The importance and effectiveness of nutritional counselling in patients with autoimmune thyroid diseases in Poland.

BACKGROUND: Autoimmune thyroid diseases are the most common diseases in humans. Their pathogenesis is complex, pushing patients to search different ways of alleviating their effects, one of which is diet change. The aim of this study was to assess the role of medical personnel in shaping eating habits in patients with autoimmune thyroid disease based on experiences declared by patients. METHODS: We examined 208 individuals, of which 205 were qualified for final investigation. We selected study participants using accidental sampling, based on their appearance in health care facilities, including the ones providing endocrinological advices. The relationships between the qualitative features were tested using the Chi-square test of independence, assuming the significance level of p < 0.05. In the case of the expected cardinality < 10, the Chi-square test with correction for Yates continuity was used, while for the cardinality < 5-the Fisher exact test. RESULTS: People with thyroid disease are statistically more likely to use dietitian advice than people without thyroid disease. The highest percentage of respondents decided to modify their nutrition due to their own initiative. In addition, patients with autoimmune thyroid disease are statistically more likely to consider changing their diet to improve their well-being. The connection between the source of advice and modification of eating behaviour was also noted. CONCLUSION: Thanks to the joint effort of medical staff, patients can receive reliable knowledge about their disease, treatment and nutrition adapted to their needs. Trial registration approved by the Bioethics Committee of Medical University of Silesia in Katowice (opinion no.: PCN/0022/KB1/80/2).

Population aging and migration - history and UN forecasts in the EU-28 and its east and south near neighborhood - one century perspective 1950-2050.

BACKGROUND: There is a gap in knowledge on long term pace of population aging acceleration and related net-migration rate changes in WHO European Region and its adjacent MENA countries. We decided to compare European Union (EU-28) region with the EU Near Neighborhood Policy Region East and EU Near Neighborhood Policy Region South in terms of these two essential features of third demographic transition. One century long perspective dating back to both historical data and towards reliable future forecasts was observed. METHODS: United Nation's Department of Economic and Social Affairs estimates on indicators of population aging and migration were observed. Time horizon adopted was 1950-2050. Targeted 44 countries belong to either one of three regions named by EU diplomacy as: European Union or EU-28, EU Near Neighborhood Policy Region East (ENP East) and EU Near Neighborhood Policy Region South (ENP South). RESULTS: European Union region currently experiences most advanced stage of demographic aging. The latter one is the ENP East region dominated by Slavic nations whose fertility decline continues since the USSR Era back in late 1980s. ENP South region dominated by Arab League nations remains rather young compared to their northern counterparts. However, as the Third Demographic Transition is inevitably coming to these societies they remain the spring of youth and positive net emigration rate. Probably the most prominent change will be the extreme fall of total fertility rate (children per woman) in ENP South countries (dominantly Arab League) from 6.72 back in 1950 to medium-scenario forecasted 2.10 in 2050. In the same time net number of migrants in the EU28 (both sexes combined) will grow from - 91,000 in 1950 to + 394,000 in 2050. CONCLUSIONS: Long term migration from Eastern Europe westwards and from MENA region northwards is historically present for many decades dating back deep into the Cold War Era. Contemporary large-scale migrations outsourcing from Arab League nations towards rich European Protestant North is probably the peak of an iceberg in long migration routes history. However, in the decades to come acceleration of aging is likely to question sustainability of such movements of people.

Estradiol decreases blood pressure in association with redox regulation in preeclampsia.

In this study, we tested a hypothesis that a short-term estradiol therapy may reduce blood pressure in preeclampsia by modulating plasma oxidative stress. The intramuscular injections of 10 mg 17-beta-estradiol were prescribed to preeclamptic pregnant women during the 3-day therapy before a labor induction. The analyses of mean arterial pressure (MAP), serum estradiol concentrations, plasma superoxide anion (O2.), hydrogen peroxide (H2O2), nitrites (NO2-), and peroxynitrite (ONOO-) were conducted before and during the therapy. We found that the plasma concentrations of oxidative stress markers, such as O2- and H2O2, are higher in preeclampsia and positively correlated with the MAP value. Moreover, it was shown that the plasma concentration of NO2- as an indicator of NO levels is higher in preeclampsia. A short-term intramuscular application of estradiol decreases the MAP value and the plasma concentration of O.-, H2O2, NO2-, and ONOO- in preeclampsia. A positive correlation between the decrease of MAP values and the decrease of plasma concentrations of O2-, H2O2, and ONOO- was found in preeclampsia during a short-term estradiol therapy. We conclude that the short-term estradiol therapy decreases the MAP value in preeclampsia by modulating the plasma oxidative stress. We speculate that the estradiol metabolism in preeclampsia is an important mechanism that contributes to vascular dysfunction.

Costs differences among monoclonal antibodies-based first-line oncology cancer protocols for breast cancer, colorectal carcinoma and non-Hodgkin's lymphoma.

PURPOSE: To assess and compare the costs of first-line monoclonal antibodies (mAbs) treatment protocols in breast cancer, non-Hodgkin lymphoma and colorectal carcinoma in South-Eastern Europe. METHODS: A retrospective, bottom-up case series study design was implemented with one-year time horizon and payer's perspective. The study sample size was 265 patients (breast cancer, N=137; colorectal cancer, N=44; and non-Hodgkin lymphoma, N=84), while treatment protocols included adjuvant mAbs: trastuzumab (N=137), bevacizumab (N=28), rituximab (N=16) and cetuximab (N=84). ICD-10 related resources use included history of medical services utilization, chronology (time out of service provision) and unit consumption of examinations, drugs prescribed, imaging, radiotherapy and surgical procedures provided etc., direct medical and lost productivity costs (€) across treatment groups during 2010-2013. RESULTS: The average length of observation was 125+97 days per patient. Total mean direct and indirect costs of care were: trastuzumab for breast cancer group € 17,740 per patient; bevacizumab for colorectal carcinoma group €8,775 per patient; cetuximab for colorectal carcinoma group € 27,181 per patient; and rituximab for non-Hodgkin lymphoma group €19,431 per patient. An average mAbs-treated patient incurred €17,897 costs of medical care. The total combined budget of these 330 patients was €4,742,775. CONCLUSIONS: The use of mAbs strongly correlated with high costs in first-line cancer medical care and dominated other cost domains. Cetuximab-based treatment protocols in colorectal carcinoma patients was substantially more expensive compared to trastuzumab (C50), bevacizumab (C20), and rituximab (C80) alternatives. Extremely high costs of mAbs are the key-issue for Eastern European policy makers by crossing the upper limits of affordability in middle-income economies.

The Expression of IL-1ß Correlates with the Expression of Galectin-3 in the Tissue at the Maternal-Fetal Interface during the Term and Preterm Labor.

The inflammatory processes that occur at the maternal−fetal interface are considered one of the factors that are responsible for preterm birth. The pro-inflammatory roles of the Gal-3-induced activation of NLRP3 inflammasome and the consecutive production of IL-1ß have been described in several acute and chronic inflammatory diseases, but the role of this inflammatory axis in parturition has not been studied. The aim of this study was to analyze the protein expression of Gal-3, NLRP3, and IL-1ß in the decidua, villi, and fetal membranes, and to analyze their mutual correlation and correlation with the clinical parameters of inflammation in preterm birth (PTB) and term birth (TB). The study included 40 women that underwent a preterm birth (gestational age of 25.0−36.6) and histological chorioamnionitis (PTB) and control subjects, 22 women that underwent a term birth (gestational age of 37.0−41.6) without histological chorioamnionitis (TB). An analysis of the tissue sections that were stained with anti- Gal-3, -NLRP3, and -IL-1ß antibodies was assessed by three independent investigators. The expression levels of Gal-3 and IL-1ß were significantly higher (p < 0.001) in the decidua, villi, and fetal membranes in the PTB group when they compared to those of the TB group, while there was no difference in the expression of NLRP3. A further analysis revealed that there was no correlation between the protein expression of NLRP3 and the expression of Gal-3 and IL-1ß, but there was a correlation between the expression of Gal-3 and IL-1ß in decidua (R = 0.401; p = 0.008), villi (R = 0.301; p = 0.042) and the fetal membranes (R = 0.428; p = 0.002) in both of the groups, PTB and TB. In addition, the expression of Gal-3 and IL-1ß in decidua and the fetal membranes was in correlation with the parameters of inflammation in the maternal and fetal blood (C-reactive protein, leukocyte number, and fibrinogen). The strong correlation between the expression of Gal-3 and IL-1ß in the placental and fetal tissues during labor indicates that Gal-3 may participate in the regulation of the inflammatory processes in the placenta, leading to increased production of IL-1ß, a cytokine that plays the main role in both term and preterm birth.

