Micro-eliminating HCV in 8 diverse prisons that serve a general population of 3.7 million in the Yorkshire region of England

Background: National Health Service England (NHSE) plans to eliminate Hepatitis C (HCV) by 2025. With a reported HCV prevalence of about 6% in male prisons, and about 12% in female prisons, secure environments are an essential component of this elimination plan. Yorkshire is a region in England with a general population of about 3.7 M. PPG is the provider of healthcare to 9 prisons in Yorkshire, with approximately 6,000 residents, many of whom are current, or previous, substance users. Description of model of care/intervention: To support NHSE in the elimination of HCV, a partnership between Gilead Sciences, Practice Plus Group (PPG) and the Hepatitis C Trust (HCT) was formed in 2019. This partnership works with prison and hospital teams to optimise test and treat pathways for new prison admissions. In addition, whole prison HCV Intensive Test and Treat events (HITT programmes) were run in targeted prisons to ensure testing of residents who were incarcerated before these optimisations were implemented. Effectiveness: HCV screening, within 7 days of prison entry, increased from 27% in May 2019 to 93% in January 2022. This increase was achieved despite COVID-19 restrictions remaining in place since March 2020 across all English prisons. In addition, HITT programmes were used to test residents who were missed at prison entry. The overall result is that 8/9 prisons have achieved microelimination status, as defined by: >= 95% of prison residents tested within the previous 12 months, >= 90% of RNA positive patients treated or initiated on treatment and presence of a robust system to review ongoing testing and treatment performance to ensure these targets are maintained. Conclusion and next steps: Micro-elimination of HCV will now need to be maintained in these prisons by ensuring the uptake of HCV testing remains>95%. Plans are in place to micro-eliminate the final prison-which is a high-security prison presenting unique challenges to HCV micro-elimination.

Things that dropped off during COVID

Introduction: The COVID-19 pandemic placed a renewed focus on transmission of respiratory infections in healthcare settings. However, little is known about the direct and indirect impacts on surveillance and infection prevention and control activities to limit transmission of other communicable diseases such as multidrug-resistant organisms (MDROs). Method(s): We conducted retrospective cross-sectional audits of compliance with routine screening and cleaning practices for MDROs (including vancomycin-resistant enterococci [VRE] and extended-spectrum beta-lactamase-[ESBL]-producing and carbapenemase-producing [CPE] Enterobacterales) in a tertiary hospital, where patients admitted to high-risk wards are screened upon admission and weekly. We correlated this with observed transmission events and an organisation-wide point-prevalence survey for MDRO colonisation. Result(s): Compliance with routine MDRO screening practices was lower than pre-pandemic. Additionally, interventions to limit environmental contamination with CPE had been neglected during the pandemic. This corresponded with an increase in CPE transmission. Audits of clinical staff infection prevention and control practices found missed opportunities to screen and identify colonised patients, as well as curtailed control measures during the pandemic, both correlating with MDRO transmission. Conclusion(s): Ongoing engagement of staff and senior decision makers in healthcare facilities is critical to maintaining infection control standards. At our institution, we found a lapse in standards during the COVID-19 pandemic was associated with an increase in MDRO transmission.Copyright © 2022

Qualitative Analysis of Video-Based Culinary Training on Pediatric Critical Care Clinician Perceptions of Wellness: A Pilot Study

Video conference software has been increasingly used during the COVID-19 pandemic, but it is unknown if pediatric critical care providers would participate in culinary training via video conference in an effort to improve their wellness. The study aims were to (1) assess the feasibility of implementing a video-based culinary training wellness intervention;and (2) understand the barriers and motivators to attaining wellness from the perspective of pediatric critical care clinicians. We conducted, transcribed, and analyzed pre- and post-intervention semi-structured interviews using a directed content analysis approach. Four participants were included in this study. Pre-intervention qualitative analysis identified 3 themes: (1) Job-specific constraints contributed to poorer eating habits;(2) Poor nutrition was related to anxiety levels and job stress;(3) Meal preparation improved healthy eating. Post-intervention analysis identified 3 themes: (1) Wellness intervention was enhanced by involving loved ones;(2) Course improvement suggestions focused on more participants;(3) Major impacts from the course focused on cooking higher quality meals, obtaining new cooking tools, and applying new techniques. By providing pediatric critical care clinicians an opportunity to participate in virtual interactive culinary training experiences, we found that participants reported increased motivation to prepare quick and nutritious meals to improve their overall wellness. © Copyright 2023 The Author(s).

From gym rat to rock star! Negotiating constraints to leisure experience via a strengths and substitutability approach

This commentary shares my recent personal experience of having to find a new and realistic way to strength-train, my longstanding serious physically-active leisure preference, during the recent gym closures and widespread social restrictions in place due to the coronavirus (COVID-19) pandemic. While thoroughly considering how to negotiate specific leisure experience constraints, I incorporate familiar concepts and processes from the strengths perspective, identity, and leisure substitutability theories. The result of this process led to a creative solution that retained, or perhaps even amplified, my motivation and ability to continue to progress at my preferred serious leisure activity while also experiencing the activity quite differently. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

SARS-CoV-2 raw wastewater surveillance from student residences on an urban university campus.

The COVID-19 pandemic brought about an urgent need to monitor the community prevalence of infection and detect the presence of SARS-CoV-2. Testing individual people is the most reliable method to measure the spread of the virus in any given community, but it is also the most expensive and time-consuming. Wastewater-based epidemiology (WBE) has been used since the 1960s when scientists implemented monitoring to measure the effectiveness of the Polio vaccine. Since then, WBE has been used to monitor populations for various pathogens, drugs, and pollutants. In August 2020, the University of Tennessee-Knoxville implemented a SARS-CoV-2 surveillance program that began with raw wastewater surveillance of the student residence buildings on campus, the results of which were shared with another lab group on campus that oversaw the pooled saliva testing of students. Sample collection began at 8 am, and the final RT-qPCR results were obtained by midnight. The previous day's results were presented to the campus administrators and the Student Health Center at 8 am the following morning. The buildings surveyed included all campus dormitories, fraternities, and sororities, 46 buildings in all representing an on-campus community of over 8,000 students. The WBE surveillance relied upon early morning "grab" samples and 24-h composite sampling. Because we only had three Hach AS950 Portable Peristaltic Sampler units, we reserved 24-h composite sampling for the dormitories with the highest population of students. Samples were pasteurized, and heavy sediment was centrifuged and filtered out, followed by a virus concentration step before RNA extraction. Each sample was tested by RT-qPCR for the presence of SARS-CoV-2, using the CDC primers for N Capsid targets N1 and N3. The subsequent pooled saliva tests from sections of each building allowed lower costs and minimized the total number of individual verification tests that needed to be analyzed by the Student Health Center. Our WBE results matched the trend of the on-campus cases reported by the student health center. The highest concentration of genomic copies detected in one sample was 5.06 × 107 copies/L. Raw wastewater-based epidemiology is an efficient, economical, fast, and non-invasive method to monitor a large community for a single pathogen or multiple pathogen targets.

On Classification and Taxonomy of Coronaviruses (Riboviria, Nidovirales, Coronaviridae) with Special Focus on Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2)

Coronaviruses are highly virulent and therefore important human and veterinary pathogens worldwide. This study presents the first natural hierarchical classification of Coronaviridae. We also demonstrate a "one-step” solution to incorporate the principles of binomial (binary) nomenclature into taxonomy of Coronaviridae. We strongly support the complete rejection of the non-taxonomic category "virus” in any future taxonomic study in virology. This will aid future recognition of numerous virus species, particularly in the currently monotypic subgenus Sarbecovirus. Commenting on the nature of SARS-CoV-2, the authors emphasize that no member of the Sarbecovirus clade is an ancestor of this virus, and humans are the only natural known host © 2022, Mathematical Biology and Bioinformatics.All Rights Reserved.

