CONTEXT: First-generation somatostatin receptor ligands (fg-SRLs) represent the mainstay of medical therapy for acromegaly, but they provide biochemical control of disease in only a subset of patients. Various pretreatment biomarkers might affect biochemical response to fg-SRLs. OBJECTIVE: To identify clinical predictors of the biochemical response to fg-SRLs monotherapy defined as biochemical response (insulin-like growth factor (IGF)-1 ≤ 1.3 × ULN (upper limit of normal)), partial response (>20% relative IGF-1 reduction without normalization), and nonresponse (≤20% relative IGF-1 reduction), and IGF-1 reduction. DESIGN: Retrospective multicenter study. SETTING: Eight participating European centers. METHODS: We performed a meta-analysis of participant data from 2 cohorts (Rotterdam and Liège acromegaly survey, 622 out of 3520 patients). Multivariable regression models were used to identify predictors of biochemical response to fg-SRL monotherapy. RESULTS: Lower IGF-1 concentration at baseline (odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.72-0.95 IGF-1 ULN, P = .0073) and lower bodyweight (OR = 0.99, 95% CI 0.98-0.99 kg, P = .038) were associated with biochemical response. Higher IGF-1 concentration at baseline (OR = 1.40, (1.19-1.65) IGF-1 ULN, P ≤ .0001), the presence of type 2 diabetes (oral medication OR = 2.48, (1.43-4.29), P = .0013; insulin therapy OR = 2.65, (1.02-6.70), P = .045), and higher bodyweight (OR = 1.02, (1.01-1.04) kg, P = .0023) were associated with achieving partial response. Younger patients at diagnosis are more likely to achieve nonresponse (OR = 0.96, (0.94-0.99) year, P = .0070). Baseline IGF-1 and growth hormone concentration at diagnosis were associated with absolute IGF-1 reduction (β = 0.90, standard error (SE) = 0.02, P ≤ .0001 and β  = 0.002, SE = 0.001, P = .014, respectively). CONCLUSION: Baseline IGF-1 concentration was the best predictor of biochemical response to fg-SRL, followed by bodyweight, while younger patients were more likely to achieve nonresponse.

• MeSH
• akromegalie krev   diagnóza   farmakoterapie   MeSH
• biologické markery analýza   metabolismus   MeSH
• biomarkery farmakologické * analýza   metabolismus   MeSH
• cyklické peptidy terapeutické užití   MeSH
• dospělí MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský růstový hormon krev   MeSH
• ligandy MeSH
• multivariační analýza MeSH
• oktreotid terapeutické užití   MeSH
• prognóza MeSH
• receptory somatostatinu agonisté   MeSH
• retrospektivní studie MeSH
• somatostatin analogy a deriváty   terapeutické užití   MeSH
• teoretické modely * MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Effective treatment of acromegaly with pegvisomant (PEGV), a growth hormone receptor antagonist, requires an appropriate dose titration. PEGV doses vary widely among individual patients, and various covariates may affect its dosing and pharmacokinetics. OBJECTIVE: To identify predictors of the PEGV dose required to normalize insulin-like growth factor I (IGF-I) levels during PEGV monotherapy and in combination with long-acting somatostatin analogues (LA-SSAs). DESIGN: Two retrospective cohorts (Rotterdam + Liège Acromegaly Survey (LAS), total n = 188) were meta-analyzed as a form of external replication to study the predictors of PEGV dosing in addition to LA-SSA, the LAS (n = 83) was used to study the predictors of PEGV monotherapy dosing. Multivariable regression models were used to identify predictors of the PEGV dose required to normalize IGF-I levels. RESULTS: For PEGV dosing in combination with LA-SSA, IGF-I levels, weight, height and age, were associated with the PEGV normalization dosage (P ≤ 0.001, P ≤ 0.001, P = 0.028 and P = 0.047 respectively). Taken together, these characteristics predicted the PEGV normalization dose correctly in 63.3% of all patients within a range of ±60 mg/week (21.3% within a range of ±20 mg/week). For monotherapy, only weight was associated with the PEGV normalization dose (P ≤ 0.001) and predicted this dosage correctly in 77.1% of all patients within a range of ±60 mg/week (31.3% within a range of ±20 mg/week). CONCLUSION: In this study, we show that IGF-I levels, weight, height and age can contribute to define the optimal PEGV dose to normalize IGF-I levels in addition to LA-SSA. For PEGV monotherapy, only the patient's weight was associated with the IGF-I normalization PEGV dosage.

• MeSH
• akromegalie krev   farmakoterapie   MeSH
• biologické modely * MeSH
• dospělí MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský růstový hormon aplikace a dávkování   analogy a deriváty   MeSH
• retrospektivní studie MeSH
• somatostatin aplikace a dávkování   analogy a deriváty   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Component-resolved diagnosis (CRD) has revealed significant associations between IgE against individual allergens and severity of hazelnut allergy. Less attention has been given to combining them with clinical factors in predicting severity. AIM: To analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy. METHODS: Patients reporting hazelnut allergy (n = 423) from 12 European cities were tested for IgE against individual hazelnut allergens. Symptoms (reported and during Double-blind placebo-controlled food challenge [DBPCFC]) were categorized in mild, moderate, and severe. Multiple regression models to predict severity were generated from clinical factors and sensitization patterns (CRD- and extract-based). Odds ratios (ORs) and areas under receiver-operating characteristic (ROC) curves (AUCs) were used to evaluate their predictive value. RESULTS: Cor a 9 and 14 were positively (OR 10.5 and 10.1, respectively), and Cor a 1 negatively (OR 0.14) associated with severe symptoms during DBPCFC, with AUCs of 0.70-073. Combining Cor a 1 and 9 improved this to 0.76. A model using a combination of atopic dermatitis (risk), pollen allergy (protection), IgE against Cor a 14 (risk) and walnut (risk) increased the AUC to 0.91. At 92% sensitivity, the specificity was 76.3%, and the positive and negative predictive values 62.2% and 95.7%, respectively. For reported symptoms, associations and generated models proved to be almost identical but weaker. CONCLUSION: A model combining CRD with clinical background and extract-based serology is superior to CRD alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions.

• MeSH
• alergeny imunologie   MeSH
• alergie na ořechy diagnóza   imunologie   MeSH
• antigeny rostlinné imunologie   MeSH
• dvojitá slepá metoda MeSH
• imunoglobulin E krev   MeSH
• lidé MeSH
• líska imunologie   MeSH
• multivariační analýza MeSH
• plocha pod křivkou MeSH
• ROC křivka MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

• MeSH
• lidé MeSH
• psychologické modely MeSH
• psychometrie MeSH
• Check Tag
• lidé MeSH

Cíl Klinický průběh onemocnění pacientů s chronickou lymfocytární leukémií (chronic lymphocytic leukemia, CLL) je velmi variabilní; někteří pacienti mají indolentní onemocnění a nevyžadují žádnou léčbu, zatímco jiní mají agresivní onemocnění vyžadující časné léčení. Zahájení terapie se nadále řídí kritérii pro aktivní onemocnění. Provedli jsme mnohorozměrnou analýzu s cílem určit prognostické faktory spojené nezávisle s dobou do první léčby pacientů s CLL. Pacienti a metody V mnohorozměrné analýze byly vyhodnoceny tradiční laboratorní a klinické prognostické faktory a nové prognostické faktory, jimiž jsou např. fluorescenční hybridizace in situ (fluorescent in situ hybridization, FISH), mutační status IGHV a exprese ZAP-70 vyšetřené při první návštěvě v MD Anderson Cancer Center, s dobou do první léčby. Tento mnohorozměrný model byl použit k sestrojení nomogramu – statisticky váženého nástroje pro výpočet 2leté a 4leté pravděpodobnosti zahájení léčby a mediánu doby do prvního léčení. Výsledky Bylo zjištěno 930 dosud neléčených pacientů, kteří podstoupili vyšetření tradičních a nových prognostických faktorů; pacienti, kteří neměli během 3 měsíců po první návštěvě aktivní CLL vyžadující zahájení léčby, byli pozorováni k zjištění doby do prvního léčení. S kratší dobou do prvního léčení byly nezávisle spojeny následující charakteristiky: tři lokalizace postižených lymfatických uzlin, zvětšení cervikálních krčních uzlin, přítomnost delece 17p nebo delece 11q podle FISH, zvýšená koncentrace laktátdehydrogenázy v séru a mutační status IGHV bez mutace. Závěr Vytvořili jsme mnohorozměrný model, jehož součástí jsou tradiční a novější prognostické faktory, k určení pacientů s vysokým rizikem progrese vyžadující léčbu. Tento model by mohl být užitečný k určení pacientů vhodných pro zařazení do studií časných intervencí.

• MeSH
• časové faktory MeSH
• chronická lymfatická leukemie genetika   metabolismus   terapie   MeSH
• delece genu MeSH
• dospělí MeSH
• hodnocení rizik MeSH
• imunohistochemie MeSH
• Kaplanův-Meierův odhad MeSH
• L-laktátdehydrogenasa genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• multivariační analýza MeSH
• mutace MeSH
• nádorové biomarkery metabolismus   MeSH
• nomogramy MeSH
• odds ratio MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• protein-tyrosinkináza ZAP-70 metabolismus   MeSH
• průtoková cytometrie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• těžké řetězce imunoglobulinů genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Texas MeSH

In comparison with analytical tools, bioassays provide higher sensitivity and more complex evaluation of environmental samples and are indispensable tools for monitoring increasing in anthropogenic pollution. Nevertheless, the disadvantage in cellular assays stems from the material variability used within the assays, and an interlaboratory adaptation does not usually lead to satisfactory test sensitivities. The aim of this study was to evaluate the influence of material variability on CXCL12 secretion by T47D cells, the outcome of the CXCL-test (estrogenic activity assay). For this purpose, the cell line sources, sera suppliers, experimental and seeding media, and the amount of cell/well were tested. The multivariable linear model (MLM), employed as an innovative approach in this field for parameter evaluation, identified that all the tested parameters had significant effects. Knowledge of the contributions of each parameter has permitted step-by-step optimization. The most beneficial approach was seeding 20,000 cells/well directly in treatment medium and using DMEM for the treatment. Great differences in both basal and maximal cytokine secretions among the three tested cell lines and different impacts of each serum were also observed. Altogether, both these biologically based and highly variable inputs were additionally assessed by MLM and a subsequent two-step evaluation, which revealed a lower variability and satisfactory reproducibility of the test. This analysis showed that not only parameter and procedure optimization but also the evaluation methodology must be considered from the perspective of interlaboratory method adaptation. This overall methodology could be applied to all bioanalytical methods for fast multiparameter and accurate analysis.

• MeSH
• biotest MeSH
• buněčné linie MeSH
• chemické látky znečišťující vodu * MeSH
• estrogeny * toxicita   MeSH
• estron MeSH
• lineární modely MeSH
• monitorování životního prostředí metody   MeSH
• reprodukovatelnost výsledků MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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
• biliární cirhóza farmakoterapie   MeSH
• biologické markery analýza   MeSH
• cholagoga a choleretika terapeutické užití   MeSH
• diskriminační analýza MeSH
• interpretace statistických dat MeSH
• kyselina ursodeoxycholová terapeutické užití   MeSH
• lidé MeSH
• lineární modely MeSH
• longitudinální studie MeSH
• počítačová simulace MeSH
• progrese nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PRIMARY OBJECTIVE: To assess predisposing and precipitating risk factors and create a predictive model for post-stroke delirium. RESEARCH DESIGN: A prospective observational study in a cohort of consecutive patients with ischemic stroke or intracerebral haematoma admitted within 24 hours of stroke onset. METHODS: Patients were assessed daily for delirium during the first week by means of DSM-IV criteria and risk factors were recorded. RESULTS: One hundred patients completed a 7-day evaluation (47 women and 53 men, median age 77 years). An episode of delirium was detected in 43 patients (43%). Using multivariate logistic regression, a predictive statistical model was developed that utilized independent risk factors: age (OR = 1.08; 95% CI = 1.02-1.15); intracerebral haemorrhage (OR = 6.11; 95% CI = 1.62-22.98), lesion volume > 40 ccm (OR = 3.99; 95% CI = 1.29-12.39) and either elevated gamma-glytamyl transferase (OR = 4.88; 95% CI = 1.45-16.35) and elevated serum bilirubin (OR = 3.70; 95% CI = 1.32-10.38) or maximum sequential organ failure assessment score >2 (OR = 3.33; 95% CI = 1.06-10.45) with acceptable sensitivity and specificity (69.0% and 80.7%). In ischemic strokes, total anterior circulation infarctions were more frequently associated with delirium (73.3% developed delirium) compared with the remainder of the groups combined (p = 0.004; OR = 6.66; 95% CI = 1.85-24.01). CONCLUSION: Higher age, metabolic disturbances, intracerebral haemorrhage and larger ischemic hemispheric strokes increase the risk of post-stroke delirium.

