British Society for Rheumatology guideline on management of adult and juvenile onset Sjögren disease.

Sjögren disease (SD) is a chronic, autoimmune disease of unknown aetiology with significant impact on quality of life. Although dryness (sicca) of the eyes and mouth are the classically described features, dryness of other mucosal surfaces and systemic manifestations are common. The key management aim should be to empower the individual to manage their condition-conserving, replacing and stimulating secretions; and preventing damage and suppressing systemic disease activity. This guideline builds on and widens the recommendations developed for the first guideline published in 2017. We have included advice on the management of children and adolescents where appropriate to provide a comprehensive guideline for UK-based rheumatology teams.

Intraoperative and Postoperative Hemodynamic Predictors of Acute Kidney Injury in Pediatric Heart Transplant Recipients.

Acute kidney injury (AKI) is common after pediatric heart transplantation (HT) and is associated with inferior patient outcomes. Hemodynamic risk factors for pediatric heart transplant recipients who experience AKI are not well described. We performed a retrospective review of 99 pediatric heart transplant patients at Lucile Packard Children's Hospital Stanford from January 1, 2015, to December 31, 2019, in which clinical and demographic characteristics, intraoperative perfusion data, and hemodynamic measurements in the first 48 postoperative hours were analyzed as risk factors for severe AKI (Kidney Disease: Improving Global Outcomes [KDIGO] stage ≥ 2). Univariate analysis was conducted using Fisher's exact test, Chi-square test, and the Wilcoxon rank-sum test, as appropriate. Multivariable analysis was conducted using logistic regression. Thirty-five patients (35%) experienced severe AKI which was associated with lower intraoperative cardiac index ( p = 0.001), higher hematocrit ( p < 0.001), lower body temperature ( p < 0.001), lower renal near-infrared spectroscopy ( p = 0.001), lower postoperative mean arterial blood pressure (MAP: p = 0.001), and higher central venous pressure (CVP; p < 0.001). In multivariable analysis, postoperative CVP >12 mm Hg (odds ratio [OR] = 4.27; 95% confidence interval [CI]: 1.48-12.3, p = 0.007) and MAP <65 mm Hg (OR = 4.9; 95% CI: 1.07-22.5, p = 0.04) were associated with early severe AKI. Children with severe AKI experienced longer ventilator, intensive care, and posttransplant hospital days and inferior survival ( p = 0.01). Lower MAP and higher CVP are associated with severe AKI in pediatric HT recipients. Patients, who experienced AKI, experienced increased intensive care unit (ICU) morbidity and inferior survival. These data may guide the development of perioperative renal protective management strategies to reduce AKI incidence and improve patient outcomes.

Effectiveness of a mindfulness-based intervention for persons with early psychosis: A multi-site randomized controlled trial.

BACKGROUND: The Mindfulness Ambassador Program (MAP) is a group-based, facilitated mindfulness-based intervention (MBI). We sought to determine the effectiveness of MAP on reducing negative psychotic symptoms and enhancing mindfulness skills among persons experiencing early psychosis. METHODS: We conducted a pragmatic randomized controlled trial (RCT) at three early psychosis intervention (EPI) programs in Ontario, Canada. Participants (N = 59) were randomly assigned to receive MAP (n = 29) for 1-hour weekly sessions over 3 months, or to treatment as usual (TAU, n = 30). Assessments were conducted at baseline, 3 months, and 6 months using the Self-Evaluation of Negative Symptoms (SNS) and Kentucky Inventory of Mindfulness Skills (KIMS). Linear mixed methods were used to assess the joint effects of group and time. RESULTS: At 3 months, participants who received MAP (n = 17) demonstrated greater reductions on the SNS relative to TAU (n = 15), which were clinically and statistically significant (-4.1; 95%CI -7.5, -0.7; p = 0.019). At 6 months, the difference between MAP (n = 10) and TAU (n = 13) was no longer statistically significant (-1.2; 95%CI -5.2,2.7; p = 0.54). On the KIMS, no significant effects were found at 3 months (+0.3; 95%CI -2.0,2.5; p = 0.82) or 6 months (+0.4; 95%CI -2.2,2.9; p = 0.79). CONCLUSIONS: We conducted one of the first multi-site RCTs of a MBI for early psychosis. Our findings indicated that MAP was more effective in reducing negative symptoms compared to TAU in the short term. Earlier reductions in negative psychotic symptoms may help facilitate recovery in the long term.

