFB4 interacts with FBXO28 to promote HIF-1α signaling in glioblastoma.

Glioblastoma is a highly aggressive brain tumor for which there is no cure. The metabolic enzyme 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4 (PFKFB4) is essential for glioblastoma stem-like cell (GSC) survival but its mode of action is unclear. Understanding the role of PFKFB4 in tumor cell survival could allow it to be leveraged in a cancer therapy. Here, we show the importance of PFKFB4 for glioblastoma growth in vivo in an orthotopic patient derived mouse model. In an evaluation of patient tumor samples of different cancer entities, PFKFB4 protein was found to be overexpressed in prostate, lung, colon, mammary and squamous cell carcinoma, with expression level correlating with tumor grade. Gene expression profiling in PFKFB4-silenced GSCs revealed a downregulation of hypoxia related genes and Western blot analysis confirmed a dramatic reduction of HIF (hypoxia inducible factor) protein levels. Through mass spectrometric analysis of immunoprecipitated PFKFB4, we identified the ubiquitin E3 ligase, F-box only protein 28 (FBXO28), as a new interaction partner of PFKFB4. We show that PFKFB4 regulates the ubiquitylation and subsequent proteasomal degradation of HIF-1α, which is mediated by the ubiquitin ligase activity of FBXO28. This newly discovered function of PFKFB4, coupled with its cancer specificity, provides a new strategy for inhibiting HIF-1α in cancer cells.

Impact of Tigecycline on C. difficile Outcomes: Case Series and Propensity-Matched Retrospective Study.

This case series and propensity-matched cohort study on the use of tigecycline in Clostridioides difficile infection (CDI) evaluated the effect of tigecycline on 30-day mortality. Adjusted for ATLAS Score, hypotension, treatment time period, and serum lactate, tigecycline did not significantly improve 30-day mortality (odds ratio: 0.89; 95% confidence interval: 0.25-3.12; P = 0.853). A randomized controlled trial is needed to determine efficacy and safety of tigecycline in severe or refractory CDI.

The Role of Digital Competence in CME Uptake: A Short Communication.

The digitisation of society has reached almost every facet of our daily lives. The COVID-19 pandemic has further showcased the role of information and communications technology (ICT) in society and so much so in continuing medical education (CME). This has provided the CME industry with remarkable opportunities to design better educational programmes and reach more audiences. However, for healthcare professionals to take full advantage of these developments, they need to be digitally competent, at least at a basic level. While digital competence influences CME uptake in the internet age, several factors, in turn, can influence digital competence. These factors come from both within and outside the influence of healthcare professionals and educators. In this article, we explore how digital competence influences CME uptake and recommend ways to improve digital competence among healthcare professionals.

Examining physical activity participation barriers among adults 50 years and older: a scoping review protocol.

Background: Despite the benefits of physical activity (PA), 61% of adults 50 years and older do not meet the recommended levels of PA. One method of increasing PA participation is assessing and addressing PA participation barriers. Currently, no guidance on methodologies for assessing PA participation barriers exist. Objective: The primary objective of this scoping review is to map the methodologies used to examine potential PA participation barriers faced by community-dwelling adults 50 years and older. A secondary objective is to evaluate the clinimetric properties of these methodologies. Methods: This scoping review protocol is registered with Open Science Framework (https://osf.io/wd2hx). A systematic search of the following databases will be performed: PubMed, PsycINFO, CINAHL, Web of Science, and PEDro. Included studies will 1) present either a) data on development or clinimetric properties of PA participation barrier tool (s); or b) relative risk or odds ratios of PA participation barrier(s); 2) compare PA participation barriers or PA participation barrier tool(s) to either subjective or objective measures of PA; and 3) comprise of community-dwelling participants with a mean age of 50 years and older. A two-phase blinded independent screening process will be conducted to select the included publications. Data will be extracted using a standardized form and cross-checked by the first author. A narrative summary will accompany the results presented in tables and figures. Conclusion: This scoping review will provide a comprehensive understanding of current literature and gaps related to PA participation barrier methodologies used with adults 50 years and older.

A novel patient stratification strategy to enhance the therapeutic efficacy of dasatinib in glioblastoma.

BACKGROUND: Glioblastoma is the most common primary malignancy of the central nervous system with a dismal prognosis. Genomic signatures classify isocitrate dehydrogenase 1 (IDH)-wildtype glioblastoma into three subtypes: proneural, mesenchymal, and classical. Dasatinib, an inhibitor of proto-oncogene kinase Src (SRC), is one of many therapeutics which, despite promising preclinical results, have failed to improve overall survival in glioblastoma patients in clinical trials. We examined whether glioblastoma subtypes differ in their response to dasatinib and could hence be evaluated for patient enrichment strategies in clinical trials. METHODS: We carried out in silico analyses on glioblastoma gene expression (TCGA) and single-cell RNA-Seq data. In addition, in vitro experiments using glioblastoma stem-like cells (GSCs) derived from primary patient tumors were performed, with complementary gene expression profiling and immunohistochemistry analysis of tumor samples. RESULTS: Patients with the mesenchymal subtype of glioblastoma showed higher SRC pathway activation based on gene expression profiling. Accordingly, mesenchymal GSCs were more sensitive to SRC inhibition by dasatinib compared to proneural and classical GSCs. Notably, SRC phosphorylation status did not predict response to dasatinib treatment. Furthermore, serpin peptidase inhibitor clade H member 1 (SERPINH1), a collagen-related heat-shock protein associated with cancer progression, was shown to correlate with dasatinib response and with the mesenchymal subtype. CONCLUSION: This work highlights further molecular-based patient selection strategies in clinical trials and suggests the mesenchymal subtype as well as SERPINH1 to be associated with response to dasatinib. Our findings indicate that stratification based on gene expression subtyping should be considered in future dasatinib trials.

Ancient anomalies: Twinned and supernumerary incisors in a medieval Nubian.

During the analysis of a skeletal assemblage from a medieval cemetery in Nubia (c. AD 500-1550), a young adult female with abnormally developed maxillary incisors was discovered. The possible causes of the two dental anomalies found in this individual and their archaeological context are discussed. The remains are from a medieval assemblage from the Fourth Cataract region of Nubia, which forms part of the Nubian collection curated at the British Museum. The left central incisor has a twinned crown with two root canals, and a supernumerary tooth is present on the right side between the central incisor and lateral incisors. Although two different dental anomalies are present, the bilateral expression suggests that the same biological mechanism could be responsible.

Pseudohomozygous dysfibrinogenemia.

Hypodysfibrinogenemia (HD) is a heterogeneous disorder in which plasma fibrinogen antigen and function are both reduced but discordant. This report addresses the key clinical question of whether genetic analysis enables clinically useful subclassification of patients with HD. We report a new case and identify a further eight previously documented cases that have the laboratory features of HD but biallelic inheritance of quantitative and qualitative fibrinogen gene variants. The cases displayed both bleeding and thrombosis and sometimes had undetectable fibrinogen activity. In all cases, the predicted effect of the coinherited variants is reduced levels of circulating fibrinogen that is all dysfunctional. We propose the term pseudohomozygous dysfibrinogenemia for this subtype of recessively inherited HD that is distinct from the more commonly recognized monoallelic HD caused by a single fibrinogen gene variant.