InterARTIC: an interactive web application for whole-genome nanopore sequencing analysis of SARS-CoV-2 and other viruses.

MOTIVATION: InterARTIC is an interactive web application for the analysis of viral whole-genome sequencing (WGS) data generated on Oxford Nanopore Technologies (ONT) devices. A graphical interface enables users with no bioinformatics expertise to analyse WGS experiments and reconstruct consensus genome sequences from individual isolates of viruses, such as SARS-CoV-2. InterARTIC is intended to facilitate widespread adoption and standardisation of ONT sequencing for viral surveillance and molecular epidemiology. WORKED EXAMPLE: We demonstrate the use of InterARTIC for the analysis of ONT viral WGS data from SARS-CoV-2 and Ebola virus, using a laptop computer or the internal computer on an ONT GridION sequencing device. We showcase the intuitive graphical interface, workflow customisation capabilities and job-scheduling system that facilitate execution of small- and large-scale WGS projects on any common virus. IMPLEMENTATION: InterARTIC is a free, open-source web application implemented in Python that executes best-practice command line workflows from the ARTIC network. The application can be downloaded as a set of pre-compiled binaries that are compatible with all common Linux distributions, Windows with Linux subsystems, MacOSX and ARM systems. For further details please visit: https://github.com/Psy-Fer/interARTIC/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Remote Consultations Versus Standard Face-to-Face Appointments for Liver Transplant Patients in Routine Hospital Care: Feasibility Randomized Controlled Trial of myVideoClinic.

BACKGROUND: Using technology to reduce the pressure on the National Health Service (NHS) in England and Wales is a key government target, and the NHS Long-Term Plan outlines a strategy for digitally enabled outpatient care to become mainstream by 2024. In 2020, the COVID-19 response saw the widespread introduction of remote consultations for patient follow-up, regardless of individual preferences. Despite this rapid change, there may be enduring barriers to the effective implementation of remote appointments into routine practice once the unique drivers for change during the COVID-19 pandemic no longer apply, to which pre-COVID implementation studies can offer important insights. OBJECTIVE: This study aims to evaluate the feasibility of using real-time remote consultations between patients and secondary care physicians for routine patient follow-up at a large hospital in the United Kingdom and to assess whether patient satisfaction differs between intervention and usual care patients. METHODS: Clinically stable liver transplant patients were randomized to real-time remote consultations in which their hospital physician used secure videoconferencing software (intervention) or standard face-to-face appointments (usual care). Participants were asked to complete postappointment questionnaires over 12 months. Data were analyzed on an intention-to-treat basis. The primary outcome was the difference in scores between baseline and study end by patient group for the three domains of patient satisfaction (assessed using the Visit-Specific Satisfaction Instrument). An embedded qualitative process evaluation used interviews to assess patient and staff experiences. RESULTS: Of the 54 patients who were randomized, 29 (54%) received remote consultations, and 25 (46%) received usual care (recruitment rate: 54/203, 26.6%). The crossover between study arms was high (13/29, 45%). A total of 129 appointments were completed, with 63.6% (82/129) of the questionnaires being returned. Patient satisfaction at 12 months increased in both the intervention (25 points) and usual care (14 points) groups. The within-group analysis showed that the increases were significant for both intervention (P<.001) and usual care (P=.02) patients; however, the between-group difference was not significant after controlling for baseline scores (P=.10). The qualitative process evaluation showed that-according to patients-remote consultations saved time and money, were less burdensome, and caused fewer negative impacts on health. Technical problems with the software were common, and only 17% (5/29) of patients received all appointments over video. Both consultants and patients saw remote consultations as positive and beneficial. CONCLUSIONS: Using technology to conduct routine follow-up appointments remotely may ease some of the resource and infrastructure challenges faced by the UK NHS and free up clinic space for patients who must be seen face-to-face. Our findings regarding the advantages and challenges of using remote consultations for routine follow-ups of liver transplant patients have important implications for service organization and delivery in the postpandemic NHS. TRIAL REGISTRATION: ISRCTN Registry 14093266; https://www.isrctn.com/ISRCTN14093266. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-018-2953-4.

