المؤلفون: Stefanie Schoenen, Johan Verbeeck, Lukas Koletzko, Isabella Brambilla, Mathieu Kuchenbuch, Maya Dirani, Georg Zimmermann, Holger Dette, Ralf-Dieter Hilgers, Geert Molenberghs, Rima Nabbout

المصدر: Orphanet Journal of Rare Diseases, Vol 19, Iss 1, Pp 1-13 (2024)

مصطلحات موضوعية: Bias assessment with multiple endpoints, Finite populations, Multiple endpoints, Natural history modelling, Rare disease clinical trials, Similarity of subgroups, Medicine

الوصف: Abstract Background The conduct of rare disease clinical trials is still hampered by methodological problems. The number of patients suffering from a rare condition is variable, but may be very small and unfortunately statistical problems for small and finite populations have received less consideration. This paper describes the outline of the iSTORE project, its ambitions, and its methodological approaches. Methods In very small populations, methodological challenges exacerbate. iSTORE’s ambition is to develop a comprehensive perspective on natural history course modelling through multiple endpoint methodologies, subgroup similarity identification, and improving level of evidence. Results The methodological approaches cover methods for sound scientific modeling of natural history course data, showing similarity between subgroups, defining, and analyzing multiple endpoints and quantifying the level of evidence in multiple endpoint trials that are often hampered by bias. Conclusion Through its expected results, iSTORE will contribute to the rare diseases research field by providing an approach to better inform about and thus being able to plan a clinical trial. The methodological derivations can be synchronized and transferability will be outlined.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1750-1172Test

الوصول الحر: https://doaj.org/article/cf18059f5f1f47b2a01bc312b83b7039Test

المؤلفون: Thomas Pixner, Tatsiana Chaikouskaya, Wanda Lauth, Georg Zimmermann, Katharina Mörwald, Julia Lischka, Dieter Furthner, Elisabeth Awender, Sabine Geiersberger, Katharina Maruszczak, Anders Forslund, Christian-Heinz Anderwald, Janne Cadamuro, Daniel Weghuber, Peter Bergsten

المصدر: Frontiers in Endocrinology, Vol 15 (2024)

مصطلحات موضوعية: glucagon, OGTT, obesity, pediatric, liver-alpha cell axis, insulin, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: BackgroundFasting levels of glucagon are known to be elevated in youth and adults with type 2 diabetes mellitus (T2D). Children and adolescents with obesity were previously reported to show increasing fasting and post-glucose-challenge hyperglucagonemia across the spectrum of glucose tolerance, while no data are available in those with impaired fasting glucose (IFG).Materials and methodsIndividuals from the Beta-JUDO study population (Uppsala and Salzburg 2010–2016) (n=101, age 13.3 ± 2.8, m/f =50/51) were included (90 with overweight or obesity, 11 with normal weight). Standardized OGTT were performed and plasma glucose, glucagon and insulin concentrations assessed at baseline, 5, 10, 15, 30, 60, 90 and 120 minutes. Patients were grouped according to their glycemic state in six groups with normal glucose metabolism (NGM) and normal weight (NG-NW), NGM with obesity or overweight (NG-O), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IGT+IFG and T2D, and in two groups with NGM and impaired glucose metabolism (IGM), for statistical analysis.Results and conclusionGlucagon concentrations were elevated in young normoglycemic individuals with overweight or obesity (NG-O) compared to normoglycemic individuals with normal weight. Glucagon levels, fasting and dynamic, increased with progressing glycemic deterioration, except in IFG, where levels were comparable to those in NG-O. All glycemic groups showed an overall suppression of glucagon during OGTT. An initial increase of glucagon could be observed in T2D. In T2D, glucagon showed a strong direct linear correlation with plasma glucose levels during OGTT. Glucagon in adolescents, as in adults, may play a role in the disease progression of T2D.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fendo.2024.1368570/fullTest; https://doaj.org/toc/1664-2392Test

