The impact of structured education of breast cancer patients receiving capecitabine on mental disorders.

PURPOSE: This study was conducted to assess the impact of structured education of breast cancer patients receiving capecitabine treatment on depression, anxiety and stress. METHODS: The study included 142 breast cancer patients who were receiving capecitabine at the Institute of Oncology and Radiology of Serbia in 2016 and 2017. Patients were randomized into two study groups: the experimental group had additional individual, structured, specific education, before chemotherapy by using a Serbian version of the Multinational Association of Supportive Care in Cancer (MASCC) Oral Agent Teaching Tool (MOATT V1.0), while the control group had usual standard education. Patients were followed up for 3 weeks, during their first chemotherapy cycle. Two instruments were used: specifically designed, for the purpose of this study, sociodemographic questionnaire and the Serbian version of the Depression Anxiety Stress Scales-21 (DASS 21) self-report questionnaire. RESULTS: Before starting capecitabine and education, breast cancer patients with metastatic disease had symptoms of depression (29.58%), anxiety (35.92%) and stress (21.13%), mostly mild and moderate. These symptoms were decreased in the whole group of patients after the first and the third week from education, with significant difference in depression and anxiety. Depression, anxiety and stress were decreased significantly in experimental group of patients from the initial measurement to the one-week and three-week follow-up, comparing to the control group of patients. CONCLUSIONS: Structured education has a significant positive impact on depression, anxiety and stress symptoms of breast cancer patients receiving capecitabine. Therefore, it may be recommended for use in everyday clinical practice.

Cigarette smoking and heavy coffee consumption affecting response to olanzapine: The role of genetic polymorphism.

Objectives: To evaluate the effect of cigarette smoking and heavy coffee consumption on efficacy and safety of olanzapine treatment in schizophrenia patients, in relation to genetic polymorphism.Methods: The study involved 120 patients with schizophrenia, treated with olanzapine for 30 days. Therapy efficacy was determined using three different psychiatric scales, and safety by assessing metabolic adverse effects and extrapyramidal symptoms. Genotyping included CYP1A2*1C, CYP1A2*1F and CYP1A1/1A2 intergenic polymorphism, as well as CYP2D6*3, CYP2D6*4 and CYP2D6*6.Results: Cigarette smoking and heavy coffee consumption decreased the efficacy and increased the safety of olanzapine treatment (P < 0.001). Although the effect was detected only in carriers of CYP1A2*1F allele, covariate analysis revealed that it is independent of CYP1A2 genotype. Olanzapine dose was inversely correlated with the drug efficacy (P ≤ 0.002) and LDL level (P = 0.004). Women and older subjects responded better to therapy (P < 0.026), but had more certain adverse effects (P ≤ 0.049). When controlling for other relevant factors, CYP2D6 metabolizer status affects olanzapine efficacy (P = 0.032).Conclusions: We confirm the effect of cigarette smoking and heavy coffee consumption on olanzapine efficacy and safety. The relevance of CYP1A2 genotype for the described effect needs further investigation. Olanzapine treatment outcome is also affected by dose, sex, age and CYP2D6 metabolizer status.

Positive impact of prescribed physical activity on symptoms of schizophrenia: randomized clinical trial.

BACKGROUND: The purpose of this study was to examine functional capacity of cardio-respiratory system in patients with schizophrenia, and to evaluate the effects of 12 weeks prescribed physical activity on aerobic capacity and symptoms of schizophrenia. SUBJECTS AND METHODS: Study involved 80 hospitalized patients with any of the subtypes of schizophrenia (42 men, 38 women). They were divided into two groups: exercise and control group, both with 40 patients. Maximal aerobic capacity (VO2 max) as an indicator of cardiovascular fitness has been obtained by cardiopulmonary stress test on a treadmill. Twelve weeks program of prescribed physical activity (45 minutes, four times per week) was made for every patient individually. Patients in exercise group practiced in training zone between 65 and 75% of their maximum heart rate (HR). Target HR was controlled by Polar F4 monitors. Symptoms of schizophrenia were measured by using Positive and Negative Symptoms Scale (PANSS). RESULTS: Before the exercise program was introduced, measured VO2 max was significantly lower in patients with schizophrenia, than the expected average value in matched healthy subjects (p<0.001). After twelve weeks, patients in exercise group showed a significant increase of VO2max (p=0.002), and significantly higher level of VO2max compared to the control group (p=0.000). Significant differences were also observed on PANSS general psychopathology subscale (p=0.007) and on PANSS total score (p=0.001). The pharmacotherapy and exercise had influence on PANSS general psychopathology (p=0.002) and PANSS total score (p=0.001). CONCLUSIONS: Individuals with schizophrenia have lower levels of aerobic capacity compared to general population. Prescribed physical activity significantly improves aerobic capacity in people with schizophrenia and it is effective in amelioration of some psychiatric symptoms. Prescribed physical activity could be an effective adjunctive treatment for patients with schizophrenia, not only for prevention and treatment of comorbidities, but also having an impact on symptoms of schizophrenia.

Prostitution as a Psychiatric Situation: Ethical Aspects.

This paper presents the morally controversial phenomenon of prostitution. As the basis for contemplating the prostitution issue the most important is revealing and understanding its primitive ethical root. For understanding its "soul", its essence, also important is comprehending sexual, "elementary thoughts" of mankind, through the relationship between prostitution and religious, social, political and spiritual life, and its nature as a reflection of the sexual-ethical concepts in different epochs and nations. We emphasize the connection between prostitution and psychiatry. Placing a special focus on importance of personality for deciding to become a prostitute, and by pulling it through a moral prism we define prostitution as a new medical situation. In favor of that, we stress the importance of the presence, position and role of psychiatrists within an indispensable multidisciplinary team, which is complementary despite its heterogeneousness, synergistically and simultaneously dealing with psychological, physical and social health-problems of women engaged in prostitution. We propose peer education as a way of promoting healthy and safer behaviors among the subculture of prostitutes, where we see another important role of psychiatrists in selecting/recruiting, training and motivating peer educators among them.

The prevalence and socioeconomic correlates of depressive and anxiety symptoms in a group of 1,940 Serbian university students.

UNLABELLED: BACKGROUND/AIM. Mental health of university students is under increasing concern worldwide, because they face challenges which predisposes them to depression and anxiety. The aim of this study was to identify demographic and socioeconomic variables associated with depressive and anxiety symptoms among university students. METHODS: This cross-sectional study on 1,940 university students was performed using a questionnaire including demographic and socioeconomic variables, Beck Depression Inventory and Beck Anxiety Inventory. RESULTS: The prevalence of depressive symptoms in students was 23.6%, while the prevalence of anxiety symptoms was 33.5%. The depressive symptoms were significantly related to the study year (p = 0.002), type of faculty (p = 0.014), satisfaction with college major choice (p < 0.001), satisfaction with grade point average (p < 0.001). Female students (odds ratio--OR = 1.791, 95% confidence interval--CI = 1.351-2.374), older students (OR = 1.110, 95% CI = 1.051-1.172), students who reported low family economic situation (OR = 2.091, 95% CI = 1.383-3.162), not owning the room (OR = 1.512, 95%CI = 1.103-2.074), dissatisfaction with graduate education (OR = 1.537, 95% CI = 1.165-2.027) were more likely toshow depressive symptoms. The anxiety symptoms were significantly related to study year (p = 0.034), type of faculty(p < 0.001), family economic situation (p = 0.011), college residence (p = 0.001) satisfaction with the college major choice (p = 0.001), and satisfaction with graduate education(p < 0.001). Female students (OR = 1.901, 95% CI =1.490-2.425), and students who reported parents high expectations of academic success (OR = 1.290, 95% CI =1.022-1.630) were more likely to show anxiety symptoms. CONCLUSION: This is one of the largest study examining mental disorders in a sample of university students in Serbia. These findings underscore the importance of early detections of mental problems and prevention interventions in university students.

Parameters of Calcium Metabolism Fluctuated during Initiation or Changing of Antipsychotic Drugs.

OBJECTIVE: Serum parameters of calcium homeostasis were measured based on previously published evidence linking osteoporotic fractures and/or bone/mineral loss with antipsychotics. METHODS: Prospective, four-week, time-series trial was conducted and study population consisted of patients of both genders, aged 35-85 years, admitted within the routine practice, with acute psychotic symptoms, to whom an antipsychotic drug was either introduced or substituted. Serial measurements of serum calcium, phosphorous, magnesium, 25(OH)D, parathyroid hormone, calcitonin, osteocalcin and C-telopeptide were made from patient venous blood samples. RESULTS: Calcium serum concentrations significantly decreased from baseline to the fourth week (2.42±0.12 vs. 2.33±0.16 mmol/L, p=0.022, n=25). The mean of all calcemia changes from the baseline was -2.6±5.7% (-24.1 to 7.7) with more decreases than increases (78 vs. 49, p=0.010) and more patents having negative sum of calcemia changes from baseline (n=28) than positive ones (n=10) (p=0.004). There were simultaneous falls of calcium and magnesium from baseline (63/15 vs. 23/26, p<0.001; OR=4.75, 95% CI 2.14-10.51), phosphorous (45/33 vs. 9/40, p<0.001; 6.06, 2.59-14.20) and 25(OH)D concentrations (57/21 vs. 13/35, p<0.001; 7.31, 3.25-16.42), respectively. Calcemia positively correlated with magnesemia, phosphatemia and 25(OH)D values. Parathyroid hormone and C-telopeptide showed only subtle oscillations of their absolute concentrations or changes from baseline; calcitonin and osteocalcin did not change. Adjustment of final calcemia trend (depletion/accumulation) for relevant risk factors, generally, did not change the results. CONCLUSION: In patients with psychotic disorders and several risks for bone metabolism disturbances antipsychotic treatment was associated with the decrease of calcemia and changes in levels of the associated ions.

Meta-analysis of the changes in correlations between depression instruments used in longitudinal studies.

BACKGROUND: Correlations between instruments measuring the same construct reflect their concurrent validity. Little is known about changes in correlations between such instruments employed in studies with repeated assessment. The aim of this meta-analysis was to examine the changes in correlations between depression instruments in the course of longitudinal studies. METHODS: A literature search was conducted using MEDLINE and PsycINFO for the period from 1960 to 2013. The total number of collected articles was 3723, of which 61 were included. Three meta-analyses were performed for the changes in correlations between each pair of the three depression scales: Hamilton Rating Scale for Depression (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI). The effect size in these meta-analyses was obtained by the z-transformation of correlation coefficients. RESULTS: Correlations between depression scales increased over time in 52 studies. Significant changes in correlation coefficients were found for correlations between HAMD and BDI (p<0.001) and for correlations between HAMD and MADRS (p<0.001). An increase in correlations between the scales was associated with a decrease in depression scores and increase in their variability. LIMITATIONS: Univariable and multivariable meta-regression models were not obtained in all three meta-analyses because of the lack of data. CONCLUSIONS: A finding that correlations between depression instruments tended to increase over time has significant implications for assessment of the concurrent validity of these instruments. In longitudinal designs it is important to estimate correlations between depression scales over time because different thresholds for scale correlations indicate acceptable concurrent validity at different times.

Effects of hormone replacement therapy on depressive and anxiety symptoms after oophorectomy.

AIM: To assess the effect of hormone replacement therapy on postoperative depression and anxiety symptoms. METHODS: In observational prospective study 80 women divided into two groups were evaluated: women who received estrogen and androgen replacement therapy after hysterectomy with bilateral oophorectomy before onset of menopause (35-45 years old) and a control group that consisted of perimenipausal women (45-55 years old). Hormone replacement therapy began one week after surgery. The severity of depression and anxiety was evaluated through the use of Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale. Subjects from the study group were interviewed right after the surgical treatment, one, two and three months later. Subjects from the control group were interviewed only once. RESULTS: The women who underwent surgery had a statistically significantly higher score in Hamilton Depression Scale (p les than 0.001) and Hamilton Anxiety Scale (p=0.002) compared to the control perimenopausal women. There was a significant reduction of depressive and anxiety symptoms during hormone replacement therapy. Statistically significant difference in depressive score was found immediately after one month of hormone replacement therapy (first week/one month later: p=0.0057). Statistically significant difference in anxiety score appeared three months after the introduction of hormone therapy (first week/one month later: p=0.309; first week/two months later: p=0.046; first week/three months later: p les than 0.001). Level of serum luteinizing hormone was in correlation with depressive and anxiety score. CONCLUSION: Estrogen-androgen replacement therapy may reduce the risk of psychiatric disorders developing in women with bilateral oophorectomy (indication for hysterectomy with oophorectomy was leiomyomata uteri).

Development of an international schedule for the assessment and staging of care for dementia.

BACKGROUND: A reliable and valid global staging scale has been lacking within dementia care. OBJECTIVE: To develop an easy-to-use multi-dimensional clinical staging schedule for dementia. METHODS: The schedule was developed through: i) Two series of focus groups (40 and 48 participants, respectively) in Denmark, France, Germany, Netherlands, Spain, Switzerland, and UK with a multi-disciplinary group of professionals working within dementia care, to assess the need for a dementia-staging tool and to obtain suggestions on its design and characteristics; ii) A pilot-study over three rounds to test inter-rater reliability of the newly developed schedule using written case histories, with five members of the project's steering committee and 27 of their colleagues from Netherlands, France, and Spain as participants; and iii) A field-study to test the schedule's inter-rater reliability in clinical practice in France, Germany, Netherlands, Spain, Italy, Turkey, South Korea, Romania, and Serbia, which included 209 dementia patients and 217 of their caregivers as participants. RESULTS: Focus group participants indicated a clear need for a culture-fair international dementia staging scale and reached consensus on face validity and content validity. Accordingly, the schedule has been composed of seven dimensions including behavioral, cognitive, physical, functional, social, and care aspects. Overall, the schedule showed adequate face validity, content validity, and inter-rater reliability; in the nine field-sites, intraclass correlation coefficients (ICCs; absolute agreement) for individual dimensions ranged between 0.38 and 1.0, with 84.4% of ICCs over 0.7. ICCs for total sum scores ranged between 0.89 and 0.99 in the nine field-sites. CONCLUSION: The IDEAL schedule looks promising as tool for the clinical and social management of people with dementia globally, though further reliability and validity testing is needed.

[Development of forensic psychiatry in Serbia].

The development of legislation in the field of mental health in our region is linked with the emergence and development of the oldest psychiatric hospitals in Serbia.The principle that the mentally ill who committed a criminal offense need to be placed in a psychiatric hospital instead of a prison was introduced at the same time as in the most developed European countries. The founders of the Serbian forensic psychiatry, Dr. Jovan Danic, Dr.Vojislav Subotic Jr. and Dr. Dusan Subotic, were all trained at the first Serbian Psychiatric Hospital ("Home for the Unsound of Mind") that was founded in 1861 in the part of Belgrade called Guberevac. Their successors were psychiatric enthusiasts Prof. Dr.Vladimir F.Vujic and Prof. Dr. Laza Stanojevic. A formal establishment of the School of Medicine of Belgrade, with acquirement of new experience and positive shifts within this field, based on the general act of the University in 1932, led to the formation of the Council of the School of Medicine, which, as a collective body passed expert opinions. Thus, the first Forensic Medicine Committee of the School of Medicine was formed and started its activities in 1931 when Forensic Medicine Committee Regulations were accepted. After the World War II prominent educators in the field of mental health, and who particularly contributed to further development of forensic psychiatry in Serbia were Prof. Dr. Uros Jekic, Prof Dr. Dusan Jevtic, Dr. Stevan Jovanovic, Prof. Dr. Borislav Kapamadzija, Prof. Dr. Maksim Sternic, Prof. Dr. Josif Vesel and Prof. Dr. Dimitrije Milovanovic.

Antipsychotics can modulate the cytokine profile in schizophrenia: attenuation of the type-2 inflammatory response.

