Showing papers by "James N. Galloway published in 2022"
TL;DR: In patients hospitalised with COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials.
95 citations
TL;DR: In this paper , the authors developed EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD).
Abstract: Objectives To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). Methods An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member. Results Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >15–30 mg of prednisolone or equivalent for >2–4 weeks. Conclusions These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.
16 citations
TL;DR: Prevalence rates and baseline predictors of adverse events (AEs) over the first year of treatment in patients with RA starting MTX were estimated to help patients make informed decisions whether to start MTX, potentially increasing adherence to treatment.
Abstract: Abstract Objectives To estimate prevalence rates and identify baseline predictors of adverse events (AEs) over the first year of treatment in patients with RA starting MTX. Methods Data came from the UK Rheumatoid Arthritis Medication Study (RAMS), a prospective cohort of patients with RA starting MTX. This analysis included patients aged ≥18 years with physician diagnosed RA and symptom duration ≤2 years, who were commencing MTX for the first time. AEs were recorded by interviewing patients at 6- and 12-month follow-up visits. The period prevalence rates of AEs are reported for 0–6 months, 6–12 months and 0–12 months of follow-up. The associations between baseline characteristics and AEs were assessed using multivariable logistic regression. Results A total of 1069 patients were included in the analysis. Overall, 77.5% experienced at least one AE. The most commonly reported AEs were: gastrointestinal (42.0%), neurological (28.6%), mucocutaneous (26.0%), pulmonary (20.9%), elevated alanine transaminase (18.0%) and haematological AEs (5.6%). Factors associated with increased odds of AEs were: women vs men (gastrointestinal, mucocutaneous, neurological) and alcohol consumption (nausea, alopecia, mucocutaneous). Older age, higher estimated glomerular filtration rate and alcohol consumption were associated with less reporting of haematological AEs. Conclusions AEs were common among patients over the first year of MTX, although most were not serious. Knowledge of the rates and factors associated with AE occurrence are valuable when communicating risks prior to commencing MTX. This can help patients make informed decisions whether to start MTX, potentially increasing adherence to treatment.
5 citations
TL;DR: In this article , a structured literature review was conducted to summarize reports of opportunistic infections associated with JAK inhibitor treatment for rheumatoid arthritis in clinical trials, and the highest exposure-adjusted incidence rate was reported for herpes zoster (any form), followed by OI (any) and tuberculosis based on limited data from clinical trials with approved doses of JAK inhibitors.
3 citations
TL;DR: This article proposes the ON Time Mobility framework: that all children have the right to be mobile throughout their development to explore, engage in relationships, and develop agency to cocreate their lives.
Abstract: Mobility is a human right. The traditional definition of mobility in physical therapy practice is centered on translocation and, while accurate, is not comprehensive. In this article, we propose the ON Time Mobility framework: that all children have the right to be mobile throughout their development to explore, engage in relationships, and develop agency to cocreate their lives. This perspective highlights interconnected principles of timing, urgency, multimodal, frequency, and sociability to begin discussions on supporting the right to hours of active mobility each day for all children. We propose critical evaluation and discussion of these principles followed by a call to action to shift our conceptualization and enactment of mobility. This mobility rights perspective challenges current medical systems, industry, and government to collaborate with children with disabilities, their families and communities to support mobility as a source of physical and social interactions that define and develop individuals (see Supplemental Digital Content 1, the Video Abstract, available at: http://links.lww.com/PPT/A398).
3 citations
TL;DR: In this article , the authors performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets.
Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.
3 citations
TL;DR: In this article , the authors established a production-oriented life cycle model to quantify and compare the farm-to-gate environmental impacts and food nutritional qualities underlying rural and urban diets in China from 1980 to 2019.
1 citations
TL;DR: Stokstad et al. as mentioned in this paper discuss the issues that may be addressed by a new plastic treaty, including pollution resulting from fishing activities, which is a serious and pervasive threat to the integrity of ecosystems.
Abstract: In his News story “World’s nations start to hammer out first global treaty on plastic pollution” (23 February, https://scim.ag/ unplastictreaty), E. Stokstad discusses the issues that may be addressed by a new plastic treaty (1), including pollution resulting from fishing activities. Because fishing gear is often made from long-lasting synthetic polymers, such as nylon (2), lost and abandoned gear is a long-term problem. This type of pollution, known as ghost gear, is a serious and pervasive threat to the integrity of ecosystems (2). The first plastic treaty must address ghost gear in marine (3) and freshwater environments. Ghost gear affects aquatic ecosystems on every continent. Abandoned or lost nets, for example, trap and often kill large fish (e.g., elasmobranchs), crustaceans (decapods), turtles, mammals (including cetaceans), and other organisms (4–7). Although reports are more frequent from marine ecosystems, damage has occurred in inland water ecosystems as well (2, 7). Other animals, such as birds, are attracted to potential prey trapped in the ghost gear and can become entangled themselves (5, 8), generating a negative cascade effect (5). As Stokstad notes, the problem is exacerbated by the lack of reliable data on the frequency and degree of impact of ghost gear in aquatic ecosystems around the world. Given the increasing demand for resources to feed the world’s growing population, fishing will intensify in coming Aquatic species risk becoming entangled in fishing nets that have been lost or abandoned.
1 citations
TL;DR: Junge is considered by many to be the founder of the modern discipline of atmospheric chemistry and has made seminal contributions to atmospheric chemistry, including the discovery of the stratospheric sulfate layer (known as the Junge layer), recognition of the relationship between the variability of the concentrations of trace gases and their atmospheric lifetimes, his studies of aerosol size and number distributions, his development of the first quantitative model of tropospheric ozone, and other significant scientific investigations as discussed by the authors .
Abstract: Abstract Christian Junge (1912–1996) is considered by many to be the founder of the modern discipline of atmospheric chemistry. In studies from the 1950s through the 1970s, Junge was able to link chemical measurements in a few scattered locations around the earth and integrate them with meteorology to develop the first global view of the basic chemical and physical processes that control the sources, transport, transformations, and fate of particles and gases in the atmosphere. In this paper we summarize and comment upon a number of Junge’s seminal research contributions to atmospheric chemistry, including his discovery of the stratospheric sulfate layer (known as the Junge layer), his recognition of the relationship between the variability of the concentrations of trace gases and their atmospheric lifetimes, his studies of aerosol size and number distributions, his development of the first quantitative model of tropospheric ozone, and other significant scientific investigations. We also discuss Junge’s professional life, his many international leadership positions and honors, as well as some memories and reflections on his many abilities that led to his outstanding contributions to the science of atmospheric chemistry.
TL;DR: Multiorgan involvement, response to steroids, and chronic course are hallmarks of pediatric sarcoidosis.
Abstract: Objective To describe the phenotype, disease course, and treatment of a large cohort of children with sarcoidosis. Methods Patients with biopsies consistent with sarcoidosis, performed between 2010 and 2020, were included in this study. Patients’ notes were reviewed retrospectively. Children with disease onset before 5 years of age were compared with older children. Regression analysis was performed to determine predictors of treatment outcome. Results In total, 48 children with a mean age at diagnosis of 9.5 years, with a male to female ratio of 0.71, were identified. In total, 72% of the children were of Black race and 94% had multiorgan disease, with an average of 4.8 organs involved, most commonly lymph nodes (65%), skin (63%), and eyes (60%). Laboratory findings of note included raised serum calcium in 23% of patients and raised angiotensin-converting enzyme in 76% of patients. Out of 14 patients tested, 6 had mutations in NOD2. In total, 81% of patients received systemic steroids and 90% received conventional disease-modifying antirheumatic drugs (DMARDs); in 25% of patients, a biologic was added, mostly anti–tumor necrosis factor (anti-TNF). Although most patients could be weaned off steroids (58%), most remained on long-term DMARDs (85%). Children under the age of 5 years presented more often with splenomegaly (P = 0.001), spleen involvement (P = 0.003), and higher C-reactive protein (P = 0.10). Weight loss was more common in adolescents (P = 0.006). Kidney (P = 0.004), eye (P = 0.005), and liver involvement (P = 0.03) were more common in Black patients. Regression analysis identified no single factor associated with positive treatment outcomes. Conclusion Multiorgan involvement, response to steroids, and chronic course are hallmarks of pediatric sarcoidosis. The phenotype significantly varies by age and race. Where conventional DMARDs were not efficacious, the addition of an anti-TNF agent was beneficial.
