We have developed a method to longitudinally classify subjects into two or more prognostic groups using longitudinally observed values of markers related to the prognosis. We assume the availability of a training data set where the subjects' allocation into the prognostic group is known. The proposed method proceeds in two steps as described earlier in the literature. First, multivariate linear mixed models are fitted in each prognostic group from the training data set to model the dependence of markers on time and on possibly other covariates. Second, fitted mixed models are used to develop a discrimination rule for future subjects. Our method improves upon existing approaches by relaxing the normality assumption of random effects in the underlying mixed models. Namely, we assume a heteroscedastic multivariate normal mixture for random effects. Inference is performed in the Bayesian framework using the Markov chain Monte Carlo methodology. Software has been written for the proposed method and it is freely available. The methodology is applied to data from the Dutch Primary Biliary Cirrhosis Study.

• MeSH
• Liver Cirrhosis, Biliary drug therapy   MeSH
• Biomarkers analysis   MeSH
• Cholagogues and Choleretics therapeutic use   MeSH
• Discriminant Analysis MeSH
• Data Interpretation, Statistical MeSH
• Ursodeoxycholic Acid therapeutic use   MeSH
• Humans MeSH
• Linear Models MeSH
• Longitudinal Studies MeSH
• Computer Simulation MeSH
• Disease Progression MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Bacteria with a reduced susceptibility against antimicrobials pose a major threat to public health. Therefore, large programs have been set up to collect minimum inhibition concentration (MIC) values. These values can be used to monitor the distribution of the nonsusceptible isolates in the general population. Data are collected within several countries and over a number of years. In addition, the sampled bacterial isolates were not tested for susceptibility against one antimicrobial, but rather against an entire range of substances. Interest is therefore in the analysis of the joint distribution of MIC data on two or more antimicrobials, while accounting for a possible effect of covariates. In this regard, we present a Bayesian semiparametric density estimation routine, based on multivariate Gaussian mixtures. The mixing weights are allowed to depend on certain covariates, thereby allowing the user to detect certain changes over, for example, time. The new approach was applied to data collected in Europe in 2010, 2012, and 2013. We investigated the susceptibility of Escherichia coli isolates against ampicillin and trimethoprim, where we found that there seems to be a significant increase in the proportion of nonsusceptible isolates. In addition, a simulation study was carried out, showing the promising behavior of the proposed method in the field of antimicrobial resistance.

• MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Drug Resistance, Bacterial * MeSH
• Bayes Theorem MeSH
• Drug Monitoring * MeSH
• Multivariate Analysis MeSH
• Models, Theoretical MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

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 * therapeutic use   MeSH
• Biological Products therapeutic use   MeSH
• Crohn Disease * drug therapy   MeSH
• Child MeSH
• Antibodies, Monoclonal, Humanized therapeutic use   MeSH
• Infliximab * therapeutic use   MeSH
• Humans MeSH
• Adolescent MeSH
• Proportional Hazards Models MeSH
• Prospective Studies MeSH
• Registries * MeSH
• Propensity Score MeSH
• Ustekinumab therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

An adverse prognostic impact of statin use in lymphoma was first suspected from in vitro data showing an impairment of anti-CD20 antibody binding. However, further clinical studies suggested an improved outcome associated with their use in hematological malignancies. In particular, a survival benefit was reported for patients with follicular lymphoma on statins. Our objective was to assess the outcome of follicular lymphoma patients treated in the PRIMA study with immunochemotherapy according to the use of statins. Among the 1,217 patients enrolled in the PRIMA study, 1,135 were included in the present study. Concomitant treatments at registration were available for all patients. Among those 1,135 patients, 119 were on statins (10.5%) at diagnosis. Adverse events frequencies, event-free survival (EFS), time to next lymphoma treatment (TTNLT), time to next chemotherapy (TTNCT), and overall survival (OS) were evaluated according to the use of statins. The rates of overall and specific cardiovascular adverse events between the two groups of patients were comparable both during induction and maintenance. Outcome in terms of response rates or EFS, TTNLT, TTNCT, and OS were similar regardless of the use of statins (P = 0.57, P = 0.85, P = 0.30, and P = 0.43, respectively) in univariate analysis and after further adjustments for potential confounding factors in multivariate analysis. In conclusion, statin use does not impact the prognosis of patients with follicular lymphoma treated with immunochemotherapy.

• MeSH
• Adult MeSH
• Lymphoma, Follicular diagnosis   drug therapy   mortality   MeSH
• Cohort Studies MeSH
• Drug Interactions MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Young Adult MeSH
• Prognosis MeSH
• Proportional Hazards Models MeSH
• Antineoplastic Combined Chemotherapy Protocols adverse effects   therapeutic use   MeSH
• Randomized Controlled Trials as Topic MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects   therapeutic use   MeSH
• Neoplasm Grading MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Only 50% of patients with relapsed Hodgkin lymphoma (HL) can be cured with intensive induction chemotherapy, followed by high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). Based on the results of the HDR2 trial two courses of DHAP and subsequent HDCT/ASCT are the current standard of care in relapsed HL. In order to assess the prognostic relevance of DHAP dose density, we performed a retrospective multivariate analysis of the HDR2 trial (N=266). In addition to four risk factors (early or multiple relapse, stage IV disease or anemia at relapse, and grade IV hematotoxicity during the first cycle of DHAP) a delayed start of the second cycle of DHAP>day 22 predicted a significantly poorer progression-free survival (PFS, p=0.0356) and overall survival (OS, p=0.0025). In conclusion, our analysis strongly suggests that dose density of DHAP has a relevant impact on the outcome of relapsed HL patients.

• MeSH
• Radiotherapy, Adjuvant MeSH
• Cisplatin adverse effects   therapeutic use   MeSH
• Cytarabine adverse effects   therapeutic use   MeSH
• Dexamethasone adverse effects   therapeutic use   MeSH
• Adult MeSH
• Hodgkin Disease drug therapy   mortality   pathology   MeSH
• Combined Modality Therapy MeSH
• Middle Aged MeSH
• Humans MeSH
• Retreatment MeSH
• Prognosis MeSH
• Proportional Hazards Models MeSH
• Antineoplastic Combined Chemotherapy Protocols adverse effects   therapeutic use   MeSH
• Recurrence MeSH
• Neoplasm Staging MeSH
• Hematopoietic Stem Cell Transplantation MeSH
• Treatment Outcome MeSH
• Salvage Therapy MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Geographicals
• Germany MeSH

• MeSH
• Software MeSH

• Conspectus
• Lékařské vědy. Lékařství
• NML Fields
• lékařská informatika

The aim was to estimate the impacts of invasive Impatiens parviflora on forests' herbal layer communities. A replicated Before-After-Control-Impact field experiment and comparisons with adjacent uninvaded plots were used. The alien's impact on species richness was tested using hierarchical generalized mixed effect models with Poisson error structure. Impact on species composition was tested using multivariate models (DCA, CCA, RDA) and Monte-Carlo permutation tests. Removal plots did not differ in native species richness from neither invaded nor adjacent uninvaded plots, both when the treatment's main effect or its interaction with sampling time was tested (Chi(2) = 0.4757, DF = 2, p = 0.7883; Chi(2) = 7.229, DF = 8, p = 0.5121 respectively). On the contrary, ordination models revealed differences in the development of plots following the treatments (p = 0.034) with the invaded plots differing from the adjacent uninvaded (p = 0.002). Impatiens parviflora is highly unlikely to impact native species richness of invaded communities, which may be associated with its limited ability to create a dense canopy, a modest root system or the fact the I. parviflora does not represent a novel and distinctive dominant to the invaded communities. Concerning its potential impacts on species composition, the presence of native clonal species (Athyrium filix-femina, Dryopteris filix-mas, Fragaria moschata, Luzula luzuloides, Poa nemoralis) on the adjacent uninvaded plots likely makes them different from the invaded plots. However, these competitive and strong species are more likely to prevent the invasion of I. parviflora on the adjacent uninvaded plots rather than being themselves eliminated from the invaded communities.

• MeSH
• Models, Biological MeSH
• Species Specificity MeSH
• Impatiens growth & development   MeSH
• Biota MeSH
• Trees growth & development   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH

• MeSH
• Computer Systems MeSH
• Statistics as Topic MeSH

• Conspectus
• Statistika
• NML Fields
• statistika, zdravotnická statistika
• lékařská informatika

• MeSH
• Longitudinal Studies MeSH
• Multivariate Analysis MeSH
• Regression Analysis MeSH

• Conspectus
• Statistika
• NML Fields
• statistika, zdravotnická statistika

Cíl: Hodnocení léčebných výsledků, radiační toxicity a prognostických faktorů ovlivňujících délku přežití bez progrese u pacientů s nízkostupňovými gliomy ozářených na gama noži. Soubor a metodika: Celkově 88 pacientů jsme ozářili na gama noži hypofrakcionačním režimem. Medián minimální aplikované dávky do plánovacího cílového objemu byl 25 Gy (12–35). Předepsaná minimální dávka byla zohledněna následujícími faktory: počtem frakcí, předchozí radioterapií, plánovacím cílovým objemem (PTV) a věkem. Radiační toxicita a závažnost příznaků (neurological functional class, NFC) byla hodnocena systémem RTOG/EORTC. Ve skupině pacientů jsme sledovali několik faktorů ovlivňujících přežití bez progrese (PFS) po léčbě a radiační toxicitu (stupeň nádoru, věk, objem, biologicky efektivní dávku, předchozí radioterapie, závažnost neurologických příznaků před ozářením). Užili jsme univariační (Kaplan-Meier s Log-rank testem) a multivariační analýzu (Coxovu regresi) k detekci rozdílů v křivkách přežití a k detekci faktorů spojených s toxicitou. Výsledky: Desetileté přežití bez progrese bylo zaznamenáno u 78 % pacientů. Dle očekávání jsme detekovali vyšší procento déle přežívajících bez progrese u pacientů s histopatologickým stupněm I (5leté přežití 91 %, 10leté přežití 88 %) než u pacientů s histopatologickým stupňem II (5leté přežití 79 %, 10leté 67 %); p = 0,010 Log-rank; p = 0,025 Cox). Ze zmíněných faktorů byly jako příznivé detekovány: věk < 30 let (p = 0,044 Log-rank), BED 85–110 Gy, tj. prostřední kategorie (p = 0,019 Log-rank), bez předchozího ozáření (p = 0,032 Log-rank; p = 0,075 Cox). Ve skupině jsme zaznamenali toxicitu stupeň 3 u 10 % případů. Z analyzovaných faktorů nebyl ve vztahu ke komplikacím žádný statisticky signifikantní. Závěry: Ozáření na gama noži může být léčbou pro objemově vhodné recidivy či rezidua nízkostupňových gliomů s relativně dlouhodobým příznivým léčebným efektem.

Objective: To evaluate treatment results, radiation-related toxicity and prognostic factors for progression free survival (PFS) in patients with low-grade glioma irradiated by Leksell Gamma Knife. Materials and methods: A total of 88 patients underwent hypofractionated stereotactic irradiation to treat low-grade glioma. The median minimum applied dose to the planning target volume (PTV) was 25 Gy (12–35). The dosage was prescribed with respect to the several conditions: number of fractions, previous irradiation, planning target volume and age. The radiation toxicity and severity of symptoms (neurological functional class [NFC]) were evaluated according to the RTOG/EORTC system. We analyzed variables affecting progression-free survival (PFS) after treatment and radiation-induced late toxicity (grade, age, volume, biologically effective dose, previous radiotherapy, NFC score before treatment). We used univariate analysis (Kaplan-Meier with log-rank test) and multivariate analysis (Cox regression) to detect differences in survival curves, as well as correlation analysis to detect variables associated with toxicity. Results: 10-year PFS was 78%. As expected, we found a greater surviving proportion among grade I patients, (91% surviving at 5 years, 88% at 10 years) than grade II patients (79% surviving at 5 years, 67% at 10 years), p = 0.010 log-rank, p = 0.025 Cox. Among the other variables we detected as significant positive prognostic factors: age < 30 years (p = 0.044 log-rank), BED 85–110 Gy, which is an intermediate category, (p = 0.019 log-rank), and not previously irradiated (p = 0.032 log-rank, p = 0.075 Cox). In our group of patients we observed grade 3 late toxicity in 10% of cases. Among the variables analyzed we found none associated with incidence of toxicity. Conclusion: Radiosurgery is a treatment modality for small residual or reoccurrence volumes of low-grade glioma with relatively long-term local control.

• MeSH
• Glioma diagnosis   classification   radiotherapy   MeSH
• Evaluation Studies as Topic MeSH
• Humans MeSH
• Meta-Analysis as Topic MeSH
• Disease-Free Survival MeSH
• Prognosis MeSH
• Disease Progression MeSH
• Radiosurgery methods   utilization   MeSH
• Statistics as Topic MeSH
• Stereotaxic Techniques instrumentation   utilization   MeSH
• Outcome and Process Assessment, Health Care MeSH
• Check Tag
• Humans MeSH