Hepatitis B Elimination in Children of Slovenian Origin Born in Slovenia After the Introduction of Preventive Strategies: the Results of a National Study

IntroductionIn Slovenia national strategies to prevent hepatitis B virus (HBV) infection in children were introduced in the mid-nineties. The aim of the present study was to analyze the epidemiological characteristics of chronic hepatitis B infection in children in Slovenia after the introduction of mandatory HBV vaccination of children and mandatory screening of pregnant women for HBV surface antigen (HBsAg) with consecutive active and passive immunization of newborns of HBsAg-positive mothers.MethodsChildren from all regions of Slovenia whose blood samples tested positive for HBsAg at the national reference laboratory for viral hepatitis between January 1997 and December 2010 were included. Demographic, epidemiological and virological data were reviewed retrospectively. Statistical evaluation of the patients’ characteristics was performed and possible trends during the observation period determined.ResultsAmong 52 HBsAg-positive children, there were 22 (42.3%) girls and 30 (57.7%) boys. Among 40 children tested for HBeAg, 17 were positive (42.5%). The most frequent risk factor for acquiring HBV infection was “presence of HBV infection within the family” (24/35; 68.8%). A significant association between the presence of HBeAg and a viral load of >20,000 IU/ml was found (p=0.001). The difference in the proportion of children of Slovenian origin born before 1994 and after was statistically significant (p=0.039). A statistically significant negative linear trend of the number of diagnosed children in the observed period was found (p=0.006).ConclusionsPrevention strategies adopted in the mid-nineties have resulted in the elimination of chronic hepatitis B in children of Slovenian origin born in Slovenia.     

Hepatitis C virus genotypes in 1,504 patients in Slovenia, 1993–2007

In order to identify the main routes of hepatitis C (HCV) transmission and to determine the HCV genotype distribution and its dynamics during a 15‐year period in Slovenia, HCV genotypes were detected using the INNO‐LiPA HCV II (Innogenetics) test for serum samples obtained from 1,504 patients representing 72.6% of all patients with chronic hepatitis C diagnosed from 1993 to 2007. HCV genotype 1 was predominant (56%), followed by genotypes 3, 2, and 4, with a prevalence of 37.8%, 5%, and 1.2%, respectively. HCV genotypes 5 and 6 were not detected in any patient. Patients infected with HCV genotype 3 were significantly younger (mean age 28.9 ± 8.5 years) than those infected with genotype 1 (mean age 38.9 ± 14.8 years; P < 0.0001) and those infected with HCV genotype 2 (mean age 50.3 ± 18.2 years; P < 0.0001). Intravenous drug use was identified as the most frequent possible HCV transmission route (34.3%), followed by medical‐related transmission such as transfusion of HCV‐contaminated blood or blood products, and hemodialysis (12.5%). Being an intravenous drug user was found to be strongly associated with HCV genotype 3 (OR, 3.71 [95% CI, 2.97–4.65]; P < 0.0001) and reporting infection by transfusion of blood or blood products was found to be strongly associated with HCV genotype 1 (OR, 3.28 [95% CI, 2.18–4.95]; P < 0.0001). During the 15‐year period, the proportion of genotype 3 increased substantially, reflecting the fact that the HCV epidemic in Slovenia is driven mostly by intravenous drug use. J. Med. Virol. 81:634–639, 2009 © 2009 Wiley‐Liss, Inc.     

Association of BDNF with anorexia, bulimia and age of onset of weight loss in six European populations

Several genes with an essential role in the regulation of eating behavior and body weight are considered candidates involved in the etiology of eating disorders (ED), but no relevant susceptibility genes with a major effect on anorexia nervosa (AN) or bulimia nervosa (BN) have been identified. Brain-derived neurotrophic factor (BDNF) has been implicated in the regulation of food intake and body weight in rodents. We previously reported a strong association of the Met66 allele of the Val66Met BDNF variant with restricting AN (ANR) and low minimum body mass index in Spanish patients. Another single nucleotide polymorphism located in the promoter region of the BDNF gene (-270C>T) showed lack of association with any ED phenotype. In order to replicate these findings in a larger sample, we performed a case-control study in 1142 Caucasian patients with ED consecutively recruited in six different centers from five European countries (France, Germany, Italy, Spain and UK) participating in the 'Factors in Healthy Eating' project. We have found that the Met66 variant is strongly associated to all ED subtypes (AN, ANR, binge-eating/purging AN and BN), and that the -270C BDNF variant has an effect on BN and late age at onset of weight loss. These are the first two variants associated with the pathophysiology of ED in different populations and support a role for BDNF in the susceptibility to aberrant eating behaviors.     

Rare copy number variants in neuropsychiatric disorders: Specific phenotype or not?

From a number of genome-wide association studies it was shown that de novo and/or rare copy number variants (CNVs) are found at an increased frequency in neuropsychiatric diseases. In this study we examined the prevalence of CNVs in six genomic regions (1q21.1, 2p16.3, 3q29, 15q11.2, 15q13.3, and 16p11.2) previously implicated in neuropsychiatric diseases. Hereto, a cohort of four neuropsychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, and intellectual disability) and control individuals from three different populations was used in combination with Multilpex Amplicon Quantifiaction (MAQ) assays, capable of high resolution (kb range) and custom-tailored CNV detection. Our results confirm the etiological candidacy of the six selected CNV regions for neuropsychiatric diseases. It is possible that CNVs in these regions can result in disturbed brain development and in this way lead to an increased susceptibility for different neuropsychiatric disorders, dependent on additional genetic and environmental factors. Our results also suggest that the neurodevelopmental component is larger in the etiology of schizophrenia and intellectual disability than in mood disorders. Finally, our data suggest that deletions are in general more pathogenic than duplications. Given the high frequency of the examined CNVs (1-2%) in patients of different neuropsychiatric disorders, screening of large cohorts with an affordable and feasible method like the MAQ assays used in this study is likely to result in important progress in unraveling the genetic factors leading to an increased susceptibility for several psychiatric disorders. ? 2012 Wiley Periodicals, Inc.     

Sustained attention to response task (SART) shows impaired vigilance in a spectrum of disorders of excessive daytime sleepiness

The sustained attention to response task comprises withholding key presses to one in nine of 225 target stimuli; it proved to be a sensitive measure of vigilance in a small group of narcoleptics. We studied sustained attention to response task results in 96 patients from a tertiary narcolepsy referral centre. Diagnoses according to ICSD-2 criteria were narcolepsy with (n=42) and without cataplexy (n=5), idiopathic hypersomnia without long sleep time (n=37), and obstructive sleep apnoea syndrome (n=12). The sustained attention to response task was administered prior to each of five multiple sleep latency test sessions. Analysis concerned error rates, mean reaction time, reaction time variability and post-error slowing, as well as the correlation of sustained attention to response task results with mean latency of the multiple sleep latency test and possible time of day influences. Median sustained attention to response task error scores ranged from 8.4 to 11.1, and mean reaction times from 332 to 366ms. Sustained attention to response task error score and mean reaction time did not differ significantly between patient groups. Sustained attention to response task error score did not correlate with multiple sleep latency test sleep latency. Reaction time was more variable as the error score was higher. Sustained attention to response task error score was highest for the first session. We conclude that a high sustained attention to response task error rate reflects vigilance impairment in excessive daytime sleepiness irrespective of its cause. The sustained attention to response task and the multiple sleep latency test reflect different aspects of sleep/wakefulness and are complementary.     

Identification of rare copy number variants in high burden schizophrenia families

Over the last years, genome‐wide studies consistently showed an increased burden of rare copy number variants (CNVs) in schizophrenia patients, supporting the “common disease, rare variant” hypothesis in at least a subset of patients. We hypothesize that in families with a high burden of disease, and thus probably a high genetic load influencing disease susceptibility, rare CNVs might be involved in the etiology of schizophrenia. We performed a genome‐wide CNV analysis in the index patients of eight families with multiple schizophrenia affected members, and consecutively performed a detailed family analysis for the most relevant CNVs. One index patient showed a DRD5 containing duplication. A second index patient presented with an NRXN1 containing deletion and two adjacent duplications containing MYT1L and SNTG2. Detailed analysis in the subsequent families showed segregation of the identified CNVs. With this study we show the importance of screening high burden families for rare CNVs, which will not only broaden our knowledge concerning the molecular genetic mechanisms involved in schizophrenia but also allow the use of the obtained genetic data to provide better clinical care to these families in general and to non‐symptomatic causal CNV carriers in particular. © 2013 Wiley Periodicals, Inc.     

Observation of treatment of depression in primary care setting in first week - what happens in first week of treatment with antidepressants?

Depression is frequently diagnosed and treated by general practicioners. In observational study we investigated the influence of the severity of depressive and anxiety symptoms on the frequency of patients' questions about mental disorder and their tendency to misinterpret the signs and symptoms of depression as side effects of medication. In 60 public health centers across Slovenia a total of 422 patients with depression treated with paroxetine were included. After one week of treatment one quarter of patients reported adverse effects and 15% of these patients misinterpreted signs of depression and anxiety for adverse effects. These patients tend to be more anxious and more depressed at the beginning of treatment. Half of them could not accept the explanation of their misinterpretation. A total of 55% patients had additional questions about illness at the second visit and these patients were also more anxious and more depressed at the beginning of treatment.