An overview of RB1 transcript alterations detected during retinoblastoma genetic screening.

Identification of pathogenic RB1 variants aids in the clinical management of families with retinoblastoma. We routinely screen DNA for RB1 variants, but transcript analysis can also be used for variant screening, and to help decide variant pathogenicity. DNA was screened by conformation analysis followed by Sanger sequencing. Large deletion/insertions were detected by polymorphism analysis, MLPA and quantitative-PCR. Methylation-specific PCR was used to detect hypermethylation. RNA screening was performed when a DNA pathogenic variant was missing, or to determine effects on splicing.Two hundred and thirteen small coding variants were predicted to affect splicing in 207 patients. Splice donor (sd) variants were nearly twice as frequent as splice acceptor (sa) with the most affected positions being sd + 1 and sa-1. Some missense and nonsense codons altered splicing, while some splice consensus variants did not. Large deletion/insertions can disrupt splicing, but RNA analysis showed that some of these are more complex than indicated by DNA testing. RNA screening found pathogenic variants in 53.8% of samples where DNA analysis did not. RB1 splicing is altered by changes at consensus splice sites, some missense and nonsense codons, deep intronic changes and large deletion/insertions. Common alternatively spliced transcripts may complicate analysis. An effective molecular screening strategy would include RNA analysis to help determine pathogenicity.

Biomarkers of erythropoiesis response to intravenous iron in a crossover pilot study in unexplained anemia of the elderly.

Anemia is common in older adults, but often unexplained. Previously, we conducted a randomized, controlled trial of intravenous (IV) iron sucrose to study its impact on the 6-minute walk test and hemoglobin in older adults with unexplained anemia and ferritin levels of 20-200 ng/mL. In this report, we present for the first time the response of hemoglobin, as well as the dynamic response of biomarkers of erythropoiesis and iron indices, in a pooled analysis of the initially IV iron-treated group of 9 subjects and the subsequently IV iron treated 10 subjects from the delayed treatment group. We hypothesized that there would be a reproducible hemoglobin response from IV iron, and that iron indices and erythropoietic markers would reflect appropriate iron loading and reduced erythropoietic stress. To investigate the biochemical response of anemia to IV iron, we studied the dynamics of soluble transferrin receptor (STfR), hepcidin, erythropoietin (EPO), and iron indices over 12 weeks after treatment. In total, all 19 treated subjects were evaluable: 9 from initial treatment and 10 after cross-over. Hemoglobin rose from 11.0 to 11.7 g/dL, 12 weeks after initiating IV iron treatment of 1000 mg divided weekly over 5 weeks. We found early changes of iron loading after 1-2 IV iron dose: serum iron increased by 184 mcg/dL from a baseline of 66 mcg/dL, ferritin by 184 ng/mL from 68 ng/mL, and hepcidin by 7.49 ng/mL from 19.2 ng/mL, while STfR and serum EPO declined by 0.55 mg/L and 3.5 mU/mL from 19.2 ng/mL and 14 mU/mL, respectively. The erythroid response and evidence of enhanced iron trafficking are consistent with the hypothesis that IV iron overcomes iron deficient or iron-restricted erythropoiesis. These data provide new insight that iron-restricted erythropoiesis is a potential and targetable mechanism for patients diagnosed with unexplained anemia of the elderly and offers support for larger prospective trials of IV iron among anemic older adults of low to normal ferritin.

'Stuck in the System': An Interpretative Phenomenological Analysis of Transmasculine Experiences of Gender Transition in the UK.

