Observational Outcome Measures to Evaluate Assistive Technology Use by People with Dementia - Report Series # 12

This report describes a digital video-audio behavioural observation methodology for use in a naturalistic setting to evaluate communication rehabilitation interventions for older adults with dementia. Behavioural observation via recorded video-audio offers a number of advantages over other data collection methodologies, which can be subject to a number of biases and limitations, some of which are discussed. In this study, high quality digital audio-video recordings were collected on participants attending a respite care day program. Recording equipment was inconspicuously placed, and measurement occurred either during normal day-to-day activities or during more directed activities (e.g., playing bingo). The recordings can be used to document the occurrence of behaviours and paired behaviours of interest over extended periods of time or selected samples of interest can be downloaded for detailed analysis including lag-sequential analyses. It was found that behavioural observation can complement traditional objective measures of impairment and subjective questionnaire measures, in accordance with the World Health Organization’s (WHO) International Classification of Functioning, Disability, and Health (2001)

Locally performed postoperative circulating tumour DNA testing performed during routine clinical care to predict recurrence of colorectal cancer

Background: Identifying patients at high risk for colorectal cancer recurrence is essential for improving prognosis. In the postoperative period, circulating tumour DNA (ctDNA) has been demonstrated as a significant prognostic indicator of recurrence. These results have been obtained under the strict rigours of clinical trials, but not validated in a real-world setting using in-house testing. We report the outcomes of locally performed postoperative ctDNA testing conducted during routine clinical care and the association with the recurrence of colorectal cancer. Methods: We recruited 36 consecutive patients with newly diagnosed colorectal cancer between 2018 and 2020. Postoperative plasma samples were collected at the first outpatient review following resection. Tumour-informed ctDNA analysis was performed using droplet digital polymerase chain reaction or targeted next-generation sequencing. Results: At the time of surgery, there were 24 patients (66.7%) with localized cancer, nine (25%) with nodal spread, and three (8.3%) with metastatic disease. The median time from surgery to plasma sample donation was 22 days (IQR 20–28 days). At least one somatic mutation was identified in primary tumour tissue for 28 (77.8%) patients. Postoperative ctDNA was detected in five patients (13.9%). The median duration of follow-up was 32.0 months (IQR 27.2–38.1 months). Two patients (5.56%) developed metastatic recurrence. However, neither had detectable postoperative ctDNA. There were no instances of loco-regional recurrence. Conclusion: Analysis of postoperative ctDNA testing can be performed locally, however this study did not reproduce the adverse association between detectable postoperative ctDNA and the development of colorectal cancer recurrence seen in clinical trials

The Grizzly, February 27, 1981

Police Involvement: Fraternity Pledging Marred by Bad Reports • Lewis Thomas Graduation Speaker • FCA Gearing Up for Special Olympics • Off-Campus Housing Explored by USGA • USGA Notes • Wickersham Outlines Fall Semester Senior Symposium • Departmental Focus: Romance Languages • Middle East: Soviet Rivalry Topic of Forum • Beta Sig to Sponsor Franken & Davis • Cafe International Opens Tonight • Bierprobe Taste-Testing a Big Success • Reborn Songfest Loses Appeal • IFC Dance Slated for March 20 • You See UC to Become Regular Friday Feature • Registration Delayed • Gifford Heading for Nationals • Lady Swimmers End Season at .500 • Basketball Shooting for NCAA Tournament • Aquabears Have High Hopes for MACs • Sweeney, DiMattia Take 1sts in Indoor Track • Women Hoopsters Enter Playoffs Looking for Titlehttps://digitalcommons.ursinus.edu/grizzlynews/1054/thumbnail.jp

GLA-modified RNA treatment lowers GB3 levels in iPSC-derived cardiomyocytes from Fabry-affected individuals

Recent studies in non-human model systems have shown therapeutic potential of nucleoside-modified messenger RNA (modRNA) treatments for lysosomal storage diseases. Here, we assessed the efficacy of a modRNA treatment to restore the expression of the galactosidase alpha (GLA), which codes for α-Galactosidase A (α-GAL) enzyme, in a human cardiac model generated from induced pluripotent stem cells (iPSCs) derived from two individuals with Fabry disease. Consistent with the clinical phenotype, cardiomyocytes from iPSCs derived from Fabry-affected individuals showed accumulation of the glycosphingolipid Globotriaosylceramide (GB3), which is an α-galactosidase substrate. Furthermore, the Fabry cardiomyocytes displayed significant upregulation of lysosomal-associated proteins. Upon GLA modRNA treatment, a subset of lysosomal proteins were partially restored to wild-type levels, implying the rescue of the molecular phenotype associated with the Fabry genotype. Importantly, a significant reduction of GB3 levels was observed in GLA modRNA-treated cardiomyocytes, demonstrating that α-GAL enzymatic activity was restored. Together, our results validate the utility of iPSC-derived cardiomyocytes from affected individuals as a model to study disease processes in Fabry disease and the therapeutic potential of GLA modRNA treatment to reduce GB3 accumulation in the heart.</p

Migalastat HCl reduces globotriaosylsphingosine (Lyso- Gb3) in Fabry transgenic mice and in the plasma of Fabry patients

