Inertial Effects on Finite Length Pipe Seismic Response

A seismic analysis for soil-pipe interaction which accounts for length and constraining conditions at the ends of a continuous pipe is developed. The Winkler model is used to schematize the soil-structure interaction. The approach is focused on axial strains, since bending strains in a buried pipe due to the wave propagation are typically a second-order effect. Unlike many works, the inertial terms are considered in solving equations. Accurate numerical simulations are carried out to show the influence of pipe length and constraint conditions on the pipe seismic strain. The obtained results are compared with results inferred from other models present in the literature. For free-end pipelines, inertial effects have significant influence only for short length. On the contrary, their influence is always important for pinned pipes. Numerical simulations show that a simple rigid model can be used for free-end pipes, whereas pinned pipes need more accurate models

Uplift and magma intrusion at Long Valley caldera from InSAR and gravity measurements

The Long Valley caldera (California) formed ~760,000 yr ago following the massive eruption of the Bishop Tuff. Postcaldera volcanism in the Long Valley volcanic fi eld includes lava domes as young as 650 yr. The recent geological unrest is characterized by uplift of the resurgent dome in the central section of the caldera (75 cm in the past 33 yr) and earthquake activity followed by periods of relative quiescence. Since the spring of 1998, the caldera has been in a state of low activity. The cause of unrest is still debated, and hypotheses range from hybrid sources (e.g., magma with a high percentage of volatiles) to hydrothermal fl uid intrusion. Here, we present observations of surface deformation in the Long Valley region based on differential synthetic aperture radar interferometry (InSAR), leveling, global positioning system (GPS), two-color electronic distance meter (EDM), and microgravity data. Thanks to the joint application of InSAR and microgravity data, we are able to unambiguously determine that magma is the cause of unrest

In vitro folliculogenesis in mammalian models: a computational biology study

In vitro folliculogenesis (ivF) has been proposed as an emerging technology to support follicle growth and oocyte development. It holds a great deal of attraction from preserving human fertility to improving animal reproductive biotechnology. Despite the mice model, where live offspring have been achieved,in medium-sized mammals, ivF has not been validated yet. Thus, the employment of a network theory approach has been proposed for interpreting the large amount of ivF information collected to date in different mammalian models in order to identify the controllers of the in vitro system. The WoS-derived data generated a scale-free network, easily navigable including 641 nodes and 2089 links. A limited number of controllers (7.2%) are responsible for network robustness by preserving it against random damage. The network nodes were stratified in a coherent biological manner on three layers: the input was composed of systemic hormones and somatic- oocyte paracrine factors; the intermediate one recognized mainly key signaling molecules such as PI3K, KL, JAK-STAT, SMAD4, and cAMP; and the output layer molecules were related to functional ivF endpoints such as the FSH receptor and steroidogenesis. Notably, the phenotypes of knock-out mice previously developed for hub.BN indirectly corroborate their biological relevance in early folliculogenesis. Finally, taking advantage of the STRING analysis approach, further controllers belonging to the metabolic axis backbone were identified, such as mTOR/FOXO, FOXO3/SIRT1, and VEGF, which have been poorly considered in ivF to date. Overall, this in silico study identifies new metabolic sensor molecules controlling ivF serving as a basis for designing innovative diagnostic and treatment methods to preserve female fertility

Equine chorionic gonadotropin as an effective fsh replacement for in vitro ovine follicle and oocyte development

The use of assisted reproductive technologies (ART) still requires strategies through which to maximize individual fertility chances. In vitro folliculogenesis (ivF) may represent a valid option to convey the large source of immature oocytes in ART. Several efforts have been made to set up ivF cultural protocols in medium-sized mammals, starting with the identification of the most suitable gonadotropic stimulus. In this study, Equine Chorionic Gonadotropin (eCG) is proposed as an alternative to Follicle Stimulating Hormone (FSH) based on its long superovulation use, trans-species validation, long half-life, and low costs. The use of 3D ivF on single-ovine preantral (PA) follicles allowed us to compare the hormonal effects and to validate their influence under two different cultural conditions. The use of eCG helped to stimulate the in vitro growth of ovine PA follicles by maximizing its influence under FBS-free medium. Higher performance of follicular growth, antrum formation, steroidogenic activity and gap junction marker expression were recorded. In addition, eCG, promoted a positive effect on the germinal compartment, leading to a higher incidence of meiotic competent oocytes. These findings should help to widen the use of eCG to ivF as a valid and largely available hormonal support enabling a synchronized in vitro follicle and oocyte development