A gender dysphoria diagnosis is currently required in the UK to access NHS transition-related treatment. However, this approach has been criticised by academics and activists as pathologising, 'gatekeeping' transgender identities, and can be viewed by the transgender community as a barrier to necessary medical care. The present research examines transmasculine experiences of gender transition in the UK, focusing on exploring the barriers encountered during identity development and medical transition. Semi-structured interviews were conducted with three individuals, and nine individuals took part in a single focus group. The data were analysed using Interpretative Phenomenological Analysis producing three main themes: 'Conceptualising Stages of Transition'; 'NHS Communication and Support'; and 'Medicalisation, Power and Non-disclosure'. Participants conceptualised access to transition-related treatment as an intrusive and complicated process that negatively impacts identity development. They spoke of barriers such as lack of trans-specific healthcare knowledge, insufficient communication and support from healthcare professionals, and restricted autonomy arising from the pathologisation of trans identities. Results suggest transmasculine individuals may face numerous barriers when trying to access healthcare, and therefore, a move towards the Informed Consent Model could ameliorate many of these barriers and would empower service-users to make informed choices.

C-Reactive protein rise in rheumatology patients following COVID-19 vaccination.

Objective: The aim was to determine the proportion of patients with inflammatory arthritis who have a flare of their rheumatological disease within 4 weeks of receiving a coronavirus disease 2019 (COVID-19) vaccine, using CRP as a surrogate marker. Methods: A retrospective review was conducted of notes for patients with inflammatory arthritis within 30 days of their COVID-19 vaccine. An electronic database (DAWN) was used to identify all patients who were currently on a DMARD or biologic therapy. This was then correlated with vaccine data from the National Immunisation and Vaccination System (NIVS) and CRP within 30 days of their vaccination. Results: From the DAWN database, 1620 adults were identified (mean age 61 years, 64% female). Three types of vaccinations were administered: AstraZeneca (AZ), BioNTech-Pfizer or Moderna. Vaccine uptake was 1542 of 1620 (95.2% for the first dose), 1550 of 1620 (95.7% for the second dose) and 1437 of 1620 (88.7% for the third dose). One hundred and ninety-two of 1542 patients (12.5%) had a CRP rise of >10 mg/l within 30 days of their vaccine, which was higher than the baseline flare rate of 8.6% (P = 0.0004). Conclusion: Patients with inflammatory arthritis and on DMARDs have a high uptake of COVID-19 vaccine (95%), which is greater than the national average. A CRP rise >10 mg/l within 30 days of vaccination was observed in ∼1 in 10 patients in our study population after all three doses. There might be a slight increase in disease flare in patients with inflammatory arthritis after COVID-19 vaccinations, and additional research is required to assess this association further.

Evaluating the feasibility and potential impacts of a recovery-oriented psychosocial rehabilitation toolkit in a health care setting in Kenya: A mixed-methods study.

OBJECTIVES: This pilot study evaluated the feasibility and potential impacts of delivering the Psychosocial Rehabilitation (PSR) Toolkit for people with serious mental illness within a health care setting in Kenya. METHOD: This study used a convergent mixed-methods design. Participants were people with serious mental illness (n = 23), each with an accompanying family member, who were outpatients of a hospital or satellite clinic in semirural Kenya. The intervention consisted of 14 weekly group sessions of PSR cofacilitated by health care professionals and peers with mental illness. Quantitative data were collected from patients and family members using validated outcome measures before and after the intervention. Qualitative data were collected from focus groups with patients and family members, and individual interviews with facilitators, after the intervention. RESULTS: Quantitative findings indicated that patients experienced moderate improvement in illness management and, in contrast to qualitative findings, family members experienced moderate worsening in attitudes toward recovery. Qualitative findings revealed positive outcomes for both patients and family members, as reflected in greater feelings of hope and mobilization to reduce stigma. Factors that facilitated participation included: helpful and accessible learning materials; committed and involved stakeholders; and flexible solutions to promote continued involvement. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: This pilot study found that delivery of the Psychosocial Rehabilitation Toolkit was feasible within a health care setting in Kenya and associated with overall positive outcomes among patients with serious mental illness. Further research on its effectiveness on a larger scale and using culturally validated measures is needed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Me, myself, and nature: living with dementia and connecting with the natural world - more than a breath of fresh air? A literature review.

OBJECTIVE: Despite growing awareness of the importance of engagement with the natural world for people living with dementia, little is known about the impact specifically for people living independently in their own home. This review identifies, analyses and synthesises existing research, incorporating first-person narrative accounts of the benefits and potential challenges experienced in forging meaningful connections with the natural world. METHODS: Six databases were searched from February 2000 to February 2021. Relevant organisations and authors were contacted, and a hand search of included study reference lists was conducted. The findings of included studies were synthesised using a thematic analysis approach. FINDINGS: Sixteen studies were included: 13 qualitative and three mixed methods. Eight themes and three sub-themes were identified, revealing how contact with the natural world held a significance for people living with dementia, associated with a sense of pleasure, comfort, stimulation, freedom and meaning. Support and the use of adaptive strategies afforded opportunities for continued engagement with meaningful outdoor activities and the promotion of identity, independence, social interaction, enhanced wellbeing and quality of life for people living independently with dementia. CONCLUSION: Meaningful connections with the natural world offer far more than a 'breath of fresh air'. When support mechanisms are in place, engaging with the natural world can be a valuable arena for enablement and continuity, providing a sense of connectedness to self, place and others.

Safety and efficacy of filgotinib, lanraplenib and tirabrutinib in Sjögren's syndrome: a randomized, phase 2, double-blind, placebo-controlled study.

OBJECTIVE: The aim of this study was to characterize the safety and efficacy of filgotinib, lanraplenib and tirabrutinib in patients with active SS. METHODS: This multicentre, double-blind study randomized patients with active primary or secondary SS [EULAR SS disease activity index (ESSDAI) ≥5) to receive filgotinib 200 mg (Janus kinase-1 inhibitor), lanraplenib 30 mg (spleen tyrosine kinase inhibitor), tirabrutinib 40 mg (Bruton's tyrosine kinase inhibitor), or placebo. The composite primary end point was the week-12 proportion of patients fulfilling protocol-specified improvement criteria (based on CRP and SS-related symptoms). The EULAR SS patient-reported index (ESSPRI) and the ESSDAI change from baseline (CFB) were secondary end points. Exploratory end points included disease-related biomarkers. Treatment-emergent adverse events (AEs) represented safety outcomes. RESULTS: The mean of the baseline ESSDAI was 10.1, and of ESSPRI was 6.2 in the 150 patients who were treated; 125 completed the 24-week placebo-controlled treatment period. At week 12, 43.3% of the filgotinib group achieved the primary end point (P = 0.17 vs placebo) vs 42.3% (P = 0.16), 34.7% (P = 0.33), and 26.7% of lanraplenib, tirabrutinib, and placebo groups, respectively. Neither secondary end point was met. Biomarker reductions included immunoglobulins classically associated with SS disease activity. Filgotinib ESSDAI CFB appeared more pronounced in subgroups with baseline ESSDAI ≥14 or without DMARDs/CSs. Most AEs were Grade 1 or 2. CONCLUSION: Three drugs with disparate mechanisms were tested, but no significant differences vs placebo in primary or secondary end points were observed. These results may be considered hypothesis-generating, given the drug tolerability, subgroup analysis, and biomarker findings. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03100942.

The evolution of coordination: a phylogenetic meta-analysis and systematic review.

To solve many cooperative problems, humans must have evolved the ability to solve physical problems in their environment by coordinating their actions. There have been many studies conducted across multiple different species regarding coordinating abilities. These studies aim to provide data which will help illuminate the evolutionary origins of cooperative problem solving and coordination. However, it is impossible to make firm conclusions about the evolutionary origins of coordinating abilities without a thorough comparative analysis of the existing data. Furthermore, there may be certain aspects of the literature that make it very difficult to confidently address evolutionary and meta-analytic questions. This study aimed to rectify this by using meta-analysis, phylogenetic analysis and systematic review to analyse the data already obtained across multiple studies, and to assess the reliability of this data. We found that many studies did not provide the information necessary for meta-analysis, or were not comparable enough to other studies to be included in analyses, meaning meta-analyses were underpowered or could not be conducted due to low samples of both studies and different species. Overall, we found that many studies reported small positive effects across studies, but the standard errors of these effects frequently traversed zero.

A pilot study of participatory video in early psychosis: Qualitative findings.

