Search

Your search keyword '"Lasch, Florian"' showing total 15 results
Start Over Author "Lasch, Florian" Search Limiters Available in Library Collection
15 results on '"Lasch, Florian"'

1. Comparison of g-estimation approaches for handling symptomatic medication at multiple timepoints in Alzheimer's Disease with a hypothetical strategy

Author

Lasch, Florian, Guizzaro, Lorenzo, and Loh, Wen Wei

Subjects
Statistics - Methodology
Abstract

For handling intercurrent events in clinical trials, one of the strategies outlined in the ICH E9(R1) addendum targets the hypothetical scenario of non-occurrence of the intercurrent event. While this strategy is often implemented by setting data after the intercurrent event to missing even if they have been collected, g-estimation allows for a more efficient estimation by using the information contained in post-IE data. As the g-estimation methods have largely developed outside of randomised clinical trials, optimisations for the application in clinical trials are possible. In this work, we describe and investigate the performance of modifications to the established g-estimation methods, leveraging the assumption that some intercurrent events are expected to have the same impact on the outcome regardless of the timing of their occurrence. In a simulation study in Alzheimer disease, the modifications show a substantial efficiency advantage for the estimation of an estimand that applies the hypothetical strategy to the use of symptomatic treatment while retaining unbiasedness and adequate type I error control.

Published
2024

5. Microbiota-associated Risk Factors for Clostridioides difficile Acquisition in Hospitalized Patients: A Prospective, Multicentric Study

Author

Solbach, Philipp, Chhatwal, Patrick, Woltemate, Sabrina, Tacconelli, Evelina, Buhl, Michael, Autenrieth, Ingo B., Vehreschild, Maria J. G. T., Jazmati, Nathalie, Gerhard, Markus, Stein-Thoeringer, Christoph K., Rupp, Jan, Ulm, Kurt, Ott, Armin, Lasch, Florian, Koch, Armin, Manns, Michael P., Suerbaum, Sebastian, Bachmann, Oliver, Solbach, Philipp, Chhatwal, Patrick, Woltemate, Sabrina, Tacconelli, Evelina, Buhl, Michael, Autenrieth, Ingo B., Vehreschild, Maria J. G. T., Jazmati, Nathalie, Gerhard, Markus, Stein-Thoeringer, Christoph K., Rupp, Jan, Ulm, Kurt, Ott, Armin, Lasch, Florian, Koch, Armin, Manns, Michael P., Suerbaum, Sebastian, and Bachmann, Oliver

Abstract

Background Asymptomatic C. difficile colonization is believed to predispose to subsequent C. difficile infection (CDI). While emerging insights into the role of the commensal microbiota in mediating colonization resistance against C. difficile have associated CDI with specific microbial components, corresponding prospectively collected data on colonization with C. difficile are largely unavailable. Methods C. difficile status was assessed by GDH EIA and real-time PCR targeting the toxin A (tcdA) and B (tcdB) genes. 16S V3 and V4 gene sequencing results from fecal samples of patients tested positive for C. difficile were analyzed by assessing alpha and beta diversity, LefSe, and the Piphillin functional inference approach to estimate functional capacity. Results 1506 patients were recruited into a prospective observational study (DRKS00005335) upon admission into one of five academic hospitals. 936 of them provided fecal samples on admission and at discharge and were thus available for longitudinal analysis. Upon hospital admission, 5.5% (83/1506) and 3.7% (56/1506) of patients were colonized with toxigenic (TCD) and non-toxigenic C. difficile (NTCD), respectively. During hospitalization, 1.7% (16/936) acquired TCD. Risk factors for acquisition of TCD included pre-existing lung diseases, lower GI endoscopy and antibiotics. Species protecting against hospital-related C. difficile acquisition included Gemmiger spp., Odoribacter splanchnicus, Ruminococcus bromii and other Ruminococcus spp. Metagenomic pathway analysis identified steroid biosynthesis as the most underrepresented metabolic pathway in patients who later acquire C. difficile colonization. Conclusions Gemmiger spp., Odoribacter splanchnicus, Ruminococcus bromii and other Ruminococci were associated with a decreased risk of C. difficile acquisition. In this prospective, multicentric study Gemmiger spp., Odoribacter splanchnicus, Ruminococcus bromii, and other Ruminococcus spp. could be identified as biomarker

Published
2021

6. Comparison of MRI and VQ-SPECT as a Screening Test for Patients With Suspected CTEPH: CHANGE-MRI Study Design and Rationale