Asian innovation in pharmaceutical and medical device industry - beyond tomorrow.

The Asian region has passed a long and rocky road during the past several decades to establish itself as the second leading regional biotech market globally. China has become the second largest pharmaceutical market while Japan holds a strong second position as the global hub for medical devices development and innovation. Pharmaceutical expenditure continues to outpace real GDP growth in most of these countries. The trend is likely to be continued for a decade ahead, driven by a myriad of factors ranging from aging populations, rapidly growing welfare and increased citizen expectations raising demand for novel medicines and technologies. Satisfaction of these unmet needs in terms of supply is coming from the large multinational companies in wealthier among these societies. Domestic born and largely state-owned manufacturing industries continue to play a crucial role in an array of middle-income countries. Global biotech hub of Singapore is hosting over 1.5 times more headquarters of large pharmaceutical companies than Beijing, Tokyo, Shanghai and Hong Kong combined together. Japanese Takeda, Astellas, Daiichi Sankyo and Otsuka and Chinese Sinopharm, Guangzhou Pharmaceuticals Corporation, SPH and Yunnan Baiyao are now enlisted in leading Top 25 pharmaceutical companies rankings as per their annual net revenues in 2020-2021. Global industry landscape is evolving with ever more Asian companies obtaining the sharp innovative competitiveness leading development of cutting-edge medical technologies. Asian societies demand for pharmaceuticals and medical services continue to be characterized with unmet needs and striving to increase supply capacities. Financial obstacles of affordability of life saving medicines to the ordinary citizens shall be gradually overcome with an array of reimbursement strategies and extended insurance coverage policies. Observing the broad landscape throughout Asian region, we may witness that optimism in terms of domestic real GDP growth and consecutive biotech industry forecasts remains firmly rooted in years to come. Biosimilars are not a focus of the paper.

The Global South political economy of health financing and spending landscape - history and presence.

The Global South nations and their statehoods have presented a driving force of economic and social development through most of the written history of humankind. China and India have been traditionally accounted as the economic powerhouses of the past. In recent decades, we have witnessed reestablishment of the traditional world economic structure as per Agnus Maddison Project data. These profound changes have led to accelerated real GDP growth across many LMICs and emerging countries of the Global South. This evolution had a profound impact on an evolving health financing landscape. This review revealed hidden patterns and explained the driving forces behind the political economy of health spending in these vast world regions. The medical device and pharmaceutical industry play a crucial role in addressing the unmet medical needs of rising middle class citizens across Asia, Latin America, and Africa. Domestic manufacturing has only been partially meeting this ever rising demand for medical services and medicines. The rest was complemented by the participation of multinational pharmaceutical industry, whose focus on investment into East Asia and ASEAN nations remains part of long-term market access strategies. Understanding of the past remains essential for the development of successful health strategies for the present. Political economy has been driving the evolution of health financing landscape since the establishment of early modern health systems in these countries. Fiscal gaps these governments face in diverse ways might be partially overcome with the spreading of cost-effectiveness based decision-making and health technology assessment capacities. The considerable remaining challenges ranging from insufficient reimbursement rates, large out-of-pocket spending, and lengthy lag in the introduction of cutting-edge technologies such as monoclonal antibodies, biosimilars, or targeted oncology agents, might be partially resolved only in the long run.

Correlation between serum biochemical markers and early amniocentesis in diagnosis of congenital fetal anomalies.

