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Pediatric Rheumatology Online Journal Jul 2021Although fatigue is a prevalent distressing symptom in children and adolescents with Pediatric Rheumatic Conditions (PRCs), intervention studies designed for reducing...
BACKGROUND
Although fatigue is a prevalent distressing symptom in children and adolescents with Pediatric Rheumatic Conditions (PRCs), intervention studies designed for reducing fatigue in PRCs are limited.
AIM
To systematically review evidence regarding the efficacy of interventions intended to reduce fatigue in patients with PRCs.
METHODS
Comprehensive electronic searches were performed in PubMed/ MEDLINE, Embase, Web of Science and Cinahl. The risk of bias was assessed using the 'Revised Cochrane risk-of-bias tool for randomized trials' and 'Quality Assessment Tool for Before-After Studies With No Control Group' for respectively studies with and without a control group.
RESULTS
Ten out of 418 studies were included with a total of 240 participants (age range 5-23 years). Interventions included land-based and aquatic-based exercise therapy, prednisolone, vitamin-D and creatine supplementation, psychological therapy and a transition program into an adult rheumatology program. Fatigue was assessed with self-reported questionnaires in all included studies. Land-based exercise therapy was effective in one pre-post intervention study, whereas not effective in two randomized controlled trials. Aquatic-based exercise therapy was found more effective than land-based exercise therapy. Two placebo-controlled studies showed a significant positive effect in reducing subjective fatigue with prednisolone and vitamin-D. Creatine was not found effective. Cognitive therapy was effective in one pre-post intervention study, while one RCT did not show an effect in reducing fatigue. A transition program based on health education showed a small reducing effect, however, it was not clear if this was a significant effect. Six studies showed a high risk of bias, three studies a moderate risk, and one study had a low risk of bias.
CONCLUSIONS
Insufficient evidence is provided to substantiate the efficacy of current interventions to reduce fatigue in PRCs. The low number of studies, non-comparable interventions, risk of bias, and inconclusive outcomes of the included studies denote future research should focus on intervention studies aimed at the treatment of fatigue in children and adolescents with PRCs. Identification of possible underlying biological and psychosocial mechanisms as possible treatment targets to reduce complaints of fatigue in children and adolescents with PRCs is warranted.
Topics: Adolescent; Child; Child, Preschool; Exercise Therapy; Fatigue; Humans; Rheumatic Diseases; Young Adult
PubMed: 34238314
DOI: 10.1186/s12969-021-00580-8 -
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 -
Frontiers in Medicine 2021Macrophage Activation Syndrome (MAS) is a very severe complication of different rheumatic diseases, including pediatric Systemic Lupus Erythematosus (pSLE). MAS is not...
Macrophage Activation Syndrome (MAS) is a very severe complication of different rheumatic diseases, including pediatric Systemic Lupus Erythematosus (pSLE). MAS is not considered as a frequent complication of pSLE; however, its occurrence could be under-estimated and the diagnosis can be challenging. In order to address this issue, we performed a systematic review of the available medical literature, aiming to retrieve all those papers providing diagnostic (clinical/laboratory) data on patients with pSLE-related MAS, in individual or aggregated form. The selected case reports and series provided a pool of 46 patients, accounting for 48 episodes of MAS in total. We re-analyzed these patients in light of the diagnostic criteria for MAS validated in systemic Juvenile Idiopathic Arthritis (sJIA) patients and the preliminary diagnostic criteria for MAS in pSLE, respectively. Five clinical studies were also selected and used to support this analysis. This systematic review confirms that MAS diagnosis in pSLE patients is characterized by several diagnostic challenges, which could lead to delayed diagnosis and/or under-estimation of this complication. Specific criteria should be considered to diagnose MAS in different rheumatic diseases; as regards pSLE, the aforementioned preliminary criteria for MAS in pSLE seem to perform better than the sJIA-related MAS criteria, because of a lower ferritin cut-off.
