Attitudes and Knowledge of Electroconvulsive Therapy: An Exploration of Medical Students' Perspectives.

AIMS: To explore knowledge and attitudes of medical students before and after exposure to a technology-enhanced learning and teaching (TELT) session about electroconvulsive therapy (ECT). BACKGROUND: Adequate knowledge of and attitudes toward ECT is essential for medical students. However, the impact of teaching on knowledge and attitudes is infrequently studied. METHODS: Fourth- and fifth year medical students at the University of Glasgow were provided with an online questionnaire before and after engaging in a remote TELT session, led by a consultant psychiatrist with expertise in ECT. The online teaching session used resources developed by a multidisciplinary team who specialize in ECT. The teaching session lasted around 1 hour. The questionnaire contained 3 sections: baseline demographics, knowledge of ECT, and attitudes toward ECT. Changes in scores were analyzed. RESULTS: Sixty-seven students completed the teaching session. Response rate to the precourse questionnaire was 68.7% (n = 46), and the postcourse questionnaire was 44.8% (n = 30). Prior to engaging with the learning materials, 9 students reported no knowledge of ECT and a third believed that ECT did not cause a seizure. In general, students who had personal experience of mental illness (friend, relative, or self) had more positive attitudes toward ECT and higher knowledge scores. In general, an increase in knowledge and attitude scores was found in the postcourse questionnaire. CONCLUSIONS: Exposing medical students to a TELT session focused on ECT during their psychiatric placement appeared to improve knowledge and attitudes surrounding ECT.

Does the visual field improve after initiation of intraocular pressure lowering in the United Kingdom Glaucoma Treatment Study?

PURPOSE: Evidence to support the hypothesis that visual field (VF) status can improve after initiation of intraocular pressure (IOP) reducing treatment is controversial. We take advantage of participant eligibility data from the United Kingdom Glaucoma Treatment Study (UKGTS) to test this hypothesis in newly diagnosed glaucomatous patients randomised to IOP lowering therapy or placebo. DESIGN: Multicentre, randomised, triple-masked, placebo-controlled trial. PARTICIPANTS: Newly diagnosed open-angle glaucoma patients in the UKGTS with eligibility and baseline data (n = 202 and n = 205 participants from the treatment and placebo groups, respectively). METHODS: UKGTS eligibility data, including two reliable VFs (Humphrey 24-2 SITA Standard) and IOP measurements were compared to UKGTS trial baseline data acquired after allocation to treatment (topical prostaglandin analog) or placebo eye drops. Mean change in VF mean deviation (MD) and proportion of eyes that improved MD by more than different thresholds were compared across this interval in the treatment and placebo groups. Secondary analyses included stratifying the groups by level of IOP, level of VF loss and age along with pointwise analyses including change in subsets of VF locations. MAIN OUTCOME MEASURE: Mean change in VF MD. RESULTS: Mean (standard deviation [SD]) time between eligibility/baseline visits and reduction in IOP was 12 (3) weeks and 4.8 (4.2) and 1.0 (3.6) mmHg for the treated and placebo eyes, respectively. Mean (SD) change in MD was almost the same for the treated (-0.03 (1.45) dB) and placebo groups (+0.08 (1.72) dB) (P=0.47). Proportion of participants with an MD improvement of 1 dB or more were similar for both groups (P=0.25). No association was found between MD improvement and magnitude of IOP lowering. Stratifying data by IOP, level of VF loss and age did not reveal any differences between the treated and placebo groups and neither did any of the pointwise VF analyses. CONCLUSION: Initial short-term VF changes in the treatment and placebo arms of UKGTS were the same. In these newly diagnosed patients (non-advanced glaucoma) we found no evidence to support the hypothesis that VF status improves after initial lowering of IOP by medical therapy.

Real-world evidence study on the early use of cemiplimab in the UK: REACT-CEMI (Real World evidence of advanced CSCC treatment with cemiplimab).