A combined test performed at the 12th week of gestation enables us to classify the pregnancy as high risk (risk higher than 1:300) or low risk (risk lower than 1:300) for congenital foetal anomalies, with great accuracy of 85 - 90%. According to the available data, the frequency of false positive results is estimated at around 5%. The objective of the study was to examine possible correlation between the serum marker values and amniocentesis results in prenatal diagnostics of congenital foetal anomalies. The study included 745 pregnant women monitored by the Genetic Counselling Service of the Clinic of Gynaecology and Obstetrics of the Clinics Centre Kragujevac. The subjects were included in the study under condition that CRL (embryonic crown-rump length) was from 45 to 84 mm and that the gestational age was at 11-13+6 weeks. Free beta HCG and PAPP-A were determined from venous blood using commercial DPS-USA tests. Tests were based on the analytic principle of the immuno-chemiluminescence technique and were performed by application of the automatic Immulite 2000 analyzer by DPC-USA. The foetal nuchal translucency thickness (NT) and CRL were measured by Colour Doppler. The chromosome identification was performed after a certain number of cell divisions by stopping the cell division in metaphase of mitosis when the chromosomes were the most distinguishable. The foetal karyotype was prepared using G bands. In the total sample of pregnant women (n=745), there were six cases of pathological foetal karyotype. A statistical paradox in the frequency of congenital foetal anomalies in favour of younger population was noticed. A high coefficient of Spearman's rank correlation suggests great importance of the combined test in the detection of congenital foetal anomalies (p<0,05). A high consistency was also proved for components of biochemical screening and ultrasonographic markers. The combined test, as a method of prenatal screening in the first trimester of pregnancy, if used at 11 - 13+6 weeks' gestation and for CRL of 45-84 mm, has a great importance in the detection of congenital foetal anomalies.

Monitoring of drug-associated electrolyte disturbances in a hospital.

PURPOSE: The aim of our study was to find drug-associated changes in serum levels of major electrolytes using clinical-event monitoring method. METHODS: During 1-year period, electrolyte disturbances in serum samples from patients of Clinical Center Kragujevac, Serbia, were monitored in central biochemical facility. A sample of 982 patients was randomly selected from total population of 43,120 patients whose electrolyte serum levels were measured in the facility during the study period. RESULTS: Clinically important drug-associated electrolyte disturbances were detected in 181 patient. There were 25 significant associations between the drugs and electrolyte values outside the reference range. However, only four causal connections were established: use of normal saline infusion with hypernatremia (OR 6.97, 95%CI 2.24-21.67), theophylline with acid-base disturbances (7.75, 1.46-41.02), polygeline infusion with decrease in bicarbonate levels (4.08, 1.42-11.73), and association of risperidone and hypocalcemia (4.10, 1.42-11.81). CONCLUSION: Although clinical-event monitoring method is far from optimal, it could quantify the known risks and provide evidence for credible hypothesis of drug adverse reactions, based on both relevant biological pathways and reasonable clinical thinking, as it was the case in our study.

Cost-effectiveness of ritodrine and fenoterol for treatment of preterm labor in a low-middle-income country: a case study.

OBJECTIVES: In countries with high income, tocolytic therapy with beta-mimetic agents is a cost-effective strategy compared to placebo. In our study, the cost-effectiveness of two beta-mimetic agents, ritodrine and fenoterol, used in the management of preterm labor was compared in the setting of a low-middle-income transitional country, Serbia & Montenegro. METHODS: This case study was conducted at the Gynecology-Obstetrics Clinic, Clinical Center "Kragujevac," in Kragujevac, Serbia & Montenegro, between October 2004 and January 2006. In total, 235 pregnant patients with threatened preterm labor were enrolled, but 35 were lost to follow-up. Of the remaining 200 patients, 85 were given ritodrine, and 115 fenoterol. The perspective of Republic Institute for Health Insurance in Serbia was taken into account. Only direct costs were calculated; primary outcomes of the study were length of pregnancy (in weeks), time passed from the onset of uterine contractions to delivery (in weeks), and score on modified Flanagan's quality-of-life scale for chronic diseases, measured after discharge from hospital. RESULTS: Prolongation of pregnancy was significantly longer in the fenoterol group (12.7 +/- 8.4 weeks) than in the ritodrine group (11.6 +/- 7.1 weeks). The mean duration of hospitalization was shorter in the fenoterol group (11.9 +/- 8.8 days) than in the ritodrine group (14.9 +/- 11.3 days). The treatment with fenoterol was less costly and more cost-effective than the treatment with ritodrine, but the difference in cost-effectiveness was not statistically significant. The cost of treatment per gained week of pregnancy prolongation was 3345.51 +/- 7668.04 CSD in the fenoterol group, and 4181.96 +/- 12,069.83 CSD in the ritodrine group. CONCLUSIONS: The observed differences in treatment costs and duration of hospitalization per patient did not translate into significant differences in cost-effectiveness ratios, because of low costs of hospitalization and human labor in Serbian health system. Nevertheless, fenoterol treatment still has a tendency to be more cost-effective, and its lower acquisition cost is an advantage to this treatment option.

Significance of pregnancy-associated plasma protein A (PAPP-A) concentration determination in the assessment of final outcome of pregnancy.

BACKGROUND/AIM: Pregnancy-associated plasma protein A (PAPP-A) is high molecular matrix metalloproteinase originally isolated in the serum of pregnant women. The aim of this study was to analyze the values of concentration of PAPP-A in assessment of progress and outcome of pregnancy in pregnant women diagnosed with threatening preterm delivery, preeclampsia and fetal growth restriction in relation to physiological pregnancy of the same gestational age. METHODS: The study included 60 pregnant women that were divided into three groups according to gestational age and the diagnosis of imminent premature birth upon reception, preeclampsia and fetal growth restriction as follows: the group I from 28 to 32 weeks of gestation, a total of 25 pregnant women, the group II from 33 to 36 weeks of gestation, a total of 23 pregnant women, and the group III from 37 to 41 weeks of gestation, a total of 12 pregnant women. The control group consisted of 60 pregnant women without complications of pregnancy that were identically divided into three groups according to gestational age as in the sample. We performed quantitative determination of PAPP-A from the venous blood of patients by using commercial tests of the company Diagnostics Product Corporation (DPC), Los Angeles, California, USA. RESULTS: There was a statistically significant difference in PAPP-A values in the examined groups in all gestational ages (p < 0.01). The value of the PAPP-A concentration in different gestational ages with equal statistical significance indicated the possibility of complications, which was examined during pregnancy in relation to the control group of pregnant women with physiological pregnancies. This study confirmed that there was a statistically significant difference in fetal body weight at birth (p < 0.05), Apgar score in 5 min after birth (p < 0.05), and gestational age at birth (p < 0.05), as parameters of the outcome of pregnancy course, between the examined groups of pregnant women in relation to the value of PAPP-A concentration. The age of pregnant women was not statistically different in the examined groups (p > 0.05). CONCLUSION: Differences in PAPP-A concentration should point out to the obstetrician the need for more intensive antepartum fetal surveillance in order to increase the chances of favorable perinatal outcome, regardless gestational age.

[Changes in parameters of glycoregulation in gestational diabetes mellitus patients with different approach to insulin therapy introduction].

INTRODUCTION: Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. The diagnosis of GDM is made by performing the oral glucose tolerance test (OGTT) in women with risk factors, usually during 24th to 28th week of gestation. The most common used insulin therapy regime is a conventional intensive insulin therapy with four daily doses. OBJECTIVE: The aim of our study was to determine the changes in parameters of glycoregulation in GDM patients with different approach to the introduction of insulin therapy. METHODS: Study group consisted of 50 pregnant women divided into two groups depending on the parameters of glycoregulation (glycemic profile and HbA1). Group 1 consisted of pregnant women initially treated with diet only and then, according to glycemic profile and HbA1 profile, in the next few weeks with insulin therapy. Group 2 were pregnant women who were treated with insulin therapy immediately after GDM diagnosis. RESULTS: There was a statistically significant difference in mean glycemia values in the 60th and 120th minute between the two groups (p = 0.001). There was a difference in mean value of fasting blood and postprandial glucose between the two groups; it was higher in Group 2. There was a statistically significant difference between the two groups in HbA1c value at the beginning (5.1 +/- 0.4% vs. 5.42 +/- 0.43%, p = 0.005) and at the end of therapy (4.87 +/- 0.29% vs. 5.1 +/- 0.39 %, p = 0.018). CONCLUSION: Satisfactory glycoregulation was achieved in both studied groups.

Effects of methyldopa and nifedipine on uteroplacental and fetal hemodynamics in gestational hypertension.

OBJECTIVE: Investigation of methyldopa and nifedipine effects on maternal and fetal hemodynamics in women with mild gestational hypertension during the third pregnancy trimester. METHODS: A prospective cohort study. Methyldopa effects were followed in 28 patients, and nifedipine effects in another 28 patients. There were also 28 healthy controls. RESULTS: Uterine artery blood velocity waveform indices were improved only by nifedipine. Neither of the drugs affected the indices in umbilical and fetal middle cerebral artery. Both drugs normalized maternal blood pressure and pulse. CONCLUSIONS: Methyldopa and nifedipine did not show clinically significant influence on umbilical artery and fetal cerebral blood flow.

[The ultrasonographic diagnosis of fetal encephalocele at 13th gestational week].

BACKGROUND: Encephalocele presents a rare anomaly of central nervous system, developed as a consequence of neural tube closing defect during early embrional development, and it is described by a baggy formation which prolaborates through the pores of the scull, filled with brain tissue, cerebrospinal liquor and entwined with meninges. According to literature search, until this day, the earliest it can be ultrasonically detected is the 13th gestation week, with the appliance of three-dimensional ultrasound. CASE REPORT: We presented 25 years old patient, ultrasonically diagnosed with occipital fetal encephalocela at the 13th gestation week. A gestation sack was located in the right uteral corn of the two-corned uterus with one cervix. The diagnosis was confirmed also by trippled value of alpha-fetoprotein in maternal serum: 75.98 IU/mL. CONCLUSION: Ultrasonic examination is the method of choice for prenatal detection of a fetal anomaly. It is possible to diagnose encephalocele if it prominates above the limits of the scull.

[Hyperlipidemia and pregnancy].

During pregnancy of healthy women, it is usual for blood lipids to increase significantly. Total cholesterol, HDL- and LDL-cholesterol increase 25-50%, while triglycerides increase twice to four times, and there is also an increase ofapolipoproteins B. However, this lipid expansion in blood does not lead to endothelial disfunction. Clinical problem are therapy dilemas about the women who were treated with antihyperlipemics during preconception period, possibility of diagnosing hyperlipidemia in pregnancy and their treatment during the pregnancy, then lactacy. It is generally accepted that neither of antihyperlipemic groups is completely harmless to be applied in preconception period, pregnancy and lactacy period. Those patients who had low to medium increased values of triglycerides prior to pregnancy may develop severe hypertriglyceridemia, especially in the third trimester. They must be educared about dietetic measures and body mass reduction even in preconcepticon period, while during pregnancy they must be supervised and in case of triglycerides increase above 11.5 mmol/l and the resulting risk of pancreatitis, other therapy options must be taken into consideration. In women who had hypercholesterolemia before pregnancy as well as those who developed it only during pregnancy, there is a risk of atherosclerosis development in fetus at the birth itself. Besides, children born by mothers with hypercholesterolemia have a risk of faster progression of these fatty streak during the first living year. Although statins do not represent major teratogenic substances in human pathology, it is advised to stop their application either before conception in planned pregnancy, or at the very moment when pregnany is confirmed (abortions are not encouraged).

A study of alloreactivity in couples with habitual abortions of unknown etiology.

During 2003, we investigated 22 couples with three or more consecutive spontaneous abortions without liveborn children. The study group consisted of 9 couples with three or more successive spontaneous abortions without liveborn children and without known endogenous or exogenous causes of habitual abortions. The first control group comprised 9 couples with liveborn children, while the second one included 9 randomly selected couples without children. The immunologic status was evaluated in regard to functional capacity of lymphocytes, response of T-lymphocytes to disabled histocompatible antigens of partner's lymphocytes, and T-lymphocytes to partner's alloantigens. In women from study and control groups there were no statistically significant differences in general immunologic status functional capacity of lymphocytes). In women from the study group, T-lymphocytes response to stimulation by disabled partner's lymphocytes was significantly lower compared to both control groups (P < 0.05). However, the immunologic reaction of women from the study group to alloantigens of men from control groups did not show any significant difference compared to control groups results (P > 0.05). According to our study, it can be concluded that immunologic factors have an important role in a great proportion of habitual abortions with unknown etiology.