OBJECTIVE: Juvenile systemic sclerosis (SSc) is an orphan disease, associated with high morbidity and mortality. New treatment strategies are much needed, but clearly defining appropriate outcomes is necessary if successful therapies are to be developed. Our objective here was to propose such outcomes. METHODS: This proposal is the result of 4 face-to-face consensus meetings with a 27-member multidisciplinary team of pediatric rheumatologists, adult rheumatologists, dermatologists, pediatric cardiologists, pulmonologists, gastroenterologists, a statistician, and patients. Throughout the process, we reviewed the existing adult data in this field, the more limited pediatric literature for juvenile SSc outcomes, and data from 2 juvenile SSc patient cohorts to assist in making informed, data-driven decisions. The use of items for each domain as an outcome measure in an open label 12-month clinical trial of juvenile SSc was voted and agreed upon using a nominal group technique. RESULTS: After voting, the domains agreed on were global disease activity, skin, Raynaud's phenomenon, digital ulcers, musculoskeletal, cardiac, pulmonary, renal, and gastrointestinal involvement, and quality of life. Fourteen outcome measures had 100% agreement, 1 item had 91% agreement, and 1 item had 86% agreement. The domains of biomarkers and growth/development were moved to the research agenda. CONCLUSION: We reached consensus on multiple domains and items that should be assessed in an open label, 12-month clinical juvenile SSc trial as well as a research agenda for future development.

• MeSH
• dítě MeSH
• dospělí MeSH
• konsensus MeSH
• kvalita života MeSH
• lidé MeSH
• Raynaudova nemoc * farmakoterapie   MeSH
• systémová sklerodermie * diagnóza   farmakoterapie   komplikace   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVES: A third paediatric report has been generated from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). The purpose of EUROMACS, which is operated by the European Association for Cardio-Thoracic Surgery, is to gather data related to durable mechanical circulatory support for scientific purposes and to publish reports with respect to the course of mechanical circulatory support therapy. Since the first report issued, efforts to increase compliance and participation have been extended. Additionally, the data provided the opportunity to analyse patients of younger age and lower weight. METHODS: Participating hospitals contributed pre-, peri- and long-term postoperative data on mechanical circulatory support implants to the registry. Data for all implants in paediatric patients (<19 years of age) performed from 1 January 2000 to 31 December 2020 were analysed. This report includes updates of patient characteristics, implant frequency, outcome (including mortality rates, transplants and recovery rates) as well as adverse events including neurological dysfunction, device malfunction, major infection and bleeding. RESULTS: Twenty-five hospitals contributed 537 registered implants in 480 patients. The most frequent aetiology of heart failure was any form of cardiomyopathy (59%), followed by congenital heart disease and myocarditis (15% and 14%, respectively). Competing outcomes analysis revealed that a total of 86% survived to transplant or recovery or are ongoing; at the 2-year follow-up examination, 21.9% died while on support. At 12 months, 45.1% received transplants, 7.5% were weaned from their device and 20.8% died. The 3-month adverse events rate was 1.59 per patient-year for device malfunction including pump exchange, 0.7 for major bleeding, 0.78 for major infection and 0.71 for neurological events. CONCLUSIONS: The overall survival rate was 79.2% at 12 months following ventricular assist device implant. The comparison of survival rates of the early and later eras shows no significant difference. A focus on specific subgroups showed that survival was less in patients of younger age (<1 year of age; P = 0.01) and lower weight (<20 kg; P = 0.015). Transplant rates at 6 months continue to be low (33.2%).