Health-related quality of life, uncertainty and coping strategies in solid organ transplant recipients during shielding for the COVID-19 pandemic.

Strict isolation of vulnerable individuals has been a strategy implemented by authorities to protect people from COVID-19. Our objective was to investigate health-related quality of life (HRQoL), uncertainty and coping behaviours in solid organ transplant (SOT) recipients during the COVID-19 pandemic. A cross-sectional survey of adult SOT recipients undergoing follow-up at our institution was performed. Perceived health status, uncertainty and coping strategies were assessed using the EQ-5D-5L, Short-form Mishel Uncertainty in Illness Scale (SF-MUIS) and Brief Cope, respectively. Interactions with COVID-19 risk perception, access to health care, demographic and clinical variables were assessed. The survey was completed by 826 of 3839 (21.5%) invited participants. Overall, low levels of uncertainty in illness were reported, and acceptance was the major coping strategy (92%). Coping by acceptance, feeling protected, self-perceived susceptibility to COVID-19 were associated with lower levels of uncertainty. Health status index scores were significantly lower for those with mental health illness, compromised access to health care, a perceived high risk of severe COVID-19 infection and higher levels of uncertainty. A history of mental health illness, risk perceptions, restricted healthcare access, uncertainty and coping strategies was associated with poorer HRQoL in SOT recipients during strict isolation. These findings may allow identification of strategies to improve HRQoL in SOT recipients during the pandemic.

New dimensions for hospital services and early detection of disease: a Review from the Lancet Commission into liver disease in the UK.

This Review, in addressing the unacceptably high mortality of patients with liver disease admitted to acute hospitals, reinforces the need for integrated clinical services. The masterplan described is based on regional, geographically sited liver centres, each linked to four to six surrounding district general hospitals-a pattern of care similar to that successfully introduced for stroke services. The plan includes the establishment of a lead and deputy lead clinician in each acute hospital, preferably a hepatologist or gastroenterologist with a special interest in liver disease, who will have prime responsibility for organising the care of admitted patients with liver disease on a 24/7 basis. Essential for the plan is greater access to intensive care units and high-dependency units, in line with the reconfiguration of emergency care due to the COVID-19 pandemic. This Review strongly recommends full implementation of alcohol care teams in hospitals and improved working links with acute medical services. We also endorse recommendations from paediatric liver services to improve overall survival figures by diagnosing biliary atresia earlier based on stool colour charts and better caring for patients with impaired cognitive ability and developmental mental health problems. Pilot studies of earlier diagnosis have shown encouraging progress, with 5-6% of previously undiagnosed cases of severe fibrosis or cirrhosis identified through use of a portable FibroScan in primary care. Similar approaches to the detection of early asymptomatic disease are described in accounts from the devolved nations, and the potential of digital technology in improving the value of clinical consultation and screening programmes in primary care is highlighted. The striking contribution of comorbidities, particularly obesity and diabetes (with excess alcohol consumption known to be a major factor in obesity), to mortality in COVID-19 reinforces the need for fiscal and other long delayed regulatory measures to reduce the prevalence of obesity. These measures include the food sugar levy and the introduction of the minimum unit price policy to reduce alcohol consumption. Improving public health, this Review emphasises, will not only mitigate the severity of further waves of COVID-19, but is crucial to reducing the unacceptable burden from liver disease in the UK.

Analytical validity of nanopore sequencing for rapid SARS-CoV-2 genome analysis.

