Schreiner A.,Janssen Cilag GmbH |
Niehaus D.,Flexivest Fourteen Research Center |
Shuriquie N.A.,Al Rashid Hospital |
Aadamsoo K.,North Estonian Regional Hospital |
And 7 more authors.
Journal of Clinical Psychopharmacology | Year: 2012
Metabolic effects are generally more pronounced with second-generation than first-generation antipsychotics. This study was designed to compare long-term metabolic effects and efficacy of paliperidone extended release (ER) with those of oral olanzapine in patients with schizophrenia. In this 6-month, multicenter, prospective, randomized, controlled, open-label, parallel-group study, adults with schizophrenia were treated with paliperidone ER (6-9 mg/d; n = 239) or oral olanzapine (10-15 mg/d; n = 220). The primary outcome was mean change in the ratio of serum triglyceride level to high-density lipoprotein level (TG/HDL), a marker of insulin resistance. Other outcome measures included the Positive and Negative Syndrome Scale scores, measures of lipid and glucose metabolism, and body weight. Significant improvements in psychotic symptoms were observed with both treatments (P < 0.0001). The TG/HDL ratio was significantly higher at end point versus baseline with olanzapine compared with that of paliperidone ER. Mean end point change in TG/HDL ratio was 0.097 ± 2.72 for olanzapine (P < 0.0001, reflecting worsening), with no significant change for paliperidone ER (-0.17 ± 2.51). Newly diagnosed impairment in TG and metabolic syndrome was more common with olanzapine (P < 0.05). Insulin resistance, as measured by the homeostasis model assessment of insulin resistance, worsened significantly with olanzapine (P = 0.0003), but not with paliperidone ER. Glucose sensitivity for insulin worsened significantly with olanzapine (P < 0.03), with no significant changes for paliperidone ER. End point increase in body weight was significantly higher with olanzapine than paliperidone ER (3.8 vs 1.2 kg; P = 0.0013). In summary, both paliperidone ER and olanzapine effectively treated schizophrenia; however, undesirable metabolic effects were significantly greater with olanzapine. © 2012 Lippincott Williams & Wilkins.
Anier A.,Tallinn University of Technology |
Lipping T.,Tampere University of Technology |
Ferenets R.,Tallinn University of Technology |
Puumala P.,University of Helsinki |
And 3 more authors.
British Journal of Anaesthesia | Year: 2012
BackgroundSeveral measures have been developed to quantify the change in EEG from wakefulness to deep anaesthesia. Measures of signal complexity or entropy have been popular and even applied in commercial monitors. These measures quantify different features of the signal, however, and may therefore behave in an incomparable way when calculated for standardized EEG patterns.MethodsTwo measures widely studied for anaesthesia EEG analysis were considered: spectral entropy and approximate entropy. First, we generated surrogate signals which had the same spectral entropy as a prototype signal, the sawtooth wave. Secondly, EEG samples where rhythmic pattern caused a peak in the power spectrum in the α-frequency band were modified by enhancing or suppressing the corresponding rhythm.ResultsWe found that the value of spectral entropy does not, in general, correlate with the visual impression of signal regularity. Also, the two entropy measures interpret a standardized artificially modified EEG signal in opposite directions: spectral peak of increasing amplitude in the α-frequency band causes spectral entropy to increase but decreases approximate entropy when low frequencies are present in the signal.ConclusionsSpectral entropy and approximate entropy of EEG are two totally different measures. They change similarly in deepening anaesthesia due to an increase in slow activity. In some cases, however, they may change in opposite directions when the EEG signal properties change during anaesthesia. Failure to understand the behaviour of these measures can lead to misinterpretation of the monitor readings or study results if no reference to the raw EEG signal is taken. © 2012 The Author .
Gillgren P.,Karolinska Institutet |
Gillgren P.,Stockholm Soder Hospital |
Drzewiecki K.T.,Copenhagen University |
Niin M.,North Estonian Regional Hospital |
And 5 more authors.