For people with psychotic disorders, developing a personal narrative about one's experiences with psychosis can help promote recovery. This pilot study examined participants' reactions to and experiences of participatory video as an intervention to help facilitate recovery-oriented narrative development in early psychosis. Outpatients of an early psychosis intervention program were recruited to participate in workshops producing short documentary-style videos of their collective and individual experiences. Six male participants completed the program and took part in a focus group upon completion and in an individual semistructured interview three months later. Themes were identified from the focus group and interviews and then summarized for descriptive purposes. Prominent themes included impacts of the videos on the participants and perceived impacts on others, fulfilment from sharing experiences and expressing oneself, value of collaboration and cohesion in a group, acquiring interpersonal and technological skills, and recommendations for future implementation. Findings of this study suggest that participatory video is an engaging means of self-definition and self-expression among young people in recovery from early psychosis.

Experiences of Reproductive Coercion in Queensland Women.

Reproductive coercion is any interference with a person's reproductive autonomy that seeks to control if and when they become pregnant, and whether the pregnancy is maintained or terminated. It includes sabotage of contraceptive methods and intervention in a woman's access to health care. Our study sought to explore the prevalence and associations with reproductive coercion within Queensland, Australia, where legislation addressing domestic violence and abortion are largely state based and undergoing a period of law reform. The study was a retrospective analysis of 3,117 Queensland women who contacted a telephone counseling and information service regarding an unplanned pregnancy. All data were collected by experienced counselors regarding circumstances within a current pregnancy between January 2015 and July 2017. Overall, experience of current domestic violence was significantly more likely to co-occur with reproductive coercion (21.1%) compared with reproductive coercion identified in the absence of other domestic violence (3.1%). Furthermore, significantly more mental health issues were reported by 36.6% of women affected by reproductive coercion, compared with 14.1% of women with no reproductive coercion present. Disclosure for reproductive coercion, violence, and mental health issues was much higher among women who made a repeat contact to the counselors about their pregnancy (17.8%) compared with those who disclosed at first contact (5.9%). These findings demonstrate the importance for health services to ensure that appropriate screening (and re-screening) for reproductive coercion is completed as a distinct part of screening for violence during a health care relationship.

Impact of a clinical pathway on acute kidney injury in patients undergoing heart transplant.

BACKGROUND: To evaluate the impact of a clinical pathway on the incidence and severity of acute kidney injury in patients undergoing heart transplant. METHODS: This was a 2.5-year retrospective evaluation using 3 years of historical controls within a cardiac intensive care unit in an academic children's hospital. Patients undergoing heart transplant between May 27, 2014, and April 5, 2017 (pre-pathway) and May 1, 2017, and November 30, 2019 (pathway) were included. The clinical pathway focused on supporting renal perfusion through hemodynamic management, avoiding or delaying nephrotoxic medications, and providing pharmacoprophylaxis against AKI. RESULTS: There were 57 consecutive patients included. There was an unadjusted 20% reduction in incidence of any acute kidney injury (p = .05) and a 17% reduction in Stage 2/3 acute kidney injury (p = .09). In multivariable adjusted analysis, avoidance of Stage 2/3 acute kidney injury was independently associated with the clinical pathway era (AOR -1.3 [95% CI -2.5 to -0.2]; p = .03), achieving a central venous pressure of or less than 12 mmHg (AOR -1.3 [95% CI -2.4 to -0.2]; p = .03) and mean arterial pressure above 60 mmHg (AOR -1.6 [95% CI -3.1 to -0.01]; p = .05) in the first 48 h post-transplant, and older age at transplant (AOR - 0.2 [95% CI -0.2 to -0.06]; p = .002). CONCLUSIONS: This report describes a renal protection clinical pathway associated with a reduction in perioperative acute kidney injury in patients undergoing heart transplant and highlights the importance of normalizing perioperative central venous pressure and mean arterial blood pressure to support optimal renal perfusion.

Treatment strategies for Sjögren's syndrome with childhood onset: a systematic review of the literature.