الوصول الحر: https://doaj.org/article/5791e53625f141b086aef801b27573acTest

المؤلفون: Vanessa N. Frey, Patrick B. Langthaler, Nora Renz, Georg Zimmermann, Christopher Höhn, Kerstin Schwenker, Aljoscha Thomschewski, Alexander B. Kunz, Yvonne Höller, Raffaele Nardone, Eugen Trinka

المصدر: Frontiers in Medical Technology, Vol 6 (2024)

مصطلحات موضوعية: movement preparation, paraplegia, physical activity, transcranial magnetic stimulation, cortical excitability, Medical technology, R855-855.5

الوصف: BackgroundPatients with spinal cord injury (SCI) show abnormal cortical excitability that might be caused by deafferentation. We hypothesize a reduced short-interval intracortical inhibition preceding movement in patients with SCI compared with healthy participants. In addition, we expect that neuroplasticity induced by different types of sports can modulate intracortical inhibition during movement preparation in patients with SCI.MethodsWe used a reaction test and paired-pulse transcranial magnetic stimulation to record cortical excitability, assessed by measuring amplitudes of motor-evoked potentials in preparation of movement. The participants were grouped as patients with SCI practicing wheelchair dancing (n = 7), other sports (n = 6), no sports (n = 9), and healthy controls (n = 24).ResultsThere were neither significant differences between healthy participants and the patients nor between the different patient groups. A non-significant trend (p = .238), showed that patients engaged in sports have a stronger increase in cortical excitability compared with patients of the non-sportive group, while the patients in the other sports group expressed the highest increase in cortical excitability.ConclusionThe small sample sizes limit the statistical power of the study, but the trending effect warrants further investigation of different sports on the neuroplasticity in patients with SCI. It is not clear how neuroplastic changes impact the sensorimotor output of the affected extremities in a patient. This needs to be followed up in further studies with a greater sample size.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmedt.2024.1297552/fullTest; https://doaj.org/toc/2673-3129Test

الوصول الحر: https://doaj.org/article/5fbb0d2f36ef47dfa9ac7ea5c70907f0Test

المؤلفون: Martin Geroldinger, Johan Verbeeck, Andrew C. Hooker, Konstantin E. Thiel, Geert Molenberghs, Joakim Nyberg, Johann Bauer, Martin Laimer, Verena Wally, Arne C. Bathke, Georg Zimmermann

المصدر: Orphanet Journal of Rare Diseases, Vol 18, Iss 1, Pp 1-12 (2023)

مصطلحات موضوعية: Cross-over, Epidermolysis bullosa simplex, Generalized pairwise comparison (GPC), Guidance, Model averaging, NparLD, Medicine

الوصف: Abstract Background Recommendations for statistical methods in rare disease trials are scarce, especially for cross-over designs. As a result various state-of-the-art methodologies were compared as neutrally as possible using an illustrative data set from epidermolysis bullosa research to build recommendations for count, binary, and ordinal outcome variables. For this purpose, parametric (model averaging), semiparametric (generalized estimating equations type [GEE-like]) and nonparametric (generalized pairwise comparisons [GPC] and a marginal model implemented in the R package nparLD) methods were chosen by an international consortium of statisticians. Results It was found that there is no uniformly best method for the aforementioned types of outcome variables, but in particular situations, there are methods that perform better than others. Especially if maximizing power is the primary goal, the prioritized unmatched GPC method was able to achieve particularly good results, besides being appropriate for prioritizing clinically relevant time points. Model averaging led to favorable results in some scenarios especially within the binary outcome setting and, like the GEE-like semiparametric method, also allows for considering period and carry-over effects properly. Inference based on the nonparametric marginal model was able to achieve high power, especially in the ordinal outcome scenario, despite small sample sizes due to separate testing of treatment periods, and is suitable when longitudinal and interaction effects have to be considered. Conclusion Overall, a balance has to be found between achieving high power, accounting for cross-over, period, or carry-over effects, and prioritizing clinically relevant time points.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1750-1172Test

