Publications
98 results found
Dixon L, Colquhoun M, Taylor E, et al., 2023, Orbital giant cell arteritis: two cases of bilateral orbital inflammation and arterial diffusion restriction on MRI, Journal of Neurology, Pages: 1-5, ISSN: 0340-5354
Youngstein T, Haskard D, 2023, Obituary: Professor Justin Charles Mason, RHEUMATOLOGY, ISSN: 1462-0324
Dhaun N, Pugh D, Youngstein T, 2023, Percutaneous Intervention in Takayasu Arteritis Potential Advantages of Procedural Perseverance, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 81, Pages: 65-67, ISSN: 0735-1097
Maughan R, Porter A, Dahanayake C, et al., 2022, Evaluating the Safety and Factors Associated with Treatment Cessation in Takayasu Arteritis, Publisher: WILEY, Pages: 4568-4569, ISSN: 2326-5191
Taylor E, Tona F, Singh-Curry V, et al., 2022, DWI scalp dot sign: superficial temporal artery restricted diffusion in giant cell arteritis, RHEUMATOLOGY, ISSN: 1462-0324
Abhishek A, Boyton RJ, Peckham N, et al., 2022, Effect of a 2-week interruption in methotrexate treatment versus continued treatment on COVID-19 booster vaccine immunity in adults with inflammatory conditions (VROOM study): a randomised, open label, superiority trial, The Lancet Respiratory Medicine, Vol: 10, Pages: 840-850, ISSN: 2213-2600
BACKGROUND: Immunosuppressive treatments inhibit vaccine-induced immunity against SARS-CoV-2. We evaluated whether a 2-week interruption of methotrexate treatment immediately after the COVID-19 vaccine booster improved antibody responses against the S1 receptor-binding domain (S1-RBD) of the SARS-CoV-2 spike protein compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. METHODS: We did an open-label, prospective, two-arm, parallel-group, multicentre, randomised, controlled, superiority trial in 26 hospitals in the UK. We recruited adults from rheumatology and dermatology clinics who had been diagnosed with an immune-mediated inflammatory disease (eg, rheumatoid arthritis, psoriasis with or without arthritis, axial spondyloarthritis, atopic dermatitis, polymyalgia rheumatica, and systemic lupus erythematosus) and who were taking low-dose weekly methotrexate (≤25 mg per week) for at least 3 months. Participants also had to have received two primary vaccine doses from the UK COVID-19 vaccination programme. We randomly assigned the participants (1:1), using a centralised validated computer randomisation program, to suspend methotrexate treatment for 2 weeks immediately after their COVID-19 booster (suspend methotrexate group) or to continue treatment as usual (continue methotrexate group). Participants, investigators, clinical research staff, and data analysts were unmasked, while researchers doing the laboratory analyses were masked to group assignment. The primary outcome was S1-RBD antibody titres 4 weeks after receiving the COVID-19 booster vaccine dose, assessed in the intention-to-treat population. This trial is registered with ISRCT, ISRCTN11442263; following the pre-planned interim analysis, recruitment was stopped early. FINDINGS: Between Sept 30, 2021 and March 3, 2022, we recruited 340 participants, of whom 254 were included in the interim analysis and had been randomly assigned to one of the two groups: 127 in the co
Chilcott J, Mcbeath K, Cole G, et al., 2022, Development of a new cardiac amyloid multidisciplinary team in a tertiary London centre, Publisher: WILEY, Pages: 104-105, ISSN: 1388-9842
Rosas IO, Brau N, Waters M, et al., 2022, Tocilizumab in patients hospitalised with COVID-19 pneumonia: Efficacy, safety, viral clearance, and antibody response from a randomised controlled trial (COVACTA), ECLINICALMEDICINE, Vol: 47
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Pugh D, Karabayas M, Basu N, et al., 2022, Large-vessel vasculitis, Nature Reviews Disease Primers, Vol: 7, ISSN: 2056-676X
Large-vessel vasculitis (LVV) manifests as inflammation of the aorta and its major branches and is the most common primary vasculitis in adults. LVV comprises two distinct conditions, giant cell arteritis and Takayasu arteritis, although the phenotypic spectrum of primary LVV is complex. Non-specific symptoms often predominate and so patients with LVV present to a range of health-care providers and settings. Rapid diagnosis, specialist referral and early treatment are key to good patient outcomes. Unfortunately, disease relapse remains common and chronic vascular complications are a source of considerable morbidity. Although accurate monitoring of disease activity is challenging, progress in vascular imaging techniques and the measurement of laboratory biomarkers may facilitate better matching of treatment intensity with disease activity. Further, advances in our understanding of disease pathophysiology have paved the way for novel biologic treatments that target important mediators of disease in both giant cell arteritis and Takayasu arteritis. This work has highlighted the substantial heterogeneity present within LVV and the importance of an individualized therapeutic approach. Future work will focus on understanding the mechanisms of persisting vascular inflammation, which will inform the development of increasingly sophisticated imaging technologies. Together, these will enable better disease prognostication, limit treatment-associated adverse effects, and facilitate targeted development and use of novel therapies.
Duncan CF, Youngstein T, Kirrane MD, et al., 2021, Diagnostic Challenges in Sepsis, CURRENT INFECTIOUS DISEASE REPORTS, Vol: 23, ISSN: 1523-3847
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- Citations: 6
Charania AS, Vergis N, Phillips R, et al., 2021, Multi-Arm Trial of Inflammatory Signal Inhibitors (MATIS) for Hospitalised Patients with Mild or Moderate COVID-19 Pneumonia: A Structured Summary of a Study Protocol for a Randomised Controlled Trial, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Goulden B, Youngstein T, Giles I, et al., 2021, Haemophagocytic lymphohistiocytosis in pregnancy, CLINICAL MEDICINE, Vol: 21, Pages: E682-E683, ISSN: 1470-2118
Wilson-Morkeh H, Frise C, Youngstein T, 2021, Haemophagocytic lymphohistiocytosis in pregnancy, OBSTETRIC MEDICINE, Vol: 15, Pages: 79-90, ISSN: 1753-495X
Maughan R, Lang M, Olsson A, et al., 2021, Endothelial Cells from Patients with DMARD Naive, Active Inflammatory Arthritis Demonstrate Pro-inflammatory Sensitisation That Is Reversed by Therapy Initiation, Publisher: WILEY, Pages: 74-76, ISSN: 2326-5191
Porter A, Maughan R, Pericleous C, et al., 2021, Investigating Adenosine Deaminase 2 Activity in Large Vessel Vasculitis, Publisher: WILEY, Pages: 3903-3905, ISSN: 2326-5191
The REMAP-CAP, ACTIV-4a, and ATTACC Investigators, 2021, Therapeutic anticoagulation with heparin in critically Ill patients with Covid-19, New England Journal of Medicine, Vol: 385, Pages: 777-789, ISSN: 0028-4793
BACKGROUNDThrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.METHODSIn an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.RESULTSThe trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support–free days was 1 (interquartile range, −1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, −1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis.CONCLUSIONSIn critically ill patients with Covid-19, an initial strategy of therapeu
The ATTACC, ACTIV-4a, and REMAP-CAP Investigators, 2021, Therapeutic anticoagulation with heparin in noncritically Ill patients with Covid-19, New England Journal of Medicine, Vol: 385, Pages: 790-802, ISSN: 0028-4793
BACKGROUNDThrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.METHODSIn this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care–level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.RESULTSThe trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support–free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic
Arabi Y, Gordon A, Derde L, et al., 2021, Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized control trial, Intensive Care Medicine, Vol: 47, Pages: 867-886, ISSN: 0342-4642
Purpose: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19) Methods: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir, and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ-support free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR >1 is favorable. Results: We randomized 694 patients to receive lopinavir-ritonavir (n=255), hydroxychloroquine (n=50), combination therapy (n=27) or control (n=362). The median (IQR) organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (–1 to 15), 0 (–1 to 9) and –1 (–1 to 7), respectively, compared to 6 (–1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥99.0%), and high probabilities of harm (98.0%, 99.9% and >99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively). Conclusion: Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.Trial registration Clinicaltrials.gov identifier: NCT02735707
Domingo P, Mur I, Mateo GM, et al., 2021, Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19, JAMA, ISSN: 0098-7484
Importance Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.Objective To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.Data Sources Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.Study Selection Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria.Data Extraction and Synthesis In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance–weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality.Main Outcomes and Measures The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.Results A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL
Porter A, Youngstein T, Babar S, et al., 2021, A rare life-threatening presentation of Takayasu arteritis, RHEUMATOLOGY, Vol: 60, Pages: 6-8, ISSN: 1462-0324
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Satta G, Youngstein T, Lightstone L, et al., 2021, The utility of a local multidisciplinary working group to oversee the establishment of rapidly evolving standards of care and to support trial recruitment during the COVID-19 pandemic, Clinical medicine (London, England), Vol: 21, Pages: e287-e289, ISSN: 1470-2118
Coronavirus disease 2019 (COVID-19) was first identified in December 2019 in Wuhan, China. The first analyses of cases described high numbers of critically ill patients requiring intensive care admission with significant late inflammatory features. By the time the first cases of SARS-CoV-2 infection were diagnosed in the UK, a wide range of drugs were under consideration and it became clear that the input of clinicians covering all organ systems (in particular, infectious diseases, haematology, rheumatology, renal medicine and intensive care) and of expert specialist pharmacists was necessary at the local level. Thus, an expert multidisciplinary (MDT) group within our organisation was convened to offer a standardised approach and robust clinical governance for the treatment of COVID-19 patients admitted to our hospitals and rapidly develop standards of care as evidence evolved. This commentary explores the methods and mechanisms for creating an MDT COVID-19 treatment working group which are applicable to any hospital likely to admit and care for high numbers of COVID-19 patients and demonstrates how the structure and governance of the group allowed for rapid adoption of both dexamethasone and tocilizumab into standard of care as data became available.
Gordon A, Mouncey P, Al-Beidh F, et al., 2021, Interleukin-6 receptor antagonists in critically Ill patients with Covid-19, New England Journal of Medicine, Vol: 384, Pages: 1491-1502, ISSN: 0028-4793
BACKGROUNDThe efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.METHODSWe evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support–free days, on an ordinal scale combining in-hospital death (assigned a value of −1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support–free days, or both.RESULTSBoth tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support–free days was 10 (interquartile range, −1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, −1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleuki
Vergis N, Phillips R, Cornelius V, et al., 2021, Multi-arm Trial of Inflammatory Signal Inhibitors (MATIS) for hospitalised patients with mild or moderate COVID-19 pneumonia: a structured summary of a study protocol for a randomised controlled trial, Trials, Vol: 22, ISSN: 1745-6215
OBJECTIVES: The primary objective of MATIS is to determine the efficacy of ruxolitinib (RUX) or fostamatinib (FOS) compared to standard of care (SOC) with respect to reducing the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia. Secondary objectives, at 14 and 28 days, are to: Determine the efficacy of RUX or FOS to reduce mortality Determine the efficacy of RUX or FOS to reduce the need for invasive ventilation or ECMO Determine the efficacy of RUX or FOS to reduce the need for non-invasive ventilation Determine the efficacy of RUX or FOS to reduce the proportion of participants suffering significant oxygen desaturation Determine the efficacy of RUX or FOS to reduce the need for renal replacement therapy Determine the efficacy of RUX and FOS to reduce the incidence of venous thromboembolism Determine the efficacy of RUX and FOS to reduce the severity of COVID-19 pneumonia [graded by a 9-point modified WHO Ordinal Scale* Determine the efficacy of RUX or FOS to reduce systemic inflammation Determine the efficacy of RUX or FOS to the incidence of renal impairment Determine the efficacy of RUX or FOS to reduce duration of hospital stay Evaluate the safety of RUX and FOS for treatment of COVID-19 pneumonia. TRIAL DESIGN: A multi-arm, multi-stage (3-arm parallel-group, 2-stage) randomised controlled trial that allocates participants 1:1:1 and tests for superiority in experimental arms versus standard of care. PARTICIPANTS: Patients will be recruited while inpatients during hospitalisation for COVID-19 in multiple centres throughout the UK including Imperial College Healthcare NHS Trust. INCLUSION: Patients age ≥ 18 years at screening Patients with mild or moderate COVID-19 pneumonia, defined as Grade 3 or 4 severity by the WHO COVID-19 Ordinal Scale Patients meeting criteria: Hospitalization AND SARS-CoV2 infection (clinically suspected or laboratory confirmed) AND Radiological change consistent with COVID-19 disease C
Rosas IO, Brau N, Waters M, et al., 2021, Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 384, Pages: 1503-1516, ISSN: 0028-4793
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Papa R, Lane T, Minden K, et al., 2021, INSAID Variant Classification and Eurofever Criteria Guide Optimal Treatment Strategy in Patients with TRAPS: Data from the Eurofever Registry, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 9, Pages: 783-+, ISSN: 2213-2198
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Uy CP, Tarkin JM, Gopalan D, et al., 2021, The impact of integrated non-invasive imaging in the management of takayasu arteritis, JACC: Cardiovascular Imaging, Vol: 14, Pages: 495-500, ISSN: 1876-7591
Sivalokanathan S, Foley M, Cole G, et al., 2021, Gastroenteritis and cardiogenic shock in a healthcare worker: a case report of COVID-19 myocarditis confirmed with serology, European Heart Journal: Case Reports, Vol: 5, Pages: 1-5, ISSN: 2514-2119
BackgroundCoronavirus disease 2019 (COVID-19) myocarditis is emerging as a component of the hyperactive inflammatory response secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Isolated gastrointestinal symptoms are uncommon presenting features in adults with COVID-19 myocarditis. The availability of antibody testing is a valuable addition to the confirmation of COVID-19, when repeated reverse transcriptase–polymerase chain reaction of nasopharyngeal swabs are negative.Case summaryA young healthcare worker presented with dizziness and pre-syncope, 4 weeks after his original symptoms that included fever, lethargy, and diarrhoea. Despite 2 weeks of isolation, followed by a quiescent spell, his symptoms had returned. Shortly after, he presented in cardiogenic shock (left ventricular ejection fraction 25%), that required vasopressor support, at the height of the COVID-19 pandemic. Cardiac magnetic resonance imaging suggested florid myocarditis. Three nasopharyngeal swabs (Days 1, 3, and 5) were negative for SARS-CoV-2, but subsequent serology (Day 13) confirmed the presence of SARS-CoV-2 IgG. Treatment with intravenous immunoglobulin and glucocorticoids led to full recovery.DiscussionOur case study highlights the significance of the use of the available serological assays for diagnosis of patients presenting late with SARS-CoV-2. Importantly, it supports further research in the use of immunomodulatory drugs for the hyperinflammatory microenvironment induced by COVID-19.
Dixon L, Coughlan C, Karunaratne K, et al., 2021, Immunosuppression for intracranial vasculitis associated with SARS-CoV-2: therapeutic implications for COVID-19 cerebrovascular pathology, JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol: 92, Pages: 103-+, ISSN: 0022-3050
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- Citations: 20
Amigues I, Pearlman AH, Patel A, et al., 2020, Coronavirus disease 2019: investigational therapies in the prevention and treatment of hyperinflammation, EXPERT REVIEW OF CLINICAL IMMUNOLOGY, Vol: 16, Pages: 1185-1204, ISSN: 1744-666X
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Kim AHJ, Sparks JA, Liew JW, et al., 2020, A Rush to Judgment? Rapid Reporting and Dissemination of Results and Its Consequences Regarding the Use of Hydroxychloroquine for COVID-19., Ann Intern Med, Vol: 172, Pages: 819-821
Hydroxychloroquine, an essential treatment for many patients with rheumatologic conditions, has recently garnered widespread attention as a potential treatment for COVID-19 infection. The authors appraise the study generating this interest and highlight the potential consequences of rapid dissemination of overinterpreted data, particularly for people with conditions for which hydroxychloroquine has demonstrated benefits in preventing organ damage and life-threatening disease flares.
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