Viral whole-genome sequencing (WGS) provides critical insight into the transmission and evolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Long-read sequencing devices from Oxford Nanopore Technologies (ONT) promise significant improvements in turnaround time, portability and cost, compared to established short-read sequencing platforms for viral WGS (e.g., Illumina). However, adoption of ONT sequencing for SARS-CoV-2 surveillance has been limited due to common concerns around sequencing accuracy. To address this, here we perform viral WGS with ONT and Illumina platforms on 157 matched SARS-CoV-2-positive patient specimens and synthetic RNA controls, enabling rigorous evaluation of analytical performance. We report that, despite the elevated error rates observed in ONT sequencing reads, highly accurate consensus-level sequence determination was achieved, with single nucleotide variants (SNVs) detected at >99% sensitivity and >99% precision above a minimum ~60-fold coverage depth, thereby ensuring suitability for SARS-CoV-2 genome analysis. ONT sequencing also identified a surprising diversity of structural variation within SARS-CoV-2 specimens that were supported by evidence from short-read sequencing on matched samples. However, ONT sequencing failed to accurately detect short indels and variants at low read-count frequencies. This systematic evaluation of analytical performance for SARS-CoV-2 WGS will facilitate widespread adoption of ONT sequencing within local, national and international COVID-19 public health initiatives.

P40 Video clinics versus standard face-to-face appointments for liver transplant patients in routine hospital care: a feasibility randomised controlled trial of myVideoClinic

IntroductionThere has recently been a rapid increase in the number of health and social care organisations offering remote consultations in order to minimise the spread of disease following the outbreak of COVID-19, but their effectiveness is unclear. The majority of studies focusing on remote consultations to date have evaluated telephone appointments. Although some studies have used video conferencing technology in the secondary care sector, the sample sizes have been small and they differ in their findings. This study evaluated the feasibility of implementing video clinics at a large hospital trust in the UK and assessed whether the intervention improved patient satisfaction compared to standard face-to-face appointments for liver transplant patients.MethodsClinically stable liver transplant patients were randomised to video clinic appointments (intervention) or standard face-to-face appointments (usual care). The intervention group had routine follow-up appointments via secure video link. Participants were asked to complete post-appointment questionnaires over 12 months. The primary outcome was the difference in scores between baseline and study end by patient group for three domains of patient satisfaction using the Visit-Specific Satisfaction Instrument (VSQ-9). An embedded qualitative process evaluation used interviews to assess patient and staff experiences.ResultsFifty four patients were randomised: 29 to receive video clinics and 25 to usual care (recruitment rate 26.6%). Crossover from intervention to usual care was high (44.8%). 129 appointments were completed with 64% of questionnaires returned. Patient satisfaction (intention-to-treat analysis) increased in both intervention and usual care groups but the between-group difference was not significant after controlling for baseline scores. Video appointments were perceived to save patients time and money, and patients found video clinics to be less burdensome, with fewer negative impacts on their health. Technical problems with the software were common, however, the software is constantly evolving and as time goes on these types of problems should ease. Both clinicians and patients saw video clinic appointments as positive and beneficial.DiscussionThe UK National Health Service is facing huge challenges with regards to staffing, budgets and space due to increasing patient numbers. Being innovative by using available technology to offer routine follow-up appointments via secure video link may help ease some of the burdens and free up clinic space for those patients who need to be seen face-to-face. This study outlines our experiences of using a remote video consultation system and the associated advantages and pitfalls.

Genopo: a nanopore sequencing analysis toolkit for portable Android devices.

The advent of portable nanopore sequencing devices has enabled DNA and RNA sequencing to be performed in the field or the clinic. However, advances in in situ genomics require parallel development of portable, offline solutions for the computational analysis of sequencing data. Here we introduce Genopo, a mobile toolkit for nanopore sequencing analysis. Genopo compacts popular bioinformatics tools to an Android application, enabling fully portable computation. To demonstrate its utility for in situ genome analysis, we use Genopo to determine the complete genome sequence of the human coronavirus SARS-CoV-2 in nine patient isolates sequenced on a nanopore device, with Genopo executing this workflow in less than 30 min per sample on a range of popular smartphones. We further show how Genopo can be used to profile DNA methylation in a human genome sample, illustrating a flexible, efficient architecture that is suitable to run many popular bioinformatics tools and accommodate small or large genomes. As the first ever smartphone application for nanopore sequencing analysis, Genopo enables the genomics community to harness this cheap, ubiquitous computational resource.

Arbitrating Covid-19 Contract Disputes Under Civil and Common Law Principles

The contractual disputes now emerging from the Covid-19 pandemic will require arbitral tribunals to apply civil or common law principles to resolve the parties' competing claims.