Jerzy Romaszko

Antihypertensive efficacy and tolerability of aliskiren/hydrochlorothiazide (HCT) single-pill combinations in patients who are non-responsive to HCT 25 mg alone

ABSTRACT Objective: Thiazide diuretics such as hydrochlorothiazide (HCT) are a widely used first-line treatment for hypertension, but most patients will not achieve blood pressure (BP) control with HCT alone and so will require combination therapy. In this study the efficacy, safety and tolerability of a single-pill combination (SPC) of the direct renin inhibitor aliskiren with HCT were investigated in patients non-responsive to HCT 25 mg therapy. Methods: In this study, 722 patients with hypertension and an inadequate response to 4 weeks of HCT 25 mg (mean sitting diastolic BP ≥90 and <110 mmHg) were randomized to once-daily, double-blind treatment for 8 weeks with an SPC of aliskiren/HCT 300/25 mg or 150/25 mg, or continued HCT 25 mg monotherapy. Least-squares mean changes in mean sitting systolic/diastolic BP (msSBP/DBP) from double-blind baseline were analyzed for the ITT population at week 8 endpoint. Results: Aliskiren/HCT 300/25 mg and 150/25 mg SPCs lowered msSBP/DBP from baseline by 16.7/10.7 and 12.9/8.5 mmHg, respectively, both significantly greater reductions than HCT 25 mg alone (7.1/4.8 mmHg; both p < 0.001). Rates of BP control (<140/90 mmHg) were also significantly higher with aliskiren/HCT 300/25 mg (58%) and 150/25 mg (49%) than with HCT (26%; both p < 0.001). Aliskiren/HCT 300/25 mg provided significantly greater msSBP/DBP reductions and rates of BP control than the 150/25 mg SPC dose (all p < 0.05). Aliskiren/HCT SPC treatment showed similar tolerability to HCT alone and a numerically lower incidence of hypokalemia (serum potassium <3.5 mmol/L; aliskiren/HCT, 1.3–2.2%: HCT alone, 3.4%). Conclusion: Aliskiren/HCT SPCs provide clinically significant BP reductions and improved BP control rates in patients who are non-responsive to HCT 25 mg monotherapy. Limitations of the study were the mainly Caucasian patient population and the non-responder design.

The impact of red cabbage fermentation on bioavailability of anthocyanins and antioxidant capacity of human plasma.

The effect of red cabbage fermentation on anthocyanin bioavailability and plasma antioxidant capacity in humans was studied. In a randomized crossover study, 13 volunteers consumed fresh and fermented red cabbage. Blood and urine samples were collected before and after consumption. Analyses of anthocyanins by HPLC-MS/MS and plasma antioxidant capacity by photochemiluminescence assay were conducted. Red cabbage products contained 20 different nonacylated and acylated anthocyanins with the main structure of cyanidin triglucosides. The anthocyanins ingested were present in physiological fluids in form of 18 native anthocyanins and 12 metabolites (methylated, glucuronided, sulfated). Among cyanidin metabolites identified, methylated forms were predominant. Bioavailability of anthocyanin from fresh red cabbage was over 10% higher than from fermented red cabbage. Upon fresh cabbage consumption, volunteers plasma showed higher antioxidant capacity than after fermented cabbage intake. The study has shown that fermentation process affects red cabbage anthocyanins bioavailability and human plasma antioxidant capacity.

Exposure of breastfed infants to quercetin after consumption of a single meal rich in quercetin by their mothers

SCOPE The exposure to quercetin (Q) has not been studied in breastfed infants whose mothers were consuming a Q-rich diet. The objective of the study was to determine whether plant-origin antioxidant-Q passes from the mothers diet to her milk and to calculate the pharmacokinetic parameters of this phenomenon. METHODS AND RESULTS Eleven breastfeeding women were included in this controlled case study. Volunteers followed a Q-restricted diet for 5 consecutive days with the exception of the 3rd day when they received a single meal providing 1 mg of Q per kg of body weight. Urine analysis showed the presence of Q already in the first collected samples after the test (1.5-4 h), which indicated its rapid absorption from the meal. The Cmax = 68 ± 8.44 nmol/L concentration of Q in the milk was calculated for Tmax = 11.89 ± 3.37 h. It was significantly different (p = 0.007) from 40 nmol/L and (p = 0.016) from 42 nmol/L of Q concentration before and 48 h after the test, respectively. CONCLUSIONS Q was shown to be a component of human milk at the nmol/L level. Infants breastfed by mothers consuming a diet rich in Q are exposed to a dose of approximately 0.01 mg of Q daily.

