Martin Lablans

An international registry for primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder leading to chronic upper and lower airway disease. Fundamental data on epidemiology, clinical presentation, course and treatment strategies are lacking in PCD. We have established an international PCD registry to realise an unmet need for an international platform to systematically collect data on incidence, clinical presentation, treatment and disease course. The registry was launched in January 2014. We used internet technology to ensure easy online access using a web browser under www.pcdregistry.eu. Data from 201 patients have been collected so far. The database is comprised of a basic data form including demographic and diagnostic information, and visit forms designed to monitor the disease course. To establish a definite PCD diagnosis, we used strict diagnostic criteria, which required two to three diagnostic methods in addition to classical clinical symptoms. Preliminary analysis of lung function data demonstrated a mean annual decline of percentage predicted forced expiratory volume in 1 s of 0.59% (95% CI 0.98–0.22). Here, we present the development of an international PCD registry as a new promising tool to advance the understanding of this rare disorder, to recruit candidates for research studies and ultimately to improve PCD care. A registry to systematically collect data on clinical presentation, disease course and treatment of PCD http://ow.ly/TtGAR

Phenotypic Spectrum of Children with Nephronophthisis and Related Ciliopathies

BACKGROUND AND OBJECTIVES Genetic heterogeneity and phenotypic variability are major challenges in familial nephronophthisis and related ciliopathies. To date, mutations in 20 different genes (NPHP1 to -20) have been identified causing either isolated kidney disease or complex multiorgan disorders. In this study, we provide a comprehensive and detailed characterization of 152 children with a special focus on extrarenal organ involvement and the long-term development of ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We established an online-based registry (www.nephreg.de) to assess the clinical course of patients with nephronophthisis and related ciliopathies on a yearly base. Cross-sectional and longitudinal data were collected. Mean observation time was 7.5±6.1 years. RESULTS In total, 51% of the children presented with isolated nephronophthisis, whereas the other 49% exhibited related ciliopathies. Monogenetic defects were identified in 97 of 152 patients, 89 affecting NPHP genes. Eight patients carried mutations in other genes related to cystic kidney diseases. A homozygous NPHP1 deletion was, by far, the most frequent genetic defect (n=60). We observed a high prevalence of extrarenal manifestations (23% [14 of 60] for the NPHP1 group and 66% [61 of 92] for children without NPHP1). A homozygous NPHP1 deletion not only led to juvenile nephronophthisis but also was able to present as a predominantly neurologic phenotype. However, irrespective of the initial clinical presentation, the kidney function of all patients carrying NPHP1 mutations declined rapidly between the ages of 8 and 16 years, with ESRD at a mean age of 11.4±2.4 years. In contrast within the non-NPHP1 group, there was no uniform pattern regarding the development of ESRD comprising patients with early onset and others preserving normal kidney function until adulthood. CONCLUSIONS Mutations in NPHP genes cause a wide range of ciliopathies with multiorgan involvement and different clinical outcomes.

A RESTful interface to pseudonymization services in modern web applications

BackgroundMedical research networks rely on record linkage and pseudonymization to determine which records from different sources relate to the same patient. To establish informational separation of powers, the required identifying data are redirected to a trusted third party that has, in turn, no access to medical data. This pseudonymization service receives identifying data, compares them with a list of already reported patient records and replies with a (new or existing) pseudonym. We found existing solutions to be technically outdated, complex to implement or not suitable for internet-based research infrastructures. In this article, we propose a new RESTful pseudonymization interface tailored for use in web applications accessed by modern web browsers.MethodsThe interface is modelled as a resource-oriented architecture, which is based on the representational state transfer (REST) architectural style. We translated typical use-cases into resources to be manipulated with well-known HTTP verbs. Patients can be re-identified in real-time by authorized users’ web browsers using temporary identifiers. We encourage the use of PID strings for pseudonyms and the EpiLink algorithm for record linkage. As a proof of concept, we developed a Java Servlet as reference implementation.ResultsThe following resources have been identified: Sessions allow data associated with a client to be stored beyond a single request while still maintaining statelessness. Tokens authorize for a specified action and thus allow the delegation of authentication. Patients are identified by one or more pseudonyms and carry identifying fields. Relying on HTTP calls alone, the interface is firewall-friendly. The reference implementation has proven to be production stable.ConclusionThe RESTful pseudonymization interface fits the requirements of web-based scenarios and allows building applications that make pseudonymization transparent to the user using ordinary web technology. The open-source reference implementation implements the web interface as well as a scientifically grounded algorithm to generate non-speaking pseudonyms.

