Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10−33; LPA:p<10−19; 1p13.3:p<10−17) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5×10−7). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06–1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ∼4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes.

Background The coronavirus disease (COVID-19) pandemic has led to rapid acceleration in the deployment of new digital technologies to improve both accessibility to and quality of care, and to protect staff. Mixed-reality (MR) technology is the latest iteration of telemedicine innovation; it is a logical next step in the move toward the provision of digitally supported clinical care and medical education. This technology has the potential to revolutionize care both during and after the COVID-19 pandemic. Objective This pilot project sought to deploy the HoloLens2 MR device to support the delivery of remote care in COVID-19 hospital environments. Methods A prospective, observational, nested cohort evaluation of the HoloLens2 was undertaken across three distinct clinical clusters in a teaching hospital in the United Kingdom. Data pertaining to staff exposure to high-risk COVID-19 environments and personal protective equipment (PPE) use by clinical staff (N=28) were collected, and assessments of acceptability and feasibility were conducted. Results The deployment of the HoloLens2 led to a 51.5% reduction in time exposed to harm for staff looking after COVID-19 patients (3.32 vs 1.63 hours/day/staff member; P=.002), and an 83.1% reduction in the amount of PPE used (178 vs 30 items/round/day; P=.02). This represents 222.98 hours of reduced staff exposure to COVID-19, and 3100 fewer PPE items used each week across the three clusters evaluated. The majority of staff using the device agreed it was easy to set up and comfortable to wear, improved the quality of care and decision making, and led to better teamwork and communication. In total, 89.3% (25/28) of users felt that their clinical team was safer when using the HoloLens2. Conclusions New technologies have a role in minimizing exposure to nosocomial infection, optimizing the use of PPE, and enhancing aspects of care. Deploying such technologies at pace requires context-specific information security, infection control, user experience, and workflow integration to be addressed at the outset and led by clinical end-users. The deployment of new telemedicine technology must be supported with objective evidence for its safety and effectiveness to ensure maximum impact.

BackgroundSo far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels.MethodsWe used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ∼60 000 individuals in the discovery stage and ∼90 000 samples in the replication stage.ResultsOur study resulted in the identification of five new associations with circulating lipid levels at four loci. All four loci are within genes that can be linked biologically to lipid metabolism. One of the variants, rs116843064, is a damaging missense variant within the ANGPTL4 gene.ConclusionsThis study illustrates that GWAS with high-scale imputation may still help us unravel the biological mechanism behind circulating lipid levels.

Background Heterogeneous access to clinical learning opportunities and inconsistency in teaching is a common source of dissatisfaction among medical students. This was exacerbated during the COVID‐19 pandemic, with limited exposure to patients for clinical teaching. Methods We conducted a proof‐of‐concept study at a London teaching hospital using mixed reality (MR) technology (HoloLens2™) to deliver a remote access teaching ward round. Results Students unanimously agreed that use of this technology was enjoyable and provided teaching that was otherwise inaccessible. The majority of participants gave positive feedback on the MR (holographic) content used (n = 8 out of 11) and agreed they could interact with and have their questions answered by the clinician leading the ward round (n = 9). Quantitative and free text feedback from students, patients and faculty members demonstrated that this is a feasible, acceptable and effective method for delivery of clinical education. Discussion We have used this technology in a novel way to transform the delivery of medical education and enable consistent access to high‐quality teaching. This can now be integrated across the curriculum and will include remote access to specialist clinics and surgery. A library of bespoke MR educational resources will be created for future generations of medical students and doctors to use on an international scale.

RATIONALE: COVID-19 poses a unique challenge; caring for patients with a novel, infectious disease whilst protecting staff. Some interventions used to give oxygen therapy are aerosol generating procedures. Staff delivering such interventions require PPE and are exposed to a significant viral load resulting in sick days and even death. We aim to reduce this risk using an augmented-reality communication device: The HoloLens by Microsoft. OBJECTIVES: In a tertiary centre in London we aim to implement HoloLens technology, allowing other medical staff to remotely join the consulting clinician when in a high-risk patient area delivering oxygen therapy. The study primary outcome was to reduce the exposure to staff and demonstrate non-inferiority staff satisfaction when compared to not using the device. Our secondary outcome was to reduce extrapolated PPE costs when using the device. METHODS: Our study was conducted in March and April 2020, within a respiratory unit delivering aerosolising oxygen therapies (High flow nasal oxygen, Continuous positive airway pressure and non-invasive ventilation) to patients with suspected or confirmed COVID-19 infection. MEASUREMENTS: Self-reported questionnaires to assess satisfaction in key areas of patient care. An infrared people counting device was also used to assess staff in and out of the unit. MAIN RESULTS: Mean self-reported time in the high-risk zone was less when using HoloLens (2.69 hours) compared to usual practice (3.96 hours) although this difference was not statistically significant (p = 0.3657). HoloLens showed non-inferiority when compared to usual practice in staff satisfaction score for all domains. Furthermore, mean staff satisfaction score encouragingly improved when using HoloLens. Self-reported PPE counts from this study showed 12 staff members changing PPE 25.8 times per shift, almost double the 13.5 times in the HoloLens count. CONCLUSIONS: We have demonstrated HoloLens can reduce the number of staff exposed to aerosol generating areas in a novel infectious disease. Our results show it did not impair communication, medical staff availability or end of life care. HoloLens technology may also reduce the use of PPE, which has equipment availability and cost benefits. This study provides grounding for further use of the HoloLens device by bringing a bedside experience to experts remote to the situation.