Data-driven discovery of changes in clinical code usage over time: a case-study on changes in cardiovascular disease recording in two English electronic health records databases (2001-2015)

[EN] Objectives To demonstrate how data-driven variability methods can be used to identify changes in disease recording in two English electronic health records databases between 2001 and 2015. Design Repeated cross-sectional analysis that applied data-driven temporal variability methods to assess month-by-month changes in routinely collected medical data. A measure of difference between months was calculated based on joint distributions of age, gender, socioeconomic status and recorded cardiovascular diseases. Distances between months were used to identify temporal trends in data recording. Setting 400 English primary care practices from the Clinical Practice Research Datalink (CPRD GOLD) and 451 hospital providers from the Hospital Episode Statistics (HES). Main outcomes The proportion of patients (CPRD GOLD) and hospital admissions (HES) with a recorded cardiovascular disease (CPRD GOLD: coronary heart disease, heart failure, peripheral arterial disease, stroke; HES: International Classification of Disease codes I20-I69/G45). Results Both databases showed gradual changes in cardiovascular disease recording between 2001 and 2008. The recorded prevalence of included cardiovascular diseases in CPRD GOLD increased by 47%-62%, which partially reversed after 2008. For hospital records in HES, there was a relative decrease in angina pectoris (-34.4%) and unspecified stroke (-42.3%) over the same time period, with a concomitant increase in chronic coronary heart disease (+14.3%). Multiple abrupt changes in the use of myocardial infarction codes in hospital were found in March/April 2010, 2012 and 2014, possibly linked to updates of clinical coding guidelines. Conclusions Identified temporal variability could be related to potentially non-medical causes such as updated coding guidelines. These artificial changes may introduce temporal correlation among diagnoses inferred from routine data, violating the assumptions of frequently used statistical methods. Temporal variability measures provide an objective and robust technique to identify, and subsequently account for, those changes in electronic health records studies without any prior knowledge of the data collection process.VN is funded by a Public Health England PhD Studentship. RWA is supported by a Wellcome Trust Clinical Research Career Development Fellowship (206602/Z/17/Z). JMGG and CS contributions to this work were partially supported by the MTS4up Spanish project (National Plan for Scientific and Technical Research and Innovation 2013-2016, No. DPI2016-80054-R), the CrowdHealth H2020-SC1-2016-CNECT project (No. 727560) (JMGG) and the Inadvance H2020-SC1-BHC-2018-2020 project (No. 825750). PR and DA did not receive any direct funding for this project. Access to the Clinical Practice Research Datalink was supported by the UK Economic and Social Research Council (ES/P008321/1). Access to aggregated Hospital Episode Statistics was provided by Public Health England. This work was further supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and the Wellcome Trust.Rockenschaub, P.; Nguyen, V.; Aldridge, RW.; Acosta, D.; Garcia-Gomez, JM.; Sáez Silvestre, C. (2020). Data-driven discovery of changes in clinical code usage over time: a case-study on changes in cardiovascular disease recording in two English electronic health records databases (2001-2015). BMJ Open. 10(2):1-9. https://doi.org/10.1136/bmjopen-2019-034396S19102Hripcsak, G., & Albers, D. J. (2013). Next-generation phenotyping of electronic health records. 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Clusters of Extragalactic Ultra Compact HII Regions

We report on the detection of optically thick free-free radio sources in the galaxies M33, NGC 253, and NGC 6946 using data in the literature. We interpret these sources as being young, embedded star birth regions, which are likely to be clusters of ultracompact HII regions. All 35 of the sources presented in this article have positive radio spectral indices alpha>0 suggesting an optically thick thermal bremsstrahlung emission arising in the HII region surrounding hot stars. Energy requirements indicate a range of a several to >500 O7V star equivalents powering each HII region. Assuming a Salpeter IMF, this corresponds to integrated stellar masses of 0.1--60,000 Msun. For roughly half of the sources in our sample, there is no obvious optical counterpart, giving further support for their deeply embedded nature. Their luminosities and radio spectral energy distributions are consistent with HII regions having electron densities from 1500 cm^-3 to 15000 cm^-3 and radii of 1 - 7 pc. We suggest that the less luminous of these sources are extragalactic ultracompact HII region complexes, those of intermediate luminosity are similar to W49 in the Galaxy, while the brightest will be counterparts to 30 Doradus. These objects constitute the lower mass range of extragalactic ``ultradense HII regions'' which we argue are the youngest stages of massive star cluster formation yet observed. This sample is beginning to fill in the continuum of objects between small associations of ultracompact HII regions and the massive extragalactic clusters that may evolve into globular clusters.Comment: 37 pages, uses AASTeX; scheduled to appear in ApJ v. 559 October 2001. Full postscript version available from http://www.astro.wisc.edu/~chip/Papers/Johnson_Kobulnicky_etal_ApJ559.ps.g

On the Stability of Quasi-Equilibrium Self-Gravitating Configurations in a Tidal Field

The possibility that quasi-equilibrium self-gravitating galaxy-like configurations exist in a tidal field is analyzed in this paper. More specifically, we address the question of how to predict initial configurations modeling galaxies that are able to survive environmental effects in a dense environment for a Hubble time or so, provided thay dynamical friction is neglected. The initial quasi-equilibrium configurations have been built up taking into account the external tidal field produced by the halo. It modifies the escape velocity field of the configuration, compared with isolated configurations. The survival of the configurations as they orbit inside the halos has been studied through N-body simulations. As a general result, it has been found out that the bulk of the models is conserved along 12.5 Gyears of evolution, and that the low rates of mass losses they experience are consistent with those expected when the adiabatic protection hypothesis is at work. So, solutions for galaxy configurations in tidal quasi-equilibrium have been found, showing that tidal stripping in quiescent phases does not seem to be very important, unless that the density of the galaxy environment at its formation had been much lower than that of the galaxy environment at the point of its orbit where the tidal perturbation is maximum. (Abridged)Comment: 36 pages, 7 postscript figures, to be published in Ap

Searches for Giant Pulses from Extragalactic Pulsars

We discuss the giant-pulse phenomenon exhibited by pulsars and the distances to which giant pulses might be detected from extragalactic pulsars. We describe the conditions under which a single-pulse search is more sensitive than a standard periodicity search. We find that, for certain pulse-amplitude distribution power laws and time series lengths, single-pulse searches can be superior. We present the results of searches toward several extragalactic targets, including M33, the LMC (PSR B0540-69) and several other galaxies. While we have not conclusively detected giant pulses from any of these targets, these searches illustrate the methodology of, issues related to and difficulties in these types of searches.Comment: Accepted by Ap

Superbeams versus Neutrino Factories

We compare the physics potential of planned superbeams with the one of neutrino factories. Therefore, the experimental setups as well as the most relevant uncertainties and errors are considered on the same footing as much as possible. We use an improved analysis including the full parameter correlations, as well as statistical, systematical, and degeneracy errors. Especially, degeneracies have so far not been taken into account in a numerical analysis. We furthermore include external input, such as improved knowledge of the solar oscillation parameters from the KamLAND experiment. This allows us to determine the limiting uncertainties in all cases. For a specific comparison, we choose two representatives of each class: For the superbeam, we take the first conceivable setup, namely the JHF to SuperKamiokande experiment, as well as, on a longer time scale, the JHF to HyperKamiokande experiment. For the neutrino factory, we choose an initially conceivable setup and an advanced machine. We determine the potential to measure the small mixing angle sin^2 2 theta_{13}, the sign of Delta m^2_{31}, and the leptonic CP phase \deltacp, which also implies that we compare the limitations of the different setups. We find interesting results, such as the complete loss of the sensitivity to the sign of Delta m^2_{31} due to degeneracies in many cases.Comment: Revised version with JHF energy resolution corrected, discussion of detector issues added (App. B), and references added. Summary and conclusions unchanged. 51 pages, 28 figures, 4 table

PANIC: the new panoramic NIR camera for Calar Alto

PANIC is a wide-field NIR camera, which is currently under development for the Calar Alto observatory (CAHA) in Spain. It uses a mosaic of four Hawaii-2RG detectors and covers the spectral range from 0.8-2.5 micron(z to K-band). The field-of-view is 30x30 arcmin. This instrument can be used at the 2.2m telescope (0.45arcsec/pixel, 0.5x0.5 degree FOV) and at the 3.5m telescope (0.23arcsec/pixel, 0.25x0.25 degree FOV). The operating temperature is about 77K, achieved by liquid Nitrogen cooling. The cryogenic optics has three flat folding mirrors with diameters up to 282 mm and nine lenses with diameters between 130 mm and 255 mm. A compact filter unit can carry up to 19 filters distributed over four filter wheels. Narrow band (1%) filters can be used. The instrument has a diameter of 1.1 m and it is about 1 m long. The weight limit of 400 kg at the 2.2m telescope requires a light-weight cryostat design. The aluminium vacuum vessel and radiation shield have wall thicknesses of only 6 mm and 3 mm respectively.Comment: This paper has been presented in the SPIE of Astronomical Telescopes and Instrumentation 2008 in Marseille (France

Evaluation with in vivo optical coherence tomography and histology of the vascular effects of the everolimus-eluting bioresorbable vascular scaffold at two years following implantation in a healthy porcine coronary artery model: implications of pilot results for future pre-clinical studies

To quantify with in vivo OCT and histology, the device/vessel interaction after implantation of the bioresorbable vascular scaffold (BVS). We evaluated the area and thickness of the strut voids previously occupied by the polymeric struts, and the neointimal hyperplasia (NIH) area covering the endoluminal surface of the strut voids (NIHEV), as well as the NIH area occupying the space between the strut voids (NIHBV), in healthy porcine coronary arteries at 2, 3 and 4 years after implantation of the device. Twenty-two polymeric BVS were implanted in the coronary arteries of 11 healthy Yucatan minipigs that underwent OCT at 2, 3 and 4 years after implantation, immediately followed by euthanasia. The areas and thicknesses of 60 corresponding strut voids previously occupied by the polymeric struts and the size of 60 corresponding NIHEV and 49 NIHBV were evaluated with both OCT and histology by 2 independent observers, using a single quantitative analysis software for both techniques. At 3 and 4 years after implantation, the strut voids were no longer detectable by OCT or histology due to complete polymer resorption. However, analysis performed at 2 years still provided clear delineation of these structures, by both techniques. The median [ranges] areas of these strut voids were 0.04 [0.03–0.16] and 0.02 [0.01–0.07] mm2 by histology and OCT, respectively. The mean (±SD) thickness by histology and OCT was 220 ± 40 and 120 ± 20 μm, respectively. The median [ranges] NIHEV by histology and OCT was 0.07 [0.04–0.20] and 0.03 [0.01–0.08] mm2, while the mean (±SD) NIHBV by histology and OCT was 0.13 ± 0.07 and 0.10 ± 0.06 mm2. Our study indicates that in vivo OCT of the BVS provides correlated measurements of the same order of magnitude as histomorphometry, and is reproducible for the evaluation of certain vascular and device-related characteristics. However, histology systematically gives larger values for all the measured structures compared to OCT, at 2 years post implantation

Synergies between the first-generation JHF-SK and NuMI superbeam experiments

We discuss synergies in the combination of the first-generation JHF to Super-Kamiokande and NuMI off-axis superbeam experiments. With synergies we mean effects which go beyond simply adding the statistics of the two experiments. As a first important result, we do not observe interesting synergy effects in the combination of the two experiments as they are planned right now. However, we find that with minor modifications, such as a different NuMI baseline or a partial antineutrino running, one could do much richer physics with both experiments combined. Specifically, we demonstrate that one could, depending on the value of the solar mass squared difference, either measure the sign of the atmospheric mass squared difference or CP violation already with the initial stage experiments. Our main results are presented in a way that can be easily interpreted in terms of the forthcoming KamLAND result.Comment: 29 pages, 10 figure

Alpha helix-coil phase transition: analysis of ab initio theory predictions

In the present paper we present results of calculations obtained with the use of the theoretical method described in our preceding paper [1] and perform detail analysis of alpha helix-random coil transition in alanine polypeptides of different length. We have calculated the potential energy surfaces of polypeptides with respect to their twisting degrees of freedom and construct a parameter-free partition function of the polypeptide using the suggested method [1]. From the build up partition function we derive various thermodynamical characteristics for alanine polypeptides of different length as a function of temperature. Thus, we analyze the temperature dependence of the heat capacity, latent heat and helicity for alanine polypeptides consisting of 21, 30, 40, 50 and 100 amino acids. Alternatively, we have obtained same thermodynamical characteristics from the use of molecular dynamics simulations and compared them with the results of the new statistical mechanics approach. The comparison proves the validity of the statistical mechanic approach and establishes its accuracy.Comment: 34 pages, 12 figure