Notes

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He eventually restarted anticoagulation under direction of his primary care doctor.The global pandemic of COVID-19 has challenged the management of hypoxaemic respiratory failure and strained intensive care unit resources. While prone positioning (PP) is an established therapy in mechanically ventilated patients with acute respiratory distress syndrome (ARDS), its role in conscious patients is less well defined. We retrospectively reviewed our experience of implementing early PP in a cohort of 24 patients with acute hypoxaemic respiratory failure due to COVID-19 who required support with continuous positive airway pressure (CPAP). The use of PP alongside CPAP significantly increased both the ROX index and arterial oxygen pressurefractional inspired oxygen (PaO2FiO2) ratio from baseline values (ROX index 7.0±2.5 baseline vs 11.4±3.7 CPAP+PP, p less then 0.0001; PaO2FiO2 ratio 143±73 mm Hg baseline vs 252±87 mm Hg CPAP+PP, p less then 0.01), and the changes to both the ROX index and PaO2FiO2 ratio remained significant 1 hour after cessation of proning. The mean duration of PP in the first 24 hours was 8±5 hours. CW069 Few complications were observed and PP was continued for a mean of 10±5 days. From our experience in a dedicated COVID-19 respiratory high care unit, PP alongside CPAP therapy was feasible, tolerated, safe and improved oxygenation. The use of conscious PP in ARDS warrants further investigation in randomised controlled trials.Antimicrobial resistance (AMR) continues to be a global problem and continues to be addressed through national strategies to improve diagnostics, develop new antimicrobials and promote antimicrobial stewardship. Patients who attend general (ambulatory) practice with symptoms of respiratory tract infections (RTIs) are invariably assessed by some sort of clinical decision rule (CDR). However, CDRs rely on a cluster of non-specific clinical observations. A narrative review of the literature was undertaken to ascertain the value of C reactive protein (CRP) point-of-care testing (POCT) to guide antibacterial prescribing in adult patients presenting to general practitioner (GP) practices with symptoms of RTI. Studies that were included were Cochrane reviews, systematic reviews, randomised controlled trials, cluster randomised trials, controlled before and after studies, cohort studies and economic evaluations. An overwhelming number of studies demonstrated that the use of CRP tests in patients presenting with RTI symptoms reduces index antibacterial prescribing. GPs and patients report a good acceptability for a CRP POCT and economic evaluations show cost-effectiveness of CRP POCT over existing RTI management in primary care. POCTs increase diagnostic precision for GPs in the better management of patients with RTI. With the rapid development of artificial intelligence, patients will expect greater precision in diagnosing and managing their illnesses. Adopting systems that markedly reduce antibiotic consumption is a no-brainer for governments that are struggling to address the rise in AMR.Motile and morphological cellular processes require a spatially and temporally coordinated branched actin network that is controlled by the activity of various regulatory proteins, including the Arp2/3 complex, profilin, cofilin and tropomyosin. We have previously reported that myosin 1b regulates the density of the actin network in the growth cone. Here, by performing in vitro F-actin gliding assays and total internal reflection fluorescence (TIRF) microscopy, we show that this molecular motor flattens (reduces the branch angle) in the Arp2/3-dependent actin branches, resulting in them breaking, and reduces the probability of new branches forming. This experiment reveals that myosin 1b can produce force sufficient enough to break up the Arp2/3-mediated actin junction. Together with the former in vivo studies, this work emphasizes the essential role played by myosins in the architecture and dynamics of actin networks in different cellular regions.This article has an associated First Person interview with the first author of the paper.Cytokinesis in land plants involves the formation of a cell plate that develops into the new cell wall. Callose, a β-1,3 glucan, accumulates at later stages of cell plate development, presumably to stabilize this delicate membrane network during expansion. Cytokinetic callose is considered specific to multicellular plant species, because it has not been detected in unicellular algae. Here we present callose at the cytokinesis junction of the unicellular charophyte, Penium margaritaceum Callose deposition at the division plane of P. margaritaceum showed distinct, spatiotemporal patterns likely representing distinct roles of this polymer in cytokinesis. Pharmacological inhibition of callose deposition by endosidin 7 resulted in cytokinesis defects, consistent with the essential role for this polymer in P. margaritaceum cell division. Cell wall deposition at the isthmus zone was also affected by the absence of callose, demonstrating the dynamic nature of new wall assembly in P. margaritaceum The identification of candidate callose synthase genes provides molecular evidence for callose biosynthesis in P. margaritaceum The evolutionary implications of cytokinetic callose in this unicellular zygnematopycean alga is discussed in the context of the conquest of land by plants.This article has an associated First Person interview with the first author of the paper.
GPs have a central role in decisions about prescribing anticipatory medications to help control symptoms at the end of life. Little is known about GPs' decision-making processes in prescribing anticipatory medications, how they discuss this with patients and families, or the subsequent use of prescribed drugs.