Fabry disease (FD) results from mutations in the gene (GLA) that encodes the lysosomal enzyme a-galactosidase A (a-Gal A), and involves pathological accumulation of globotriaosylceramide (GL-3) and globotriaosylsphingosine (lyso-Gb3). Migalastat hydrochloride (GR181413A) is a pharmacological chaperone that selectively binds, stabilizes, and increases cellular levels of a-Gal A. Oral administration of migalastat HCl reduces tissue GL-3 in Fabry transgenic mice, and in urine and kidneys of some FD patients. A liquid chromatography-tandem mass spectrometry method was developed to measure lyso-Gb3 in mouse tissues and human plasma. Oral administration of migalastat HCl to transgenic mice reduced elevated lyso-Gb3 levels up to 64%, 59%, and 81% in kidney, heart, and skin, respectively, generally equal to or greater than observed for GL-3. Furthermore, baseline plasma lyso-Gb3 levels were markedly elevated in six male FD patients enrolled in Phase 2 studies. Oral administration of migalastat HCl (150 mg QOD) reduced urine GL-3 and plasma lyso-Gb3 in three subjects (range: 15% to 46% within 48 weeks of treatment). In contrast, three showed no reductions in either substrate. These results suggest that measurement of tissue and/or plasma lyso-Gb3 is feasible and may be warranted in future studies of migalastat HCl or other new potential therapies for FD

Multi-drug resistant Acinetobacter infections in critically injured Canadian forces soldiers

<p>Abstract</p> <p>Background</p> <p>Military members, injured in Afghanistan or Iraq, have returned home with multi-drug resistant <it>Acinetobacter baumannii </it>infections. The source of these infections is unknown.</p> <p>Methods</p> <p>Retrospective study of all Canadian soldiers who were injured in Afghanistan and who required mechanical ventilation from January 1 2006 to September 1 2006. Patients who developed <it>A. baumannii </it>ventilator associated pneumonia (VAP) were identified. All <it>A. baumannii </it>isolates were retrieved for study patients and compared with <it>A. baumannii </it>isolates from environmental sources from the Kandahar military hospital using pulsed-field gel electrophoresis (PFGE).</p> <p>Results</p> <p>During the study period, six Canadian Forces (CF) soldiers were injured in Afghanistan, required mechanical ventilation and were repatriated to Canadian hospitals. Four of these patients developed <it>A. baumannii </it>VAP. <it>A. baumannii </it>was also isolated from one environmental source in Kandahar – a ventilator air intake filter. Patient isolates were genetically indistinguishable from each other and from the isolates cultured from the ventilator filter. These isolates were resistant to numerous classes of antimicrobials including the carbapenems.</p> <p>Conclusion</p> <p>These results suggest that the source of <it>A. baumannii </it>infection for these four patients was an environmental source in the military field hospital in Kandahar. A causal linkage, however, was not established with the ventilator. This study suggests that infection control efforts and further research should be focused on the military field hospital environment to prevent further multi-drug resistant <it>A. baumannii </it>infections in injured soldiers.</p

Enhancing authenticity, diagnosticity and equivalence (AD-Equiv) in multicentre OSCE exams in health professionals education: protocol for a complex intervention study

Introduction: Objective structured clinical exams (OSCEs) are a cornerstone of assessing the competence of trainee healthcare professionals, but have been criticised for (1) lacking authenticity, (2) variability in examiners’ judgements which can challenge assessment equivalence and (3) for limited diagnosticity of trainees’ focal strengths and weaknesses. In response, this study aims to investigate whether (1) sharing integrated-task OSCE stations across institutions can increase perceived authenticity, while (2) enhancing assessment equivalence by enabling comparison of the standard of examiners’ judgements between institutions using a novel methodology (video-based score comparison and adjustment (VESCA)) and (3) exploring the potential to develop more diagnostic signals from data on students’ performances. Methods and analysis: The study will use a complex intervention design, developing, implementing and sharing an integrated-task (research) OSCE across four UK medical schools. It will use VESCA to compare examiner scoring differences between groups of examiners and different sites, while studying how, why and for whom the shared OSCE and VESCA operate across participating schools. Quantitative analysis will use Many Facet Rasch Modelling to compare the influence of different examiners groups and sites on students’ scores, while the operation of the two interventions (shared integrated task OSCEs; VESCA) will be studied through the theory-driven method of Realist evaluation. Further exploratory analyses will examine diagnostic performance signals within data. Ethics and dissemination: The study will be extra to usual course requirements and all participation will be voluntary. We will uphold principles of informed consent, the right to withdraw, confidentiality with pseudonymity and strict data security. The study has received ethical approval from Keele University Research Ethics Committee. Findings will be academically published and will contribute to good practice guidance on (1) the use of VESCA and (2) sharing and use of integrated-task OSCE stations

Body-composition reference data for simple and reference techniques and a 4-component model: A new UK reference child

Background: A routine pediatric clinical assessment of body composition is increasingly recommended but has long been hampered by the following 2 factors: a lack of appropriate techniques and a lack of reference data with which to interpret individual measurements. Several techniques have become available, but reference data are needed. Objective: We aimed to provide body-composition reference data for use in clinical practice and research. Design: Body composition was measured by using a gold standard 4-component model, along with various widely used reference and bedside methods, in a large, representative sample of British children aged from 4 to ≥20 y. Measurements were made of anthropometric variables (weight, height, 4 skinfold thicknesses, and waist girth), dual-energy X-ray absorptiometry, body density, bioelectrical impedance, and total body water, and 4-component fat and fat-free masses were calculated. Reference charts and SD scores (SDSs) were constructed for each outcome by using the lambda-mu-sigma method. The same outcomes were generated for the fat-free mass index and fat mass index. Results: Body-composition growth charts and SDSs for 5-20 y were based on a final sample of 533 individuals. Correlations between SDSs by using different techniques were ≥0.68 for adiposity outcomes and ≥0.80 for fat-free mass outcomes. Conclusions: These comprehensive reference data for pediatric body composition can be used across a variety of techniques. Together with advances in measurement technologies, the data should greatly enhance the ability of clinicians to assess and monitor body composition in routine clinical practice and should facilitate the use of body-composition measurements in research studies. © 2012 American Society for Nutrition