Implementation of facemask sampling for the detection of infectious individuals with SARS-CoV-2 in high stakes clinical examinations - a feasibility study.

Introduction: SARS-CoV-2 may transmit across vaccinated cohorts during practical clinical examinations. We sought to assess the feasibility of facemask sampling (FMS) to identify individuals emitting SARS-CoV-2 during a mock PACES exam. Methods: In May 2022 we recruited participants from a mock PACES examination in Leicester, UK. Following a negative lateral flow test assay, all participants wore modified facemasks able to capture exhaled virus during the assessment (FMS). A concomitant upper respiratory tract sample (URTS) was provided prior to FMS. Exposed facemasks were processed by removal and dissolution of sampling matrices fixed within the mask and cycle thresholds values quantified by RT-qPCR. Participants were asked to grade statements regarding the comfort, effort, ethics and communication when providing FMS; laboratory technicians were asked to grade key statements surrounding suitability of samples for processing. Results: 34 participants provided concomitant URTS and FMS during the examination. One participant was positive for SARS-CoV-2, with a cycle threshold value of 22.5 on URTS, but negative (no viral RNA detected) on FMS; no transmission to others was identified from this individual. Participants responded positively to statements regarding FMS describing all four domains; however, 69% of participants felt that a positive result from FMS alone was insufficient for diagnosis and that further tests were required. All but one FMS sample was suitable for processing. Discussion: FMS during PACES exams are acceptable among participants and samples provided are suitable for processing. Our results demonstrate feasibility of FMS within practical examination settings and support the further assessment of FMS as a scalable tool that can be compared with URTS to identify those who are infectious.

Are outcomes of locally advanced cervical cancer associated with prebrachytherapy hemoglobin values and transfusion practice? An observational study comparing two large academic centres with divergent clinical guidelines.

BACKGROUND AND PURPOSE: Anemia is common in locally advanced cervical cancer. Clinical practice varies greatly for management of anemia during brachytherapy, with some centres providing red cell transfusion to increase hemoglobin levels above 100 g/L. MATERIALS AND METHODS: This is a retrospective observational cohort study of adult patients with cervical cancer treated with brachytherapy at two academic hospitals. One hospital (H1) uses a liberal transfusion strategy with hemoglobin threshold of 100 g/L during brachytherapy and the other uses a restrictive target of 70 g/L (H2). RESULTS: Overall, 336 patients met inclusion criteria (H1: 150 patients, H2: 186 patients). 11 patients were excluded (2 at H1, 9 at H2). Demographics at both sites were comparable, except for cancer stage and smoking history. External beam radiation and chemotherapy provided was similar. Hemoglobin values were compared at baseline (within 4 weeks of oncology consult), and prior to the first and second brachytherapy treatments. In total, 101red blood cell (RBC) units were transfused to patients at H1 and 19 units to patients at H2. Patients were followed for a median of 37.0 months (0.6-80.5) at H1, and 33.3 months (1.6-82.0) at H2. There was no significant difference in progression-free or overall survival. Multivariable logistic regression analysis showed that FIGO stage was a predictor for both overall survival and cancer progression. Age, tumor size, chemotherapy, and hemoglobin levels were not predictors of disease progression or mortality. CONCLUSIONS: The practice of liberal transfusion should be re-evaluated in the absence of robust data to support its use.

Propensity score matching analysis comparing the efficacy of Ruxolitinib to historical controls in second-line or beyond treatment for chronic GvHD after steroid failure.

