ASAH1 pathogenic variants associated with acid ceramidase deficiency: Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy.

Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy are a spectrum of rare lysosomal storage disorders characterized by acid ceramidase deficiency (ACD), resulting from pathogenic variants in N-acylsphingosine amidohydrolase 1 (ASAH1). Other than simple listings provided in literature reviews, a curated, comprehensive list of ASAH1 mutations associated with ACD clinical phenotypes has not yet been published. This publication includes mutations in ASAH1 collected through the Observational and Cross-Sectional Cohort Study of the Natural History and Phenotypic Spectrum of Farber Disease (NHS), ClinicalTrials.gov identifier NCT03233841, in combination with an up-to-date curated list of published mutations. The NHS is the first to collect retrospective and prospective data on living and deceased patients with ACD presenting as Farber disease, who had or had not undergone hematopoietic stem cell transplantation. Forty-five patients representing the known clinical spectrum of Farber disease (living patients aged 1-28 years) were enrolled. The curation of known ASAH1 pathogenic variants using a single reference transcript includes 10 previously unpublished from the NHS and 63 that were previously reported. The publication of ASAH1 variants will be greatly beneficial to patients undergoing genetic testing in the future by providing a significantly expanded reference list of disease-causing variants.

The European network for care of children with paediatric rheumatic diseases: care across borders.

OBJECTIVES: To provide an overview of the paediatric rheumatology (PR) services in Europe, describe current delivery of care and training, set standards for care, identify unmet needs and inform future specialist service provision. METHODS: An online survey was developed and presented to national coordinating centres of the Paediatric Rheumatology International Trials Organisation (PRINTO) (country survey) and to individual PR centres (centre and disease surveys) as a part of the European Union (EU) Single Hub and Access point for paediatric Rheumatology in Europe project. The survey contained components covering the organization of PR care, composition of teams, education, health care and research facilities and assessment of needs. RESULTS: Response rates were 29/35 (83%) for country surveys and 164/288 (57%) for centre surveys. Across the EU, approximately one paediatric rheumatologist is available per million population. In all EU member states there is good access to specialist care and medications, although biologic drug availability is worse in Eastern European countries. PR education is widely available for physicians but is insufficient for allied health professionals. The ability to participate in clinical trials is generally high. Important gaps were identified, including lack of standardized clinical guidelines/recommendations and insufficient adolescent transition management planning. CONCLUSION: This study provides a comprehensive description of current specialist PR service provision across Europe and did not reveal any major differences between EU member states. Rarity, chronicity and complexity of diseases are major challenges to PR care. Future work should facilitate the development, dissemination and implementation of standards of care, treatment and service recommendations to further improve patient-centred health care across Europe.

Prednisone versus prednisone plus ciclosporin versus prednisone plus methotrexate in new-onset juvenile dermatomyositis: a randomised trial.

