Clozapine levels and outcomes in Serbian patients with treatment-resistant psychotic disorders previously treated without measuring clozapine levels (CLOSER).

Clozapine remains the only pharmacological treatment option for treatment-resistant schizophrenia. Therapeutic drug monitoring (TDM) of clozapine is recommended, although evidence for the therapeutic range of 350-600 ng/ml is limited. In various countries including Serbia, TDM of clozapine is not routinely performed. This study evaluated the distribution of clozapine levels and their relationship with clinical outcomes in Serbian patients who had not undergone prior TDM. 140 Patients with treatment-resistant schizophrenia and schizo-affective disorder were enrolled. Clozapine levels were measured by dried blood spot (DBS) analysis. Side effects were evaluated by GASS-c, severity of symptoms and functional impairment with WHODAS, CGI-S and GAF. Of the patients, 51.2% had subtherapeutic levels, 24.8% were in the therapeutic window, and 24% had supratherapeutic levels. Clozapine levels showed no association with side effects and a weak positive association with symptom severity and functional impairment. No serious side effects were observed in patients with clozapine levels surpassing 1000 ng/ml (n = 8). Based on these findings, we propose that the upper limit of the therapeutic range should not be regarded as an absolute barrier, and guidelines should allow for a personalized approach when prescribing clozapine.

Using machine learning algorithms and techniques for defining the impact of affective temperament types, content search and activities on the internet on the development of problematic internet use in adolescents' population.

Background: By using algorithms and Machine Learning - ML techniques, the aim of this research was to determine the impact of the following factors on the development of Problematic Internet Use (PIU): sociodemographic factors, the intensity of using the Internet, different contents accessed on the Internet by adolescents, adolescents' online activities, life habits and different affective temperament types. Methods: Sample included 2,113 adolescents. The following instruments were used: questionnaire about: socio-demographic characteristics, intensity of the Internet use, content categories and online activities on the Internet; Facebook (FB) usage and life habits; The Internet Use Disorder Scale (IUDS). Based on their scores on the scale, subjects were divided into two groups - with or without PIU; Temperament Evaluation of Memphis, Pisa, Paris, and San Diego scale for adolescents (A-TEMPS-A). Results: Various ML classification models on our data set were trained. Binary classification models were created (class-label attribute was PIU value). Models hyperparameters were optimized using grid search method and models were validated using k-fold cross-validation technique. Random forest was the model with the best overall results and the time spent on FB and the cyclothymic temperament were variables of highest importance for these model. We also applied the ML techniques Lasso and ElasticNet. The three most important variables for the development of PIU with both techniques were: cyclothymic temperament, the longer use of the Internet and the desire to use the Internet more than at present time. Group of variables having a protective effect (regarding the prevention of the development of PIU) was found with both techniques. The three most important were: achievement, search for contents related to art and culture and hyperthymic temperament. Next, 34 important variables that explain 0.76% of variance were detected using the genetic algorithms. Finally, the binary classification model (with or without PIU) with the best characteristics was trained using artificial neural network. Conclusion: Variables related to the temporal determinants of Internet usage, cyclothymic temperament, the desire for increased Internet usage, anxious and irritable temperament, on line gaming, pornography, and some variables related to FB usage consistently appear as important variables for the development of PIU.

Personality traits and attitude towards euthanasia among medical students in Serbia.

OBJECTIVE: Various factors may influence the attitudes of medical students towards euthanasia, including personal values, beliefs, and personality traits. The objective of this study was to examine the attitudes of 2nd and 5th year medical students about euthanasia and the relationship between these attitudes and students' personality traits. METHODS: Medical students from the Universities of Kragujevac and Belgrade, Serbia, participated in this study. A questionnaire was administered assessing attitudes toward euthanasia and student personality traits (honesty-humility, emotionality, extraversion, agreeableness, conscientiousness, and openness using the HEXACO-60). RESULTS: More than 50% of students in the second year and 60% of students in the fifth year were supportive of euthanasia. Students in the 5th year were 2.5 times more likely to express a concern that euthanasia needs to be clearly regulated by law compared to students in the second year. Adjusted analyses indicated that lower levels of honesty-humility and emotionality were positively correlated with students' belief that euthanasia should be legalized. CONCLUSION: Many medical students in Serbia have a positive attitude towards euthanasia. It is important to consider the possible influences of culture, religion, and the law on attitudes towards euthanasia. Undergraduate medical training should include more hours dedicated to palliative care and end-of-life topics to raise awareness of patients' preferences in this regard.