Established first-line therapy for chronic graft-versus-host disease (cGvHD) comprises corticosteroids with/without calcineurin inhibitors, but about half of cGvHD patients are refractory to corticosteroid therapy. The present study retrospectively analyzed treatment outcomes in 426 patients and undertook a propensity-score matching (PSM) analysis between ruxolitinib (RUX) treated group and a historical group of cGvHD patients treated with best available treatment (BAT). PSM process adjusted unbalanced risk factors between the 2 groups, including GvHD severity, HCT-CI score, and treatment line, extracting 88 patients (44 in BAT/RUX groups each) for final analysis. In PSM subgroup, RUX group showed 74.7% 12 months' FFS rate vs 19.1% for BAT group (p < 0.001), whereas 12 months' OS rates were 89.2% and 77.7%, respectively. Multivariate analysis for FFS confirmed RUX superiority over BAT together with HCT-CI score 0-2 vs ≥3. For OS, RUX was superior to BAT, while age ≥60 years and severe grade cGvHD adversely impacted OS. In PSM subgroup, at months 0, 3, and 6, 4.5%, 12.2% and 22.2% more patients in RUX group could discontinue prednisone compared to BAT group, respectively. In conclusion, the current study showed that for FFS, RUX was superior to BAT as second-line therapy or beyond in cGvHD patients after therapy failure.

Eelgrass (Zostera spp.) associated phytomyxids are host-specific congeneric parasites and predominant eukaryotes in the eelgrass rhizosphere on a global scale.

Together with increasing environmental and anthropogenic pressures, pathogenic diseases are one of the important factors contributing to the ongoing decline of seagrass meadows worldwide; yet the diversity and ecology of the microorganisms acknowledged as seagrass parasites remain critically understudied. Here, we investigate phytomyxid parasites (Rhizaria: Endomyxa: Phytomyxea) of three different eelgrass (Zostera spp.) species found in the Northern hemisphere. We present molecular evidence that Plasmodiophora bicaudata, a long-recognized parasite of dwarf eelgrass taxa, is closely related to the novel phytomyxid recently discovered in root hairs of Zostera marina, and together they form a distinct clade within the order Phagomyxida, proposed here as Feldmanniella gen. nov. A full life cycle is systematically described in a phagomyxid representative for the first time, proving its conformity with the generalized phytomyxid life history, despite previous uncertainties. The presence of primary infection stages in nearly all collected eelgrass specimens, and subsequent analysis of amplicon sequences from a global Z. marina dataset, reveal phytomyxids to be ubiquitous and one of the predominant microeukaryotes associated with eelgrass roots on a global scale. Our discoveries challenge the current view of Phytomyxea as rare entities in seagrass meadows and suggest their generally low pathogenicity in natural ecosystems.

A Multicenter, Retrospective Study Evaluating Clinical Outcomes of Ruxolitinib Therapy In Heavily Pretreated Chronic GVHD Patients With Steroid Failure.

Although ruxolitinib is emerging as the treatment of choice for steroid-refractory or -dependent chronic graft versus host disease (cGVHD) based on randomized control trial data, there is relatively little real-world data published on ruxolitinib for this indication. We wanted to evaluate the real-world efficacy and safety of ruxolitinib in cGVHD patients who have failed any previous systemic therapy for cGVHD. We retrospectively evaluated the efficacy of ruxolitinib in 115 heavily pretreated patients with steroid-refractory or -dependent chronic GVHD across 5 transplantation centers. The majority of the study population had severe cGVHD (60%) and received ruxolitinib at the fourth treatment line or beyond (82%, n = 96). The median duration of follow-up in this study population was 13 months. The overall response rate (ORR) was 48.6%, 54.9%, and 48.5% at 3, 6, and 12 months, respectively. Clinical benefit (an outcome metric combining ORR with steroid reduction) was observed in 58.7%, 64.8%, and 60.6% of patients at 3, 6, and 12 months, respectively. Approximately one third of patients (37.9%) were able to discontinue prednisone at 12 months, and 63.8% were able to taper prednisone to a daily dose <0.1 mg/kg at 12 months. Failure-free survival at 12 months was 64.6% (54.1%-73.2%). Multivariate analysis identified that patients with severe cGVHD were at a higher risk of failure because of a therapy switch, whereas a pretransplantation hematopoietic stem cell transplantation-comorbidity index score ≥ 3 was associated with a high risk of failure because of increasing risk of non-relapse mortality. Overall, this study demonstrates the therapeutic efficacy of ruxolitinib for cGVHD in a heavily pretreated real-world population.

Real-time auditory feedback may reduce abnormal movements in patients with chronic stroke.

