MoRe – Mobile Research: App-basierte Studien nach dem Baukastenprinzip

Die Erfassung der Effektivität von Behandlungsmethoden sowie von Therapieergebnissen steht in einer ergebnisorientierten medizinischen Versorgung immer mehr im Vordergrund klinischen und wissenschaftlichen Interesses. Daher erwarten Experten von mobilen Gesundheitslösungen (mHealth) unter anderem Verbesserungen in der Gesundheitsvorsorge und Krankheitsfrüherkennung, Kosteneinsparungen und/oder Qualitätsverbesserungen in der Leistungserbringung. Ziel des Projektes ist die Etablierung einer universellen Applikation, die es dem Anwender ermöglicht - entsprechend aktueller Standards in Bezug auf Patientensicherheit und Datenschutz und guter klinischer Praxis - ohne individuelle Programmierkenntnisse ein eigenes Forschungsprojekt zur systematischen und hochwertigen Datenerfassung von Patienten mit unterschiedlichsten Pathologien zusammenzustellen. Dabei werden, gemäß der immer wichtiger werdenden Versorgungsforschung, Patient-reported Outcome Parameter als wertvolles und zunehmend etabliertes Instrument zur Untersuchung von Therapieergebnissen eingesetzt. Lebensqualität als wichtiger messbarer Parameter bei nicht-vitalen Indikationen sei hier nur als Beispiel genannt. Zusammengestellte Studien werden über eine Smartphone-App für den Patienten zugänglich. Die hierdurch erfassten Daten kann der Wissenschaftler über eine webbasierte Oberfläche analysieren und zur weiteren Auswertung herunterladen. Öffentliche Studien können weltweit innerhalb der App gesucht werden. Geschlossene Studien sind privat

PHC9 COST-EFFECTIVENESS OF RIVAROXABANVERSUS ENOXAPARIN FORTHROMBOPROPHYLAXIS AFTER TOTAL HIP REPLACEMENT IN THE UK

Vitis vinifera cell cultures respond to pathogens and elicitors by synthesizing and extracellularly accumulating stilbenoid phytoalexins. Large amounts of trans-resveratrol (t-R) are produced when a cell culture is elicited with methylated cyclodextrins (MBCD), either alone or combined with methyl jasmonate (MeJA). t-R transport to the extracellular medium, which represents the apoplastic space, would place this antifungal defense right in the battlefield to efficiently fight against pathogen attack. Yet despite their physiological relevance, these transport pathways are mostly unknown. A broad hypothesis-free DIGE-based proteomic experiment of a temporal series of elicited grapevine cell cultures was performed to explore the expression profiles of t-R biosynthetic proteins and other co-expressing proteins potentially involved in such a cell response. A correlation between two tau class glutathione-S-transferases (GSTs) with several stilbene synthase and phenylalanine ammonia-lyase isoforms, and with the t-R metabolite itself, was found and further assessed by a qRT-PCR gene expression analysis. The best candidate, GSTU-2, was cloned from the cDNA of the MBCD + MeJA-elicited grapevine cells and used for Agrobacterium-mediated grapevine cell transformation. The non-elicited lines that overexpressed GSTU-2 displayed an extracellular t-R accumulating phenotype, but stabilization of t-R required the addition to culture medium of adsorbent compounds, e.g., PVP or β-cyclodextrin. The wild-type cell cultures accumulated no t-R, not even in the presence of adsorbents. The transient expression of the GSTU-2-GFP fusion proteins in grapevine cells showed localisation in the plasma membrane, and the immunoprecipitation of HA-tagged GSTU-2 revealed its interaction with HIR, a plasma membrane-bound protein. These findings are consistent with a functional role in transport. This is the first report providing several pieces of experimental evidence for the involvement of a specific tau class GST in t-R transport to the extracellular medium

Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study

Background The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months. Methods SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM). Results Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score. Conclusion Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity

Frugal FAIR Data Point: A Document-Based Implementation for Enhanced Interoperability and Accessibility

This paper presents a novel approach to publishing metadata in a FAIR manner, according to the FAIR Data Point specifications. This approach focuses on a document-based methodology that aligns with stringent infrastructure policies and caters to institutions with limited IT resources. While adhering to the standard FDP specifications, this implementation offers a lean solution that utilizes the filesystem with a lean web server for metadata publication, ensuring broad accessibility and interoperability

De-duplicating patient records from three independent data sources reveals the incidence of rare neuromuscular disorders in Germany