Towards better social integration through mobile web 2.0 ambient assisted living devices

Within a few decades, the number of elderly people in Europe and Northern America will increase significantly. One of the challenges of this development is to keep elderly people integrated in society. We present a prototype for a Web 2.0-enabled ambient assisted living (AAL) device that offers easy-to-use functionality to help elderly people keep and establish new contacts, find events that match their interests and be aided in sustaining their mobility. An evaluation with probands from the target group indicates that such a device can improve an elderly persons social life.

OSSE – open source registry software solution.

Project goal OSSE (Open Source-Registersystem fur Seltene Erkrankungen in der EU / Open Source Registry System for Rare Diseases in the EU) provides patient organizations, physicians and scientists with open-source software for the creation of patient registries. As a result, the national registry landscape is improved to comply with European principles regarding e.g. minimum data set and data quality, as summarized in the EUCERD recommendation on rare disease registries. Also, the necessary interoperability is achieved to facilitate federation of those registries on a national and international level.

Integrating clinical decision support systems for pharmacogenomic testing into clinical routine - a scoping review of designs of user-system interactions in recent system development

BackgroundPharmacogenomic clinical decision support systems (CDSS) have the potential to help overcome some of the barriers for translating pharmacogenomic knowledge into clinical routine. Before developing a prototype it is crucial for developers to know which pharmacogenomic CDSS features and user-system interactions have yet been developed, implemented and tested in previous pharmacogenomic CDSS efforts and if they have been successfully applied. We address this issue by providing an overview of the designs of user-system interactions of recently developed pharmacogenomic CDSS.MethodsWe searched PubMed for pharmacogenomic CDSS published between January 1, 2012 and November 15, 2016. Thirty-two out of 118 identified articles were summarized and included in the final analysis. We then compared the designs of user-system interactions of the 20 pharmacogenomic CDSS we had identified.ResultsAlerts are the most widespread tools for physician-system interactions, but need to be implemented carefully to prevent alert fatigue and avoid liabilities. Pharmacogenomic test results and override reasons stored in the local EHR might help communicate pharmacogenomic information to other internal care providers. Integrating patients into user-system interactions through patient letters and online portals might be crucial for transferring pharmacogenomic data to external health care providers. Inbox messages inform physicians about new pharmacogenomic test results and enable them to request pharmacogenomic consultations. Search engines enable physicians to compare medical treatment options based on a patient’s genotype.ConclusionsWithin the last 5 years, several pharmacogenomic CDSS have been developed. However, most of the included articles are solely describing prototypes of pharmacogenomic CDSS rather than evaluating them. To support the development of prototypes further evaluation efforts will be necessary. In the future, pharmacogenomic CDSS will likely include prediction models to identify patients who are suitable for preemptive genotyping.

An Architecture for Translational Cancer Research As Exemplified by the German Cancer Consortium

Networking of medical institutions by means of a capable data infrastructure has the potential to open up vast amounts of routine data to translational cancer research. However, the secondary use of information collected independently in several institutions is a challenging task of data integration. In this review, we discuss the requirements and common challenges involved in the establishment of such a platform. We present methods and tools from the field of medical informatics as solutions to semantic and technical heterogeneity, questions of data protection and record linkage, as well as issues of trust and data ownership. We also describe the architecture of an existing cancer research network as an exemplary application of these methods.

