BACKGROUND: We aimed to evaluate the predictors of sustainability of biologic drugs for paediatric patients with Crohn's disease (CD). METHODS: The Czech National Prospective Registry of Biologic and Targeted Therapy of Inflammatory Bowel Disease (CREdIT) was used to identify the biologic treatment courses in paediatric patients with CD. Mixed-effects Cox models and propensity score analyses were employed to evaluate predictors of treatment sustainability. RESULTS: Among the 558 observations of 473 patients, 264 were treated with adalimumab (47%), 240 with infliximab (43%), 41 with ustekinumab (7%), and 13 with vedolizumab (2%). Multivariable analysis revealed higher discontinuation risk with infliximab compared to adalimumab (HR = 0.600, 95%CI 0.389-0.926), both overall and in first-line treatment (HR = 0.302, 95%CI 0.103-0.890). Infliximab versus adalimumab was associated with shorter time to escalation (HR = 0.094, 95%CI 0.043-0.203). Propensity-score analysis demonstrated lower sustainability of infliximab (HR = 0.563, 95%CI 1.159-2.725). The time since diagnosis to treatment initiation (HR = 0.852, 95%CI 0.781-0.926) was the most important predictor. Baseline immunosuppressive therapy prolonged sustainability with infliximab (HR = 2.899, 95%CI 1.311-6.410). CONCLUSIONS: Given the results suggesting shorter sustainability, the need for earlier intensification and thus higher drug exposure, and the greater need for immunosuppression with infliximab than with adalimumab, the choice of these drugs cannot be considered completely equitable. IMPACT: Our study identified predictors of sustainability of biologic treatment in paediatric patients with Crohn's disease, including adalimumab (versus infliximab), early initiation of biologic treatment, and normalised baseline haemoglobin levels. Infliximab treatment was associated with earlier intensification, higher drug exposure, and a greater need for immunosuppression. Parents and patients should be fully informed of the disadvantages of intravenous infliximab versus adalimumab during the decision-making process. This study emphasises the importance of not delaying the initiation of biologic therapy in paediatric patients with Crohn's disease.

• MeSH
• adalimumab * terapeutické užití   MeSH
• biologické přípravky terapeutické užití   MeSH
• Crohnova nemoc * farmakoterapie   MeSH
• dítě MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• infliximab * terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• registrace * MeSH
• tendenční skóre MeSH
• ustekinumab terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Narativní přehledový článek se zabývá tematikou predikace a prevence zánětlivých střevních onemocnění (IBD). Při stále se zvyšující celkové incidenci, nízké přirozené mortalitě a zvyšující se délce dožití lze předpokládat, že prevalence brzy dosáhne 1 %. Vzhledem k nákladům na léčbu tak IBD představují, a do budoucna stále více budou, velký zdravotní problém. Díky pokrokům v porozumění některých mechanizmů při rozvoji IBD se začíná zlepšovat jejich predikce. To otvírá nové pole pro případné terapeutické zásahy ještě v době, kdy se obraz IBD plně nerozvine. Jsou popsány některé zásadní predikční modely a teoreticky je pojednáno o některých již běžících a budoucích možných preventivních programech.

This narrative review summarizes data on prediction and prevention of inflammatory bowel disease (IBD). With increasing incidence, low natural mortality and increasing life expectancy, we can expect IBD that prevalence will soon reach about 1%. This in combination with high therapeutic costs means that IBD represent a significant health problem, which is expected to increase in the near future. The identification of IBD development mechanisms has led to an increasing prediction accuracy. This is opening a new field for therapeutic interventions in early stages of IBD development. We describe some of the essential prediction models and prevention programs that are under way or could be introduced in future.

• MeSH
• idiopatické střevní záněty * genetika   imunologie   prevence a kontrola   MeSH
• lidé MeSH
• prevalence MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH

Studies showing a substantial frequency of dermatologic complications in paediatric Crohn's disease (CD) patients on anti-tumour necrosis factor (TNF) therapy preferentially include patients treated with infliximab. We aimed to identify risk factors for the cumulative incidence of skin complications in a paediatric cohort receiving either adalimumab or infliximab and found an association between current skin complications and the patient's current clinical condition. This study retrospectively evaluated dermatologic complications in an inception cohort of 100 paediatric CD patients receiving the first anti-TNF (Motol PIBD cohort). Patient data were collected every 3 months. The lesions were classified as psoriatic, atopic dermatitis, or others. We used Cox regression to evaluate the association between predefined variables and the time to complication and a generalised linear mixed model to assess the association between the patient's current condition and the occurrence of complications. Among the 89 included children, 35 (39%) presented with dermatologic lesions. The only predictor associated with any complication was infliximab (versus adalimumab) therapy (hazard ratio [HR]: 2.07; 95% confidence interval [CI]: 1.03-4.17; p = 0.04). Infliximab therapy (HR: 5.5; 95%CI: 1.59-19.06; p = 0.01) and a family history of atopy (HR: 3.4; 95%CI 1.35-8.57, p = 0.002) were associated with early manifestation of atopic dermatitis. Lower C-reactive protein levels (odds ratio [OR], 0.947; 95% CI, - 0.898 to 0.998; p = 0.046) and infliximab (versus adalimumab) were associated with the occurrence of any dermatologic complications (OR, 5.93; 95% CI, 1.59-22.07; p = 0.008).Conclusion: The frequency of skin complications seems high in paediatric CD patients treated with anti-TNF and is even higher in those treated with infliximab. What is Known: •The dermatologic complications occur during treatment with anti-tumour necrosis factor. •The frequency of skin complications in paediatric patients with Crohn's disease is high. What is New: •Infliximab (vs. adalimumab) was identified as a strong risk factor for the cumulative incidence of skin complications. •Lower C-reactive protein levels were associated with the current occurrence of dermatologic complications.

• MeSH
• Crohnova nemoc * komplikace   farmakoterapie   MeSH
• dítě MeSH
• infliximab škodlivé účinky   MeSH
• inhibitory TNF * MeSH
• lidé MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• TNF-alfa MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The numbers of coronavirus disease 2019 (COVID-19) deaths per million people differ widely across countries. Often, the causal effects of interventions taken by authorities are unjustifiably concluded based on the comparison of pure mortalities in countries where interventions consisting different strategies have been taken. Moreover, the possible effects of other factors are only rarely considered. METHODS: We used data from open databases (European Centre for Disease Prevention and Control, World Bank Open Data, The BCG World Atlas) and publications to develop a model that could largely explain the differences in cumulative mortality between countries using non-interventional (mostly socio-demographic) factors. RESULTS: Statistically significant associations with the logarithmic COVID-19 mortality were found with the following: proportion of people aged 80 years and above, population density, proportion of urban population, gross domestic product, number of hospital beds per population, average temperature in March and incidence of tuberculosis. The final model could explain 67% of the variability. This finding could also be interpreted as follows: less than a third of the variability in logarithmic mortality differences could be modified by diverse non-pharmaceutical interventions ranging from case isolation to comprehensive measures, constituting case isolation, social distancing of the entire population and closure of schools and borders. CONCLUSIONS: In particular countries, the number of people who will die from COVID-19 is largely given by factors that cannot be drastically changed as an immediate reaction to the pandemic and authorities should focus on modifiable variables, e.g. the number of hospital beds.

• MeSH
• COVID-19 mortalita   MeSH
• dospělí MeSH
• HIV infekce epidemiologie   MeSH
• hrubý domácí produkt MeSH
• hustota populace MeSH
• incidence MeSH
• komorbidita MeSH
• kouření epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• městské obyvatelstvo statistika a číselné údaje   MeSH
• mladiství MeSH
• nadváha epidemiologie   MeSH
• obložnost MeSH
• pandemie prevence a kontrola   MeSH
• poskytování zdravotní péče organizace a řízení   MeSH
• prevalence MeSH
• SARS-CoV-2 * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• socioekonomické faktory MeSH
• teplota MeSH
• tuberkulóza epidemiologie   MeSH
• věkové rozložení MeSH
• veřejné zdravotnictví MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

• Publikační typ
• abstrakt z konference MeSH

OBJECTIVES: Therapeutic drug monitoring of thiopurine erythrocyte levels is not available in all centers and it usually requires quite a long time to obtain the results. The aims of this study were to build a model predicting low levels of 6-thioguanine and 6-methylmercaptopurine in pediatric inflammatory bowel disease (IBD) patients and to build a model to predict nonadherence in patients treated with azathioprine (AZA). METHODS: The study consisted of 332 observations in 88 pediatric IBD patients. Low AZA dosing was defined as 6-thioguanine levels <125 pmol/8 × 10 erythrocytes and 6-methylmercaptopurine levels <5700 pmol/8 × 10 erythrocytes. Nonadherence was defined as undetectable levels of 6-thioguanine and 6-methylmercaptopurine <240 pmol/8 × 10 erythrocytes. Data were divided into training and testing part. To construct the model predicting low 6-thioguanine levels, nonadherence, and the level of 6-thioguanine, the modification of random forest method with cross-validation and resampling was used. RESULTS: The final models predicting low 6-thioguanine levels and nonadherence had area under the curve, 0.87 and 0.94; sensitivity, 0.81 and 0.82; specificity, 0.80 and 86; and distance, 0.31 and 0.21, respectively, when applied on the testing part of the dataset. When the final model for prediction of 6-thioguanine values was applied on testing dataset, a root-mean-square error of 110 was obtained. CONCLUSIONS: Using easily obtained laboratory parameters, we constructed a model with sufficient accuracy to predict patients with low 6-thioguanine levels and a model for prediction of AZA treatment nonadherence (web applications: https://hradskyo.shinyapps.io/6TG_prediction/ and https://hradskyo.shinyapps.io/Non_adherence/).

• MeSH
• adherence k farmakoterapii * MeSH
• biologické modely MeSH
• dítě MeSH
• erytrocyty metabolismus   MeSH
• idiopatické střevní záněty krev   farmakoterapie   metabolismus   MeSH
• imunosupresiva aplikace a dávkování   farmakokinetika   terapeutické užití   MeSH
• lidé MeSH
• merkaptopurin aplikace a dávkování   analogy a deriváty   farmakokinetika   terapeutické užití   MeSH
• mladiství MeSH
• monitorování léčiv MeSH
• plocha pod křivkou MeSH
• prediktivní hodnota testů MeSH
• senzitivita a specificita MeSH
• thioguanin metabolismus   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH

• MeSH
• Crohnova nemoc terapie   MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• idiopatické střevní záněty * diagnóza   genetika   terapie   MeSH
• lidé MeSH
• management nemoci MeSH
• ulcerózní kolitida terapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• přehledy MeSH

• Publikační typ
• komentáře MeSH

BACKGROUND: Inflammatory bowel diseases (IBD) are associated with altered bone health and increased risk for fractures. Vitamin D deficiency is frequently found in IBD; however, the effect of vitamin D supplementation on bone health of children with IBD is poorly understood. We aimed to observe the changes in volumetric bone density and dynamic muscle functions after vitamin D substitution in a cohort of pediatric patients with IBD. METHODS: This was a prospective observational study of 55 patients (aged 5-19 years) with IBD. Bone quality was assessed using peripheral quantitative computed tomography and muscle functions by jumping mechanography at baseline and after a median of 13.8 (interquartile range, 12.0-16.0) months of daily substitution of 2000 IU of cholecalciferol. RESULTS: Median serum levels of 25-hydroxyvitamin D increased from 58 nmol/L at the baseline visit to 85 nmol/L at the last follow-up visit (P < 0.001); no signs of overdose were reported. The Z-scores of trabecular bone mineral density, cortical bone cross-sectional area, and maximal muscle power improved significantly during the follow-up period (+0.5, P = 0.001, +0.3, P = 0.002 and +0.5, P = 0.002, respectively). Cholecalciferol substitution was positively associated with trabecular bone mineral density and maximal muscle power (estimates 0.26, 95% confidence interval 0.14-0.37, P < 0.0001 and 0.60, 95% confidence interval 0.32-0.85, P < 0.0001, respectively) but not with the Strength-Strain Index or maximal muscle force (Fmax). CONCLUSIONS: We observed an improvement in bone and muscle parameters after cholecalciferol substitution in pediatric patients with IBD. Therefore, vitamin D substitution can be considered in such patients.

• MeSH
• cholekalciferol aplikace a dávkování   MeSH
• dítě MeSH
• idiopatické střevní záněty patofyziologie   terapie   MeSH
• inhibitory kostní resorpce aplikace a dávkování   MeSH
• kostní denzita účinky léků   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• potravní doplňky * MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• svalová síla účinky léků   MeSH
• trabekulární kostní tkáň účinky léků   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

• MeSH
• dietoterapie metody   MeSH
• fytoterapie MeSH
• idiopatické střevní záněty * dietoterapie   terapie   MeSH
• interakce bylin a léků MeSH
• komplementární terapie * metody   MeSH
• léčivé rostliny MeSH
• lidé MeSH
• pohybová aktivita MeSH
• Check Tag
• lidé MeSH