Search

Seizures are a primary and early disease manifestation of Tuberous Sclerosis Complex (TSC). We aimed to describe the age-stratified patterns of antiseizure drug (ASD) treatments among children, adolescents, and adults with TSC in Germany. Additionally, we reviewed real-world and clinical study evidence regarding ASD utilization in patients with TSC.We evaluated the pattern of routine ASD use and everolimus prescriptions based on a 2019 multicenter survey of 268 individuals with TSC-associated epilepsy. We contextualized the results with a structured review of real-world and clinical study evidence.TSC-associated epilepsy treatment comprises a wide variety of ASDs. In this German sample, the majority of patients were treated with polytherapy, and lamotrigine (34.7%), valproate (32.8%), oxcarbazepine (28.7%), vigabatrin (19.0%), and levetiracetam (17.9%) were identified as the most-commonly used ASDs. In addition, everolimus was used by 32.5% of patients. In adherence to current TSC guidelines, the disease-modifying ASD vigabatrin was widely used in children (58% below the age of 5 years), whereas treatment in adults did not necessarily reflect guideline preference for (partial) GABAergic ASDs.The selection of ASDs for patients with TSC-associated epilepsy follows well-evaluated recommendations, including the guidelines regarding vigabatrin use in children. Several characteristics, such as the comparatively high frequency of valproate use and polytherapy, reflect the severity of TSC-associated epilepsy.

Objective To report and analyze the indications and results of endovascular and open surgical treatment for uretero-arterial fistula. Methods We retrospectively reviewed the clinical data of 25 consecutive patients with uretero-arterial fistulas admitted to our hospital from 2011 to 2020. Endpoints were technical success, freedom from open conversion, stent-graft/graft-related complications, and 30-day and one-year mortality. Results The study included 25 patients (68% female, n = 17) with 27 uretero-arterial fistulas by bilateral pathologies in two patients. The mean age was 61 ± 11 years (range 35–80). The most common predisposing factors for uretero-arterial fistula were history of pelvic operations for malignancy in 21 patients (84%), radiotherapy in 21 patients (84%), previous pelvic vascular bypass in 2 patients (8%), and iliac aneurysms in 2 patients (8%). On average, the period between the primary pelvic surgery and the diagnosis of uretero-arterial fistulas was 46 months (range 7–255). Twenty patients (80%) underwent endovascular treatment of the uretero-arterial fistulas. The primary technical success of the endovascular treatment was 95%, and the freedom from open conversion was 40% at six months and 30% at one year. Thirteen uretero-arterial fistulas (48%) underwent delayed open conversion due to recurrent bleeding in six cases (46%), stent-graft infection in three cases (23%), or pelvic abscess in four cases (31%). Primary open surgery was applied for five (20%) patients. After a mean follow-up of 34 months, early (Conclusions Uretero-arterial fistula is a late complication of prior pelvic surgery, radiation, and indwelling ureteral stents. Endovascular treatment remains an effective and less invasive modality in controlling the related life-threatening arterial bleeding of the uretero-arterial fistula. Open surgical treatment is still required for patients with local sepsis, previously failed endovascular treatment or infected stent-grafts.

