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Zagreb, Croatia

Coles A.J.,University of Cambridge | Fox E.,MS Clinic of Central Texas | Vladic A.,Clinical Hospital sveti Duh | Gazda S.K.,INTEGRA Clinical Research | And 9 more authors.
The Lancet Neurology

Background: Alemtuzumab is a humanised monoclonal antibody that depletes lymphocytes, causing long-term immunomodulation. In a 3-year, rater-blinded phase 2 study (the CAMMS223 study) in patients with relapsing-remitting multiple sclerosis (RRMS), alemtuzumab reduced relapse rate and the risk of sustained accumulation of disability compared with subcutaneous interferon beta-1a, and the mean expanded disability status scale (EDSS) score of the alemtuzumab cohort improved compared with baseline. Adverse events included infusion-associated reactions, predominantly mild to moderate infections, thyroid disorders, and immune thrombocytopenia. In this study, we further analysed the CAMMS223 data with the aim of determining whether demographic and baseline disease-related characteristics affect the beneficial effects of alemtuzumab. Additionally, we aimed to describe a new outcome measure in multiple sclerosis research: sustained reduction in disability. Methods: 334 treatment-naive patients with active, early RRMS were randomly assigned in a 1:1:1 ratio to receive interferon beta-1a (44 μg subcutaneously three times per week), or 24 mg per day or 12 mg per day alemtuzumab intravenously for 2 or 3 annual cycles. We analysed freedom from clinical disease activity (CDA; defined as no relapses and no sustained accumulation of disability) and occurrence of sustained reduction in disability (SRD; a ≥1 point decrease on the EDSS sustained for 6 consecutive months for patients with a baseline EDSS ≥2), and analysed efficacy outcomes for subgroups based on age, sex, geographic region, MRI-T1 brain volume, MRI-T2 lesion volume, disease duration, number of previous relapses within 2 years, and EDSS. Findings: 322 patients were analysed. 161 of 215 patients treated with alemtuzumab were free of CDA at 36 months (Kaplan-Meier estimate 71·8%, 95% CI 63·1-78·8%) compared with 52 of 107 patients treated with interferon beta-1a (42·6%, 32·4-52·4%; hazard ratio [HR]=0·31, 0·20-0·46; p<0·0001). For the 199 patients with a baseline EDSS score greater than or equal to 2, SRD was more likely (HR=2·61, 1·54-4·43; p=0·0004) among patients treated with alemtuzumab (66 of 133 patients, Kaplan-Meier estimate 51·6%, 95% CI 43·2-60·7%) than patients treated with interferon beta-1a (15 of 66 patients, 27·2%, 17·2-41·4%). All disability and relapse outcomes showed evidence of beneficial effects of alemtuzumab compared with interferon beta-1a across all analysed patient subsets, and no subgroup of patients consistently responded better than others to alemtuzumab. Interpretation: Alemtuzumab reduced disease activity compared with interferon beta-1a in most of the analysed subgroups. Significantly greater numbers of patients experienced sustained improvement in disability after treatment with alemtuzumab than interferon beta-1a. The efficacy offered by alemtuzumab is a substantial advance in the treatment of multiple sclerosis. Funding: Genzyme and Bayer Schering Pharma. © 2011 Elsevier Ltd. Source

Predojevic M.,University of Zagreb | Stanojevic M.,Clinical Hospital sveti Duh | Vasilj O.,University of Zagreb | Kadic A.S.,University of Zagreb
Journal of Maternal-Fetal and Neonatal Medicine

In this case report, we present prenatal and postnatal neurological evaluation of a fetus and newborn from pregnancy complicated with intrauterine growth restriction, fetal hypoxemia, and preterm labor. Despite unfavorable intrauterine conditions, this premature infant showed normal early neurological development that was verified not only by postnatal tests but also with a new prenatal neurological screening test. © 2011 Informa UK, Ltd. Source

Rados I.,University Hospital Center Osijek | Sakic Zdravcevic K.,Clinical Hospital sveti Duh | Hrgovic Z.,University Hospital Center Osijek
European Neurology

Background: The painDETECT questionnaire (PD-Q) is a fast and uncomplicated way to ascertain the percentage of neuropathic pain in 'total pain' and is designed to detect neuropathic pain components in back pain. The purpose of this randomized, prospective study is to compare, with the assessment of the PD-Q, the efficacy of interlaminar (IL) and transforaminal (TF) steroid injections in patients with unilateral chronic lumbar radicular pain. Methods: Patients were treated fluoroscopically with epidural steroids, using the IL or TF method and with confirmation of the epidural space by contrast, using random computerized classification. The patients received a series of three IL or TF epidural steroid injections (ESI) at 2-week intervals. The patients were monitored for 6 months from the first steroid injection. Results: By analyzing the average values of the total sum of points in the PD-Q a dropping trend is confirmed for both groups. The trend equation (y = -1.1393x + 25.269) for the TF ESI shows a faster recovery than the IL ESI (y = -0.8089x + 26.654). The statistically significant difference in the two groups is proved between the first and the sixth visit (IL ESI, p = 0.014; TF ESI, p = 0.001). There is no statistically significant difference in the efficiency of the two dosages and the volumes of steroids between the IL and TF distribution of steroids. Conclusions: Steroids are efficient; besides alleviating the overall pain, they also reduce the neuropathic component in chronic lumbar radicular pain, whether it is distributed epidurally by the IL or TF approach. © 2012 S. Karger AG, Basel. Source

Klarica M.,University of Zagreb | Mise B.,University of Zagreb | Vladic A.,Clinical Hospital sveti Duh | Rados M.,University of Zagreb | Oreskovic D.,Ruder Boskovic Institute

Acute osmolar loading of cerebrospinal fluid within one lateral ventricle of dogs was examined as a cause of water extraction from the bloodstream and an increase in intracranial pressure. We have shown that a certain amount of 3H2O from the bloodstream enters osmotically loaded cerebrospinal fluid significantly faster, hence causing a significant increase in intracranial pressure. The noted phenomenon in which intracranial pressure still significantly increases, but in which the hyperosmolarity of the cerebrospinal fluid is no longer present, was named "compensated hyperosmolarity". In the case of the sub-chronic application of hyperosmolar solutions into cat ventricles, we observed an increase in cerebrospinal fluid volume and a more pronounced development of hydrocephalus in the area of application, but without significant increase in intracranial pressure and without blockage of cerebrospinal fluid pathways. These results support the newly proposed hypothesis of cerebrospinal fluid hydrodynamics and the ability to develop new strategies for the treatment of cerebrospinal fluid-related diseases. © 2013 IBRO. Source

Milanovic S.M.,University of Zagreb | Milanovic S.M.,Croatian Institute of Public Health | Erjavec K.,Clinical Hospital sveti Duh | Poljicanin T.,Croatian Institute of Public Health | And 2 more authors.
Psychiatria Danubina

Background: Depression is a growing public health problem still under-recognised in primary care settings. By focusing primarily on somatic complaints and diseases, general practitioners often fail to identify an underlying mental disorder. The aim of this study was to assess the prevalence of patients with unrecognised depression symptoms in general practice and identify associated socio-demographic factors. Subjects and methods: The study included 769 patients without previous psychiatric disorder who attended their primary care physicians in the Health Centre Zagreb - Zapad in January 2011. Data on patients' age, sex, level of education, marital and employment status were collected. All participants completed The Zung Self-Rating Depression Scale. Results: Among the 25.5% of participants whose Zung score was outside the normal range, 19.38% were mildly, 4.64% moderately, and 0.91% severely depressed. Statistically significant differences were observed among groups defined according to level of education, employment and marital status (p<0.001). Lower Zung scores were found in individuals with a higher level of education, who were unmarried, employed or still undergoing education. Multivariate logistic regression model revealed that older age (p<0.001), unemployment (p=0.001) or unmarried status (p=0.025) were significant predictors of depression symptoms. Conclusions: The study revealed a high prevalence of depression symptoms among primary care patients who had not been previously suspected to have any psychiatric co-morbidity. Awareness of depression symptoms and disorders should be raised among general practitioners, focusing on older, unemployed and unmarried people. © Medicinska naklada. Source

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