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The angle between the rotation and orbital axes of stars in binary systems -- the obliquity -- is an important indicator of how these systems form and evolve but few such measurements exist. We combine the sample of astrometric orbital inclinations from Gaia DR3 with a sample of solar-like oscillators in which rotational inclinations have been measured using asteroseismology. We supplement our sample with one binary whose visual orbit has been determined using speckle interferometry and present the projected spin-orbit alignments in five systems. We find that each system, and the overall sample, is consistent with alignment but there are important caveats. First, the asteroseismic rotational inclinations are fundamentally ambiguous and, second, we can only measure the projected (rather than true) obliquity. If rotational and orbital inclinations are independent and isotropically-distributed, however, the likelihood of drawing our data by chance is less than a few per cent. Though small, our data set argues against uniformly random obliquities in binary systems. We speculate that dozens more measurements could be made using data from NASA's TESS mission, mostly in red giants. ESA's PLATO mission will likely produce hundreds more spin-orbit measurements in systems with main-sequence and subgiant stars., Comment: Accepted for publication in MNRAS. 4 pages, 3 figures, 1 table. Scripts to reproduce Figs 1 & 2 and data in Table 1 are available at https://gitlab.com/warrickball/kepler-gaia-spin-orbit

The Birmingham Solar Oscillations Network (BiSON) observes acoustic oscillations of the Sun. The dominant noise source is caused by fluctuations of Earth’s atmosphere, and BiSON seeks to mitigate this effect by combining multiple rapid observations in alternating polarization states. Current instrumentation uses bespoke Pockels-effect cells to select the polarization state. Here, we investigate an alternative off-the-shelf solution, a liquid crystal (LC) retarder, and discuss the potential impact of differences in performance. We show through electrical simulation of the photodiode-based detectors, and assessment of both types of polarization device, that although the switching rate is slower the off-the-shelf LC retarder is a viable replacement for a bespoke Pockels-effect cell. The simplifications arising from the use of off-the-shelf components allow easier and quicker instrumentation deployment.

Background Although modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccination is approved for smallpox and monkeypox prevention, immunological persistence and booster effects remain undescribed. Methods Participants naive to smallpox vaccination were randomized to 1 dose MVA-BN (1×MVA, n = 181), 2 doses MVA-BN (2×MVA, n = 183), or placebo (n = 181). Participants with previous smallpox vaccination received 1 MVA-BN booster (HSPX, n = 200). Subsets of the formerly naive groups (approximately 75 each) received an MVA-BN booster 2 years later. Results Neutralizing antibody (nAb) geometric mean titers (GMTs) increased from 1.1 (baseline, both naive groups) to 7.2 and 7.5 (week 4, 1×MVA and 2×MVA, respectively), and further to 45.6 (week 6, 2×MVA after second vaccination). In HSPX, nAb GMT rapidly increased from 21.6 (baseline) to 175.1 (week 2). At 2 years, GMTs for 1×MVA, 2×MVA, and HSPX were 1.1, 1.3, and 10.3, respectively. After boosting in the previously naive groups, nAb GMTs increased rapidly in 2 weeks to 80.7 (1×MVA) and 125.3 (2×MVA), higher than after primary vaccination and comparable to boosted HSPX subjects. Six months after boosting, GMTs were 25.6 (1×MVA) and 49.3 (2×MVA). No safety concerns were identified. Conclusions Anamnestic responses to boosting without sustained high nAb titers support presence of durable immunological memory following primary MVA-BN immunization. Clinical Trials Registration. NCT00316524 and NCT00686582.