Strategien zur Vernetzung von Biobanken

ZusammenfassungHintergrundNicht selten benötigt ein medizinisches Forschungsvorhaben mehr biologisches Material, als in einer einzigen Biobank verfügbar ist. Daher unterstützt eine Vielzahl von Strategien das Auffinden potentieller Forschungspartner mit passenden Proben, auch ohne dass diese zuvor in einer zentralisierten Sammlung zusammengeführt werden müssen.ZielDer vorliegende Beitrag beschreibt die Klassifizierung verschiedener Strategien zur Vernetzung von Biomaterialbanken, speziell zur Probensuche, sowie eine IT-Infrastruktur, die diese Ansätze kombiniert.Material und MethodenBestehende Strategien lassen sich nach drei Kriterien klassifizieren: a) Granularität der Probendaten: grobe Daten auf Bankebene (Katalog) vs. feingranulare Daten auf Probenebene, b) Speicherort der Probendaten: zentrale (zentraler Suchdienst) vs. dezentrale Datenhaltung (föderierte Suchdienste) und c) Automatisierungsgrad: automatisch (abfragebasiert, föderierter Suchdienst) vs. halbautomatisch (anfragebasiert, dezentrale Suche). Alle genannten Suchdienste setzen eine Datenintegration voraus; dabei helfen Metadaten bei der Überwindung semantischer Heterogenität.ErgebnisseDer „Common Service IT“ in BBMRI-ERIC („Biobanking and Biomolecular Resources Research Infrastructure-European Research Infrastructure Consortium“) vereint einen Katalog, die dezentrale Suche und Metadaten in einer integrierten Plattform, um Forschern vielseitige Werkzeuge zur Suche nach passendem Probenmaterial zu geben und bei den Biobankern gleichzeitig ein hohes Maß an Datenhoheit zu bewahren.DiskussionTrotz ihrer Unterschiede schließen sich die vorgestellten Strategien zur Vernetzung von Biomaterialbanken gegenseitig nicht aus. Vielmehr lassen sie sich in gemeinsamen Forschungsinfrastrukturen sinnvoll ergänzen und sie können sogar voneinander profitieren.AbstractBackgroundMedical research projects often require more biological material than can be supplied by a single biobank. For this reason, a multitude of strategies support locating potential research partners with matching material without requiring centralization of sample storage.ObjectivesClassification of different strategies for biobank networks, in particular for locating suitable samples. Description of an IT infrastructure combining these strategies.Materials and methodsExisting strategies can be classified according to three criteria: (a) granularity of sample data: coarse bank-level data (catalogue) vs. fine-granular sample-level data, (b) location of sample data: central (central search service) vs. decentral storage (federated search services), and (c) level of automation: automatic (query-based, federated search service) vs. semi-automatic (inquiry-based, decentral search). All mentioned search services require data integration. Metadata help to overcome semantic heterogeneity.ResultsThe “Common Service IT” in BBMRI-ERIC (Biobanking and BioMolecular Resources Research Infrastructure) unites a catalogue, the decentral search and metadata in an integrated platform. As a result, researchers receive versatile tools to search suitable biomaterial, while biobanks retain a high degree of data sovereignty.ConclusionsDespite their differences, the presented strategies for biobank networks do not rule each other out but can complement and even benefit from each other.

