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The Cochrane Database of Systematic... Jan 2022Paediatric flat feet are a common presentation in primary care; reported prevalence approximates 15%. A minority of flat feet can hurt and limit gait. There is no... (Review)
Review
BACKGROUND
Paediatric flat feet are a common presentation in primary care; reported prevalence approximates 15%. A minority of flat feet can hurt and limit gait. There is no optimal strategy, nor consensus, for using foot orthoses (FOs) to treat paediatric flat feet.
OBJECTIVES
To assess the benefits and harms of foot orthoses for treating paediatric flat feet.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and Embase to 01 September 2021, and two clinical trials registers on 07 August 2020.
SELECTION CRITERIA
We identified all randomised controlled trials (RCTs) of FOs as an intervention for paediatric flat feet. The outcomes included in this review were pain, function, quality of life, treatment success, and adverse events. Intended comparisons were: any FOs versus sham, any FOs versus shoes, customised FOs (CFOs) versus prefabricated FOs (PFOs).
DATA COLLECTION AND ANALYSIS
We followed standard methods recommended by Cochrane.
MAIN RESULTS
We included 16 trials with 1058 children, aged 11 months to 19 years, with flexible flat feet. Distinct flat foot presentations included asymptomatic, juvenile idiopathic arthritis (JIA), symptomatic and developmental co-ordination disorder (DCD). The trial interventions were FOs, footwear, foot and rehabilitative exercises, and neuromuscular electrical stimulation (NMES). Due to heterogeneity, we did not pool the data. Most trials had potential for selection, performance, detection, and selective reporting bias. No trial blinded participants. We present the results separately for asymptomatic (healthy children) and symptomatic (children with JIA) flat feet. The certainty of evidence was very low to low, downgraded for bias, imprecision, and indirectness. Three comparisons were evaluated across trials: CFO versus shoes; PFO versus shoes; CFO versus PFO. Asymptomatic flat feet 1. CFOs versus shoes (1 trial, 106 participants): low-quality evidence showed that CFOs result in little or no difference in the proportion without pain (10-point visual analogue scale (VAS)) at one year (risk ratio (RR) 0.85, 95% confidence interval (CI) 0.67 to 1.07); absolute decrease (11.8%, 95% CI 4.7% fewer to 15.8% more); or on withdrawals due to adverse events (RR 1.05, 95% CI 0.94 to 1.19); absolute effect (3.4% more, 95% CI 4.1% fewer to 13.1% more). 2. PFOs versus shoes (1 trial, 106 participants): low to very-low quality evidence showed that PFOs result in little or no difference in the proportion without pain (10-point VAS) at one year (RR 0.94, 95% CI 0.76 to 1.16); absolute effect (4.7% fewer, 95% CI 18.9% fewer to 12.6% more); or on withdrawals due to adverse events (RR 0.99, 95% CI 0.79 to 1.23). 3. CFOs versus PFOs (1 trial, 108 participants): low-quality evidence found no difference in the proportion without pain at one year (RR 0.93, 95% CI 0.73 to 1.18); absolute effect (7.4% fewer, 95% CI 22.2% fewer to 11.1% more); or on withdrawal due to adverse events (RR 1.00, 95% CI 0.90 to 1.12). Function and quality of life (QoL) were not assessed. Symptomatic (JIA) flat feet 1. CFOs versus shoes (1 trial, 28 participants, 3-month follow-up): very low-quality evidence showed little or no difference in pain (0 to 10 scale, 0 no pain) between groups (MD -1.5, 95% CI -2.78 to -0.22). Low-quality evidence showed improvements in function with CFOs (Foot Function Index - FFI disability, 0 to 100, 0 best function; MD -18.55, 95% CI -34.42 to -2.68), child-rated QoL (PedsQL, 0 to 100, 100 best quality; MD 12.1, 95% CI -1.6 to 25.8) and parent-rated QoL (PedsQL MD 9, 95% CI -4.1 to 22.1) and little or no difference between groups in treatment success (timed walking; MD -1.33 seconds, 95% CI -2.77 to 0.11), or withdrawals due to adverse events (RR 0.58, 95% CI 0.11 to 2.94); absolute difference (9.7% fewer, 20.5 % fewer to 44.8% more). 2. PFOs versus shoes (1 trial, 25 participants, 3-month follow-up): very low-quality evidence showed little or no difference in pain between groups (MD 0.02, 95% CI -1.94 to 1.98). Low-quality evidence showed no difference between groups in function (FFI-disability MD -4.17, 95% CI -24.4 to 16.06), child-rated QoL (PedsQL MD -3.84, 95% CI -19 to 11.33), or parent-rated QoL (PedsQL MD -0.64, 95% CI -13.22 to 11.94). 3. CFOs versus PFsO (2 trials, 87 participants): low-quality evidence showed little or no difference between groups in pain (0 to scale, 0 no pain) at 3 months (MD -1.48, 95% CI -3.23 to 0.26), function (FFI-disability MD -7.28, 95% CI -15.47 to 0.92), child-rated QoL (PedsQL MD 8.6, 95% CI -3.9 to 21.2), or parent-rated QoL (PedsQL MD 2.9, 95% CI -11 to 16.8).
AUTHORS' CONCLUSIONS
Low to very low-certainty evidence shows that the effect of CFOs (high cost) or PFOs (low cost) versus shoes, and CFOs versus PFOs on pain, function and HRQoL is uncertain. This is pertinent for clinical practice, given the economic disparity between CFOs and PFOs. FOs may improve pain and function, versus shoes in children with JIA, with minimal delineation between costly CFOs and generic PFOs. This review updates that from 2010, confirming that in the absence of pain, the use of high-cost CFOs for healthy children with flexible flat feet has no supporting evidence, and draws very limited conclusions about FOs for treating paediatric flat feet. The availability of normative and prospective foot development data, dismisses most flat foot concerns, and negates continued attention to this topic. Attention should be re-directed to relevant paediatric foot conditions, which cause pain, limit function, or reduce quality of life. The agenda for researching asymptomatic flat feet in healthy children must be relegated to history, and replaced by a targeted research rationale, addressing children with indisputable foot pathology from discrete diagnoses, namely JIA, cerebral palsy, congenital talipes equino varus, trisomy 21 and Charcot Marie Tooth. Whether research resources should continue to be wasted on studying flat feet in healthy children that do not hurt, is questionable. Future updates of this review will address only relevant paediatric foot conditions.
Topics: Child; Flatfoot; Foot Orthoses; Humans; Pain; Pain Measurement; Quality of Life
PubMed: 35029841
DOI: 10.1002/14651858.CD006311.pub3 -
The Journal of Infection Sep 2022Antibiotics are amongst the most commonly used drugs in children. In addition to inducing antibiotic resistance, antibiotic exposure has been associated with adverse... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antibiotics are amongst the most commonly used drugs in children. In addition to inducing antibiotic resistance, antibiotic exposure has been associated with adverse long-term health outcomes.
METHODS
A systematic search using PRISMA guidelines to identify original studies reporting associations between antibiotic exposure and adverse long-term health outcomes in children. Overall pooled estimates of the odds ratios (ORs) were obtained using random-effects models.
RESULTS
We identified 160 observational studies investigating 21 outcomes in 22,103,129 children. Antibiotic exposure was associated with an increased risk of atopic dermatitis (OR 1.40, 95% confidence interval (CI) 1.30-1.52, p < 0.01), allergic symptoms (OR 1.93, 95%CI 1.66-2.26, p < 0.01), food allergies (OR 1.35, 95%CI 1.20-1.52, p < 0.01), allergic rhinoconjunctivitis (OR 1.66, 95%CI 1.51-1.83, p < 0.01), wheezing (OR 1.81, 95%CI 1.65-1.97, p < 0.01), asthma (OR 1.96, 95%CI 1.76-2.17, p < 0.01), increased weight gain or overweight (OR 1.18, 95%CI 1.11-1.26, p < 0.01), obesity (OR 1.21, 95%CI 1.05-1.40, p < 0.01), juvenile idiopathic arthritis (OR 1.74, 95%CI 1.21-2.52, p < 0.01), psoriasis (OR 1.75, 95%CI 1.44-2.11, p < 0.01), autism spectrum disorders (OR 1.19, 95%CI 1.04-1.36, p = 0.01) and neurodevelopment disorders (OR 1.29, 95%CI 1.09-1.53, p < 0.01). Dose-response effects and stronger effects with broad-spectrum antibiotic were often reported. Antibiotic exposure was not associated with an altered risk of allergic sensitisation, infantile colic, abdominal pain, inflammatory bowel disease, celiac disease, type 1 diabetes, fluorosis, and attention deficit hyperactivity disorder.
CONCLUSION
Although a causal association cannot be determined from these studies, the results support the meticulous application of sound antibiotic stewardship to avoid potential adverse long-term health outcomes.
Topics: Anti-Bacterial Agents; Asthma; Attention Deficit Disorder with Hyperactivity; Child; Dermatitis, Atopic; Humans; Outcome Assessment, Health Care
PubMed: 35021114
DOI: 10.1016/j.jinf.2022.01.005 -
Rheumatology International Feb 2022Juvenile idiopathic arthritis (JIA), as a chronic condition, is associated with symptoms negatively impacting health-related quality of life (HRQL). Regarding growing...
Non-disease specific patient-reported outcome measures of health-related quality of life in juvenile idiopathic arthritis: a systematic review of current research and practice.
Juvenile idiopathic arthritis (JIA), as a chronic condition, is associated with symptoms negatively impacting health-related quality of life (HRQL). Regarding growing interest in the implementation of the patient-reported outcome measures (PROMs), we aimed to review the non-disease specific PROMs addressing HRQL assessment, potentially useful in the clinical care of JIA and daily practice. A systematic literature search was conducted using MEDLINE/PubMed, Google Scholar, Scopus and Embase databases (1990 to 2021), with a focus on the recent 5-years period. Entry keywords included the terms: "children", "adolescents", "JIA", "chronic diseases", "HRQL", "PROMs" and wordings for the specific tools. Several available PROMs intended to measure HRQL, non-specific to JIA, were identified. The presented outcomes differed in psychometric properties, yet all were feasible in assessing HRQL in healthy children and those with chronic diseases. Both EQ-5D-Y and PedsQL have already been tested in JIA, showing relevant reliability, validity, and similar efficiency as disease-specific measurements. For PROMIS® PGH-7 and PGH-7 + 2, such validation and cross-cultural adaptation need to be performed. Considering the future directions in pediatric rheumatology, the large-scale implementation of PROMIS® PGH-7 and PGH-7 + 2 in JIA offers a particularly valuable opportunity. The PROMs reflect the patient perception of the chronic disease and allow to understand child's opinions. The PROMs may provide an important element of the holistic medical care of patients with JIA and a standardized tool for clinical outcomes, monitoring disease severity and response to treatment.
Topics: Adolescent; Arthritis, Juvenile; Child; Child, Preschool; Female; Health Status; Humans; Male; Patient Reported Outcome Measures; Quality of Life
PubMed: 34971434
DOI: 10.1007/s00296-021-05077-x -
Journal of Immunology Research 2021To evaluate the effectiveness of Janus kinase (JAK) inhibitors for the treatment of patients with autoimmune disease and associated inflammatory ocular diseases. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the effectiveness of Janus kinase (JAK) inhibitors for the treatment of patients with autoimmune disease and associated inflammatory ocular diseases.
METHODS
We identified relevant literature by screening the MEDLINE, PubMed, and Cochrane databases for randomized controlled trials, cohort studies, case controls, and case reports.
RESULTS
Seven studies, including 11 patients, were included in the final systematic analysis. Of the 11 patients, there were 5 cases of juvenile idiopathic arthritis- (JIA-) associated uveitis, 1 case of rheumatoid arthritis- (RA-) associated keratitis, 1 case of RA-associated scleritis, 1 case of psoriasis-associated conjunctivitis, 2 cases of noninfectious scleritis, and 1 case of uveitis with suspected autoimmune disease. None of these 11 patients responded adequately to conventional treatments, including biological agents; these were all refractory cases and switched to JAK inhibitor therapy. Irrespective of whether they were suffering from uveitis, scleritis, or other types of ocular inflammation, all 11 patients showed an improvement to JAK inhibitors without significant side effects. Different types of JAK inhibitors might be associated with different responses when used to treat ocular inflammation.
CONCLUSIONS
JAK inhibitors may represent an alternative treatment option for patients with autoimmune ocular inflammation.
Topics: Animals; Autoimmune Diseases; Disease Management; Disease Susceptibility; Eye Diseases; Humans; Inflammation; Janus Kinase Inhibitors; Molecular Targeted Therapy; Treatment Outcome
PubMed: 34966823
DOI: 10.1155/2021/2324400 -
European Journal of Pediatrics Apr 2022The immunogenicity of vaccines in children with juvenile autoimmune rheumatic diseases (JARDs) can be reduced, there are additional safety concerns around vaccination,... (Review)
Review
UNLABELLED
The immunogenicity of vaccines in children with juvenile autoimmune rheumatic diseases (JARDs) can be reduced, there are additional safety concerns around vaccination, and there is a potential for worsening in disease activity. In this systematic review, we summarise studies that investigated the immunogenicity and safety of routine vaccines in children and adolescents with JARD on immunosuppressive treatment. We identified 37 studies investigating 2571 children and adolescents with JARD on immunosuppressive treatment and 4895 control children. Of the 56 geometric mean antibody titres measured, 19 (34%) were lower, six (11%) higher, and 31 (55%) similar; of the 39 seroprotection rates measured, 10 (26%) were lower, two (5%) higher, and 27 (69%) similar; and of the 27 seroconversion rates measured, nine (33%) were lower, two (8%) higher, and 16 (59%) similar in children with JARD on immunosuppressive treatment compared with control children. However, many of the studies were underpowered, and not designed to show non-inferiority between children with JARD and controls. Subgroup analysis for different types of immunosuppressive treatments was not feasible, as most studies did not report results by treatment. Severe adverse events were reported in 38 children (33 with juvenile idiopathic arthritis, four with systemic lupus erythematosus, and one in a healthy child); most of them were likely not related to the vaccination (e.g. elective hospitalisation or surgery). A worsening in disease activity was reported in 44 (2%) children with JARD; again, many of them were likely not related to the vaccination. There were no safety concerns with live attenuated vaccines; however, only few studies reported results for this.
CONCLUSION
Vaccination in children with JARD on immunosuppressive treatment is safe and should be promoted, especially since these children are at increased risk for infection. The importance for the completion of vaccination schedules should be stressed. Strategies to compensate for the lower vaccine responses, which are found in approximately one-third of these children, include measuring antibody levels to determine the optimal timing for the administration of additional booster doses.
WHAT IS KNOWN
• Children with juvenile autoimmune rheumatic diseases (JARDs) are at higher risk for infections, due to their underlying disease and their immunosuppressive treatment. • In children with JARD, the immunogenicity of vaccines might be reduced, and concerns about safety or the potential for worsening in disease activity after vaccination exist.
WHAT IS NEW
• Our systematic review shows that vaccines in children with JARDs on immunosuppressive treatment are safe and immunogenic. • There are several limitations of the currently published studies, including random timing of measuring vaccine responses and age differences between children with JARD and control groups. Many of the studies were underpowered, and not designed to show non-inferiority between children with JARD and controls.
Topics: Adolescent; Child; Humans; Immunization Schedule; Immunosuppressive Agents; Rheumatic Diseases; Vaccination; Vaccines, Attenuated
PubMed: 34936010
DOI: 10.1007/s00431-021-04283-w -
Deutsches Arzteblatt International Jan 2022Involvement of the temporomandibular joint can be shown in 40-90% of patients with rheumatoid arthritis and juvenile idiopathic arthritis (JIA), although it is often...
BACKGROUND
Involvement of the temporomandibular joint can be shown in 40-90% of patients with rheumatoid arthritis and juvenile idiopathic arthritis (JIA), although it is often asymptomatic. Restricted jaw mobility and jaw pain can be found in approximately 20% of patients with JIA (prevalence: 70 per 100 000 persons). Early diagnosis and treatment of the underlying disease are essential for a good outcome, but uniform, consensus-based management is still lacking.
METHODS
The clinical practice guideline is based on the findings of a systematic literature review in multiple databases and a Delphi procedure to obtain consensus on the recommendations.
RESULTS
Most of the identified studies were retrospective. Patients with JIA should undergo clinical screening with a structured examination protocol once per year in childhood and adolescence, and thereafter as well if the temporomandibular joint is involved. The diagnosis of chronic rheumatoid arthritis of the temporomandibular joint is established with contrast-enhanced magnetic resonance imaging. Conservative treatment (antirheumatic basal therapy, local measures) is unsuccessful in less than 10% of patients. In such cases, arthroscopy and arthrocentesis can be used for temporary symptom relief and functional improvement. Intra-articular corticosteroid injections should be given only once, and only in otherwise intractable cases. In severe cases where all other options have been exhausted (<1%), open surgical treatment can be considered, including alloplastic joint replacement.
CONCLUSION
Oligosymptomatic and asymptomatic cases are common even with radiologic evidence of marked joint damage. The possibility of rheumatic involvement of the temporomandibular joint must be kept in mind so that serious complications can be avoided. Regular clinical evaluation of the temporomandibular joint is recommended, particularly for patients with juvenile idiopathic arthritis.
Topics: Adolescent; Arthritis, Juvenile; Arthritis, Rheumatoid; Humans; Magnetic Resonance Imaging; Retrospective Studies; Temporomandibular Joint; Temporomandibular Joint Disorders
PubMed: 34874262
DOI: 10.3238/arztebl.m2021.0388 -
Therapeutic Advances in Musculoskeletal... 2021The past decade has seen increasingly rapid advances in understanding the pathogenic nature of adult-onset Still's disease (AOSD) and its shared symptoms with the... (Review)
Review
INTRODUCTION
The past decade has seen increasingly rapid advances in understanding the pathogenic nature of adult-onset Still's disease (AOSD) and its shared symptoms with the systemic juvenile idiopathic arthritis (sJIA). Interleukin-1 (IL-1) blocking agents are key elements in the treatment. In this updated systematic review, we focus on studies on efficacy and safety of IL-1 blockers published in the past 5 years and review on latest available therapies.
METHODS
We conducted searches using Medline, Biosis, Embase, and Cochrane databases between 2016 and 2021 using the terms AOSD, IL1, IL-18, canakinumab, anakinra, tadekinig, and rilonacept and if applicable their trade names. Duplicates, case reports, and manuscripts with incomplete data were excluded.
RESULTS
Of the 1013 screened publications, 17 were eligible after careful selection. We only found two published randomized controlled studies in the past 5 years. Review manuscripts of rare diseases, like our work, usually rely on retrospective studies and case series. Anakinra and canakinumab can be successfully used as first- or further-line treatment in patients with AOSD refractory to steroids. A homogeneous outcome is not established yet. Thus, a combination of clinical and laboratory tests can support the experienced clinician in the decision-making process.
CONCLUSION
The approval of IL-1 inhibitors for AOSD brought us into a new era in the treatment of AOSD. The overall efficacy-safety profile of the IL-1 inhibitors is favorable reflecting a targeted approach as standard of care. We can expect that the successful treatment of AOSD with IL-1 inhibition will facilitate further clinical and basic research with impact on other auto-inflammatory and hyper-inflammatory conditions.
PubMed: 34868356
DOI: 10.1177/1759720X211059598 -
Pediatric Rheumatology Online Journal Oct 2021Juvenile Idiopathic Arthritis (JIA) requires complex care that generate elevated costs, which results in a high economic impact for the family. The aim of this...
BACKGROUND
Juvenile Idiopathic Arthritis (JIA) requires complex care that generate elevated costs, which results in a high economic impact for the family. The aim of this systematic review was to collect and cluster the information currently available on healthcare costs associated with JIA after the introduction of biological therapies.
METHODS
We comprehensively searched in MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Databases for studies from January 2000 to March 2021. Reviewers working independently and in duplicate appraised the quality and included primary studies that report total, direct and/or indirect costs related to JIA for at least one year. The costs were converted to United States dollars and an inflationary adjustment was made.
RESULTS
We found 18 eligible studies including data from 6,540 patients. Total costs were reported in 10 articles, ranging from $310 USD to $44,832 USD annually. Direct costs were reported in 16 articles ($193 USD to $32,446 USD), showing a proportion of 55 to 98 % of total costs. Those costs were mostly related to medications and medical appointments. Six studies reported indirect costs ($117 USD to $12,385 USD). Four studies reported costs according to JIA category observing the highest in polyarticular JIA. Total and direct costs increased up to three times after biological therapy initiation. A high risk of reporting bias and inconsistency of the methodology used were found.
CONCLUSION
The costs of JIA are substantial, and the highest are derived from medication and medical appointments. Indirect costs of JIA are underrepresented in costs analysis.
Topics: Arthritis, Juvenile; Cost of Illness; Cost-Benefit Analysis; Health Care Costs; Humans
PubMed: 34627296
DOI: 10.1186/s12969-021-00641-y -
Rheumatology (Oxford, England) Feb 2022JIA is the most common paediatric rheumatic disease, thought to be influenced by both genetics and the environment. Identifying environmental factors associated with... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
JIA is the most common paediatric rheumatic disease, thought to be influenced by both genetics and the environment. Identifying environmental factors associated with disease risk will improve knowledge of disease mechanism and ultimately benefit patients. This review aimed to collate and synthesize the current evidence of environmental factors associated with JIA.
METHODS
Four databases (MEDLINE, Embase, Web of Science and Cumulative Index to Nursing and Allied Health Literature) were searched from inception to January 2020. Study quality was rated using the Newcastle-Ottawa Scale. Pooled estimates for each environmental factor were generated using a random-effects, inverse-variance method, where possible. The remaining environmental factors were synthesized in narrative form.
RESULTS
This review includes 66 environmental factors from 39 studies (11 cohort and 28 case-control studies) over 45 years. Study sample sizes ranged from 41 to 1.9 million participants. Eight environmental factors from ten studies were meta-analysed. Caesarean section delivery was associated with increased JIA risk [pooled odds ratio (OR) 1.11, 95% CI: 1.01, 1.22]. Conversely, presence (vs absence) of siblings (pooled OR 0.60, 95% CI: 0.44, 0.81) and maternal prenatal smoking (pooled OR 0.70, 95% CI: 0.58, 0.84) were associated with decreased JIA risk.
CONCLUSION
This review identifies several environmental factors associated with JIA and demonstrates the huge breadth of environmental research undertaken over five decades. We also highlight the challenges of combining data collected over this period due to limited between study comparability, evolution in healthcare and social practices, and changing environment, which warrant consideration when planning future studies.
Topics: Arthritis, Juvenile; Environmental Exposure; Humans; Risk Factors
PubMed: 34382060
DOI: 10.1093/rheumatology/keab627 -
Rheumatology (Oxford, England) Mar 2022SS with childhood onset is a rare autoimmune disease characterized by heterogeneous presentation. The lack of validated classification criteria makes it challenging to...
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.
Topics: Antirheumatic Agents; Azathioprine; Cyclophosphamide; Cyclosporine; Glucocorticoids; Humans; Hydroxychloroquine; Methotrexate; Rituximab; Sjogren's Syndrome
PubMed: 34289032
DOI: 10.1093/rheumatology/keab579