MODERATING EFFECT OF BODY HEIGHT ON THE ASSOCIATION OF BODY WEIGHT AND DISABILITY CAUSED BY NON SPECIFIC CHRONIC LOW BACK PAIN IN WOMEN AND MEN.

The aim of the study was testing the hypothesis that body height has a moderating effect on the association of weight and chronic low back pain (LBP) induced disability, and that this moderating effect is different in women and men. We performed a nested cross-sectional analysis using data collected at baseline in a prospective cohort study conducted in 2008-2009 at a special hospital for medical rehabilitation in Croatia. The outcome was the Roland-Morris Disability Questionnaire (RMDQ) score. The independent variable was body weight. The focal moderators were body height and sex. The moderation analysis was adjusted for seven sociodemographic and clinical covariates. We analyzed data on 72 patients with a median (interquartile range) age of 50 (43-55) years, 36 (50%) of whom were women, treated for nonspecific, chronic LBP. The interaction of sex, body weight and height was a significant predictor of the RMDQ score after adjustments for all covariates (increase of R2=0.13; p=0.001; false discovery rate <5%). In both sexes, the correlation between body weight and the RMDQ score was significantly moderated by body height but in opposite ways. In conclusion, the effects of body weight on physical disability are moderated by body height, but this moderation effect differs between women and men.

COVID-19 Pandemic Effects on Breast Cancer Diagnosis in Croatia: A Population- and Registry-Based Study.

BACKGROUND: Our objective was to assess the effects of COVID-19 antiepidemic measures and subsequent changes in the function of the health care system on the number of newly diagnosed breast cancers in the Republic of Croatia. SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective, population- and registry-based study during 2020. The comparator was the number of patients newly diagnosed with breast cancer during 2017, 2018, and 2019. The outcome was the change in number of newly diagnosed breast cancer cases. RESULTS: The average monthly percent change after the initial lockdown measures were introduced was -11.0% (95% confidence interval - 22.0% to 1.5%), resulting in a 24% reduction of the newly diagnosed breast cancer cases in Croatia during April, May, and June compared with the same period of 2019. However, during 2020, only 1% fewer new cases were detected than in 2019, or 6% fewer than what would be expected based on the linear trend during 2017-2019. CONCLUSION: It seems that national health care system measures for controlling the spread of COVID-19 had a detrimental effect on the number of newly diagnosed breast cancer cases in Croatia during the first lockdown. As it is not plausible to expect an epidemiological change to occur at the same time, this may result in later diagnosis, later initiation of treatment, and less favorable outcomes in the future. However, the effect weakened after the first lockdown and COVID-19 control measures were relaxed, and it has not reoccurred during the second COVID-19 wave. Although the COVID-19 lockdown affected the number of newly diagnosed breast cancers, the oncology health care system has shown resilience and compensated for these effects by the end of 2020. IMPLICATIONS FOR PRACTICE: It is possible to compensate for the adverse effects of COVID-19 pandemic control measures on breast cancer diagnosis relatively promptly, and it is of crucial importance to do it as soon as possible. Moreover, as shown by this study's results on the number of newly diagnosed breast cancer cases during the second wave of the pandemic, these adverse effects are preventable to a non-negligible extent.

A pilot investigation of accelerated deep transcranial magnetic stimulation protocols in treatment-resistant depression.

Accelerated repetitive transcranial magnetic stimulation (rTMS) protocols are being increasingly studied because of their potential to provide quicker and enhanced treatment efficacy. However, there is a lack of accelerated deep TMS with H1-coil (adTMS) treatment research. This randomized pilot study investigated the efficacy and safety of adTMS protocols. Twenty-eight TRD patients received 20-min sessions twice daily for 10 or 15 days. Primary outcomes were changes in Hamilton Depression Rating Scale (HDRS) scores and discontinuation because of adverse events (AE). Secondary outcomes were response, remission, daily changes in Beck Depression Inventory-II (BDI-II) scores, and AE incidence. HDRS scores decreased by 13 (95% CI 11-17; 59%, 95% CI 45-73%) and 13 (95% CI 11-14; 62%, 95% CI 54-69%) points in the 10- and 15-day protocols, respectively. The adjusted difference between the two protocols was not significant or clinically relevant. Remission was achieved by 38% and 42% after 10-day and 15-day protocols, respectively. The intervention was discontinued because of AEs in 3/33 (9%) patients. The BDI-II decreases were significant and clinically relevant during the first 8 days. Twice-daily adTMS for 10 days seems to be safe and effective, with rapid clinical benefits during the first week of treatment. These promising results warrant further investigation in larger randomized clinical trials comparing adTMS with the standard dTMS protocol.

Real-world safety and efficacy of nivolumab for ≥ 2nd line treatment of metastatic renal cell carcinoma: A retrospective cohort study in Croatia, Hungary, and Malta.

The objective of our study was to assess the real-world safety and efficacy of nivolumab in the second- or later-line treatment of metastatic renal cell carcinoma (mRCC). We conducted a multicenter, retrospective, observational study of real-world data from patients who were treated with nivolumab under a patient expanded access program from 2015 to 2017 in Croatia, Hungary, and Malta. The primary safety endpoint was the discontinuation of therapy because of adverse events. The primary efficacy endpoint was overall survival (OS). We collected data from 87 patients with a median (interquartile range (IQR)) age of 63 (57-68) years, and 21% were females. The median (IQR) follow-up was 11 (5-31) months. Treatment was discontinued because of toxicity in 4 (5%) patients. Four (5%) patients experienced treatment-related adverse events of grade 3 or 4. The OS was 18.0 (95% CI: 11.0 to 28.6) months, and the PFS was 8.5 (95% CI: 4.9 to 12.1) months. Our study indicated a good safety and efficacy profile of nivolumab in the second- or later-line treatment of mRCC patients in a real-world clinical practice environment, which is comparable with the findings of the registrational trial.

Salivary cortisol response to psychosocial stress in patients with first-episode psychosis.

AIM: To analyze the difference in the salivary cortisol response to psychosocial stress between the patients with the first episode of psychosis (FEP) and the control group. METHODS: We performed a cross-sectional analysis of the baseline measurements of a prospective cohort study conducted from 2015 to 2018 at two Croatian psychiatric hospitals. The study consecutively enrolled 53 patients diagnosed with FEP and 63 healthy controls. The primary outcome was the difference in the changes of salivary cortisol concentration during the stress test. The secondary outcome was the difference in the baseline levels of salivary cortisol between patients with FEP and controls. The tertiary outcome were the correlations of salivary cortisol levels with the results of the Positive and Negative Syndrome Scale for Schizophrenia, Rosenberg Self-Esteem Scale, and the International Personality Item Pool. RESULTS: Patients with FEP had significantly higher baseline salivary cortisol than controls, but their salivary cortisol increased significantly less during the stress test. CONCLUSION: Patients with FEP respond differently to stressful stimuli than controls, as shown by the increased baseline salivary cortisol and blunted cortisol response, possibly indicating a greater vulnerability to psychosocial stress.

Difference of Symptoms Networks in Early and Late Phase Schizophrenia; A Cross-Sectional Network Analysis.

OBJECTIVE: The functional remission or recovery of schizophrenia patients is a challenging task which relies on pharmacotherapy but also on the timing of psychotherapy and other therapeutic interventions. The study aimed to assess the difference in strength and structure of symptoms networks between early and late phase schizophrenia. Our secondary objective was to check whether the overall, positive, negative, and general symptoms severity change over the course of treatment and disorder. METHODS: This nested cross-sectional analysis combined the samples from two studies performed during 2014-2016 at University Psychiatric Hospital Vrapce, Zagreb, Croatia on the consecutive sample of men 30-60 years old diagnosed with schizophrenia, 85 of them in the early (≤5 years from diagnosis), and 143 in the late phase of the illness. The study was funded by the project: "Biomarkers in schizophrenia - integration of complementary methods in longitudinal follow up of FEP patients". RESULTS: Median (IQR) age of the participant in the early phase was 36 (32-45) years and in the late phase 44 (38-49) years. Patients in the early phase had significantly higher odds for being in the symptomatic remission compared to the patients in the late-phase schizophrenia (OR=2.11; 95% CI 1.09-4.09) and had 10% less pronounced negative symptoms. The global strength, density, and structure of the symptoms network were not significantly different between the two study groups. CONCLUSIONS: Negative symptoms severity change with the course of illness and differ from the early to the late phase of schizophrenia. However, the overall network of psychotic symptoms is relatively stable, and overall strengths or density and the partial relationship between particular symptoms do not change significantly. The observed worsening of negative symptoms is probably at least partially caused by the lack of clear guidelines and effective treatment options aimed specifically toward negative symptoms.

General Functioning in Patients With First-Episode Psychosis After the First 18 Months of Treatment.

BACKGROUND: One of the main goals in the treatment of first-episode psychosis (FEP) is achieving functional remission. This study aims to analyze whether initial neurocognitive status and the use of specific pharmacological and psychosocial treatment options in FEP can predict general functioning after 18 months of treatment. METHODS: We conducted a longitudinal naturalistic study with a sample of 129 patients with FEP treated at 2 Croatian psychiatric clinics from 2016until 2018. Ordinal regression was used to predict the global level of functioning assessed with the Global Assessment of Functioning scale (GAF) at the 18th month of treatment from the baseline symptoms (assessed with a set of neurocognitive tests) and different treatment options. RESULTS: Higher score on GAF at the 18th month was significantly predicted by female sex, better baseline verbal memory and GAF scores, and the type of treatment. Group multimodal psychosocial treatment, antipsychotic polytherapy, and not being treated with sedatives at baseline predicted better GAF scores at follow-up. In the exploratory analysis, taking sedatives in the final assessment and being rehospitalized due to relapse predicted worse GAF scores at the end of follow-up. CONCLUSIONS: Although baseline neurocognitive features and baseline general functioning seem to influence the overall long-term functioning of persons with FEP, addition of a multimodal group psychosocial treatment program and appropriate medication seem to be equally important for improving the patients' level of functioning after the FEP.

Time from the Admission as the Predictor of Aggressive Behavior of Inpatients with Schizophrenia Spectrum Disorder.

The aim was to assess the incidence of aggressive events (AE) committed by patients diagnosed with schizophrenia spectrum disorethder (SSD) after the first 7 days of hospitalization in psychiatric institution, in comparison to other psychiatric patients. This retrospective cohort study was performed at Psychiatric Hospital "Sveti Ivan", Zagreb, Croatia, using hospital safety records of all patients admitted between 2015 and 2017. Primary outcome was the proportion of patients who committed AE more than a week after the admission to the hospital. Secondary outcome was the time in days from admission to the first incident of AE. The primary analysis was performed using a multivariable binary logistic regression. SSD patients committed AE more often than other patients (incidence rate ratio 3.97 (95% CI 2.35-6.69; p < 0.001; FDR q = 0.002), but these occurred earlier in the course of hospitalization: median (IQR) 2 (1-10) days from admission compared to 11 (2-32) days in other patients. SSD patients had significantly and clinically relevantly lower odds for AE after the first week of hospitalization adjusted for the large number of pre-planned possible confounders (OR = 0.10; 95% CI 0.02-0.45; p = 0.003; FDR q = 0.002). SSD patients seem to express more aggression earlier in the course of hospitalization. Findings of this study indicate that hospitalization-inherent AE risk factors may play an important role in the etiology of AE and inpatients aggressive behavior. Their possible moderating effect should be included in risk-assessment instruments.

CHARACTERISTICS AND PROGNOSIS OF TRIPLE-NEGATIVE BREAST CANCER PATIENTS: A CROATIAN SINGLE INstitution RETROSPECTIVE COHORT STUDY.

Triple-negative breast cancer (TNBC) occurs in around one-sixth of all breast cancer (BC) patients, with the most aggressive behavior and worst prognosis of all BC subtypes. It is a heterogeneous disease, with specific molecular characteristics and natural dynamics of early recurrence and fast progression. Due to the lack of biomarkers or any valid treatment targets, it can only be treated with classic cytotoxic chemotherapy. We analyzed a cohort of 152 patients, median age 58 years, diagnosed with and treated for early stage TNBC at the University Hospital for Tumors, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia, during the 2009-2012 period. Patients were treated with primary surgical approach, adjuvant chemotherapy and adjuvant irradiation. We observed a relatively large proportion of locally advanced TNBC at diagnosis, with large tumor size and nodal involvement, with high grade and high proliferation index Ki67. Patient age, tumor size and lymph node involvement, as expected, were significant and clinically most important prognostic factors for 5-year disease-free survival (67%; 95% CI 60%-75%) and overall absolute survival rate (74%; 95% CI 66%-81%).

