Czech Registry of Monoclonal Gammopathies - Technical Solution, Data Collection and Visualisation.

BACKGROUND: The Registry of Monoclonal Gammopathies (RMG) was established by the Czech Myeloma Group in 2007. RMG is a registry designed for the collection of clinical data concerning diagnosis, treatment, treatment results and survival of patients with monoclonal gammopathies. Data on patients with monoclonal gammopathy of undetermined significance (MGUS), Waldenström macroglobulinaemia (WM), multiple myeloma (MM) or primary AL ("amyloid light-chain") amyloidosis are collected in the registry. DATA: Nineteen Czech centres and four Slovak centres currently contribute to the registry. The registry currently contains records on more than 5,000 patients with MM, almost 3,000 patients with MGUS, 170 patients with WM and 26 patients with primary AL amyloidosis, i.e. more than 8,000 records on patients with monoclonal gammopathies altogether. RESULTS: This paper describes technology employed for the collection, storage and subsequent online visualisation of data. The CLADE-IS platform is introduced as a new system for the collection and storage of data from the registry. The form structure and functions of the new system are described for all diagnoses in general; these functions facilitate data entry to the registry and minimise the error rate in data. Publicly available online visualisations of data on patients with MGUS, WM, MM or primary AL amyloidosis from all Czech or Slovak centres are introduced, together with authenticated visualisations of data on patients with MM from selected centres. CONCLUSION: The RMG represents a data basis that makes it possible to monitor the disease course in patients with monoclonal gammopathies on the population level.Key words: Registry of Monoclonal Gammopathies - RMG - registries - monoclonal gammopathies - CLADE-IS - data visualisation - database.

Assessment of the ability of the Privigen® purification process to deplete thrombogenic factor XIa from plasma.

BACKGROUND AND OBJECTIVES: Activated clotting factor FXI (FXIa) has been postulated to play a significant role in thromboembolic events potentially associated with the administration of intravenous immunoglobulin. The purpose of this study was to demonstrate that thrombogenic agents, in particular FXIa and FXI, are depleted or inactivated in Privigen(®) . MATERIALS AND METHODS: The ability of the purification process to deplete FXIa from plasma was studied. All steps of the Privigen(®) production were investigated for potential activation of FXI to FXIa with spiking experiments. RESULTS: Privigen(®) contains no procoagulant activity as determined by FXIa chromogenic assay, non-activated partial thromboplastin time (NaPTT) and thrombin generation assays (TGA, FXIa-like activity). The coagulation times were >200 s in the NaPTT test. FXIa was below the detection limit of 0·14 ng/ml (chromogenic assay) and below the quantification limit of 0·2 ng/ml (TGA). FXIa spiking experiments showed that the analytical methods used can detect traces of procoagulant activity in immunoglobulin samples. FXIa spiking and kinetic experiments during the octanoic acid fractionation step showed that a substantial reduction in FXIa specific activity (by ≥99·9% within 40 min of octanoic acid incubation) was reached already at an early stage of the manufacturing process. These results were confirmed in vivo: in a modified Wessler test, no thrombus was reported. CONCLUSION: The Privigen(®) manufacturing process has the capability to remove thrombogenic factors: octanoic acid precipitation, designed to remove a variety of contaminants during immunoglobulin purification, also removes almost all FXIa from plasma and further purification steps do not activate FXI.

Inter- and intra-rater-reliability of a clinical framework for spine-related neck-arm pain.

