E-referrals: improving the routine interspecialty inpatient referral system.

Interspecialty referrals are an essential part of most inpatient stays. With over 130 referrals occurring per week at the Royal Devon and Exeter Hospital, the process must be efficient and safe. The current paper-based 'white card' system was felt to be inefficient, and a Trust incident highlighted patient safety concerns. Questionnaires reinforced the need for improvement, with concerns such as a lack of referral traceability and delays in the referral delivery due to workload. The aims of the project were to improve patient safety and junior doctor efficiency in the referral process. Through appreciative enquiry and the PDSA (Plan-Do-Study-Act) model, an electronic referral system was developed, piloted within two specialties and later expanded to others with improvements made along the way based on user feedback. The system includes novel features including specialties 'acknowledging' a referral to allow referral progress to be tracked. The system stores all referrals, creating a fully auditable inpatient referral pathway. Qualitative data indicated improvement to patient safety and user experience (n=31). Timings for referrals were measured over a 6-month period; referrals became faster with the electronic system, with average time from decision to refer to referral submission improving from 2.1 hours to 1.9 hours, with a noted statistically significant improvement in timings on a statistical process control chart. An unexpected benefit was that patients were also reviewed faster by specialties. Measuring these changes presented a significant challenge due to the complexity of the referral process, and this was a big limitation. Overall, the re-design of a paper-based referral system into an electronic system has been proven to be more efficient and felt to be safer for patients. This is a sustainable change which is being rolled out Trust-wide. We hope that the reporting of this project will help others considering reviewing their inpatient referral pathways.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.Publishe

The involvement of palliative care with neurology – a comparison of UK, Switzerland and Italy

Objectives: To ascertain the involvement of palliative care with neurology services in the care of people with amyotrophic lateral sclerosis (ALS) in the United Kingdom, Italy and Switzerland, in particular the collaboration with and referral from neurology, the involvement in multidisciplinary team care and in the respiratory support of ALS patients. Methods: In 2019, two online surveys were undertaken of palliative care specialists, using specialist groups of the European Academy of Neurology, European Association of Palliative Care and the Association of Palliative Medicine for Great Britain and Ireland. Results: The respondents were specialist palliative care professionals, predominantly senior doctors, involved in the care of people with ALS. As the numbers of respondents from many countries were in single figures the analysis was restricted to the United Kingdom, Italy and Switzerland. The time of involvement varied, with early involvement commonest in the UK. Barriers to referral included neurologists not referring and financial issues, particularly in Switzerland. The reluctance of patients and families to see palliative care services was reported as less than 20% in all countries. Respondents were often involved in the care of people receiving noninvasive ventilation (NIV), in all countries. and with tracheostomy ventilation (TV), particularly in Italy. Conclusions: Palliative care services are often involved in the care of people with ALS, but the extent and timing of involvement varies. The use of clinical guidelines and education on palliative care for neurology services may encourage collaboration, for the benefit of people with ALS and their families

Validating AU Microscopii d with Transit Timing Variations

AU Mic is a young (22 Myr) nearby exoplanetary system that exhibits excess TTVs that cannot be accounted for by the two known transiting planets nor stellar activity. We present the statistical "validation" of the tentative planet AU Mic d (even though there are examples of "confirmed" planets with ambiguous orbital periods). We add 18 new transits and nine midpoint times in an updated TTV analysis to prior work. We perform the joint modeling of transit light curves using EXOFASTv2 and extract the transit midpoint times. Next, we construct an O-C diagram and use Exo-Striker to model the TTVs. We generate TTV log-likelihood periodograms to explore possible solutions for the period of planet d and then follow those up with detailed TTV and RV MCMC modeling and stability tests. We find several candidate periods for AU Mic d, all of which are near resonances with AU Mic b and c of varying order. Based on our model comparisons, the most-favored orbital period of AU Mic d is 12.73596+/-0.00793 days (T_{C,d}=2458340.55781+/-0.11641 BJD), which puts the three planets near a 4:6:9 mean-motion orbital resonance. The mass for d is 1.053+/-0.511 M_E, making this planet Earth-like in mass. If confirmed, AU Mic d would be the first known Earth-mass planet orbiting a young star and would provide a valuable opportunity in probing a young terrestrial planet's atmosphere. Additional TTV observation of the AU Mic system are needed to further constrain the planetary masses, search for possible transits of AU Mic d, and detect possible additional planets beyond AU Mic c.Comment: 89 pages, 35 figures, 34 tables. Redid EXOFASTv2 transit modeling to recover more reasonable stellar posteriors, so redid Exo-Striker TTV modeling for consistency. Despite these changes, the overall results remain unchanged: the 12-7-day case is still the most favored. Submitted to AAS Journals on 2023 Feb 9t