Expenditures on Oncology Drugs and Cancer Mortality-to-Incidence Ratio in Central and Eastern Europe.

BACKGROUND: There is a steady decline in cancer mortality in Western Europe (WE), but this trend is not so obvious in Central and Eastern Europe (CEE). One of the largest discrepancies between WE and CEE is the level of investment in cancer care. The objective of our analysis was to examine the correlation between mortality-to-incidence (M/I) ratio and expenditures on oncology drugs in CEE and WE. MATERIALS AND METHODS: This cross-sectional analysis was done on publicly available data. Data on expenditures for oncology drugs were obtained from QuintilesIMS, and data on M/I ratio from Globocan. The main outcome was mortality-to-incidence ratio, and the primary analysis was performed by Spearman's rank correlation. RESULTS: There is a large discrepancy in expenditure on oncology drugs per cancer case between WE and CEE, and within CEE. Average expenditure on oncology drugs per capita as well as per new cancer case was 2.5 times higher in WE than in CEE. Availability of oncology drugs was highest in Germany (100%), relatively similar in WE (average of 91%), but in CEE it ranged from 37% to 86%, with an average of 70%. Annual expenditures on all oncology drugs per new cancer case was significantly negatively correlated with the M/I ratio (Spearman's ρ = -0.90, p < .001). CONCLUSION: There is a financial threshold for oncology drugs per cancer case needed to increase survival. Based on significantly lower expenditures for oncology drugs in CEE in comparison with WE, more investment for drugs as well as better, more organized, value- oriented consumption is needed. IMPLICATIONS FOR PRACTICE: Cancer is not treated equally successfully in Western Europe (WE) and in Central and Eastern Europe (CEE). This study showed that success in treatment of cancer is associated with the amount of money invested in oncology drugs. CEE countries spend on average 2.5 times less than WE countries for oncology drugs per new cancer case. These findings should be used by health care providers and oncologists struggling for more resources and better, more organized, evidence-based allocation of these resources as well as better oncology outcomes.

Differences in Facial Emotional Recognition Between Patients With the First-Episode Psychosis, Multi-episode Schizophrenia, and Healthy Controls.

OBJECTIVES: The aim of our study was to assess the differences in facial emotional recognition (FER) between patients with first-episode psychosis (FEP), patients with multi-episode schizophrenia (SCH), and healthy controls (HC) and to find possible correlations of FER with psychopathology in the two patient groups. METHODS: We performed a cross-sectional study enrolling 160 patients from two psychiatric hospitals in Croatia (80 FEP and 80 SCH) and 80 HC during the period from October 2015 until October 2017. Patients were assessed once during their hospital treatment, using the Penn Emotion Recognition Task for assessment of FER, rating scales for psychopathology and depression and self-reporting questionnaires for impulsiveness, aggression, and quality of life. RESULTS: The number of correctly identified emotions significantly decreased from HC to FEP [Δ -7%; 95% confidence interval (CI) [-12% to -3%], effect size r = 0.30] and more markedly in SCH (Δ -15%; 95% CI [-25% to -10%], effect size r = 0.59) after the adjustment for age and gender and correction for multiple testing. Correct FER for negative emotions, but not for happiness and neutral emotions, had a statistically significant negative correlation with some features on the scales of psychopathology, impulsivity and aggression in both patient groups. CONCLUSIONS: Impairment of FER is present from the first episode of schizophrenia and increases further with multiple psychotic episodes, but it may depend on or contribute to clinical symptoms. Therefore, assessment of FER should be included in the clinical assessment and integrated in the plan of treatment from the beginning of the illness. (JINS, 2019, 25, 165-173).

Utilization of somatic healthcare in Croatian patients with schizophrenia spectrum disorder, major depression, PTSD and the general population.

BACKGROUND: Utilization of somatic healthcare services is highly predictive of the development of chronic physical illnesses and increased mortality risks. The objective of this study was to assess the differences in healthcare utilization among patients with schizophrenia spectrum disorders (SSD), major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) and the general population in Croatia. METHODS: We enrolled 566 Croatian participants from the general population, 282 with SSD, 178 with MDD, and 86 with PTSD. The primary outcome was a self-reported specialist consultation for non-psychiatric (e.g., somatic) causes within the previous 12 months. RESULTS: Although SSD patients with chronic physical illnesses were significantly more often hospitalized for physical illness than the general population, the proportion of patients who had a specialist consultation were equal in SSD and the general population. MDD and PTSD patients had significantly higher adjusted odds for specialist consultation than the general population and SSD patients (MDD compared to SSD: OR = 2.14; 95% CI 1.27-3.59; PTSD compared to SSD: OR = 2.03; 95% CI 1.00-4.10). CONCLUSIONS: SSD patients' utilization of somatic healthcare is equal to the general population, despite their increased healthcare needs. However, their utilization is lower than in MDD and PTSD patients and, therefore, probably not adequate. TRIAL REGISTRATION: The study protocol was registered at ClinicalTrials.gov ( NCT02773108 ) on May 16, 2016.

Hand grip endurance moderating the effect of grip force on functional ability and disease activity in rheumatoid arthritis patients: a cross-sectional study.

To examine the effect of endurance on the relationship between grip force and measures of functional capacity and disease activity, we performed a cross-sectional study at the University Department of Rheumatology, Physical medicine and Rehabilitation from January 2017 to August 2018. Functional capacity of the hand was measured by ABILHAND-RA questionnaire and disease activity was assessed by the Disease Activity Score (DAS-28-CRP). All participants underwent dynamometric measurements of maximal grip force and hand grip endurance during repeated gripping. We analyzed the data from 34 RA patients at the median (IQR) age of 57 (51-61), 31 (91%) of them women, and 44 healthy participants at the age of 55 (50-59), 39 (89%) of them women. The moderating effect of endurance on the correlation between maximum grip force and the ABILHAND-RA score was not significant in healthy participants (b = 0.000, 95% CI - 0.005-0.004, p = 0.862), but it was in RA patients (b = 0.003, 95% CI 0.000-0.005, p = 0.027). In RA patients, the effect of maximum grip force on the ABILHAND-RA score increased with the increase in hand grip endurance. In RA patients, the interaction between endurance and grip force significantly explained the 15% more variance of the disease activity than main effects of these two measures, age, gender and body mass index alone. Hand grip endurance during repeated gripping affects the correlation between maximum grip force and the ABILHAND-RA score in a pattern that differs in RA patients and in the healthy population. In RA patients, hand grip endurance significantly moderates the correlation between maximum grip force and the DAS-28-CRP.

Association of Breast Cancer Symptoms with Patients' Quality of Life and Depression; A Croatian Cross-Sectional Study.

AIM: To find out which symptoms are the most associated with a breast cancer patients' quality of life (QoL) and depression. SUBJECTS AND METHODS: We performed this cross-sectional study from February to April 2015 at the Department of Medical Oncology, University Hospital for Tumors, Zagreb University Hospital Center "Sestre milosrdnice", Zagreb, Croatia on the sample of 147 breast cancer patients. Primary outcomes were EORTC QLQ-C30 version 3.0 Global QoL scale and Beck Depression Inventory II. RESULTS: After the adjustment for other symptoms, sociodemographic and clinical variables, fatigue (ß=-0.47, P<0.001), pain (ß=-0.24, P=0.023), and appetite loss (ß=-0.18, P=0.037) were statistically significantly correlated with QoL. Fatigue was the only symptom significantly associated with depression (ß=0.39, P=0.006). CONCLUSION: Fatigue, pain, appetite loss contributes the most to the overall breast cancer patients QoL. Although correlated, fatigue and pain contribution to lower QoL is independent from each other. Future studies should investigate whether there is an interaction between fatigue and pain changes over course of treatment. Fatigue and number of children are positively, while age and treatment in daily hospital are negatively associated with depression measured by BDI-II.

Neurocognitive Profiles of Patients with the First Episode of Psychosis and Schizophrenia Do not Differ Qualitatively: a Nested Cross-Sectional Study.