Author

Lasch, Florian, primary, Karch, Annika, additional, Koch, Armin, additional, Derlin, Thorsten, additional, Voskrebenzev, Andreas, additional, Alsady, Tawfik Moher, additional, Hoeper, Marius M., additional, Gall, Henning, additional, Roller, Fritz, additional, Harth, Sebastian, additional, Steiner, Dagmar, additional, Krombach, Gabriele, additional, Ghofrani, Hossein Ardeschir, additional, Rengier, Fabian, additional, Heußel, Claus Peter, additional, Grünig, Ekkehard, additional, Beitzke, Dietrich, additional, Hacker, Marcus, additional, Lang, Irene M., additional, Behr, Jürgen, additional, Bartenstein, Peter, additional, Dinkel, Julien, additional, Schmidt, Kai-Helge, additional, Kreitner, Karl-Friedrich, additional, Frauenfelder, Thomas, additional, Ulrich, Silvia, additional, Hamer, Okka W., additional, Pfeifer, Michael, additional, Johns, Christopher S., additional, Kiely, David G., additional, Swift, Andrew James, additional, Wild, Jim, additional, and Vogel-Claussen, Jens, additional

Published
2020
Full Text
View/download PDF

7. Simplified Measurement of Maximum Strength After Knee Surgery: Application-Based Knee-Training Device Compared to Isokinetic Testing

Author

Horstmann, Hauke, Medico, Pascal, Lasch, Florian, Krutsch, Werner, and Weber-Spickschen, Thomas Sanjay

Subjects
knee, exergame, app-based rehabilitation, isokinetic, Open Access Journal of Sports Medicine, Original Research
Abstract

Hauke Horstmann, 1 Pascal Medico, 2 Florian Lasch, 3 Werner Krutsch, 4 Thomas Sanjay Weber-Spickschen 2 1Department of Orthopaedic Surgery, Hannover Medical School, Hannover 30625, Germany; 2Institute of Sports Medicine, Hannover Medical School, Hannover 30625, Germany; 3Institute for Biometry, Hannover Medical School, Hannover 30625, Germany; 4Trauma Department, University of Regensburg, Regensburg 93053, GermanyCorrespondence: Hauke HorstmannDiakovere – Annastift, Department of Orthopaedic Surgery, Hannover Medical School, Anna-von-Borries-Street 1-7, Hannover 30625, GermanyTel +49 5115354568Email hauke.horstmann@diakovere.deContext: Isokinetic testing is used as a standard tool in measuring strength in professional athletes. It is often used to evaluate improvement during rehabilitation. The disadvantages of isokinetic testing include its costs, the fact that it is not portable, and its risk of injury, which makes it not suitable for early postoperative rehabilitation.Hypothesis: The aim of this study was to investigate the relationship between the results of the isokinetic testing and the measurements of an application-based knee-training device.Study Design: Exploratory diagnostic study.Methods: In this monocentric study, 100 subjects performed an isokinetic maximum strength examination and an assessment on the application-based knee-training device in a randomized order. The isokinetic testing was based on the Swiss Olympic protocol with 3 sets of 5 repetitions of maximum strength testing for flexion and extension. The subjects consisted of 50 healthy professional athletes and 50 healthy recreational athletes, half male and half female, between the ages of 18 to 30 years old.Results: No medical or technical issues were reported. The analysis of the relationship between application-based knee-training device and extension showed a Pearson correlation coefficient of r=0.667 for the left knee and r=0.604 for the right knee. For flexion, the Pearson correlation coefficient was r=0.640 for the left side and r=0.673 for the right side. When strength measured by the application-based knee-training device was adjusted for height and weight of the subjects, the Pearson correlation was even stronger (extension left: r=0.727, right: r=0.689; flexion left: r=0.641, right: r=0.711).Conclusion: The study shows a moderate to high correlation between isokinetic testing and the application-based knee-training device. These results suggest that the application-based knee-training device is effective for early strength rehabilitation without the risk of injury.Keywords: knee, isokinetic, app-based rehabilitation, exergame

Published
2020

8. Additional file 1 of Randomized placebo-controlled clinical trial investigating the effect of antioxidants and a vasodilator on overall safety and residual hearing preservation in cochlear implant patients

Author

Scheper, Verena, Schmidtheisler, Melanie, Lasch, Florian, Leyen, Heiko Von Der, Koch, Armin, Schwieger, Jana, Büchner, Andreas, Lesinski-Schiedat, Anke, and Lenarz, Thomas

Abstract

Additional file 1. Includes the general medical history for all patients in the ITT-set as Supplement 1. Ear specific medical history for the implanted ear is stated in Supplement 2 of the additional file 1. Supplement 3 shows the aetiology of the implanted ear. Concomitant medication for the ITT-set summarized by events is stated in Supplement 4. Supplement 5 gives the hearing loss over time at 500 Hz with imputation of 110 dB if the upper detection limit is reached or 120 dB if the measurement is missing. Supplement 6 reports the hearing preservation measured by air conducted audiometry at 500 Hz including all timepoints analyzed in the modified ITT population using a mixed model with change from baseline as dependent variable and treatment, baseline hearing threshold, surgeon, electrode length, electrode length - visit interaction and visit-treatment interaction as fixed effects. The mixed model for repeated measures was conducted adjusting for either the planned electrode length (Supplement Table 6.1) as was done in the primary analysis model, or by adjusting for the used electrode length (Supplement Table 6.2). The estimated mean hearing loss at all time points with 95%-confidence intervals based on the mixed model for repeated measures adjusted for the planned electrode length is illustrated in supplementary figure 6. AEs are listed in supplement 7.