الوصول الحر: https://doaj.org/article/4f9b12e7fc3f4ae699a506a509e41b49Test

المؤلفون: Alexandra Domnica Hoeggerl, Verena Nunhofer, Wanda Lauth, Natalie Badstuber, Nina Held, Georg Zimmermann, Christoph Grabmer, Lisa Weidner, Christof Jungbauer, Nadja Lindlbauer, Heidrun Neureiter, Tuulia Ortner, Maria Flamm, Jürgen Osterbrink, Eva Rohde, Sandra Laner-Plamberger

المصدر: BMC Infectious Diseases, Vol 23, Iss 1, Pp 1-13 (2023)

مصطلحات موضوعية: SARS-CoV-2, COVID-19, Post-COVID-19-syndrome (PCS), Long-COVID, EBV, Infectious and parasitic diseases, RC109-216

الوصف: Abstract Purpose Post-COVID-19-Syndrome (PCS) frequently occurs after an infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the understanding of causative mechanisms is still limited. Aim of this study was to determine the PCS rate among SARS-CoV-2 seropositive blood donors as representatives of supposedly healthy adults, who had experienced an asymptomatic or mild COVID-19 disease course, and to examine whether Epstein-Barr virus (EBV) is reactivated in individuals reporting PCS. Methods The PCS rate was determined using questionnaires that included questions about infection and persistent symptoms. Pre-pandemic blood samples and samples collected at regular, pre-defined times after a SARS-CoV-2 infection were analysed for neopterin, a marker for antiviral immune responses, by an enzyme-linked immunosorbent assay (ELISA). Additionally, we determined the rate of SARS-CoV-2 anti-N total antibodies using an electrochemiluminescence immunoassay (ECLIA). Furthermore, quantitative real-time polymerase chain reaction (qPCR) to detect EBV DNA and ECLIA screening for EBV viral capsid-antigen (VCA) IgM, IgG and EBV nuclear antigen 1 (EBNA) IgG were performed. Results Our data reveal that 18% of all infections result in PCS, with symptoms lasting for up to one year. In individuals reporting PCS, no elevated levels of neopterin were detected, indicating no persisting pro-inflammatory, antiviral immune response. SARS-CoV-2 antibody levels were declining in all participants in comparable manner over time, pointing to a successful virus clearance. In individuals with PCS, no EBV DNA could be detected. Furthermore, no differences in EBV specific antibody levels could be shown in PCS groups compared to non-PCS groups. Conclusion Our data suggest that PCS in per se healthy, immunocompetent adults cannot be ascribed to a reactivation of EBV.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2334Test

الوصول الحر: https://doaj.org/article/d4a43a0fa6f04143b5874dd6cf128c24Test

المؤلفون: Katharina Zeman-Kuhnert, Alexander J. Gaggl, Gian B. Bottini, Joern Wittig, Georg Zimmermann, Christoph Steiner, Wanda Lauth, Christian Brandtner

المصدر: Journal of Clinical Medicine, Vol 13, Iss 11, p 3110 (2024)

مصطلحات موضوعية: head and neck cancer, oral cancer, dental rehabilitation, alveolar ridge reconstruction, quality of life, oral health-related quality of life, Medicine

الوصف: Background/Objectives: Dental rehabilitation after extended tumour resection and jaw reconstruction is challenging. The present study aimed to report the prosthetic outcome and quality of life (QoL) in patients with head and neck cancer (HNC) after microvascular alveolar ridge reconstruction. Methods: The prosthetic outcomes of all consecutive patients with HNC who underwent microvascular alveolar ridge reconstruction at the University Hospital Salzburg between 2011 and 2018 were investigated. Oral health-related QoL (OHrQoL) and overall QoL were assessed using the validated Oral Health Impact Profile-49 (OHIP-49) and Short Form-36 questionnaires. Results: During the study period, 115 consecutive patients with head and neck cancer underwent microvascular jaw reconstruction. Among them, 23.3% and 27.4% received conventional tissue-borne prostheses and implant-supported prostheses, respectively, while 48.7% did not undergo dental rehabilitation. The prosthetic outcome was not associated with tumour stage (p = 0.32). Oral health-related quality of life (OHrQoL) was best in patients with implant-supported dental rehabilitation (OHIP-49 median score = 7) and worst in those with conventional removable dentures (OHIP-49 median score = 54). The corresponding OHIP-49 median score for patients who could not undergo dental rehabilitation was 30.5. All Short Form-36 subscale scores were equal to or higher than the malignancy norm scores. Conclusions: After microvascular jaw reconstruction, approximately one-third of the HNC patients received adequate implant-supported dental rehabilitation. However, the risk of dental rehabilitation failure was 50%. The different prosthetic outcomes affected OHrQoL, but not overall QoL.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2077-0383/13/11/3110Test; https://doaj.org/toc/2077-0383Test