The incidence of pulmonary tuberculosis among the homeless in north-eastern Poland

Tuberculosis (TB) is a disease particularly affecting the poorest socioeconomic groups. One such group in Central Europe are the homeless. We developed a prevention programme that targets, among others, homeless individuals in Warmia and Mazury Province (in the northeast of Poland). We investigated 121 homeless persons. We performed surveys, X-rays and microbiological tests of the sputum for TB. Five cases of pulmonary TB were found. The prevalence of TB in this community was estimated at 4132 per 100,000 (4.13%). Efficient TB control justifies continued prevention programmes aimed at the systematic monitoring of the homeless population.

Prediction of antimicrobial activity of imidazole derivatives by artificial neural networks

The main goal of our study is the analysis of data obtained from molecular modeling for a series of imidazole derivatives that possess strong antifungal activity. The research was designed to use artificial neural network (ANN) analysis to determine quantitative relationships between the structural parameters and anti-Streptococcus pyogenes activity of a series of imidazole derivatives. ANN in association with quantitative structure-activity relationships (QSAR) represents a promising tool in the search for drug candidates among the practically unlimited number of possible derivatives. In this work, a series of 286 imidazole derivatives presented as cationic three-dimensional structures was used. The activity was expressed as a logarithm of the reciprocal of the minimal inhibitory concentrations, log 1/MIC. Multilayer perceptron ANN was used for predictions of antimicrobial potency of new imidazole derivatives on the basis of their structural descriptors. The obtained correlation coefficient equaled 0.9461 for the learning set, 0.9060 for the validation set and 0.8824 for the testing set of imidazole derivatives. Hence, satisfactory and practically useful predictions of anti-Streptococcus pyogenes activity for a series of imidazole derivatives was obtained, supporting the future successful interpretation of QSAR analysis for those compounds.

Mortality among the homeless: Causes and meteorological relationships.

Background The homeless constitute a subpopulation particularly exposed to atmospheric conditions, which, in the temperate climate zone, can result in both cold and heat stress leading to the increased mortality hazard. Environmental conditions have become a significant independent risk factor for mortality from specific causes, including circulatory or respiratory diseases. It is known that this group is particularly prone to some addictions, has a shorter life span, its members often die of different causes than those of the general population and may be especially vulnerable to the influence of weather conditions. Materials and methods The retrospective analysis is based on data concerning 615 homeless people, out of which 176 died in the analyzed period (2010–2016). Data for the study was collected in the city of Olsztyn, located in north-east Poland, temperate climatic zone of transitional type. To characterize weather conditions, meteorological data including daily minimum and maximum temperatures and the Universal Thermal Climate Index (UTCI) were used. Results The average life span of a homeless person was shorter by about 17.5 years than that recorded for the general population. The average age at death of a homeless male was 56.27 years old (SD 10.38), and 52.00 years old (SD 9.85) of a homeless female. The most frequent causes of death were circulatory system diseases (33.80%). A large number of deaths were attributable to smoking (47.18%), whereas a small number was caused by infectious diseases, while a relatively large proportion of deaths were due to tuberculosis (2.15%). Most deaths occurred in the conditions of cold stress (of different intensity). Deaths caused by hypothermia were thirteen-fold more frequently recorded among the homeless than for the general population. A relative risk of death for a homeless person even in moderate cold stress conditions is higher (RR = 1.84) than in thermoneutral conditions. Conclusions Our results indicate excessive mortality among the homeless as well as the weak and rather typical influence of atmospheric conditions on mortality rates in this subpopulation, except for a greater risk of cold related deaths than in the general population. UTCI may serve as a useful tool to predict death risk in this group of people.

Artificial neural networks approach to early lung cancer detection

Lung cancer is rated with the highest incidence and mortality every year compared with other forms of cancer, therefore early detection and diagnosis is essential. Artificial Neural Networks (ANNs) are “artificial intelligence” software which have been used to assess a few prognostic situations. In this study, a database containing 193 patients from Diagnostic and Monitoring of Tuberculosis and Illness of Lungs Ward in Kuyavia and Pomerania Centre of the Pulmonology (Bydgoszcz, Poland) was analysed using ANNs. Each patient was described using 48 factors (i.e. age, sex, data of patient history, results from medical examinations etc.) and, as an output value, the expected presence of lung cancer was established. All 48 features were retrospectively collected and the database was divided into a training set (n=97), testing set (n=48) and a validating set (n=48). The best prediction score of the ANN model (MLP 48-9-2) was above 0.99 of the area under a receiver operator characteristic (ROC) curve. The ANNs were able to correctly classify 47 out of 48 test cases. These data suggest that Artificial Neural Networks can be used in prognosis of lung cancer and could help the physician in diagnosis of patients with the suspicion of lung cancer.