Correlation of the OCT Double-Layer Sign with Type 1 Non-Exudative Neovascularization on OCT-A in Age-Related Macular Degeneration.

Background and Objectives: Early diagnosis of the exudative form of age-related macular degeneration (AMD) is very important for a timely first treatment, which is directly related to the preservation of functional visual acuity over a long period. The goal of this paper was to examine the correlation between the double-layer sign (DLS) and the presence of non-exudative macular neovascularization (MNV). Materials and Methods: Our research included 60 patients with AMD, exudative in one eye and non-exudative in the other eye. We analyzed only the non-exudative form using optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A). The patients were classified into three groups, depending on the duration of the disease (<2 years, 2 to 5 years, >5 years). The onset of the disease was deemed the moment of establishing a diagnosis of exudative AMD in one eye. We defined the presence or absence of a DLS using OCT and the presence of non-exudative MNV using OCT-A, both on 3 × 3 mm and 6 × 6 mm sections. DLS was used as a projection biomarker for non-exudative MNV, with the aim of establishing a rapid diagnosis and achieving early treatment of the disease. Results: We found that there was a statistically significant correlation between the DLS diagnosed using OCT and non-exudative MNV diagnosed by OCT-A for both 3 × 3 mm (p < 0.001) and 6 × 6 mm (p < 0.001) imaging. There was a statistically significant difference between the frequencies of both DLS and MNV in Groups I and III on both 3 × 3 and 6 × 6 mm imaging. A statistically significant difference was also noted in the frequencies of DLS and MNV on 6 × 6 mm imaging, but not on 3 × 3 mm imaging, between Groups I and II. No differences were found between the frequencies of DLS and MNV between Groups II and III. Conclusions: The DLS on OCT can be used as a projection biomarker to assess the presence of a non-exudative MNV.

Association between affective temperaments and psychosomatic symptoms in women with Hashimoto's thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) is a prevalent autoimmune disease of thyroid gland with a shared immunological mechanism with mood disorders. Affective temperament (AT) is a biologically determined personality trait that has been linked to mood disorders. The aim of this study was to examine the association between dominant AT and levels of psychosomatic symptoms in women newly diagnosed with HT in comparison to clinically healthy subjects. METHODS: The observational cross-sectional study with nested case control study was involving 146 consecutive participants, who were divided into three groups. The two study groups consisted of women with HT (73), including 49 with hypothyroid HT and 24 with euthyroid HT, and the third group was a control group of healthy participants (73). The Serbian version of the TEMPS-A was utilized to assess AT, while the 4DSQ was used to measure psychosomatic symptoms. RESULTS: The results showed that hyperthymic AT was dominant in all examined groups. The groups with HT differed from the control group in terms of depressive and cyclothymic AT. Furthermore, the study found higher levels of psychosomatic symptoms in the group with HT compared to the control group, with significant differences in distress (p = 0.005) and somatization (p = 0.023) levels. All AT was associated with levels of psychosomatic symptoms in subjects with hypothyroid HT. In contrast, in subjects with euthyroid HT, the association was only found between depressive and cyclothymic AT with distress and depression levels, as well as between somatization and cyclothymic AT. No association was found between AT and anxiety levels in subjects with euthyroid HT. CONCLUSION: The research found differences between study groups in the association between AT and levels of psychosomatic symptoms. Further research with a larger sample size is necessary to more clearly define the associations between affective temperaments and psychosomatic symptoms in women with euthyroid and hypothyroid HT.

The Influence of Sociodemographic Factors on the Level of Hope in Women with Breast Cancer.

