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Wohlfahrt P.,Charles University | Wohlfahrt P.,St Anns University Hospital | Wohlfahrt P.,Institute for Clinical and Experimental Medicine | Lopez-Jimenez F.,Mayo Medical School | And 8 more authors.
Journal of Stroke and Cerebrovascular Diseases | Year: 2015

Background Although obesity is a risk factor for stroke and achieving normal weight is advocated to decrease stroke risk, the risk associated with obesity and weight loss after stroke has not been well established. The aim of this study was to assess the association of obesity at the time of stroke admission and weight loss after stroke with total mortality. Methods We analyzed 736 consecutive patients (mean age, 66 ± 11 years; 58% men) hospitalized for their first ischemic stroke. Body weight at hospital admission and at the outpatient visit during follow-up was used in the analysis. Results After multivariate adjustment, obesity at admission was associated with lower mortality risk as compared with normal weight (hazard ratio [HR],.50, P =.03). At the outpatient visit, with a median follow-up time of 16 months, 21% of patients had lost more than 3 kg of weight. Stroke severity, heart failure, transient ischemic attack, and depression after stroke were independently associated with significant weight loss. Weight loss of more than 3 kg was associated with increased mortality risk (HR, 5.87; P =.001) independently of other factors. Similar results were seen when weight loss was defined as losing more than 3% of baseline weight (HR, 4.97; P =.004). Weight gain of more than 5% of the baseline weight tended to be associated with better survival when compared with no weight change (log-rank test, P =.07). Conclusions Normal weight at hospital admission and weight loss after ischemic stroke are independently associated with increased mortality. Overweight and obesity at baseline do not decrease the risk associated with weight loss. © 2015 National Stroke Association.


Constantine R.J.,University of South Florida | Jentz S.,University of South Florida | Bengtson M.,University of South Florida | Mcpherson M.,University of South Florida | And 3 more authors.
Pharmacoepidemiology and Drug Safety | Year: 2012

Purpose: This study aims the following: (i) to describe the exposure to antipsychotic medications over a 4-year period experienced by a cohort of children who initiated antipsychotic treatment before their sixth birthday; and (ii) to identify variables associated with the risk of antipsychotic exposure. Methods: Children were identified who initiated an index episode of antipsychotic treatment before their sixth birthday in Florida's fee for service Medicaid program. With the use of claims data, the medication utilization of these children was tracked during the year before and the 4years following the start of their index episodes (pre-index and four post-index periods). Generalized estimating equations were used to identify variables associated with the risk of additional days of antipsychotic exposure. Results: Five hundred twenty-eight children were included in the cohort. The mean total number of days of exposure was 821.9 (±431.9), representing 56.3% of all days during the four post-index periods. The mean days of exposure to combinations of antipsychotics and other classes of psychotherapeutic medications were 623.8±447.6days. Children with primary diagnoses of pervasive developmental disorders and affective disorders were at greater risk of additional days of exposure than children with attention deficit/hyperactivity disorder. Exposure tended to be greater among children with indicators of clinical complexity including the presence of secondary diagnoses and the use of other classes of psychotherapeutic medications in addition to antipsychotics. Conclusions: Exposure to antipsychotic mediations was extensive. Although these children may have had complex and severe problems, additional research is urgently needed on the benefits and risks of long-term antipsychotic exposure among very young children. © 2011 John Wiley & Sons, Ltd.


Wohlfahrt P.,Charles University | Wohlfahrt P.,Institute for Clinical and Experimental Medicine | Wohlfahrt P.,St Anns University Hospital | Krajcoviechova A.,Charles University | And 7 more authors.
Atherosclerosis | Year: 2013

Background: Carotid-femoral pulse wave velocity (PWV), as a parameter of aortic stiffness, is an established marker of cardiovascular risk. There has been increasing use of arterial stiffness parameters combining aortic and muscular stiffness or a parameter derived from PWV - the stiffness index beta (BETA=ln(systolic/diastolic pressure)×2 blood viscosity/pulse pressure×PWV2). The aim of this study was to compare different arterial stiffness parameters in a general population random sample. Methods and results: In 809 individuals from the Czech post-MONICA study (aged 54±13.5 years, 47% men), we compared the association of carotid-femoral PWV (cfPWV), carotid-ankle PWV (caPWV), and BETA with cardiovascular risk factors, parameters of subclinical organ damage, and presence of manifest cardiovascular disease.Both cfPWV and caPWV were similarly associated with blood pressure and glucose level, while cfPWV was more strongly associated with age, cholesterol level and glomerular filtration rate whereas caPWV with Sokolow-Lyon index. BETA derived from cfPWV and caPWV was less dependent on blood pressure, while it showed a closer association with coronary heart disease presence, as compared to cfPWV and caPWV. Conclusions: Addition of lower extremity to aortic stiffness has an effect on the association with cardiovascular risk factors while having no effect on the association with manifest cardiovascular disease. Beta transformation of PWV decreases its dependence on blood pressure and may increase its power in cardiovascular risk prediction. © 2013 Elsevier Ireland Ltd.


Wohlfahrt P.,Charles University | Wohlfahrt P.,St Anns University Hospital | Wohlfahrt P.,Institute for Clinical and Experimental Medicine | Krajcoviechova A.,Charles University | And 6 more authors.
Journal of Hypertension | Year: 2015

Objectives: There is no agreement on optimal blood pressure (BP) level during the acute phase of stroke, because studies on the relation between BP and stroke outcome have shown contradicting results. The aim of this study was to compare the relationship of admission, maximal, discharge BP and its components during hospitalization for the first-ever acute ischemic stroke with total mortality after stroke. Methods: In 532 consecutive patients (mean age 66 ± 10 years, 59% of men) hospitalized for their first-ever ischemic stroke, the association between BP and total mortality during a median follow-up of 66 weeks (interquartile range 33-119 weeks) was analyzed. Results: In multivariate analysis, both admission mean BP (MBP) and discharge SBP quartiles were independent predictors of mortality and outperformed other parameters of BP. After multivariate adjustments, patients with admission MBP below 100 mmHg had a higher risk of death than those with MBP between 100-110 and 110-121 mmHg, whereas the risk of mortality did not differ from the group with admission MBP above 122 mmHg. Similarly, patients with discharge SBP below 120 mmHg had an increased risk of death as compared to groups with SBP between 120-130 and 130-141 mmHg, whereas the risk of death was similar to that with discharge SBP above 141 mmHg. Conclusion: Among patients hospitalized for their first-ever ischemic stroke, the risk of all-cause death is significantly increased in those with admission MBP below 100 mmHg and discharge SBP below 120 mmHg, even after adjustments for other confounders. © 2015 Wolters Kluwer Health, Inc.


Wohlfahrt P.,Charles University | Wohlfahrt P.,Institute for Clinical and Experimental Medicine | Wohlfahrt P.,St Anns University Hospital | Krajcoviechova A.,Charles University | And 8 more authors.
Hypertension Research | Year: 2013

While determinants of aortic pulse wave velocity (aPWV) are well known, much less is known about factors affecting lower-extremity pulse wave velocity (lePWV). Unlike aPWV, increased lePWV does not predict cardiovascular risk, but limits lower-extremity blood flow and is associated with increased left ventricular mass. The aim of this study was to compare the effect of cardiovascular risk factors on aPWV and lePWV. A total of 911 individuals from the Czech post-MONICA study (a randomly selected 1% representative population sample, mean age 54±13.5 years, 47% men) were examined. Pulse wave velocity was measured using the SphygmoCor device. Aging had a large effect on aPWV, but only a small effect on lePWV. After adjustment for covariates, we observed that hypertension, diabetes, chronic kidney disease and dyslipidemia were positively and significantly associated with aPWV. However, only hypertension had a significant effect on lePWV. Increased ankle systolic blood pressure was associated with increased aPWV independently of brachial blood pressure. Ankle systolic blood pressure was more closely related to aPWV than lePWV. Subjects with an ankle-brachial index <1.0 had higher aPWV and lower lePWV compared with individuals with a normal ankle-brachial index. Lower-extremity arterial stiffness is affected by age and cardiovascular risk factors to a lesser extent than aortic stiffness. Increased ankle systolic blood pressure is linked not only to increased lower-extremity arterial stiffness, but also increased aortic stiffness. In subjects with a low ankle-brachial index, lower-extremity arterial stiffness is spuriously decreased. © 2013 The Japanese Society of Hypertension. All rights reserved.