TL;DR: It is unclear if people with immune-mediated inflammatory diseases (IMIDs; joint, bowel and skin) and on immune-modifying therapy have an increased risk of serious COVID-19 outcomes.
Abstract: Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immunemodifying therapies: a nationwide cohort study in the OpenSAFELY platform Sin ead Langan, Brian McKenna, Nicholas Kennedy, Amir Mehkar, Anna Rowan, James Galloway, Julian Matthewman, Kathryn Mansfield, Katie Bechman, Mark Yates, Jeremy Brown, Anna Schultze, Sam Norton, Alex Walker, Caroline Morton, David Harrison, Krishnan Bhaskaran, Christopher Rentsch, Elizabeth Williamson, Richard Croker, Seb Bacon, George Hickman, Tom Ward, Simon Davy, Amelia Green, Louis Fisher, William Hulme, Chris Bates, Helen Curtis, John Tazare, Rosalind Eggo, David Evans, Peter Inglesby, Jonathan Cockburn, Helen McDonald, Laurie Tomlinson, Rohini Mathur, Angel Wong, Harriet Forbes, John Parry, Frank Hester, Sam Harper, Ian Douglas, Liam Smeeth, Charlie Lees, Stephen Evans, Ben Goldacre and Catherine Smith London School of Hygiene and Tropical Medicine, London, UK; Guy’s and St Thomas’ NHS Foundation Trust and Kings College London, London, UK; University of Oxford, Oxford, UK; Royal Devon & Exeter NHS Foundation Trust, Exeter, UK; University of Exeter, Exeter, UK; King’s College London, London, UK; Intensive Care National Audit & Research Centre (ICNARC), London, UK; London School of Hygiene and Tropical Medicine, London, UK; TPP, Leeds, UK; University of Bristol, Bristol, UK; and University of Edinburgh, Edinburgh, UK It is unclear if people with immune-mediated inflammatory diseases (IMIDs; joint, bowel and skin) and on immune-modifying therapy have an increased risk of serious COVID-19 outcomes. With the approval of NHS England, we conducted a cohort study, using OpenSAFELY, analysing routinely collected primary care data linked to hospital admission, death and previously unavailable hospital prescription data. We used Cox regression (adjusting for confounders) to estimate hazard ratios (HRs) comparing risk of COVID-19-death, death/critical care admission and hospitalization (March–September 2020) in (i) people with IMIDs vs. the general population and (ii) people with IMIDs on targeted immune-modifying drugs (e.g. biologics) vs. those on standard systemic treatment (e.g. methotrexate). We identified 17 672 065 adults. Of 1 163 438 (7%) with IMIDs, 19 119 people received targeted immune-modifying drugs, and 200 813 received standard systemic treatment. We saw evidence of increased COVID-19 death [HR 1.23, 95% confidence interval (CI) 1.20–1.27)] and COVID-19 hospitalization (HR 1.32, 95% CI 1.29–1.35) in individuals with IMIDs vs. individuals without IMIDs of the same age, sex, deprivation and smoking status. We saw no evidence of increased COVID-19 death in those on targeted vs. standard systemic treatments (HR 1.03, 95% CI 0.80–1.33). There was no evidence of increased COVID-19-related death in those prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/23, IL-7, IL-6 or Janus kinase inhibitors vs. standard systemics. Rituximab was associated with increased COVID-19 death (HR 1.68, 95% CI 1.11–2.56); however, this finding may relate to confounding. COVID-19 deaths and hospitalizations were higher in people with IMIDs. We saw no increased risk of adverse COVID-19 outcomes in those on targeted immune-modifying drugs for IMIDs vs. those on standard systemic treatment.
TL;DR: The incidence of covid-19 infection in this cohort is comparable to that of London (12%), despite an extremely clinically vulnerable population, and vaccine uptake was lower in sarcoid patients (69%) than the national comparator in adults and was especially low in the black ethnic population.
Abstract: Abstract Background/Aims Sarcoidosis is a multi-system inflammatory disorder, characterised by the formation of non-caseating granulomas. In the UK, a decision was made to include sarcoid patients in the clinically extremely vulnerable group, and they were advised to shield during the COVID-19 pandemic. We investigated the incidence of covid-19 infection and uptake of COVID-19 vaccine within this patient group. Methods Consecutive patients attending the King’s College Hospital sarcoidosis clinic over 18 months between 1st January 2018 and 31st August 2020, and were still alive on 31st January 2020, were included in this report. Electronic primary care records and hospital records were reviewed for each patient to evaluate the incidence of RT-PCT confirmed covid-19 infection, hospitalisation, and vaccination status, defined as at least one vaccination. Hospitalisation data was available from four South-East London trusts. Results The King’s College Hospital database identified 416 patients with biopsy confirmed sarcoidosis. Of the complete cohort, the median age was 55.7 years, 193 patients (46%) were male, and 178 patients (43%) were of black ethnicity. A proportion of patients were taking prednisolone (n = 116, 28%) and DMARDs (n = 73, 18%). The incidence of RT-PCR confirmed covid-19 infection was 48/416 patients (12%). Of these infections, 16/48 (33%) were prior to vaccine availability, including one patient who required an intensive care admission. Post vaccine availability, 9/32 infections were in vaccinated individuals, 8/32 in unvaccinated and 15/32 were of unknown timing; there were 2 recorded hospital admissions but no intensive care admissions, neither patient was immunosuppressed and one was unvaccinated. Uptake of at least one covid-19 vaccine was 287/416 patients (69%). Of the cohort who opted not to have a vaccine (n = 129), the median age was 53.7 years, 60 patients (47%) were male, 58 (45%) were black ethnicity and 22 (17%) were white ethnicity. The only demographic variable to predict covid-19 vaccine uptake was ethnicity; patients of black ethnicity were less likely to have the vaccine than those of white ethnicity (OR = 0.56, p = 0.041). In vaccinated individuals, there were 9/287 cases (3%) of RT-PCT confirmed covid-19 infection, of which one patient required hospitalisation but not intensive care. Conclusion The incidence of covid-19 infection in our cohort is comparable to that of London (12%), despite an extremely clinically vulnerable population. Vaccine uptake was lower in sarcoid patients (69%) than the national comparator in adults (90%) and was especially low in the black ethnic population. Disclosure D. Nagra: None. S.A. Gunawardana: None. K. Bechman: None. S. Birring: None. A. Patel: None. J. Galloway: None.
TL;DR: The first two COVID-19 lockdown periods in England had an ongoing impact on the mental health of patients with inflammatory arthritis (IA) as discussed by the authors , and four main themes impacting on mental wellbeing were identified from the data: (1) Pandemic fatigue versus pandemic acclimatisation, (2) Social interaction and isolation, (3) Clarity of information, (4) Seasonal changes.
Abstract: During the first UK COVID-19 lockdown, studies identified over half of inflammatory arthritis (IA) patients in the UK reported a worsening of emotional distress. Given the prolonged nature of the pandemic, and the strict 'shielding' restrictions imposed on 'extremely clinically vulnerable' populations, it is likely that the implementation of the second lockdown period in England, during November 2020, may also have had a negative impact on the mental health of IA patients. The aim of this study was to qualitatively explore the impact of consecutive lockdown periods on mental wellbeing in people with IA.Nine IA patients took part in semi-structured telephone interviews at both baseline (June/July 2020) and follow-up (November 2020). The interview schedule, which was developed and piloted with a Patient Research Partner, explored patient experiences and mental health impacts of the COVID-19 lockdown periods. Interviews were analysed using inductive thematic analysis.Five males and four females, with rheumatoid arthritis, psoriatic arthritis, or spondylarthritis, aged between 24-79 years (mean = 49.9, SD = 20.9) were included in the sample. Four main themes impacting on mental wellbeing were identified from the data: (1) Pandemic fatigue versus pandemic acclimatisation, (2) Social interaction and isolation, (3) Clarity of information, (4) Seasonal changes.The first two COVID-19 lockdown periods in England had an ongoing impact on the mental health of patients with IA. Healthcare professionals, in conjunction with government support, should ensure that adequate information and mental health resources are available to support IA patients during periods of ongoing restrictions, whilst also continuing to encourage behaviours which promote good mental health and wellbeing.
TL;DR: In this article , the authors investigated the relationship between deprivation and obesity with self-reported disability and disease activity in people with RA, and determined whether BMI mediates the relationships between area-level deprivation and these outcomes.
Abstract: Abstract Objectives To understand the relationships between deprivation and obesity with self-reported disability and disease activity in people with RA, and to determine whether BMI mediates the relationship between area-level deprivation and these outcomes. Methods Data came from the Rheumatoid Arthritis Medication Study (RAMS), a 1-year multicentre prospective observational cohort of people with RA recruited from rheumatology centres across England commencing MTX for the first time. A total of 1529 and 1626 people were included who had a baseline and at least one follow-up measurement at 6 or 12 months of HAQ—Disability Index (HAQ-DI) and DAS in 28 joints (DAS28), respectively. Linear mixed models estimated the associations of deprivation and obesity with repeated measures HAQ-DI and DAS28. Causal mediation analyses estimated the mediating effect of BMI on the relationship between deprivation and RA outcomes. Results Higher deprivation and obesity were associated with higher disability [adjusted regression coefficients highest vs lowest deprivation fifths 0.32 (95% CI 0.19, 0.45); obesity vs no obesity 0.13 (95% CI 0.06, 0.20)] and higher disease activity [adjusted regression coefficients highest vs lowest deprivation fifths 0.34 (95% CI 0.11, 0.58); obesity vs no obesity 0.17 (95% CI 0.04, 0.31)]. BMI mediated part of the association between higher deprivation and self-reported disability (14.24%) and DAS (17.26%). Conclusions People with RA living in deprived areas have a higher burden of disease, which is partly mediated through obesity. Weight-loss strategies in RA could be better targeted towards those living in deprived areas.
TL;DR: Many mortality risk factors were identified, though heterogeneity was high with low quality of evidence and risk of publication bias, and studies from East Asia predominate and may mask risk factors relevant to other IIM subgroups or populations.
Abstract: Objective Idiopathic inflammatory myopathy (IIM)–associated interstitial lung disease (ILD) can range from rapidly progressive disease with high mortality to indolent disease with minimal morbidity. This systematic review and metaanalysis describe immunological, clinical, and radiographical predictors of mortality in IIM-ILD. Methods MEDLINE and Embase database searches were completed on October 18, 2021, to identify articles providing survival data according to baseline characteristics in patients with concurrent IIM and ILD. Prognostic factors common to more than 5 papers were included in the metaanalysis using a random-effects model to report odds ratios (ORs) for binary variables and Hedges g for continuous variables. Risk of bias was assessed using the Newcastle-Ottawa Scale score and the Egger test for publication bias. Results From 4433 articles, 62 papers were suitable for inclusion; among these studies, 38 different variables were considered. The OR for risk of death regarding the presence of anti–melanoma differentiation–associated protein 5 (MDA5) antibodies was 6.20 (95% CI 3.58-10.71), and anti–tRNA synthetase antibodies were found to be protective (OR 0.24, 95% CI 0.14-0.41). Neither antinuclear antibodies, anti–52-kDa Ro antigen antibodies, nor SSA significantly altered mortality, nor was MDA5 titer predictive. Examples of prognostic factors that are significantly associated with mortality in this study include the following: age; male sex; acute/subacute onset; clinically amyopathic dermatomyositis; dyspnea; ulceration; fever; raised C-reactive protein, ferritin, lactate dehydrogenase, alveolar to arterial O2 (A-aO2) gradient, ground-glass opacity on high-resolution computed tomography (HRCT), and overall HRCT score; and reduced albumin, lymphocytes, ratio of partial pressure of oxygen in the arterial blood to fraction of inspired oxygen (PF ratio), percentage predicted transfer factor for carbon monoxide, and percentage predicted forced vital capacity. Baseline surfactant protein-D and Krebs von den Lungen-6 levels were not predictors of mortality. Conclusion Many mortality risk factors were identified, though heterogeneity was high, with a low quality of evidence and a risk of publication bias. Studies regarding anti-MDA5 antibody–positive disease and and those from East Asia predominate, which could mask risk factors relevant to other IIM subgroups or populations.