Background: We aimed to determine the level of hope in breast cancer patients along with the influence of sociodemographic characteristics on the expressed level of hope. Methods: A descriptive cross-sectional study was conducted on the sample size of 72 female patients with breast cancer diagnosis. The study was conducted at the University Clinical Center of Kragujevac, Serbia from November 2020 until March 2022. Data were collected from the patients in a form of the Sociodemographic Variables Questionnaire (Q-SV). The Herth Hope Index (HHI) was used in assessing the level of hope. Results: The value of the total HHI score was ranging from 14 to 48, whereas the mean value of the HHI score was 40.00±5.92. The significantly higher level of hope was reported in female patients who: searched the Internet for gathering information on their disease (39.24±6.23; P=0.047), were religious (38.77±6.13; P=0.003), believed in God (38.45±5.51; P=0.004), had no formal medical education (38.44±5.75; P=0.036) and after therapy (38.76±6.49; P=0.022). Conclusion: Hope is an existential internal resource possibly affecting the manner in which female patients perceive their own health state and future as well. A better understanding of the meaning of hope during treatment can be of great value in supporting cancer patients.

Interleukin 12 in the Acute Phase of the Immune Response after Excimer Laser Treatment.

BACKGROUND AND OBJECTIVES: The aim of the research was to investigate the differences in the concentrations of IL-12, IL-4, IL-10, and IFN-γ in tears after LASIK and PRK procedures. MATERIALS AND METHODS: The study included 68 myopic eyes up to -3.0 D refractive spherical equivalent, divided into two groups: Group 1 LASIK (n = 31) and Group 2 PRK (n = 37). Three tear samples were taken from each eye: immediately before the procedure (t0), 1 h after the procedure (t1), and 24 h after the procedure (t2). The concentrations of IL-12p70, IL-4, IL-10, and IFN-γ in the tear samples were determined by flow cytometry. Participants were not taking anti-inflammatory therapy 24 h after the procedure. RESULTS: IL-4 levels 1 h after treatment did not differ between LASIK and PRK (p = 0.990), while 24 h after PRK there was a significant decrease in IL-4 levels (p < 0.05), but not after LASIK (p = 0.476). In both the LASIK (p < 0.05) and PRK (p < 0.05) groups, there is an increase in IL-10 concentrations 1 h after treatment, which persists 24 h after LASIK (p < 0.05) but not after PRK (p = 0.081). There is an increase in IL-12p70 concentration 1 h after treatment in both the LASIK (p < 0.001) and PRK groups (p < 0.001). There is also an increase in IL-12p70 concentration 24 h after PRK (p < 0.005), but not after LASIK (p = 0.775). CONCLUSIONS: IL-4 concentration shows a significantly higher value in the LASIK group than in the PRK group after 24 h. IL-10 and IL-12p70 levels increase one hour after surgery in both groups. After 24 h, the IL-10 levels remain elevated in the LASIK group, and the IL-12p70 levels remain elevated in the PRK group. Thus, LASIK and PRK procedures show different inflammatory dynamics.

Clozapine prescription rates in Southeast Europe: A cross-sectional study.

Introduction: International reports indicate that clozapine is under prescribed. Yet, this has not been explored in Southeast European (SEE) countries. This cross-sectional study investigates clozapine prescription rates in a sample of 401 outpatients with psychosis from Bosnia and Herzegovina, Kosovo by United Nations resolution, North Macedonia, Montenegro and Serbia. Methods: Descriptive analysis was used to explore clozapine prescription rates; daily antipsychotic dosage was calculated and converted into olanzapine equivalents. Patients receiving clozapine were compared to those not receiving clozapine; next those that were on clozapine monotherapy were compared to those who were on clozapine polytherapy regime. Results: It was showed that clozapine was prescribed to 37.7% of patients (with cross-country variation: from 25% in North Macedonia to 43.8% in Montenegro), with average dose of 130.7 mg/daily. The majority of patients on clozapine (70.5%) were prescribed at least one more antipsychotic (the most frequent combination was with haloperidol). Discussion: Our findings suggested that clozapine prescription rate in SEE outpatients is higher than in Western Europe. The average dose is significantly below the optimal therapeutic dosage recommended by clinical guidelines, and clozapine polytherapy is common. This might indicate that clozapine is prescribed mainly for its sedative effect rather than antipsychotic. We hope that this finding will be taken up by relevant stakeholders to address this non-evidence-based practice.

Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom.

PURPOSE/BACKGROUND: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis. METHODS: Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions. FINDINGS/RESULTS: Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year. IMPLICATIONS/CONCLUSIONS: The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries.

Do people diagnosed with psychosis spectrum disorders share the same personality space as the general population? Big Five complemented by the proneness to psychotic-like experiences/behaviors.

OBJECTIVE: Disintegration is a recently proposed broad, trait-like reconceptualization of the proneness to psychotic-like experiences/behaviors. METHODS: We tested the assumption that the 6-factor model (Five-Factor traits plus Disintegration) was the most adequate one and that it was invariant across clinical and non-clinical populations. The clinical sample (n = 161) consisted of patients who had at least one psychotic episode, duration of illness less than 10 years, currently in remission. The general population (n = 409) was matched with the patient sample by age, gender, and education. NEO PI-R and DELTA were used to measure personality dimensions in both samples. Invariance of one to six-factor solutions was tested by Exploratory Structural Equation Modeling. RESULTS: We found that: (a) several criteria for deciding on the number of factors to retain converged to the conclusion that the assumed 6-factor model was the most adequate one, (b) the assumed factorial structure appeared to satisfy the criteria for the scalar invariance across the two samples, (c) all nine Disintegration subdimensions separated from the Big Five, forming the Disintegration factor, and (d) Disintegration was unrelated to Openness. CONCLUSION: The Big Five personality structure-complemented with disintegration-was invariant across individuals from the general population and patients with psychosis.

Risperidone Induced Hyperprolactinemia: From Basic to Clinical Studies.

Risperidone is one of the most commonly used antipsychotics (AP), due to its safety and efficacy in reducing psychotic symptoms. Despite the favorable side effect profile, the therapy is accompanied by side effects due to the non-selectivity of this medicine. This review will briefly highlight the most important basic and clinical findings in this area, consider the clinical effects of AP-induced hyperprolactinemia (HPL), and suggest different approaches to the treatment.The route of application of this drug primarily affects the daily variation and the total concentration of drug levels in the blood, which consequently affects the appearance of side effects, either worsening or even reducing them. Our attention has been drawn to HPL, a frequent but neglected adverse effect observed in cases treated with Risperidone and its secondary manifestations. An increase in prolactin levels above the reference values result in impairment of other somatic functions (lactation, irregular menses, fertility) as well as a significant reduction in quality of life. It has been frequently shown that the side effects of the Risperidone are the most common cause of non-compliance with therapy, resulting in worsening of psychiatric symptoms and hospitalization. However, the mechanism of Risperidone-induced HPL is complicated and still far from fully understood. Most of the preclinical and clinical studies described in this study show that hyperprolactinemia is one of the most common if not the leading side effect of Risperidone therefore to improve the quality of life of these patients, clinicians must recognize and treat HPL associated with the use of these drugs.

HEXACO-60 Personality Trait Inventory: Psychometric characteristics in a sample of medical students from Serbia.

The 60-item HEXACO (HEXACO-60) Personality Trait Inventory may be strategically more important for researchers compared to the 100-item HEXACO. The aim of this study was to assess the psychometric properties of the 60-item HEXACO questionnaire in the Serbian language. This cross-sectional study, conducted at three of five Faculties of Medicine during the summer semester of the 2016/2017 academic year, included 617 students. Relevant data were collected by an anonymous questionnaire. Cronbach's α and McDonald's ω coefficients for the total scale were .71 and .72, respectively. Apart from Agreeableness, all other domains showed an adequate level of internal consistency (both Cronbach's α and McDonald's ω coefficients were >.70). Random data eigenvalues obtained on the parallel analysis had higher values than initial exploratory factor analysis eigenvalues up to the sixth factor. Accordingly, it was concluded that six factors should be extracted from the Serbian HEXACO-60. These factors corresponded in item distribution with the original ones. Based on the confirmatory factor analysis, using both 60 items and 24 facets, overall goodness of fit of the Serbian HEXACO-60 was acceptable. Moreover, there were no domains with completely invalid indices, as there were at least two indices that were acceptable for each domain. The Serbian version of the HEXACO-60 has acceptable psychometric properties. This shorter version with 60 items may be more suitable for brief surveys or when the time allocated to fill in a questionnaire is limited.

Prescription attitudes and practices regarding clozapine among Serbian psychiatrists: results of a nationwide survey.

OBJECTIVE: Despite clozapine being the most effective treatment for treatment-resistant schizophrenia (TRS), a clear explanation as to why it is underutilized and why its initiation is delayed remains unclear. The first aim of the study was to conduct a nation-wide assessment of both the psychiatrists' attitudes of the obstacles for prescribing clozapine as well as their prescription practices. The second aim was to make recommendations, based on the results obtained, for improving the Serbian clozapine guidelines. METHODS: A questionnaire was conducted consisting of two parts. One regarded the clinical characteristics of the psychiatrists, while the second contained questions about indications for clozapine initiation, clozapine prescribing tendencies, and barriers to clozapine use. The questionnaire was sent to 302 Serbian psychiatrists. RESULTS: With 161 out of the 302 psychiatrists returning the questionnaires, the response rate was 53.3%. Nearly 60% of the psychiatrists treated 10 or more patients with clozapine, with TRS being the most common indication. Only four psychiatrists (2.5%) had no patients currently on clozapine. Psychiatrists indicated that their fear of agranulocytosis (68%) constituted the greatest obstacle for clozapine prescription, followed closely by weight gain (56%), and sedation (39%). Despite their fear of agranulocytosis, only 83.9% of the psychiatrists monitored leukocytes regularly. CONCLUSION: In general, psychiatrists in Serbia seem to be confident in prescribing clozapine, even in the absence of clear monitoring guidelines and the possibility of therapeutic drug monitoring. In order to reduce obstacles for clozapine prescription, monitoring laxity, and an overreliance on personal experience, we recommend three modifications of the existing clozapine guideline.

The Glasgow antipsychotic side-effects scale for clozapine in inpatients and outpatients with schizophrenia or schizoaffective disorder.

BACKGROUND: The inconsistency in clinician and patient ratings of clozapine-induced side effects underscore the need to supplement clinician-based estimates of side effects with patient-reported ones. AIMS: The main aims of the study are validation of the Glasgow antipsychotic side-effects scale for clozapine (GASS-C) in Serbian inpatients/outpatients with schizophrenia or schizo-affective disorder and recommendations for its future use, based on common and rare clozapine-associated side-effects. METHODS: The GASS-C was administered to 95 outpatients/inpatients diagnosed with schizophrenia, schizoaffective, or chronic psychotic disorder. RESULTS: The scale showed good overall reliability, with an internal consistency coefficient of α = 0.84, an average retest coefficient of rho = 0.76, and a Spearman-Brown coefficient of validity of 0.81. Side effects were absent or mild in 64.2% of the patients, moderate in 31.6%, severe in 4.2%; 14% of the subjects considered their symptoms distressing. The most commonly reported side-effects were drowsiness, thirst, frequent urination, and dry mouth. Women reported more side effects than men, and patients not in a relationship reported significantly fewer side effects than patients in a relationship. Results indicate a weak positive correlation (rho = 0.231; p = .025) between severity of side effects and clozapine dose. CONCLUSIONS: The GASS-C showed good psychometric characteristics in clinical population of patients on clozapine. In future studies, clozapine serum concentrations should be measured when using the GASS-C to monitor side effects.

The effects of zofenopril on cardiac function and pro-oxidative parameters in the streptozotocin-induced diabetic rat heart.