OBJECTIVES: SS with childhood onset is a rare autoimmune disease characterized by heterogeneous presentation. The lack of validated classification criteria makes it challenging to diagnose. Evidence-based guidelines for treatment of juvenile SS are not available due to the rarity of disease and the paucity of research in this patient population. This systematic review aims to summarize and appraise the current literature focused on pharmacological strategies for management of SS with childhood onset. METHODS: PubMed and MEDLINE/Scopus databases up to December 2020 were screened for suitable reports highlighting pharmacological treatment of SS with childhood onset using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 reporting checklist. Animal studies were excluded. RESULTS: A total of 43 studies (34 case reports, 8 mini case series and 1 pilot study) were eligible for analysis. The studies retrieved included girls in 88% (120/137) of cases and had very low confidence levels. HCQ was prescribed for parotid swelling, as well as in association with MTX and NSAIDs in patients with arthritis and arthralgia. Corticosteroids such as long courses of oral prednisone and i.v. methylprednisolone were commonly prescribed for children with severe disease presentations. Rituximab was mainly indicated for mucosa-associated lymphoid tissue lymphoma and renal and nervous system complications. Other conventional DMARDs were prescribed in selected cases with extraglandular manifestations. CONCLUSION: Various therapies are used for the management of juvenile SS and are prescribed based on expert clinician's opinion. There are currently no good-quality studies that allow clinical recommendations for treatment of SS with childhood onset.

Dressings and dignity in community nursing.

Although dignity has been widely explored in the context of healthcare, it has rarely been the subject of empirical exploration when care is delivered by community district nursing teams. This paper demonstrates how a commonplace community nursing task (changing dressings) can constitute a clinical lens through which to explore the ways in which community nurses can influence patients' dignity. This ethnographic study involved two research methods: interviews with patients and nurses (n=22) and observations of clinical interactions (n=62). Dignity can manifest during routine interactions between community nurses and patients. Patient-participants identified malodour from their ill-bodies as a particular threat to dignity. Nurses can reinforce the dignity of their patients through relational aspects of care and the successful concealment of 'leaky' bodies.

Safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults in the UK (ComFluCOV): a multicentre, randomised, controlled, phase 4 trial.

BACKGROUND: Concomitant administration of COVID-19 and influenza vaccines could reduce burden on health-care systems. We aimed to assess the safety of concomitant administration of ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine. METHODS: In this multicentre, randomised, controlled, phase 4 trial, adults in receipt of a single dose of ChAdOx1 or BNT162b2 were enrolled at 12 UK sites and randomly assigned (1:1) to receive concomitant administration of either an age-appropriate influenza vaccine or placebo alongside their second dose of COVID-19 vaccine. 3 weeks later the group who received placebo received the influenza vaccine, and vice versa. Participants were followed up for 6 weeks. The influenza vaccines were three seasonal, inactivated vaccines (trivalent, MF59C adjuvanted or a cellular or recombinant quadrivalent vaccine). Participants and investigators were masked to the allocation. The primary endpoint was one or more participant-reported solicited systemic reactions in the 7 days after first trial vaccination(s), with a difference of less than 25% considered non-inferior. Analyses were done on an intention-to-treat basis. Local and unsolicited systemic reactions and humoral responses were also assessed. The trial is registered with ISRCTN, ISRCTN14391248. FINDINGS: Between April 1 and June 26, 2021, 679 participants were recruited to one of six cohorts, as follows: 129 ChAdOx1 plus cellular quadrivalent influenza vaccine, 139 BNT162b2 plus cellular quadrivalent influenza vaccine, 146 ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine, 79 BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine, 128 ChAdOx1 plus recombinant quadrivalent influenza vaccine, and 58 BNT162b2 plus recombinant quadrivalent influenza vaccine. 340 participants were assigned to concomitant administration of influenza and a second dose of COVID-19 vaccine at day 0 followed by placebo at day 21, and 339 participants were randomly assigned to concomitant administration of placebo and a second dose of COVID-19 vaccine at day 0 followed by influenza vaccine at day 21. Non-inferiority was indicated in four cohorts, as follows: ChAdOx1 plus cellular quadrivalent influenza vaccine (risk difference for influenza vaccine minus placebos -1·29%, 95% CI -14·7 to 12·1), BNT162b2 plus cellular quadrivalent influenza vaccine (6·17%, -6·27 to 18·6), BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine (-12·9%, -34·2 to 8·37), and ChAdOx1 plus recombinant quadrivalent influenza vaccine (2·53%, -13·3 to 18·3). In the other two cohorts, the upper limit of the 95% CI exceeded the 0·25 non-inferiority margin (ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine 10·3%, -5·44 to 26·0; BNT162b2 plus recombinant quadrivalent influenza vaccine 6·75%, -11·8 to 25·3). Most systemic reactions to vaccination were mild or moderate. Rates of local and unsolicited systemic reactions were similar between the randomly assigned groups. One serious adverse event, hospitalisation with severe headache, was considered related to the trial intervention. Immune responses were not adversely affected. INTERPRETATION: Concomitant vaccination with ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine raises no safety concerns and preserves antibody responses to both vaccines. Concomitant vaccination with both COVID-19 and influenza vaccines over the next immunisation season should reduce the burden on health-care services for vaccine delivery, allowing for timely vaccine administration and protection from COVID-19 and influenza for those in need. FUNDING: National Institute for Health Research Policy Research Programme.