BACKGROUND: The aim of study was to analyze neurocognitive profiles in patients with first-episode psychosis (FEP) and patients with schizophrenia (SCH), and their correlations with other clinical features. SUBJECTS AND METHODS: We performed a multicentric cross sectional study including 100 FEP and 100 SCH recruited from three Croatian hospitals during 2015-2017. Assessment included a set of neurocognitive tests, psychiatric scales and self-reporting questionnaires. The main analysis was done by multigroup latent profile analysis. RESULTS: Multigroup latent profile analysis resulted in three structurally equivalent neurocognitive profiles ("Best", "Medium", "Worst"), with differences in the severity of neurocognitive deficits measured with successfulness in solving domain specific tasks. The "Best" profile was statistically significantly more prevalent in FEP and "Worst" profile in the SCH. Negative symptom score was the highest in patients with the "Worst" profile and the lowest among those with the "Best" profiles. CONCLUSIONS: Differences in neurocognitive profiles between FEP and SCH appear to be quantitative rather than qualitative nature, possibly reflecting a specific trait of illness that may progress over time. Defining neurocognitive profiles from the first episode of psychosis could help in tailoring individualized treatment options with focus on neurocognitive and negative symptoms and possible influence on patients' overall clinical outcome.

Efficacy of Center for Integrative Psychiatry Multimodal Early Intervention Services in Early-Phase Psychosis on Hospital Readmission.

BACKGROUND: Growing body of evidence has opened new opportunities to enhance treatment outcomes during early-phase psychosis (EPP). The objective of this study was to evaluate the effect of the Centre for integrative psychiatry (CIP) multimodal Early Intervention Services (EIS) on time to relapse in the patients with early-phase psychosis (EPP) during 12 and 24 month period. SUBJECTS AND METHODS: We performed a retrospective cohort study on the sample of 454 EPP patients (duration of the diagnosed disorder ≤5 years) admitted to Psychiatric Hospital "Sveti Ivan", Zagreb Croatia, from January 2, 2015, to December 5, 2018, for the acute treatment of EPP. The end of follow up was March 5, 2019. The primary outcome was the time to rehospitalization because of relapse during the 12 months from the hospital discharge. Independent variable was the EIS. RESULTS: We analyzed 454 EPP patients, 260 in EIS group and 194 in no EIS group. After the adjustment for twenty possible confounding factors using the Cox proportional hazard regression, patients who received EIS had significantly and clinically relevantly lower hazard for rehospitalization because of relapse during the first 12 months (HR=0.39; CI95% 0.21-0.61; p<0.001), and during the first 24 months from the hospital discharge (HR=0.56; CI95% 0.39-0.80; p=0.003; sequential Holm-Bonferroni corrected pcorr=0.004). CONCLUSIONS: Our study indicated efficacy of the CIP multimodal EIS in patients with EPP demonstrated through the time to the hospital readmission because of relapse during the 12 and 24 months from the hospital discharge. These results strongly support the need for implementation of multimodal EIS in all patients with EPP.

Integration of complementary biomarkers in patients with first episode psychosis: research protocol of a prospective follow up study.

In this project, we recruited a sample of 150 patients with first episode of psychosis with schizophrenia features (FEP) and 100 healthy controls. We assessed the differences between these two groups, as well as the changes between the acute phase of illness and subsequent remission among patients over 18-month longitudinal follow-up. The assessments were divided into four work packages (WP): WP1- psychopathological status, neurocognitive functioning and emotional recognition; WP2- stress response measured by saliva cortisol during a stress paradigm; cerebral blood perfusion in the resting state (with single photon emission computed tomography (SPECT) and during activation paradigm (with Transcranial Ultrasonography Doppler (TCD); WP3-post mortem analysis in histologically prepared human cortical tissue of post mortem samples of subjects with schizophrenia in the region that synaptic alteration was suggested by WP1 and WP2; WP4- pharmacogenetic analysis (single gene polymorphisms and genome wide association study (GWAS). We expect that the analysis of these data will identify a set of markers that differentiate healthy controls from patients with FEP, and serve as an additional diagnostic tool in the first episode of psychosis, and prediction tool which can be then used to help tailoring individualized treatment options. In this paper, we describe the project protocol including aims and methods and provide a brief description of planned post mortem studies and pharmacogenetic analysis.

Significantly lower right middle cerebral artery blood flow velocity in the first episode of psychosis during neurocognitive testing.

