Development and feasibility of a telemedicine tool for patients with recurrent urinary tract infection: myRUTIcoach.

INTRODUCTION AND HYPOTHESIS: Patients with recurrent urinary tract infection (rUTI) have limited knowledge of preventive strategies to lower the risk of UTI. We aimed to develop and test the feasibility of an eHealth system for women with rUTI, named myRUTIcoach, and explored the facilitators and barriers related to its adoption. METHODS: We developed myRUTIcoach in a structured iterative process and tested its feasibility among 25 women with rUTI over 2 months. Subsequent questionnaires covered satisfaction, accessibility, and experiences with myRUTIcoach. A random selection of participants and relevant stakeholders took part in semi-structured interviews to explore adoption. Data were analyzed and elaborated using inductive and deductive approaches using the Non-adoption, Abandonment, Spread, Scale-up, and Sustainability (NASSS) framework. RESULTS: MyRUTIcoach was not only widely accepted but also facilitated communication with health care professionals (HCPs) and contributed to greater knowledge of rUTI. Women graded the system a mean of 8.0 (±0.6) out of 10, with 89% stating that they would recommend it to others. Patients indicated that self-management skills were the major facilitators and barriers related to adoption, whereas HCPs stated that the disconnect between myRUTIcoach and electronic health care records (EHRs) was the major barrier. CONCLUSIONS: This research describes the development and testing of myRUTIcoach for women with rUTI. Patients and HCPs reported high satisfaction and compliance with myRUTIcoach. However, adoption by the intended users is complex and influenced by all examined domains of the NASSS framework. We have already improved linkage to EHRs, but further optimization to meet patient needs may improve the effectiveness of this self-management tool for rUTI.

Complement component 4A protein levels are negatively related to frontal volumes in patients with schizophrenia spectrum disorders.

BACKGROUND: Excessive C4A-gene expression may result in increased microglia-mediated synaptic pruning. As C4A overexpression is observed in schizophrenia spectrum disorders (SSD), this mechanism may account for the altered brain morphology (i.e. reduced volume and cortical thickness) and cognitive symptoms that characterize SSD. Therefore, this study investigates the association of C4A serum protein levels with brain morphology and cognition, and in particular whether this association differs between recent-onset SSD (n = 69) and HC (n = 40). METHODS: Serum C4A protein levels were compared between groups. Main outcomes included total gray matter volume, mean cortical thickness and cognitive performance. Regression analysis on these outcomes included C4A level, group (SSD vs. HC), and C4A*Group interactions. All statistical tests were corrected for age, sex, BMI, and antipsychotic medication dose. Follow-up analyses were performed on separate brain regions and scores on cognitive sub-tasks. RESULTS: The group difference in C4A levels was not statistically significant (p = 0.86). The main outcomes did not show a significant interaction effect (p > 0.13) or a C4A main effect (p > 0.27). Follow-up analyses revealed significant interaction effects for the left medial orbitofrontal and left frontal pole volumes (p < 0.001): C4A was negatively related to these volumes in SSD, but positively in HC. CONCLUSION: This study demonstrated that C4A was negatively related to - specifically - frontal brain volumes in SSD, but this relation was inverse for HC. The results support the hypothesis of complement-mediated brain volume reduction in SSD. The results also suggest that C4A has a differential association with brain morphology in SSD compared to HC.

[The translation of genetic risk variants to molecular disease mechanisms]. / De vertaling van genetische risicovarianten naar moleculaire ziektemechanismen.

BACKGROUND: Genetic studies have found large numbers of genetic risk variants that increase the risk to develop neuropsychiatric disorders. AIM: We aim to explain how to investigate the effects of these genetic risk variants on the expression of genes and whether this plays a potential role in neuropsychiatric disorders. METHOD: We describe the main findings of a study that we recently performed to study the association between genetic risk factors for neuropsychiatric disorders and gene expression in microglia, the immune cells of the brain. RESULTS: Part of the risk variants for neuropsychiatric disorders could be related to gene expression in microglia. These
associations were particularly strong for neurodegenerative disorders. CONCLUSION: Our study provided more insight into how genetic risk to neuropsychiatric disorders is related to gene expression in microglia. These findings show suggestions for potential new treatment options.

GENType: all-in-one preimplantation genetic testing by pedigree haplotyping and copy number profiling suitable for third-party reproduction.

STUDY QUESTION: Is it possible to develop a comprehensive pipeline for all-in-one preimplantation genetic testing (PGT), also suitable for parents-only haplotyping and, for the first time, third-party reproduction? SUMMARY ANSWER: Optimized reduced representation sequencing (RRS) by GENType, along with a novel analysis platform (Hopla), enables cheap, accurate and comprehensive PGT of blastocysts, even without the inclusion of additional family members or both biological parents for genome-wide embryo haplotyping. WHAT IS KNOWN ALREADY: Several haplotyping strategies have proven to be effective for comprehensive PGT. However, these methods often rely on microarray technology, whole-genome sequencing (WGS) or a combination of strategies, hindering sample throughput and cost-efficiency. Moreover, existing tools (including other RRS-based strategies) require both prospective biological parents for embryo haplotyping, impeding application in a third-party reproduction setting. STUDY DESIGN, SIZE, DURATION: This study included a total of 257 samples. Preliminary technical validation was performed on 81 samples handpicked from commercially available cell lines. Subsequently, a clinical validation was performed on a total of 72 trophectoderm biopsies from 24 blastocysts, tested for a monogenic disorder (PGT-M) (n = 15) and/or (sub)chromosomal aneuploidy (PGT-SR/PGT-A) (n = 9). Once validated, our pipeline was implemented in a diagnostic setting on 104 blastocysts for comprehensive PGT. PARTICIPANTS/MATERIALS, SETTING, METHODS: Samples were whole-genome amplified (WGA) and processed by GENType. Quality metrics, genome-wide haplotypes, b-allele frequencies (BAFs) and copy number profiles were generated by Hopla. PGT-M results were deduced from relative haplotypes, while PGT-SR/PGT-A results were inferred from read-count analysis and BAF profiles. Parents-only haplotyping was assessed by excluding additional family members from analysis and using an independently diagnosed embryo as phasing reference. Suitability for third-party reproduction through single-parent haplotyping was evaluated by excluding one biological parent from analysis. Results were validated against reference PGT methods. MAIN RESULTS AND THE ROLE OF CHANCE: Genome-wide haplotypes of single cells were highly accurate (mean > 99%) compared to bulk DNA. Unbalanced chromosomal abnormalities (>5 Mb) were detected by GENType. For both PGT-M as well as PGT-SR/PGT-A, our technology demonstrated 100% concordance with reference PGT methods for diverse WGA methods. Equally, for parents-only haplotyping and single-parent haplotyping (of autosomal dominant disorders and X-linked disorders), PGT-M results were fully concordant. Furthermore, the origin of trisomies in PGT-M embryos was correctly deciphered by Hopla. LIMITATIONS, REASONS FOR CAUTION: Intrinsic to linkage-analysis strategies, de novo single-nucleotide variants remain elusive. Moreover, parents-only haplotyping is not a stand-alone approach and requires prior diagnosis of at least one reference embryo by an independent technology (i.e. direct mutation analysis) for haplotype phasing. Using a haplotyping approach, the presence of a homologous recombination site across the chromosome is biologically required to distinguish meiotic II errors from mitotic errors during trisomy origin investigation. WIDER IMPLICATIONS OF THE FINDINGS: We offer a generic, fully automatable and accurate pipeline for PGT-M, PGT-A and PGT-SR as well as trisomy origin investigation without the need for personalized assays, microarray technology or WGS. The unique ability to perform single-parent assisted haplotyping of embryos paves the way for cost-effective PGT in a third-party reproduction setting. STUDY FUNDING/COMPETING INTEREST(S): L.D.W. is supported by the Research Foundation Flanders (FWO; 1S74619N). L.R. and B.M. are funded by Ghent University and M.B., S.S., K.T., F.V.M. and A.D. are supported by Ghent University Hospital. Research in the N.C. lab was funded by Ghent University, VIB and Kom op Tegen Kanker. A.D.K and N.C. are co-inventors of patent WO2017162754A1. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

The Patient Pathway for Men with Chronic Urinary Retention: Treatments, Complications, and Consequences.