• MeSH
• dítě MeSH
• hrudní chirurgické výkony * MeSH
• lidé MeSH
• podpůrné srdeční systémy * škodlivé účinky   MeSH
• registrace MeSH
• retrospektivní studie MeSH
• srdeční selhání * epidemiologie   etiologie   chirurgie   MeSH
• vrozené srdeční vady * epidemiologie   chirurgie   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: During the initial 26-week SPARK (Safety Paediatric efficAcy phaRmacokinetic with Kuvan®) study, addition of sapropterin dihydrochloride (Kuvan®; a synthetic formulation of the natural cofactor for phenylalanine hydroxylase, tetrahydrobiopterin; BH4), to a phenylalanine (Phe)-restricted diet, led to a significant improvement in Phe tolerance versus a Phe-restricted diet alone in patients aged 0-4 years with BH4-responsive phenylketonuria (PKU) or mild hyperphenylalaninaemia (HPA). Based on these results, the approved indication for sapropterin in Europe was expanded to include patients < 4 years of age. Herein, we present results of the SPARK extension study (NCT01376908), evaluating the long-term safety, dietary Phe tolerance, blood Phe concentrations and neurodevelopmental outcomes in patients < 4 years of age at randomisation, over an additional 36 months of treatment with sapropterin. RESULTS: All 51 patients who completed the 26-week SPARK study period entered the extension period. Patients who were previously treated with a Phe-restricted diet only ('sapropterin extension' group; n = 26), were initiated on sapropterin at 10 mg/kg/day, which could be increased up to 20 mg/kg/day. Patients previously treated with sapropterin plus Phe-restricted diet, remained on this regimen in the extension period ('sapropterin continuous' group; n = 25). Dietary Phe tolerance increased significantly at the end of the study versus baseline (week 0), by 38.7 mg/kg/day in the 'sapropterin continuous' group (95% CI 28.9, 48.6; p < 0.0001). In the 'sapropterin extension' group, a less pronounced effect was observed, with significant differences versus baseline (week 27) only observed between months 9 and 21; dietary Phe tolerance at the end of study increased by 5.5 mg/kg/day versus baseline (95% CI - 2.8, 13.8; p = 0.1929). Patients in both groups had normal neuromotor development and growth parameters. CONCLUSIONS: Long-term treatment with sapropterin plus a Phe-restricted diet in patients who initiated sapropterin at < 4 years of age with BH4-responsive PKU or mild HPA maintained improvements in dietary Phe tolerance over 3.5 years. These results continue to support the favourable risk/benefit profile for sapropterin in paediatric patients (< 4 years of age) with BH4-responsive PKU. Frequent monitoring of blood Phe levels and careful titration of dietary Phe intake to ensure adequate levels of protein intake is necessary to optimise the benefits of sapropterin treatment. Trial registration ClinicalTrials.gov, NCT01376908. Registered 17 June 2011, https://clinicaltrials.gov/ct2/show/NCT01376908 .

• MeSH
• biopteriny analogy a deriváty   terapeutické užití   MeSH
• dítě MeSH
• fenylalanin MeSH
• fenylalaninhydroxylasa * MeSH
• fenylketonurie * farmakoterapie   MeSH
• lidé MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

INTRODUCTION: Since the beginning of COVID-19 pandemic, it is known that the severe course of the disease occurs mostly among the elderly, whereas it is rare among children and young adults. Comorbidities, in particular, diabetes and hypertension, clearly associated with age, besides obesity and smoke, are strongly associated with the need for intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Thus, there is concern that children treated for cancer may allso be at risk for an unfavourable course of infection. Along the same line, anecdotal information from Wuhan, China, mentioned a severe course of COVID-19 in a child treated for leukaemia. AIM AND METHODS: We made a flash survey on COVID-19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short Web-based survey. RESULTS: We received reports from 25 countries, where approximately 10,000 patients at risk are followed up. At the time of the survey, more than 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease, and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken and treatment options in immunocompromised children with COVID-19. CONCLUSION: Thus, even children receiving anticancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than that observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment.

• MeSH
• antitumorózní látky terapeutické užití   MeSH
• Betacoronavirus * MeSH
• dítě MeSH
• koronavirové infekce komplikace   farmakoterapie   MeSH
• lidé MeSH
• mladiství MeSH
• nádory komplikace   farmakoterapie   MeSH
• pandemie MeSH
• průzkumy a dotazníky MeSH
• virová pneumonie komplikace   farmakoterapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Treosulfan-based conditioning prior to allogeneic transplantation has been shown to have myeloablative, immunosuppressive, and antineoplastic effects associated with reduced non-relapse mortality (NRM) in adults. Therefore, we prospectively evaluated the safety and efficacy of treosulfan-based conditioning in children with hematological malignancies in this phase II trial. Overall, 65 children with acute lymphoblastic leukemia (35.4%), acute myeloid leukemia (44.6%), myelodysplastic syndrome (15.4%), or juvenile myelomonocytic leukemia (4.6%) received treosulfan intravenously at a dose of 10 mg/m2/day (7.7%), 12 g/m2/day (35.4%), or 14 g/m2/day (56.9%) according to their individual body surface area in combination with fludarabine and thiotepa. The incidence of complete donor chimerism at day +28 was 98.4% with no primary and only one secondary graft failure. At 36 months, NRM was only 3.1%, while relapse incidence was 21.7%, and overall survival was 83.0%. The cumulative incidence of acute graft-vs.-host disease was 45.3% for grades I-IV and 26.6% for grades II-IV. At 36 months, 25.8% overall and 19.4% moderate/severe chronic graft-vs.-host disease were reported. These data confirm the safe and effective use of treosulfan-based conditioning in pediatric patients with hematological malignancies. Therefore, treosulfan/fludarabine/thiotepa can be recommended for myeloablative conditioning in children with hematological malignancies.

• MeSH
• busulfan analogy a deriváty   MeSH
• dítě MeSH
• hematologické nádory * terapie   MeSH
• lidé MeSH
• nemoc štěpu proti hostiteli * MeSH
• příprava pacienta k transplantaci * MeSH
• thiotepa MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• vidarabin analogy a deriváty   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Background: Vedolizumab, an anti-integrin antibody, has proven to be effective in adults with inflammatory bowel disease [IBD], but the data in paediatrics are limited. We describe the short-term effectiveness and safety of vedolizumab in a European multi-centre paediatric IBD cohort. Method: Retrospective review of children [aged 2-18 years] treated with vedolizumab from 19 centres affiliated with the Paediatric IBD Porto group of ESPGHAN. Primary outcome was Week 14 corticosteroid-free remission [CFR]. Results: In all, 64 children were included (32 [50%] male, mean age 14.5 ± 2.8 years, with a median follow-up 24 weeks [interquartile range 14-38; range 6-116]); 41 [64%] cases of ulcerative colitis/inflammatory bowel disease unclassified [UC/IBD-U] and 23 [36%] Crohn's disease [CD]. All were previously treated with anti-tumour necrosis factor [TNF] [28% primary failure, 53% secondary failure]. Week 14 CFR was 37% in UC, and 14% in CD [P = 0.06]. CFR by last follow-up was 39% in UC and 24% in CD [p = 0.24]. Ten [17%] children required surgery, six of whom had colectomy for UC. Concomitant immunomodulatory drugs did not affect remission rate [42% vs 35%; p = 0.35 at Week 22]. There were three minor drug-related adverse events. Only 3 of 16 children who underwent endoscopic evaluation had mucosal healing after treatment (19%). Conclusions: Vedolizumab was safe and effective in this cohort of paediatric refractory IBD. These data support previous findings of slow induction rate of vedolizumab in CD and a trend to be less effective compared with patients with UC.

• MeSH
• Crohnova nemoc farmakoterapie   MeSH
• dítě MeSH
• humanizované monoklonální protilátky škodlivé účinky   terapeutické užití   MeSH
• idiopatické střevní záněty farmakoterapie   MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• ulcerózní kolitida farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

PURPOSE: There is disregard in the scientific literature for the evaluation of psychiatric in-patient care as rated directly by patients. In this context, we aimed to explore satisfaction of people treated in mental health in-patient facilities. The project was a part of the Young Psychiatrist Program by the Association for the Improvement of Mental Health Programmes. METHODS: This is an international multicentre cross-sectional study conducted in 25 hospitals across 11 countries. The research team at each study site approached a consecutive target sample of 30 discharged patients to measure their satisfaction using the five-item study-specific questionnaire. Individual and institution level correlates of 'low satisfaction' were examined by comparisons of binary and multivariate associations in multilevel regression models. RESULTS: A final study sample consisted of 673 participants. Total satisfaction scores were highly skewed towards the upper end of the scale, with a median total score of 44 (interquartile range 38-48) out of 50. After taking clustering into account, the only independent correlates of low satisfaction were schizophrenia diagnosis and low psychiatrist to patient ratio. CONCLUSION: Further studies on patients' satisfaction should additionally pay attention to treatment expectations formed by the previous experience of treatment, service-related knowledge, stigma and patients' disempowerment, and power imbalance.