BackgroundHuman immunodeficiency virus (HIV) viral load (VL) monitoring is critical for antiretroviral therapy (ART) management. Point-of-care (POC) VL testing has been reported to be feasible and preferred over standard-of-care (SOC) testing in many low- and middle-income country settings where rapid results could improve patient outcomes.MethodsThe timeliness of receipt of VL results was evaluated in an open-label, randomized, controlled trial among patients newly initiating ART. Clinical outcomes with POC VL monitoring using Cepheid Xpert vs SOC VL at Jos University Teaching Hospital and Comprehensive Health Centre Zamko in Nigeria were assessed. We determined time between specimen collection and recording of VL in patient charts, receipt of results, and ART switch for those who met virologic failure criteria.ResultsBetween April 2018 and October 2019, we screened 696 ART-naive individuals; 273 were randomized to POC and 268 to SOC HIV-1 VL testing. Participants in the POC arm received VL results significantly faster than those in the SOC arm (0.1 median days, interquartile range [IQR], 0.1–0.2 vs 143.1 days, IQR, 56.0–177.1, respectively; P < .0001). Participants in the POC arm with confirmed virologic failure vs those in the SOC arm were switched more rapidly to a second-line regimen (0 median days, IQR, 0–28 vs 66 days, IQR, 63–123, respectively; P = .03).ConclusionsPOC VL testing resulted in significant improvement in the timeliness of VL result receipt by patients and use for effective HIV clinical management. In patients experiencing VL failure, POC monitoring enabled prompt switching to second-line ART regimens.Clinical Trials RegistrationNCT03533868.

Background Point-of-care (POC) viral load (VL) tests provide results within hours, enabling same-day treatment interventions. We assessed treatment outcomes with POC vs standard-of-care (SOC) VL monitoring. Methods We implemented a randomized controlled trial at an urban and rural hospital in Nigeria. Participants initiating antiretroviral therapy (ART) were randomized 1:1 for monitoring via the POC Cepheid Xpert or SOC Roche COBAS (v2.0) HIV-1 VL assays. Viral suppression (VS) and retention in care at 12 months were compared via intention-to-treat (ITT) and per-protocol (PP) analyses. Post-trial surveys for POC patients and healthcare workers (HCWs) evaluated acceptability. Results During April 2018–October 2019, 268 SOC and 273 POC patients enrolled in the trial. Viral suppression at Conclusions POC VL monitoring did not improve 12-month VS among those with results but did improve retention and VS documentation and was preferred by most patients and HCWs. Further research can inform best POC implementation conditions and approaches to optimize patient care. Clinical Trials Registration NCT03533868.

Background/Aims Exercise has shown a promising effect in reducing central sensitisation (CS), but it is unknown which exercise type is the most effective. This review aimed to rank and compare the effectiveness of different exercise interventions on CS in people with or without chronic musculoskeletal pain. This will help to identify the optimal exercise intervention to improve pain by reducing CS for subsequent use in clinical trials. Methods We searched MEDLINE, EMBASE, AMED, CINAHL, SPORTDiscus, CENTRAL, PEdro, SCOPUS, as well as references cited in the selected papers, and grey literature from inception to February 2022. We included randomized controlled trials (RCTs) that assessed the effect of exercise interventions on CS indices in humans. RCTs where a specific effect of exercise could not be determined were excluded. Pairwise and network meta-analyses (frequentist and Bayesian) were conducted using random effects models. Effect sizes were calculated using standardized mean difference (SMD). P-score as well as SUCRA score were used to rank the exercise interventions (from best to worst) in both frequentist and Bayesian approaches, respectively. Results The search returned 93,657 records, of which 143 RCTs (5,362 participants [4890 participants had musculoskeletal pain (122 studies), and 427 were pain free (21 studies)]) were eligible. Firstly, we performed the pairwise meta-analysis to examine the effect of all exercise interventions on all CS outcomes. It showed moderate improvement of CS outcomes (SMD - 0.77, 95% confidence interval (95%CI) -0.89 to -0.65, I2 = 87%, p Conclusion Our meta-analysis suggested that various exercise interventions are effective in improving CS. Multicomponent exercise tends to be the most effective, but some exercise combinations might be better than others. Strengthening and stretching combination shows the greatest likelihood among other combinations of being the optimal exercise type. These findings might have utility informing future treatment recommendations for people with CS features. However, Further research should be considered to explore cost-effectiveness of different interventions. Disclosure A.A. Abd Elkhabir: None. D.F. McWilliams: Grants/research support; grant support from Pfizer and Eli Lilly. S. Smith: None. W. Chaplin: None. M. Salimian: None. V. Georgopoulos: None. A. Kouraki: None. D.A. Walsh: Consultancies; Since 2015 DAW has undertaken consultancy through the University of Nottingham to AbbVie Ltd, Pfizer Ltd, Eli Lilly and Company, Love Productions,, Reckitt Benckiser Health Limited and GSK (each non-personal, pecuniary). Honoraria; He has contributed to educational materials through the University of Nottingham, supported by Medscape Education, New York,, International Association for the Study of Pain, and Osteoarthritis Research Society International (OARSI), each of which received financial support from commercial and non-commercial entities, (each non-personal, pecuniary).. Member of speakers’ bureau; He has received speaker fees from the Irish Society for Rheumatology (personal pecuniary).. Grants/research support; He has been responsible for research funded by Pfizer, Eli Lilly, UCB Pharma (non-personal, pecuniary). Other; He receives salary from the University of Nottingham, who have received funding for that purpose from Sherwood Forest Hospitals NHS Foundation Trust,, Nottingham University Hospitals NHS Trust and UKRI/Versus Arthritis (personal, pecuniary).

We describe a new spectrophotometer for the Birmingham Solar Oscillations Network (BiSON), based on a next generation observation platform, BiSON:NG, a significantly miniaturised system making use of inexpensive consumer-grade hardware and off-the-shelf components, where possible. We show through system modelling and simulation, along with a summer observing campaign, that the prototype instrument produces data on the Sun's low-degree acoustic (p-mode) oscillations that are of equal quality and can be seamlessly integrated into the existing network. Refreshing the existing ageing hardware, and the extended observational network potential of BiSON:NG, will secure our ongoing programme of high-quality synoptic observations of the Sun's low-degree oscillations (e.g., for seismic monitoring of the solar cycle at a "whole Sun" level)., 8 pages, 8 figures, 1 table. Accepted by RAS Techniques and Instruments: 2022 September 26

Introduction Frailty is a long-term condition with potentially significant associated healthcare costs and resource usage. The gold standard evidence-based intervention is a comprehensive geriatric assessment. The NHS Long Term Plan highlights the importance of ageing well and developing proactive services in the community. Care home residents often have unmet health and social care needs, and are frequently frail. Methods 59 patients with severe or very severe frailty (Rockwood clinical frailty score 7 or 8) across three care homes with both residential and nursing provision were reviewed in person. They were then discussed in an MDT comprised of geriatricians, GPs, community matrons, district nurses, community therapists and care home staff in order to complete a virtual CGA resulting in a personalised care plan. Results In the 8 weeks after MDT, compared to the 8 weeks before, there was a 49% reduction in GP contacts (28 vs 55) and a 17% reduction in ED attendances (5 vs 6). There was a 133% increase in proactive referrals (7 vs 3) and 20 advanced care plans were completed. 74 medications were reduced or stopped whilst 4 medications were started, with a cost saving of £812.58 over the 8 week follow up. Conclusions Despite a small sample size and a short follow up period, these results suggest that intervention with a proactive CGA provides benefits to frail care home residents, particularly with regards to reductions in polypharmacy and improved access to advanced care planning. These results also suggest potential benefits to the wider system, with reductions in GP contacts and unplanned hospital attendance. We suggest that in future a CGA should be completed for each new resident to a care home as the basis of a personalised care plan.

Similar to many cities across the nation, Hayward, CA, is experiencing an uptick in gun-related violence. From 2015 to 2021, the City of Hayward experienced a 147% increase in assaults with a firearm and a 106% increase in firearm discharges. Gun crimes continue to threaten the safety of the community and its first responders. Likewise, technological advancements and the availability of non-serialized firearms, such as ghost guns, are becoming an increasing threat to community members. Through an evaluation of firearm-related criminal cases from 2015 to 2021, researchers seek to understand the extent and nature of gun violence in the City of Hayward, crime control efforts, and how firearm-related crimes have changed over time. The goal is to analyse trends in gun-related incidents to help shape future policies, data collection, and responses to gun-related calls for service.