Over the past three decades, educational research, policy, and practice have become increasingly interested in relationships and collaboration. In response, social network analysis (SNA) emerged as a theoretical and methodological framework, offering tools to explore relationships in depth. Compared to then existing approaches, SNA allows capturing relationships in a more nuanced way, by focusing on the patterns and qualities of relationships (Borgatti, Mehra, Brass, & Labianca, 2009). SNA offers a valuable perspective for examining whether and to what degree interaction and collaboration take place in education. Another key strength of SNA is that it offers several tools to visualize relationships (Hogan, Carrasco, & Wellman, 2007), which not only creates opportunities for (visual) research but also for practice (e.g., for intervention and feedback purposes). The potential of SNA is reflected in a surge in publications from 37 in 2003 to more than 400 a decade later in the Education Resources Information Center (ERIC; Froehlich, Rehm, & Rienties, 2019). SNA has established its usefulness in various educational sub-fields, for instance, in examining the role of relationships for student achievement (Moolenaar, Sleegers, & Daly, 2012), reform and improvement (Penuel, Bell, Bevan, Buffington, & Falk, 2016), policy implementation (Coburn, Russell, Kaufman, & Stein, 2012), and leadership (Spillane & Shirrell, 2017). No other methodological framework is that much focused on the in-depth exploration of the roles of relationships and structures in learning and instruction (Moolenaar, 2012; Sweet, 2016). The surge in SNA publications across the academic disciplines is largely driven by quantitative SNA studies (Freeman, 2004). Despite its merits, this formalized approach to network analysis has been criticized for a lack of attention to the qualitative aspects of relationships (Fuhse & Mützel, 2011; Hollstein, 2011). Recent work convincingly addresses these concerns by combining quantitative and qualitative approaches. These approaches succeed in addressing research questions not only related to the formal or structural side of relationships and networks. They also attend to questions related to the actual content and meaning of interactions, the (day to day) variability of social relationships, the developments of nodes and ties, and the idea of agency (Crossley, 2010; Crossley & Edwards, 2016).In this article, we posit that mixing methods within SNA is an original innovation that will help to answer new sets of research questions in education research (Bolíbar, 2015; Domínguez & Hollstein, 2014). We argue that a systematic review of mixed method social network analysis (MMSNA) is needed (1) to offer an overview of the existing body of work in education, (2) to show the merits of this approach, and (3) to develop a set of pointers for conducting rigorous MMSNA research and to support scholars in conducting future MMSNA research.

Background The approval of everolimus (EVE) for the treatment of angiomyolipoma (2013), subependymal giant cell astrocytoma (2013) and drug-refractory epilepsy (2017) in patients with tuberous sclerosis complex (TSC) represents the first disease-modifying treatment option available for this rare and complex genetic disorder. Objective The objective of this study was to analyse the use, efficacy, tolerability and treatment retention of EVE in patients with TSC in Germany from the patient’s perspective. Methods A structured cross-age survey was conducted at 26 specialised TSC centres in Germany and by the German TSC patient advocacy group between February and July 2019, enrolling children, adolescents and adult patients with TSC. Results Of 365 participants, 36.7% (n = 134) reported the current or past intake of EVE, including 31.5% (n = 115) who were taking EVE at study entry. The mean EVE dosage was 6.1 ± 2.9 mg/m2 (median: 5.6 mg/m2, range 2.0–15.1 mg/m2) in children and adolescents and 4 ± 2.1 mg/m2 (median: 3.7 mg/m2, range 0.8–10.1 mg/m2) in adult patients. An early diagnosis of TSC, the presence of angiomyolipoma, drug-refractory epilepsy, neuropsychiatric manifestations, subependymal giant cell astrocytoma, cardiac rhabdomyoma and overall multi-organ involvement were associated with the use of EVE as a disease-modifying treatment. The reported efficacy was 64.0% for angiomyolipoma (75% in adult patients), 66.2% for drug-refractory epilepsy, and 54.4% for subependymal giant cell astrocytoma. The overall retention rate for EVE was 85.8%. The retention rates after 12 months of EVE therapy were higher among adults (93.7%) than among children and adolescents (88.7%; 90.5% vs 77.4% after 24 months; 87.3% vs 77.4% after 36 months). Tolerability was acceptable, with 70.9% of patients overall reporting adverse events, including stomatitis (47.0%), acne-like rash (7.7%), increased susceptibility to common infections and lymphoedema (each 6.0%), which were the most frequently reported symptoms. With a total score of 41.7 compared with 36.8 among patients not taking EVE, patients currently being treated with EVE showed an increased Liverpool Adverse Event Profile. Noticeable deviations in the sub-items ‘tiredness’, ‘skin problems’ and ‘mouth/gum problems’, which are likely related to EVE-typical adverse effects, were more frequently reported among patients taking EVE. Conclusions From the patients’ perspective, EVE is an effective and relatively well-tolerated disease-modifying treatment option for children, adolescents and adults with TSC, associated with a high long-term retention rate that can be individually considered for each patient. Everolimus therapy should ideally be supervised by a centre experienced in the use of mechanistic target of rapamycin inhibitors, and adverse effects should be monitored on a regular basis.