• MeSH
• bilirubin krev   MeSH
• C-reaktivní protein metabolismus   MeSH
• časové faktory MeSH
• cerebrální krvácení krev   komplikace   patofyziologie   MeSH
• cévní mozková příhoda krev   komplikace   patofyziologie   MeSH
• delirium krev   etiologie   patofyziologie   MeSH
• Diagnostický a statistický manuál mentálních poruch MeSH
• gama-glutamyltransferasa krev   MeSH
• lidé MeSH
• míra přežití MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• teoretické modely MeSH
• věkové faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIMS: To develop and validate a clinically useful risk prediction tool for patients with adult congenital heart disease (ACHD). METHODS AND RESULTS: A risk model was developed in a prospective cohort of 602 patients with moderate/complex ACHD who routinely visited the outpatient clinic of a tertiary care centre in the Netherlands (2011-2013). This model was externally validated in a retrospective cohort of 402 ACHD patients (Czech Republic, 2004-2013). The primary endpoint was the 4-year risk of death, heart failure, or arrhythmia, which occurred in 135 of 602 patients (22%). Model development was performed using multivariable logistic regression. Model performance was assessed with C-statistics and calibration plots. Of the 14 variables that were selected by an expert panel, the final prediction model included age (OR 1.02, 95%CI 1.00-1.03, p = 0.031), congenital diagnosis (OR 1.52, 95%CI 1.03-2.23, p = 0.034), NYHA class (OR 1.74, 95%CI 1.07-2.84, p = 0.026), cardiac medication (OR 2.27, 95%CI 1.56-3.31, p < 0.001), re-intervention (OR 1.41, 95%CI 0.99-2.01, p = 0.060), BMI (OR 1.03, 95%CI 0.99-1.07, p = 0.123), and NT-proBNP (OR 1.63, 95%CI 1.45-1.84, p < 0.001). Calibration-in-the-large was suboptimal, reflected by a lower observed event rate in the validation cohort (17%) than predicted (36%), likely explained by heterogeneity and different treatment strategies. The externally validated C-statistic was 0.78 (95%CI 0.72-0.83), indicating good discriminative ability. CONCLUSION: The proposed ACHD risk score combines six readily available clinical characteristics and NT-proBNP. This tool is easy to use and can aid in distinguishing high- and low-risk patients, which could further streamline counselling, location of care, and treatment in ACHD.

• MeSH
• dospělí MeSH
• hodnocení rizik metody   normy   MeSH
• kohortové studie MeSH
• lidé MeSH
• následné studie MeSH
• prediktivní hodnota testů MeSH
• prospektivní studie MeSH
• reprodukovatelnost výsledků MeSH
• teoretické modely * MeSH
• vrozené srdeční vady diagnostické zobrazování   epidemiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Nizozemsko MeSH

BACKGROUND: To identify predictors of survival in patients treated with docetaxel chemotherapy for castration-resistant prostate cancer (CRPC). METHODS: We retrospectively analyzed clinical data from 186 patients who underwent docetaxel chemotherapy for CRPC from 2005 to 2016 at a single center. Pretreatment baseline variables including demographic and clinicopathological data were reviewed. Disease progression was defined by imaging and/or consecutive prostate-specific antigen (PSA) elevation. The systemic immune-inflammation index (SII), the modified Glasgow Prognostic Score (mGPS), and the neutrophil-lymphocyte ratio (NLR) were calculated. Univariable and multivariable Cox proportional hazards regression analyses reporting hazard ratios assessed the risk for disease progression and overall survival (OS). A survival nomogram was constructed. RESULTS: Most patients (n = 139, 74.7%) completed at least 6 cycles of docetaxel chemotherapy. 156 patients (82.9%) experienced disease progression during the studied period. Only mGPS was independently associated with disease progression in a multivariable model (P < 0.01). During the studied period, 98 patients (52.1%) died. The built survival nomogram included statistically significant variables for OS in univariable analysis: hemoglobin, PSA, alkaline phosphatase (AP), lactate dehydrogenase, SII, neutrophil-lymphocyte ratio, mGPS, and site of metastases; and had a concordance index of 0.703. At decision curve analysis, the nomogram led to superior outcomes for any decision associated with a threshold probability of above 40%. In multivariable analysis, only AP (P = 0.02), hemoglobin and PSA (P < 0.01, respectively) remained associated with OS. CONCLUSIONS: PSA, AP, and hemoglobin are independent prognosticators for OS. Although mGPS is a promising marker for tumor progression and SII is a plausible prognostic marker for OS, valid integration of inflammatory indices into a prognostic model requires validation studies. Predictive and prognostic biomarkers are desperately needed to guide physicians in treatment counseling given the heterogeneous nature of CRPC and the plethora of effective therapies.

• MeSH
• časové faktory MeSH
• docetaxel terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory prostaty rezistentní na kastraci farmakoterapie   mortalita   MeSH
• prognóza MeSH
• protinádorové látky terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• statistické modely MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH