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White-Sutton syndrome (WHSUS) is a rare neurodevelopmental disorder caused by heterozygous variants in the POGZ gene. With slightly over 100 reported cases, the diagnosis of WHSUS remains challenging due to its variable and non-specific clinical features. We report a novel case of WHSUS carrying a heterozygous de novo variant in the POGZ gene and with characteristic clinical features including global developmental delay, autism spectrum disorder, generalised myoclonic epilepsy, hypotonia and distinct dysmorphic features. Notably, the patient also presented with mild gastrointestinal symptoms and was diagnosed with celiac disease (CD) based on elevated tissue transglutaminase IgA levels, confirmatory duodenal biopsy and HLA typing. Based on the recent evidence implicating chromatin remodelling genes in CD and the known role of the POGZ protein as a regulator of chromatin remodelling, we cautiously propose, for the first time, to our knowledge that the POGZ gene may contribute to the pathogenesis of the celiac disease, providing evidence of a possible association between White-Sutton syndrome and CD. Comprehensive functional, genetic and epidemiological studies are needed to explore further this potential association, which may broaden the clinical spectrum of WHSUS and improve the understanding of CD-related epigenetic factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Stigmatising attitudes towards mentally ill people are present among healthcare professionals. The aim of the study was to evaluate medical students' attitudes in five medical schools from Albania, Bulgaria, Moldova, Romania and Serbia and to determine if psychiatry clerkship improves these attitudes., Methods: In the first stage, the study included students from the first and final years of medical school; in the second stage, only final-year students were included; The Mental Illness Clinicians' Attitude Scale (MICA-2) and the Attribution Questionnaire (AQ-9) were used in this study. The total sample comprised 1,526 medical students in the first stage and 614 in the second stage., Results: The analysis of the average AQ-9 and MICA-2 scores between countries revealed significant differences (p<0.05). Multivariable analysis showed that female students were 30% more likely to have elevated AQ-9 scores than male students (p=0.029). Final-year students had a significantly lower chance of having a higher MICA-2 score compared to first-year students (OR=0.7; p<0.05)., Conclusions: Psychiatry clerkship contributes to a decrease in the level of stigmatising attitudes among medical students. Further research is required to assess the curricula to achieve better results in reducing stigma among future doctors., (© 2024 Sanja Harhaji et al., published by Sciendo.)

Objectives: To compare the prevalence, regulations, and pharmacovigilance practices of clozapine use in Eastern European countries (except Russia)., Methods: Questionnaires and data from administrative databases (2016 and 2021), package inserts and national guidelines were collected from 21 co-authors from 21 countries. Reports of clozapine adverse drug reactions (ADRs) sent to the global pharmacovigilance database (VigiBase™) were analyzed from introduction to December 31, 2022., Results: Clozapine prescription among antipsychotics in 2021 varied six-fold across countries, from 2.8 % in the Czech Republic to 15.8 % in Montenegro. The utilization of antipsychotics in both 2016 and 2021 was highest in Croatia, and lowest in Serbia in 2016, and Montenegro in 2021, which had half the defined daily dose (DDD)/1000/day compared to the Croatian data. From 2016 to 2021, the prevalence of antipsychotic use increased in almost all countries; the proportion of clozapine use mainly remained unchanged. Differences were detected in hematological monitoring requirements and clozapine approved indications. Only a few national schizophrenia guidelines mention clozapine-induced myocarditis or individual titration schemes. The VigiBase search indicated major underreporting regarding clozapine and its fatal outcomes. By comparison, the United Kingdom had less than half the population of these Eastern European countries but reported to VigiBase more clozapine ADRs by 89-fold and clozapine fatal outcomes by almost 300-fold., Conclusion: Clozapine is under-utilized in Eastern European countries. Introducing individualized clozapine treatment schedules may help to maximize clozapine benefits and safety. Major improvement is needed in reporting clozapine ADRs and fatal outcomes in Eastern European countries., Competing Interests: Declaration of competing interest In the last 3 years, MS participated in lectures for the following companies: Alkaloid, Angelini, Belupo, Gedeon Richter, Jadran Galenski Laboratorij, Johnson & Johnson, Lundbeck, Pliva, Stada and Viatris; participated in clinical trials for Krka and Boeringer Ingelheim; and is a member of the advisory board of Lundbeck. AW has received research support from Angelini, Biogen, Eli Lilly and Company, Janssen-Cilag, Lundbeck, Polpharma, Sanofi and Valeant, and Termedia. MT participated in lectures for the following companies: Gedeon Richter, Johnson & Johnson, Lundbeck, Medochemie, Olainfarm, Grindex, and is a member of the advisory board of Biogen. MK participated in lectures for the following companies: Angeliny, Gedeon Richter, Johnson & Johnson, Lundbeck and is a member of the advisory board of Angeliny and Lundbeck. UP participated in lectures for the following companies: Krka, Lundbeck, Nobel, Sandoz, and Sun Pharmaceuticals. RM is a member of the advisory board of Johnson & Johnson, and gave lectures for Lundbeck and Gedeon Richter. AC participated in lectures for the following companies: Teva, Krka, Gedeon Richter, Bonifar, Lundbeck, and Janssen; and participated in a clinical trial for Krka. DIR developed lectures and presented clozapine lectures with the support of Viatris, Galenika and Remedica; she received speaker ́s honoraria from Teva Serbia, Krka, Alkaloid and Gooodwill. DB participated in lectures for the following companies: Angelini, Gedeon Richter, Johnson & Johnson, Krka, Lundbeck, Schwabe; participated in clinical trials for IQVIA, Johnson & Johnson, Otsuka Pharmaceuticals.In the last 3 years, the other authors report no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Enzyme replacement therapy is already recognized as the gold standard of care for patients with Gaucher disease. Taliglucerase alfa is one of the three alternatives recommended for treatment of Gaucher disease in children and adults., Aim: This study aims to evaluate the long-term efficacy and safety of Taliglucerase alfa in children and adolescents with Type 1 Gaucher disease., Patients and Methods: Over a six-year period, we monitored the efficacy of continuous treatment in 10 patients by assessing various parameters, including hemoglobin concentration, platelet count, liver and spleen volume, bone mineral density, glucosylsphingosine level, chitotriosidase activity, and growth parameters . Safety was evaluated by immunogenicity and adverse event monitoring., Results: The mean age of patients was 13.4 ± 3.6 years and the treatment duration was 60.24 ± 13.4 months. From baseline to end line the parameters change as follows: hemoglobin concentration improved from 12.7 (±1.3) to 14.6 (±1.5) and platelet count from 180 (±74) to 198 (±79). The spleen volume, was reduced by 46% ( p  = 0,007). The chitotriosidase activity decreased from 4,019.7 (±3,542.0) nmoles/ml/hr to 2,039.5 (±1,372.2) nmoles/ml/hr (46% reduction). Glucoylsphingosine level dropped from 119.2 (±70.4) ng/ml to 86.2 (±38.1) ng/ml, indicating a reduction of 28%. Bone mineral density Z-score, improved from -1.47 (±1.76) to -0.46 (±0.99) (69.7% reduction). Out of the 1,301 total administrations, our patients reported only 37 (2.8%) infusion-related adverse events which were mild and transitory., Conclusion: Taliglucerase alfa exhibits good efficacy and a safe profile in the treatment of children and adolescents with Type 1 Gaucher disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Cullufi, Tomori, Velmishi, Gjikopulli, Akshija, Tako, Dervishi, Hoxha, Tanka, Troja and Tabaku.)

Diets-Jongmans syndrome, DIJOS, is a very recently described autosomal dominant condition, which is caused by heterozygous pathogenic variants in KDM3B gene and characterized by impaired intellectual development, short stature, as well as facial dysmorphism. We describe a new DIJOS patient harboring a heterozygous, novel, de novo and likely pathogenic variant in KDM3B gene, which is the first case reported after Diets et al.`s publication, to the best of our knowledge., Competing Interests: The authors declare no conflict of interest., (© 2022 Published by Elsevier Inc.)

Background: Non-pharmacological treatment for schizophrenia includes educational, psychotherapeutic, social, and physical interventions. Despite growing importance of these interventions in the holistic treatment of individuals with schizophrenia, very little is known about their availability in South-East European countries (SEE)., Objective: To explore mental health care experts' opinions of the availability of non-pharmacological treatment for people with schizophrenia in SEE., Methods: An online survey containing 11 questions was completed by one mental health expert from each of the following SEE countries: Albania, Bosnia and Herzegovina (B&H), Bulgaria, Croatia, Greece, Kosovo † , Montenegro, Moldova, North Macedonia, Romania, Serbia, and Slovenia. Data were collected on estimated rates of received non-pharmacological interventions, type of services delivering these interventions, and expert views of availability barriers., Results: In eight countries, the estimated percentage of people with schizophrenia who receive non-pharmacological treatments was below 35%. The primary explanations for the low availability of non-pharmacological treatments were: lack of human and financial resources, lack of training for clinicians, and pharmacotherapy dominance in the treatment for schizophrenia., Conclusion: Lack of personal and institutional resources and state support were identified as primary obstacles to staff training and delivering non-pharmacological treatments to people with schizophrenia on individual and systemic levels, respectively. This evidence can be used to improve holistic, evidence-based treatment for schizophrenia in the SEE countries.

This study aimed to analyze treatment guidelines of 12 SEE countries to identify non-pharmacological interventions recommended for schizophrenia, explore the evidence base supporting recommendations, and assess the implementation of recommended interventions. Desk and content analysis were employed to analyze the guidelines. Experts were surveyed across the 12 countries to assess availability of non-pharmacological treatments in leading mental health institutions, staff training, and inclusion in the official service price list. Most SEE countries have published treatment guidelines for schizophrenia focused on pharmacotherapy. Nine countries-Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Greece, Moldova, Montenegro, North Macedonia, and Serbia-included non-pharmacological interventions. The remaining three countries-Kosovo (UN Resolution), Romania, and Slovenia-have not published such treatment guidelines, however they are on offer in leading institutions. The median number of recommended interventions was seven (range 5-11). Family therapy and psychoeducation were recommended in most treatment guidelines. The majority of recommended interventions have a negative or mixed randomized controlled trial evidence base. A small proportion of leading mental health institutions includes these interventions in their official service price list. The interventions recommended in the treatment guidelines seem to be rarely implemented within mental health services in the SEE countries., (© 2022. The Author(s).)

Background: Although psychoactive substance use disorders (PSUDs) are a domain of mental health, addiction psychiatry is only formally recognized as a subspecialty in a few European countries, and there is no standardized training curriculum. Methods: A 76-item questionnaire was developed and disseminated through an online anonymous data-collecting system and hand-to-hand amongst psychiatric trainees from the 47 European countries of the Council of Europe plus Israel and Belarus. Results: 1,049/1,118 psychiatric trainees from 30 European countries completed the questionnaire. Fifty-nine-point nine percent of trainees stated to have training in addictions. Amongst the trainees who described having training in addictions, 43% documented a not well-structured training and 37% an unsatisfactory training, mainly due to poor acquired knowledge. Overall, 97% of trainees stated that addiction represents a core curriculum for their training. Overall, general adult psychiatric trainees reported a better knowledge in addictions, compared to trainees in child and adolescent psychiatry. Conclusion: Despite a growing spread of PSUDs in European countries, addiction psychiatry is a relatively poorly trained field within psychiatry training programs. Further research should investigate reasons for poor training and timings of the educational activities to optimize experiential education training in addiction psychiatry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Orsolini, Rojnić Palavra, Papanti, Potočan, Quattrone, Martens, Sklenářová, Levola, Grichy, Naughton, Grinevičiene, Kuiters, Gondek, Panfil, Borovcanin, San Roman Uria, Biskup, Sönmez Güngör, Casanova Dias, Tomori, Banjac, Marinova-Djambazova and Pinto da Costa.)

Gaucher disease (GD) is a recessive metabolic disorder caused by a deficiency of the GBA gene-encoded enzyme β-glucocerebrosidase. We characterized a cohort of 36 Albanian GD patients, 31 with GD type 1 and 5 affected by GD types 2, 3, and an intermediate GD phenotype between type 2 and type 3. Of the 12 different GBA alleles that we detected, the most frequently observed was p.Asn409Ser, followed by p.[Asp448His;His294Gln]. The prevalence of the p.Leu483Pro allele was approximately 10-fold lower than reported in other populations. We identified a novel pathogenic missense variant (c.1129G>A; p.Ala377Thr). All five of our non-type 1 patients had genotypes consisting of the p.[Asp448His;His294Gln] allele in combination with another severe GBA allele. The median Lyso-Gb1 level of treated patients carrying the p.[Asp448His;His294Gln] and no p.Asn409Ser allele was significantly higher than that of treated individuals homozygous or compound heterozygous for the p.Asn409Ser allele. In conclusion, the most important distinguishing features of the Albanian GD patient population are the underrepresentation of the p.Leu483Pro allele and an unusually high number of p.[Asp448His;His294Gln] alleles originating from a common Balkan founder event. The presence of at least one p.Asn409Ser allele is associated with mild disease and low Lyso-Gb1 biomarker levels, while compound heterozygosity involving p.[Asp448His;His294Gln] and no p.Asn409Ser entails severe phenotypes and high Lyso-Gb1 levels., Competing Interests: Paskal Cullufi, Mirela Tabaku, Virtut Velmishi, Agim Gjikopulli, Sonila Tomori, Ermira Dervishi, Aferdita Tako, Anika Leubauer, and Stefan Wirth,4 declare that they have no conflict of interest. Ana Westenberger is a contract worker for CENTOGENE GmbH; Claudia Cozma, Christian Beetz, Peter Bauer, and Arndt Rolfs are employees of CENTOGENE GmbH., (© 2020 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)

Gaucher disease (GD) is a lysosomal storage disorder that responds well to enzyme replacement therapy (ERT). Certain laboratory parameters, including blood concentration of glucosylsphingosine (Lyso-Gb1), the lyso-derivate of the common glycolipid glucocerebroside, correlate with clinical improvement and are therefore considered candidate-monitoring biomarkers. Whether they can indicate a reduction or loss of treatment efficiency, however, has not been systematically addressed for obvious reasons. We established and validated measurement of Lyso-Gb1 from dried blood spots (DBSs) by mass spectrometry. We then characterized the assay's longitudinal performance in 19 stably ERT-treated GD patients by dense monitoring over a 3-year period. The observed level of fluctuation was accounted for in the subsequent development of a unifying data normalization concept. The resulting approach was eventually applied to data from Lyso-Gb1 measurements after an involuntary treatment break for all 19 patients. It enabled separation of the "under treatment" versus "not under treatment" conditions with high sensitivity and specificity. We conclude that Lyso-Gb1 determination from DBSs indicates treatment issues already at an early stage before clinical consequences arise. In addition to its previously shown diagnostic utility, Lyso-Gb1 thereby qualifies as a monitoring biomarker in GD patients.

Introduction: Combining a successful career with family planning has become increasingly important in recent years. However, maintaining a relationship, deciding upon the optimal time for pregnancy and other family planning decisions can still be quite challenging, especially for junior doctors whose training is long and demanding. Currently, women form an important part of the medical workforce, and there is noticeable feminization in migration. However, little is known about the personal characteristics of junior doctors in Europe and how these play a role in their decision to migrate. Methods: Survey of psychiatric trainees in 33 European countries, exploring how personal characteristics, such as gender, relationship status and parenthood, impact their attitudes toward migration. Results: 2,281 psychiatric trainees in Europe took part in the study. In this sample, the majority of psychiatric trainees were in a relationship, but only one quarter had children, although there were variations across Europe. Both men and women indicated personal reasons as their top reason to stay. However, women ranked personal reasons as the top reason to leave, and men financial reasons. Single woman were the most likely of all subgroups to choose academic reasons as their top reason to leave. Interestingly, when women were in a relationship or had children, their attitudes toward migration changed. Conclusions: In this study, a low number of psychiatric trainees in Europe had children, with differences across Europe. These findings raise awareness as to the role of parental conditions, which may be favoring or discouraging parenthood in junior doctors in different countries.

Background: Graves' disease (GD) accounts for 10-15% of thyroid disorders in patients less than 18 years of age. It is the most common cause of thyrotoxicosis in children and accounts for at least 95% of cases in children. Pediatric Treatment of Graves' disease consists of anti-thyroid drugs, radioactive iodide and thyroidectomy but the optimal treatment of GD in children is still controversial., Objective: To review treatment outcome of pediatric Graves' disease in Albania., Material and Method: Descriptive review of 15 children with Graves' disease, diagnosed from Jan.2007 to Dec. 2013, at the Division of Pediatric Endocrinology, Department of Pediatrics, University Hospital Centre "Mother Teresa", Albania was performed., Results: All patients, mean age 10.56 ± 3.37 years, (range 2.02-16.09 years) were presented with goiter and increased serum FT4, mean 39.80 ± 16.02 ng/mL, (range 21.0-74.70 ng/mL), serum FT3, mean 12.98 ± 3.45 pg/mL, (range 6.90 -17.90 pg/mL) and suppressed TSH levels, mean 0.02 ± 0.01 mUI/L, (range 0.01-0.05 mUI/L). Anti TSH Receptor were positive in 100% of patients mean value 6.51 ± 3.61 UI/mL (range 1.63 - 14.10 UI/mL). Anti-thyroglobulin and Anti-TPO antibodies were positive in 60% and 46.6% respectively. Clinical course of 15 patients after treatment with anti-thyroid drugs mainly MMI for 3.19 ± 1.48 (range 0.60 - 6.20) years is as follows: seven (46.66%) underwent remission, five out of seven (71.41%) who underwent remission, relapsed. Three of them (20%) were treated with I(131), and two (13.3%) underwent to total thyroidectomy., Conclusion: MMI was the most common first line therapy in the presented patients with Graves' disease. Remission rate was 46.66% after an average 1.48 ± 0.71 years (range 0.60 - 2.70 years) of treatment with anti-thyroid drugs. Remission period was 2.70 ± 0.36 years (2.1 - 3.1 years) Relapse occurred in 71.41% of patient. I(131) and thyroidectomy were used as second line therapy in the present study.