Background: Estimation of incidence in rare diseases is often challenging due to unspecific and incomplete coding and recording systems. Patient- and health care provider-driven data collections are held with different organizations behind firewalls to protect the privacy of patients. They tend to be fragmented, incomplete and their aggregation leads to further inaccuracies, as the duplicated records cannot easily be identified. We here report about a novel approach to evaluate the incidences of Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) in Germany. Methods: We performed a retrospective epidemiological study collecting data from patients with dystrophinopathies (DMD and Becker muscular dystrophy) and SMA born between 1995 and 2018. We invited all neuromuscular centers, genetic institutes and the patient registries for DMD and SMA in Germany to participate in the data collection. A novel web-based application for data entry was developed converting patient identifying information into a hash code. Duplicate entries were reliably allocated to the distinct patient. Results: We collected 5409 data entries in our web-based database representing 1955 distinct patients with dystrophinopathies and 1287 patients with SMA. 55.0% of distinct patients were found in one of the 3 data sources only, while 32.0% were found in 2, and 13.0% in all 3 data sources. The highest number of SMA patients was reported by genetic testing laboratories, while for DMD the highest number was reported by the clinical specialist centers. After the removal of duplicate records, the highest yearly incidence for DMD was calculated as 2.57:10,000 in 2001 and the highest incidence for SMA as 1.36:10,000 in 2014. Conclusion: With our novel approach (compliant with data protection regulations), we were able to identify unique patient records and estimate the incidence of DMD and SMA in Germany combining and de-duplicating data from patient registries, genetic institutes, and clinical care centers. Although we combined three different data sources, an unknown number of patients might not have been reported by any of these sources. Therefore, our results reflect the minimal incidence of these diseases

SMArtCARE - A platform to collect real-life outcome data of patients with spinal muscular atrophy

Abstract Background Survival and quality of life for patients affected by spinal muscular atrophy (SMA) are thought to have improved over the last decade due to changes in care. In addition, targeted treatments for SMA have been developed based on a better understanding of the molecular pathology. In 2016 and 2017, nusinersen was the first drug to be approved for treatment of all types of SMA in the United States and in Europe based on well-controlled clinical trials in a small subgroup of pediatric SMA patients. Systems are required to monitor treated and untreated SMA patients in a real-life environment to optimize treatment and care, and to provide outcome data to regulators, payers, and the SMA community. Methods Within SMArtCARE, we conduct a prospective, multicenter non-randomized registration and outcome study. SMArtCARE collects longitudinal data on all available SMA patients independent of their actual treatment regime as disease-specific SMA registry. For this purpose, we provide an online platform for SMA patients seen by health-care providers in Germany, Austria and Switzerland. All data are collected during routine patient visits. Items for data collection are aligned with the international consensus for SMA registries. Data analysis is carried out independent of commercial partners. Conclusion A prospective monitoring of all SMA patients will lead to a better understanding of the natural history of SMA and the influence of drug treatment. This is crucial to improve the care of SMA patients. Further, we will establish a network for neuromuscular centers to share experience with SMA patients and to promote research projects on SMA. Trial registration German Clinical Trials Register (“Deutsches Register klinischer Studien”) DRKS00012699. Registered 09 August 2018. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00012699

The TREAT-NMD Care and Trial Site Registry: A powerful tool for clinical research on neurodegenerative and neuromuscular diseases

<p>Established in 2007 in the scope of the TREAT-NMD project (EU-funded Network of Excellence, FP6) to identify possible trial sites for rare neuromuscular diseases, the Care and Trial Site Registry (CTSR) collects information on personnel and the experience of the study team, facilities and equipment, as well as patient numbers per disease and age group.</p> <p>Within the CARE-NMD project (2010-2013, funded by DG Sanco) the CTSR was extended with Duchenne-specific care questions and used to evaluate current clinical practice in different European countries.</p> <p>In September 2013, the CTSR expanded to cover the field of rare neurodegenerative diseases as a branch of NeurOmics (FP7, 2012-2017) and now encompasses 32 rare diseases.</p> <p>The CTSR is an online self-registration database hosted by the University Medical Center Freiburg, Germany. This allows swift self-registration and update of information by any web browser and regardless of geographic location. Once registered, data is entered into online forms organised by topic categories such as Patient Cohort, Diagnostic Tools, Personnel and Experience, Equipment, Care Settings and Research and Education. The quality of the data is ensured by regularly contacting the sites and asking them to update their records, usually when an official enquiry has been submitted to the CTSR.</p> <p>As of September 2013 the CTSR contained 280 centres in 44 countries with an overall count of 41,500 reported patients.</p> <p>Fourteen official requests for site identification, often in combination with TREAT-NMD patient registry information, were received between 2009 and 2013: Ten were trial feasibiltiy enquiries from major industrial firms and four enquiries from academia..</p> <p>As an ideal complement to patient registries, the CTSR provides a powerful infrastructure for feasibility and trial site selection by pharmaceutical industry and investigators, as well as improving clinical networking in rare diseases.</p