OBJECTIVE: To explore the treatment options for chronic urinary retention (CUR) in men, including treatment-related complications and consequences. METHODS: This retrospective cohort study included male patients diagnosed with a non-neurogenic, symptomatic and/or high-risk, CUR >150 mL in a large Dutch non-academic teaching hospital. Data for treatments, complications, and consequences (eg, diagnostics, additional treatments, and hospital contact) were recorded and incidence rate ratios (IRRs) were calculated. RESULTS: We enrolled 177 patients (median age, 77 years; range, 44-94) with a median follow-up of 68 months (range, 1-319) during which they had a median of 8 events (range, 1-51). Most patients initially received a urethral catheter (74%) and some form of catheterization as their final treatment (87%). Compared with non-surgical cases, catheterization was more likely to be stopped after de-obstructive prostate surgery (IRR, 4.18; P < 0.001). Urinary tract infection (IRR, 3.68; P < 0.001) and macroscopic hematuria (IRR, 5.35; P < 0.001) were more common with catheterization, but post-renal problems were more likely in patients with no catheterization (IRR, 25.36; P < 0.001). The lowest chance of complication was with clean intermittent catheterization, and complications were usually managed in outpatient (77%) or emergency (6%) departments, rather than by admission (17%). CONCLUSION: Most patients require catheterization for CUR, with clean intermittent catheterization preferred due to its comparatively lower complication risk. De-obstructive prostate surgery increases the chance of stopping catheterization and may be considered in suitable cases.

CRISPR/Cas gene editing in the human germline.

The ease and efficacy of CRISPR/Cas9 germline gene editing in animal models paved the way to human germline gene editing (HGGE), by which permanent changes can be introduced into the embryo. Distinct genes can be knocked out to examine their function during embryonic development. Alternatively, specific sequences can be introduced which can be applied to correct disease-causing mutations. To date, it has been shown that the success of HGGE is dependent on various experimental parameters and that various hurdles (i.e. loss-of-heterozygosity and mosaicism) need to be overcome before clinical applications should be considered. Due to the shortage of human germline material and the ethical constraints concerning HGGE, alternative models such as stem cells have been evaluated as well, in terms of their predictive value on the genetic outcome for HGGE approaches. This review will give an overview of the state of the art of HGGE in oocytes and embryos, and its accompanying challenges.

Emerging technologies and their potential for generating new assistive technologies.

Limited access to assistive technology (AT) is a well-recognized global challenge. Emerging technologies have potential to develop new assistive products and bridge some of the gaps in access to AT. However, limited analyses exist on the potential of these technologies in the AT field. This paper describes a study that aimed to provide an overview of emerging technological developments and their potential for the AT field. It involved conducting a gray literature review and patent analysis to create an overview of the emerging enabling technologies that may foster the development of new AT products and services and identify emerging AT applications. The analysis identified seven enabling technologies that are relevant to the AT field. These are artificial intelligence, emerging human-computer interfaces, sensor technology, robotics, advances in connectivity and computing, additive manufacturing and new materials. Whilst there are over 3.7 million patents related to these enabling technologies, only a fraction of them - 11,000 patents were identified in the analysis specifically related to AT (0.3%). The paper presents some of the promising examples. Overall, the results indicate that there is an enormous potential for new AT solutions that capitalize on emerging technological advances.

High seroprevalence of COVID-19 infection in a large slum in South India; what does it tell us about managing a pandemic and beyond?

People living in urban slums or informal settlements are among the most vulnerable communities, highly susceptible to coronavirus disease 2019 (COVID-19) infection and vulnerable to the consequences of the measures taken to control the spread of the virus. Fear and stigma related to infection, mistrust between officials and the population, the often-asymptomatic nature of the disease is likely to lead to under-reporting. We conducted a cross-sectional study to determine the seroprevalence of COVID-19 infection in a large slum in South India 3 months after the index case and recruited 499 adults (age >18 years). The majority (74.3%) were females and about one-third of the population reported comorbidities. The overall seroprevalence of IgG antibody for COVID-19 was 57.9% (95% CI 53.4-62.3). Age, education, occupation and the presence of reported comorbidities were not associated with seroprevalence (P-value >0.05). Case-to-undetected-infections ratio was 1:195 and infection fatality rate was calculated as 2.94 per 10 000 infections. We estimated seroprevalence of COVID-19 was very high in our study population. The focus in this slum should shift from infection prevention to managing the indirect consequences of the pandemic. We recommend seroprevalence studies in such settings before vaccination to identify the vulnerability of COVID-19 infection to optimise the use of insufficient resources. It is a wake-up call to societies and nations, to dedicate paramount attention to slums into recovery and beyond - to build, restore and maintain health equity for the 'Health and wellbeing of all'.

Assessment and treatment of recurrent urinary tract infections in women: development of a questionnaire based on a qualitative study of patient expectations in secondary care.