Wohlfahrt P.,Charles University | Wohlfahrt P.,St Anns University Hospital | Wohlfahrt P.,Institute for Clinical and Experimental Medicine | Krajcoviechova A.,Charles University | And 7 more authors.
Journal of Hypertension | Year: 2014

OBJECTIVE: Aortic stiffness is increased in lacunar stroke. The precise mechanism linking aortic stiffness to symptomatic lacunar stroke is not well understood. The aim of this study was to compare the effects of aortic stiffness, carotid stiffness, central blood pressure, and cerebrovascular resistance on carotid flow pulsatility according to stroke subtype. METHODS: Two hundred and one consecutive patients were examined 13 months after hospitalization for their first-ever ischemic stroke. The stroke subtype was classified using the Causative Classification of Stroke System. Carotid-femoral pulse wave velocity (PWV) was used as a measure of aortic stiffness. Common carotid flow pulsatility was expressed as resistive index. Central blood pressure was measured using applanation tonometry. RESULTS: Complete data were available for 174 patients (mean age... 67±10 years, 64% men). In patients with lacunar stroke, aortic PWV was higher (13.11±2.74m/s) than in individuals with large artery atherosclerosis (9.98±1.87m/s, P<0.001), cardioembolic (11.31±3.18m/s, P=0.04) or cryptogenic stroke (11.13±3.2m/s, P=0.01). Similarly, central SBP and resistive index were higher in patients with lacunar stroke (145±23mmHg and 0.80±0.04, respectively) than those with large artery atherosclerosis (128±18mmHg, P<0.01 and 0.74±0.07, P<0.01, respectively) or cryptogenic stroke (132±18mmHg, P<0.01 and 0.76±0.07, P<0.05, respectively). In multivariate analysis, aortic stiffness and central pulse pressure were the main determinants of resistive index independent of stroke subtype. CONCLUSION: Our results suggest that aortic stiffening, by reducing the buffering function of the aorta and thereby increasing the transmission of pressure and flow pulsatility into the cerebral arterioles, may contribute to the pathogenesis of lacunar stroke. © 2014 Wolters Kluwer Health / Lippincott Williams & Wilkins.


Bojkova M.,University of Ostrava | Dite P.,University of Ostrava | Dvorackova J.,University of Ostrava | Novotny I.,Masaryk Oncological Institute | And 5 more authors.
Digestive Diseases | Year: 2014

Background: Immunoglobulin G4 (IgG4)-related diseases are a group of diseases characterized by enlargement of the affected organs, elevation of serum IgG4, massive infiltration of affected organs with lymphocytes and plasma cells with IgG4 positivity and tissue fibrosis. Type I autoimmune pancreatitis is one form of IgG4-related disease. For IgG4-related diseases, various localizations are described for up to 10% of malignancies. The aim of our study was to examine IgG4 serum levels and pancreatic tissue with respect to the simultaneous presence of autoimmune pancreatitis in patients with pancreatic cancer. Methods: IgG4 serum levels were examined In 106 patients with histologically confirmed pancreatic cancer. The level of 135 mg/dl was considered as the normal value. Pancreatic tissue was histologically examined with respect to the presence of markers of autoimmune pancreatitis. Results: A higher IgG4 level than the cut-off value of 135 mg/dl was proven in 11 patients with pancreatic cancer. Of these 11 patients, 7 had levels twice the normal limit (65.6%). Autoimmune pancreatitis was diagnosed in these individuals. In the case of 1 patient, it was basically an unexpected finding; another patient was initially diagnosed with autoimmune pancreatitis. Repeated biopsy of the pancreas at the time of diagnosis did not confirm the presence of tumour structures, therefore steroid therapy was started. At a check-up 6 months after starting steroid therapy, the condition of the patient improved subjectively and IgG4 levels decreased. However, endosonographically, malignancy was suspected, which was subsequently confirmed histologically. This patient also demonstrated an IgG4 level twice the normal limit. Conclusion: IgG4-related diseases can be accompanied by the simultaneous occurrence of malignancies, which also applies to autoimmune pancreatitis. Chronic pancreatitis is considered a risk factor for pancreatic cancer. It cannot be reliably confirmed whether this also applies to autoimmune pancreatitis. In accordance with other works, however, it is evident that, despite the described high sensitivity and specificity for IgG4 elevation in the case of autoimmune pancreatitis, even levels twice the normal limit are demonstrable in some individuals with pancreatic cancer, without the presence of autoimmune pancreatitis. We believe that patients with IgG4-related disease, including autoimmune pancreatitis, must be systematically monitored with respect to the potential presence of malignancy. © 2014 S. Karger AG, Basel.


Jelinkova I.,Academy of Sciences of the Czech Republic | Jelinkova I.,Masaryk University | Safarikova B.,Academy of Sciences of the Czech Republic | Safarikova B.,Masaryk University | And 13 more authors.
Biochemical Pharmacology | Year: 2014

In search for novel strategies in colon cancer treatment, we investigated the unique ability of platinum(IV) complex LA-12 to efficiently enhance the killing effects of tumor necrosis factor-related apoptosis inducing ligand (TRAIL), and compared it with the sensitizing action of cisplatin. We provide the first evidence that LA-12 primes human colon cancer cells for TRAIL-induced cytotoxicity by p53-independent activation of the mitochondrial apoptotic pathway. The cooperative action of LA-12 and TRAIL was associated with stimulation of Bax/Bak activation, drop of mitochondrial membrane potential, caspase-9 activation, and a shift of the balance among Bcl-2 family proteins in favor of the pro- apoptotic members. In contrast to cisplatin, LA-12 was a potent inducer of ERK-mediated Noxa and BimL protein upregulation, and more effectively enhanced TRAIL-induced apoptosis in the absence of Bax. The cooperative action of LA-12 and TRAIL was augmented following the siRNA-mediated silencing of Mcl-1 in both Bax proficient/deficient cells. We newly demonstrated that LA-12 induced ERK-mediated c-Myc upregulation, and proved that c-Myc silencing inhibited the mitochondrial activation and apoptosis in colon cancer cells treated with LA-12 and TRAIL. The LA-12-mediated sensitization to TRAIL-induced apoptosis was demonstrated in several colon cancer cell lines, further underscoring the general relevance of our findings. The selective action of LA-12 was documented by preferential priming of cancer but not normal colon cancer cells to TRAIL killing effects. Our work highlights the promising potential of LA-12 over cisplatin to enhance the colon cancer cell sensitivity to TRAIL-induced apoptosis, and provides new mechanistic insights into their cooperative action. © 2014 Elsevier Inc. All rights reserved.


Drotar P.,Brno University of Technology | Mekyska J.,Brno University of Technology | Rektorova I.,St Anns University Hospital | Masarova L.,St Anns University Hospital | And 2 more authors.
Artificial Intelligence in Medicine | Year: 2016

Objective: We present the PaHaW Parkinson's disease handwriting database, consisting of handwriting samples from Parkinson's disease (PD) patients and healthy controls. Our goal is to show that kinematic features and pressure features in handwriting can be used for the differential diagnosis of PD. Methods and material: The database contains records from 37 PD patients and 38 healthy controls performing eight different handwriting tasks. The tasks include drawing an Archimedean spiral, repetitively writing orthographically simple syllables and words, and writing of a sentence. In addition to the conventional kinematic features related to the dynamics of handwriting, we investigated new pressure features based on the pressure exerted on the writing surface. To discriminate between PD patients and healthy subjects, three different classifiers were compared: K-nearest neighbors (K-NN), ensemble AdaBoost classifier, and support vector machines (SVM). Results: For predicting PD based on kinematic and pressure features of handwriting, the best performing model was SVM with classification accuracy of P acc =81.3% (sensitivity P sen =87.4% and specificity of P spe =80.9%). When evaluated separately, pressure features proved to be relevant for PD diagnosis, yielding P acc =82.5% compared to P acc =75.4% using kinematic features. Conclusion: Experimental results showed that an analysis of kinematic and pressure features during handwriting can help assess subtle characteristics of handwriting and discriminate between PD patients and healthy controls. © 2016 Elsevier B.V.


PubMed | Brno University of Technology, St Anns University Hospital and Signal Processing Group
Type: | Journal: Artificial intelligence in medicine | Year: 2016

We present the PaHaW Parkinsons disease handwriting database, consisting of handwriting samples from Parkinsons disease (PD) patients and healthy controls. Our goal is to show that kinematic features and pressure features in handwriting can be used for the differential diagnosis of PD.The database contains records from 37 PD patients and 38 healthy controls performing eight different handwriting tasks. The tasks include drawing an Archimedean spiral, repetitively writing orthographically simple syllables and words, and writing of a sentence. In addition to the conventional kinematic features related to the dynamics of handwriting, we investigated new pressure features based on the pressure exerted on the writing surface. To discriminate between PD patients and healthy subjects, three different classifiers were compared: K-nearest neighbors (K-NN), ensemble AdaBoost classifier, and support vector machines (SVM).For predicting PD based on kinematic and pressure features of handwriting, the best performing model was SVM with classification accuracy of Pacc=81.3% (sensitivity Psen=87.4% and specificity of Pspe=80.9%). When evaluated separately, pressure features proved to be relevant for PD diagnosis, yielding Pacc=82.5% compared to Pacc=75.4% using kinematic features.Experimental results showed that an analysis of kinematic and pressure features during handwriting can help assess subtle characteristics of handwriting and discriminate between PD patients and healthy controls.

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