Background: Cemiplimab was licensed in the United Kingdom (UK) in 2019 for the treatment of patients with locally advanced and metastatic CSCC not suitable for curative surgery or radiotherapy (advanced CSCC [aCSCC]). No UK multi-center studies have investigated the real-world experience of cemiplimab post marketing authorization in aCSCC. Methods: This non-interventional retrospective study (10 UK centers) involved data collection from medical records of patients with aCSCC who initiated cemiplimab treatment between 2 July 2019 and 30 November 2020. The study period was a minimum of 12 and a maximum of 36 months post cemiplimab initiation. The primary objective was to describe the real-world clinical effectiveness of cemiplimab (primary outcome: overall response rate [ORR]). Results: Of 105 patients, 70% (n=73/105) were male (median [range] age at index of 78.5 [55.4-93.2] years); most patients (63% [n=50/80]) had an Eastern Cooperative Oncology Group (ECOG) score of 1 and 62% (n=63/102) had metastatic disease. The ORR within 12 months was 42% (95% confidence interval [CI] 32%-51%) and the disease control rate was 62% (n=65/105). The median (95% CI) real-world progression-free survival and overall survival from index was 8.6 (6.0-18.7) and 21.0 (14.7-25.2) months, respectively. The median (range) number of cemiplimab infusions was 11.0 (1.0-44.0). Eighty-seven percent experienced no cemiplimab treatment interruptions; 13% (n=14/105) interrupted treatment due to immune-related adverse reactions (irARs) (47% [n=9/19] of treatment interruption events). Eighty-five percent (n=89/105) of patients had discontinued cemiplimab treatment by the end of the study; where reasons for discontinuation were recorded, 20% (n=17/87) discontinued due to the completion of their 2-year treatment course. Nineteen percent (n=20/105) of patients experienced irARs. Conclusion: Effectiveness and safety data in this study are broadly similar to previous real-world studies of cemiplimab and the EMPOWER-CSCC1 clinical trial; with our cohort representing a broader population (included immunocompromised and transplant patients). Results support the use of cemiplimab for the treatment of aCSCC in a real-world setting.

Addressing Technical Failures in a Diabetic Retinopathy Screening Program.

Purpose: Diabetic retinopathy (DR) is a preventable cause of blindness detectable through screening using retinal digital photography. The Irish National Diabetic Retina Screening (DRS) programme, Diabetic RetinaScreen, provides free screening services to patients with diabetes from aged 12 years and older. A technical failure (TF) occurs when digital retinal imaging is ungradable, resulting in delays in the diagnosis and treatment of sight-threatening disease. Despite their impact, the causes of TFs, and indeed the utility of interventions to prevent them, have not been extensively examined. Aim: Primary analysis aimed to identify factors associated with TF. Secondary analysis examined a subset of cases, assessing patient data from five time points between 2019 and 2021 to identify photographer/patient factors associated with TF. Methods: Patient data from the DRS database for one provider were extracted for analysis between 2018 and 2022. Information on patient demographics, screening results, and other factors previously associated with TF were analyzed. Primary analysis involved using mixed-effects logistic regression models with nested patient-eye random effects. Secondary analysis reviewed a subset of cases in detail, checking for causes of TF. Results: The primary analysis included a total of 366,528 appointments from 104,407 patients over 5 years. Most patients had Type 2 diabetes (89.2%), and the overall TF rate was 4.9%. Diabetes type and duration, dilate pupil status, and the presence of lens artefacts on the camera were significantly associated with TF. The Secondary analysis identified the primary cause of TF was found to be optically dense cataracts, accounting for over half of the TFs. Conclusion: This study provides insight into the causes of TF within the Irish DRS program, highlighting cataracts as the primary contributing factor. The identification of patient-level factors associated with TF facilitates appropriate interventions that can be put in place to improve patient outcomes and minimize delays in treatment and diagnosis.

Outcomes from a national screening program for Ukrainian refugees at risk of drug resistant tuberculosis in Wales.

High rates of drug-resistant tuberculosis in Ukraine suggest screening is necessary to mitigate public health hazards for host populations. A pathway was implemented in Wales and data prospectively collected Between 8 April and 21 December 2022. Of 5425 Ukrainian arrivals, notifications were received by TB teams on 2395 (44%) of whom 1955 (82%) were screened. The refugees were young (median age 30, IQR 14-41), and predominantly female (66.1%). Interferon- gamma release assay (IGRA) tests were positive in 112 (6.5%). One Case of active tuberculosis was identified (0.05%). Our data supports European guidelines that routine screening of this population is not recommended, but we remain uncertain as to the risks of this population going forwards.

Measures of multiple deprivation and visual field loss in glaucoma clinics in England: lessons from big data.

BACKGROUND/OBJECTIVES: To examine the association between multiple deprivation with late diagnosis and rapid worsening of glaucoma in patients in English hospital eye services (HES). METHODS: 602,439 visual fields (VFs) were extracted from five regionally different glaucoma clinics in England. Mean Deviation (MD) worse than -12 dB was used as a surrogate definition for advanced VF loss at diagnosis in patients with ≥2 reliable VF records. MD loss worse than -1 dB per year was used to define rapid VF progression in patients with ≥6 VFs. Patient data were stratified into deciles of the Index of Multiple Deprivation (IMD) from residential postcodes. RESULTS: There was an association between IMD and advanced VF loss at diagnosis in 44,956 patients with 18% (293/1608) and 11% (771/6929) in the most and least deprived IMD decile, respectively. Age-corrected odds ratio (OR) for having advanced VF loss at entry into HES was 1.42 (95% confidence interval [CI] 1.21-1.67) and 0.75 (95% CI: 0.66-0.85) in the most and least deprived IMD decile respectively (reference = fifth decile). In 15,094 patients with follow up data (median [interquartile range] of 6.9 [4.5, 10.0] years), the proportion having rapid VF progression did not differ across the IMD spectrum. CONCLUSION: Large-scale VF data from clinics indicates that glaucoma severity at presentation to English HES is associated with levels of multiple deprivation. We found no evidence to suggest likelihood of having rapid VF progression during follow-up is associated with IMD; this hints at equity of glaucoma care and outcomes once patients are in English HES.

Hydrogel-forming microarray patch mediated transdermal delivery of tetracycline hydrochloride.

Antibiotic resistance is one of the most serious health problems today and is expected to worsen in the coming decades. It has been suggested that antibiotic administration routes that bypass the human gut could potentially tackle this problem. In this work, an antibiotic hydrogel-forming microarray patch (HF-MAP) system, which can be used as an alternative antibiotic delivery technology, has been fabricated. Specifically, poly(vinyl alcohol)/poly(vinylpyrrolidone) (PVA/PVP) microarray showed excellent swelling properties with >600% swelling in PBS over 24 h. The tips on the HF-MAP were proven to be able to penetrate a skin model which is thicker than stratum corneum. The antibiotic (tetracycline hydrochloride) drug reservoir was mechanically robust and dissolved completely in an aqueous medium within a few minutes. In vivo animal studies using a Sprague Dawley rat model showed antibiotic administration using HF-MAP achieved a sustained release profile, in comparison with animals receiving oral gavage and intravenous (IV) injection, with a transdermal bioavailability of 19.1% and an oral bioavailability of 33.5%. The maximum drug plasma concentration for HF-MAP group reached 7.40 ± 4.74 µg/mL at 24 h, whereas the drug plasma concentration for both oral (5.86 ± 1.48 µg/mL) and IV (8.86 ± 4.19 µg/mL) groups peaked soon after drug administration and had decreased to below the limit of detection at 24 h. The results demonstrated that antibiotics can be delivered by HF-MAP in a sustained manner.

Large-scale physically accurate modelling of real proton exchange membrane fuel cell with deep learning.