Socioeconomic Characteristics, Health Risk Factors and Alcohol Consumption among the Homeless in North-Eastern Part of Poland

BACKGROUND Homelessness is a form of social pathology, which is for various reasons undesirable and as far as possible limited by efforts such as programmes that assist in transitioning out of homelessness. Because, as time passes, the homeless population undergoes both quantitative and qualitative changes, the process of developing these programmes requires up-to-date information on the extent and profile of this phenomenon that takes into account the characteristics of a given country. METHODS A 12-month study of homeless individuals (ETHOS categories 1.1, 2.1 and 3.1) was conducted between December 2013 and November 2014 in Olsztyn, Poland. Demographic, sociological, psychological, and medical data were collected. RESULTS The study population comprised 98 homeless individuals. The average homeless individual in our study population was a single (93.88%), most commonly divorced (59.18%), alcohol-dependent (78.57%), smoking (84.69%), middle-aged (54.33 years, SD 9.70) male (92.86%) with a low level of education (10.19 years of completed education, SD 3.09). The individual was most commonly an unemployed person suffering profound privation, living off various types of benefits, and spending a significant proportion of his income on alcohol and cigarettes. The person often resigned from social welfare due to his alcohol dependence. Almost a third of the study population (32.65%) declared that they occasionally went hungry. The principal source of food were meals provided by welfare services (89.80%). CONCLUSIONS Our results indicate that the design of the social welfare system for homeless people should always take into account issues related to alcohol dependence, and each homeless person should be evaluated for possible alcohol dependence. Institutionalised material support provided to homeless individuals should be organised in such a way as to minimise the risk of promoting alcohol and nicotine dependence.

Identification of clinical risk factors of atrial fibrillation in congestive heart failure

BACKGROUND Factors associated with the development of atrial fibrillation (AF) in general population have been described, but it is still unknown whether the same risk factors apply to heart failure (HF) patients. The aim of this study was to identify clinical factors related to various forms of AF in HF patients. METHODS The clinical and echocardiographic characteristics were assessed in 155 HF patients: 50 with sinus rhythm, 52 with non-permanent AF, and 53 with permanent AF. RESULTS Multivariate logistic regression analysis showed that the increase in the NYHA class was an independent risk factor for both forms of AF. The occurrence of permanent AF in comparison to sinus rhythm group was independently associated with hs-C-reactive protein (CRP) elevation above 1 mg/dL (OR 1.87, 95% CI 1.05-3.35), left atrial dimension above 4 cm (OR 3.78, 95% CI 1.29-11.06) and tricuspid maximal pressure gradient elevation above 35 mm Hg (OR 5.01, 95% CI 1.38-18.27). The presence of coronary disease was independently associated with less frequent occurrence of permanent AF in comparison to sinus rhythm group (OR 0.21, 95% CI 0.06-0.67). CONCLUSIONS More advanced congestive HF was associated with presence of both types of AF. Non-ischemic etiology of HF and elevated CRP are independently associated with permanent AF compared to sinus rhythm. Left ventricular diastolic dysfunction indicators (increased tricuspid maximal pressure gradient and left artial dimension) are independently associated with permanent AF.

ANN as a prognostic tool after treatment of non-seminoma testicular cancer

Testicular cancer is rare but is the most common cancer in males between 15 and 34 years of age. Two principal types of testicular cancer are distinguished: seminomas and non-seminomas. If detected early, the overall cure rate for testicular cancer exceeds 90%. In this study, artificial neural network (ANN) analysis as a prognostic tool was demonstrated regard to five year recurrence after the non-seminoma treatment. Data from 202 patients treated for non-seminoma were available for evaluation and comparison. A total of 32 variables were analysed using the ANN. The ANN approach, as an advanced multivariate data processing method, was demon-strated to provide objective prognostic data. Some of these prognostic factors are consistent or even imperceptible with previously evaluated by other statistical methods.