BACKGROUND: To develop a questionnaire to facilitate the inventorying of women's expectations for the assessment and treatment of recurrent urinary tract infection (UTI) in secondary care. METHODS: Semi-structured interviews were conducted among women with recurrent UTI referred to our urology department. The interviews were conducted by one interviewer, recorded, transcribed verbatim, and analyzed thematically by two researchers. We first developed 35 questions to identify potential themes, and we then tested them among women with and without recurrent UTI. Changes were made according to the feedback received. RESULTS: Six interviews were conducted before saturation was reached. Thematic analysis identified three themes: patient pathway, personal knowledge, and social implications. All respondents had received multiple antibiotic courses but no prophylactic antibiotic therapy, and although all were aware of some preventive measures, they wanted more information about their disease. However, some women were afraid to access information for fear of what they might learn. Recurrent UTI also significantly affected the daily lives all respondents. Some women expressed fears over frequent antibiotic use, and others felt that there must be something wrong with their body to have so many UTIs. Women expected the urologist to provide an explanation and to start adequate therapy for their recurrent UTI. We created a 32-item questionnaire based on these themes CONCLUSION: This study not only developed a questionnaire for use when assessing patient expectations of recurrent UTI management in secondary care but also provided novel insights into the thoughts, opinions, and expectations of women who are referred.

No association between anti-thyroidperoxidase antibodies and bipolar disorder: a study in the Dutch Bipolar Cohort and a meta-analysis.

BACKGROUND: Thyroid autoimmunity has been associated with bipolar disorder (BD). However, results from previous studies on the seroprevalence of anti-thyroid peroxidase antibodies (TPO-abs) in BD are inconsistent. OBJECTIVES: The aim of the present study is to investigate whether the seroprevalence and titer levels of TPO-abs are related to BD. METHOD: TPO-abs were measured in plasma samples of 760 patients with bipolar disorder, 261 first-degree relatives and 363 controls by enzyme-linked immunosorbent assay (ELISA). To address methodological limitations of previous studies, we assessed clinical characteristics with several (self-reported) questionnaires to investigate whether TPO-abs positivity is related to particular clinical subgroups of BD patients. We performed an additional meta-analysis of seroprevalences of TPO-abs in BD patients including data from present and previous studies. RESULTS: Seroprevalence or titer levels of TPO-abs did not significantly differ between patients with BD, their first-degree relatives, and controls. In BD patients, the prevalence of TPO-abs was unrelated to specific clinical factors, including lithium use. Our meta-analysis of twelve studies showed an overall odds ratio of 1.3 (CI 95 %: 0.7-2.3; p = 0.30), reaffirming the absence of an association of BD with TPO-abs. CONCLUSIONS: In the largest study of TPO-abs in BD to date, our findings indicate that TPO-abs are not associated with (the risk for) bipolar disorder.

Vitamin D concentration and psychotic disorder: associations with disease status, clinical variables and urbanicity.

BACKGROUND: The association between schizophrenia and decreased vitamin D levels is well documented. Low maternal and postnatal vitamin D levels suggest a possible etiological mechanism. Alternatively, vitamin D deficiency in patients with schizophrenia is presumably (also) the result of disease-related factors or demographic risk factors such as urbanicity. METHODS: In a study population of 347 patients with psychotic disorder and 282 controls, group differences in vitamin D concentration were examined. Within the patient group, associations between vitamin D, symptom levels and clinical variables were analyzed. Group × urbanicity interactions in the model of vitamin D concentration were examined. Both current urbanicity and urbanicity at birth were assessed. RESULTS: Vitamin D concentrations were significantly lower in patients (B = -8.05; 95% confidence interval (CI) -13.68 to -2.42; p = 0.005). In patients, higher vitamin D concentration was associated with lower positive (B = -0.02; 95% CI -0.04 to 0.00; p = 0.049) and negative symptom levels (B = -0.03; 95% CI -0.05 to -0.01; p = 0.008). Group differences were moderated by urbanicity at birth (χ2 = 6.76 and p = 0.001), but not by current urbanicity (χ2 = 1.50 and p = 0.224). Urbanicity at birth was negatively associated with vitamin D concentration in patients (B = -5.11; 95% CI -9.41 to -0.81; p = 0.020), but not in controls (B = 0.72; 95% CI -4.02 to 5.46; p = 0.765). CONCLUSIONS: Lower vitamin D levels in patients with psychotic disorder may in part reflect the effect of psychosis risk mediated by early environmental adversity. The data also suggest that lower vitamin D and psychopathology may be related through direct or indirect mechanisms.

Genetic vulnerability to DUSP22 promoter hypermethylation is involved in the relation between in utero famine exposure and schizophrenia.

