Maintaining face-to-face contact during the COVID-19 pandemic: a longitudinal qualitative investigation in UK primary care.

BACKGROUND: In March 2020, the COVID-19 pandemic required a rapid reconfiguration of UK general practice to minimise face-to-face contact with patients to reduce infection risk. However, some face-to-face contact remained necessary and practices needed to ensure such contact could continue safely. AIM: To examine how practices determined when face-to-face contact was necessary and how face-to-face consultations were reconfigured to reduce COVID-19 infection risk. DESIGN & SETTING: Qualitative interview study in general practices in Bristol, North Somerset, and South Gloucestershire. METHOD: Longitudinal semi-structured interviews with clinical and managerial practice staff were undertaken at four timepoints between May and July 2020. RESULTS: Practices worked flexibly within general national guidance to determine when face-to-face contact with patients was necessary, influenced by knowledge of the patient, experience, and practice resilience. For example, practices prioritised patients according to clinical need using face-to-face contact to resolve clinician uncertainty or provide adequate reassurance to patients. To make face-to-face contact as safe as possible and keep patients separated, practices introduced a heterogeneous range of measures that exploited features of their indoor and outdoor spaces, and altered their appointment processes. As national restrictions eased in June and July, the number and proportion of patients seen face to face generally increased. However, the reconfiguration of buildings and processes reduced the available capacity and put increased pressure on practices. CONCLUSION: Practices responded rapidly and creatively to the initial lockdown restrictions. The variety of ways practices organised face-to-face contact to minimise infection highlights the need for flexibility in guidance.

Implementation of remote consulting in UK primary care following the COVID-19 pandemic: a mixed-methods longitudinal study.

BACKGROUND: To reduce contagion of COVID-19, in March 2020 UK general practices implemented predominantly remote consulting via telephone, video, or online consultation platforms. AIM: To investigate the rapid implementation of remote consulting and explore impact over the initial months of the COVID-19 pandemic. DESIGN AND SETTING: Mixed-methods study in 21 general practices in Bristol, North Somerset and South Gloucestershire. METHOD: Longitudinal observational quantitative analysis compared volume and type of consultation in April to July 2020 with April to July 2019. Negative binomial models were used to identify if changes differed among different groups of patients. Qualitative data from 87 longitudinal interviews with practice staff in four rounds investigated practices' experience of the move to remote consulting, challenges faced, and solutions. A thematic analysis utilised Normalisation Process Theory. RESULTS: There was universal consensus that remote consulting was necessary. This drove a rapid change to 90% remote GP consulting (46% for nurses) by April 2020. Consultation rates reduced in April to July 2020 compared to 2019; GPs and nurses maintained a focus on older patients, shielding patients, and patients with poor mental health. Telephone consulting was sufficient for many patient problems, video consulting was used more rarely, and was less essential as lockdown eased. SMS-messaging increased more than three-fold. GPs were concerned about increased clinical risk and some had difficulties setting thresholds for seeing patients face-to-face as lockdown eased. CONCLUSION: The shift to remote consulting was successful and a focus maintained on vulnerable patients. It was driven by the imperative to reduce contagion and may have risks; post-pandemic, the model will need adjustment.

A novel endothelial damage inhibitor for the treatment of vascular conduits in coronary artery bypass grafting: protocol and rationale for the European, multicentre, prospective, observational DuraGraft registry.

BACKGROUND: Vein graft disease (VGD) impairs graft patency rates and long-term outcomes after coronary artery bypass grafting (CABG). DuraGraft is a novel endothelial-damage inhibitor developed to efficiently protect the structural and functional integrity of the vascular endothelium. The DuraGraft registry will evaluate the long-term clinical outcomes of DuraGraft in patients undergoing CABG procedures. METHODS: This ongoing multicentre, prospective observational registry will enrol 3000 patients undergoing an isolated CABG procedure or a combined procedure (ie, CABG plus valve surgery or other surgery) with at least one saphenous vein grafts or one free arterial graft (ie, radial artery or mammary artery). If a patient is enrolled, all free grafts (SVG and arterial will be treated with DuraGraft. Data on baseline, clinical, and angiographic characteristics as well as procedural and clinical events will be collected. The primary outcome measure is the occurrence of a major adverse cardiac event (MACE; defined as death, non-fatal myocardial-infarction, or need for repeat-revascularisation). Secondary outcome measures are the occurrence of major adverse cardiac and cerebrovascular events (MACCE; defined as death, non-fatal myocardial-infarction, repeat-revascularisation, or stroke), patient-reported quality of life, and health-economic data. Patient assessments will be performed during hospitalisation, at 1-month, 1-year, and annually thereafter to 5 years post-CABG. Events will be adjudicated by an independent clinical events committee. This European, multi-institutional registry will provide detailed insights into clinical outcome associated with DuraGraft. DISCUSSION: This European, multi-institutional registry will provide detailed insights into clinical outcome associated with the use of DuraGraft. Beyond that, and given the comprehensive data sets comprising of patient, procedural, and graft parameters that are being collected, the registry will enable for multiple subgroup analyses targeting focus groups or specific clinical questions. These may include analysis of subpopulations such as patients with diabetes or multimorbid high-risk patients (patient level), evaluation of relevance of harvesting technique including endoscopic versus open conduit harvesting (procedural level), or particular graft-specific aspects (conduit level). TRIAL REGISTRATION: ClinicalTrials.gov NCT02922088 . Registered October 3, 2016. ETHICS AND DISSEMINATION: The regional ethics committees have approved the registry. Results will be submitted for publication.

Fendiline Enhances the Cytotoxic Effects of Therapeutic Agents on PDAC Cells by Inhibiting Tumor-Promoting Signaling Events: A Potential Strategy to Combat PDAC.

The L-type calcium channel blocker fendiline has been shown to interfere with Ras-dependent signaling in K-Ras mutant cancer cells. Earlier studies from our lab had shown that treatment of pancreatic cancer cells with fendiline causes significant cytotoxicity and interferes with proliferation, survival, migration, invasion and anchorage independent growth. Currently there are no effective therapies to manage PDACs. As fendiline has been approved for treatment of patients with angina, we hypothesized that, if proven effective, combinatorial therapies using this agent would be easily translatable to clinic for testing in PDAC patients. Here we tested combinations of fendiline with gemcitabine, visudyne (a YAP1 inhibitor) or tivantinib (ARQ197, a c-Met inhibitor) for their effectiveness in overcoming growth and oncogenic characteristics of PDAC cells. The Hippo pathway component YAP1 has been shown to bypass K-Ras addiction, and allow tumor growth, in a Ras-null mouse model. Similarly, c-Met expression has been associated with poor prognosis and metastasis in PDAC patients. Our results presented here show that combinations of fendiline with these inhibitors show enhanced anti-tumor activity in Panc1, MiaPaCa2 and CD18/HPAF PDAC cells, as evident from the reduced viability, migration, anchorage-independent growth and self-renewal. Biochemical analysis shows that these agents interfere with various signaling cascades such as the activation of Akt and ERK, as well as the expression of c-Myc and CD44 that are altered in PDACs. These results imply that inclusion of fendiline may improve the efficacy of various chemotherapeutic agents that could potentially benefit PDAC patients.

A pigeonpea gene confers resistance to Asian soybean rust in soybean.

Asian soybean rust (ASR), caused by the fungus Phakopsora pachyrhizi, is one of the most economically important crop diseases, but is only treatable with fungicides, which are becoming less effective owing to the emergence of fungicide resistance. There are no commercial soybean cultivars with durable resistance to P. pachyrhizi, and although soybean resistance loci have been mapped, no resistance genes have been cloned. We report the cloning of a P. pachyrhizi resistance gene CcRpp1 (Cajanus cajan Resistance against Phakopsora pachyrhizi 1) from pigeonpea (Cajanus cajan) and show that CcRpp1 confers full resistance to P. pachyrhizi in soybean. Our findings show that legume species related to soybean such as pigeonpea, cowpea, common bean and others could provide a valuable and diverse pool of resistance traits for crop improvement.

Identification of Phakopsora pachyrhizi Candidate Effectors with Virulence Activity in a Distantly Related Pathosystem.

Phakopsora pachyrhizi is the causal agent of Asian Soybean Rust, a disease that causes enormous economic losses, most markedly in South America. P. pachyrhizi is a biotrophic pathogen that utilizes specialized feeding structures called haustoria to colonize its hosts. In rusts and other filamentous plant pathogens, haustoria have been shown to secrete effector proteins into their hosts to permit successful completion of their life cycle. We have constructed a cDNA library from P. pachyrhizi haustoria using paramagnetic bead-based methodology and have identified 35 P. pachyrhizi candidate effector (CE) genes from this library which are described here. In addition, we quantified the transcript expression pattern of six of these genes and show that two of these CEs are able to greatly increase the susceptibility of Nicotiana benthamiana to Phytophthora infestans. This strongly suggests that these genes play an important role in P. pachyrhizi virulence on its hosts.