Strategien zur Vernetzung von Biobanken Klassifizierung verschiedener Ansätze zur Probensuche und Ausblick auf die Zukunft in der BBMRI-ERIC

ZusammenfassungHintergrundNicht selten benötigt ein medizinisches Forschungsvorhaben mehr biologisches Material, als in einer einzigen Biobank verfügbar ist. Daher unterstützt eine Vielzahl von Strategien das Auffinden potentieller Forschungspartner mit passenden Proben, auch ohne dass diese zuvor in einer zentralisierten Sammlung zusammengeführt werden müssen.ZielDer vorliegende Beitrag beschreibt die Klassifizierung verschiedener Strategien zur Vernetzung von Biomaterialbanken, speziell zur Probensuche, sowie eine IT-Infrastruktur, die diese Ansätze kombiniert.Material und MethodenBestehende Strategien lassen sich nach drei Kriterien klassifizieren: a) Granularität der Probendaten: grobe Daten auf Bankebene (Katalog) vs. feingranulare Daten auf Probenebene, b) Speicherort der Probendaten: zentrale (zentraler Suchdienst) vs. dezentrale Datenhaltung (föderierte Suchdienste) und c) Automatisierungsgrad: automatisch (abfragebasiert, föderierter Suchdienst) vs. halbautomatisch (anfragebasiert, dezentrale Suche). Alle genannten Suchdienste setzen eine Datenintegration voraus; dabei helfen Metadaten bei der Überwindung semantischer Heterogenität.ErgebnisseDer „Common Service IT“ in BBMRI-ERIC („Biobanking and Biomolecular Resources Research Infrastructure-European Research Infrastructure Consortium“) vereint einen Katalog, die dezentrale Suche und Metadaten in einer integrierten Plattform, um Forschern vielseitige Werkzeuge zur Suche nach passendem Probenmaterial zu geben und bei den Biobankern gleichzeitig ein hohes Maß an Datenhoheit zu bewahren.DiskussionTrotz ihrer Unterschiede schließen sich die vorgestellten Strategien zur Vernetzung von Biomaterialbanken gegenseitig nicht aus. Vielmehr lassen sie sich in gemeinsamen Forschungsinfrastrukturen sinnvoll ergänzen und sie können sogar voneinander profitieren.AbstractBackgroundMedical research projects often require more biological material than can be supplied by a single biobank. For this reason, a multitude of strategies support locating potential research partners with matching material without requiring centralization of sample storage.ObjectivesClassification of different strategies for biobank networks, in particular for locating suitable samples. Description of an IT infrastructure combining these strategies.Materials and methodsExisting strategies can be classified according to three criteria: (a) granularity of sample data: coarse bank-level data (catalogue) vs. fine-granular sample-level data, (b) location of sample data: central (central search service) vs. decentral storage (federated search services), and (c) level of automation: automatic (query-based, federated search service) vs. semi-automatic (inquiry-based, decentral search). All mentioned search services require data integration. Metadata help to overcome semantic heterogeneity.ResultsThe “Common Service IT” in BBMRI-ERIC (Biobanking and BioMolecular Resources Research Infrastructure) unites a catalogue, the decentral search and metadata in an integrated platform. As a result, researchers receive versatile tools to search suitable biomaterial, while biobanks retain a high degree of data sovereignty.ConclusionsDespite their differences, the presented strategies for biobank networks do not rule each other out but can complement and even benefit from each other.

Preserving the owner’s autonomy in networks of patient registries and biobanks

Background To achieve statistical significance in rare disease research, bioor data samples taken from one patient registry or biobank may need to be complemented by those of other institutions [1,2]. While a first overview of potential research partners can be obtained using public catalogues as established by BBMRI [3] or Orphanet [4], this article focuses on mediation services, which provide deeper insight on available material using criteria-based search on fine-grained, non-aggregated datasets. Until now, these datasets were provided either beforehand via regular uploads (central search, e.g. CRIP [5] and the NCI’s specimen resource locator [6]) or on-demand via distributed queries (federated search, e.g. i2b2 SHRINE [7] and EHR4CR [8]). However, both ways give third parties whom the data or sample owners may neither know nor trust insight into their databases. The requirement for self-disclosure places owners in a dilemma: On the one hand, they want to contribute to promising collaborative research projects. On the other hand, they “frequently hold proprietary views on their data” [9] and want to carefully consider with whom to share their assets collected over years without facing pressure of justification for rejecting a proposal.