PURPOSE: The current pilot study assesses the use of real-time auditory feedback to help reduce abnormal movements during an active reaching task in patients with chronic stroke. MATERIALS AND METHODS: 20 patients with chronic stroke completed the study with full datasets (age: M = 53 SD = 14; sex: male = 75%; time since stroke in months: M = 34, SD = 33). Patients undertook 100 repetitions of an active reaching task while listening to self-selected music which automatically muted when abnormal movement was detected, determined by thresholds set by clinical therapists. A within-subject design with two conditions (with auditory feedback vs. without auditory feedback) presented in a randomised counterbalanced order was used. The dependent variable was the duration of abnormal movement as a proportion of trial duration. RESULTS: A significant reduction in the duration of abnormal movement was observed when patients received auditory feedback, F(1,18) = 9.424, p = 0.007, with a large effect size (partial η2 = 0.344). CONCLUSIONS: Patients with chronic stroke can make use of real-time auditory feedback to increase the proportion of time they spend in optimal movement patterns. The approach provides a motivating framework that encourages high dose with a key focus on quality of movement. Trial Registration: ISRCTN12969079 https://www.isrctn.com/ISRCTN12969079 ISRTCN trial registration REF: ISRCTN12969079IMPLICATIONS FOR REHABILITATIONMovement quality during upper limb rehabilitation should be targeted as part of a well-balanced rehabilitation programme.Auditory feedback is a useful tool to help patients with chronic stroke reduce compensatory movements.

Structural basis for acyl chain control over glycosphingolipid sorting and vesicular trafficking.

The complex sphingolipids exhibit a diversity of ceramide acyl chain structures that influence their trafficking and intracellular distributions, but it remains unclear how the cell discerns among the different ceramides to affect such sorting. To address the mechanism, we synthesize a library of GM1 glycosphingolipids with naturally varied acyl chains and quantitatively assess their sorting among different endocytic pathways. We find that a stretch of at least 14 saturated carbons extending from C1 at the water-bilayer interface dictate lysosomal sorting by exclusion from endosome sorting tubules. Sorting to the lysosome by the C14∗ motif is cholesterol dependent. Perturbations of the C14∗ motif by unsaturation enable GM1 entry into endosomal sorting tubules of the recycling and retrograde pathways independent of cholesterol. Unsaturation occurring beyond the C14∗ motif in very long acyl chains rescues lysosomal sorting. These results define a structural motif underlying the membrane organization of sphingolipids and implicate cholesterol-sphingolipid nanodomain formation in sorting mechanisms.

Differences in outcomes following an intensive upper-limb rehabilitation program for patients with common central nervous system-acting drug prescriptions.

Background: Difficulty using the upper-limb is a major barrier to independence for many patients post-stroke or brain injury. High dose rehabilitation can result in clinically significant improvements in function even years after the incident; however, there is still high variability in patient responsiveness to such interventions that cannot be explained by age, sex, or time since stroke. Methods: This retrospective study investigated whether patients prescribed certain classes of central nervous system-acting drugs-γ-aminobutyric acid (GABA) agonists, antiepileptics, and antidepressants-differed in their outcomes on the three-week intensive Queen Square Upper-Limb program. For 277 stroke or brain injury patients (167 male, median age 52 years (IQR: 21), median time since incident 20 months (IQR: 26)) upper-limb impairment and activity was assessed at admission to the program and at six months post-discharge, using the upper limb component of the Fugl-Meyer, Action Research Arm Test, and Chedoke Arm and Hand Activity Inventory. Drug prescriptions were obtained from primary care physicians at referral. Specification curve analysis was used to protect against selective reporting results and add robustness to the conclusions of this retrospective study. Results: Patients with GABA agonist prescriptions had significantly worse upper-limb scores at admission but no evidence for a significant difference in program-induced improvements was found. Additionally, no evidence of significant differences in patients with or without antiepileptic drug prescriptions on either admission to, or improvement on, the program was found in this study. Although no evidence was found for differences in admission scores, patients with antidepressant prescriptions experienced reduced improvement in upper-limb function, even when accounting for anxiety and depression scores. Conclusions: These results demonstrate that, when prescribed typically, there was no evidence that patients prescribed GABA agonists performed worse on this high-intensity rehabilitation program. Patients prescribed antidepressants, however, performed poorer than expected on the Queen Square Upper-Limb rehabilitation program. While the reasons for these differences are unclear, identifying these patients prior to admission may allow for better accommodation of differences in their rehabilitation needs.