Published
2020
Full Text
View/download PDF

10. Simplified Measurement of Maximum Strength After Knee Surgery: Application-Based Knee-Training Device Compared to Isokinetic Testing

Author

Horstmann,Hauke, Medico,Pascal, Lasch,Florian, Krutsch,Werner, Weber-Spickschen,Thomas Sanjay, Horstmann,Hauke, Medico,Pascal, Lasch,Florian, Krutsch,Werner, and Weber-Spickschen,Thomas Sanjay

Abstract

Hauke Horstmann, 1 Pascal Medico, 2 Florian Lasch, 3 Werner Krutsch, 4 Thomas Sanjay Weber-Spickschen 2 1Department of Orthopaedic Surgery, Hannover Medical School, Hannover 30625, Germany; 2Institute of Sports Medicine, Hannover Medical School, Hannover 30625, Germany; 3Institute for Biometry, Hannover Medical School, Hannover 30625, Germany; 4Trauma Department, University of Regensburg, Regensburg 93053, GermanyCorrespondence: Hauke HorstmannDiakovere – Annastift, Department of Orthopaedic Surgery, Hannover Medical School, Anna-von-Borries-Street 1-7, Hannover 30625, GermanyTel +49 5115354568Email hauke.horstmann@diakovere.deContext: Isokinetic testing is used as a standard tool in measuring strength in professional athletes. It is often used to evaluate improvement during rehabilitation. The disadvantages of isokinetic testing include its costs, the fact that it is not portable, and its risk of injury, which makes it not suitable for early postoperative rehabilitation.Hypothesis: The aim of this study was to investigate the relationship between the results of the isokinetic testing and the measurements of an application-based knee-training device.Study Design: Exploratory diagnostic study.Methods: In this monocentric study, 100 subjects performed an isokinetic maximum strength examination and an assessment on the application-based knee-training device in a randomized order. The isokinetic testing was based on the Swiss Olympic protocol with 3 sets of 5 repetitions of maximum strength testing for flexion and extension. The subjects consisted of 50 healthy professional athletes and 50 healthy recreational athletes, half male and half female, between the ages of 18 to 30 years old.Results: No medical or technical issues were reported. The analysis of the relationship between application-based knee-training device and extension showed a Pearson correlation coefficient of r=0.667 for the left knee and r=0.604 for the right knee. For flexion, the Pearson corr

Published
2020

12. Erste Ergebnisse der monozentrischen klinischen Studie 'Prohearing' – Effekt oral applizierten ACEMgs auf funktionale Parameter in CI-Patienten

Author

Scheper, Verena, Koch, Armin, Lasch, Florian, Lesinski-Schiedat, Anke, Büchner, Andreas, Lenarz, Thomas, and Leifholz, Melanie

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Die Insertion des CI-Elektrodenträgers ist mit einem potentiellen mechanischen Trauma der Cochlea verbunden. Dies führt oftmals zu einem nicht unerheblichen Verlust des Resthörvermögens. Es konnte gezeigt werden, dass eine spezielle Kombination aus Antioxidantien (Vitamine A, C und E)sowie dem Vasodilator Magnesium (zusammen: ACEMg)zu besseren Hörschwellen im Vergleich zu Kontrollgruppen führt. Es wurde der mögliche protektive Effekt ACEMgs auf das Restgehör von CI-Patienten untersucht. Es wurden Knochen- und Luftleitungshörschwellen bestimmt, aber auch Impedanzen gemessen, das Sprachverstehen mittels OLSA und Freiburger Sprachtest ermittelt, Fragebögen wurden ausgefüllt und die Ergebnisse in Hinblick auf die Behandlung (Verum vs. Placebo), den Zeitverlauf und die Elektrodenlänge verglichen. Studienvisiten fanden prä-OP, post-OP, zur Erstanpassung des Prozessors, sowie 3, 6, 9 und 12 Monate nach der Erstanpassung statt. Die Rekrutierung wurde beendet, n=51 Patienten sind eingeschlossen. Hiervon wurden n=2 mit einer Flex16, n=5 mit einer Flex 20, n=10 mit einer Flex 24 und n=32 mit einer Flex 28 der Fa. MED-El elektronische Geräte GmbH versorgt. Momentan befindet sich die Studie in der Bereinigungs- und Analysephase. Eine Entblindung kann noch nicht erfolgen, so dass noch keine Aussagen über den Effekt des ACEMgs getroffen werden können. Die vorläufige Auswertung der Hörverluste nach 12 Monaten zeigt einen medianen Hörverlust für die Frequenzen 125 – 1500 Hz von 12,5 dB für Flex 16, 17,0 dB für FLEX 20, 25,0 dB für FLEX 24 und 28,0 dB für FLEX 28. Über den Effekt der ACEMg-Behandlung auf das Restgehör kann noch keine Aussage getroffen werden. Kürzere Elektrodenlängen des CIs scheinen einen besseren Resthörerhalt nach OP zu bedingen. Unterstützt durch: Diese Studie wurde durch die EU im Rahmen des FP7-Projektes „ProHearing“ gefördert. Der Erstautor gibt keinen Interessenkonflikt an., GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; 13:Doc112