• MeSH
• dospělí MeSH
• duševní poruchy terapie   MeSH
• internacionalita MeSH
• lidé středního věku MeSH
• lidé MeSH
• propuštění pacienta MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• spokojenost pacientů statistika a číselné údaje   MeSH
• ústavy pro duševně nemocné * MeSH
• víceúrovňová analýza MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: Sapropterin dihydrochloride, a synthetic formulation of BH4, the cofactor for phenylalanine hydroxylase (PAH, EC 1.14.16.1), was initially approved in Europe only for patients ≥4 years with BH4-responsive phenylketonuria. The aim of the SPARK (Safety Paediatric efficAcy phaRmacokinetic with Kuvan®) trial was to assess the efficacy (improvement in daily phenylalanine tolerance, neuromotor development and growth parameters), safety and pharmacokinetics of sapropterin dihydrochloride in children <4 years. RESULTS: In total, 109 male or female children <4 years with confirmed BH4-responsive phenylketonuria or mild hyperphenylalaninemia and good adherence to dietary treatment were screened. 56 patients were randomly assigned (1:1) to 10 mg/kg/day oral sapropterin plus a phenylalanine-restricted diet or to only a phenylalanine-restricted diet for 26 weeks (27 to the sapropterin and diet group and 29 to the diet-only group; intention-to-treat population). Of these, 52 patients with ≥1 pharmacokinetic sample were included in the pharmacokinetic analysis, and 54 patients were included in the safety analysis. At week 26 in the sapropterin plus diet group, mean phenylalanine tolerance was 30.5 (95% confidence interval 18.7-42.3) mg/kg/day higher than in the diet-only group (p < 0.001). The safety profile of sapropterin, measured monthly, was acceptable and consistent with that seen in studies of older children. Using non-linear mixed effect modelling, a one-compartment model with flip-flop pharmacokinetic behaviour, in which the effect of weight was substantial, best described the pharmacokinetic profile. Patients in both groups had normal neuromotor development and stable growth parameters. CONCLUSIONS: The addition of sapropterin to a phenylalanine-restricted diet was well tolerated and led to a significant improvement in phenylalanine tolerance in children <4 years with BH4-responsive phenylketonuria or mild hyperphenylalaninemia. The pharmacokinetic model favours once per day dosing with adjustment for weight. Based on the SPARK trial results, sapropterin has received EU approval to treat patients <4 years with BH4-responsive phenylketonuria. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01376908 . Registered June 17, 2011.

• MeSH
• algoritmy MeSH
• biopteriny aplikace a dávkování   analogy a deriváty   metabolismus   terapeutické užití   MeSH
• dieta metody   MeSH
• fenylalanin aplikace a dávkování   krev   MeSH
• fenylalaninhydroxylasa metabolismus   MeSH
• fenylketonurie krev   dietoterapie   farmakoterapie   MeSH
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

• MeSH
• antiarytmika terapeutické užití   MeSH
• atrioventrikulární blokáda diagnostické zobrazování   farmakoterapie   mortalita   MeSH
• dexamethason aplikace a dávkování   MeSH
• digoxin terapeutické užití   MeSH
• flekainid terapeutické užití   MeSH
• hydrops fetalis epidemiologie   farmakoterapie   MeSH
• komorová tachykardie diagnostické zobrazování   epidemiologie   MeSH
• lidé MeSH
• nemoci plodu * diagnostické zobrazování   mortalita   terapie   MeSH
• plod MeSH
• síňové extrasystoly diagnostické zobrazování   epidemiologie   MeSH
• supraventrikulární tachykardie diagnostické zobrazování   farmakoterapie   MeSH
• ultrasonografie prenatální MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

OBJECTIVE: To evaluate the safety and effectiveness of novel biodegradable (BD) stents to treat bronchial anastomotic stenosis in patients after lung transplantation. METHODS: Twenty BD stents were implanted endoscopically in six patients (median age 41.5 years (range 35-57 years)) with post-transplant bronchial anastomotic stenoses, between 2006 and 2010. All stents were custom-made from bio-absorbable polydioxanone (PDS). The median stent diameter was 12 mm (8-17 mm) and median length was 20mm (12-30 mm). All patients were evaluated clinically, by bronchoscopy and high-definition computed tomography (CT). RESULTS: The stenosis was initially relieved in all cases. There was no bleeding, perforation or displacement after BD stent implantation. Four patients needed multiple stenting for anastomotic re-stenosis. Median time to any re-stenting was 5 months (2-15 months). There was one sudden death, 1 year after the last BD stent implantation, from a pulmonary embolus. All five survivors are in good clinical condition up to 4 years' follow-up (median 40 months, range 7-48 months) since first stenting and intervention-free up to 44 months (median 24 months, range 7-44 months). CONCLUSIONS: This small pilot study shows that BD stents are a safe, effective and reliable alternative to classical metallic stents in patients with anastomotic stenosis after lung transplantation, and may avoid the need for permanent stenting.

• MeSH
• anastomóza chirurgická škodlivé účinky   MeSH
• bronchiální nemoci etiologie   chirurgie   MeSH
• bronchoskopie MeSH
• dospělí MeSH
• epidemiologické metody MeSH
• lidé středního věku MeSH
• lidé MeSH
• obstrukce dýchacích cest etiologie   chirurgie   MeSH
• polydioxanon MeSH
• protézy - design MeSH
• stenóza etiologie   chirurgie   MeSH
• stenty MeSH
• transplantace plic škodlivé účinky   MeSH
• vstřebatelné implantáty MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH