Treatment of Ulcerative Colitis: Impact on Platelet Aggregation.

Background and Objectives: Ulcerative colitis is chronic and/or progressive inflammation of the colorectal mucosa and submucosa and represents one of two major inflammatory bowel diseases. Ulcerative colitis has been associated with increased risk of arteriosus and venous thrombosis. There are numerous factors responsible for this; one of them is platelet activation and aggregation. The objective of our study was to determine if different treatment options for ulcerative colitis have an impact on platelet aggregation. Materials and Methods: This research was a prospective, observational study and included 94 newly diagnosed patients with UC divided into four treatment groups. For all patients, we measured platelet aggregability by using an impedance aggregometry method with a multiplate analyzer before and after treatment with infliximab, adalimumab, vedolizumab and azathioprine. A Paired Samples t test was performed in order to determine the difference in platelet aggregability before and after a certain therapy, since the data followed a normal distribution. Taking into account the impact of some clinical characteristics, multiple linear regression was conducted for the purpose of estimating the effect of therapy on the level of reduction in platelet aggregability. Results: All four drugs significantly reduced platelet aggregability. After we excluded the influence of clinical and endoscopic scores and disease localization on the results, we found that infliximab had the greatest anti-platelet activity. Conclusions: In addition to the well-known traditional risk factors for atherosclerosis, activation and aggregation of platelets play a significant role in the development of arterial thrombosis, and our results suggested that therapy use for the treatment of UC, especially infliximab, can have a great impact on cardiovascular morbidity and mortality by decreasing platelet aggregability.

Predictors of Non-Adherence to Medications in Hypertensive Patients.

Background: Elevated blood pressure (BP) is one of the leading causes for developing major cardiovascular events and still represents a major public health challenge worldwide. We aimed to provide data on predictors of poor adherence to medication in hypertensive patients in Serbia. Methods: Observational, analytical study was undertaken at a group of 388 patients who refilled their medications in the Pharmacy Institution, "Apoteka Kragujevac", Kragujevac, Serbia between Jan and Mar 2019. Afterward, we conducted a case-control study to evaluate the influence of the variables associated with the adherence. We used a self-developed questionnaire and SF-36 to assess the influence of the quality of life on medication adherence. Results: Results revealed four independent predictors of non-adherence: increased number of medications, living in a city, forgetfulness of the dosing regimen and low energy. The odds of non-adherence were the highest among the participants living in the city and the low energy was the only factor inversely associated with the level of non-adherence. Conclusion: Many factors were associated with the non-adherence to medication. Further studies are needed to find the most appropriate protocol to promote adherence. The four risk factors (increased number of medications, living in a city, forgetfulness of the dosing regimen and low energy) are associated with non-adherence in adult hypertensive patients.

Social support score in patients with malignant diseases-with sociodemographic and medical characteristics.

Introduction: Social support as a complex construct has a positive influence not only on a patient's condition but also on the process of the patient's emotional adjustment to cancer. The goal of this study is to investigate aspects of the level of social support in oncology patients and its interconnection with sociodemographic and medical variables. Method: The study was conducted as a prospective observational study in 2020, including 250 patients aged 19 and over, both sexes, with a diagnosis of oncological disease. The research was conducted in the Department of General Medicine of the Health Center Trstenik, Central Serbia, after approval by the Ethics Committee of the Health Center Trstenik, Central Serbia. A social support assessment questionnaire (Oslo-3 Social Support Scale) was used as a research instrument. Results: Data collected from the entire study population showed that bad social support was present in almost 90% of cases. Univariate and multivariate regression analysis showed a statistically significant influence of the following variables on the bad social support: education level, activity limitation, difficulties in performing daily activities, the impact of pain on the performance of activities, the need for additional help with activity, the need for help at home, unfulfilled needs for health care, means of information, anxiety score and depression score. Conclusion: Interventions to increase social support may be important for enhancing mental health and quality of life in cancer patients.

The functional consequences in severe and critical covid-19 survivors - A pilot study.