Background Tuberous sclerosis complex (TSC) is a monogenetic, multisystemic disease characterised by the formation of benign tumours that can affect almost all organs, caused by pathogenic variations in TSC1 or TSC2. In this multicentre study from Germany, we investigated the influence of sociodemographic, clinical, and therapeutic factors on quality of life (QoL) among individuals with TSC. Methods We assessed sociodemographic and clinical characteristics and QoL among adults with TSC throughout Germany using a validated, three-month, retrospective questionnaire. We examined predictors of health-related QoL (HRQoL) using multiple linear regression analysis and compared the QoL among patients with TSC with QoL among patients with other chronic neurological disorders. Results We enrolled 121 adults with TSC (mean age: 31.0 ± 10.5 years; range: 18–61 years, 45.5% [n = 55] women). Unemployment, a higher grade of disability, a higher number of organ manifestations, the presence of neuropsychiatric manifestations or active epilepsy, and a higher burden of therapy-related adverse events were associated with worse QoL, as measured by two QoL instruments (EuroQoL-5 dimensions [EQ-5D] and Quality of Life in Epilepsy Patients [QOLIE-31]). Neuropsychiatric and structural nervous system manifestations, the number of affected organs, and therapy-related adverse events were also associated with higher depression, as measured by the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). In multiple regression analysis, more severe therapy-related adverse events (large effect, p p p = 0.003) were independently associated with worse HRQoL, explaining 65% of the variance (p p Conclusions Active epilepsy, neuropsychiatric manifestations (such as anxiety and depression), and therapy-related adverse events are important independent predictors of worse quality of life among adults with TSC. Generic quality of life in TSC with several manifestations is similar to uncontrolled severe chronic diseases and significantly negatively correlates with TSC severity. Trial registration DRKS, DRKS00016045. Registered 01 March 2019.

Background: Diagnosis and treatment of paediatric tuberculosis resistant to both isoniazid and rifampicin (MDR-pTB) remain challenging due to paucibacillary disease, low sensitivity and specificity of diagnostic tools and frequently changing guidelines Aims and objective: This study aimed to describe epidemiology, clinical characteristics and outcome of MDR-TB among children and adolescents in Germany. Methods: We collected all cases of MDR-pTB registered in Germany from 2010 to 2020 and compared their data to an adequate control sample with drug-sensitive TB. Results: 52 subjects with MDR-pTB (24 active MDR-TB, 28 MDR-LTBI) and 56 controls were included. The annual incidence of MDR-TB rose from two in 2010 to nine in 2020. Time to diagnosis was longer in MDR-pTB compared to drug-sensitive TB (43 vs. 8 days, p Conclusions: Early diagnosis, identification of potential MDR index, appropriate treatment and follow-up are essential in MDR-pTB. Therefore, better cooperation between clinics and public health care is required in Germany. In children with an MDR-TB index case or in those born in a MDR high-incidence country, bacteriological confirmation including PCR-based susceptibility testing should always be initiated. The individual drug regimen has to be adapted to the patients’ or index’ susceptibility testing results.

Heart failure (HF) is a prevalent disease that remains costly and associated with a high mortality rate. HF is also associated with poor neurocognitive functioning. For the treatment for HF patients with severe mitral regurgitation, the MitraClip device has emerged as a promising interventional tool that reduces the mitral valve leakage and thus increases cardiac output. Currently, there is only limited knowledge on changes in cognitive and psychosocial functioning before and after the MitraClip intervention.Cognitive function (memory and executive function) and psychosocial measures (depression, anxiety, and quality of life) were assessed before and after the MitraClip intervention in 24 HF patients and 23 healthy participants (comparison group).MitraClip intervention in HF patients was followed by improvements in figural long-term memory (p = .003) and executive function (planning ability, p < .001) relative to the comparison group. In addition, the intervention resulted in a significant improvement in depression (p = .002), anxiety (p = .003) and quality of life scores (physical p = .017, mental p = .013) as well as improved 6-minute walk test results over time (p = .002).The presented data provide evidence of a significant improvement in memory and executive function as well as in depression, anxiety, and quality of life scores in patients with chronic HF after MitraClip intervention. Further research is needed to shed light on the long-term development of cognitive function, psychosocial well-being, and clinical parameters after MitraClip intervention and how these factors depend on one another.

Renal cysts occur in approximately 50% of patients with tuberous sclerosis complex, but their clinical significance and response to treatment are unknown. Abdominal imaging of 15 patients with tuberous sclerosis complex-associated renal cystic disease who had received mammalian target of rapamycin inhibitor therapy for other tuberous sclerosis complex-related indications was evaluated. Reductions in cyst number, sum diameter, and volume were observed.