OBJECTIVE: A mechanism-based clinical framework for spine-related pain differentiates (i) somatic referred pain, ii) heightened nerve mechanosensitivity, iii) radicular pain, iv) radiculopathy and mixed-pain. This study aimed to determine the reliability of proposed framework. METHOD: Fifty-one people with unilateral spine-related neck-arm pain were assessed and categorized by examiner-1. The classifications were compared to those made by two other examiners, based on written documentation of examiner-1. Cohens kappa was calculated between examiner-pairs; Fleiss Kappa among all examiners to assess agreement in classifying subgroups and entire framework. RESULT: Inter-rater-reliability showed moderate to almost perfect reliability (somatic: no variation, mechanosensitivity: 0.96 (95% CI 0.87-1.0) to 1.0 (95% CI: 1.0-1.0), radicular pain: 0.46 (95% CI: 0.19-0.69) to 0.62 (95% CI: 0.42-0.81), radiculopathy: 0.65 (95% CI: 0.43-0.84) to 0.80 (95% CI: 0.63-0.96) mixed-pain: 0.54 (95% CI: 0.21-0.81) to 0.75 (95% CI: 0.48-0.94). There was almost perfect to moderate reliability among all examiners (somatic: no variation, mechanosensitivity: 0.97 (95% CI: 0.82-1.0), radicular pain: 0.56 (95% CI: 0.40-0.71), radiculopathy: 0.74 (95% CI: 0.58-0.90), mixed-pain: 0.63 (95% CI: 0.47-0.79), entire framework: 0.64 (95% CI: 0.57-0.71)). Intra-rater-reliability showed substantial to almost perfect reliability (somatic: no variation, mechanosensitivity: 0.96 (95% CI: 0.87-1.0), radicular pain: 0.76 (95% CI: 0.57-0.92), radiculopathy: 0.84 (95% CI: 0.67-0.96), mixed-pain: 0.83 (95% CI: 0.60-1.0), entire framework: 0.80 (95% CI: 0.61-0.92). CONCLUSION: Moderate to almost perfect reliability in subgrouping people with spine-related neck-arm pain and substantial reliability for entire framework support this classification's reliability.

[Universities need to have high quality education as well as an effective quality control of their students' (products') knowledge and skill base]. / Vysoké skoly musí mít nejen kvalitní výuku, ale také úcinnou kontrolu kvality znalostí a schopností studentu (produktu) vysoké zkoly.

In order for the schools of medicine to produce high quality physicians, they have to provide high quality education as well as they must ensure that knowledge building is taking place in the course of the programme and that the students whose efforts and/or abilities do not allow achievement of the required criteria are eliminated. Exams used to be the standard quality control tool. However, current information technologies allow doubling-up of this control; retaining the traditional examinations but preceding them with the requirement to complete multiple-choice tests. The text summarizes our experience with examining the students' mental presence during teaching with tests and our plans for the combined form of exit control using tests, completion of which will be prerequisite to admission to the exam itself. We do not believe that tests should completely replace exams but we do believe that the requirement to pass the exam should only take place following previous successful completion ofa test. This is achievable ifwe manage to establish a computer teaching room, i.e. examination room, and transform a vast number of questions into high quality multiple choice tests.

A new mathematical procedure to evaluate peaks in complex chromatograms.

Automatic peak evaluation in chromatograms and subsequent quantification of compound concentrations is still a challenge in the analysis of complex samples containing hundreds or thousands of compounds. Although a number of software packages for peak evaluation exist, baseline definition and overlapping peaks of different shapes are the main reasons which prevent reliable automatic analysis of complex chromatograms. A new mathematical procedure is presented which uses peak shapes extracted from the chromatogram itself and modified by nonlinear (in fact, hyperbolic) stretching of the peak head and tail. With this approach, the peak parameters are position, height, scale of front, scale of tail, and smoothness of transition from front to tail scaling. This approach is found to give a substantially better fit than traditional analytically defined peak shapes. Together with a good peak finding heuristic and nonlinear optimization of parameters this allows a reliable automatic analysis of chromatograms with a large number of peaks, even with large groups of overlapping peaks. The analysis matches the quality of standard interactive methods, but still permits interactive refinement. This approach has been implemented and tested on a large set of data from chromatography of hydrocarbons in ambient air samples.

Description and characterization of an on-line system for long-term measurements of isoprene, methyl vinyl ketone, and methacrolein in ambient air.

In this work we present a detailed technical description of the system that was set up for long-term on-line measurements of isoprene and two of its major degradation products, methyl vinyl ketone and methacrolein in order to provide a better understanding of the role of forest stands as a complex source of reactive trace gases into the troposphere and to elucidate the role of forests as chemical reactors. Volatile organic compounds (VOCs) are preconcentrated on cartridges containing a package of two solid adsorbents (Tenax TA and Carbopack X). Ozone removal is performed prior to sampling by titration with nitrogen monoxide. For the calibration and characterization of the system, a diffusion source was built to produce standard gas mixtures of up to 16 different compounds with mixing ratios at tens ppt (parts per trillion) level mixing ratios and high accuracy. The developed system allows a reliable quantification of these VOCs (detection limit approximately 10 ppt, reproducibility approximately 5%) with a high temporal resolution (approximately 30 min) and has proven to be stable and run automatically without major maintainence.