Introduction Chronic pain is associated with frailty. We hypothesised that painful comorbidities would be more strongly associated with frailty than non-painful comorbidities. Method Data were from Investigating Musculoskeletal Health and Wellbeing, a UK-based cohort of people with or at risk of musculoskeletal problems or frailty. Average pain over the previous month was assessed using an 11-point numerical rating scale (NRS). The original FRAIL questionnaire comprises five self-report items: Fatigue, Resistance, Ambulation, Illnesses and Loss of weight. In this study risk of frailty was operationalised using a modified FRAIL questionnaire, omitting the “illnesses” item which related to comorbidities. Comorbidities were classified as either ‘painful’ or ‘non-painful’ based on the International Association for the Study of Pain chronic pain classification criteria. Ordinal logistic regression models explored associations of comorbidity counts with frailty. Results Cross-sectional data were from 2473 participants, 57% female, median age 72 (range 40 to 96) years. 518 (21%) participants were classified as frail. Mean (SD) pain score was 5.5 (2.5). Median (IQR) painful comorbidities was 2 (1 to 3) and non-painful 1 (0 to 2). Highest comorbidity frequency: arthritis (66%) and hypertension (38%). Pain was associated with frailty (OR 1.58 (1.52 to 1.64)). Painful comorbidities (aOR 1.64 (1.54 to 1.75) and non-painful comorbidities (aOR 1.31 (1.21 to 1.41)) were both associated with frailty when included in the same multivariable model adjusted for age, sex and BMI. Conclusions Painful comorbidities were most strongly associated with frailty, although non-painful comorbidities also contributed. Pain and frailty are interconnected, and this might in part be due to comorbidities or their treatments. These findings provide justification for further research to identify the mechanisms through which pain is involved in frailty and to include pain management in interventions to ameliorate frailty.

Objectives The aims were to explore the nature of methods/techniques applied to improve adherence to physical activity (PA) and exercise in people with inflammatory arthritis and to identify whether studies were theory based and/or used behaviour change techniques (BCTs). Methods Searches were undertaken of English language articles within four databases: Embase, Medline, PsycINFO and Cochrane. Articles were included if they assessed adherence to a PA and/or exercise intervention. A narrative synthesis of the findings is reported. Results Of 1909 studies screened, 18 studies met inclusion criteria. Adherence was most frequently included as a secondary outcome. Reporting of adherence measures was poor, in that 13 studies did not use a validated measure of adherence, with only three validated measures being identified. The majority of studies were not theory driven (n = 13), although the health belief model was the most used theoretical framework (n = 5). Only two studies mentioned both theory and BCTs. Four studies reported components that were mapped onto BCTs, with goal setting being the most prevalent. Conclusion This scoping review found that adherence to PA and/or exercise interventions was rarely the focus of research, despite its importance in maintaining health in people with inflammatory arthritis. Where research has been conducted in this area, serious shortcomings were revealed, in that psychological theory, evidence-based BCTs derived from theory and valid adherence measures were not used to inform intervention design and target adherence, meaning that interventions were suboptimal. These results suggest that there is considerable room for improvement and that more high-quality research is required to investigate determinants of adherence and develop impactful interventions.

Background The ongoing monkeypox outbreak, a WHO-declared PHEIC, requires fast and broad rollout of MVA-BN vaccinations among risk groups. An initial single-dose strategy, followed by a delayed second dose beyond the approved 4-week interval, could help managing tight vaccine resources. Methods Bavarian Nordic has run a study in vaccinia-naïve participants, randomized to receive either 1 MVA-BN vaccination (N = 181) or 2 MVA-BN vaccinations 4 weeks apart (N = 183). Of note, this study also evaluated participants with prior smallpox vaccination, who received 1 MVA-BN boost (N = 200). Subsets of approximately 75 participants of the vaccinia-naïve subjects having received either 1 or 2 doses of the vaccine were administered an MVA-BN boost 2 years later. Neutralizing antibodies (nAb) were measured using Vaccinia PRNT. Results The 1xMVA-BN and 2xMVA-BN groups responded as expected to the primary regimen, with modest increases in nAb GMTs at Week 2 (5.1 and 4.8, respectively) that further increased at Week 4 (7.2 and 7.5). Two weeks after the second primary vaccination (at Week 6) (2xMVA-BN) nAb GMTs peaked (45.6) before stabilizing at Week 8 (34.0). In both the 1x and 2xMVA-BN groups, the nAb levels were near baseline 2 years after primary vaccination. After the MVA-BN boost at 2 years, both groups exhibited rapid anamnestic responses with nAb GMTs that peaked 2 weeks post-boost (80.7 and 125.3), at higher levels than those observed at any timepoint following primary vaccination, remaining elevated at 6 months post-boost (25.6 and 49.3). These anamnestic responses support the presence of durable immunological memory in both groups. No safety concerns were identified and the most common adverse event following a 2-year MVA-BN boost was injection site erythema in 82.2% of participants. Conclusion A single dose of MVA-BN elicits a durable memory immune response for at least 2 years. Similarly, high nAb responses following a boost dose among subjects in the initial 1xMVA-BN or 2xMVA-BN groups indicate that the approved 4-week interval of the two-dose regimen could optionally be extended up to at least 2 years. NCT00316524 and NCT00686582 Disclosures Heinz Weidenthaler, MD, Bavarian Nordic GmbH: Employee and received warrants Florian Lienert, PhD, Bavarian Nordic GmbH: employee Employee and received warrants Daniela Reichhardt, PhD, Bavarian Nordic A/S: employee Employee and received warrants Darja Schmidt, Dr, Bavarian Nordic GmbH: Employee and received warrants Günter Silbernagl, MSc, Bavarian Nordic: Employed|Bavarian Nordic GmbH: employee Employee and received warrants Paul Chaplin, PhD, Bavarian Nordic A/S: employee (CEO)|Bavarian Nordic A/S: Stocks/Bonds.