PURPOSE: To perform pulmonary function tests (PFT) in severe COVID-19 survivors one and five months after hospital discharge in order to assess the lung function, as well to identify clinical characteristics and PFT parameters associated with worse cardiopulmonary exercise testing (CPET). MATERIAL AND METHODS: A prospective study included 75 patients with severe form of COVID-19. PFT was conducted one and five months after hospital discharge, in addition to CPET in a second assessment. Patients with a previous history of chronic respiratory diseases were excluded from our study. RESULTS: One month after hospital discharge, all examined patients had diffusion lung capacity for carbon-monoxide(DLco%) below the 80% of predicted values (in mean 58%), with 40% of patients having a restrictive pattern (total lung capacity(TLC) < 80%). In a repeated assessment after five months, pathological DLco% persisted in 40% of patients, while all other PFT parameters were normal. CPET showed reduced maximum oxygen consumption during exercise testing (VO2peak%) values in 80% of patients (in mean 69%), and exercise ventilatory inefficiency in 60%. Patients with VO2peak < 60% had significantly lower values of examined PFT parameters, both one and five months after hospital discharge. Patients with VO2peak% ≥ 60% had a significantly higher increase after the second assessment for Forced expiratory volume in 1st second (FEV1%), Forced expiratory volume in 1st second and forced vital capacity ratio (FEV1/FVC), DLco% and Diffusion lung capacity for carbon monoxide corrected for alveolar volume (DLco/VA). CONCLUSION: Significant functional abnormalities, according to PFT and CPET, was present both one and five months in severe COVID-19 survivors, thus emphasizing the importance of a comprehensive follow-up including both resting and dynamic functional assessment in these patients.

Resource Use and Costs Related to Hematological Complications of Chemotherapy: Cost of Illness Study Based on Data from Balkan Country with Recent History of Socioeconomic Transition.

Background: The administration of chemotherapy positively correlates with diverse adverse drug reactions, including the significant impact of hematological hazards such as anemia, leukopenia-neutropenia, thrombocytopenia, and pancytopenia. This pilot pharmacoeconomic study aimed to estimate the total direct costs of treating hematological toxicity induced by chemotherapy and its main determinants. Methods: The study was conducted as a retrospective cost of illness study using the "from bottom to the top" approach from the perspective of the Republic Health Insurance Fund. This study included 88 patients treated due to developing at least one episode of one of the types of hematological complications of cytostatics in 2018 at the Oncology Clinic of the University Clinical Center Kragujevac, Kragujevac, the Republic of Serbia. Results: Among cancer patients who developed haematological toxicity, treating pancytopenia was most demanding in a pharmacoeconomic manner compared to neutropenia and thrombocytopenia, with an estimated value of direct costs of 264,14, 178,19 and 157,76 euros per patient per year respectively. Regarding total direct costs, the main determinants were the costs of drugs, their parenteral administration, and costs due to hospitalization. Conclusion: Due to the rising cancer incidence and obligatory hospital treatment of hematological toxicity induced by chemotherapy, the identification of the pharmacoeconomic aspects of the treatment of these complications is needed. Future research should focus on the development of new modalities of treatment regarding patient characteristics anticipating high costs.

The significant role of dietary intake of vitamin D in non-menopausal women health.

Optimal vitamin D status is very important for reflecting not only bone but overall woman's health. The aim of the study was to determine pharmacokinetic variability of 25-hydroxy vitamin D, to reveal and quantify the most significant factors that affect its variability in the population of healthy non-menopausal women using the population pharmacokinetic (PopPK) approach. The study population consisted of 74 healthy reproductive women aged from 35 to 50 years, without the use of any supplement. A population pharmacokinetics analysis was conducted using a nonlinear mixed-effects model software. A total of 35 factors were assessed: demographic, clinical, biochemical data and lifestyle factors. The average age and bodyweight of our participants were 40.11 ± 4.35 years 65.30 ± 6.80 kg, respectively. The observed mean serum concentration of 25-hydroxy vitamin D was 26.51 ± 13.49 ng/mL with a wide range of 6.97 to 59.89 ng/mL. Development final PopPK model of the clearance of 25-hydroxy vitamin D showed that only the average daily dose of vitamin D intake from food had a significant influence, with a magnitude of its effects of 0.00401. These results could help when individualizing vitamin D intake in the form of supplements, especially during the wintertime, in healthy reproductive women.

Disability, Work Absenteeism, Sickness Benefits, and Cancer in Selected European OECD Countries-Forecasts to 2020.