Validating AU Microscopii d with Transit Timing Variations

AU Mic is a young (22 Myr), nearby exoplanetary system that exhibits excess transit timing variations (TTVs) that cannot be accounted for by the two known transiting planets nor stellar activity. We present the statistical “validation” of the tentative planet AU Mic d (even though there are examples of “confirmed” planets with ambiguous orbital periods). We add 18 new transits and nine midpoint times in an updated TTV analysis to prior work. We perform the joint modeling of transit light curves using EXOFASTv2 and extract the transit midpoint times. Next, we construct an O − C diagram and use Exo-Striker to model the TTVs. We generate TTV log-likelihood periodograms to explore possible solutions for d’s period, then follow those up with detailed TTV and radial velocity Markov Chain Monte Carlo modeling and stability tests. We find several candidate periods for AU Mic d, all of which are near resonances with AU Mic b and c of varying order. Based on our model comparisons, the most-favored orbital period of AU Mic d is 12.73596 ± 0.00793 days ( T _C _,d = 2458340.55781 ± 0.11641 BJD), which puts the three planets near 4:6:9 mean-motion resonance. The mass for d is 1.053 ± 0.511 M _⊕ , making this planet Earth-like in mass. If confirmed, AU Mic d would be the first known Earth-mass planet orbiting a young star and would provide a valuable opportunity in probing a young terrestrial planet’s atmosphere. Additional TTV observations of the AU Mic system are needed to further constrain the planetary masses, search for possible transits of AU Mic d, and detect possible additional planets beyond AU Mic c

The application of Diffusive Gradients in Thin Films (DGT) for improved understanding of metal behaviour at marine disposal sites

Assessment of the effects of sediment metal contamination on biological assemblages and function remains a key question in marine management, especially in relation to disposal activities. However, the appropriate description of bioavailable metal concentrations within pore-waters has rarely been reported. Here, metal behaviour and availability at contaminated dredged material disposal sites within UK waters were investigated using Diffusive Gradient in Thin films (DGT). Three stations, representing contrasting history and presence of dredge disposal were studied. Depth profiles of five metals were derived using DGT probes as well as discrete analysis of total metal concentrations from sliced cores. The metals analysed were: iron and manganese, both relevant to sediment biogeochemistry; cadmium, nickel and lead, classified as priority pollutants. DGT time-integrated labile flux profiles of the metals display behaviour consistent with increasingly reduced conditions at depth and availability to DGT (iron and manganese), subsurface peaks and a potential sedimentary source to the water column related to the disposal activity (lead and nickel) and release to pore-water linked to decomposition of enriched phytodetritus (cadmium). DGT data has the potential to improve our current understanding of metal behaviour at impacted sites and is suitable as a monitoring tool. DGT data can provide information on metal availability and fluxes within the sediment at high depth-resolution (5 mm steps). Differences observed in the resulting profiles between DGT and conventional total metal analysis illustrates the significance of considering both total metals and a potentially labile fraction. The study outcomes can help to inform and improve future disposal site impact assessment, and could be complemented with techniques such as Sediment Profile Imagery for improved biologically relevance, spatial coverage and cost-effective monitoring and sampling of dredge material disposal sites. Additionally, the application of this technology could help improve correlative work on biological impacts under national and international auspices when linking biological effects to more biologically relevant metal concentrations

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification