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Orphanet Journal of Rare Diseases Jul 2019Hereditary hemochromatosis (HH) is a genetic disorder that causes excess absorption of iron and can lead to a variety of complications including liver cirrhosis,... (Review)
Review
Hereditary hemochromatosis (HH) is a genetic disorder that causes excess absorption of iron and can lead to a variety of complications including liver cirrhosis, arthritis, abnormal skin pigmentation, cardiomyopathy, hypogonadism, and diabetes. Hemojuvelin (HJV) is the causative gene of a rare subtype of HH worldwide. This study aims to systematically review the genotypic and phenotypic spectra of HJV-HH in multiple ethnicities, and to explore the genotype-phenotype correlations. A comprehensive search of PubMed database was conducted. Data were extracted from 57 peer-reviewed original articles including 132 cases with HJV-HH of multiple ethnicities, involving 117 biallelic cases and 15 heterozygotes. Among the biallelic cases, male and female probands of Caucasian ancestry were equally affected, whereas males were more often affected among East Asians (P=1.72×10). Hepatic iron deposition and hypogonadism were the most frequently reported complications. Hypogonadism and arthropathy were more prevalent in Caucasians than in East Asians (P=9.30×10, 1.69×10). Among the recurrent mutations, G320V (45 unrelated cases) and L101P (7 unrelated cases) were detected most frequently and restricted to Caucasians. [Q6H; C321*] was predominant in Chinese patients (6 unrelated cases). I281T (Chinese and Greek), A310G (Brazilian and African American), and R385* (Italian and North African) were reported across different ethnicities. In genotype-phenotype correlation analyses, 91.30% of homozygotes with exon 2-3 mutations developed early-onset HH compared to 66.00% of those with exon 4 mutations (P=2.40×10). Hypogonadism occurred more frequently in homozygotes with missense mutations (72.55%) than in those with nonsense mutations (35.71%; P=2.43×10). Liver biopsy was accepted by more probands with frame-shift or missense mutations (85.71% and 60.78%, respectively) than by those with nonsense mutations (28.57%; P=2.37×10, 3.93×10). The present review suggests that patients' ethnicity, geographical region, and genetic predisposition should be considered in the diagnosis, prognosis and management of HJV-HH.
Topics: Female; Humans; Male; alpha-Galactosidase; Cross-Sectional Studies; Genotype; Hemochromatosis; Mutation; Hemochromatosis Protein
PubMed: 31286966
DOI: 10.1186/s13023-019-1097-2 -
ARP Rheumatology 2022To develop the first Ophthalmology joint guidelines with Paediatric Rheumatology with recommendations on the screening, monitoring and medical treatment of juvenile...
The 2021 Portuguese Society of Ophthalmology joint guidelines with Paediatric Rheumatology on the screening, monitoring and medical treatment of juvenile idiopathic arthritis-associated uveitis.
AIM
To develop the first Ophthalmology joint guidelines with Paediatric Rheumatology with recommendations on the screening, monitoring and medical treatment of juvenile idiopathic arthritis-associated uveitis (JIA-U), endorsed by the Portuguese Society of Ophthalmology (SPO).
METHODS
A systematic literature review was conducted to include publications up to July 14th 2020, with no language restrictions, in order to include all the international position papers/guidelines concerning the medical management of JIA-U and randomised clinical trials assessing the efficacy and safety of medical treatment in this field. We searched through MEDLINE (PubMed), Scopus, Web of Science and Cochrane Library. The Delphi modified technique to generate consensus was used. Preliminary evidence statements were subject to an anonymous agreement assessment and discussion process using an online survey, followed by further discussion and update at a national meeting. A draft of the manuscript with all recommendations was then circulated among all participants and suggestions were incorporated. The final version was again circulated before publication.
RESULTS
Twenty-six recommendations were developed focusing on the following topics: general management (3), screening and follow-up of uveitis (4), treatment (17) and health education in JIA-U among patients and families (2).
CONCLUSION
These guidelines were designed to support the shared medical management of patients with JIA-U and emphasize the need for a multidisciplinary approach between Ophthalmology and Paediatric Rheumatology regarding the comprehensive care of JIA-U. We acknowledge that updating these recommendations will be warranted in the future, as more evidence becomes available.
KEY-WORDS
juvenile idiopathic arthritis, uveitis, biological treatment, conventional immunosuppressive treatment, multidisciplinary management, guidelines, consensus, review, Delphi Technique.
Topics: Arthritis, Juvenile; Child; Humans; Ophthalmology; Portugal; Rheumatology; Uveitis
PubMed: 35633577
DOI: No ID Found -
Medicine May 2024The goal of this study was to estimate the relative efficacy and safety of different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab,... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
The goal of this study was to estimate the relative efficacy and safety of different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) compared with placebo for systemic juvenile idiopathic arthritis (JIA) patients, through a network meta-analysis.
METHODS
Pubmed, Embase, and Cochrane Library were searched from database inception to July 2023 for randomized controlled trials comparing different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) or placebo directly or indirectly in JIA. Bayesian network meta-analyses were conducted. Data was extracted and analyzed by R with gemtc package. The treatment options were ranked using the surface under the cumulative ranking curve (SUCRA) value.
RESULTS
We identified 10 randomized controlled trials and analyzed 898 participants. Canakinumab (odds ratio 55.0, 95% credible intervals 2.4-67.0) was more effective than the placebo, and the difference was statistically significant. However, there was no statistical significance between other drugs versus placebo in terms of the modified ACRpedi30 (P > .05). The SUCRA shows that canakinumab ranked first (SUCRA, 86.9%), anakinra ranked second (SUCRA, 77.7%), adalimumab ranked third (SUCRA, 61.9%), and placebo ranked the last (SUCRA, 6.3%). Nevertheless, there were no notable discrepancies in the occurrence of adverse events, hepatic-related adverse events, infectious adverse event, serious adverse events, and serious infection following treatment with canakinumab, anakinra, tocilizumab, rilonacept, or the placebo. Based on the clustergram of modified ACRpedi30 and adverse events, canakinumab is suggested for JIA according to the surface under SUCRAs considering the symptom and adverse events simultaneously.
CONCLUSIONS
Among patients with JIA, canakinumab exhibited the highest likelihood of being the optimal treatment for achieving the modified ACRpedi30 response rate, and neither of the tested biological agents carried a significant risk of serious adverse events.
Topics: Arthritis, Juvenile; Humans; Network Meta-Analysis; Antirheumatic Agents; Randomized Controlled Trials as Topic; Treatment Outcome; Adalimumab; Antibodies, Monoclonal, Humanized; Interleukin 1 Receptor Antagonist Protein; Bayes Theorem
PubMed: 38701278
DOI: 10.1097/MD.0000000000038002 -
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 -
Rheumatology (Oxford, England) Aug 2021To identify how refractory disease (or relevant terminology variations) in RA and polyarticular JIA (polyJIA) is defined and establish the key components of such...
OBJECTIVES
To identify how refractory disease (or relevant terminology variations) in RA and polyarticular JIA (polyJIA) is defined and establish the key components of such definitions.
METHODS
Searches were undertaken of English-language articles within six medical databases, including manual searching, from January 1998 to March 2020 (PROSPERO: CRD42019127142). Articles were included if they incorporated a definition of refractory disease, or non-response, in RA/polyJIA, with clear components to the description. Qualitative content analysis was undertaken to describe refractory disease in RA/polyJIA and classify each component within each definition.
RESULTS
Of 6251 studies screened, 646 met the inclusion criteria; 581 of these applied non-response criteria while 65 provided refractory disease definitions/descriptions. From the non-response studies, 39 different components included various disease activity measures, emphasizing persistent disease activity and symptoms, despite treatment with one or more biologic DMARD (bDMARD). From papers with clear definitions for refractory disease, 41 components were identified and categorized into three key themes: resistance to multiple drugs with different mechanisms of action, typically two or more bDMARDs; persistence of symptoms and disease activity; and other contributing factors. The most common term used was 'refractory' (80%), while only 16.9% reported explicitly how their definition was generated (e.g. clinical experience or statistical methods).
CONCLUSION
Refractory disease is defined as resistance to multiple drugs with different mechanisms of action by persistence of physical symptoms and high disease activity, including contributing factors. A clear unifying definition needs implementing, as the plethora of different definitions makes study comparisons and appropriate identification of patients difficult.
Topics: Arthritis, Juvenile; Arthritis, Rheumatoid; Humans; Terminology as Topic
PubMed: 33710321
DOI: 10.1093/rheumatology/keab237 -
Medical Ultrasonography Dec 2022In this systematic review we analyzed the published articles related to the predictive value for flare of subclinical synovitis assessed by ultrasound (US) in juvenile... (Review)
Review
Ultrasound versus physical examination in predicting disease flare in children with juvenile idiopathic arthritis: a systematic literature review and qualitative synthesis.
In this systematic review we analyzed the published articles related to the predictive value for flare of subclinical synovitis assessed by ultrasound (US) in juvenile idiopathic arthritis (JIA). Medline, Embase and Cochrane databases were searched from 1990 to 2020 by two authors, using PICO methodology. The study is built and reported according to PRISMA guidelines. Searches identified four articles comprising a total of 187 JIA patients in clinical remission from at least 3 months. Two of the articles found US subclinical signs of synovitis to be predictive for flare, with a five times higher risk (with Power Doppler signal as an important feature), while in the other two baseline US abnormalities did not predict a clinical flare. The articles differed for protocols, definitions, and length of follow-up. US has an expanding role in pediatric rheumatology, with interest-ing applications especially during the follow-up, potentially identifying subclinical inflammatory signs predictive of flare. However, the few studies available do not allow definite conclusions at this time.
Topics: Humans; Child; Arthritis, Juvenile; Symptom Flare Up; Ultrasonography; Synovitis; Physical Examination
PubMed: 35045140
DOI: 10.11152/mu-3303 -
BMJ Open Dec 2023External control arms (ECAs) provide useful comparisons in clinical trials when randomised control arms are limited or not feasible. We conducted a systematic review to...
OBJECTIVES
External control arms (ECAs) provide useful comparisons in clinical trials when randomised control arms are limited or not feasible. We conducted a systematic review to summarise applications of ECAs in trials of immune-mediated inflammatory diseases (IMIDs).
DESIGN
Systematic review with an appraisal of ECA source quality rated across five domains (data collection, study populations, outcome definitions, reliability and comprehensiveness of the dataset, and other potential limitations) as high, low or unclear quality.
DATA SOURCES
Embase, Medline and Cochrane Central Register of Controlled Trial were searched through to 12 September 2023.
ELIGIBILITY CRITERIA
Eligible studies were single-arm or randomised controlled trials (RCTs) of inflammatory bowel disease, pouchitis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and atopic dermatitis in which an ECA was used as the comparator.
DATA EXTRACTION AND SYNTHESIS
Two authors independently screened the search results in duplicate. The characteristics of included studies, external data source(s), outcomes and statistical methods were recorded, and the quality of the ECA data source was assessed by two independent authors.
RESULTS
Forty-three studies met the inclusion criteria (inflammatory bowel disease: 16, pouchitis: 1, rheumatoid arthritis: 12, juvenile idiopathic arthritis: 1, ankylosing spondylitis: 5, psoriasis: 3, multiple indications: 4). The majority of these trials were single-arm (33/43) and enrolled adult patients (34/43). All included studies used a historical control rather than a contemporaneous ECA. In RCTs, ECAs were most often derived from the placebo arm of another RCT (6/10). In single-arm trials, historical case series were the most common ECA source (19/33). Most studies (31/43) did not employ a statistical approach to generate the ECA from historical data.
CONCLUSIONS
Standardised ECA methodology and reporting conventions are lacking for IMIDs trials. The establishment of ECA reporting guidelines may enhance the rigour and transparency of future research.
Topics: Adult; Humans; Spondylitis, Ankylosing; Pouchitis; Arthritis, Rheumatoid; Psoriasis; Inflammatory Bowel Diseases; Immunomodulating Agents
PubMed: 38070932
DOI: 10.1136/bmjopen-2023-076677 -
Pediatric Rheumatology Online Journal Jul 2019Juvenile Idiopathic Arthritis associated Uveitis (JIA-U) represents its most frequent extra-articular manifestation and the main cause of childhood uveitis in in...
BACKGROUND
Juvenile Idiopathic Arthritis associated Uveitis (JIA-U) represents its most frequent extra-articular manifestation and the main cause of childhood uveitis in in developed countries. The broad variety of outcome measures utilized makes the comparison of the disease course, risk for complications, impairment in visual function, and responses to treatment quite difficult. Our aim was to summarize evidence regarding the current availability of outcome measures in JIA-U.
METHODS
A systematic review between January 2000 and December 2018 was performed to identify studies investigating outcome measures used in JIA-U.
RESULTS
The initial search identified 8254 articles of which 89 were potentially eligible. After the full text revision, a total of 27 studies, including 2 RCTs, were included. Among these studies 12 outcome measures for JIA-U use have been identified (grade of cells in the AC, grade of flare in the AC, VA, amblyopia, structural complications, use and sparing of oral corticosteroids and immunosuppressive drugs, surgery requirement, biomarkers, bilateral disease, JIA persistence, quality of life assessments, uveitis subtype). As regards primary outcome measures, 44% among studies included one or more variables related to disease activity (i.e. grade of flare, grade of cells); 56% included visual function performance (i.e. visual acuity); 68% (17/25) included one or more variables of disease-associated tissue damage or complications (i.e. cataract, amblyopia); 24% included disease features (i.e. bilateral disease; uveitis subtype); 44% included laboratory features (i.e. biomarkers); 8% included JIA features (i.e. persistence of disease); 12% included quality of life (i.e. EYE-Q); 44% included management (i.e. use and sparing of oral corticosteroids and other immunosuppressive drugs; surgery requirement).
CONCLUSIONS
Our systematic review surveys the heterogeneity around outcome measures related to JIA-U in children, even in RCTs. It does not provide the solution to overcome the heterogeneity in uveitis studies, but it does provide an estimate of the scale of the problems and provides data to inform this important debate; highlighting the requirement to obtain a new consensus regarding a common approach to identify suitable and efficient outcome measures in JIA-U.
Topics: Adrenal Cortex Hormones; Amblyopia; Arthritis, Juvenile; Consensus; Humans; Immunosuppressive Agents; Outcome Assessment, Health Care; Quality of Life; Severity of Illness Index; Uveitis; Visual Acuity
PubMed: 31296236
DOI: 10.1186/s12969-019-0330-9 -
RMD Open Aug 2020This meta-analysis investigated the frequency of ocular involvement in childhood and adult spondyloarthritis (SpA). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This meta-analysis investigated the frequency of ocular involvement in childhood and adult spondyloarthritis (SpA).
METHODS
A systematic review of the literature was conducted. Medline, Web of Science and Cochrane databases were searched upto October 2018 identifying publications related to SpA, including ankylosing spondylitis (AS) with ocular conditions (OC) (uveitis, iritis, retinitis, chorioretinitis and other ocular involvement). The rates of OC were extracted and random effects models estimated their frequency. Heterogeneity was evaluated using I. Inclusion criteria were studies in SpA of either children or adults who included a frequency of OC.
RESULTS
3164 studies were identified, and 41 analysed which included frequencies of uveitis/iritis. Other OC were too infrequent to analyse. A pooled random effects model showed that the prevalence of uveitis was 24% in adult AS (23 studies, 11 943 patients), 10% in adult psoriatic arthritis (PsA) (9 studies, 1817) and 17% in undifferentiated adult SpA (9 studies, 6568 patients). In juveniles with AS, the prevalence of uveitis was 27% (8 studies, 927 patients), in juvenile PsA it was 16% (5 studies, N=498) and in juvenile undifferentiated SpA, uveitis occurred in 7% (2 studies, 1531 patients). In all evaluated SpA subgroups, there were no statistical differences in the frequency of uveitis between juveniles and adults.
CONCLUSIONS
Uveitis in adult versus child-onset SpA is similar in AS but more common in adult-onset undifferentiated SpA, and less frequent in adult-onset PsA compared to child-onset PsA, but the differences were not significant.
Topics: Adult; Arthritis, Juvenile; Arthritis, Psoriatic; Humans; Spondylarthritis; Spondylitis, Ankylosing; Uveitis
PubMed: 32868451
DOI: 10.1136/rmdopen-2020-001196 -
Journal of Ophthalmology 2021To systematically review the results of comparative studies of modern cataract surgery in pediatric uveitis with or without intraocular lens (IOL) implantation and to... (Review)
Review
PURPOSE
To systematically review the results of comparative studies of modern cataract surgery in pediatric uveitis with or without intraocular lens (IOL) implantation and to perform comparative meta-analyses to compare visual acuity outcomes and complication rates.
METHODS
On 12 November 2020, we systematically searched the Cochrane Central, PubMed/MEDLINE, EMBASE, ClinicalTrials.gov, and all affiliated databases of the Web of Science. Two authors independently reviewed studies and extracted data. Studies were reviewed qualitatively in text and quantitatively with meta-analyses. Outcome measures were preoperative and postoperative best-corrected visual acuity (BCVA), inflammation control, and rates of postoperative complications.
RESULTS
Ten studies of 288 eyes were eligible for review of which the majority were eyes with juvenile idiopathic arthritis-associated uveitis. Summary estimates revealed that the BCVA was better in pseudophakic eyes vs. aphakic eyes (1-year postoperative: -0.23 logMAR, 95% CI: -0.43 to -0.03 logMAR, =0.027; 5-year postoperative: -0.35 logMAR, 95% CI: -0.51 to -0.18 logMAR, =0.000036). Pseudophakic eyes had more visual axis opacification (OR 6.76, 95% CI: 2.73 to 16.8, =0.000036) and less hypotony (OR 0.19, 95% CI: 0.04 to 0.95, =0.044).
CONCLUSIONS
In modern era cataract surgery on eyes with pediatric uveitis with IOL implantation leads to satisfactory and superior visual outcomes and no differences in complication rates apart from an increased prevalence of visual axis opacification and a decreased prevalence of hypotony when compared to aphakia. However, limitations of the retrospective design and the presence of selection bias necessitate a careful interpretation.
PubMed: 34221492
DOI: 10.1155/2021/5481609