To explore GPs' decision-making processes in the prescribing and use of anticipatory medications for patients at the end of life.

A qualitative interview study with GPs working in one English county.

Semi-structured interviews were conducted with a purposive sample of 13 GPs. Interview transcripts were analysed inductively using thematic analysis.

Three themes were constructed from the data something we can do, getting the timing right, and delegating care while retaining responsibility. Anticipatory medications were a tangible intervention GPs felt they could offer patients approaching death (something we can do). The prescribing of anticipatory medications was recognised as a harbinger of dehe prescription. GPs need regular access to nurses and rely on their skills to administer drugs appropriately. Patients' and families' experiences of anticipatory medications, and their preferences for involvement in decision making, warrant urgent investigation.
The first wave of the London COVID-19 epidemic peaked in April 2020. Attention initially focused on severe presentations, intensive care capacity, and the timely supply of equipment. While general practice has seen a rapid uptake of technology to allow for virtual consultations, little is known about the pattern of suspected COVID-19 presentations in primary care.

To quantify the prevalence and time course of clinically suspected COVID-19 presenting to general practices, to report the risk of suspected COVID-19 by ethnic group, and to identify whether differences by ethnicity can be explained by clinical data in the GP record.

Cross-sectional study using anonymised data from the primary care records of approximately 1.2 million adults registered with 157 practices in four adjacent east London clinical commissioning groups. The study population includes 55% of people from ethnic minorities and is in the top decile of social deprivation in England.

Suspected COVID-19 cases were identified clinically andmain as predictors of suspected COVID-19, with levels of risk similar to hospital admission reports. Further understanding of these differences requires social and occupational data.
New healthcare models are being explored to enhance care coordination, efficiency, and outcomes. Evidence is scarce regarding the impact of vertical integration of primary and secondary care on emergency department (ED) attendances, unplanned hospital admissions, and readmissions.

To examine the impact of vertical integration of an NHS provider hospital and 10 general practices on unplanned hospital care DESIGN AND SETTING A retrospective database study using synthetic controls of an NHS hospital in Wolverhampton integrated with 10 general practices, providing primary medical services for 67 402 registered patients.

For each vertical integration GP practice, a synthetic counterpart was constructed. The difference in rate of ED attendances, unplanned hospital admissions, and unplanned hospital readmissions was compared, and pooled across vertical integration practices versus synthetic control practices pre-intervention versus post-intervention.

Across the 10 practices, pooled rates of ED attendances dions and readmissions in this study. Further work is required to understand the mechanisms involved in this complex intervention, to assess the generalisability of these findings, and to determine the impact on patient satisfaction, health outcomes, and GP workload.
Skin complaints are common in primary care, and poor outcomes in long-term conditions are often due to low adherence to treatment. Shared decision making and self-management support may help, yet there is little understanding of patient involvement or the support provided by GPs.

To describe the content of primary care consultations for skin problems, including shared decision making practice, delivery of self-management advice, and follow-up.

Cross-sectional study of video-recorded UK adult GP consultations and linked data.

A coding tool was developed and applied to all consultations with skin problems. Shared decision making was assessed using the observer OPTION
scale.

A total of 45/318 consultations (14.2%) related to one or more skin problems, which were discussed alongside other problems in 71.1% (32/45) of consultations. Of the 100 different problems discussed in these consultations, 51 were dermatological. The mean amount of time spent on skin problems in the consultations was 4 minutes 16 and self-management advice not consistently given, with re-attendance for the same problem common. GPs' training should reflect how frequently skin problems are seen and seek to improve patient involvement in decision making and support self-management.
Recently, necroptosis has attracted increasing attention in arthritis research; however, it remains unclear whether its regulation is involved in osteoarthritis (OA) pathogenesis. Since receptor-interacting protein kinase-3 (RIP3) plays a pivotal role in necroptosis and its dysregulation is involved in various pathological processes, we investigated the role of the RIP3 axis in OA pathogenesis.

Experimental OA was induced in wild-type or
knockout mice by surgery to destabilise the medial meniscus (DMM) or the intra-articular injection of adenovirus carrying a target gene (Ad-Rip3 and Ad-Trim24 shRNA). RIP3 expression was examined in OA cartilage from human patients; Trim24, a negative regulator of RIP3, was identified by microarray and in silico analysis. Connectivity map (CMap) and in silico binding approaches were used to identify RIP3 inhibitors and to examine their direct regulation of RIP3 activation in OA pathogenesis.

RIP3 expression was markedly higher in damaged cartilage from patients with OA than in undamaged cartilage.
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