MYCN amplification levels in primary retinoblastoma tumors analyzed by Multiple Ligation-dependent Probe Amplification.

Background: Retinoblastoma (Rb) is a childhood tumor of the developing retina where predisposition is caused by RB1 pathogenic variants. MYCN amplification (MYCNA) has been implicated in around 2% of sporadic unilateral Rb tumors with no detectable RB1 variants. We audited data from tumors collected between 1993 and 2019 to determine if this is the case for patients treated at Barts Health NHS Trust, and how often it occurred alongside RB1 variants. Materials and methods: Screening for MYCNA was carried out by Multiple Ligation Probe Analysis of tumor and blood samples collected for RB1 genetic screening. The cohort consisted of 149 tumors, of which 114 had matched blood samples. Results: 10/149 (6.7%) tumors were positive for MYCNA in a population containing a disproportionate number of cases negative for RB1 pathogenic variants. Of 65 unbiased tumors collected from 2014 to 2019, 2 (3.1%) had MYCNA. All MYCNA samples were from sporadic, unilateral patients and 3/10 (30%) had RB1 pathogenic variants. MYCNA was not detected in any blood sample. No MYCNA tumor had 6p gain which is usually a common alteration in Rbs. Conclusions:MYCNA occurs in a small fraction of Rbs and can occur in the presence of pathogenic RB1 variants. However, where it occurs alongside RB1 alterations, the age of onset appears to be later. MYCNA has yet to be seen as a heritable change. In sporadic cases with early diagnosis, Rbs with no RB1 pathogenic variant identified should be tested for MYCNA. Conversely, tumors with MYCNA should still be screened for RB1 pathogenic variants.

'When I asked for help and support it was not there': current NHS employment practice and its impact on people with systemic lupus erythematosus.

OBJECTIVES: The aim was to investigate whether National Health Service (NHS) employees with SLE, for whom work disability and early retirement are high, are supported effectively in at work. METHODS: An online survey of 393 people with lupus was completed through the LUPUS UK website, investigating participants' experiences in maintaining employment. Quantitative and qualitative data were collected. Disease fluctuation, invisibility and fatigue were identified as having substantial negative impacts on employment. This study examined data from a large subgroup (n = 72, 18.74%) of current/previous NHS employees. Descriptive statistics and thematic analysis were used to explore and characterize the demography and experiences of participants. RESULTS: The NHS subgroup (n = 72) represented 18.74% of the whole cohort; 100% were female and of working age (18-64 years). Fifty-one were currently (70.8%) and 21 previously (29.2%) NHS employees. Forty-nine (60%) were clinicians. Twenty-one (29.16%) of this working-age subgroup had left any employment. Negative effects of SLE on employment were universal (including an impact on career choices, work disability, enforced part-time working, lower income and early retirement). NHS support for participants to maintain employment was inconsistent, with more negative experiences than positive. The impact of SLE on employment seemed to be poorly understood. CONCLUSION: A punitive approach to NHS employees with SLE was more common than a proactive, flexible, problem-solving one despite inclusive rhetoric, resulting in the loss of skills and experience to the service. Characterizing conditions such as SLE and long coronavirus disease 2019 as fluctuating, invisible conditions with constitutional symptoms highlights features with negative employment impact, potentially facilitating much-needed change in NHS organizations, with greater use of occupational health, vocational rehabilitation, redeployment and retraining opportunities, highlighting the need for evidence-based employment interventions and improved management of fatigue.