Diabetes mellitus is a chronic condition that continues to increase in both incidence and prevalence. Renin-Angiotensin-Aldosterone System is one of the main modulators of chronic hyperglycaemia and, thus, its influence on tissues. Hyperglycaemia-induced oxidative stress is an important factor in diabetic cardiomyopathy. The present study was carried out on 24 adult male Wistar albino rats (8-week-old and with body masses of 190 ± 10 g). We evaluated the influence of acute administration of zofenopril on ex vivo myocardial function from rats with streptozotocin-induced diabetes mellitus, with a special emphasis on cardiodynamic and oxidative stress parameters in diabetic rat hearts. Rats were divided randomly into two groups (12 animals per group): control non-diabetic animals (C) were healthy rats perfused with 1.5 µM of zofenopril, and STZ-treated diabetic animals (DM) were diabetic animals perfused with 1.5 µM of zofenopril 4 weeks after the induction of diabetes. Our results demonstrated that diabetic rats are characterized by a depressed cardiac performance and that oxidative markers are related to alterations in cardiac function in rats with 4 weeks of STZ-induced diabetes. Additionally, the use of zofenopril as a monotherapy slightly diminished cardiac damage induced by chronic hyperglycaemia. However, long-term follow-up intervention trials are necessary to fully demonstrate the benefit of zofenopril in this context. A challenge for future investigations will be to identify the effects of chronic administration or combination therapy with angiotensin-converting enzyme inhibitors in various models of diabetes.

Factors Influencing The Six-Month Mortality Rate In Patients With A Hip Fracture: DEJAVNIKI, KI VPLIVAJO NA SESTMESECNO STOPNJO UMRLJIVOSTI PRI BOLNIKIH Z ZLOMOM KOLKA.

BACKGROUND: There are several potential risk factors in patients with a hip fracture for a higher rate of mortality that include: comorbid disorders, poor general health, age, male gender, poor mobility prior to injury, type of fracture, poor cognitive status, place of residence. The aim of this study was to assess the influence of potential risk factors for six-month mortality in hip fracture patients. METHODS: The study included all patients with a hip fracture older than 65 who had been admitted to the Clinic for orthopaedic surgery during one year. One hundred and ninety-two patients were included in the study. RESULTS: Six months after admission due to a hip fracture, 48 patients had died (6-month mortality rate was 25%). The deceased were statistically older than the patients who had survived. Univariate regression analysis indicated that six variables had a significant effect on hip fracture patients' survival: age, mobility prior to the fracture, poor cognitive status, activity of daily living, comorbidities and the place where they had fallen. Multivariate regression modelling showed that the following factors were independently associated with mortality at 6 months post fracture: poor cognitive status, poor mobility prior to the fracture, comorbid disease. CONCLUSION: Poor cognitive status appeared to be the strongest mortality predictor. The employment of brief tests for cognitive status evaluation would enable orthopaedists to have good criteria for the choice of treatment for each patient screened.

Food allergy in children.

Food allergy represents a highly up-to-date and continually increasing problem of modern man. Although being present in all ages, it most often occures in children aged up to three years. Sensitization most often occurs by a direct way, but it is also possible to be caused by mother's milk, and even transplacentally. Predisposition of inadequate immune response to antigen stimulation, reaginic or nonreaginic, is of non-selective character so that food allergy is often multiple and to a high rate associated with inhalation and/or contact hypersensitivity. Also, due to antigen closeness of some kinds of food, cross-reactive allergic reaction is also frequent, as is the case with peanuts, legumes and tree nuts or cow's, sheep's and goat's milk. Most frequent nutritive allergens responsible for over 90% of adverse reactions of this type are proteins of cow's milk, eggs, peanuts, tree nuts, wheat, soy, fish, shellfish, crustaceans, and cephalopods. Allergy intolerance of food antigens is characterized by a very wide spectrum of clinical manifestations. Highly severe systemic reactions, sometimes fatal, are also possible.The diagnosis of food allergy is based on a detailed personal and family medical history, complete clinical examination, and corresponding laboratory and other examinations adapted to the type of hypersensitivity and the character of patient's complaints, and therapy on the elimination diet. A positive effect of elimination diet also significantly contributes to the diagnosis. Although most children "outgrow" their allergies, allergy to peanuts, tree nuts, fish, shellfish, crustaceans, and cephalopods are generally life-long allergies.

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.