Detection of human adenovirus F41 in wastewater and its relationship to clinical cases of acute hepatitis of unknown aetiology

As of 8 July 2022, the World Health Organization (WHO) have reported 1010 probable cases of acute hepatitis of unknown aetiology in children worldwide, including approximately 250 cases in the United Kingdom (UK). Clinical presentations have often been severe, with liver transplantation a frequent clinical outcome. Human adenovirus F41 (HAdV-F41) has been detected in most children with acute hepatitis, but its role in the pathogenesis of this infection has yet to be established. Wastewater-based epidemiology (WBE) has become a well-established tool for monitoring the community spread of SARS-CoV-2, as well as other pathogens and chemicals. In this study, we adopted a WBE approach to monitoring levels of HAdV-F40/41 in wastewater before and during an acute hepatitis outbreak in Northern Ireland. We report increasing detection of HAdV-F40/41 in wastewater, concomitant with increasing numbers of clinical cases. Amplicon whole genome sequencing further classified the wastewater-derived HAdV as belonging to the F41 genotype which in turn was homologous to clinically derived sequences. We propose that WBE has the potential to inform community surveillance of HAdV-F41 and can further contribute to the ongoing global discussion supporting HAdV-F41 involvement in acute hepatitis cases. © 2022 The Authors

The Return to Craft: Taylor Swift, Nostalgia, and Covid-19

What I term "the return to craft” is a distillation of a pervasive phenomenon–the nostalgic, folk esthetic of contemporary Western society that has arisen partly in response to the Covid-19 pandemic but also to neoliberalism and climate change. It arises as a reaction to turmoil, offering the comfort of an imagined past, a tangible tactility, and a reconnection with the "old ways,” with nature, and the wild. In this paper, I explore the return to craft as a societal search for foundations via a case-study of its most commercially successful lockdown output, Taylor Swift's folklore (2020). © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Risk factors for SARS-CoV-2 infection in healthcare workers following an identified nosocomial COVID-19 exposure during waves 1-3 of the pandemic in Ireland.

Healthcare workers (HCWs) have increased exposure and subsequent risk of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This case-control study was conducted to investigate the contemporaneous risks associated with confirmed SARS-CoV-2 infection amongst HCWs following in-work exposure to a confirmed coronavirus disease-2019 (COVID-19) case. We assessed the influence of demographic (age, sex, nationality, high risk co-morbidities and vaccination status) and work-related factors (job role, exposure location, contact type, personal protective equipment (PPE) use) on infection risk following nosocomial SARS-CoV-2 exposure. All contact tracing records within the hospital site during waves 1-3 of the COVID-19 pandemic in Ireland were screened to identify exposure events, cases and controls. In total, 285 cases and 1526 controls were enrolled, as a result of 1811 in-work exposure events with 745 index cases. We demonstrate that male sex, Eastern European nationality, exposure location, PPE use and vaccination status all impact the likelihood of SARS-CoV-2 infection following nosocomial SARS-CoV-2 exposure. The findings draw attention to the need for continuing emphasis on PPE use and its persisting benefit in the era of COVID-19 vaccinations. We suggest that non-work-related factors may influence infection risk seen in certain ethnic groups and that infection risk in high-risk HCW roles (e.g. nursing) may be the result of repeated exposures rather than risks inherent to a single event.

Wastewater-based epidemiology (WBE) for the detection and prediction of respiratory syncytial virus (RSV) outbreaks

Wastewater-based epidemiology (WBE) has the capacity to provide effective surveillance of entire communities by determining levels of health-associated biomarkers, viruses, and bacteria. WBE has been used globally as a key metric in determining prevalence of SARS-CoV-2 in the community. However, the application of WBE for the surveillance of other respiratory viruses has been poorly studied. Respiratory syncytial virus (RSV) is a seasonal outbreak disease that can cause severe infections in infants, immunocompromised or elderly individuals. Currently, the administration of RSV immunoprophylaxis products for high-risk patients relies on pre-emptively determining when an outbreak of RSV may occur in the community. However, in 2021 unexpected seasonal RSV outbreaks were reported which were likely due to the relaxation of Covid-19 regulations (social distancing, face coverings etc.) posing challenges over when to initiate the supply of immunoprophylaxis. The aims of this study were to monitor the circulation of RSV in wastewater (WW), investigate if increasing detection of RSV in WW precedes the onset of clinical cases and determine the molecular epidemiology of RSV A and B genotypes. Untreated WW samples from 20 WW inlet treatment sites across Northern Ireland (NI) were collected between August 2021 and July 2022 and concentrated. Viral nucleic acid was amplified and quantified using an RSV specific RT-qPCR assay. The gene copies/L were normalised based on the rainfall flow rate and population size and then compared to the clinical case rate. For a selection of WW sites, the glycoprotein G gene was sequenced, and phylogenetic analysis was carried out. RSV concentration in wastewater mirrored the rise in clinical cases, with WW surveillance leading clinical diagnostic testing by ~1 week. WW surveillance is a valuable tool to detect and monitor outbreaks of circulating and clinically relevant respiratory viruses. Therefore, WBE has the potential to establish guidelines for diagnostic testing and preventative measures and to assist with clinical resource planning.

Detection of human adenovirus F41 in wastewater and its relationship to clinical cases of acute hepatitis of unknown aetiology

As of 8 July 2022, the World Health Organization (WHO) have reported 1010 probable cases of acute hepatitis of unknown aetiology in children worldwide, including approximately 250 cases in the United Kingdom (UK). Clinical presentations have often been severe, with liver transplantation a frequent clinical outcome. Human adenovirus F41 (HAdV-F41) has been detected in most children with acute hepatitis, but its role in the pathogenesis of this infection has yet to be established. Wastewater-based epidemiology (WBE) has become a well-established tool for monitoring the community spread of SARS-CoV-2, as well as other pathogens and chemicals. In this study, we adopted a WBE approach to monitoring levels of HAdV-F40/41 in wastewater before and during an acute hepatitis outbreak in Northern Ireland. We report increasing detection of HAdV-F40/41 in wastewater, concomitant with increasing numbers of clinical cases. Amplicon whole genome sequencing further classified the wastewater-derived HAdV as belonging to the F41 genotype which in turn was homologous to clinically derived sequences. We propose that WBE has the potential to inform community surveillance of HAdV-F41 and can further contribute to the ongoing global discussion supporting HAdV-F41 involvement in acute hepatitis cases.

Can we increase bladder outlet obstruction surgery day case rates to tackle the post-Covid Elective Recovery?

Introduction: There is growing recognition that bladder outlet obstruction (BOO) surgery can often be safely performed as a day case procedure. The BOO surgery day case rate (DCR) is a Getting It Right First Time (GIRFT) quality metric. Patients awaiting BOO surgery represent the largest group awaiting elective surgical treatment in urology. This unmet need has expanded considerably due to the Covid-19 pandemic. Patients and Methods: Model Hospital (MH) is a datadriven improvement tool for English NHS trusts, which utilises routinely collected national level data. MH describes performance metrics for transurethral resection of prostate, laser prostatectomy, prostatic urethral lift, and bladder neck incision. MH data were analysed for all 115 trusts performing BOO surgery over 12 months to October 2021. Associations between service delivery and outcome metrics were tested. Results: Table 1 shows national Trust-level metrics for DCR, length of stay (LOS), 30-day readmission rate (30D), annual centre volume (ACV), and waiting list time (WLT). Analysis indicated no significant association between any of the following;DCR and 30D (Spearman rank correlation coefficient (rs)=-0.085, p=0.37), ACV and 30D (rs=- 0.019, p=0.84), DCR and WLT (rs=0.16, p=0.096). Conclusion: There is wide variation in DCR and WLT nationally. The absence of association between DCR and 30D suggests that many trusts can safely increase DCR for BOO surgery. Optimising DCR could help to facilitate the post-Covid Elective Recovery for surgery. The lack of association between DCR and WLT, however, suggests that further resource constraints beyond elective inpatient bed availability influence the provision of BOO surgery.

Reshaping the diagnostic pathways for investigation of haematuria during and after the COVID-19 pandemic: Diagnostic accuracy of strategies for the detection of bladder cancer from the IDENTIFY cohort study

Background: Haematuria often requires investigation with an imaging test and flexible cystoscopy to rule out urinary tract cancers. With a reduction in diagnostic services due to the COVID-19 pandemic there is a risk of compromise in the care of patients referred with haematuria. We aimed to provide a pragmatic strategy that optimises the use of scarce resources by reducing patient visits to hospital and allocating the appropriate diagnostic tests according to risk of bladder cancer. Methods: The IDENTIFY study was an international, prospective, multicentre cohort study of over 11,000 patients referred to secondary care for investigation of newly suspected urinary tract cancer. Patients underwent cystoscopy, imaging tests, urine cytology and transurethral resection of bladder tumour (TURBT), where indicated. We developed strategies using combinations of imaging and cytology as triage tests to flexible cystoscopy. These strategies aimed to maximise cancer detection within a pragmatic pathway in a resource-limited environment. Findings: 8112 patients (74 4%) received an ultrasound or a CT urogram, with or without cytology. 5737 (70 7%) patients had visible haematuria (VH) and 2375 (29 3%) had non-visible haematuria (NVH). Amongst all patients, 1474 (18 2%) had bladder cancer;1333 (23 2%) in VH group and 141 (5 94%) in NVH group. Diagnostic test performance was used to determine optimal age cut-offs for each proposed strategy. We recommended proceeding directly to TURBT for patients of any age with positive triage tests for cancer. Patients with negative triage tests under 35-years-old with VH, or under 50-years-old with NVH can safely be discharged without undergoing flexible cystoscopy. The remaining patients may undergo flexible cystoscopy, with a greater priority for older patients (threshold of 60-years-old with VH, or 70-years-old with NVH) to capture high risk bladder cancer. Interpretation: We suggest diagnostic strategies in patients with haematuria, which focus on detection of bladder cancer, whilst reducing the burden to healthcare services in a resource-limited setting.

Has COVID changed the perception about regional anaesthesia? – A survey among patients, anaesthetists and surgeons- a single centre specialist orthopaedic hospital study

91 Figure 1Abstract 91 Figure 2Overall changes in patient responses before and after having a RA during the pandemic[Figure omitted. See PDF]Abstract 91 Figure 3Overall change before and after the first wave among patients, surgeons and anaesthetists[Figure omitted. See PDF]ConclusionsPrevious exposure to RA techniques increases the acceptance by patients and surgeons in the future. Anxiety about being awake/feeling pain among patients can be mitigated by reassurance and counselling during the preoperative visit. A focus on upskilling non-RA anaesthetists on high valuable Plan A blocks should be encouraged[1] These points should be utilised to increase RA use after the pandemic as well.

Rapid detection of intact SARS-CoV-2 viral particles using silicon nanomembranes

The SARS-CoV-2 pandemic has revealed the need for rapid and inexpensive diagnostic testing to enable population-based screening for active infection. Neither standard diagnostic testing, the detection and measurement of viral RNA (via polymerase chain reaction), or serological testing (via enzyme-linked immunosorbent assay) has the capability to definitively determine active infection. The former due to a lack of ability to distinguish between replicable and inert viral RNA, and the latter due to varying immune responses (ranging from latent to a complete lack of immune response altogether). Despite many companies producing rapid point-of-care (POC) tests, none will address the global scale of testing needed and few help to combat the ever growing issue of testing resource scarcity. Here we discuss our efforts towards the development of a highly manufacturable, microfluidic device that instantly indicates active viral infection status from ~ 20 μL of nasal mucus or phlegm and requires no external power. The device features a biotin functionalized silicon nanomembrane within an acrylic body containing channels and ports for sample introduction and analysis. Virus capture and target confirmation are done using affinity-based capture and size-based occlusion respectively. Modularity of the device is proven with bead and vaccinia virus capture as we work towards testing with both pure SARS-CoV-2 virus and human samples. With success on all fronts, we could achieve an inexpensive POC diagnostic which can determine an individual’s infection status, aiding containment efforts in the current and future pandemics. In addition to direct viral detection, our method can be used as a rapid POC sample preparation tool that limits the application of PCR reagents to those samples which already display viral size and antigen-based positivity through our device. © 2021 SPIE.

Reshaping the diagnostic pathways for investigation of haematuria during and after the covid-19 pandemic: Diagnostic accuracy of strategies for detection of bladder cancer from the identify cohort study

Introduction: Diagnostic haematuria services have been reduced due to the COVID-19 pandemic, compromising patient care, and necessitating a more pragmatic pathway. Method: The IDENTIFY study was an international, prospective, multicentre cohort study of over 11,000 patients referred to secondary care for investigation of haematuria. Using this data, we developed strategies using combinations of imaging and cytology as triage tests to maximise cancer detection within a pragmatic pathway. Results: 8112 patients (74 4%) received an ultrasound or a CT urogram, with or without cytology. 5737 (70 7%) patients had visible haematuria (VH) and 2375 (29 3%) had non-visible haematuria (NVH). Diagnostic test performance was used to determine optimal age cut-offs for four proposed strategies. We recommended proceeding directly to transurethral resection of bladder tumour for patients of any age with positive triage tests for cancer. Patients with negative triage tests under 35-years-old with VH, or under 50-years-old with NVH can safely be discharged without undergoing flexible cystoscopy. The remaining patients may undergo flexible cystoscopy, with a greater priority for older patients to capture high risk bladder cancer. Conclusions: We suggest diagnostic strategies in patients with haematuria, which focus on detection of bladder cancer, whilst reducing the burden to healthcare services in a resource-limited setting.

A multidisciplinary evaluation of suspected, non-confirmed cases of COVID-19 including chest CT, as compared to World Health Organization recommendations.

AIM: To report an audit of the evaluation of suspected, unconfirmed cases of COVID-19 including chest computed tomography (CT), as compared to World Health Organization recommendations. METHODS: A clinical audit was undertaken examining the evaluation of patients with suspected COVID-19 with negative SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) results, with comparison to WHO recommendations. A retrospective chart review was undertaken for 90 patients examining investigations, in particular CT, used to clarify the diagnosis. RESULTS: Ninety patients underwent additional investigation. Seventy-five per cent adherence to WHO recommendations was observed. Fifty-two men (57.78%) and 38 (42.22%) women were investigated, with a median age of 69 years (range 20-96 years). Seventy-nine chest CT examinations demonstrated positive, indeterminate, and negative rates for COVID-19 of 3.79%, 24.1%, and 72.15% respectively. Three patients had discordant swab results with initially negative and subsequently positive results for SARS-CoV-2, resulting in false-negative rates of 5.1% for those retested. Combining discordant RT-PCR swab results, positive radiology, and patients treated as COVID-19-positive due to indeterminate radiology and highly consistent symptoms, resulted in a false-negative rate for initial SARS-CoV-2 RT-PCR swabs of 16.67%. CONCLUSION: Seventy-five per cent compliance with relevant WHO guidance and a false-negative rate for initial swabs of 16.67% was demonstrated. Further evidence is needed to fully determine the utility of chest CT in the diagnosis of COVID-19 in the context of initial false-negative RT-PCR results.

The provision of a time-critical elective surgical service during the COVID-19 Crisis: a UK experience.

INTRODUCTION: With the emergence of the COVID-19 pandemic, all elective surgery was temporarily suspended in the UK, allowing for diversion of resource to manage the anticipated surge of critically unwell patients. Continuing to deliver time-critical surgical care is important to avoid excess morbidity and mortality from pathologies unrelated to COVID-19. We describe the implementation and short-term surgical outcomes from a system to deliver time-critical elective surgical care to patients during the COVID-19 pandemic. MATERIALS AND METHODS: A protocol for the prioritisation and safe delivery of time-critical surgery at a COVID-19 'clean' site was implemented at the Nuffield Health Exeter Hospital, an independent sector hospital in the southwest of England. Outcomes to 30 days postoperatively were recorded, including unplanned admissions after daycase surgery, readmissions and complications, as well as the incidence of perioperative COVID-19 infection in patients and staff. RESULTS: A total of 128 surgical procedures were performed during a 31-day period by a range of specialties including breast, plastics, urology, gynaecology, vascular and cardiology. There was one unplanned admission and and two readmissions. Six complications were identified, and all were Clavien-Dindo grade 1 or 2. All 128 patients had preoperative COVID-19 swabs, one of which was positive and the patient had their surgery delayed. Ten patients were tested for COVID-19 postoperatively, with none testing positive. CONCLUSION: This study has demonstrated the implementation of a safe system for delivery of time-critical elective surgical care at a COVID-19 clean site. Other healthcare providers may benefit from implementation of similar methodology as hospitals plan to restart elective surgery.

An in vitro investigation into the release of fugitive medical aerosols into the environment during manual ventilation.

BACKGROUND: During manual resuscitation, nebulizer therapy may be used to deliver therapeutics to patients in respiratory distress. However, the devices used to generate and deliver these medical aerosols have the potential to release these therapeutics into the local environment and expose caregivers to unwanted medical aerosols. AIM: To quantify the levels of fugitive medical aerosol released into the environment during aerosol drug delivery using a manual resuscitation bag with and without filtration. METHODS: Time-varying fugitive aerosol concentrations were measured using an aerodynamic particle sizer placed at a position designed to mimic a caregiver. Two nebulizer types were assessed, a vibrating mesh nebulizer and a jet nebulizer. The aerosol dose delivered to the simulated patient lung was also quantified. FINDINGS: Filtration of the exhalation port of the manual resuscitation bag was seen to reduce fugitive medical aerosols to ambient levels for both nebulizer types. The vibrating mesh nebulizer delivered the greatest quantity of aerosol to the simulated adult patient (18.44 ± 1.03% versus 3.64 ± 0.26% with a jet nebulizer). CONCLUSIONS: The results highlight the potential for exposure to fugitive medical aerosols released during the delivery of aerosol therapy with a manual resuscitation bag and also the potential for significant variation in patient lung dose depending on nebulizer type.