Survival analysis is commonly conducted in medical and public health research to assess the association of an exposure or intervention with a hard end outcome such as mortality. The Cox (proportional hazards) regression model is probably the most popular statistical tool used in this context. However, when the exposure includes compositional covariables (that is, variables representing a relative makeup such as a nutritional or physical activity behaviour composition), some basic assumptions of the Cox regression model and associated significance tests are violated. Compositional variables involve an intrinsic interplay between one another which precludes results and conclusions based on considering them in isolation as is ordinarily done. In this work, we introduce a formulation of the Cox regression model in terms of log-ratio coordinates which suitably deals with the constraints of compositional covariates, facilitates the use of common statistical inference methods, and allows for scientifically meaningful interpretations. We illustrate its practical application to a public health problem: the estimation of the mortality hazard associated with the composition of daily activity behaviour (physical activity, sitting time and sleep) using data from the U.S. National Health and Nutrition Examination Survey (NHANES).

• Klíčová slova
• Cox regression, NHANES, Survival analysis, accelerometry, compositional data, physical activity, sedentary behaviour, time use,
• MeSH
• cvičení * MeSH
• proporcionální rizikové modely MeSH
• regresní analýza MeSH
• výživa - přehledy MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• metody MeSH
• mortalita MeSH
• regresní analýza * MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

Previous studies suggested that increased activity of haem oxygenase 1 may ameliorate autoimmune neuroinflammation in experimental models of multiple sclerosis. This increased activity is associated with an augmented number of GT repeats (≥ 25) within the HMOX1 gene promoter. Here we examined 338 patients with multiple sclerosis to determine the influence of their HMOX1 gene promoter (GT)n polymorphism and other individual characteristics on the course of the disease. The patients were divided into those with "rapid" or "delayed" course, based on reaching expanded disability status scale step 4 within nine years of disease onset, and the correlations between the disease course and the investigated characteristics were sought using logistic regression analysis. No statistically significant effect of HMOX1 gene promoter (GT)n polymorphism on the rate of disability progression was found (P = 0.9). This was confirmed by Cox regression analysis, which did not find any difference in the cumulative risk of reaching expanded disability status scale step 4 between the patients with long and short HMOX1 gene promoter (P = 0.7). In contrast, covariates significantly associated with the faster disability progression were: progressive course of multiple sclerosis, shorter duration of disease-modifying treatment and older age at disease onset (P ≤ 0.04). The observed absence of effect of the HMOX1 promoter (GT)n polymorphism could be attributed to its known dualistic role in the pathogenesis of autoimmune disorders. As a secondary outcome, we have seen that disease-modifying drugs have the potential to delay disability progression in patients with multiple sclerosis.

• MeSH
• autoimunitní nemoci genetika   MeSH
• časové faktory MeSH
• dospělí MeSH
• genetické markery MeSH
• hemoxygenasa-1 genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• prognóza MeSH
• progrese nemoci MeSH
• promotorové oblasti (genetika) * MeSH
• proporcionální rizikové modely MeSH
• regresní analýza MeSH
• roztroušená skleróza genetika   metabolismus   MeSH
• věk při počátku nemoci MeSH
• zánět MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• genetické markery MeSH
• hemoxygenasa-1 MeSH

OBJECTIVES: Evidence suggests a positive effect of metformin on cancer incidence and outcome. To date, the effect of metformin use on prognosis in urothelial carcinoma of the bladder (UCB) remains uninvestigated. We tested the hypothesis that metformin use affects oncologic outcomes of patients treated with radical cystectomy for UCB. METHODS AND MATERIALS: We retrospectively evaluated 1,502 patients treated at 4 institutions with radical cystectomy and pelvic lymphadenectomy without neoadjuvant therapy. Cox regression models addressed the association of diabetes mellitus (DM) and metformin use with disease recurrence, cancer-specific mortality, and any-cause mortality. RESULTS: A total of 200 patients (13.3%) had DM, 80 patients (5.3%) used metformin. Within a median follow-up of 34 months, 509 patients (33.9%) experienced disease recurrence, 402 patients (26.8%) died of UCB, and 551 patients (36.7%) died from any cause. In univariable Cox regression analyses, DM without metformin use was associated with increased risk of disease recurrence (hazard ratio [HR]: 1.40, 95% confidence interval [CI] 1.05-1.87, P = 0.02), cancer-specific mortality (HR: 1.60, 95% CI 1.17-2.17, P = 0.003), and any-cause mortality (HR: 1.55, 95% CI 1.18-2.03, P = 0.002), whereas metformin use was associated with decreased risk of disease recurrence (HR: 0.61, 95% CI 0.37-0.98, P = 0.04), cancer-specific mortality (HR: 0.56, 95% CI 0.33-0.97, P = 0.04), and any-cause mortality (HR: 0.54, 95% CI 0.33-0.88, P = 0.01). In multivariable Cox regression analyses, DM treated without metformin use remained associated with worse cancer-specific mortality (HR: 1.53, 95% CI 1.12-2.09, P = 0.007) and any-cause mortality (HR: 1.52, 95% CI 1.16-2.00, P = 0.003) but not disease recurrence. CONCLUSIONS: Diabetic patients who do not use metformin appear to be at higher risk of cancer-specific and any-cause mortality than patients without DM. It remains unclear, whether the severity of DM in this group of patients or the use of metformin itself affects outcomes of UCB. The mechanisms behind the effect of DM on patients with UCB and the potential protective effect of metformin need further elucidation.

• Klíčová slova
• Bladder cancer, Diabetes mellitus, Metformin, Outcomes, Radical cystectomy,
• MeSH
• cystektomie metody   MeSH
• diabetes mellitus farmakoterapie   MeSH
• hodnocení výsledků zdravotní péče metody   statistika a číselné údaje   MeSH
• hypoglykemika terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• karcinom z přechodných buněk mortalita   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• lymfadenektomie MeSH
• metformin terapeutické užití   MeSH
• míra přežití MeSH
• nádory močového měchýře mortalita   chirurgie   MeSH
• následné studie MeSH
• pánev MeSH
• příčina smrti MeSH
• proporcionální rizikové modely MeSH
• regresní analýza MeSH
• rizikové faktory MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• hypoglykemika MeSH
• metformin MeSH

BACKGROUND: The effects of antiretroviral therapy on risk of severe bacterial infections in people with high CD4 cell counts have not been well described. In this study, we aimed to quantify the effects of immediate versus deferred ART on the risk of severe bacterial infection in people with high CD4 cell counts in a preplanned analysis of the START trial. METHODS: The START trial was a randomised controlled trial in ART-naive HIV-positive patients with CD4 cell count of more than 500 cells per μL assigned to immediate ART or deferral until their CD4 cell counts were lower than 350 cells per μL. We used Cox proportional hazards regression to model time to severe bacterial infection, which was defined as a composite endpoint of bacterial pneumonia (confirmed by the endpoint review committee), pulmonary or extrapulmonary tuberculosis, or any bacterial infectious disorder of grade 4 severity, that required unscheduled hospital admissions, or caused death. This study is registered with ClinicalTrials.gov, number NCT00867048. FINDINGS: Patients were recruited from April 15, 2009, to Dec 23, 2013. The data cutoff for follow-up was May 26, 2015. Of 4685 HIV-positive people enrolled, 120 had severe bacterial infections (immediate-initiation group n=34, deferred-initiation group n=86; median 2·8 years of follow-up). Immediate ART was associated with a reduced risk of severe bacterial infection compared with deferred ART (hazard ratio [HR] 0·39, 95% CI 0·26-0·57, p<0·0001). In the immediate-initiation group, average neutrophil count over follow-up was 321 cells per μL higher, and average CD4 cell count 194 cells per μL higher than the deferred-initiation group (p<0·0001). In univariable analysis, higher time-updated CD4 cell count (0·78, 0·71-0·85, p=0·0001) was associated with reduced risk of severe bacterial infection. Time-updated neutrophil count was not associated with severe bacterial infection. After adjustment for time-updated factors in multivariable analysis, particularly the CD4 cell count, the HR for immediate-initiation group moved closer to 1 (HR 0·84, 0·50-1·41, p=0·52). These results were consistent when subgroups of the severe bacterial infection composite were analysed separately. INTERPRETATION: Immediate ART reduces the risk of several severe bacterial infections in HIV-positive people with high CD4 cell count. This is partly explained by ART-induced increases in CD4 cell count, but not by increases in neutrophil count. FUNDING: National Institute of Allergy and Infectious Diseases National Institutes of Health, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales, Bundesministerium für Bildung und Forschung, European AIDS Treatment Network, Australian National Health and Medical Research Council, UK National Institute for Health Research and Medical Research Council, Danish National Research Foundation.

• MeSH
• bakteriální infekce epidemiologie   imunologie   MeSH
• bakteriální pneumonie epidemiologie   MeSH
• dospělí MeSH
• HIV infekce komplikace   farmakoterapie   imunologie   virologie   MeSH
• látky proti HIV škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• oportunní infekce doprovázející AIDS epidemiologie   MeSH
• počet CD4 lymfocytů * MeSH
• proporcionální rizikové modely MeSH
• regresní analýza MeSH
• rozvrh dávkování léků MeSH
• tuberkulóza epidemiologie   MeSH
• virová nálož MeSH
• vysoce aktivní antiretrovirová terapie * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Austrálie MeSH
• Názvy látek
• látky proti HIV MeSH

UNLABELLED: The aim of our study was to clarify whether the CD44 adhesion molecule as a cancer stem cell marker could also serve as a prognostic factor in patients with epithelial ovarian cancer (EOC). A retrospective study was performed on 87 patients with histologically verified EOC. Specimens of both primary tumour and implantation metastases were tested from 48 of them. CD44 expression was detected by immunohistochemistry. We looked for the cut-off levels of CD44 expression using the Cox regression model. We confirmed statistically significant prognostic factors for overall survival (OS) and disease-free interval (DFI) to be: stage of the disease, postoperative residual tumour and papillary serous histological type. We demonstrated a statistically significant correlation between low CD44 expression and serous papillary carcinoma histotype, tumour recurrence and chemoresistance at a value below 2%. CD44 was neither a prognostic factor of OS nor of DFI. IMPACT STATEMENT What is already known about this subject: Epithelial ovarian cancer is the second most common gynaecological cancer in developed countries. Despite great efforts devoted to ovarian cancer research during past decades, levels of patient mortality have changed very little. Cancer stem cells (CSCs) are subpopulations of cells with typical characteristics of stem cells - i.e. the ability to self-renew and differentiate in a variety of cell types. The main surface marker typical for CSCs is CD44. The aim of our study was to clarify whether the CD44 as a CSCs marker could serve as a prognostic factor in patients with epithelial ovarian cancer. Previous studies published on this topic revealed controversial results. The novelty of our study lies in looking for the cut-off using the Cox regression model. WHAT THIS STUDY ADDS: We demonstrated a statistically significant correlation between low CD44 expression and serous papillary carcinoma histotype, tumour recurrence and chemoresistance at a value below 2%, however, CD44 was neither a prognostic factor of overall survival nor of disease-free interval. We propose to investigate other markers including other CSCs as a prognostic factors or potential aims for targeted therapy in ovarian cancer.

• Klíčová slova
• CD44, cancer stem cells, epithelial ovarian cancer,
• MeSH
• antigeny CD44 analýza   metabolismus   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• karcinom metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery analýza   metabolismus   MeSH
• nádorové kmenové buňky metabolismus   MeSH
• nádory glandulární a epitelové metabolismus   patologie   MeSH
• nádory vaječníků metabolismus   patologie   MeSH
• ovarium patologie   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• regresní analýza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• Názvy látek
• antigeny CD44 MeSH
• CD44 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH

BACKGROUND: This study had two aims: to describe patients suffering from first-episode schizophrenia who had stopped taking any antipsychotic medication, and to gain information on the predictors of successful discontinuation. METHODS: We investigated data from the European First Episode Schizophrenia Trial (EUFEST). From the 325 patients included, 15.7% discontinued all antipsychotic medication. In a first analysis, clinical and sociodemographical predictors of discontinuing any antipsychotic medication were identified, using Cox regression. In the second analysis, logistic regression was used to determine variables associated with those patients who had stopped taking antipsychotic medication and had a favourable outcome, i.e., successful discontinuation. A good outcome was defined as a) having had no relapse within the whole observation period (80.6%), and b) having had no relapse and symptomatic remission at 12-month-follow-up (37.2%). RESULTS: Cox regression revealed that a higher proportion of patients from Western European countries and Israel stopped antipsychotic medication than from Central and Eastern European countries, that relapse was associated with discontinuation, and that discontinuers had lower compliance and higher quality of life. Predictors of successful discontinuation differed with the outcome definition used. Using definition b), successful discontinuers had a better baseline prognosis and better baseline social integration. Using definition a), successful discontinuers more often were from Western European countries. CONCLUSIONS: Region and clinical factors were associated with discontinuation. Prognosis and social integration played an important role in predicting successful discontinuation. As this study had several limitations, for example the observational design regarding discontinuation, further studies are needed to identify predictors of successful discontinuation.

• Klíčová slova
• Antipsychotic medication, First episode, Predictors, Prospective studies, Schizophrenia,
• MeSH
• akutní nemoc MeSH
• antipsychotika terapeutické užití   MeSH
• dospělí MeSH
• interview psychologický MeSH
• lidé MeSH
• logistické modely MeSH
• mladiství MeSH
• mladý dospělý MeSH
• následné studie MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• schizofrenie diagnóza   farmakoterapie   MeSH
• ukončení terapie pacientem * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Izrael MeSH
• Názvy látek
• antipsychotika MeSH

AIM: To perform a comparative analysis of clinicopathological correlations of cyclooxygenase-2 (COX-2) expression in pancreatic cancer, examined by monoclonal and polyclonal antibodies. METHODS: The COX-2 expression in 85 resection specimens of pancreatic ductal adenocarcinoma was immunohistochemically examined using both monoclonal and polyclonal antibodies. The final immunoscores were obtained by multiplying the percentage of positive cells with the numeric score reflecting the staining intensity. COX-2 expression levels were classified into three categories (0, 1+, and 2+) and the clinicopathological correlations were statistically evaluated and analyzed. RESULTS: The positive tumor expression rates of COX-2 were 80.5% using monoclonal antibody and 69.4% using polyclonal antibody. In the Kaplan-Meier analysis, no significant correlations were found between levels of COX-2 expression and overall survival (OS), but trends to longer OS were found in COX-2 negative cases using monoclonal antibody. Significantly longer disease free survival was revealed in COX-2 negative cases using monoclonal antibody (P = 0.019). No correlations between COX-2 expression levels and grade (G), tumor (T) status and nodal (N) status were demonstrated. Low histological grade showed a strong association with a longer OS (P < 0.001). Correlation of survival and T status revealed a shorter OS in T3 tumors, but the results reached only marginal statistical significance (P = 0.070). In the multivariate Cox proportional hazards regression model, histological grade, T and N status remained valuable predictors of a worse survival with borderline significance for T [hazards ratio (HR) = 4.18 for G (if G = 3, P < 0.001); HR = 1.64 for T (if T = 3, P = 0.065); HR = 2.53 for N (if N = 1, P = 0.006)]. Higher grade, T or N status was associated with a worse OS. CONCLUSION: The immunohistochemically assessed level of COX-2 expression does not seem to represent a valuable independent prognostic factor and is not superior to the conventional prognostic factors.

• Klíčová slova
• Cyclooxygenase-2, Immunohistochemistry, Monoclonal antibody, Pancreatic cancer, Polyclonal antibody,
• MeSH
• cyklooxygenasa 2 biosyntéza   MeSH
• dospělí MeSH
• imunohistochemie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky metabolismus   MeSH
• nádory slinivky břišní enzymologie   chirurgie   MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• regulace genové exprese enzymů * MeSH
• regulace genové exprese u nádorů * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vývody pankreatu enzymologie   patologie   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
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• cyklooxygenasa 2 MeSH
• monoklonální protilátky MeSH

OBJECTIVES: Cyclooxygenase-2 (COX-2) and p53 represent molecules linked to oncogenesis of pancreatic cancer, and there is also a known regulatory loop between mouse double minute 2 (MDM2) and p53. The complex cross talks between p53 and COX-2 and scenarios explaining patterns of p53 and COX-2 expressions in precursor and cancer lesions have been recently reported. METHODS: The expressions of COX-2, p53, and MDM2 were examined using immunohistochemistry in 85 resection specimens of pancreatic ductal adenocarcinoma. RESULTS: The positive tumor expression rates of COX-2, p53, and MDM2 were 69.4%, 60.0%, and 41.2%, respectively. Significant correlations between COX-2 and p53 expressions and between p53 and MDM2 expressions were revealed. In the Kaplan-Meier analysis, no statistically significant correlations were found among the levels of COX-2, p53, and MDM2 expressions and survival rates. In the multivariate Cox proportional hazards regression model, grade and nodal status showed to be a valuable predictor of a worse overall survival. CONCLUSIONS: The reported findings confirmed the relationship of p53, MDM2, and COX-2 with the biological process of pancreatic cancer. The expression of none of the examined proteins showed to be a valuable independent prognostic factor. On the contrary, grade and nodal status showed to be a valuable predictor of a worse survival.

• MeSH
• cyklooxygenasa 2 biosyntéza   MeSH
• dospělí MeSH
• duktální karcinom slinivky břišní metabolismus   patologie   chirurgie   MeSH
• imunohistochemie statistika a číselné údaje   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorový supresorový protein p53 biosyntéza   MeSH
• nádory slinivky břišní metabolismus   patologie   chirurgie   MeSH
• pankreatektomie MeSH
• proporcionální rizikové modely MeSH
• protoonkogenní proteiny c-mdm2 biosyntéza   MeSH
• senioři nad 80 let MeSH
• senioři 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
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyklooxygenasa 2 MeSH
• MDM2 protein, human MeSH Prohlížeč
• nádorový supresorový protein p53 MeSH
• protoonkogenní proteiny c-mdm2 MeSH

BACKGROUND: Preoperative plasma levels of Interleukin 6 (IL6) and its soluble receptor (IL6sR) have previously been associated with oncologic outcomes in urothelial carcinoma of the bladder (UCB); however, external validation in patients treated with radical cystectomy (RC) for UCB is missing. PATIENTS/METHODS: We prospectively collected preoperative plasma from 1,036 consecutive patients at two institutes. These plasma specimens were assessed for levels of IL6 and IL6sR. Logistic and Cox regression analyses were used to assess the correlation of plasma levels with pathologic and survival outcomes. The additional clinical net benefits of preoperative IL6 and IL6sR were evaluated using decision curve analysis (DCA). RESULTS: Median IL6 and IL6sR plasma levels were significantly higher in patients with adverse pathologic features. Elevated biomarker levels were independently associated with an increased risk for lymph node metastasis and ≥ pT3 disease. Both biomarkers were independently associated with recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The addition to, respectively, fitted pre- and postoperative prognostic models improved the predictive accuracy for lymph node metastasis, ≥ pT3 disease, RFS and CSS on DCA. INTERPRETATION: We confirmed that elevated preoperative plasma levels of IL6 and IL6sR levels are associated with worse oncological disease survival in patients treated with RC for UCB in a large multicenter study. Both biomarkers hold potential in identifying patients with adverse pathological features that may benefit from intensified/multimodal therapy and warrant inclusion into predictive/prognostic models. They demonstrated the ability to improve the discriminatory power of such models and thus guide clinical decision making.

• Klíčová slova
• Biomarker, Bladder cancer, Interleukin 6, Interleukin 6 soluble receptor, MIBC, Urothelial carcinoma,
• MeSH
• biologické markery metabolismus   MeSH
• cystektomie metody   MeSH
• interleukin-6 krev   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• multivariační analýza MeSH
• nádory močového měchýře krev   chirurgie   MeSH
• pooperační období MeSH
• předoperační období MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• receptory interleukinu-6 krev   MeSH
• regresní analýza MeSH
• rozhodování MeSH
• senioři MeSH
• systémy pro podporu klinického rozhodování MeSH
• urotel patologie   chirurgie   MeSH
• výsledek terapie MeSH
• zánět MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• IL6 protein, human MeSH Prohlížeč
• IL6R protein, human MeSH Prohlížeč
• interleukin-6 MeSH
• receptory interleukinu-6 MeSH