Spinal cord stimulation:a real-world data analysis on outcomes and differences between rechargeable and non-rechargeable implantable pulse generators

Objective In this analysis, we examined differences between rechargeable and non-rechargeable spinal cord stimulation (SCS) devices in patients with pain. Methods We conducted a retrospective, longitudinal claims data analysis using a German research database comprising 5 million statutory insured patients (2012–2017). Outcomes of demographics, patient pathways, and health care resource utilization (HCRU) in patients with initial SCS were collected. Results Of 150 patients in the database, 73 (49%) received a rechargeable device and 77 (51%) a non-rechargeable device. The average age was 62.5 years (51% female and 49% male patients). A significant decrease over a 3-year follow-up was observed in analgesic prescriptions (−18%), number of patient visits to a physician, and number of patients who were hospitalized. HCRU-related figures for patients with non-rechargeable neurostimulators increased in the last follow-up year whereas the group receiving rechargeable neurostimulators showed a steady decrease. Conclusions SCS seems to be an effective way for patients with chronic pain to decrease pain and improve quality of life. Rechargeable devices seem to be superior to non-rechargeable devices owing to greater longevity and were found to be associated with continuous reduction of pain diagnoses, hospitalization, physician visits, and use of pain medication in our study

Formation of star clusters and enrichment by massive stars in simulations of low-metallicity galaxies with a fully sampled initial stellar mass function

We present new GRIFFIN project hydrodynamical simulations that model the formation of galactic star cluster populations in low-metallicity ($Z=0.00021$) dwarf galaxies, including radiation, supernova and stellar wind feedback of individual massive stars. In the simulations, stars are sampled from the stellar initial mass function (IMF) down to the hydrogen burning limit of $0.08$ M$_\odot$. Mass conservation is enforced within a radius of $1$ pc for the formation of massive stars. We find that massive stars are preferentially found in star clusters and follow a correlation set at birth between the highest initial stellar mass and the star cluster mass that differs from pure stochastic IMF sampling. With a fully sampled IMF, star clusters lose mass in the galactic tidal field according to mass-loss rates observed in nearby galaxies. Of the released stellar feedback, $60\%$ of the supernova material and up to $35\%$ of the wind material reside either in the hot interstellar medium (ISM) or in gaseous, metal enriched outflows. While stellar winds (instantaneously) and supernovae (delayed) start enriching the ISM right after the first massive stars form, the formation of supernova-enriched stars and star clusters is significantly delayed (by $>50$ Myr) compared to the formation of stars and star clusters enriched by stellar winds. Overall, supernova ejecta dominate the enrichment by mass, while the number of enriched stars is determined by continuous stellar winds. These results present a concept for the formation of chemically distinct populations of stars in bound star clusters, reminiscent of multiple populations in globular clusters.Comment: 26 pages, 23 figures. Accepted for publication in MNRA

LEDA 074886: A remarkable rectangular-looking galaxy

We report the discovery of an interesting and rare, rectangular-shaped galaxy. At a distance of 21 Mpc, the dwarf galaxy LEDA 074886 has an absolute R-band magnitude of -17.3 mag. Adding to this galaxy's intrigue is the presence of an embedded, edge-on stellar disk (of extent 2R_{e,disk} = 12 arcsec = 1.2 kpc) for which Forbes et al. reported V_rot/sigma ~ 1.4. We speculate that this galaxy may be the remnant of two (nearly edge-one) merged disk galaxies in which the initial gas was driven inward and subsequently formed the inner disk, while the stars at larger radii effectively experienced a dissipationless merger event resulting in this `emerald cut galaxy' having very boxy isophotes with a_4/a = -0.05 to -0.08 from 3 to 5 kpc. This galaxy suggests that knowledge from simulations of both `wet' and `dry' galaxy mergers may need to be combined to properly understand the various paths that galaxy evolution can take, with a particular relevance to blue elliptical galaxies.Comment: To appear in ApJ. Six pages including references and figure

Prediction of Antibiotic Susceptibility Profiles of Vibrio cholerae Isolates From Whole Genome Illumina and Nanopore Sequencing Data: CholerAegon

During the last decades, antimicrobial resistance (AMR) has become a global public health concern. Nowadays multi-drug resistance is commonly observed in strains of Vibrio cholerae, the etiological agent of cholera. In order to limit the spread of pathogenic drug-resistant bacteria and to maintain treatment options the analysis of clinical samples and their AMR profiles are essential. Particularly, in low-resource settings a timely analysis of AMR profiles is often impaired due to lengthy culturing procedures for antibiotic susceptibility testing or lack of laboratory capacity. In this study, we explore the applicability of whole genome sequencing for the prediction of AMR profiles of V. cholerae. We developed the pipeline CholerAegon for the in silico prediction of AMR profiles of 82 V. cholerae genomes assembled from long and short sequencing reads. By correlating the predicted profiles with results from phenotypic antibiotic susceptibility testing we show that the prediction can replace in vitro susceptibility testing for five of seven antibiotics. Because of the relatively low costs, possibility for real-time data analyses, and portability, the Oxford Nanopore Technologies MinION sequencing platform-especially in light of an upcoming less error-prone technology for the platform-appears to be well suited for pathogen genomic analyses such as the one described here. Together with CholerAegon, it can leverage pathogen genomics to improve disease surveillance and to control further spread of antimicrobial resistance.We thank Dr. Daniel Cadar and Heike Baum from the NGS core facility of the Bernhard Nocht Institute for Tropical Medicine for technical support. We thank the Carl-Zeiss-Stiftung (FKZ 0563-2.8/738/2), TWMMG DigLeben (5575/10-9), and DFG iDIV (FZT 118, 202548816) for financial support. Figures were finalized with Inkscape v1.0.2.S

Evaluating the use of prostate-specific antigen as an instrument for early detection of prostate cancer beyond urologists: Results of a representative cross-sectional questionnaire study of general practitioners and internal specialists

OBJECTIVES The aim of this cross-sectional study was to evaluate the value of prostate-specific antigen (PSA) testing as a tool for early detection of prostate cancer (PCa) applied by general practitioners (GPs) and internal specialists (ISs) as well as to assess criteria leading to the application of PSA-based early PCa detection. METHODS Between May and December 2012, a questionnaire containing 16 items was sent to 600 GPs and ISs in the federal state Brandenburg and in Berlin (Germany). The independent influence of several criteria on the decision of GPs and ISs to apply PSA-based early PCa detection was assessed by multivariate logistic regression analysis (MLRA). RESULTS 392 evaluable questionnaires were collected (return rate 65%). 81% of the physicians declared that they apply PSA testing for early PCa detection; of these, 58 and 15% would screen patients until the age of 80 and 90 years, respectively. In case of a pathological PSA level, 77% would immediately refer the patient to a urologist, while 13% would re-assess elevated PSA levels after 3-12 months. Based on MLRA, the following criteria were independently associated with a positive attitude towards PSA-based early PCa detection: specialisation (application of early detection more frequent for GPs and hospital-based ISs) (OR 3.12; p < 0.001), physicians who use exclusively GP or IS education (OR 3.95; p = 0.002), and physicians who recommend yearly PSA assessment after the age of 50 (OR 6.85; p < 0.001). CONCLUSIONS GPs and ISs frequently apply PSA-based early PCa detection. In doing so, 13% would initiate specific referral to a urologist in case of pathological PSA values too late. Improvement of this situation could possibly result from specific educational activities for non-urological physicians active in fields of urological core capabilities, which should be guided by joint boards of the national associations of urology and general medicine

On the dynamics of nitrite, nitrate and other biomarkers of nitric oxide production in inflammatory bowel disease

Nitrite and nitrate are frequently used surrogate markers of nitric oxide (NO) production. Using rat models of acute and chronic DSS-induced colitis we examined the applicability of these and other NO-related metabolites, in tissues and blood, for the characterization of inflammatory bowel disease. Global NO dynamics were assessed by simultaneous quantification of nitrite, nitrate, nitroso and nitrosyl species over time in multiple compartments. NO metabolite levels were compared to a composite disease activity index (DAI) and contrasted with measurements of platelet aggregability, ascorbate redox status and the effects of 5-aminosalicylic acid (5-ASA). Nitroso products in the colon and in other organs responded in a manner consistent with the DAI. In contrast, nitrite and nitrate, in both intra- and extravascular compartments, exhibited variations that were not always in step with the DAI. Extravascular nitrite, in particular, demonstrated significant temporal instabilities, ranging from systemic drops to marked increases. The latter was particularly evident after cessation of the inflammatory stimulus and accompanied by profound ascorbate oxidation. Treatment with 5-ASA effectively reversed these fluctuations and the associated oxidative and nitrosative stress. Platelet activation was enhanced in both the acute and chronic model. Our results offer a first glimpse into the systemic nature of DSS-induced inflammation and reveal a greater complexity of NO metabolism than previously envisioned, with a clear dissociation of nitrite from other markers of NO production. The remarkable effectiveness of 5-ASA to abrogate the observed pattern of nitrite instability suggests a hitherto unrecognized role of this molecule in either development or resolution of inflammation. Its possible link to tissue oxygen consumption and the hypoxia that tends to accompany the inflammatory process warrants further investigation

International variation in survival after out-of-hospital cardiac arrest : A validation study of the Utstein template

Introduction: Out-of-hospital cardiac arrest (OHCA) survival varies greatly between communities. The Utstein template was developed and promulgated to improve the comparability of OHCA outcome reports, but it has undergone limited empiric validation. We sought to assess how much of the variation in OHCA survival between emergency medical services (EMS) across the globe is explained by differences in the Utstein factors. We also assessed how accurately the Utstein factors predict OHCA survival. Methods: We performed a retrospective analysis of patient-level prospectively collected data from 12 OHCA registries from 12 countries for the period 1 Jan 2006 through 31 Dec 2011. We used generalized linear mixed models to examine the variation in survival between EMS agencies (n = 232). Results: Twelve registries contributed 86,759 cases. Patient arrest characteristics, EMS treatment and patient outcomes varied across registries. Overall survival to hospital discharge was 10% (range, 6% to 22%). Overall survival with Cerebral Performance Category of 1 or 2 (available for 8/12 registries) was 8%(range, 2% to 20%). The area-under-the-curve for the Utstein model was 0.85 (Wald CI: 0.85-0.85). The Utstein factors explained 51% of the EMS agency variation in OHCA survival. Conclusions: The Utstein factors explained 51%. of the variation in survival to hospital discharge among multiple large geographically separate EMS agencies. This suggests that quality improvement and public health efforts should continue to target modifiable Utstein factors to improve OHCA survival. Further study is required to identify the reasons for the variation that is incompletely understood.Peer reviewe

Addressing the clinical unmet needs in primary Sjögren's Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts

For many decades, the clinical unmet needs of primary Sjögren's Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-art data analytics services to address the pSS clinical unmet needs, including the development of lymphoma classification models and the identification of biomarkers for lymphomagenesis. The users of the platform have been able to successfully interlink, curate, and harmonize 21 regional, national, and international European cohorts of 7,551 pSS patients with respect to the ethical and legal issues for data sharing. Federated AI algorithms were trained across the harmonized databases, with reduced execution time complexity, yielding robust lymphoma classification models with 85% accuracy, 81.25% sensitivity, 85.4% specificity along with 5 biomarkers for lymphoma development. To our knowledge, this is the first GDPR compliant platform that provides federated AI services to address the pSS clinical unmet needs. © 2022 The Author(s