OBJECTIVE: We recently reported that the type-2 cytokine response is increased in schizophrenia. The aim of this study was to analyse the effects of antipsychotic drugs on the serum levels of type-1 (TNF-α, IFN-γ), type-2 (IL-4, IL-10), type-17 (IL-17) and regulatory cytokines (TGF-ß, IL-27 and IL-6). METHODS: Cytokine measurements in the patients were performed on day 0 and day 30 of the treatment using standard ELISA assays. Three groups of subjects were studied: patients that were unmedicated with First Episode Psychosis (FEP; n=88), patients that were treated with antipsychotics with Schizophrenia in relapse (SC in relapse; n=45) and healthy controls (n=36). RESULTS: TGF-ß levels were increased in both patient groups and were further enhanced after treatment in the FEP group (p=0.014) but not in the SC relapse group. Antipsychotic treatment was correlated with lower levels of IL-4, IL-6 and IL-27 (p<0.005) in the FEP group. Finally, the serum levels of IL-17 were not significantly altered between the two measurements but were significantly lower in the FEP group (p<0.001) when compared with healthy controls. After therapy, patients with SC who were in relapse had decreased serum levels of IL-4 (p=0.006) and IL-6 (p=0.007). We also observed a weak negative correlation between the IFN-γ/TGF-ß ratio and the total PANSS score and between the IL-17/TGF-ß ratio and the negative and general psychopathology subscales. CONCLUSION: The increased type-2 cytokine serum levels in schizophrenia appear to be downregulated by antipsychotic treatment.

Elevated serum level of type-2 cytokine and low IL-17 in first episode psychosis and schizophrenia in relapse.

Schizophrenia is chronic and debilitating mental disorder. In broad spectrum of possible causes or contributing factors, immune system and cytokines were investigated in the onset and development of schizophrenia. The aim of our study was to analyze the serum concentrations of type-1 cytokines: TNF-α, IFN-γ, type-2 cytokines: IL-4, IL-10, type-17 cytokine: IL-17 and regulatory cytokines: TGF-ß, IL-27, IL-6, in drug-naive patients with First Episode Psychosis - FEP (n = 88) and Schizophrenia in relapse - SC in relapse patients (n = 45), comparing to healthy controls (n = 36). Also, we attempted to determine potential correlation between cytokine levels and/or cytokine ratios with clinical parameters, such as severity of illness, positive, negative and general psychopathology. Our results showed decreased levels of IL-17 (p = 0.018), demonstrating that type-17 response is blunted in psychotic episode. Increased levels of IL-4 (p = 0.033) showed that type-2 response is overweight in psychotic episode. Also, levels of IL-4 in serum of SC in relapse patients were higher than controls (p < 0.0005) and patient with FEP (p = 0.003). This alteration was accompanied with increase in production of TGF-ß in psychotic patients (p = 0.009) and also in FEP (p < 0.0005) and SC in relapse (p < 0.0005). Analysis showed that TGF-ß can be a valuable marker for psychosis. The presence of enhanced anti-inflammatory/immunosuppressive activity in schizophrenia may be an attempt to counteract or limit ongoing pro-inflammatory processes and downregulating chronic inflammation. Finally we have documented decreased levels of IL-17 and IL-17/TGF-ß ratio in these types of psychotic patients, suggesting the new aspects of schizophrenia pathophysiology.

[Characteristics of reproductive health of women in their generative age].

INTRODUCTION: Any research of reproductive health has to encompass the relevant connotations of this complex term. In order to establish relevant multidimensional characteristics, it is necessary to assess intercorrelations of the characteristics most commonly used to describe it. OBJECTIVE: Our aim was to describe the characteristics of reproductive health and to establish their significance in describing this term. METHODS: Within the study of health of adult inhabitants of Serbia, on the sample of 2,817 women aged 20-49 years, the data on different reproductive health characteristics were collected by way of a structured questionnaire. By way of factorial analysis (principal components method, Kaisser Varimax criterion), representative characteristics (factors) were selected out of a large number of characteristics, describing reproductive health of women in a multidimensional way, interrelationships of the factors were explained, and carriers--the most important individual characteristics--were selected for further analysis. RESULTS: The characteristics of female reproductive health in Serbia are poor, both from the health policy standpoint and in comparison with other countries. Reproductive health describes 7 relevant factors and their carriers (characteristics which best reflect the variability of characteristics involved in a factor). These involve sexual behaviour (self-assessed HIV infection risk), contraception (use of contraceptive devices on one's own initiative), adequate protection of reproductive health (usage of gynaecological services even when healthy), abortions (pregnancy outcome), HIV control (HIV testing usage), postpartal protection (visits of field nurses after being discharged from maternity ward) and reproductive period (doctor visits after being discharged from maternity ward). CONCLUSION: All the characteristics of reproductive health used in various studies are not equally important in the description of this complex phenomenon. Factorial analysis can explain intercorrelations of the studied characteristics and make possible the selection of those most representative.

[Pharmacotherapeutical possibilities in mental disorders: current status in Serbia].

The new therapeutical approaches have direct implications on living in order to accomplish remission, stop further progression of illnesses or improve the quality of life. The life expectancy has been increased up to 10 years in the last 55 years, probably owing to the innovative drugs. The innovative drugs application in our everyday clinical practice should be analyzed, related to economical aspects and to the transitional status of a country, but also in the context of fears and misconceptions of therapists. The cost of therapy is not equal to the cost of prescribed drugs, however it also includes direct and indirect costs and medical and nonmedical burden. Countries in our region spend 4-7.3% of the total budget for antipsychotic drugs, while the costs in Serbia are about 1.5%. The new antipsychotics and the new formulations of the available antipsychotics in the treatment of schizophrenia are pharmacoeconomically justified. On the other side, the substance abuse needs other strategies, including new substitution treatments. In our country only methadone maintenance therapy is available. It is necessary to provide adequate legislation to improve the process of drug registration. In the European Union it takes from 0 to 400 days for a drug to be registered, but in Serbia the process last longerthan 3 years. Important laws approved in 2006 and 2009, are only a part of the destigmatiazation of patients with mental disorders. Treatment guidelines also help in resolving these issues. Taking all of the above into consideration, the treatment of mental disorders with innovative drugs is financially justified, but still unreachable for patients in Serbia. The voice of the professionals should be heard in these matters in order to provide the adequate treatment of people with mental health problems.

Quality of life of schizophrenic patients treated with haloperidol depot and injection preparation of long-lasting risperidone.

INTRODUCTION: In the last decades psychiatric patients' quality of life attracts great attention of researchers. Improving the quality of life of schizophrenic patients is increasingly becoming an imperative in pharmacological therapy. OBJECTIVE: Analysis of certain aspects of quality of life in patients with schizophrenia treated with depot formulations of a typical antipsychotic (haloperidol) and injection preparation of a long-acting atypical antipsychotic (risperidone). METHODS: Research was conducted as a cross-sectional study that included 60 patients of both genders. Examinees diagnosed with schizophrenia (ICD-10, F20.0-F20.9) were divided into two groups: the group of patients that received haloperidol depot (n = 30) and the group of patients that received injection preparation of long-acting risperidone (n = 30). In order to assess the quality of life, social functioning scale (SFS), satisfaction with life scale (SWLS), and short version of World Health Organization quality of life scale (WHO-QoL-Brief) were applied. RESULTS: Results showed statistically significant differences when it comes to social activity and satisfaction with life in favour of patients treated with injection preparation of long-acting risperidone. Examinees from this group were much more satisfied with themselves, their health and sleep compared to those on haloperidol depot. There was no statistically significant difference found on the quality of life scale. CONCLUSIONS: Applying the scales for the assessment of the quality of life of schizophrenic patients in terms of psychosocial functioning, statistically significant difference between groups was found. Results showed higher scores in the group of patients treated with injection preparation of long-acting risperidone concerning social activities and life satisfaction.

Differentiation between opiate addicts in relation to judicial problems.

INTRODUCTION: Some research results point to significant benefit in the use of methadone substitution treatment in reduction of criminogenic activities in opiate addicts, as in positive affect on their somatic and mental state. OBJECTIVE: The objective of the study was to indicate factors which lead to criminogenic activities in addicts with judicial problems before entering substitute, methadone program. METHODS: Addicts were divided into two groups: addicts who had judicial problems before they entered substitution methadone program (group A-46 addicts) and addicts withoutjudicial problems (group B-20 addicts). A questionnaire containing basic data about the addicts in the treatment program (Pompidou questionnaire) was for questioning. RESULTS: A statistically significant difference was recorded related to the way of taking PAS. The largest number of examinees from the group A took primal PAS intravenously (41; 89.1%), while from the group B 11 took it intravenously (55.0%). The majority of examinees in the group A committed the first criminal act before taking PAS (psychoactive substances) (19; 41.3%), then after taking so-called harder PAS (16; 34.8%), and finally after taking the so-called lighter PAS (11; 23.9%). In somewhat over half of the examinees in the group A (24; 52.2%) the measure of juvenile court was imposed. A suspended sentence was passed upon 19 (41.3%) examinee, then prison sentence in 16 (34.8%), multiple prison sentences in 6 (13.0%) and misdemeanour in 4 (8.7%). CONCLUSION: Future research at our centre should show the efficiency of methadone program in a decrease of risky behaviour, degree of criminogenic activity and judicial problems, improvement of life quality, as well as show the ways for preventive acting.

Comparison of safety between individualized and empiric dose regimen of amitriptyline in the treatment of major depressive episode.

To accomplish therapeutic goal it is necessary to adjust the dose of medication to be right for every single patient. This procedure of dose adjustment is individualized dose regimen. First of all, pharmacokinetic aspects should be revised, including parameters such as resorption, distribution, metabolism and secretion of drug. For these purposes, the authors developed and clinically assessed the modified Bayesian method supported by original basic computer program. The aim of research was to compare frequency of adverse events in cases of individualized and empiric dose regimens of amitriptyline in the treatment of major depressive episode. Sixty subjects (32- 65 years old), with major depressive disorder (International Classification of Disease, 10th revision), were randomly assigned and single- blinded to take individualized (experimental group, n=30) or empiric (control group, n=30) doses of amitriptyline for 8 weeks. CGI scale and originally designed questionnaire were used for adverse events assessment. In experimental group, 69 complaints on nine different types of adverse effects were recorded during eight-week treatment period. Severe adverse events, such as confusion or arrhythmia, were not registered in this subgroup. In control group, 111 complaints on twelve different types of adverse effects were recorded. Most common were anticholinergic effects, but during the third and fourth week from baseline, some severe adverse events were observed: tremor (16%), fatigue (16%), in one of the subjects confusion occurred and arrhythmia in another. Analyzing of the results according to CGI scale for adverse events showed that, during the treatment period, adverse events were less frequent in experimental group. This was particularly obvious in the first four weeks of treatment, when statistically significant difference (p<0.05) was observed.

[Determinants of the most significant characteristics of reproductive health].

INTRODUCTION: Reproductive health of women is determined by females' demographic and socio-economic characteristics, their behaviour, and the complex of environmental factors. OBJECTIVE: The paper examines the predictive impact of personal and environmental characteristics, health and healthcare characteristics regarding the most important aspects of reproductive health. METHODS: From a sample of 2,718 women, aged 20-49 years, we collected information on various characteristics using a structured questionnaire. Based on factorial analysis (principal components method, Kaisser Varimax criterion) we selected representative variables (factors), describing personal (demographic and socio-economic) characteristics of women, their environment (family, household, community), health (attitudes towards health, life-style, health status), healthcare (independent) and the characteristics of reproductive health (dependent variables). The predictors were analyzed by multiple regression and correlation. RESULTS: Sexual behaviour was determined by socio-economic status, personal tidiness, rest, presence of risk factor(s), health evaluation and attitude toward personal responsibility, trust in physicians etc. The predictors of contraception involved satisfaction with one's own health, serious health problems, health evaluation. The presence and number of abortions were determined by personal psychological maturity, rest, risk factors, life-style, health evaluation and its manifestations, and the continuity and timely healthcare.The predictors of adequate protection of reproductive health involved the cultural level of the community, financial standing of the household, satisfaction with one's own life, tidiness and rest, presence of risk factors, health evaluation, attitude towards personal responsibility, and trust in physicians. HIV control was determined by satisfaction with one's own life, physical activity of women, presence of serious health problems, and the content of primary healthcare. Postpartal protection was determined by the cultural level of the community, reasons for dissatisfaction with one's own life, presence of risk factors and deficiencies, and timely contraception. The predictors of reproductive period duration are availability of health care in a community and personal tidiness of women. CONCLUSION: The study confirmed predictive impact of most of the studied characteristics.