PubMed: 34150813
DOI: 10.3389/fmed.2021.681875 -
Turkish Archives of Pediatrics 2021Childhood rheumatic diseases are a group of diseases that can affect many organs and systems, resulting in pain, joint stiffness, muscle atrophy and weakness. Physical... (Review)
Review
Childhood rheumatic diseases are a group of diseases that can affect many organs and systems, resulting in pain, joint stiffness, muscle atrophy and weakness. Physical inactivity has been reported in many childhood rheumatic diseases. There are many studies in the literature comparing the effectiveness of exercise programs in children with juvenile idiopathic arthritis. Exercise and physical activity are considered major parts of the treatment of children with rheumatic disease. The aim of this review is to systematically present studies on physical activity and exercise programs in children with rheumatism from the last 5 years. An internet-based search of three databases-PubMed, PEDro and Medline- was conducted to find relevant studies. Two reviewers individually identified studies on the basis of their title, abstract or full text-as necessary-to determine their eligibility. Differences of opinion between the two examiners were resolved by discussion. Scientific studies of children with different rheumatic diagnoses have shown that physical activity and exercise have a significant effect on reducing the symptoms of the disease. However, the duration, frequency, method and evaluation of the exercises are still being discussed in the literature.
PubMed: 34104906
DOI: 10.5152/TurkArchPediatr.2021.21034 -
Journal of Ophthalmic Inflammation and... May 2021Juvenile idiopathic arthritis associated uveitis (JIA-U) is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA) and carries considerable...
BACKGROUND
Juvenile idiopathic arthritis associated uveitis (JIA-U) is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA) and carries considerable risk to vision. The aim of this systematic review was to synthesise evidence of environmental risk factors for JIA-U and identify risk factors which may be modifiable or used to stratify JIA patients.
METHODS
This systematic review was carried out in accordance with PRISMA guidelines. Four online databases - Cumulative Index of Nursing and Allied Health Literature, Web of Science, MEDLINE and Embase - were searched from database inception to 12th August 2020. Identified studies were screened by two independent reviewers against pre-defined inclusion and exclusion criteria. Data was extracted from all primary studies meeting inclusion criteria and independently checked.
RESULTS
We identified three studies from 895 unique records which met the inclusion criteria, each examining a different environmental risk factor. This systematic review includes 973, predominantly female, participants with JIA across these three studies. The use of allergy medication or documentation of "allergy"/"allergic" in the medical records was associated with an increased risk of JIA-U in all models presented. Vitamin D sufficiency was associated with reduced risk of JIA-U. There was insufficient evidence to support an association between seasonality and JIA-U.
CONCLUSIONS
This review identifies a potential role for allergy and vitamin D in JIA-U. It also illustrates the paucity of data regarding environmental risk factors for JIA-U and highlights the need for further research to both identify additional risk factors and replicate existing findings.
PubMed: 34027581
DOI: 10.1186/s12348-021-00247-1 -
Pediatric Rheumatology Online Journal Mar 2021Autoimmune rheumatic diseases (ARDs) are associated with a significant sex-bias, which becomes more evident post-puberty. This systematic review aims to elucidate the...
BACKGROUND
Autoimmune rheumatic diseases (ARDs) are associated with a significant sex-bias, which becomes more evident post-puberty. This systematic review aims to elucidate the bidirectional relationship between puberty and ARD-related outcomes.
METHODS
Studies published in English until October 2019 were identified using a systematic search of endocrinology and rheumatology literature. Information was extracted on study design, sample size, demographics, puberty outcome measures, disease outcome measures, and main findings. The methodological quality of the studies included was analysed using the Newcastle-Ottawa Scale (NOS).
RESULTS
Sixteen non-randomised studies reporting on the impact of puberty on ARD outcomes (n = 7), ARD impact on puberty-related outcomes (n = 8), or both (n = 1) have been identified. The impact of puberty on ARD outcomes were investigated in patients with juvenile idiopathic arthritis (JIA)-associated uveitis (n = 1), juvenile systemic lupus erythematosus (JSLE) (n = 5) or in healthy controls who developed adult-onset SLE (n = 1) or had non-specific symptoms (n = 1). The impact of ARD on puberty outcomes was explored in JIA (n = 4) and JSLE (n = 3). Quality assessment of studies showed a small to moderate risk of bias overall (NOS 4-9/9). Due to large heterogeneity of the studies it was not possible to perform a meta-analysis. Multiple studies reported on delayed puberty in patients with JIA/JSLE, menstrual and hormonal abnormalities, and lower height and weight than controls. Earlier (pre-pubertal) onset of JSLE was correlated with more severe disease and more need for systemic treatment.
CONCLUSION
A bidirectional relationship exists between puberty and ARDs; however, more and better research is required to elucidate the complexity of this relationship. We propose puberty-related clinical assessments in patients with ARDs, which can improve patient outcomes and facilitate future research.
Topics: Autoimmune Diseases; Humans; Puberty; Rheumatic Diseases
PubMed: 33781271
DOI: 10.1186/s12969-021-00528-y -
Pediatric Rheumatology Online Journal Mar 2021Biologic disease modifying antirheumatic drugs (bDMARDs) and Janus Kinase (JAK) inhibitors are prescribed in adult and paediatric rheumatology. Due to age-dependent...
Biologic disease modifying antirheumatic drugs and Janus kinase inhibitors in paediatric rheumatology - what we know and what we do not know from randomized controlled trials.
BACKGROUND
Biologic disease modifying antirheumatic drugs (bDMARDs) and Janus Kinase (JAK) inhibitors are prescribed in adult and paediatric rheumatology. Due to age-dependent changes, disease course, and pharmacokinetic processes paediatric patients with inflammatory rheumatic diseases (PiRD) differ from adult rheumatology patients.
METHODS
A systematic literature search for randomized clinical trials (RCTs) in PiRD treated with bDMARDs/JAK inhibitors was conducted on Medline, clinicaltrials.gov , clinicaltrialsregister.eu and conference abstracts as of July 2020. RCTs were included if (i) patients were aged ≤20 years, (ii) patients had a predefined rheumatic diagnosis and (iii) RCT reported predefined outcomes. Selected studies were excluded in case of (i) observational or single arm study or (ii) sample size ≤5 patients. Study characteristics were extracted.
RESULTS
Out of 608 screened references, 65 references were selected, reporting 35 unique RCTs. All 35 RCTs reported efficacy while 34/3 provided safety outcomes and 16/35 provided pharmacokinetic data. The most common investigated treatments were TNF inhibitors (60%), IL-1 inhibitors (17%) and IL-6 inhibitors (9%). No RCTs with published results were identified for baricitinib, brodalumab, certolizumab pegol, guselkumab, risankizumab, rituximab, sarilumab, secukinumab, tildrakizumab, or upadacitinib. In patients with juvenile idiopathic arthritis (JIA) 25/35 RCTs were conducted. The remaining 10 RCTs were performed in non-JIA patients including plaque psoriasis, Kawasaki Disease, systemic lupus erythematosus and non-infectious uveitis. In JIA-RCTs, the control arm was mainly placebo and the concomitant treatments were either methotrexate, non-steroidal anti-inflammatory drugs (NSAID) or corticosteroids. Non-JIA patients mostly received NSAID. There are ongoing trials investigating abatacept, adalimumab, baricitinib, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, risankizumab, secukinumab, tofacitinib and tildrakizumab.
CONCLUSION
Despite the FDA Modernization Act and support of major paediatric rheumatology networks, such as the Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organization (PRINTO), which resulted in drug approval for PiRD indications, there are limited RCTs in PiRD patients. As therapy response is influenced by age-dependent changes, pharmacokinetic processes and disease course it is important to consider developmental changes in bDMARDs/JAK inhibitor use in PiRD patients. As such it is critical to collaborate and conduct international RCTs to appropriately investigate and characterize efficacy, safety and pharmacokinetics of bDMARDs/JAK inhibitors in paediatric rheumatology.
Topics: Antirheumatic Agents; Child; Humans; Janus Kinase Inhibitors; Randomized Controlled Trials as Topic; Rheumatic Diseases
PubMed: 33766063
DOI: 10.1186/s12969-021-00514-4 -
Rheumatology and Therapy Jun 2021To investigate the efficacy and safety of anti-TNFα therapy in patients with juvenile idiopathic arthritis associated uveitis (JIA-U).