BACKGROUND: Disability either due to illness, aging, or both causes remains an essential contributor shaping European labor markets. Ability of modern day welfare states to compensate an impaired work ability and absenteeism arising from incapacity is very diverse. The aims of this study were to establish and explain intercountry differences among selected European OECD countries and to provide forecasts of future work absenteeism and expenditures on wage replacement benefits. METHODS: Two major public registries, European health for all database and Organization for Economic Co-operation and Development database (OECD Health Data), were coupled to form a joint database on 12 core indicators. These were related to disability, work absenteeism, and sickness benefits in European OECD countries. Time horizon 1989-2013 was observed. Forecasting analysis was done on mean values of all data for each single variable for all observed countries in a single year. Trends were predicted on a selected time horizon based on the mean value, in our case, 7 years up to 2020. For this purpose, ARIMA prediction model was applied, and its significance was assessed using Ljung-Box Q test. RESULTS: Our forecasts based on ARIMA modeling of available data indicate that up to 2020, most European countries will experience downfall of absenteeism from work due to illness. The number of citizens receiving social/disability benefits and the number being compensated due to health-related absence from work will decline. As opposed to these trends, cancer morbidity may become the top ranked disability driver as hospital discharge diagnoses. Concerning development is the anticipated bold growth of hospital discharge frequencies due to cancer across the region. This effectively means that part of these savings on social support expenditure shall effectively be spent to combat strong cancer morbidity as the major driver of disability. CONCLUSION: We have clearly growing work load for the national health systems attributable to the clinical oncology acting as the major disability contributor. This effectively means that large share of these savings on public expenditure shall effectively be spent to combat strong cancer morbidity. On another side, we have all signs of falling societal responsibility toward the citizens suffering from diverse kinds of incapacity or impaired working ability and independence. Citizens suffering from any of these causes are likely to experience progressively less social support and publicly funded care and work support compared to the golden welfare era of previous decades.

Legal Framework and Retirement Policies in Serbia from 1990 to 2016 - Gendered Perspective.

Retirement policy is an unavoidable factor for the economic and social stability of the state. In our country, Serbia, the total number of pensioners in 2015 was almost 1.8 million, which is higher in comparison to the time period from 2002 to 2014. According to increased number of pensioners, pension reforms are a crucial step of economic stability for less developed country, such as Serbia. The first step in this question in Serbia was made in 2001, and this change was referred to the raise in the retirement age. Next step was made in 2003 and involved wider ranges of changes than the previous step. Another change in this field was followed by 2005, and it was related to age limit for retirement, which was supposed to increase for 6 months each year during the period from 2008 to 2011, while another change was a gradual pension adjustment. The last step in this road of pension reforms in Serbia has become with adopted Law on Pension and Disability Insurance that entered into force in January 2015, when age limit for retirement was extended for both genders, whereby it is clear that the aim of this measure is to equalize years of service for genders by 2023 and age limit by 2032 when 65 years will be the age limit.

The New and Old Europe: East-West Split in Pharmaceutical Spending.

HIGHLIGHTS Since the geopolitical developments of 1989, former centrally planned economies of Eastern Europe followed distinctively different pathways in national pharmaceutical expenditure evolution as compared to their free market Western European counterparts.Long term spending on pharmaceuticals expressed as percentage of total health expenditure was falling in free market economies as of 1989. Back in early 1990s it was at higher levels in transitional Eastern European countries and actually continued to grow further.Public financing share of total pharmaceutical expenditure was steadily falling in most Central and Eastern European countries over the recent few decades. Opposed scenario were EU-15 countries which successfully increased their public funding of prescription medicines for the sake of their citizens.Pace of annual increase in per capita spending on medicines in PPP terms, was at least 20% faster in Eastern Europe compared to their Western counterparts. During the same years, CEE region was expanding their pharmaceuticals share of health spending in eight fold faster annual rate compared to the EU 15.Private and out-of-pocket expenditure became dominant in former socialist countries. Affordability issues coupled with growing income inequality in transitional economies will present a serious challenge to equitable provision and sustainable financing of pharmaceuticals in the long run.

Do Health Reforms Impact Cost Consciousness of Health Care Professionals? Results from a Nation-Wide Survey in the Balkans.

BACKGROUND: Serbia, as the largest market of the Western Balkans, has entered socioeconomic transition with substantial delay compared to most of Eastern Europe. Its health system reform efforts were bold during the past 15 years, but their results were inconsistent in various areas. The two waves of global recession that hit Balkan economies ultimately reflected to the financial situation of healthcare. Serious difficulties in providing accessible medical care to the citizens became a reality. A large part of the unbearable expenses actually belongs to the overt prescription of pharmaceuticals and various laboratory and imaging diagnostic procedures requested by physicians. Therefore, a broad national survey was conducted at all levels of the healthcare system hierarchy to distinguish the ability of cost containment strategies to reshape clinician's mindsets and decision-making in practice. AIMS: Assessment of healthcare professionals' judgment on economic consequences of prescribed medical interventions and evaluation of responsiveness of healthcare professionals to policy measures targeted at increasing cost-consciousness. STUDY DESIGN: Cross-sectional study. METHODS: A nationwide cross-sectional survey was conducted through a hierarchy of medical facilities across diverse geographical regions before and after policy action, from January 2010 to April 2013. In the middle of the observed period, the National Health Insurance Fund (RFZO) adopted severe cost-containment measures. Independently, pharmacoeconomic guidelines targeted at prescribers were disseminated. Administration in large hospitals and community pharmacies was forced to restrict access to high budget-impact medical care. Economic Awareness of Healthcare Professionals Questionnaire-29 (EAHPQ-29), developed in Serbian language, was used in face-to-face interviews. The questionnaire documented clinician's attitudes on: Clinical-Decision-Making-between-Alternative-Interventions (CDMAI), Quality-of-Health-Care (QHC), and Cost-Containment-Policy (CCP). The authors randomly and anonymously recruited 2000 healthcare experts, with a total of 1487 responding; after eliminating incomplete surveys, 649 participants were considered before and 651 after policy intervention. RESULTS: Dentists (1.195±0.560) had a higher mean CDMAI score compared to physicians (1.017±0.453). The surgical group compared to the internist group had a higher total EAHPQ-29 score, CCP score and CDMAI score. Policy intervention had a statistically significant negative impact on the QHC score (F=4.958; df=1; p=0.027). There was no substantial impact of policy interventions on professional behavior and judgment with regard to the CDMAI, CCP, and total EAHPQ-29 scores. CONCLUSION: Although cost savings were forcibly imposed in practice, the effects on clinical decision-making were modest. Clinicians' perceptions of quality of medical care were explained in a less effective manner due to the severely constrained resources allocated to the providers. This pioneering effort in the Balkans exposes the inefficiency of current policies to expand clinicians' cost consciousness.

Risk factors for potentially inappropriate prescribing to older patients in primary care.

PURPOSE: The aim of this study is to determine modifiable risk factors contributing to potentially inappropriate prescribing in older primary care outpatients (≥65 years). METHODS: Two separate, age- and sex-matched case-control studies were carried out simultaneously at the Primary Health Care Center Kragujevac, Serbia, during the period September 2013-September 2014. The cases were defined as patients with at least one prescription for potentially inappropriate medication (PIM) according to Screening Tool of Older Persons potentially inappropriate Prescriptions (STOPP) criteria (n = 122), and patients who had at least one potential prescribing omission (PPO) listed in Screening Tool to Alert doctors to the Right Treatment (START) criteria (n = 108), while the control groups consisted of patients without such outcomes (n = 244 and n = 216, respectively). RESULTS: A total of 138 PIM and 161 PPO events were identified using 26 (41.3 %) of STOPP criteria and 17 (77.3 %) of START indicators, respectively. The unhealthy behaviors including at least two of the following: sedentary lifestyle, improper nutrition, active smoking or heavy alcohol consumption (adjusted OR 2.57, 95 % CI 1.28-5.20), use of multiple drugs (five to eight drugs, adjusted OR 3.05, 95 % CI 1.59-5.85; ≥9 of drugs adjusted OR 7.17, 95 % CI 3.07-16.74) and frequent contacts between patients chosen general practitioners (GPs) and pharmaceutical sales representatives (adjusted OR 2.28, 95 % CI 1.10-4.75), were identified as major risk factors for PIM use. Patients who were handled by GPs from smaller practices (adjusted OR 0.51, 95 % CI 0.29-0.93), those with more organ systems affected by the extremely severe disorders and those who often visited the outpatient specialist services (adjusted OR 0.88, 95 % CI 0.81-0.95), had a significantly reduced risk of PPO. CONCLUSIONS: This study suggests that avoidance of major polypharmacy, use of nonpharmacological measures to improve lifestyle habits and decreasing the exposure of physicians to drug promotional material may reduce the risk of PIM use in older primary care outpatients. The only modifiable protective factors for PPOs were working environment of the patients chosen GPs and more frequent ambulatory visits to specialists.

Population pharmacokinetics of 25-hydroxyvitamin D in healthy young adults.

OBJECTIVES: The aim of our study was to develop a population pharmacokinetic (PPK) model for 25-hydroxyvitamin D clearance in a healthy young adult population in Serbia. METHODS: Study sample consisted of 70 healthy young students of the Faculty of Medical Science, University of Kragujevac, Serbia, with a mean age and body mass index of 22.39 ± 1.82 years and 21.31 ± 2.69 kgm-2, respectively. Non-linear mixed-effect modeling (NONMEM) software was used for data analysis. A validation set of 16 participants was used to estimate the predictive performance of the pharmacokinetic model. RESULTS: In the base model (without covariates), we had parameter estimates of 0.01 L/h for apparent clearance, 0.25 L for apparent volume of distribution, while value of minimum objective function (MOF) was 383.468. The full regression model was established by estimating the effects of 12 covariates. Mean intake of vitamin D from foods (DD) and value of phosphate in serum (PHO) were covariates included in the final model, while others were excluded in this process. The estimated value in the final MOF model was 274.555. The final regression model formula was: clearance (CL) (L/h) = 0.0711 + 0.738 x DD + 0.618 x PHO. CONCLUSIONS: The PPK model obtained determined clearance of 25-hydroxyvitamin D in a healthy young adult population in Serbia. Mean intake of vitamin D from foods and serum phosphate level are the most important covariates that influence value of 25-hydroxyvitamin D clearance in healthy young adults.

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.

Risk factors for severe dental anxiety among medical students.

BACKGROUND/AIM: Severe dental anxiety (SDA) is the most severe form of dental anxiety, thus the aim of this study was to determine the factors associated with SDA in students of health-related disciplines. METHODS: In this case-control study the cases were students with severe dental anxiety. The study was conducted at the Faculty of Medical Sciences, University of Kragujevac, Serbia. The participants were undergraduate students attending lectures during spring semester 2010/2011 (n = 1,812). A random sample of 800 students was assessed for the association between various risk factors and the severe dental anxiety. The main outcome measures were the data on demographics, dental anxiety, habits concerning oral hygiene, nutrition, general anxiety and (co)morbidity which were collected from the study participants by semi-structured questionnaire. RESULTS: Less frequent visits to the dentist (OR adjusted = 7.02 [2.65; 18.60]) and visiting the dentist only when there is a dental problem (OR adjusted = 8.08 [1.28; 50.93]) were associated with severe dental anxiety. The same was true for improper oral hygiene (OR adjusted = 4.25 [1.16; 15.60]). Factors as changing toothbrush more frequently (OR adjusted = 0.33 [0.14; 0.76]) and having chronic disease (OR adjusted = 0.01 [0.00; 0.09]) were inversely associated with severe dental anxiety. The level of education of students was not associated with severe dental anxiety. CONCLUSION: Inappropriate oral hygiene, less frequent changes of a toothbrush and less frequent visits to the dentist are important risk factors for severe dental anxiety.

Assessment of viral genotype impact to the cost-effectiveness and overall costs of care for PEG-interferon-2α + ribavirine treated chronic hepatitis C patients.

BACKGROUND: Pegylated interferon alfa plus ribavirin protocol is currently considered the most efficient hepatitis C treatment. However, no evidence of costs comparison among common viral genotypes has been published. OBJECTIVES: We aimed to assess core drivers of hepatitis C medical care costs and compare cost effectiveness of this treatment among patients infected by hepatitis C virus with genotypes 1 or 4 (group I), and 2 or 3 (group II). PATIENTS AND MATERIALS: Prospective bottom-up cost-effectiveness analysis from societal perspective was conducted at Infectious Diseases Clinic, University Clinic Kragujevac, Serbia, from 2007 to 2010. There were 81 participants with hepatitis C infection, treated with peg alpha-2a interferon plus ribavirin for 48 or 24 weeks. Economic data acquired were direct inpatient medical costs, outpatient drug acquisition costs, and indirect costs calculated through human capital approach. RESULTS: Total costs were significantly higher (P = 0.035) in group I (mean ± SD: 12,751.54 ± 5,588.06) compared to group II (mean ± SD: 10,580.57 ± 3,973.02). In addition, both direct (P = 0.039) and indirect (P < 0.001) costs separately were significantly higher in group I compared to group II. Separate comparison within direct costs revealed higher total cost of medical care (P = 0.024) in first compared to second genotype group, while the similar tendency was observed for total drug acquisition (P = 0.072). CONCLUSION: HCV genotypes 1 and 4 cause more severe clinical course require more care and thus incur higher expenses compared to HCV 2 and 3 genotypes. Policy makers should consider willingness to pay threshold differentially depending upon HCV viral genotype detected.

Cross-sectional survey on complementary and alternative medicine awareness among health care professionals and students using CHBQ questionnaire in a Balkan country.

OBJECTIVE: To conduct a study on attitudes, knowledge, and use of complementary and alternative medicine (CAM) therapies in Serbia. Available data about CAM therapies in the region are scarce, opinions lacking from health sector. Balkan region countries had a delay in issuing national policies on CAM therapies. METHODS: The questionnaire used was based on previously validated CAM Health Belief Questionnaire (CHBQ), formulated as 5-item Likert type scale, adjusted for local environment. Health care students and professionals were evaluated. The questionnaire comprehended 10 closed questions on attitudes, knowledge and use of CAM therapies. This survey was conducted in eight cities of Serbia, January 2010-July 2011. A total of 797 participants was included. The second group of participants was 145 healthcare professionals (50 academic staff, 64 clinical staff, 19 pharmacists, 6 other clinical branch specialists and 6 nurses). Data were collected by an interview. Examinees could acquire maximum of 70 points, 35 representing neutral attitude. RESULTS: Students of dentistry (54.65±6.07) were better informed on CAM therapies than medicine students (50.26±7.92). Pharmacy students (51.16±7.10) accepted low-scientific CAM. Pharmacists scored better than university professors (55.12±6.55 vs. 50.29±9.50). Primary health care professionals had better awareness than pharmacists in dispensing pharmacies. Both groups of participants preferred use of vitamins over any other CAM therapy. CONCLUSION: These pioneering efforts in the region exposed weaknesses in CAM attitudes of current and future health care professionals. Nevertheless, awareness on alternative medicine treatment choices is growing among Balkan prescribers. Supportive legal framework would facilitate dissemination of CAM medical practices.

Elevated plasma levels of transforming growth factor-beta 1 (TGF-beta 1) in patients with advanced breast cancer: association with disease progression.

We examined the association between an elevated plasma TGF-beta 1 level and the disease progression of advanced breast cancer (BC) patients (n = 44). TGF-beta 1 levels were detected by an enzyme-linked immunosorbent assay (ELISA). Platelet carryover and in vitro platelet activation in our plasma samples was assessed and found to be insignificant. Plasma TGF-beta 1 values were significantly elevated (P < 0.05) in stage IIIB/IV patients (median value: 2.40 ng/ml, range: 0.13-8.48 ng/ml, n = 44) compared with healthy donors (median value: 1.30 ng/ml, range: 0.41-4.93 ng/ml, n = 36). Although pronounced in metastatic patients, especially those who had been newly diagnosed, TGF-beta 1 elevation was independent of tumour mass, site of distant metastases, histopathological type, steroid receptor (SR) content and age of the BC patients. Follow-up of 6 patients indicated a relationship between the plasma TGF-beta 1 and the patient's response. This suggests that TGF-beta 1, may be a promising prognostic marker for breast cancer patients with advanced disease. Confirmatory large-scale studies are needed, particularly given the overlap of values between our different subgroups analysed.