Introduction Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD). PAH following CHD repair (repaired PAH-CHD) is an emerging population with increased morbidity and mortality [1–3]. Risk scores that are widely used in the adult PAH population have not been validated and may not be applicable in young children with repaired PAH-CHD. Purpose To characterize the 20-year cohort of the UK National Paediatric PH Service, focusing on peri-operative characteristics and outcomes of children with repaired PAH-CHD, and develop a tailored risk stratification tool. Methods We included consecutive children presenting to our specialist service between 2001 and 2021 with a diagnosis of repaired PAH-CHD. Patients with univentricular physiology, segmental pulmonary hypertension (PH), and PH primarily due to abnormal development of the pulmonary vasculature were excluded. Univariable Cox regression analysis was performed in children with PAH present ≥3 months after CHD repair, with an outcome of death or transplantation. Time-dependent ROC analysis was used to evaluate the risk model. Results Overall, 178 patients were included (age 3.2 [1.3–7.9] years, 58.4% female). Most children (73.0%) were referred following CHD repair. Complex CHD was present in 61.2%, and 48.9% had combined pre- and post-tricuspid shunts. Down syndrome was present in 33.1%. At the first post-operative PH assessment, 53.1% of patients had symptoms, mainly breathlessness. On echocardiographic evaluation, 30.9% had moderate-severe right ventricular dilatation and 23.7% had right ventricular systolic impairment. Over a median follow-up of 6.0 [2.4–11.0] years, 30 (19.2%) patients died and 5 (3.2%) patients underwent lung transplantation. Transpant-free survival at 1, 5, and 10 years was 94.7% (95% CI: 91.2–98.3%), 85.9% (95% CI: 80.3–91.9%), and 80.1% (95% CI: 73.1–87.7%), respectively. Cox analysis identified several clinical variables associated with death or transplantation, of which the following variables assessed post-repair were used to develop the risk score: absence of pre-operative PH, breathlessness, right ventricular dysfunction, and pulmonary vascular resistance index >14 WU m2 or lesion at high risk of causing PH (Figure 1). This novel, simple risk score performed well (AUC >80% at 1, 3, 5 and 10 years) and was well-calibrated in our cohort (Figure 2, D'Agostino-Nam p=0.76). Conclusions In this national cohort of children with repaired PAH-CHD, mortality is significant. This novel, simple risk score performed well in our population and could be used in clinical practice at the time of post-operative assessment to predict outcome and direct management but requires further validation. Funding Acknowledgement Type of funding sources: None.

What is IR35 and how does off-payroll work? Dave Chaplin, CEO of tax compliance firm IR35 Shield, investigates and explains the key differences between the two schemes.