A series of diabetic ketoacidosis associated with the use of sodium-glucose co-transporter-2 inhibitors in secondary care

Background and aims: Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are associated with diabetic ketoacidosis (DKA), though limited real-world case series are published. The aim of this study is to examine the number and characteristics of patients admitted with SGLT2i-associated DKA to our hospital over a 4-month period. Method(s): Patients were identified retrospectively following referral to the diabetes team with SGLT2i-associated DKA between September-December 2021. Medical notes were reviewed and data related to the patients' characteristics, diabetes control, usual medications and previous medical comorbidities were collected. Result(s): Twenty-two patients with SGLT2i-associated DKA were iden tified;21 (95.5%) were hyperglycaemic and 1 (4.5%) was euglycaemic. Patients had a mean age (+/-standard deviation) 60.8+/-12.3 years and HbA1c 89.2+/-29.2 mmol/mol (10.3%). Of these patients 45.5% were diagnosed with DKA alone, though some had concurrent bacterial (27.3%) or COVID-19 (18.2%) infection. There was significant treatment heterogeneity;nine (40.9%) patients were treated with insulin and 13 (59.1%) patients with other agents. Thirteen (59.1%) patients had no significant medical co-morbidity, though nine (40.9%) patients had underlying cardiovascular, respiratory and/or malignant co-morbidity. Of the 22 patients admitted with DKA, 19 (86.4%) were discharged alive, and three patients (13.6%) died during the admission. Conclusion(s): We observed no specific characteristics which predisposed to SGLT2i-associated DKA or more severe ketoacidosis in this cohort, consistent with previous studies. Most cases were in hyperglycaemic DKA, and people with SGLT2i-associated euglycaemic DKA may have been missed. Given the number of cases observed in our hospital and the associated mortality, greater awareness of the condition is essential.

Awake Prone Positioning in Covid-19: A Review of Prospective Clinical Trials

PURPOSE/HYPOTHESIS: Coronavirus disease 2019 (COVID-19) may result in hypoxemic respiratory failure and death similar to acute respiratory distress syndrome (ARDS). Based on its known efficacy in ARDS, prone positioning (PP) was used to manage intubated patients with severe COVID-19 lung disease. Though less supported by evidence, awake prone positioning (APP) was also trialed in non-intubated patients with COVID-19 to preserve resources and optimize outcomes. The primary available evidence included in recent reviews on APP in COVID-19 were the resultant retrospective single group studies that showed mixed findings. While such designs expedite results, a risk of bias weakens their application. With emerging research, this focused review evaluated APP in COVID-19 based on prospective trials that included a comparison group. NUMBER OF SUBJECTS: Not applicable. MATERIALS AND METHODS: PubMed and CINAHL databases were searched through June 10, 2022 with the following strategy: [(SARS-COV-2) OR (COVID-19) OR (coronavirus)] AND [(prone) OR (proning) OR (prone positioning)]. Prospective studies investigating APP in non-intubated adults with COVID-19 compared to usual care were included. Quality of evidence was determined by the Cochrane Risk of Bias tool with recommendations made using the GRADE approach. RESULT(S): Seven articles evaluating APP in a combined total of 2604 participants (66% male, mean age: 59.8 yrs, BMI: 29.0) with mild to moderate hypoxemic respiratory failure were included. Participant characteristics were heterogeneous and the duration of proning ranged from 4 to 16 hrs/d. APP was associated with improved oxygenation;however, only one study reported a lower incidence of intubation. No effect was noted on mortality or length of stay (LOS). Adverse events were rare but APP was associated an initial worsening outcome in one instance. Lack of blinding and protocol heterogeneity were identified risks of bias. CONCLUSION(S): APP may improve oxygenation in non-intubated individuals with mild to moderate COVID-19 lung disease as compared to usual care;however, prospective controlled trials do not support a positive effect on intubation, LOS, or mortality. The lack of transference in contrast to PP in intubated patients suggests that the primary benefit of PP may be minimizing ventilator-induced lung injury. Alternatively, benefits of APP may be reserved in select individuals as patient characteristics and proning protocols may influence the response. Though serious adverse events were not reported, the potential for skin breakdown and brachial plexus injuries are noted in ventilated patients with the proning times necessary for benefit. Given these findings, the value of immobilizing awake patients in prone should be questioned and alternate active interventions investigated. CLINICAL RELEVANCE: The routine application of APP in COVID-19 lung disease to improve clinical outcomes is not supported by current literature. Based on the GRADE approach, a weak recommendation against using APP was determined. Future studies should investigate if optimal protocols matched to potential responders improve the value of APP in COVID-19.

Implications of novel Adenovirus-Host interactions in Thrombosis with Thrombocytopenia Syndrome

In this study we investigated a link between adenovirus-based vaccines, deployed to fight the SARS-CoV-2 pandemic, and lifethreatening thromboembolisms after vaccination. Post-marketing surveillance showed that, following vaccination, Vaxzevria (ChAdOx1 based, AstraZeneca) and Jcovden (Adenovirus type 26 based, Johnson & Johnson) are associated with reduced platelet counts (thrombocytopenia) and blood clots (thrombosis) in some individuals. This extremely rare condition, with a rate between 1:50,000 - 1:350,000 cases per vaccinated individual, is above background rates of thrombosis in the population and can lead to fatal ischemic events including cerebral venous thrombosis, intracranial haemorrhage, and pulmonary embolism. It has been termed vaccine induced thrombotic thrombocytopenia (VITT) or thrombosis with thrombocytopenia syndrome (TTS). Heparin induced thrombocytopenia (HIT) is another condition with a similar clinical presentation to TTS. In HIT, immunoaggregates are formed due to the presence of strong anti-selfantibodies directed against Platelet Factor 4 (PF4). When similar anti-PF4 antibodies were detected in TTS patients, we investigated whether there could be a link between the adenovirus vectors used in the vaccines and PF4. This study demonstrates a direct interaction between adenovirus capsids and PF4 using surface plasmon resonance. We then utilized an integrative structural biology workflow including cryo-electron microscopy and molecular dynamics to characterize and demonstrate the mechanism of this interaction. These results demonstrate a previously unknown adenovirushost interaction and provide critical clues as to the underlying mechanism which causes TTS, including how these pathogenic anti-PF4 antibodies may be induced. We are therefore able to present a hypothesis as to the route of pathogenesis in TTS.

Impact of the COVID-19 pandemic on disengagement from advanced diabetes technologies among racial/ethnic groups in the US T1D exchange quality improvement collaborative

Introduction: The use of continuous glucose monitors (CGM) and insulin pumps (PUMP) have been associated with improved outcomes in type 1 diabetes (T1D) care. Therefore, disengaging from these devices represents a risk for worsening health outcomes. Objective(s): We sought to evaluate the effect of the COVID-19 pandemic on device disengagement rates by race and ethnicity. Method(s): This retrospective cohort study Pre-COVID-19 [n = 15,838] + peri-COVID-19 ([n = 14,799]) used EMR data from 15 sites (i.e., 3 adult and 12 pediatric diabetes centers) within the T1D Exchange Quality Improvement Collaborative. We identified individuals using at least one Advanced Diabetes Technology (ADT [PUMP or CGM]) at their most recent visit. Individuals who continued to use that technology for at least two subsequent visits were classified as engaged. Those who reported not using ADT in two subsequent visits were classified as disengaged. Result(s): Comparing pre-COVID-19 (January 2017-March 2020) to peri-COVID-19 (April 2020-2021) time periods, we observed increases in disengagement among non-Hispanic White (NHW;42% to 45%, p = 0.03) and Hispanic (12% to 19%, p < 0.001) individuals. We found no difference among NH Black (NHB;61% to 62%, p = 0.7) individuals. Conclusion(s): The pandemic has presented self-care challenges for individuals with T1D, including continued use of ADT. NHB individuals exhibited the highest disengagement rates overall, while NHW/Hispanic individuals experienced significant pandemic-related increases in disengagement. Future research should evaluate the relative impact of intrinsic (i.e., patient-level) versus extrinsic (i.e., family-, environment-, and system-level) factors associated with race-/ethnicity- based differences in rate of disengagement.

Doing Design Differently: Hybrid Teaching in the age of Covid-19

Somewhat uniquely, in our department, we teach a version of engineering design to each of 4 year groups registered for the M.Eng (masters in engineering) in chemical engineering. These design projects culminate with a final-year group design, but students are introduced to group design in their second week of their first year of study. The first-year design project deliverables are assessed, but equally the design project serves as an opportunity for students to get to know one another through organised group work and serves as an introduction to the concept of design in a chemical engineering context. The first-year design project has traditionally been taught face-to-face (F2F), with the design project taught in 2 cohorts of ~75 students to accommodate the students enrolled in the first year of the programme (approximately 150-160 in total). Lockdown restrictions last year due to the COVID-19 pandemic (COVID) meant that the design project was redesigned as a remote teaching model which was delivered very successfully using Microsoft TEAMS. This academic year, some restrictions have lifted and as a result of which a hybrid model for teaching the first-year design project has been adopted. In this paper, this hybrid model of teaching is discussed along with the challenges faced in designing and delivering it. For example, one of the main challenges we faced was how to keep students and staff safe when they were on campus, which was not a concern pre-pandemic. Important decisions have been made about how to vary assessment measures [1] for example by having students give a pre-recorded, non-assessed group presentation, and to then use the constructive feedback to prepare a live, assessed, group presentation. Similarly, we were obliged to re-consider how best to support peer-to-peer collaboration [2] with students being set collective goals, and meeting face-to-face on a group rotational basis once a week with contribution and attendance being periodically monitored. Furthermore, students were encouraged to make use of sanitised study space in the department, and to actively converse through TEAMS as and when appropriate. Additionally, challenges arose with managing academic support effectively with most of the support offered face-to-face through team teaching in blocks. Other challenges faced included ensuring the available teaching space could be kept safe [3], and that time could be managed effectively. The disadvantages and benefits of adopting a hybrid model of teaching are explored from both staff and student viewpoints, by critically reflecting on student evaluations for the module and the perceptions of staff retrospectively. © American Society for Engineering Education, 2022

Clinical Features of the UK Myotonic Dystrophy Patient Registry

The UK Myotonic Dystrophy Patient Registry is a patient self-enrolling online database collecting clinical and genetic information about myotonic dystrophy type 1 (DM1) and type 2 (DM2). The registry was established in May 2012 with support from Muscular Dystrophy UK and the Myotonic Dystrophy Support Group and is coordinated Newcastle University. The registry aims to facilitate academic and clinical research, better characterise and understand DM, and disseminate information relating to upcoming studies and research advancements. The registry is used to capture longitudinal, selfreported data through an online portal available to patients and clinicians. Where specialised clinical or genetic information is required, the neuromuscular specialist involved in the patient's care can be invited to provide some additional information and the patient can select them from a pre-populated list at the registration stage. The registry is a Core Member of the TREAT-NMD Global Registries Network for DM1. Between May 2012 and January 2022, there were 834 patient registrations. On average there are 5 new registrations per month. For those reporting a clinical diagnosis, 96% have DM1 (of which 14% have a diagnosis of congenital DM) and 4% have DM2. Overall, 40% of patients have had genetic confirmation of their condition provided. The registry has previously supported almost 30 research enquiries to date. Since 2020, the registry has facilitated 11 enquiries including an industry enquiry, three COVID-19 surveys, and various surveys capturing information on dysphagia, pregnancy, patient preferences for future treatments and the patient/ caregiver experience. The registry continues to be a versatile, cost-effective research tool, helping facilitate and advance a range of DM research. Additional work continues to be done to improve reporting of genetic information on the registry and there are future data linkage plans between the registry and the Newcastle Research Biobank for Rare and Neuromuscular Diseases.

DREAMM-9: PHASE I STUDY OF BELANTAMAB MAFODOTIN PLUS STANDARD OF CARE IN PATIENTS WITH TRANSPLANT-INELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA

Background: The bortezomib, lenalidomide, and dexamethasone (VRd) regimen is a standard of care for newly diagnosed multiple myeloma (NDMM). Belantamab mafodotin (belamaf) is a B-cell maturation antigen-binding antibody-drug conjugate that eliminates myeloma cells by a multimodal mechanism: direct cell kill and anti-myeloma tumor immune response. Belamaf has demonstrated deep and durable responses as a monotherapy in the DREAMM-2 study of patients (pts) with relapsed/refractory multiple myeloma (RRMM). Preclinical evidence of belamaf in combination with bortezomib or lenalidomide suggests enhanced anti-myeloma activity, providing rationale for this treatment combination. Aims: To evaluate the safety and tolerability of this combination in adult pts with transplant-ineligible (TI) NDMM and establish the recommended Phase III dose. Methods: DREAMM-9 (NCT04091126) is an ongoing Phase I, open-label, randomized study of belamaf + VRd. The belamaf dose cohorts currently being evaluated are Cohort 1 (1.9 mg/kg Q3/4W), Cohort 2 (1.4 mg/kg Q6/8W), Cohort 3 (1.9 mg/kg Q6/8W), Cohort 4 (1.0 mg/kg Q3/4W), and Cohort 5 (1.4 mg/kg Q3/4W). Belamaf is given with VRd Q3W until Cycle 8, and with Rd Q4W thereafter. After evaluation of safety data for Cohort 1, Cohorts 2-5 were opened in parallel and enrolled pts were randomized 1:1:1:1. Primary endpoint is safety. Secondary endpoints include efficacy, tolerability, and pharmacokinetics (PK). Results: As of data cutoff (07 Dec 2021), 64 pts were analyzed across all cohorts. Median age (range) was 73.0 (51- 88) years, 55% were male, 80% were white, 8% had extramedullary disease, 59% were International Staging System stage II or III, 20% had amp1q, and 17% had high-risk cytogenetics (≥1 of: t(4;14), t(14;16), del17p). The median duration of follow-up varied: Cohort 1 (17.4 months [mo]), Cohort 2 (5.9 mo), Cohort 3 (6.1 mo), Cohort 4 (4.7 mo), Cohort 5 (5.8 mo). Median number of belamaf cycles were: Cohort 1 (6), Cohort 2 (3), Cohort 3 (3.5), Cohort 4 (4.5), and Cohort 5 (5). Most common adverse events (AEs) across cohorts included thrombocytopenia (49%), constipation (43%), diarrhea (32%), and peripheral sensory neuropathy (30%). AEs related to study treatment were experienced by 61 (97%) pts. Belamaf-related grade 3/4 AEs occurred in 24 (38%) pts. Belamaf dose reductions occurred in 11 (18%) pts, with dose delays in 10 (16%) pts. Three pts experienced a fatal severe AE (unrelated to study treatment);2 due to COVID-19 infection, 1 due to pancreatic adenocarcinoma. Early deep responses were observed;67-92% pts achieved ≥very good partial response (VGPR) (Table), with median time to VGPR of 2.1-2.9 months across cohorts. Of pts with ≥VGPR, 17 were minimal residual disease (MRD) negative, 10 in Cohort 1. As of data cutoff, 8-75% of pts achieved best response of complete response (CR) or stringent CR (sCR). Grade 3 corneal exam findings were reported in 25-58% of pts;grade 3 visual acuity changes were reported in 21-75% of pts. No grade 4 corneal exam findings or visual acuity changes were reported in pts receiving belamaf Q6/8W, compared with 0-17% and 0-8%, respectively, in the Q3/4W cohorts. Belamaf PK profile was similar to that in pts with RRMM, accounting for baseline characteristics. Image: Summary/Conclusion: Belamaf + VRd demonstrated high response rates in pts with TI NDMM, with a high rate of MRD negativity indicating deep responses. No new safety signals were observed relative to DREAMM-2. Study is ongoing to evaluate the safety and efficacy of variable dose intensities of belamaf in combination with VRd.