Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study

Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Assessing the Mental Health Impact of the COVID-19 Pandemic on US Fire-Based Emergency Medical Services Responders: A Tale of Two Samples (The RAPID Study I).

OBJECTIVE: This study aimed to examine the COVID-19 pandemic's impact on fire service safety culture, behavior and morale, levers of well-being, and well-being outcomes. METHODS: Two samples (Stress and Violence against fire-based EMS Responders [SAVER], consisting of 3 metropolitan departments, and Fire service Organizational Culture of Safety [FOCUS], a geographically stratified random sample of 17 departments) were assessed monthly from May to October 2020. Fire department-specific and pooled scores were calculated. Linear regression was used to model trends. RESULTS: We observed concerningly low and decreasing scores on management commitment to safety, leadership communication, supervisor sensegiving, and decision-making. We observed increasing and concerning scores for burnout, intent to leave the profession, and percentage at high risk for anxiety and depression. CONCLUSIONS: Our findings suggest that organizational attributes remained generally stable but low during the pandemic and impacted well-being outcomes, job satisfaction, and engagement. Improving safety culture can address the mental health burden of this work.

Glomerular Disease in Temporal Association with SARS-CoV-2 Vaccination: A Series of 29 Cases.

Background: Immune responses to vaccination are a known trigger for a new onset of glomerular disease or disease flare in susceptible individuals. Mass immunization against SARS-CoV-2 in the COVID-19 pandemic provides a unique opportunity to study vaccination-associated autoimmune kidney diseases. In the recent literature, there are several patient reports demonstrating a temporal association of SARS-CoV-2 immunization and kidney diseases. Methods: Here, we present a series of 29 cases of biopsy-proven glomerular disease in patients recently vaccinated against SARS-CoV-2 and identified patients who developed a new onset of IgA nephropathy, minimal change disease, membranous nephropathy, ANCA-associated GN, collapsing glomerulopathy, or diffuse lupus nephritis diagnosed on kidney biopsies postimmunization, as well as recurrent ANCA-associated GN. This included 28 cases of de novo GN within native kidney biopsies and one disease flare in an allograft. Results: The patients with collapsing glomerulopathy were of Black descent and had two APOL1 genomic risk alleles. A brief literature review of patient reports and small series is also provided to include all reported cases to date (n=52). The incidence of induction of glomerular disease in response to SARS-CoV-2 immunization is unknown; however, there was no overall increase in incidence of glomerular disease when compared with the 2 years prior to the COVID-19 pandemic diagnosed on kidney biopsies in our practice. Conclusions: Glomerular disease to vaccination is rare, although it should be monitored as a potential adverse event.

Veil-of-ignorance reasoning mitigates self-serving bias in resource allocation during the COVID-19 crisis

The COVID-19 crisis has forced healthcare professionals to make tragic decisions concerning which patients to save. Furthermore, The COVID-19 crisis has foregrounded the influence of self-serving bias in debates on how to allocate scarce resources. A utilitarian principle favors allocating scarce resources such as ventilators toward younger patients, as this is expected to save more years of life. Some view this as ageist, instead favoring age-neutral principles, such as "first come, first served". Which approach is fairer? The "veil of ignorance" is a moral reasoning device designed to promote impartial decision-making by reducing decision-makers' use of potentially biasing information about who will benefit most or least from the available options. Veil-of-ignorance reasoning was originally applied by philosophers and economists to foundational questions concerning the overall organization of society. Here we apply veil-of-ignorance reasoning to the COVID-19 ventilator dilemma, asking participants which policy they would prefer if they did not know whether they were younger or older. Two studies (pre-registered;online samples;Study 1, N = 414;Study 2 replication, N = 1,276) show that veil-of-ignorance reasoning shifts preferences toward saving younger patients. The effect on older participants is dramatic, reversing their opposition toward favoring the young, thereby eliminating self-serving bias. These findings provide guidance on how to remove self-serving biases to healthcare policymakers and frontline personnel charged with allocating scarce medical resources during times of crisis. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Unpacking overtourism as a discursive formation through interdiscursivity