The Lancet | Year: 2011
Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin. We undertook a randomised controlled trial in nine European centres. Patients with cutaneous melanoma thicker than 2 mm, at clinical stage IIA-C, were allocated to have either a 2-cm or a 4-cm surgical resection margin. Patients were randomised in a 1:1 allocation to one of the two groups and stratified by geographic region. Randomisation was done by sealed envelope or by computer generated lists with permuted blocks. Our primary endpoint was overall survival. The trial was not masked at any stage. Analyses were by intention to treat. Adverse events were not systematically recorded. The study is registered with ClinicalTrials.gov, number NCT01183936. 936 patients were enrolled from Jan 22, 1992, to May 19, 2004; 465 were randomly allocated to treatment with a 2-cm resection margin, and 471 to receive treatment with a 4-cm resection margin. One patient in each group was lost to follow-up but included in the analysis. After a median follow-up of 6·7 years (IQR 4·3-9·5) 181 patients in the 2-cm margin group and 177 in the 4-cm group had died (hazard ratio 1·05, 95 CI 0·85- 1·29; p=0.64). 5-year overall survival was 65 (95 CI 60-69) in the 2-cm group and 65 (40-70) in the 4-cm group (p=0·69). Our findings suggest that a 2-cm resection margin is sufficient and safe for patients with cutaneous melanoma thicker than 2 mm. Swedish Cancer Society and Stockholm Cancer Society. © 2011 Elsevier Ltd.
Jerotskaja J.,Tallinn University of Technology |
Uhlin F.,Linköping University |
Lauri K.,Tallinn University of Technology |
Tanner R.,Tallinn University of Technology |
And 2 more authors.
2010 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC'10 | Year: 2010
The aim of this study was to estimate the concentration of uric acid (UA) optically by using original and processed ultra violet (UV) absorbance spectra's of the spent dialysate. Also the effect of using several wavelengths for estimation was examined. Ten uremic patients from Tallinn and ten from Linköping, during 30+40 hemodialysis treatments, were followed at the Departments of Dialysis and Nephrology at North-Estonian Medical Centre and at Linköping University Hospital. The dialysate samples were taken and analyzed by means of UA concentration at the chemical laboratory and with a doublebeam spectrophotometer. From the calibration set of material three models for original and three for 1st derivate of UV absorbance were created. These models were tested on validation set of material and concentrations of UA from the different methods were compared regarding mean values and SD. It was found that the concentration of UA can be estimated by UV absorbance method whereby using processed UV absorbance spectra and absorbance values from several wavelengths gives better and more accurate results. © 2010 IEEE.
Cordon R.D.A.,Hospital Universitario Puerta Of Hierro |
Eding E.,North Estonian Regional Hospital |
Marques-Teixeira J.,University of Porto |
Milanova V.,Sofia University |
And 2 more authors.
European Archives of Psychiatry and Clinical Neuroscience | Year: 2012
A recent randomized, open-label, relapse prevention trial (ConstaTRE) compared outcomes with risperidone long-acting injectable (RLAI) versus the oral atypical antipsychotic quetiapine. This study also included a small descriptive arm in which patients could also be randomized to aripiprazole. Results of this exploratory analysis are described here. Clinically stable adults with schizophrenia or schizoaffective disorder previously treated with oral risperidone, olanzapine, or an oral conventional antipsychotic were randomized to RLAI or aripiprazole. Efficacy and tolerability were monitored for up to 24 months. A total of 45 patients were treated with aripiprazole (10-30 mg/day) and 329 patients with RLAI (25-50 mg i.m. every 2 weeks). Relapse occurred in 27.3% (95% CI: 15.0-42.8%) of aripiprazole-treated and 16.5% (95% CI: 12.7-21.0%) of RLAI-treated patients. Kaplan-Meier estimates of mean (standard error) relapse-free period were 313.7 (20.4) days for aripiprazole and 607.1 (11.4) days for RLAI patients. Remission was achieved by 34.1% (95% CI: 20.5-49.9%) of aripiprazole and 51.1% (95% CI: 45.5-56.6%) of RLAI patients. Clinical global impression-change was improved (''minimally improved'' to ''very much improved'') in 26.4% with RLAI and 15.9% with aripiprazole patients. Tolerability was generally good for both treatment groups. Weight gain (7.0% with RLAI vs. 4.4% with aripiprazole), extrapyramidal adverse events (AEs) (10.3% vs. 4.4%), and potentially prolactin-related AEs (4.6% vs. 0%) were more common with RLAI treatment, and gastrointestinal disorders were more common in aripiprazole-treated patients (22.2% vs. 6.1%). Time-torelapse in stable patients with schizophrenia or schizoaffective disorder was numerically longer in RLAI-treated patients than in aripiprazole-treated patients although not statistically significant. Both treatments were generally well tolerated. © 2011 Springer-Verlag.
Koido K.,University of Tartu |
Eller T.,University of Tartu |
Kingo K.,University of Tartu |
Koks S.,University of Tartu |
And 6 more authors.
Journal of Psychiatric Research | Year: 2010
Genetic regulation of immune system and inflammatory response may be related to the pathogenesis and manifestations of mood and anxiety disorders. In the present study we examined a range of single-nucleotide polymorphisms (SNP) in chromosomal region 1q32, the locus of interleukin 10 (IL10) gene, in patients with major depressive disorder (n = 312) and panic disorder (n = 210), and matched healthy controls (n = 356). We found no significant associations of the SNPs in IL10 family genes with either diagnostic group. Haplotype analysis revealed seven haplotype blocks, but their frequencies did not differ between patients and controls. Significant associations were detected for SNP rs1539243 in IKBKE (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon) gene showing different allelic and genotypic distributions in the total as well as in separate diagnostic groups as compared to controls. IKBKE emerged as a candidate for further studies of genetic factors associated with panic disorder and major depressive disorder. © 2009 Elsevier Ltd. All rights reserved.
PubMed | West Tallinn Central Hospital, University of Tartu and North Estonian Regional Hospital
Type: Journal Article | Journal: Nephron extra | Year: 2014
The clinical performance indicators (CPI) are important tools to assess and improve the quality of renal replacement therapy (RRT). The aim of the current study was to compare the results of a longitudinal set of CPI in RRT patients and to determine the extent to which the guidelines for anaemia, calcium phosphate management and other CPI are met in Estonian renal centres.A long-term retrospective, observational, cross-sectional CPI analysis was undertaken in RRT patients from 2007 to 2011. The following CPI set of well-designed measures based on good evidence was analysed: anaemia management variables, laboratory analyses of mineral metabolism, nutritional status variables and dialysis adequacy variables.Relatively small changes in the analysed mean CPI values were noticed during the study period. In the course of the study, we noticed an improvement in anaemia control, but not all centres achieved the standard of >80% of the dialysis patients with a haemoglobin (Hb) level >100 g/l. There was a trend of decreasing Hb concentrations below 125 g/l in both haemodialysis (HD) and peritoneal dialysis (PD) patients. In 2011, hyperphosphataemia was present in 58% of the HD and 47% of the PD patients, whereas centre differences varied between 50 and 60% of both the HD and PD patients. HD adequacy was achieved in 77% of the HD patients.An improvement in the data collection was noticed, and the analysis of CPI allows renal centres to assess and compare their practices with others. The collection and evaluation of CPI of RRT patients is an important improvement and significantly increases the awareness of nephrologists.
Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, placebo-controlled, phase 3 trial
PubMed | Shizuoka Cancer Center, Arnaud Of Villeneuve Hospital, Regional Oncology Dispensary Medgorodok, GSK Vaccines and 20 more.
Type: Journal Article | Journal: The Lancet. Oncology | Year: 2016
Fewer than half of the patients with completely resected non-small-cell lung cancer (NSCLC) are cured. Since the introduction of adjuvant chemotherapy in 2004, no substantial progress has been made in adjuvant treatment. We aimed to assess the efficacy of the MAGE-A3 cancer immunotherapeutic in surgically resected NSCLC.In this randomised, double-blind, placebo-controlled trial, we recruited patients aged at least 18 years with completely resected stage IB, II, and IIIA MAGE-A3-positive NSCLC who did or did not receive adjuvant chemotherapy from 443 centres in 34 countries (Europe, the Americas, and Asia Pacific). Patients were randomly assigned (2:1) to receive 13 intramuscular injections of recMAGE-A3 with AS15 immunostimulant (MAGE-A3 immunotherapeutic) or placebo during 27 months. Randomisation and treatment allocation at the investigator site was done centrally via internet with stratification for chemotherapy versus no chemotherapy. Participants, investigators, and those assessing outcomes were masked to group assignment. A minimisation algorithm accounted for the number of chemotherapy cycles received, disease stage, lymph node sampling procedure, performance status score, and lifetime smoking status. The primary endpoint was broken up into three co-primary objectives: disease-free survival in the overall population, the no-chemotherapy population, and patients with a potentially predictive gene signature. The final analyses included the total treated population (all patients who had received at least one treatment dose). This trial is registered with ClinicalTrials.gov, number NCT00480025.Between Oct 18, 2007, and July 17, 2012, we screened 13849 patients for MAGE-A3 expression; 12820 had a valid sample and of these, 4210 (33%) had a MAGE-A3-positive tumour. 2312 of these patients met all eligibility criteria and were randomly assigned to treatment: 1515 received MAGE-A3 and 757 received placebo and 40 were randomly assigned but never started treatment. 784 patients in the MAGE-A3 group also received chemotherapy, as did 392 in the placebo group. Median follow-up was 381 months (IQR 279-484) in the MAGE-A3 group and 395 months (279-504) in the placebo group. In the overall population, median disease-free survival was 605 months (95% CI 572-not reached) for the MAGE-A3 immunotherapeutic group and 579 months (557-not reached) for the placebo group (hazard ratio [HR] 102, 95% CI 089-118; p=074). Of the patients who did not receive chemotherapy, median disease-free survival was 580 months (95% CI 566-not reached) in those in the MAGE-A3 group and 569 months (444-not reached) in the placebo group (HR 097, 95% CI 080-118; p=076). Because of the absence of treatment effect, we could not identify a gene signature predictive of clinical benefit to MAGE-A3 immunotherapeutic. The frequency of grade 3 or worse adverse events was similar between treatment groups (246 [16%] of 1515 patients in the MAGE-A3 group and 122 [16%] of 757 in the placebo group). The most frequently reported grade 3 or higher adverse events were infections and infestations (37 [2%] in the MAGE-A3 group and 19 [3%] in the placebo group), vascular disorders (30 [2%] vs 17 [3%]), and neoplasm (benign, malignant, and unspecified (29 [2%] vs 16 [2%]).Adjuvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Based on our results, further development of the MAGE-A3 immunotherapeutic for use in NSCLC has been stopped.GlaxoSmithKline Biologicals SA.
PubMed | The National Hospital, University of Tartu and North Estonian Regional Hospital
Type: | Journal: International review of neurobiology | Year: 2015
The substituted amphetamines have had a checkered medical history intertwined with a sensational cultural history. Mankinds insatiable fascination with speed has led to widespread misuse sometimes with disastrous neurological and psychiatric consequences that may cause a permanent harm but their potential to enhance cognition should not be dismissed or forgotten. Further, smarter research could perhaps still lead to an expanded beneficial role for stimulant use in modern society.
PubMed | University of Tartu and North Estonian Regional Hospital
Type: | Journal: International review of neurobiology | Year: 2015
Methcathinone abuse is a significant cause of parkinsonism among young patients in the Eastern European countries. The drug is synthesized from over-the-counter cold remedies containing ephedrine or pseudoephedrine. The final mixture contains a high concentration of manganese if potassium permanganate is used as the oxidant agent. Though manganese is an essential trace element and its homeostasis is well maintained, exposure to a high level of manganese is neurotoxic. The use of manganese-contaminated methcathinone may cause permanent neurological damage and severe disability. Drug users develop a distinctive extrapyramidal syndrome that resembles classic manganese intoxication. Methcathinone could have additive neurotoxic effect to the progression of parkinsonism. The most prevalent symptoms are symmetrical bradykinesia, dystonias, and early postural, gait, and speech impairment. After cessation of exposure, the syndrome is generally irreversible and can even progress.