Proton exchange membrane fuel cells, consuming hydrogen and oxygen to generate clean electricity and water, suffer acute liquid water challenges. Accurate liquid water modelling is inherently challenging due to the multi-phase, multi-component, reactive dynamics within multi-scale, multi-layered porous media. In addition, currently inadequate imaging and modelling capabilities are limiting simulations to small areas (<1 mm2) or simplified architectures. Herein, an advancement in water modelling is achieved using X-ray micro-computed tomography, deep learned super-resolution, multi-label segmentation, and direct multi-phase simulation. The resulting image is the most resolved domain (16 mm2 with 700 nm voxel resolution) and the largest direct multi-phase flow simulation of a fuel cell. This generalisable approach unveils multi-scale water clustering and transport mechanisms over large dry and flooded areas in the gas diffusion layer and flow fields, paving the way for next generation proton exchange membrane fuel cells with optimised structures and wettabilities.

The Effect on Patients' Visual Acuity and Grade, Secondary to Non-Attendance at Treatment Centers, Post Referral from Diabetic RetinaScreen Ireland.

Background: Patient non-attendance following referral to hospital is a significant challenge, in particular, for persons with diabetes. Aim: We sought to determine the impact on both visual acuity and the subsequent follow-up retinopathy grade of patients when they fail to attend Diabetic Retinopathy Treatment (DRT) Centers following referral from Diabetic RetinaScreen (DRS). Methods: A retrospective analysis of patients discharged from DRT due to multiple consecutive missed appointments between January 2016 and June 2021. Patients discharged for non-attendance were compared with patients discharged from completed treatment. Results: Of the 24,945 NEC patients referred to DRT, 5900 (24%) and 9345 (37%) were discharged back to DRS due to non-attendance and completed treatment, respectively. Those discharged for non-attendance were younger (60.7 v 63.4, p < 0.001) and had higher proportions of males (67% v 63%, p < 0.001) and people with type 1 diabetes (27% v 18%, p < 0.001). After attending rescreening after discharge, those discharged for non-attendance were significantly more likely to have a worsening of DR grade (26% v 8%, p < 0.001). Conclusion: Despite being notified that further investigation (with possible treatment) was required post DRS, many diabetic patients failed to attend for further management of their eye care in DRT. These patients had worse visual outcomes compared to those that attended. Improved patient education and communication are required to mitigate against the consequences of non-attendance.

Phases of Match-Play in Professional Australian Football: Positional Demands and Match-Related Fatigue.

This study examined the influence of player position and match quarter on activity profiles during the phases of play in Australian Football. Global positioning satellite data was collected for one season from an Australian Football League team for nomadic, key position and ruck players (age: 24.8 ± 4.2 years, body mass: 88.3 ± 8.7 kg, height: 1.88 ± 0.8 m). Separate linear mixed models and effect sizes were used to analyse differences between positions and game quarter within each phase of play for values of distance, speed and metabolic power indices. There were clear differences between positions for low-speed running, high-speed running, total distance and average speed. Nomadic players generally recorded the highest match running outputs, followed by key position players and ruckmen. Within each position, offence and defence involved the highest intensities, followed by contested play and then stoppage periods. Across the four quarters, there were small to large reductions in average speed, high-speed running, high power and energy expenditure during offence, defence and contested play, but not during stoppages. Accordingly, conditioning staff should consider the intermittent intensities of the phases of match-play for each position to optimally prepare players for competition. Reductions in match intensities were evident during active periods of play providing implications for real-time monitoring to optimise the timing of rotations.

Microbial communities of halite deposits and other hypersaline environments.