Purpose As tourism destinations grapple with declines in tourist arrivals due to COVID-19 measures, scholarly debate on overtourism remains active, with discussions on solutions that could be enacted to contain the excessive regrowth of tourism and the return of "overtourism". As social science holds an important role and responsibility to inform the debate on overtourism, this paper aims to understand overtourism by examining it as a discursive formation. Design/methodology/approach The paper explores recurring thematic threads in scholarly overtourism texts, given the phrases coherence as a nodal-point is partially held in place by a collective body of texts authored by a network of scholars who have invested in it. The paper uses interdiscursivity as an interpretative framework to identify overlapping thematic trajectories found in existing discourses. Findings Overtourism, as a discursive formation, determines what can and should be said about the self-evident "truths" of excessive tourist arrivals, the changes tourists bring to destinations and the range of discursive solutions available to manage or end overtourism. As the interpellation of these thematic threads into scholarly texts is based on a sense of crisis and urgency, the authors find that the themes contain rhetoric, arguments and metaphors that problematise tourists and construct them as objects in need of control and correction. Originality/value While the persistence of the discursive formation will be determined by the degree to which scholarly and other actors recognise themselves in it, this paper may enable overtourism scholars to become aware of the limits of their discursive domain and help them to expand the discourse or weave a new one.

A case of anca vasculitis presenting with Sjögren's serology

Case report-IntroductionSjögren's is an autoimmune multisystem disorder characterised by xerostomia, keratoconjunctivitis sicca and extra glandular manifestations. The presence of sicca symptoms helps with diagnosis but up to 20% patients do not have these. The prevalence of lung involvement has been reported up to 9-24% and includes changes such as NSIP and organising pneumonia. We present an interesting patient who had no sicca symptoms but positive immunology to suggest Sjögren's. Changes in sequential CT chest scans were in keeping with Connective Tissue Disease-Associated Interstitial Lung disease (CTAILD). However, presentation with an acute renal injury resulted in a diagnosis of ANCA positive vasculitis.Case report-Case descriptionA 64-year-old Indian gentleman with medical background of controlled asthma was referred after 9 months of investigations for gluteal weakness. Initial blood tests included normal CK, ESR, CRP, vitamin B12, HbA1c and TFTs. Rheumatoid factor was low positive (20IU/ml), CCP negative. ANA was 1:80 with positive Ro, negative dsDNA. MRI of thighs was normal-no evidence of myositis. Nerve conduction studies showed no active denervation to suggest inflammatory myopathy and muscle biopsy showed myopathic features only. A CT scan revealed 3 small lung nodules recommending repeat scan.When seen in rheumatology clinic, there was additional bilateral shoulder arthralgia with no reports of sicca symptoms or rashes. A repeat autoimmune screen and CT chest was sent. His ANA was 1:1280 with Ro antibodies;CT showed new ground glass changes (with old nodules). Organising Pneumonia was suggested, and respiratory opinion sought. Extended myositis screen was negative. When seen in respiratory clinic he had new haematuria-ANCA screen showed positive anti-PR3 antibody (23U/ml) with normal U+Es, urine PCR and CRP 8mg/L. Based on these results a renal biopsy was performed-which showed no obvious morphological abnormalities. Thus, a suspected diagnosis of CTAILD with Sjögren's was made.In clinic 2 months later, there was new shortness of breath and haemoptysis. Urine dip showed haematoproteinuria and Chest X-ray showed increase in peri-hilar masses. He was admitted urgently-blood tests showed a decline in renal function-urea 26.8mmol/L, Creatinine 838umol/L, CRP of 435mg/L and Haemoglobin 100g/L. Urgent repeat renal biopsy was done and CT thorax showed deterioration with bilateral consolidation and new lung lesions. Urgent Plasma exchange and dialysis (9 cycles) was given. Initial results from renal biopsy showed presence of crescents and he was started on cyclophosphamide. On this kidney function has improved-urea 18.4mmol/L and Creatinine 302umol/L;he remains on oral cyclophosphamide.Case report-DiscussionWith ongoing symptoms, an underlying autoimmune cause of his symptoms was felt likely. However inflammatory markers remained normal and so did CK. Despite this MRI and muscle biopsies were performed-which again were normal. The only tests that were positive were immunology (Ro antibodies) and a CT chest (showing initial small lung nodules). These findings pointed toward CTAILD with Sjögren's being the likely diagnosis.As new lung nodules were seen, repeat CT scans were done-which showed gradual interstitial changes-the main radiological differential diagnosis was Organising pneumonia. Further investigations were delayed due to patient travel and COVID, but ongoing respiratory advice was sought. Even with changes in CT findings the patient remained stable with normal inflammatory markers. However, the clinical picture changed quite rapidly over a month (despite 2+ years of previous symptoms) with presentation of pulmonary-renal vasculitis. Plasma exchange and dialysis were given. A good response with a positive renal biopsy confirmed the most likely diagnosis was Granulomatosis with Polyangiitis (GPA).This case was interesting-the main complaint was of myopathy with no physical signs. Despite this biopsy were performed (muscle and kidney), which were all normal. The red herring in his case was a no mal renal biopsy-steering us in the direction of CTD-AILD instead of GPA.Case report-Key learning pointsIn patients with clear symptoms matching their investigations the diagnosis is often obvious. When this is not the case and symptomatology does not match results (i.e. no Sicca symptoms but positive immunology to suggest Sjögren's) suspicion should remain high. Multidisciplinary working can provide insight, which this case does highlight-with input required from Neurology, Respiratory and Renal medicine.Negative results should be taken in context with patients and their symptoms. Initial renal biopsy in this case was normal-however after a review, further comments were made on the sparsity of glomeruli in the sample. Therefore, tissue obtained for diagnosis should always be questioned and clinical suspicion should remain high. In addition, repeat investigations (6 monthly CT scans) can help note any interval change.Thorough history and examination in follow up of patients can help look out for evolving changes. With the new symptoms of haemoptysis and haematoproteinuria this pointed us to the eventual diagnosis. The road to diagnosis in this case was prolonged with an acute drop in kidney function and pulmonary haemorrhage needing urgent Plasma exchange and dialysis. Thankfully, the patient continues to make a good recovery.A last point to add is although isolated myalgia has been described as a presentation of systemic vasculitis in the literature, those patients have had elevated CK and positive muscle biopsy. Our patient did not have any positive findings with over 2 years of symptoms. Therefore, we feel this case was unique in presentation and has valid learning points as above.

Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021.

The 17th St Gallen International Breast Cancer Consensus Conference in 2021 was held virtually, owing to the global COVID-19 pandemic. More than 3300 participants took part in this important bi-annual critical review of the 'state of the art' in the multidisciplinary care of early-stage breast cancer. Seventy-four expert panelists (see Appendix 1) from all continents discussed and commented on the previously elaborated consensus questions, as well as many key questions on early breast cancer diagnosis and treatment asked by the audience. The theme of this year's conference was 'Customizing local and systemic therapies.' A well-organized program of pre-recorded symposia, live panel discussions and real-time panel voting results drew a worldwide audience of thousands, reflecting the far-reaching impact of breast cancer on every continent. The interactive technology platform allowed, for the first time, audience members to ask direct questions to panelists, and to weigh in with their own vote on several key panel questions. A hallmark of this meeting was to focus on customized recommendations for treatment of early-stage breast cancer. There is increasing recognition that the care of a breast cancer patient depends on highly individualized clinical features, including the stage at presentation, the biological subset of breast cancer, the genetic factors that may underlie breast cancer risk, the genomic signatures that inform treatment recommendations, the extent of response before surgery in patients who receive neoadjuvant therapy, and patient preferences. This customized approach to treatment requires integration of clinical care between patients and radiology, pathology, genetics, and surgical, medical and radiation oncology providers. It also requires a dynamic response from clinicians as they encounter accumulating clinical information at the time of diagnosis and then serially with each step in the treatment plan and follow-up, reflecting patient experiences and treatment response.

?Bridge? neoadjuvant endocrinetherapy for early stage breast cancer patients during COVID-19 at an academic hospital in NYC: Lessonslearned