Ankylosing spondylitis and undifferentiated spondyloarthritis: The relationship between living with these diseases and psychological well-being.

BACKGROUND AND PURPOSE: This study explored the psychological impact of living with chronic pain as a result of ankylosing spondylitis or undifferentiated spondyloarthritis. The aim was to investigate individual's current pain experience and their current psychological state. METHODS: A total of 161 individuals who had a clinical diagnosis of ankylosing spondylitis or undifferentiated spondyloarthritis participated in an online survey. This survey measured daily/weekly pain, quality of life and psychological wellbeing. RESULTS: Results indicated that participants reported feeling high levels of pain consistently that impaired their daily functioning more than 50% of the time. Furthermore, on average participants reported experiencing extremely severe levels of psychological distress, that significantly correlated with their experience with pain. CONCLUSIONS: This research is significant as it highlights a need to address the psychological well-being of individuals who are diagnosed with chronic rheumatic disease in conjunction with the support they receive for their physical well-being. Furthermore, health professionals need to be mindful of the degree of debilitation associated with these diseases.

Pushing the limits of recovery in chronic stroke survivors: a descriptive qualitative study of users perceptions of the Queen Square Upper Limb Neurorehabilitation Programme.

INTRODUCTION: The Queen Square Upper Limb (QSUL) Neurorehabilitation Programme is a clinical service within the National Health Service in the UK that provides 90-hours of therapy over 3-weeks to stroke survivors with persistent upper limb impairment. This study aimed to explore the perceptions of participants of this programme, including clinicians, stroke survivors and caregivers. DESIGN: Descriptive qualitative. Data analysis was performed using a conventional thematic content approach to identify main themes by four researchers to avoid any potential bias or personal motivations, promoting confirmability. SETTING: Clinical outpatient neurorehabilitation service. PARTICIPANTS: Clinicians (physiotherapists, occupational therapists, rehabilitation assistants) involved in the delivery of the QSUL Programme, as well as stroke survivors and caregivers who had participated in the programme were purposively sampled. Each focus group followed a series of semi-structured, open questions that were tailored to the clinical or stroke group. One independent researcher facilitated all focus groups, which were audio-recorded and transcribed verbatim by a professional transcription agency. RESULTS: Four focus groups were completed: three including stroke survivors (n=16) and caregivers (n=2), and one including clinicians (n=11). The main stroke survivor themes related to psychosocial aspects of the programme ('you feel valued as an individual'), as well as the behavioural training provided ('gruelling, yet rewarding'). The main clinician themes also included psychosocial aspects of the programme ('patient driven ethos-no barriers, no rules') and knowledge, skills and resources of clinicians ('it is more than intensity, it is complex'). CONCLUSIONS: As an intervention, stroke survivors and clinicians consider the QSUL Programme to be both comprehensive and complex. The nature of the interventions in the programme spans psychosocial and behavioural domains. We suggest the future clinical trials of upper limb rehabilitation consider testing the efficacy of these multiple interacting components.

Statistical modeling can determine what factors are predictive of appropriate follow-up in patients presenting with incidental pulmonary nodules on CT.

PURPOSE: To assess the performance of statistical modeling in predicting follow-up adherence of incidentally detected pulmonary nodules (IPN) on CT, based on patient variables (PV), radiology report related variables (RRRV) and physician-patient communication variables (PPCV). METHODS: 200 patients with IPN on CT were retrospectively identified and randomly selected. PV (age, gender, smoking status, ethnicity), RRRV (nodule size, patient context, whether follow-up recommendations were provided) and PPCV (whether referring physician documented IPN and ordered follow-up on the electronic medical record) were recorded. Primary outcome was whether patients received appropriate follow-up within +/- 1 month of the recommended time frame. Statistical methods included logistic regression and machine learning (K-nearest neighbors and support vector machine). RESULTS: Adherence was low, with or without recommendations provided in the radiology report (23.4 %-27.4 %). Whether the referring physician ordered follow-up was the dominant predictor of adherence in all models. The following variables were statistically significant predictors of whether referring physician ordered follow-up: recommendations provided in the radiology report, smoking status, patient context and nodule size (FDR logworth of respectively 21.18, 11.66, 2.35, 1.63, p < 0.05). Prediction accuracy varied from 72 % (PV) to 93 % (PPCV, all variables). CONCLUSION: PPCV are the most important predictors of adherence. Amongst all variables, patient context, smoking status, nodule size, and whether the radiologist provided follow-up recommendations in the report were all statistically significant predictors of patient follow-up adherence, supporting the utility of statistical modeling for analytics, quality assurance and optimization of outcomes related to IPN.

The Impact of Three-Dimensional Printed Anatomical Models on First-Year Student Engagement in a Block Mode Delivery.

Student engagement is known to have several positive effects on learning outcomes and can impact a student's university experience. High levels of engagement in content-heavy subjects can be difficult to attain. Due to a major institutional restructure, the anatomy prosection laboratory time per subject was dramatically reduced. In response, the authors set out to redesign their anatomy units with a focus on engaging the learning activities that would increase time-on-task both within and outside of the classroom. One of these curriculum changes was the implementation of a suite of anatomy learning activities centered on sets of three-dimensional printed upper limb skeleton models. A two-part mixed-method sequential exploratory design was used to evaluate these activities. Part one was a questionnaire that evaluated the students' engagement with and perceptions of the models. Part two involved focus groups interviews, which were an extension of the survey questions in part one. The results of the study indicated that the majority of students found the models to be an engaging resource that helped improve their study habits. As a result, students strongly felt that the use of the models inspired greater academic confidence and overall better performance in their assessments. Overall, the models were an effective way of increasing the engagement and deep learning, and reinforced previous findings from the medical education research. Future research should investigate the effects of these models on student's grades within osteopathy and other allied health courses.

The Place for Religious Content in Clinical Ethics Consultations: A Reply to Janet Malek.

Janet Malek (HEC Forum 31(2):91-102, 2019) argues that a "clinical ethics consultant's religious worldview has no place in developing ethical recommendations or communicating about them with patients, surrogates, and clinicians." She offers five types of arguments in support of this thesis: arguments from (i) consensus, (ii) clarity, (iii) availability, (iv) consistency, and (v) autonomy. This essay shows that there are serious problems for each of Malek's arguments. None of them is sufficient to motivate her thesis (nor are they jointly sufficient). Thus, if it is true that the religious worldview of clinical ethics consultants (CECs) should play no role whatsoever in their work as consultants, this claim will need to be defended on some other ground.

Autoimmune liver disease following acute hepatitis A infection.

A male patient in his late 30s presented to our outpatient clinic at Mortimer Market Centre with worsening liver transaminases tests 2 months after a resolved acute hepatitis A infection. A diagnosis of parainfectious autoimmune-like hepatitis phenomena was made based on the history, laboratory and histological features.

Intensive upper limb neurorehabilitation in chronic stroke: outcomes from the Queen Square programme.

OBJECTIVE: Persistent difficulty in using the upper limb remains a major contributor to physical disability post-stroke. There is a nihilistic view about what clinically relevant changes are possible after the early post-stroke phase. The Queen Square Upper Limb Neurorehabilitation programme delivers high-quality, high-dose, high-intensity upper limb neurorehabilitation during a 3-week (90 hours) programme. Here, we report clinical changes made by the chronic stroke patients treated on the programme, factors that might predict responsiveness to therapy and the relationship between changes in impairment and activity. METHODS: Upper limb impairment and activity were assessed on admission, discharge, 6 weeks and 6 months after treatment, with modified upper limb Fugl-Meyer (FM-UL, max-54), Action Research Arm Test (ARAT, max-57) and Chedoke Arm and Hand Activity Inventory (CAHAI, max-91). Patient-reported outcome measures were recorded with the Arm Activity Measure (ArmA) parts A (0-32) and B (0-52), where lower scores are better. RESULTS: 224 patients (median time post-stroke 18 months) completed the 6-month programme. Median scores on admission were as follows: FM-UL = 26 (IQR 16-37), ARAT=18 (IQR 7-33), CAHAI=40 (28-55), ArmA-A=8 (IQR 4.5-12) and ArmA-B=38 (IQR 24-46). The median scores 6 months after the programme were as follows: FM-UL=37 (IQR 24-48), ARAT=27 (IQR 12-45), CAHAI=52 (IQR 35-77), ArmA-A=3 (IQR 1-6.5) and ArmA-B=19 (IQR 8.5-32). We found no predictors of treatment response beyond admission scores. CONCLUSION: With intensive upper limb rehabilitation, chronic stroke patients can change by clinically important differences in measures of impairment and activity. Crucially, clinical gains continued during the 6-month follow-up period.

Why are we misdiagnosing urinary tract infection in older patients? A qualitative inquiry and roadmap for staff behaviour change in the emergency department.

PURPOSE: The aim of this study was to identify the psychological and behavioural factors influencing clinicians managing older people with possible UTI in urgent care settings, and to develop an improvement roadmap. METHODS: Michie's behaviour change wheel and COM-B (Capability, Opportunity, Motivation, Behaviour Change) models were used as the theoretical basis for this study. Semi-structured interviews were undertaken with 21 purposively selected medical and nursing staff in a large urban emergency department in the East Midlands, United Kingdom. Analysis was informed by the framework approach. A participatory design approach was used to develop an improvement roadmap. RESULTS: Key themes emerging from the semi-structured interviews included lack of knowledge on the role of urine dipstick testing, bias towards older people, automatic testing, time and resource constraints, pressures from peers and patients, and fear of the legal consequences of inaction. A thematic networks map indicated complex interactions between psychological and behavioural factors. Among more than 50 different intervention ideas identified by the workshop participants, two interventions were prioritised for implementation: i) controlling the use of dip stick urine tests; ii) providing individualised feedback to staff regarding the outcomes of patients diagnosed and treated for UTI. CONCLUSIONS: Psychological and behavioural factors play a significant role in the misdiagnosis of UTI in older people. Systematic approaches incorporating these factors might improve patient outcomes. Future studies should focus on implementation and evaluating their effectiveness and sustainability.

Distributed learning or medical tourism? A Canadian residency program's experience in global health.

BACKGROUND: Global health experiences (GHEs) are becoming increasingly prevalent in surgical residency education. Although it may seem intuitive that participation in GHEs develops CanMEDS competencies, this has not been studied in depth in surgery. The purpose of this study is (1) to explore if and how otolaryngology-head and neck surgery (OHNS) resident participation in GHEs facilitates the development of CanMEDS competencies and (2) to develop an OHNS GHE tool to facilitate the integration of CanMEDS into GHE participation and evaluation. METHODS: An online survey explored the GHEs of current and past OHNS residents in Canada. Based on the data collected and a literature review, a foundational tool was then created to (1) enable OHNS residents to structure their GHEs into CanMEDS-related learning objectives and (2) enable OHNS program directors to more effectively evaluate residents' GHEs with respect to CanMEDS competencies. RESULTS: Participants' GHEs varied widely. These experiences often contributed informally to the development of several CanMEDS competencies. However, few residents had concrete objectives, rarely were CanMEDS roles clearly incorporated, and most residents were not formally evaluated during their experience. Residents felt they achieved greater learning when predeparture objectives and postexperience reflections were integrated into their GHEs. CONCLUSIONS: Although GHEs vary widely, they can serve as valuable forums for developing CanMEDS competencies among participating residents. Without clear objectives that adhere to the CanMEDS framework or formal assessment methods however, residents in GHEs risk becoming medical tourists. The use of an objective and evaluation tool may facilitate the creation of predeparture learning objectives, encourage self-reflection on their GHE, and better enable program directors to evaluate residents participating in GHEs.