HIS-based Kaplan-Meier plots - a single source approach for documenting and reusing routine survival information

<p>Abstract</p> <p>Background</p> <p>Survival or outcome information is important for clinical routine as well as for clinical research and should be collected completely, timely and precisely. This information is relevant for multiple usages including quality control, clinical trials, observational studies and epidemiological registries. However, the local hospital information system (HIS) does not support this documentation and therefore this data has to generated by paper based or spreadsheet methods which can result in redundantly documented data. Therefore we investigated, whether integrating the follow-up documentation of different departments in the HIS and reusing it for survival analysis can enable the physician to obtain survival curves in a timely manner and to avoid redundant documentation.</p> <p>Methods</p> <p>We analysed the current follow-up process of oncological patients in two departments (urology, haematology) with respect to different documentation forms. We developed a concept for comprehensive survival documentation based on a generic data model and implemented a follow-up form within the HIS of the University Hospital Muenster which is suitable for a secondary use of these data. We designed a query to extract the relevant data from the HIS and implemented Kaplan-Meier plots based on these data. To re-use this data sufficient data quality is needed. We measured completeness of forms with respect to all tumour cases in the clinic and completeness of documented items per form as incomplete information can bias results of the survival analysis.</p> <p>Results</p> <p>Based on the form analysis we discovered differences and concordances between both departments. We identified 52 attributes from which 13 were common (e.g. procedures and diagnosis dates) and were used for the generic data model. The electronic follow-up form was integrated in the clinical workflow. Survival data was also retrospectively entered in order to perform survival and quality analyses on a comprehensive data set. Physicians are now able to generate timely Kaplan-Meier plots on current data. We analysed 1029 follow-up forms of 965 patients with survival information between 1992 and 2010. Completeness of forms was 60.2%, completeness of items ranges between 94.3% and 98.5%. Median overall survival time was 16.4 years; median event-free survival time was 7.7 years.</p> <p>Conclusion</p> <p>It is feasible to integrate survival information into routine HIS documentation such that Kaplan-Meier plots can be generated directly and in a timely manner.</p

Nanodiscs unravel the interaction between the SecYEG channel and its cytosolic partner SecA

The translocon is a membrane-embedded protein assembly that catalyzes protein movement across membranes. The core translocon, the SecYEG complex, forms oligomers, but the protein-conducting channel is at the center of the monomer. Defining the properties of the SecYEG protomer is thus crucial to understand the underlying function of oligomerization. We report here the reconstitution of a single SecYEG complex into nano-scale lipid bilayers, termed Nanodiscs. These water-soluble particles allow one to probe the interactions of the SecYEG complex with its cytosolic partner, the SecA dimer, in a membrane-like environment. The results show that the SecYEG complex triggers dissociation of the SecA dimer, associates only with the SecA monomer and suffices to (pre)-activate the SecA ATPase. Acidic lipids surrounding the SecYEG complex also contribute to the binding affinity and activation of SecA, whereas mutations in the largest cytosolic loop of the SecY subunit, known to abolish the translocation reaction, disrupt both the binding and activation of SecA. Altogether, the results define the fundamental contribution of the SecYEG protomer in the translocation subreactions and illustrate the power of nanoscale lipid bilayers in analyzing the dynamics occurring at the membrane