Background: Neoadjuvant endocrine therapy has traditionally been considered a treatment option for locallyadvanced and/or surgically high-risk women with hormone positive disease. Early stage hormone-positive breast cancer, on the other hand, is usually managed with upfront surgery, with post-operative hormone therapy as a risk-reducing adjunct. During the COVID-19 pandemic, however, widespread closures of operating rooms throughout thecountry resulted in many breast cancer patients being offered presurgical endocrine therapy as a bridge to surgery.We explored the demographic and clinicopathologic characteristics of these patients and quantified their rate of uptake. Methods: The Institutional Breast Cancer Database was queried for all patients who were diagnosed withER+ stage 0, I, or II breast cancer and were offered presurgical endocrine therapy (tamoxifen or aromatase inhibitor)by a medical oncologist from 3/12/2020 to 4/30/2020. Variables of interest included demographics, tumorcharacteristics, and rate of medication uptake and compliance. Results: Of 192 newly diagnosed breast cancerpatients seen at NYU Perlmutter Cancer Center during this time period, 136 patients had early stage ER+ breast cancer. Forty-five patients had not yet undergone surgery, and were recommended to receive presurgical hormonaltherapy as a bridge given the COVID-19 pandemic (Table 1). The average age was 60.5 years old (SD=13.8 years, range 31-89), and all were female. Thirty-four of 44 patients were post-menopausal (75.6%), while 10 were premenopausal (22.2%), and one was perimenopausal (2.2%). Twenty-six patients were white (57.8%), 12 were black (26.7%) 3 were Asian (6.7%), and 4 were other (8.9%). Thirty-four patients (75.6%) had invasive disease, while 8 had ductal carcinoma in situ (DCIS, 17.8%), and 3 had DCIS with microinvasion (6.7%). Nine patients (20%)did not take the medication for various reasons: 1 contracted COVID-19, 1 refused any treatment, 1 decided totransfer care out of state, 1 preferred to take a homeopathic remedy instead of endocrine therapy, 1 preferred towait for surgery without medication, and 4 were scheduled for surgery sooner than anticipated and did not start themedication. The remaining 36 patients (80%) took medication for an average of 43.6 days (SD=27.3 days, range 9-101 days) prior to surgery. Twenty-eight patients (77.8%) took an aromatase inhibitor, and 8 (22.2%) took tamoxifen.Forty-two patients have now undergone surgery (93.3%);the remainder include the patient who is refusing alltreatment, the patient who transferred out of state, and one patient who has not yet scheduled surgery, but isreportedly still taking an aromatase inhibitor. Conclusion: Improving adherence to long-term adjuvant endocrinetherapy is an urgent need as patient acceptance is low. Reported completion rates range around 50%, and have notbeen improved by educational or technology-based interventions. The unique situation posed by the current COVID-19 pandemic has temporarily changed the management of early-stage breast cancer, and resulted in a high initialacceptance of endocrine therapy (80%), although duration is shorter in this presurgical setting. Furtherinvestigations will evaluate length of use, the psychosocial and behavioral factors that influence willingness to takeendocrine therapy, and apply these lessons to management of early-stage hormone-positive breast cancer.

Problems of safety, occupational hygiene and control over infections in fighting with occupational diseases of healthcare workers with COVID-19 in treatment facilities of Ukraine

The objective of the publication was to assess the safety of treatment facilities, occupational health and infection control in Kiev, Zhytomyr and Zhytomyr region to enhance risk management of SARS-CoV-2 infection of healthcare workers and reduce occupational illness and mortality for COVID-19. Bibliosemantic, hygienic, questionnaire, statistical methods and methods of comparative and system analysis have been used. The work of doctors involved in overcoming COVID-19 pandemic is classified as dangerous (extreme). In addition to the SARS-CoV-2 virus, the working conditions of medical workers are influenced by physical, chemical factors and high physical and neuro-emotional stress. Among medical workers of the Zhytomyr region who were diagnosed with an acute occupational disease COVID-19, nurses prevailed (38.57%). Junior nurses (26.1%) - the second COVID-19 incidence, paramedics (5.31%) occupy the third place. The doctors' incidence was ranked in the following sequence: doctors of GPFM - 4.85%, surgeons - 4.16%, anesthesiologists - 2.54%, infectious disease doctors - 2.08%, radiologists - 1.85%. This distribution of medical professions is observed for all Ukraine regions. Chance of becoming infected with SARS CoV 2 for healthcare workers in October was by 3.8 times higher than the general population. Risk of dying from COVID-19 in healthcare workers is greater by 1.5 times than the general population. The high level of occupational morbidity of COVID-19 in Ukrainian medical personnel is determined by personal negligence, incomplete staffing of TF with medical workers, of medical workers with PPE;dis-use of PPE if available, absence or poor-quality instruction on labor protection;shortage of epidemiologists, hygienists and occupational pathologists.