INTRODUCTION
To investigate the efficacy and safety of anti-TNFα therapy in patients with juvenile idiopathic arthritis associated uveitis (JIA-U).
METHODS
Embase, PubMed, Cochrane Library, and Web of Science were systematically searched for studies reporting anti-TNFα treatment in patients with JIA-U. The primary outcome was the control of intraocular inflammation (CII). The pooled proportion of CII was assessed by the random-effects method when I > 50%, otherwise, by the fixed-effect method. This study was registered with PROSPERO (CRD42020161749).
RESULTS
Three randomized clinical trials (RCTs), twelve case series, three retrospective cohort studies, and three case reports were identified. A total of 399 patients were receiving anti-TNFα therapy, of which 201 patients were treated with adalimumab (ADA), 139 with infliximab (IFX), 36 with etanercept (ETA), 20 with golimumab (GLM), and 3 with certolizumab pegol (CZP). The pooled proportions of CII on observational studies were 82% (95% CI 63-96%) in patients receiving ADA, 56% (95% CI 30-80%) in IFX, 38% (95% CI 8-73%) in ETA and 65% (95% CI 42-86%) in GLM, respectively. All three patients treated with CZP reached improved activity. ADA therapy led to a significantly higher proportion of CII compared to IFX therapy (χ = 26.24, P < 0.001), or to ETA therapy (χ = 13.43, P < 0.001); but no statistical difference was observed between IFX and ETA (χ = 0.13, P = 0.71). As to safety, most reported adverse events were tolerable and two cohort studies consistently showed that ADA was safer than IFX.
CONCLUSIONS
The existing evidence suggests that ADA is better than IFX regarding efficacy and safety. The effectiveness of IFX is higher than ETA with no statistical difference. GLM and CZP may be proxies for ADA but the evidence is limited.
PubMed: 33721267
DOI: 10.1007/s40744-021-00296-x -
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 -
Gut Microbes 2021Antibiotics in childhood have been linked with diseases including asthma, juvenile arthritis, type 1 diabetes, Crohn's disease and mental illness. The underlying... (Meta-Analysis)
Meta-Analysis
Antibiotics in childhood have been linked with diseases including asthma, juvenile arthritis, type 1 diabetes, Crohn's disease and mental illness. The underlying mechanisms are thought related to dysbiosis of the gut microbiome. We conducted a systematic review of the association between antibiotics and disruption of the pediatric gut microbiome. Searches used MEDLINE, EMBASE and Web of Science. Eligible studies: association between antibiotics and gut microbiome dysbiosis; children 0-18 years; molecular techniques of assessment; outcomes of microbiome richness, diversity or composition. Quality assessed by Newcastle-Ottawa Scale or Cochrane Risk of Bias Tool. Meta-analysis where possible. A total of 4,668 publications identified: 12 in final analysis (5 randomized controlled trials (RCTs), 5 cohort studies, 2 cross-sectional studies). Microbiome richness was measured in 3 studies, species diversity in 6, and species composition in 10. Quality of evidence was good or fair. 5 studies found a significant reduction in diversity and 3 a significant reduction in richness. Macrolide exposure was associated with reduced richness for twice as long as penicillin. Significant reductions were seen in (5 studies) and (2 studies), and significant increases in Proteobacteria such as (4 studies). A meta-analysis of RCTs of the effect of macrolide (azithromycin) exposure on the gut microbiome found a significant reduction in alpha-diversity (Shannon index: mean difference -0.86 (95% CI -1.59, -0.13). Antibiotic exposure was associated with reduced microbiome diversity and richness, and with changes in bacterial abundance. The potential for dysbiosis in the microbiome should be taken into account when prescribing antibiotics for children.: CRD42018094188.
Topics: Anti-Bacterial Agents; Bacteria; Child; Child, Preschool; Dysbiosis; Gastrointestinal Microbiome; Humans; Infant; Infant, Newborn
PubMed: 33651651
DOI: 10.1080/19490976.2020.1870402