• MeSH
• diagnóza počítačová MeSH
• diferenciální diagnóza MeSH
• jaterní cirhóza diagnóza   MeSH
• nemoci jater diagnóza   MeSH
• rozhodování MeSH

• MeSH
• kauzalita MeSH
• pravděpodobnost MeSH

• Konspekt
• Přírodní vědy. Matematické vědy
• NLK Obory
• přírodní vědy
• statistika, zdravotnická statistika

Models based on ordinary differential equations (ODE) are widespread tools for describing dynamical systems. In biomedical sciences, data from each subject can be sparse making difficult to precisely estimate individual parameters by standard non-linear regression but information can often be gained from between-subjects variability. This makes natural the use of mixed-effects models to estimate population parameters. Although the maximum likelihood approach is a valuable option, identifiability issues favour Bayesian approaches which can incorporate prior knowledge in a flexible way. However, the combination of difficulties coming from the ODE system and from the presence of random effects raises a major numerical challenge. Computations can be simplified by making a normal approximation of the posterior to find the maximum of the posterior distribution (MAP). Here we present the NIMROD program (normal approximation inference in models with random effects based on ordinary differential equations) devoted to the MAP estimation in ODE models. We describe the specific implemented features such as convergence criteria and an approximation of the leave-one-out cross-validation to assess the model quality of fit. In pharmacokinetics models, first, we evaluate the properties of this algorithm and compare it with FOCE and MCMC algorithms in simulations. Then, we illustrate NIMROD use on Amprenavir pharmacokinetics data from the PUZZLE clinical trial in HIV infected patients.

• MeSH
• algoritmy MeSH
• Bayesova věta MeSH
• HIV infekce farmakoterapie   MeSH
• karbamáty farmakokinetika   MeSH
• klinické zkoušky jako téma MeSH
• látky proti HIV farmakokinetika   MeSH
• lidé MeSH
• monitorování léčiv přístrojové vybavení   metody   MeSH
• pravděpodobnostní funkce MeSH
• reprodukovatelnost výsledků MeSH
• software * MeSH
• statistické modely MeSH
• sulfonamidy farmakokinetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Head and neck squamous cell carcinomas (HNSCCs) are a molecularly, histologically, and clinically heterogeneous set of tumors originating from the mucosal epithelium of the oral cavity, pharynx, and larynx. This heterogeneous nature of HNSCC is one of the main contributing factors to the lack of prognostic markers for personalized treatment. The aim of this study was to develop and identify multi-omics markers capable of improved risk stratification in this highly heterogeneous patient population. METHODS: In this retrospective study, we approached this issue by establishing radiogenomics markers to identify high-risk individuals in a cohort of 127 HNSCC patients. Hybrid in vivo imaging and whole-exome sequencing were employed to identify quantitative imaging markers as well as genetic markers on pathway-level prognostic in HNSCC. We investigated the deductibility of the prognostic genetic markers using anatomical and metabolic imaging using positron emission tomography combined with computed tomography. Moreover, we used statistical and machine learning modeling to investigate whether a multi-omics approach can be used to derive prognostic markers for HNSCC. RESULTS: Radiogenomic analysis revealed a significant influence of genetic pathway alterations on imaging markers. A highly prognostic radiogenomic marker based on cellular senescence was identified. Furthermore, the radiogenomic biomarkers designed in this study vastly outperformed the prognostic value of markers derived from genetics and imaging alone. CONCLUSION: Using the identified markers, a clinically meaningful stratification of patients is possible, guiding the identification of high-risk patients and potentially aiding in the development of effective targeted therapies.

• MeSH
• dlaždicobuněčné karcinomy hlavy a krku diagnostické zobrazování   genetika   MeSH
• genetické markery MeSH
• hodnocení rizik MeSH
• lidé MeSH
• nádory hlavy a krku * diagnostické zobrazování   genetika   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• spinocelulární karcinom * patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• komentáře MeSH

• MeSH
• biometrie MeSH
• epidemiologické metody MeSH
• epidemiologie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• epidemiologie

BACKGROUND: Simultaneous comparisons of multiple disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS) over an extended follow-up are lacking. Here we emulate a randomised trial simultaneously comparing the effectiveness of six commonly used therapies over 5 years. METHODS: Data from 74 centres in 35 countries were sourced from MSBase. For each patient, the first eligible intervention was analysed, censoring at change/discontinuation of treatment. The compared interventions included natalizumab, fingolimod, dimethyl fumarate, teriflunomide, interferon beta, glatiramer acetate and no treatment. Marginal structural Cox models (MSMs) were used to estimate the average treatment effects (ATEs) and the average treatment effects among the treated (ATT), rebalancing the compared groups at 6-monthly intervals on age, sex, birth-year, pregnancy status, treatment, relapses, disease duration, disability and disease course. The outcomes analysed were incidence of relapses, 12-month confirmed disability worsening and improvement. RESULTS: 23 236 eligible patients were diagnosed with RRMS or clinically isolated syndrome. Compared with glatiramer acetate (reference), several therapies showed a superior ATE in reducing relapses: natalizumab (HR=0.44, 95% CI=0.40 to 0.50), fingolimod (HR=0.60, 95% CI=0.54 to 0.66) and dimethyl fumarate (HR=0.78, 95% CI=0.66 to 0.92). Further, natalizumab (HR=0.43, 95% CI=0.32 to 0.56) showed a superior ATE in reducing disability worsening and in disability improvement (HR=1.32, 95% CI=1.08 to 1.60). The pairwise ATT comparisons also showed superior effects of natalizumab followed by fingolimod on relapses and disability. CONCLUSIONS: The effectiveness of natalizumab and fingolimod in active RRMS is superior to dimethyl fumarate, teriflunomide, glatiramer acetate and interferon beta. This study demonstrates the utility of MSM in emulating trials to compare clinical effectiveness among multiple interventions simultaneously.

• MeSH
• dimethyl fumarát terapeutické užití   MeSH
• fingolimod hydrochlorid terapeutické užití   MeSH
• glatiramer acetát terapeutické užití   MeSH
• imunosupresiva terapeutické užití   MeSH
• interferon beta terapeutické užití   MeSH
• lidé MeSH
• natalizumab terapeutické užití   MeSH
• recidiva MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   MeSH
• roztroušená skleróza * farmakoterapie   MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

"Candidatus Neoehrlichia mikurensis" is the tick-borne agent of neoehrlichiosis, an infectious disease that primarily affects immunocompromised patients. So far, the genetic variability of "Ca. Neoehrlichia" has been studied only by comparing 16S rRNA genes and groEL operon sequences. We describe the development and use of a multilocus sequence analysis (MLSA) protocol to characterize the genetic diversity of clinical "Ca. Neoehrlichia" strains in Europe and their relatedness to other species within the Anaplasmataceae family. Six genes were selected: ftsZ, clpB, gatB, lipA, groEL, and 16S rRNA. Each MLSA locus was amplified by real-time PCR, and the PCR products were sequenced. Phylogenetic trees of MLSA locus relatedness were constructed from aligned sequences. Blood samples from 12 patients with confirmed "Ca. Neoehrlichia" infection from Sweden (n = 9), the Czech Republic (n = 2), and Germany (n = 1) were analyzed with the MLSA protocol. Three of the Swedish strains exhibited identical lipA sequences, while the lipA sequences of the strains from the other nine patients were identical to each other. One of the Czech strains had one differing nucleotide in the clpB sequence from the sequences of the other 11 strains. All 12 strains had identical sequences for the genes 16S rRNA, ftsZ, gatB, and groEL. According to the MLSA, among the Anaplasmataceae, "Ca. Neoehrlichia" is most closely related to Ehrlichia ruminantium, less so to Anaplasma phagocytophilum, and least to Wolbachia endosymbionts. To conclude, three sequence types of infectious "Ca. Neoehrlichia" were identified: one in the west of Sweden, one in the Czech Republic, and one spread throughout Europe.

• MeSH
• Anaplasmataceae klasifikace   genetika   izolace a purifikace   MeSH
• esenciální geny MeSH
• fylogeneze MeSH
• genetická variace * MeSH
• genotyp * MeSH
• infekce bakteriemi čeledi Anaplasmataceae epidemiologie   mikrobiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• molekulární epidemiologie metody   MeSH
• multilokusová sekvenční typizace metody   MeSH
• RNA ribozomální 16S genetika   MeSH
• senioři MeSH
• shluková analýza MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Německo MeSH
• Švédsko MeSH

• MeSH
• klinické zkoušky jako téma MeSH
• lékařská onkologie MeSH
• statistika jako téma MeSH
• Publikační typ
• příručky MeSH

• NLK Obory
• statistika, zdravotnická statistika
• onkologie

• MeSH
• fylogeneze MeSH
• kosti zápěstní anatomie a histologie   krevní zásobení   růst a vývoj   MeSH
• lidé MeSH
• osteogeneze MeSH
• vývojová biologie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• klinické zkoušky jako téma MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• diagnostika