BACKGROUND: Most data for treatment of dermatomyositis and juvenile dermatomyositis are from anecdotal, non-randomised case series. We aimed to compare, in a randomised trial, the efficacy and safety of prednisone alone with that of prednisone plus either methotrexate or ciclosporin in children with new-onset juvenile dermatomyositis. METHODS: We did a randomised trial at 54 centres in 22 countries. We enrolled patients aged 18 years or younger with new-onset juvenile dermatomyositis who had received no previous treatment and did not have cutaneous or gastrointestinal ulceration. We randomly allocated 139 patients via a computer-based system to prednisone alone or in combination with either ciclosporin or methotrexate. We did not mask patients or investigators to treatment assignments. Our primary outcomes were the proportion of patients achieving a juvenile dermatomyositis PRINTO 20 level of improvement (20% improvement in three of six core set variables at 6 months), time to clinical remission, and time to treatment failure. We compared the three treatment groups with the Kruskal-Wallis test and Friedman's test, and we analysed survival with Kaplan-Meier curves and the log-rank test. Analysis was by intention to treat. Here, we present results after at least 2 years of treatment (induction and maintenance phases). This trial is registered with ClinicalTrials.gov, number NCT00323960. FINDINGS: Between May 31, 2006, and Nov 12, 2010, 47 patients were randomly assigned prednisone alone, 46 were allocated prednisone plus ciclosporin, and 46 were randomised prednisone plus methotrexate. Median duration of follow-up was 35.5 months. At month 6, 24 (51%) of 47 patients assigned prednisone, 32 (70%) of 46 allocated prednisone plus ciclosporin, and 33 (72%) of 46 administered prednisone plus methotrexate achieved a juvenile dermatomyositis PRINTO 20 improvement (p=0.0228). Median time to clinical remission was 41.9 months in patients assigned prednisone plus methotrexate but was not observable in the other two treatment groups (2.45 fold [95% CI 1.2-5.0] increase with prednisone plus methotrexate; p=0.012). Median time to treatment failure was 16.7 months in patients allocated prednisone, 53.3 months in those assigned prednisone plus ciclosporin, but was not observable in patients randomised to prednisone plus methotrexate (1.95 fold [95% CI 1.20-3.15] increase with prednisone; p=0.009). Median time to prednisone discontinuation was 35.8 months with prednisone alone compared with 29.4-29.7 months in the combination groups (p=0.002). A significantly greater proportion of patients assigned prednisone plus ciclosporin had adverse events, affecting the skin and subcutaneous tissues, gastrointestinal system, and general disorders. Infections and infestations were significantly increased in patients assigned prednisone plus ciclosporin and prednisone plus methotrexate. No patients died during the study. INTERPRETATION: Combined treatment with prednisone and either ciclosporin or methotrexate was more effective than prednisone alone. The safety profile and steroid-sparing effect favoured the combination of prednisone plus methotrexate. FUNDING: Italian Agency of Drug Evaluation, Istituto Giannina Gaslini (Genoa, Italy), Myositis Association (USA).

Acid Ceramidase Deficiency is characterized by a unique plasma cytokine and ceramide profile that is altered by therapy.

Acid Ceramidase Deficiency (Farber disease, FD) is an ultra-rare Lysosomal Storage Disorder that is poorly understood and often misdiagnosed as Juvenile Idiopathic Arthritis (JIA). Hallmarks of FD are accumulation of ceramides, widespread macrophage infiltration, splenomegaly, and lymphocytosis. The cytokines involved in this abnormal hematopoietic state are unknown. There are dozens of ceramide species and derivatives, but the specific ones that accumulate in FD have not been investigated. We used a multiplex assay to analyze cytokines and mass spectrometry to analyze ceramides in plasma from patients and mice with FD, controls, Farber patients treated by hematopoietic stem cell transplantation (HSCT), JIA patients, and patients with Gaucher disease. KC, MIP-1α, and MCP-1 were sequentially upregulated in plasma from FD mice. MCP-1, IL-10, IL-6, IL-12, and VEGF levels were elevated in plasma from Farber patients but not in control or JIA patients. C16-Ceramide (C16-Cer) and dhC16-Cer were upregulated in plasma from FD mice. a-OH-C18-Cer, dhC12-Cer, dhC24:1-Cer, and C22:1-Cer-1P accumulated in plasma from patients with FD. Most cytokines and only a-OH-C18-Cer returned to baseline levels in HSCT-treated Farber patients. Sphingosines were not altered. Chitotriosidase activity was also relatively low. A unique cytokine and ceramide profile was seen in the plasma of Farber patients that was not observed in plasma from HSCT-treated Farber patients, JIA patients, or Gaucher patients. The cytokine profile can potentially be used to prevent misdiagnosis of Farber as JIA and to monitor the response to treatment. Further understanding of why these signaling molecules and lipids are elevated can lead to better understanding of the etiology and pathophysiology of FD and inform development of future treatments.

Consensus-based recommendations for the management of juvenile dermatomyositis.

BACKGROUND: In 2012, a European initiative called Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile dermatomyositis (JDM) is a rare disease within the group of paediatric rheumatic diseases (PRDs) and can lead to significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physicians' experience. Consequently, treatment regimens differ throughout Europe. OBJECTIVES: To provide recommendations for diagnosis and treatment of JDM. METHODS: Recommendations were developed by an evidence-informed consensus process using the European League Against Rheumatism standard operating procedures. A committee was constituted, consisting of 19 experienced paediatric rheumatologists and 2 experts in paediatric exercise physiology and physical therapy, mainly from Europe. Recommendations derived from a validated systematic literature review were evaluated by an online survey and subsequently discussed at two consensus meetings using nominal group technique. Recommendations were accepted if >80% agreement was reached. RESULTS: In total, 7 overarching principles, 33 recommendations on diagnosis and 19 recommendations on therapy were accepted with >80% agreement among experts. Topics covered include assessment of skin, muscle and major organ involvement and suggested treatment pathways. CONCLUSIONS: The SHARE initiative aims to identify best practices for treatment of patients suffering from PRD. Within this remit, recommendations for the diagnosis and treatment of JDM have been formulated by an evidence-informed consensus process to produce a standard of care for patients with JDM throughout Europe.

2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

To develop response criteria for juvenile dermatomyositis (DM). We analysed the performance of 312 definitions that used core set measures from either the International Myositis Assessment and Clinical Studies Group (IMACS) or the Paediatric Rheumatology International Trials Organisation (PRINTO) and were derived from natural history data and a conjoint analysis survey. They were further validated using data from the PRINTO trial of prednisone alone compared to prednisone with methotrexate or cyclosporine and the Rituximab in Myositis (RIM) trial. At a consensus conference, experts considered 14 top candidate criteria based on their performance characteristics and clinical face validity, using nominal group technique. Consensus was reached for a conjoint analysis-based continuous model with a total improvement score of 0-100, using absolute per cent change in core set measures of minimal (≥30), moderate (≥45), and major (≥70) improvement. The same criteria were chosen for adult DM/polymyositis, with differing thresholds for improvement. The sensitivity and specificity were 89% and 91-98% for minimal improvement, 92-94% and 94-99% for moderate improvement, and 91-98% and 85-86% for major improvement, respectively, in juvenile DM patient cohorts using the IMACS and PRINTO core set measures. These criteria were validated in the PRINTO trial for differentiating between treatment arms for minimal and moderate improvement (p=0.009-0.057) and in the RIM trial for significantly differentiating the physician's rating for improvement (p<0.006). The response criteria for juvenile DM consisted of a conjoint analysis-based model using a continuous improvement score based on absolute per cent change in core set measures, with thresholds for minimal, moderate, and major improvement.

Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis.

BACKGROUND: Interleukin-1 is pivotal in the pathogenesis of systemic juvenile idiopathic arthritis (JIA). We assessed the efficacy and safety of canakinumab, a selective, fully human, anti-interleukin-1ß monoclonal antibody, in two trials. METHODS: In trial 1, we randomly assigned patients, 2 to 19 years of age, with systemic JIA and active systemic features (fever; ≥2 active joints; C-reactive protein, >30 mg per liter; and glucocorticoid dose, ≤1.0 mg per kilogram of body weight per day), in a double-blind fashion, to a single subcutaneous dose of canakinumab (4 mg per kilogram) or placebo. The primary outcome, termed adapted JIA ACR 30 response, was defined as improvement of 30% or more in at least three of the six core criteria for JIA, worsening of more than 30% in no more than one of the criteria, and resolution of fever. In trial 2, after 32 weeks of open-label treatment with canakinumab, patients who had a response and underwent glucocorticoid tapering were randomly assigned to continued treatment with canakinumab or to placebo. The primary outcome was time to flare of systemic JIA. RESULTS: At day 15 in trial 1, more patients in the canakinumab group had an adapted JIA ACR 30 response (36 of 43 [84%], vs. 4 of 41 [10%] in the placebo group; P<0.001). In trial 2, among the 100 patients (of 177 in the open-label phase) who underwent randomization in the withdrawal phase, the risk of flare was lower among patients who continued to receive canakinumab than among those who were switched to placebo (74% of patients in the canakinumab group had no flare, vs. 25% in the placebo group, according to Kaplan-Meier estimates; hazard ratio, 0.36; P=0.003). The average glucocorticoid dose was reduced from 0.34 to 0.05 mg per kilogram per day, and glucocorticoids were discontinued in 42 of 128 patients (33%). The macrophage activation syndrome occurred in 7 patients; infections were more frequent with canakinumab than with placebo. CONCLUSIONS: These two phase 3 studies show the efficacy of canakinumab in systemic JIA with active systemic features. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT00889863 and NCT00886769.).