Large regions of Earth's surface are underlain by salt deposits that evaporated from ancient oceans and are populated by extreme halophilic microbes. While the microbiology of ancient evaporites has been well studied, the ecology of halite deposits and more recently formed NaCl "salticle" stalactite structures (speleothems) in a Triassic halite mine are less well characterized. The microbiome of Kilroot Salt Mine was profiled using conventional and enhanced culturing techniques. From this, 89 halophilic archaeal isolates from six known genera, and 55 halophilic or halotolerant bacterial isolates from 18 genera were obtained. Culture-independent metagenomic approaches also revealed that culturing techniques were inadvertently biased toward specific taxa, and the need for optimized isolation procedures are required to enhance cultivation diversity. Speleothems formed from saturated brines are unique structures that have the potential to entomb haloarchaea cells for thousands of years within fluid inclusions. The presence of such fluid inclusions, alongside the high abundance of genes related to glycerol metabolism, biofilm formation, and persister cell formation is highly suggestive of an environmental niche that could promote longevity and survivability. Finally, previous studies reporting the discovery of novel biocatalysts from the Kilroot mine microbiome, suggests that this environment may be an untapped source of chemical diversity with high biodiscovery potential.

n-Butyllithium-Induced Tandem [3,3]-Sigmatropic Rearrangement and Carbonyl Olefination of Allyl-1,1-dichlorovinyl Ethers.

Exposure of dichlorovinyl ethers 1 to n-butyllithium and addition of saturated or unsaturated aldehydes, ketones, or esters at ambient temperature furnishes rearranged α,ß-unsaturated carboxylic acids, isolated as their corresponding methyl esters 2 in 48-91% overall yields. Exposure of dichlorovinyl ethers 1 to n-butyllithium, addition of aldehydes, ketones, dialdehydes, or diketones at -78 °C, and warming to 80 °C in the presence of SiO2 provide 1,4-dienes 3 or cycloalken-1-ols (or their dehydration products) 4 in 45-72% overall yields.

Novel Phage-Derived Depolymerase with Activity against Proteus mirabilis Biofilms.

The adherence of Proteus mirabilis to the surface of urinary catheters leads to colonization and eventual blockage of the catheter lumen by unique crystalline biofilms produced by these opportunistic pathogens, making P. mirabilis one of the leading causes of catheter-associated urinary tract infections. The Proteus biofilms reduce efficiency of antibiotic-based treatment, which in turn increases the risk of antibiotic resistance development. Bacteriophages and their enzymes have recently become investigated as alternative treatment options. In this study, a novel Proteus bacteriophage (vB_PmiS_PM-CJR) was isolated from an environmental sample and fully characterized. The phage displayed depolymerase activity and the subsequent genome analysis revealed the presence of a pectate lyase domain in its tail spike protein. The protein was heterologously expressed and purified; the ability of the purified tail spike to degrade Proteus biofilms was tested. We showed that the application of the tail spike protein was able to reduce the adherence of bacterial biofilm to plastic pegs in a MBEC (minimum biofilm eradication concentration) assay and improve the survival of Galleria mellonella larvae infected with Proteus mirabilis. Our study is the first to successfully isolate and characterize a biofilm depolymerase from a Proteus phage, demonstrating the potential of this group of enzymes in treatment of Proteus infections.

In Situ Photopolymerization of Acrylamide Hydrogel to Coat Cellulose Acetate Nanofibers for Drug Delivery System.

In this study we developed electrospun cellulose acetate nanofibers (CANFs) that were loaded with a model non-steroidal anti-inflammatory drug (NSAID) (ibuprofen, Ib) and coated with poly(acrylamide) (poly-AAm) hydrogel polymer using two consecutive steps: an electrospinning process followed by photopolymerization of AAm. Coated and non-coated CANF formulations were characterized by several microscopic and spectroscopic techniques to evaluate their physicochemical properties. An analysis of the kinetic release profile of Ib showed noticeable differences due to the presence or absence of the poly-AAm hydrogel polymer. Poly-AAm coating facilitated a constant release rate of drug as opposed to a more conventional burst release. The non-coated CANFs showed low cumulative drug release concentrations (ca. 35 and 83% at 5 and 10% loading, respectively). Conversely, poly-AAm coated CANFs were found to promote the release of drug (ca. 84 and 99.8% at 5 and 10% loading, respectively). Finally, the CANFs were found to be superbly cytocompatible.