BACKGROUND: Changes in cerebral hemodynamics have been reported in schizophrenia and proposed as underlying the cognitive deficits seen in patients. The objective of our study was to compare changes of the cerebral blood flow velocity (BFV) during neurocognitive tasks between the patients with the first episode of psychosis and healthy controls. SUBJECTS AND METHODS: We recruited 46 patients with the first episode of psychosis (FEP), admitted to the University Hospital Centre Zagreb during 2016-2017 and 41 control subjects. Transcranial Doppler ultrasonography monitoring of BFV in both middle cerebral arteries was recorded during 25-minute long neurocognitive assessment with Phonemic Verbal Fluency test, Trial Making Test B and Stroop test. Between every consecutive test resting periods were recorded. RESULTS: After the adjustment for age, sex and education by quantile regression, patients with FEP had significantly lower BFV in middle cerebral arteries during the 3rd (Δ-15, Δ%-28% p=0.023) and 4th task (Δ-15, Δ%-28% p=0.031) of the Stroop test and the 1st task of Foot tapping test (Δ -16, Δ% -30% p=0.034). We observed significantly lower changes of right middle cerebral artery BFV in FEP between two consecutive tests in all four tasks of the Phonemic verbal fluency test, 1st and 2nd task of the Stroop test and Trail making test, and the1st task of Foot tapping test; and of the left artery between first three tasks of the Phonemic verbal fluency test, the last one of the Phonemic verbal fluency test and all first three tasks of the Stroop test. CONCLUSIONS: Decreased middle BFV during the execution of particular neurocognitive tasks in patients with FEP, compared to control subjects might indicate impaired hemodynamic function in the prefrontal/parietal brain areas, and possibly provide an explanation of some of the observed neurocognitive deficits in patients with the first episode of psychosis.

Trace elements concentrations association with schizophrenia symptoms; A cross-sectional study in Croatia.

BACKGROUND: Significant inconsistencies exist in findings on association of bio-elements (BE) concentrations and schizophrenia. Hypothesis of this research was that different concentrations of BE are associated with different psychopathological schizophrenia symptoms. SUBJECTS AND METHODS: This cross-sectional study was performed from 2014 to 2016 at Psychiatric Hospital "Sveti Ivan" and University Psychiatric Hospital "Vrapce", Zagreb, Croatia, on the consecutive sample of 67 patients diagnosed with schizophrenia. BE concentrations were measured by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) at the Institute for Medical Research and Occupational Health in Zagreb. Severity of schizophrenia symptoms was assessed on Brief Psychiatric Rating Scale (BPRS). RESULTS: After adjustment for all preplanned possible confounding variables, the first canonical correlation between BE and BPRS dimensions variates were statistically significant (Rc2=0.73; P=0.006). The first pair of canonical variates is defined by BPRS negative dimension (and marginally by positive symptoms and lack of resistance), and copper (Cu), lead (Pb), lithium (Li) and cobalt (Co) (marginally by cadmium (Cd) and nickel (Ni)). CONCLUSIONS: Concentrations of different BE are associated with different schizophrenia symptoms. Maximal correlation between BPRS and BE may be achieved with the weighted linear composite of negative schizophrenia symptoms and copper (Cu), lead (Pb), lithium (Li) and cobalt (Co).

Efficacy and safety of repetitive transcranial magnetic stimulation using an H1-coil or figure-8-coil in the treatment of unipolar major depressive disorder: A study protocol for a randomized controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique with few side effects that has been reported to be effective in the treatment of major depressive disorder (MDD). At present, no randomized controlled trials (RCT) have compared the efficacy and safety of rTMS delivered by the figure-8-coil and the H1-coil. We describe an industry-independent, randomized, controlled, single-blinded, single-center study protocol assessing the differences in efficacy and safety of rTMS for patients diagnosed with MDD with the H1-coil and figure-8-coil as an add-on to stable pharmacotherapy or pharmacotherapy alone. Stimulation protocols follow those that led to the FDA clearance of these treatments for MDD. The sample of 76 patents in each of the three groups will be enrolled and assessed with clinical and neuropsychological tests. The primary outcome is remission rate defined as Hamilton depression rating scale (HAM-D17) score ≤7 at the end of week-4. This clinical trial will address the efficacy and safety of rTMS modalities for MDD. The evaluation of biological markers will also help to elucidate the pathophysiology of MDD and the mechanisms of action of rTMS.