Predictors of poor response to methotrexate in polyarticular-course juvenile idiopathic arthritis: analysis of the PRINTO methotrexate trial.

OBJECTIVES: To determine whether baseline demographic, clinical, articular and laboratory variables predict methotrexate (MTX) poor response in polyarticular-course juvenile idiopathic arthritis. METHODS: Patients newly treated for 6 months with MTX enrolled in the Paediatric Rheumatology International Trials Organization (PRINTO) MTX trial. Bivariate and logistic regression analyses were used to identify baseline predictors of poor response according to the American College of Rheumatology pediatric (ACR-ped) 30 and 70 criteria. RESULTS: In all, 405/563 (71.9%) of patients were women; median age at onset and disease duration were 4.3 and 1.4 years, respectively, with anti-nuclear antibody (ANA) detected in 259/537 (48.2%) patients. With multivariate logistic regression analysis, the most important determinants of ACR-ped 70 non-responders were: disease duration > 1.3 years (OR 1.93), ANA negativity (OR 1.77), Childhood Health Assessment Questionnaire (CHAQ) disability index > 1.125 (OR 1.65) and the presence of right and left wrist activity (OR 1.55). Predictors of ACR-ped 30 non-responders were: ANA negativity (OR 1.92), CHAQ disability index > 1.14 (OR 2.18) and a parent's evaluation of child's overall well-being < or = 4.69 (OR 2.2). CONCLUSION: The subgroup of patients with longer disease duration, ANA negativity, higher disability and presence of wrist activity were significantly associated with a poorer response to a 6-month MTX course.

The PRINTO evidence-based proposal for glucocorticoids tapering/discontinuation in new onset juvenile dermatomyositis patients.

BACKGROUND: Prednisone (PDN) in juvenile dermatomyositis (JDM), alone or in association with other immunosuppressive drugs, namely methotrexate (MTX) and cyclosporine (CSA), represents the first-line treatment option for new onset JDM patients. No clear evidence based guidelines are actually available to standardize the tapering and discontinuation of glucocorticoids (GC) in JDM. Aim of our study was to provide an evidence-based proposal for GC tapering/discontinuation in new onset juvenile dermatomyositis (JDM), and to identify predictors of clinical remission and GC discontinuation. METHODS: New onset JDM children were randomized to receive either PDN alone or in combination with methotrexate (MTX) or cyclosporine (CSA). In order to derive steroid tapering indications, PRINTO/ACR/EULAR JDM core set measures (CSM) and their median absolute and relative percent changes over time were compared in 3 groups. Group 1 included those in clinical remission who discontinued PDN, with no major therapeutic changes (MTC) (reference group) and was compared with those who did not achieve clinical remission, without or with MTC (Group 2 and 3, respectively). A logistic regression model identified predictors of clinical remission with PDN discontinuation. RESULTS: Based on the median change in the CSM of 30/139 children in Group 1, after 3 pulses of methyl-prednisolone, GC could be tapered from 2 to 1 mg/kg/day in the first two months from onset if any of the CSM decreased by 50-94%, and from 1 to 0.2 mg/kg/day in the following 4 months if any CSM further decreased by 8-68%, followed by discontinuation in the ensuing 18 months. The achievement of PRINTO JDM 50-70-90 response after 2 months of treatment (ORs range 4.5-6.9), an age at onset > 9 years (OR 4.6) and the combination therapy PDN + MTX (OR 3.6) increase the probability of achieving clinical remission (p < 0.05). CONCLUSIONS: This is the first evidence-based proposal for glucocorticoid tapering/discontinuation based on the change in JDM CSM of disease activity. TRIAL REGISTRATION: Trial full title: Five-Year Single-Blind, Phase III Effectiveness Randomized Actively Controlled Clinical Trial in New Onset Juvenile Dermatomyositis: Prednisone versus Prednisone plus Cyclosporine A versus Prednisone plus Methotrexate. EUDRACT registration number: 2005-003956-37 . CLINICAL TRIAL: gov is NCT00323960 . Registered on 17 August 2005.

Intraoral condition in children with juvenile idiopathic arthritis compared to controls.

AIMS: The aims of this study were to compare the periodontal conditions in children and adolescents with juvenile idiopathic arthritis (JIA) in comparison to age-matched healthy individuals, and to describe intraoral health in relation to medical assessments. DESIGN: Forty-one JIA patients, 10-19 years old, were compared to 41 controls. Plaque, calculus, probing depth, bleeding on probing, clinical attachment loss, as well as mucosal lesions were registered. Marginal bone level was recorded on radiographs. A questionnaire was included. Data were analysed with chi-squared test, Fisher's exact test, and Mann-Whitney U-test (P < 0.05). RESULTS: The JIA patients reported pain from jaws (P = 0.001), hands (P = 0.001), and oral ulcers (P = 0.015) more often than controls. They avoided certain types of food because of oral ulcers (P = 0.037). The frequencies of sites with plaque (32% vs. 19%, P = 0.013), calculus (11% vs. 5%, 5 = 0.034), bleeding on probing (26% vs. 14%, P < 0.01), and probing depth 2 mm (32% vs. 2%, P < 0.001) were higher among JIA patients. No sites with attachment loss or reduced marginal bone level were observed. CONCLUSIONS: These obtained results are probably because of joint pain, making it difficult to perform oral hygiene as well as the use of medication and general disease activity.

Pharmacovigilance in juvenile idiopathic arthritis patients treated with biologic or synthetic drugs: combined data of more than 15,000 patients from Pharmachild and national registries.

BACKGROUND: The availability of methotrexate and the introduction of multiple biological agents have revolutionized the treatment of juvenile idiopathic arthritis (JIA). Several international and national drug registries have been implemented to accurately monitor the long-term safety/efficacy of these agents. This report aims to present the combined data coming from Pharmachild/PRINTO registry and the national registries from Germany (BiKeR) and Sweden. METHODS: Descriptive statistics was used for demographic, clinical data, drug exposure, adverse events (AEs) and events of special interest (ESIs). For the Swedish register, AE data were not available. RESULTS: Data from a total of 15,284 patients were reported: 8274 (54%) from the Pharmachild registry and 3990 (26%) and 3020 (20%) from the German and the Swedish registries, respectively. Pharmachild children showed a younger age (median of 5.4 versus 7.6 years) at JIA onset and shorter disease duration at last available visit (5.3 versus 6.1-6.8) when compared with the other registries. The most frequent JIA category was the rheumatoid factor-negative polyarthritis (range of 24.6-29.9%). Methotrexate (61-84%) and etanercept (24%-61.8%) were the most frequently used synthetic and biologic disease-modifying anti-rheumatic drugs (DMARDs), respectively. There was a wide variability in glucocorticoid use (16.7-42.1%). Serious AEs were present in 572 (6.9%) patients in Pharmachild versus 297 (7.4%) in BiKeR. Infection and infestations were the most frequent AEs (29.4-30.1%) followed by gastrointestinal disorders (11.5-19.6%). The most frequent ESIs were infections (75.3-89%). CONCLUSIONS: This article is the first attempt to present a very large sample of data on JIA patients from different national and international registries and represents the first proposal for data merging as the most powerful tool for future analysis of safety and effectiveness of immunosuppressive therapies in JIA. REGISTRY REGISTRATION: The Pharmachild registry is registered at ClinicalTrials.gov ( NCT01399281 ) and at the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) ( http://www.encepp.eu/encepp/viewResource.htm?id=19362 ). The BiKeR registry is registered at ENCePP ( http://www.encepp.eu/encepp/viewResource.htm?id=20591 ).

A survey of national and multi-national registries and cohort studies in juvenile idiopathic arthritis: challenges and opportunities.

BACKGROUND: To characterize the existing national and multi-national registries and cohort studies in juvenile idiopathic arthritis (JIA) and identify differences as well as areas of potential future collaboration. METHODS: We surveyed investigators from North America, Europe, and Australia about existing JIA cohort studies and registries. We excluded cross-sectional studies. We captured information about study design, duration, location, inclusion criteria, data elements and collection methods. RESULTS: We received survey results from 18 studies, including 11 national and 7 multi-national studies representing 37 countries in total. Study designs included inception cohorts, prevalent disease cohorts, and new treatment cohorts (several of which contribute to pharmacosurveillance activities). Despite numerous differences, the data elements collected across the studies was quite similar, with most studies collecting at least 5 of the 6 American College of Rheumatology core set variables and the data needed to calculate the 3-variable clinical juvenile disease activity score. Most studies were collecting medication initiation and discontinuation dates and were attempting to capture serious adverse events. CONCLUSION: There is a wide-range of large, ongoing JIA registries and cohort studies around the world. Our survey results indicate significant potential for future collaborative work using data from different studies and both combined and comparative analyses.

2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

OBJECTIVE: To develop response criteria for juvenile dermatomyositis (DM). METHODS: We analyzed the performance of 312 definitions that used core set measures from either the International Myositis Assessment and Clinical Studies Group (IMACS) or the Paediatric Rheumatology International Trials Organisation (PRINTO) and were derived from natural history data and a conjoint analysis survey. They were further validated using data from the PRINTO trial of prednisone alone compared to prednisone with methotrexate or cyclosporine and the Rituximab in Myositis (RIM) trial. At a consensus conference, experts considered 14 top candidate criteria based on their performance characteristics and clinical face validity, using nominal group technique. RESULTS: Consensus was reached for a conjoint analysis-based continuous model with a total improvement score of 0-100, using absolute percent change in core set measures of minimal (≥30), moderate (≥45), and major (≥70) improvement. The same criteria were chosen for adult DM/polymyositis, with differing thresholds for improvement. The sensitivity and specificity were 89% and 91-98% for minimal improvement, 92-94% and 94-99% for moderate improvement, and 91-98% and 85-86% for major improvement, respectively, in juvenile DM patient cohorts using the IMACS and PRINTO core set measures. These criteria were validated in the PRINTO trial for differentiating between treatment arms for minimal and moderate improvement (P = 0.009-0.057) and in the RIM trial for significantly differentiating the physician's rating for improvement (P < 0.006). CONCLUSION: The response criteria for juvenile DM consisted of a conjoint analysis-based model using a continuous improvement score based on absolute percent change in core set measures, with thresholds for minimal, moderate, and major improvement.

Diverse effects on vaccine-specific serum IgG titres and memory B cells upon methotrexate and anti-TNF-α therapy in children with rheumatic diseases: A cross-sectional study.

OBJECTIVES: We aimed at a comprehensive evaluation of how anti-TNF-α therapy and methotrexate treatment interferes with B cell memory in children with Paediatric Rheumatic Disease (PRD), by evaluating existing B cell phenotypes, and preserved vaccine-specific memory B cells and IgG titres generated prior to disease and treatment. METHODS: In a cross-sectional study on children with PRD on various treatments, we measured titre levels and avidity strength of serum IgG specific against measles, rubella and tetanus. We also quantified transitional B cells and resting, atypical, and activated memory B cells with flow cytometry, and enumerated antigen-specific memory B cells with ELISpot. RESULTS: For children who had received a tetanus booster, patients treated with any disease-modifying anti-rheumatic drug (DMARD) had lower tetanus serum IgG compared to healthy controls and NSAID-treated patients. Patients without a measles booster had lower levels of measles-specific memory B cells, but all vaccine-specific memory B cells were preserved in patients with booster. We furthermore found that the mature B cell compartment was phenotypically similar between patients and healthy controls. CONCLUSIONS: We concluded that the general and vaccine-specific memory B cell compartment is well preserved in children with PRD and DMARD treatment, but that they might have lower serum tetanus IgG. We emphasize the importance for these children to follow the full vaccination schedule, and suggest to re-measure tetanus titres as they reach adulthood.

Perceived Oral Health and Care of Children with Juvenile Idiopathic Arthritis: A Qualitative Study.

AIMS: To increase knowledge about how children diagnosed with juvenile idiopathic arthritis (JIA) perceive their oral health and dental care. METHODS: Fifteen interviews with children diagnosed with JIA, aged 6 to 16 years, were analyzed according to classical grounded theory. RESULTS: The children's main concern about their oral health was identified as creating a positive identity after being diagnosed with JIA and learning to live with oral health problems. While attempting to cope with this concern, the children often endured in silence, the core category in the analysis. A variety of aspects were found of this core coping strategy, which were categorized as differentiating from the disease, working on personal caretaking and positive attitude, fighting fears and sadness, control of professional aid, and building supportive relationships. The results emphasize the importance for caregivers to show empathy and interest in the child as a person, to ask precise questions when taking case histories so the child does not remain silent, to provide psychosocial support and suggest positive coping strategies, to describe and administer treatments, and to give hope for the future. CONCLUSION: Awareness of the social interaction between a child diagnosed with JIA and health professionals as well as awareness of how to approach a child with longstanding illness are crucial for disclosing and treating the child's orofacial symptoms.

Five-year follow-up of feedback microwave thermotherapy versus TURP for clinical BPH: a prospective randomized multicenter study.

OBJECTIVES: To compare the efficacy and safety of transurethral microwave thermotherapy (TUMT) with ProstaLund Feedback Treatment, using the CoreTherm device, with transurethral resection of the prostate (TURP) 5 years after treatment. METHODS: This prospective, randomized, multicenter study was conducted at 10 centers in the United States and Scandinavia. A total of 154 patients with benign prostatic hyperplasia were randomized to TUMT or TURP in a 2:1 ratio. Patients were followed up at 3, 6, 12, 24, 36, 48, and 60 months after treatment. The intermediate results at 12 and 36 months have been previously reported. The treatment outcome at 5 years was evaluated with the International Prostate Symptom Score (IPSS), quality of life question (QOL), peak urinary flow rate (Qmax), postvoid residual urine volume, and prostate volume. The CoreTherm device differs from other microwave devices in that the intraprostatic temperature is constantly measured during the procedure to guide the treatment. RESULTS: Of the 154 patients, 66% completed the 60 months of follow-up. Statistically significant improvements in the TUMT and TURP groups were observed for IPSS, QOL, and Qmax at 60 months. The average values for the TUMT group were an IPSS of 7.4, QOL score of 1.1, and Qmax of 11.4 mL/s. The values for the TURP group were IPSS of 6.0, QOL score of 1.1, and Qmax of 13.6 mL/s. No statistically significant differences were found in any of these variables between the two treatment groups. In the TUMT group, 10% needed additional treatment versus 4.3% in the TURP group. CONCLUSIONS: The clinical outcome 5 years after TUMT using the CoreTherm device was comparable to the results seen after TURP. The safety of TUMT using the CoreTherm device compared favorably with that of TURP.

Feedback microwave thermotherapy versus TURP for clinical BPH--a randomized controlled multicenter study.

OBJECTIVES: To compare the outcome of a microwave thermotherapy feedback system that is based on intraprostatic temperature measurement during treatment (ProstaLund Feedback Treatment or PLFT) with transurethral resection of the prostate (TURP) for clinical benign prostatic hyperplasia (BPH) in a randomized controlled multicenter study. The safety of the two methods was also investigated. METHODS: The study was performed at 10 centers in Scandinavia and the United States. A total of 154 patients with clinical BPH were randomized to PLFT or TURP (ratio 2:1); 133 of them completed the study and were evaluated at the end of the study 12 months after treatment. Outcome measures included the International Prostate Symptom Score (IPSS), urinary flow, detrusor pressure at maximal urinary flow (Qmax), prostate volume, and adverse events. Patients were seen at 3, 6, and 12 months. Responders were defined according to a combination of IPSS and Qmax: IPSS 7 or less, or a minimal 50% gain, and/or Qmax 15 mL/s or greater or a minimal 50% gain. RESULTS: No significant differences in outcome at 12 months were found between PLFT and TURP for IPSS, Qmax, or detrusor pressure. The prostate volume measured with transrectal ultrasonography was reduced by 30% after PLFT and 51% after TURP. Serious adverse events related to the given treatment were reported in 2% after PLFT and in 17% after TURP. Mild and moderate adverse events were more common in the PLFT group. With the criteria mentioned above, 82% and 86% of the patients were characterized as responders after 12 months in the PLFT and TURP groups, respectively. The post-treatment catheter time was 3 days in the TURP group and 14 days in the PLFT group. CONCLUSIONS: The outcome of microwave thermotherapy with intraprostatic temperature monitoring was comparable with that seen after TURP in this study. From both a simplicity and safety point of view, PLFT appears to have an advantage. Taken together, our findings make us conclude that within a 1-year perspective microwave thermotherapy with PLFT is an attractive alternative to TURP in the treatment of BPH.

Three-year follow-up of feedback microwave thermotherapy versus TURP for clinical BPH: a prospective randomized multicenter study.

OBJECTIVES: To compare, in a prospective randomized multicenter study, the efficacy and safety of transurethral microwave thermotherapy with ProstaLund Feedback Treatment (PLFT), using the CoreTherm device, with transurethral resection of the prostate (TURP) 36 months after treatment. METHODS: The study was conducted at 10 centers in the United States and Scandinavia. A total of 154 patients with benign prostatic hyperplasia were randomized to PLFT or TURP in a 2:1 ratio. The treatment outcome was evaluated on the basis of the International Prostate Symptom Score (IPSS), the quality-of-life question (QOL) of the IPSS, peak urinary flow rate (Qmax), urodynamics, and adverse events. The microwave power and treatment time were adjusted according to each patient's response to the supplied energy (ie, the intraprostatic temperature guided the PLFT). RESULTS: Statistically significant improvements in both the TURP and the PLFT groups were observed for IPSS, QOL, and Qmax at 36 months. The average value for the PLFT group was 8.2, 1.2, and 11.9 mL/s for IPSS, QOL, and Qmax, respectively. The corresponding values for the TURP group were IPSS 5.0, QOL 1.0, and Qmax 13.5 mL/s. The difference in IPSS outcome was statistically significant; however, no statistically significant differences were found in QOL or Qmax between the two treatment groups. The degree of improvement was in the same range as that observed after 12 and 24 months for both groups. During the 12 to 36-month period, the most frequent adverse events in the TURP group were impotence (15%), micturition urgency (13%), and urethral disorder (8%); in the PLFT group, impotence (8%), prostate-specific antigen increase (5%), and hematuria (4%) were the most common. CONCLUSIONS: The clinical outcome 3 years after microwave thermotherapy with PLFT was comparable to the results seen after TURP. The safety of PLFT compared favorably to that of TURP in this study.