19 research outputs found
A site assessment tool for inpatient controlled human infection models for enteric disease pathogens
The use of the controlled human infection model to facilitate product development and to advance understanding of host-pathogen interactions is of increasing interest. While administering a virulent (or infective) organism to a susceptible host necessitates an ongoing evaluation of safety and ethical considerations, a central theme in conducting these studies in a safe and ethical manner that yields actionable data is their conduct in facilities well-suited to address their unique attributes. To that end, we have developed a framework for evaluating potential sites in which to conduct inpatient enteric controlled human infection model to ensure consistency and increase the likelihood of success.publishedVersio
Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease
Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al
Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome
Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome
Team Based Learning In The Surgery Clerkship Impact On Student Examination Scores Evaluations And Perceptions
OBJECTIVE There is little evidence for effectiveness of team-based learning (TBL) in specialties such as Surgery. We developed and instituted TBLs in surgery clerkship and compared National Board of Medical Examiners (NBME) Surgery Subject Exam scores before and after implementation. We also analyzed students’ feedback for their perception of TBLs. DESIGN, SETTING, and PARTICIPATNTS The TBLs were transitioned into the curriculum during the 2013-2014 academic year. The “before” and “after” implementation periods were 2011-2013 and 2014-2016, respectively. NBME Surgery Subject Examination scores at our institution and nationally were compared using the independent samples t test. Satisfaction with the clerkship was assessed with Association of American Medical Colleges Graduate Questionnaire data. Student feedback regarding TBL was gathered at the end of each surgery rotation and were analyzed for themes, both positive and negative. RESULTS Mean NBME score was higher at our institution than nationally, both before (77.10 ± 8.75 vs. 75.20 ± 8.95, p = 0.032) and after (74.65 ± 8.0 vs. 73.10 ± 8.55, p = 0.071) TBL implementation. The mean score decreased following TBL implementation at our medical school (77.10 ± 8.75 vs. 74.65 ± 8.00, p = 0.039), but it was also lower nationally (75.20 ± 8.95 vs. 73.10 ± 8.55, p \u3c 0.001). Further, students were more likely to rate the surgery clerkship as “good and/or excellent” on the Association of American Medical Colleges Graduate Questionnaire after TBL implementation (84.6% vs. 73.7%). In qualitative assessment, learners stated that TBLs were informative, helpful in studying for the shelf exam, and viewed them as an opportunity for interactive learning, and thus requested more TBLs. Areas for improvement included reading materials, directions, and organization of sessions. CONCLUSIONS Student perception of TBL into our surgery clerkship has been both positive and provided feedback for improvement. In addition, our medical school graduates have continued to assess their surgery experience as “good” or “excellent” by a large majority. Concurrently, our NBME scores remain above the national mean. We believe our medical students benefit from a well-organized TBL and its active approach to learning during the surgery clerkship with no loss of fundamental surgery knowledge
Team Based Learning In The Surgery Clerkship Impact On Student Examination Scores Evaluations And Perceptions
OBJECTIVE There is little evidence for effectiveness of team-based learning (TBL) in specialties such as Surgery. We developed and instituted TBLs in surgery clerkship and compared National Board of Medical Examiners (NBME) Surgery Subject Exam scores before and after implementation. We also analyzed students’ feedback for their perception of TBLs. DESIGN, SETTING, and PARTICIPATNTS The TBLs were transitioned into the curriculum during the 2013-2014 academic year. The “before” and “after” implementation periods were 2011-2013 and 2014-2016, respectively. NBME Surgery Subject Examination scores at our institution and nationally were compared using the independent samples t test. Satisfaction with the clerkship was assessed with Association of American Medical Colleges Graduate Questionnaire data. Student feedback regarding TBL was gathered at the end of each surgery rotation and were analyzed for themes, both positive and negative. RESULTS Mean NBME score was higher at our institution than nationally, both before (77.10 ± 8.75 vs. 75.20 ± 8.95, p = 0.032) and after (74.65 ± 8.0 vs. 73.10 ± 8.55, p = 0.071) TBL implementation. The mean score decreased following TBL implementation at our medical school (77.10 ± 8.75 vs. 74.65 ± 8.00, p = 0.039), but it was also lower nationally (75.20 ± 8.95 vs. 73.10 ± 8.55, p \u3c 0.001). Further, students were more likely to rate the surgery clerkship as “good and/or excellent” on the Association of American Medical Colleges Graduate Questionnaire after TBL implementation (84.6% vs. 73.7%). In qualitative assessment, learners stated that TBLs were informative, helpful in studying for the shelf exam, and viewed them as an opportunity for interactive learning, and thus requested more TBLs. Areas for improvement included reading materials, directions, and organization of sessions. CONCLUSIONS Student perception of TBL into our surgery clerkship has been both positive and provided feedback for improvement. In addition, our medical school graduates have continued to assess their surgery experience as “good” or “excellent” by a large majority. Concurrently, our NBME scores remain above the national mean. We believe our medical students benefit from a well-organized TBL and its active approach to learning during the surgery clerkship with no loss of fundamental surgery knowledge
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Value of Handheld Optical Illuminated Magnifiers for Sustained Silent Reading by Visually Impaired Adults
SignificanceVision rehabilitation providers tend to recommend handheld, illuminated optical magnifiers for short-duration spot reading tasks, but this study indicates that they are also a viable option to improve sustained, continuous text reading (e.g., books or magazines), especially for visually impaired adults who read slowly with only spectacle-based near correction.PurposeThe utility of handheld optical magnifiers for sustained silent reading tasks involving normal-sized continuous text could be a valuable indication that is not recognized by vision rehabilitation providers and patients.MethodsHandheld, illuminated optical magnifiers were dispensed to 29 visually impaired adults who completed the sustained silent reading test by phone at baseline without the new magnifier and 1 month after using the magnifier. Reading speed in words per minute (wpm) was calculated from the time to read each page and then averaged across up to 10 pages or determined for the fastest read page (maximum).ResultsFrom baseline without the magnifier to 1 month with the magnifier, there was a significant improvement in mean reading speed by 14 wpm (95% confidence interval [CI], 2.6 to 24; P = .02) and for maximum reading speed by 18 wpm (95% CI, 5.4 to 30; P = .005) on average across participants. Participants who had slower baseline reading speeds without the magnifier demonstrated significantly greater improvements in mean and maximum reading speeds on average with the magnifier (95% CI, 8 to 32 [ P = .003]; 95% CI, 4 to 36 [ P = .02]). A significantly greater number of pages were read with the new magnifier than without it (Wilcoxon z = -2.5; P = .01). A significantly greater number of pages were read with the magnifier by participants who read fewer pages at baseline (95% CI, 0.57 to 5.6; P = .02) or had greater improvements in mean reading speed (95% CI, 0.57 to 5.6; P = .007).ConclusionsMany visually impaired adults read more quickly and/or read a greater number of pages after using a new magnifier for a month than compared to without it. The largest gains occurred among those with more difficulty at baseline, indicating the potential to improve reading rates with magnifiers for those with greater deficits