الوصول الحر: https://doaj.org/article/d86035fd80d54fd0a2aa33838b4a28c0Test

المؤلفون: Anna-Maria Wiesinger, Brian Bigger, Roberto Giugliani, Christina Lampe, Maurizio Scarpa, Tobias Moser, Christoph Kampmann, Georg Zimmermann, Florian B. Lagler

المصدر: Pharmaceutics, Vol 15, Iss 11, p 2596 (2023)

مصطلحات موضوعية: n/a, Pharmacy and materia medica, RS1-441

الوصف: The journal retracts the article, An Innovative Tool for Evidence-Based, Personalized Treatment Trials in Mucopolysaccharidosis [...]

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1999-4923/15/11/2596Test; https://doaj.org/toc/1999-4923Test

الوصول الحر: https://doaj.org/article/3a5b6b32ed934545a16eb5d3105323dcTest

المؤلفون: Eugen Trinka, Lucas J. Rainer, Claudia A. Granbichler, Georg Zimmermann, Markus Leitinger

المصدر: Frontiers in Epidemiology, Vol 3 (2023)

مصطلحات موضوعية: seizures, death rate, standardized mortality ratio, case fatality, epilepsy, Infectious and parasitic diseases, RC109-216

الوصف: Patients with epilepsy carry a risk of premature death which is on average two to three times higher than in the general population. The risk of death is not homogenously distributed over all ages, etiologies, and epilepsy syndromes. People with drug resistant seizures carry the highest risk of death compared to those who are seizure free, whose risk is similar as in the general population. Most of the increased risk is directly related to the cause of epilepsy itself. Sudden unexplained death in epilepsy patients (SUDEP) is the most important cause of epilepsy-related deaths especially in the young and middle-aged groups. Population based studies with long-term follow up demonstrated that the first years after diagnosis carry the highest risk of death, while in the later years the mortality decreases. Improved seizure control and being exposed to a specialized comprehensive care centre may help to reduce the risk of death in patients with epilepsy. The mortality of status epilepticus is substantially increased with case fatality rates between 4.6% and 39%, depending on its cause and duration, and the age of the population studied. The epidemiological data on overall and cause specific mortality as well as their determinants and risk factors are critically reviewed and methodological issues pertinent to the studies on mortality of epilepsy and Status epilepticus are discussed.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fepid.2023.1081757/fullTest; https://doaj.org/toc/2674-1199Test

الوصول الحر: https://doaj.org/article/94518bffe4cc4c14b9373efb53b66276Test

المؤلفون: Anna-Maria Wiesinger, Brian Bigger, Roberto Giugliani, Christina Lampe, Maurizio Scarpa, Tobias Moser, Christoph Kampmann, Georg Zimmermann, Florian B. Lagler

المصدر: Pharmaceutics, Vol 15, Iss 5, p 1565 (2023)

مصطلحات موضوعية: mucopolysaccharidosis, personalized medicine, individual treatment trials, immunomodulation, risk–benefit assessment, decision analysis framework, Pharmacy and materia medica, RS1-441

الوصف: Mucopolysaccharidosis (MPS) is a group of rare metabolic diseases associated with reduced life expectancy and a substantial unmet medical need. Immunomodulatory drugs could be a relevant treatment approach for MPS patients, although they are not licensed for this population. Therefore, we aim to provide evidence justifying fast access to innovative individual treatment trials (ITTs) with immunomodulators and a high-quality evaluation of drug effects by implementing a risk–benefit model for MPS. The iterative methodology of our developed decision analysis framework (DAF) consists of the following steps: (i) a comprehensive literature analysis on promising treatment targets and immunomodulators for MPS; (ii) a quantitative risk–benefit assessment (RBA) of selected molecules; and (iii) allocation phenotypic profiles and a quantitative assessment. These steps allow for the personalized use of the model and are in accordance with expert and patient representatives. The following four promising immunomodulators were identified: adalimumab, abatacept, anakinra, and cladribine. An improvement in mobility is most likely with adalimumab, while anakinra might be the treatment of choice for patients with neurocognitive involvement. Nevertheless, a RBA should always be completed on an individual basis. Our evidence-based DAF model for ITTs directly addresses the substantial unmet medical need in MPS and characterizes a first approach toward precision medicine with immunomodulatory drugs.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1999-4923/15/5/1565Test; https://doaj.org/toc/1999-4923Test

الوصول الحر: https://doaj.org/article/ce18867491c44ecf925bee1148e86ed2Test

المؤلفون: Julia Pilz, Lukas Hehenwarter, Georg Zimmermann, Gundula Rendl, Gregor Schweighofer-Zwink, Mohsen Beheshti, Christian Pirich

المصدر: EJNMMI Research, Vol 11, Iss 1, Pp 1-11 (2021)

مصطلحات موضوعية: [18F]-FDG PET/CT, Short acquisition time, Diagnostic equivalence, 3D Time-of-flight, Medical physics. Medical radiology. Nuclear medicine, R895-920

الوصف: Abstract Background High-performance time-of-flight (TOF) positron emission tomography (PET) systems have the capability for rapid data acquisition while preserving diagnostic image quality. However, determining a reliable and clinically applicable cut-off of the acquisition time plays an important role in routine practice. This study aimed to assess the diagnostic equivalence of short acquisition time of 57 with routine 75 seconds per bed position (s/BP) of [18F]-fluoro-deoxy-glucose (FDG) PET. Phantom studies applying EARL criteria suggested the feasibility of shortened acquisition time in routine clinical imaging by 3D TOF PET/CT scanners. Ninety-six patients with melanoma, lung or head and neck cancer underwent a standard whole-body, skull base-to-thigh or vertex-to-thigh [18F]-FDG PET/CT examination using the 3D TOF Ingenuity TF PET/CT system (Philips, Cleveland, OH). The [18F]-FDG activity applied was equal to 4MBq per kg body weight. Retrospectively, PET list-mode data were used to calculate a second PET study per patient with a reduced acquisition time of 57 s instead of routine 75 s/BP. PET/CT data were reconstructed using a 3D OSEM TOF algorithm. Blinded patient data were analysed by two nuclear medicine physicians. The number of [18F]-FDG-avid lesions per body region (head&neck, thorax, abdomen, bone, extremity) and image quality (grade 1–5) were evaluated. Semiquantitative analyses were performed by standardized uptake value (SUV) measurements using 3D volume of interests (VOI). The visual and semiquantitative diagnostic equivalence of 214 [18F]-FDG-avid lesions were analysed in the routine standard (75 s/BP) as well as the calculated PET/CT studies with short acquisition time. Statistical analyses were performed by equivalence testing and Bland–Altman plots. Results Lesion detection rate per patient’s body region agreed in > 98% comparing 57 s/BP and 75 s/BP datasets. Overall image quality was determined as equal or superior to 75 s in 80% and 69%, respectively. In the semiquantitative lesion-based analyses, a significant equivalence was found between the 75 s/BP and 57 s/BP PET/CT images both for SUVmax (p = 0.004) and SUVmean (p = 0.003). Conclusion The results of this study demonstrate significant clinical and semiquantitative equivalence between short acquisition time of 57 s/BP and standard 75 s/BP 3D TOF [18F]-FDG PET/CT scanning, which may improve the patient’s workflow in routine practice.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2191-219XTest

الوصول الحر: https://doaj.org/article/24a91d2347364e999c085c90321aa398Test