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose To provide health-system pharmacists with published examples of strategies utilized to offer buprenorphine to inpatients with opioid use disorder (OUD) along with information on challenges and legal considerations. Summary Hospitals and emergency departments (EDs) are a constant source of healthcare for patients with OUD. As a result, hospital practitioners can screen, diagnose, begin treatment, and facilitate transfer of care to the outpatient setting. Offering sublingual buprenorphine in the hospital can bridge the gap before outpatient care is established. Multiple studies have shown that initiating treatment in the ED or during inpatient hospitalization results in 47% to 74% of patients utilizing medication-assisted treatment at day 30 of follow-up, statistically superior to the rates achieved with brief interventions or referral alone. Moreover, initiating buprenorphine treatment in the ED has been shown to decrease healthcare costs. Despite the benefits of offering buprenorphine in the inpatient setting, several challenges must be solved by hospital administration, such as achieving clinician readiness to prescribe buprenorphine, developing relationships with outpatient providers of buprenorphine, and creating an efficient workflow. Treatment of OUD with buprenorphine is heavily regulated on the federal level. Pharmacists can participate in the development of these programs and ensure compliance with applicable laws. Conclusion As health systems continue to care for patients with OUD, starting buprenorphine in the inpatient setting can improve the transition to outpatient treatment. Several institutions have developed programs with positive results. With an understanding of the typical barriers and relevant laws when initiating buprenorphine in the hospital setting, health-system pharmacists can assist in the development and operation of these initiatives.

With recent advances in modelling stars using high-precision asteroseismology, the systematic effects associated with our assumptions of stellar helium abundance ($Y$) and the mixing-length theory parameter ($\alpha_\mathrm{MLT}$) are becoming more important. We apply a new method to improve the inference of stellar parameters for a sample of Kepler dwarfs and subgiants across a narrow mass range ($0.8 < M < 1.2\,\mathrm{M_\odot}$). In this method, we include a statistical treatment of $Y$ and the $\alpha_\mathrm{MLT}$. We develop a hierarchical Bayesian model to encode information about the distribution of $Y$ and $\alpha_\mathrm{MLT}$ in the population, fitting a linear helium enrichment law including an intrinsic spread around this relation and normal distribution in $\alpha_\mathrm{MLT}$. We test various levels of pooling parameters, with and without solar data as a calibrator. When including the Sun as a star, we find the gradient for the enrichment law, $\Delta Y / \Delta Z = 1.05^{+0.28}_{-0.25}$ and the mean $\alpha_\mathrm{MLT}$ in the population, $\mu_\alpha = 1.90^{+0.10}_{-0.09}$. While accounting for the uncertainty in $Y$ and $\alpha_\mathrm{MLT}$, we are still able to report statistical uncertainties of 2.5 per cent in mass, 1.2 per cent in radius, and 12 per cent in age. Our method can also be applied to larger samples which will lead to improved constraints on both the population level inference and the star-by-star fundamental parameters., Comment: 21 pages, 15 figures, 12 tables. Accepted for publication in Monthly Notices of the Royal Astronomical Society

ObjectivesTo identify how refractory disease (or relevant terminology variations) in RA and polyarticular JIA (polyJIA) is defined and establish the key components of such definitions.MethodsSearches were undertaken of English-language articles within six medical databases, including manual searching, from January 1998 to March 2020 (PROSPERO: CRD42019127142). Articles were included if they incorporated a definition of refractory disease, or non-response, in RA/polyJIA, with clear components to the description. Qualitative content analysis was undertaken to describe refractory disease in RA/polyJIA and classify each component within each definition.ResultsOf 6251 studies screened, 646 met the inclusion criteria; 581 of these applied non-response criteria while 65 provided refractory disease definitions/descriptions. From the non-response studies, 39 different components included various disease activity measures, emphasizing persistent disease activity and symptoms, despite treatment with one or more biologic DMARD (bDMARD). From papers with clear definitions for refractory disease, 41 components were identified and categorized into three key themes: resistance to multiple drugs with different mechanisms of action, typically two or more bDMARDs; persistence of symptoms and disease activity; and other contributing factors. The most common term used was ‘refractory’ (80%), while only 16.9% reported explicitly how their definition was generated (e.g. clinical experience or statistical methods).ConclusionRefractory disease is defined as resistance to multiple drugs with different mechanisms of action by persistence of physical symptoms and high disease activity, including contributing factors. A clear unifying definition needs implementing, as the plethora of different definitions makes study comparisons and appropriate identification of patients difficult.

Older frail patients have a demonstrable risk of adverse outcomes following attendance to the emergency department (ED), such as functional decline, delirium, institutionalisation, and death. With an increasing number of frail patients within the population, it is important to have a system of identification of these patients at the ‘front door’; with Comprehensive Geriatric Assessment and direction to most appropriate place of care, whilst simultaneously minimising impact on flow within ED departments that are under increasing amounts of pressure. Northumbria’s Frailty Assessment Service (FAS) operates 7 days a week, 12 hours/day into the ED. It identifies, within an hour of arrival, those frail patients >65 and delivers Comprehensive Geriatric Assessment and ‘ward level’ care within 4 hours, using a peripatetic model. It aims to reduce unnecessary hospital admissions and therefore potentially adverse outcomes within this group, whilst minimising impact of flow within the ED, and directs the patients towards the most appropriate place of care. It is Geriatric Specialist Nurse Practitioner led, with Consultant and MDT support, such that it has a workforce that has been able to increase to match demand over the last few years. Over the course of 12 months (Jan—Dec 2021), the service saw 3,430 patients. 2,962 patients were planned by ED for admission, and following FAS review, only 1,169 were admitted acutely, demonstrating a reduction in admission rate of 39.5% across the year. 17.2% of patients were seen on a Saturday or Sunday demonstrating the need for a 7-day service. Average time patients spent with FAS within the ED was 1 h12 minutes. The service demonstrates the sustainability and effectiveness of an extended hours, non-Consultant led ‘front door frailty’ service, without significant impact on the flow within the Emergency Department.

Background Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in young children and the elderly. Protective immunity is not generated after repeated infections, but vaccination may hopefully prove effective. Methods This phase 2 clinical study investigated a multivalent RSV vaccine (MVA-BN-RSV) designed to induce broad antibody and cellular immune responses by encoding RSV surface proteins F, G (for both A and B subtypes), and internal antigens (M2, N). This study evaluated the immune response in adults aged ≥55 years to identify the optimal MVA-BN-RSV dose and vaccination schedule. Results A single dose increased the levels of neutralizing (plaque reduction neutralization test to RSV A and B) and total (IgG and IgA ELISA) antibodies (1.6 to 3.4-fold increase from baseline) and induced a broad Th1-biased cellular immune response (interferon-γ ELISPOT) to all 5 vaccine inserts (5.4 to 9.7-fold increases). Antibody responses remained above baseline for 6 months. A 12-month booster dose elicited a booster effect in antibody and T-cell responses (up to 2.8-fold from preboost levels). No drug-related serious adverse events were reported. Conclusions MVA-BN-RSV induces a broad immune response that persists at least 6 months and can be boosted at 12 months, without significant safety findings. Clinical Trials Registration NCT02873286

Objectives The coronavirus disease 2019 (COVID-19) lockdown and ongoing restrictions in the UK affected access to clinical care, self-management and mental health for many patients with inflammatory arthritis. The aim of this study was to determine the impact of lockdown on inflammatory arthritis clinical care, self-management, disease outcomes and mental health. Methods In total, 338 people with inflammatory arthritis participated in a prospective study, completing a series of online questionnaires. The questionnaires assessed demographics, inflammatory arthritis condition and management, clinical care, quality of life and mental health. Visual analogue scales (VASs) were completed at each assessment. Linear regression, controlling for confounders, was conducted to determine factors associated with physical and mental health outcomes. Results More than half of participants reported worsening VAS by >10 points for patient global assessment (PGA), pain, fatigue and emotional distress during the initial lockdown. Changes in clinical care were associated with worse PGA (b = 8.95, P = 0.01), pain (b = 7.13, P = 0.05), fatigue (b = 17.01, P < 0.01) and emotional distress (b = 12.78, P < 0.01). Emotional distress and depression were also associated with worse outcomes in PGA, pain and fatigue, whereas loneliness was not. In contrast, physical activity seemed to mitigate these effects. Loneliness did not show any associations with outcomes. Over time, these effects decreased or disappeared. Conclusion Changes to clinical care owing to lockdown were associated with worse disease outcomes in patients with inflammatory arthritis. There has also been a clear impact on mental health, with possibly complex relationships between mental health and psychosocial factors. Physical activity emerged as a key influence on disease outcomes and mental health.

Background/Introduction Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD) in children and is associated with significant morbidity and mortality. The impact of different phenotypes on management and survival remains unclear. Purpose To examine the clinical features, management and outcomes of paediatric PAH-CHD patients based on the 20-year experience of the UK National Paediatric Pulmonary Hypertension (PH) Service. Methods Consecutive PAH-CHD patients entering the service between January 2001 and January 2021 were included and classified into: Eisenmenger syndrome (ES, group A), PAH related to a significant systemic-pulmonary shunt (group B), PAH with small or co-incidental CHD (group C) and PAH following defect repair (group D). Incident patients (without pre-existing PAH) were included in survival analysis. Results Of the overall PH paediatric cohort of 1104 patients, 819 (74.2%) had co-existing CHD and 354 (32.1%) patients received a diagnosis of PAH-CHD: 57.1% female, median [IQR] 4.6 [1.7–10.9] years. Group D PAH-CHD was the commonest subgroup, accounting for 36%, while the least frequent subtype was group C (14%). Group A and group B PAH-CHD represented 26% and 24%, respectively. Down syndrome was present in over one third (122, 34.5%) of PAH-CHD patients and was more commonly associated with ES (p=0.02). PAH therapy was started in 79.9% of PAH-CHD patients. At the end of follow-up, patients with group C PAH-CHD were more likely to be on combination therapy than any other group (64.6% vs. 28.4%, p The subgroup distribution of PAH-CHD at diagnosis changed from the early (2000–2005) to late (2015–2020) period (Figure 1). The proportion of ES patients decreased from 43.4% to 14.6% of PAH-CHD (p Transplant-free survival in PAH-CHD was 90.9% (95% CI: 87.8–94%) at 1 year, 77.9% (95% CI: 73.1–83.1%) at 5 years, and 74.9% (95% CI: 69.6–80.7%) at 10 years (Figure 2). Group C PAH-CHD had a lower transplant-free survival than the other 3 groups (HR 2.54, 95% CI: 1.51–4.28, p=0.0005). There was no difference in outcome between group A and group D PAH-CHD (HR 1.19, 95% CI: 0.62–2.28, p=0.6). Conclusions Repaired PAH-CHD, not ES, was the most common subtype in this large paediatric cohort. Over time, there were fewer ES patients and more “operable” patients with left-right shunts, suggesting an improvement in early diagnosis and management. Despite widespread use of PAH therapy, PAH-CHD remains a life-limiting disease with the poorest outcomes in PAH with co-incidental CHD. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr Constantine received a personal PhD fellowship grant (CHAMPION PhD Fellowship) Figure 1Figure 2

Informed consent is vital prior to any dermatological procedure. However, the approach to consent in dermatological surgery has widespread variation.(1) No formal guidance exists regarding which risks should be routinely consented for. The Montgomery ruling states consent should be individualised to each patient based on consideration of material risks.(2).

Mutations in hallmark genes are believed to be the main drivers of cancer progression. These mutations are reported in the Catalogue of Somatic Mutations in Cancer (COSMIC). Structural appreciation of where these mutations appear, in protein–protein interfaces, active sites or deoxyribonucleic acid (DNA) interfaces, and predicting the impacts of these mutations using a variety of computational tools are crucial for successful drug discovery and development. Currently, there are 723 genes presented in the COSMIC Cancer Gene Census. Due to the complexity of the gene products, structures of only 87 genes have been solved experimentally with structural coverage between 90% and 100%. Here, we present a comprehensive, user-friendly, web interface (https://cancer-3d.com/) of 714 modelled cancer-related genes, including homo-oligomers, hetero-oligomers, transmembrane proteins and complexes with DNA, ribonucleic acid, ligands and co-factors. Using SDM and mCSM software, we have predicted the impacts of reported mutations on protein stability, protein–protein interfaces affinity and protein–nucleic acid complexes affinity. Furthermore, we also predicted intrinsically disordered regions using DISOPRED3.