Published
2017
Full Text
View/download PDF

14. Applying the estimand framework to clinical pharmacology trials with a case study in bioequivalence.

Author

Lynggaard, Helle, McKendrick, Sue, Baird, Mark, Kerwash, Essam, Lanius, Vivian, Lasch, Florian, and Wright, David

Subjects
*CLINICAL pharmacology, *CLINICAL trials, *SENSITIVITY analysis, *TREATMENT effectiveness, *ACADEMIA, *GENERIC drugs
Abstract

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use has published an addendum on estimands and sensitivity analysis in clinical trials along with related training materials. These define an estimand as a precise description of the treatment effect that reflects the scientific question of interest. In December 2022, the US Food and Drug Administration released draft guidance recommending estimands of interest be specified in bioequivalence trial protocols. However, experience in implementing estimands in clinical pharmacology trials is limited and so we introduce estimands and provide step‐by‐step considerations about the estimand thinking process in this setting. We also describe a particular case study, a bioequivalence trial, illustrating how the estimand framework can provide transparency and alignment throughout the design, conduct and analysis of the trial. This involves discussion of how to identify and handle intercurrent events, which are events that can affect interpretation of the drug or metabolite endpoints. Furthermore, we discuss the broader applicability of the estimand framework to other clinical pharmacology trials. Finally, we encourage further discussion between industry, academia, regulators and the International Council for Harmonisation on whether the estimand framework should be considered in all clinical pharmacology regulatory guidance documents. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

15. Which clinical trial designs and statistical approaches have been used in assessments of orphan maintenance by the European Medicines Agency between 2012 and 2022? A cross-sectional study.

Author

Windfuhr F, Larsson K, Framke T, and Lasch F

Subjects
Cross-Sectional Studies, Humans, Drug Approval methods, Orphan Drug Production, Research Design, European Union, Clinical Trials as Topic
Abstract

Objectives: In the European Union, a new orphan medicinal product must demonstrate 'significant benefit' over approved medicinal products targeting the same indication. To demonstrate a significant benefit, comparisons between the new product and the already approved medicinal products-either directly by a head-to-head comparison within a clinical trial or indirectly as a cross-trial comparison-are necessary. In this study, we investigate the types of trial designs and statistical approaches used for demonstrating a significant benefit of a new orphan medicinal product against approved comparators used between 2012 and 2022., Design: This is a cross-sectional study based on the European Medicines Agency's 'orphan maintenance' assessment documents between 2012 and 2022. All documents were manually reviewed to extract structured data on the following outcome measures:For every comparison between a new orphan medicinal product and a comparator used for demonstrating a significant benefit as part of an orphan maintenance procedure, we recorded the type and design of the data source and the type of statistical methodology used for the comparison., Results: We identified 151 EMA orphan maintenance procedures with a positive decision that required the demonstration of a significant benefit. Within these 151 procedures, 418 comparisons between medicinal products were identified. Indirect comparisons are the most common approach for comparing the new orphan medicinal product to a relevant comparator (44%, 182/418), followed by qualitative comparisons (39%, 162/418) and direct comparisons (18%, 74/418). Among the indirect comparisons, naive side-by-side comparisons are most often used (71%, 129/182), whereas inferential approaches that adjust for population differences and quantify the uncertainty of the comparison are used less often (29%, 53/182). Although there is no clear time trend in the prevalence of any specific comparison type, we find that inferential indirect comparison methods approximately doubled between the first and second half of the reviewed time frame., Conclusions: Indirect comparisons play an important role in demonstrating a significant benefit in the assessment of orphan products. Further work is needed to evaluate the appropriateness of different methodologies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Published
2024
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results