Epigenetic changes may account for the doubled risk to develop schizophrenia in individuals exposed to famine in utero. We therefore investigated DNA methylation in a unique sample of patients and healthy individuals conceived during the great famine in China. Subsequently, we examined two case-control samples without famine exposure in whole blood and brain tissue. To shed light on the causality of the relation between famine exposure and DNA methylation, we exposed human fibroblasts to nutritional deprivation. In the famine-exposed schizophrenia patients, we found significant hypermethylation of the dual specificity phosphatase 22 (DUSP22) gene promoter (Chr6:291687-293285) (N = 153, p = 0.01). In this sample, DUSP22 methylation was also significantly higher in patients independent of famine exposure (p = 0.025), suggesting that hypermethylation of DUSP22 is also more generally involved in schizophrenia risk. Similarly, DUSP22 methylation was also higher in two separate case-control samples not exposed to famine using DNA from whole blood (N = 64, p = 0.03) and postmortem brains (N = 214, p = 0.007). DUSP22 methylation showed strong genetic regulation across chromosomes by a region on chromosome 16 which was consistent with new 3D genome interaction data. The presence of a direct link between famine and DUSP22 transcription was supported by data from cultured human fibroblasts that showed increased methylation (p = 0.048) and expression (p = 0.019) in response to nutritional deprivation (N = 10). These results highlight an epigenetic locus that is genetically regulated across chromosomes and that is involved in the response to early-life exposure to famine and that is relevant for a major psychiatric disorder.

[Is psychiatry ready to let patients review their own files? Inventory of initial experiences]. / Is de psychiatrie klaar voor de meelezende patiënt? Inventarisatie van eerste ervaringen.

BACKGROUND: Dutch patients will be granted the right to digitally access their own medical records, an option already available to the patients at the University Medical Center Utrecht since 2015. AIM: To start a conversation about the development of readily accessible online patient records. METHODS Describe the experiences of a University department of psychiatry with an online patient portal, obtained through discussions and questionnaires. RESULTS: During the next few years three legal developments will enable patients to acquire direct, remote, digital access to their medical files. Immediate online review of medical records improves accessibility and empowers the patient. Some therapists experienced a change in patient interaction. Furthermore, during documentation psychiatrists took into account that patients could review the contents at a later point. CONCLUSION: Patients' accessibility of online records will influence the patient-therapist dynamic. More research on the patient perspective and a discussion among professionals are necessary to further streamline broad implementation of online patient portals.

[In- and out-of-hospital emergency psychiatry: what is the best approach?] / Acute psychiatrie binnen en buiten het ziekenhuis.

A range of clinical syndromes may present with psychiatric symptoms, both in and out of hospital settings. In such situations agitation, suicidality, communication difficulties and legal aspects often play a role, making diagnosis and treatment a challenge. Based on several case studies, we illustrate how the recently-published Dutch open access source 'Acute Psychiatry' (www.acutepsychiatrie.com) can be of help in acute psychiatric presentations both within and outside psychiatric hospitals.

Evaluation of Dynamic Arm Supports in Real Life Environments.

Dynamic arm supports facilitate the performance of activities of daily living (ADL) in people with upper extremity limitations. For which ADL, and how devices are used in daily life differs between users, imposing a difficulty to the assessment of outcomes. Therefore this study reports on the instruments used in earlier studies. Several instruments in the domains of body functions and activities and participation were identified. Instruments used include patient reported outcome measures, questionnaires, interviews, and arm and hand function tests.

Nitrogen deposition changes ectomycorrhizal communities in Swiss beech forests.

Atmospheric pollution has implications for the health and diversity of temperate forests covering large parts of central Europe. Long-term elevated anthropogenic deposition of nitrogen (N) is driving forest ecosystems from the limitation by N to other nutrients and is found to affect tree health and ectomycorrhizal fungi (EMF), which most trees depend on for nutrient uptake. However, the consequence of EMF community changes for trees remains unclear. Therefore, we investigated changes in EMF communities on root tips and in soil of beech forests along a N deposition gradient ranging between 16 and 33kgNha-1a-1, where high N deposition was found to negatively affect tree growth and nutrient levels. The most important factors significantly explaining variation in root tip and mycelium EMF community composition in both root tips and mesh bags were increased N deposition, base saturation, growing season temperature and precipitation. With increasing N deposition, fine root length, EMF root colonization, EMF diversity on root tips and in soil, and production of extramatrical mycelium decreased significantly. Foliar P and potassium (K) were positively associated with increasing EMF diversity and we found EMF community composition to be associated with foliar P and N:P ratio. The decrease in root colonization, mesh bag ingrowth and abundance of the important species Cenococcum geophilum as well as high biomass species with increasing N availability clearly indicate repercussions for belowground carbon allocation, although some indicator species for high N deposition and low foliar P have long mycelia and may reflect a potential optimization of host P uptake. Our study supports the hypothesis that the decrease in nutrient uptake in beech forests across Europe is related to changes in EMF communities and suggests that continued high N deposition changes soil carbon and nutrient cycles, thereby affecting forest ecosystem health.

Immune involvement in the pathogenesis of schizophrenia: a meta-analysis on postmortem brain studies.

Although the precise pathogenesis of schizophrenia is unknown, genetic, biomarker and imaging studies suggest involvement of the immune system. In this study, we performed a systematic review and meta-analysis of studies investigating factors related to the immune system in postmortem brains of schizophrenia patients and healthy controls. Forty-one studies were included, reporting on 783 patients and 762 controls. We divided these studies into those investigating histological alterations of cellular composition and those assessing molecular parameters; meta-analyses were performed on both categories. Our pooled estimate on cellular level showed a significant increase in the density of microglia (P=0.0028) in the brains of schizophrenia patients compared with controls, albeit with substantial heterogeneity between studies. Meta-regression on brain regions demonstrated this increase was most consistently observed in the temporal cortex. Densities of macroglia (astrocytes and oligodendrocytes) did not differ significantly between schizophrenia patients and healthy controls. The results of postmortem histology are paralleled on the molecular level, where we observed an overall increase in expression of proinflammatory genes on transcript and protein level (P=0.0052) in patients, while anti-inflammatory gene expression levels were not different between schizophrenia and controls. The results of this meta-analysis strengthen the hypothesis that components of the immune system are involved in the pathogenesis of schizophrenia.

The seroprevalence of antithyroid peroxidase antibodies in bipolar families and bipolar twins: results from two longitudinal studies.

BACKGROUND: Previous studies of our group among bipolar offspring and bipolar twins showed significant higher prevalence's and levels of antithyroid peroxidase antibodies (TPO-Abs) in offspring and co-twins (without a mood disorder) compared to controls, suggesting that TPO-Abs might be considered as vulnerability factor (trait marker) for BD development. OBJECTIVES: Here we elucidate, in the same cohorts, but now after 12- and 6-year follow-up, whether TPO-abs should be considered as a 'trait' marker for BD. The present study aims to investigate whether TPO-Abs (1) are stable over time, (2) are associated with lithium-exposure, (3) share a common genetic background with BD and are related to psychopathology. RESULTS: In bipolar offspring and twins, the prevalence of TPO-Abs is stable over time (r s = .72 p < .001 resp. r s = .82, p < .001) and not associated with lithium use. At follow-up, an increased prevalence of TPO-abs was again observed in bipolar offspring (10,4% versus 4%) and higher TPO-abs titers were still present in co-twins of bipolar cases compared to control twins [mean 1.06 IU/ml (SD .82) versus mean .82 IU/ml (SD .67)], although statistical significance was lost. CONCLUSIONS: Although our results show a trend toward an increased inherited risk of the co-occurrence of BD and thyroid autoimmunity, large-scale studies can only draw final conclusions. Nationwide epidemiological and GWAS studies reach such numbers and support the view of a possible common (autoimmune) etiology of severe mood disorders and chronic recurrent infections and autoimmunity, including thyroid autoimmunity.

[Aggression and restlessness following baclofen overdose: the narrow line between intoxication and withdrawal symptoms]. / Agressie en onrust na overdosis baclofen.

BACKGROUND: Baclofen is increasingly prescribed for alcohol dependency. Subsequently, the risk of self-intoxication with this medicinal product is increasing. CASE DESCRIPTION: A 23-year-old man with a history of alcohol dependence was admitted to our hospital after self-intoxication with 2700 mg baclofen and 330 mg mirtazapine. Respiratory insufficiency as a result of the baclofen intoxication required intubation and admission to the ICU. During the first day, despite the use of sedatives, the patient became intermittently agitated and aggressive. In the following days, he developed severe delirium, probably due to baclofen withdrawal. The reintroduction of baclofen quickly resolved these symptoms. CONCLUSION: In the case of baclofen, in practice it is difficult to differentiate between intoxication and withdrawal. To prevent potentially severe withdrawal symptoms, we recommend reintroduction of baclofen when the first signs of restlessness and agitation arise following intoxication.