pMineR: An Innovative R Library for Performing Process Mining in Medicine

Process Mining is an emerging discipline investigating tasks related with the automated identification of process models, given realworld data (Process Discovery). The analysis of such models can provide useful insights to domain experts. In addition, models of processes can be used to test if a given process complies (Conformance Checking) with specifications. For these capabilities, Process Mining is gaining importance and attention in healthcare. In this paper we introduce pMineR, an R library specifically designed for performing Process Mining in the medical domain, and supporting human experts by presenting processes in a human-readable way

What Role Can Process Mining Play in Recurrent Clinical Guidelines Issues? A Position Paper

[EN] In the age of Evidence-Based Medicine, Clinical Guidelines (CGs) are recognized to be an indispensable tool to support physicians in their daily clinical practice. Medical Informatics is expected to play a relevant role in facilitating diffusion and adoption of CGs. However, the past pioneering approaches, often fragmented in many disciplines, did not lead to solutions that are actually exploited in hospitals. Process Mining for Healthcare (PM4HC) is an emerging discipline gaining the interest of healthcare experts, and seems able to deal with many important issues in representing CGs. In this position paper, we briefly describe the story and the state-of-the-art of CGs, and the efforts and results of the past approaches of medical informatics. Then, we describe PM4HC, and we answer questions like how can PM4HC cope with this challenge? Which role does PM4HC play and which rules should be employed for the PM4HC scientific community?Gatta, R.; Vallati, M.; Fernández Llatas, C.; Martinez-Millana, A.; Orini, S.; Sacchi, L.; Lenkowicz, J.... (2020). What Role Can Process Mining Play in Recurrent Clinical Guidelines Issues? A Position Paper. International Journal of Environmental research and Public Health (Online). 17(18):1-19. https://doi.org/10.3390/ijerph17186616S1191718Guyatt, G. (1992). Evidence-Based Medicine. JAMA, 268(17), 2420. doi:10.1001/jama.1992.03490170092032Hripcsak, G., Ludemann, P., Pryor, T. A., Wigertz, O. B., & Clayton, P. D. (1994). Rationale for the Arden Syntax. Computers and Biomedical Research, 27(4), 291-324. doi:10.1006/cbmr.1994.1023Peleg, M. (2013). Computer-interpretable clinical guidelines: A methodological review. Journal of Biomedical Informatics, 46(4), 744-763. doi:10.1016/j.jbi.2013.06.009Van de Velde, S., Heselmans, A., Delvaux, N., Brandt, L., Marco-Ruiz, L., Spitaels, D., … Flottorp, S. (2018). A systematic review of trials evaluating success factors of interventions with computerised clinical decision support. Implementation Science, 13(1). doi:10.1186/s13012-018-0790-1Rawson, T. M., Moore, L. S. P., Hernandez, B., Charani, E., Castro-Sanchez, E., Herrero, P., … Holmes, A. H. (2017). A systematic review of clinical decision support systems for antimicrobial management: are we failing to investigate these interventions appropriately? Clinical Microbiology and Infection, 23(8), 524-532. doi:10.1016/j.cmi.2017.02.028Greenes, R. A., Bates, D. W., Kawamoto, K., Middleton, B., Osheroff, J., & Shahar, Y. (2018). Clinical decision support models and frameworks: Seeking to address research issues underlying implementation successes and failures. Journal of Biomedical Informatics, 78, 134-143. doi:10.1016/j.jbi.2017.12.005Garcia, C. dos S., Meincheim, A., Faria Junior, E. R., Dallagassa, M. R., Sato, D. M. V., Carvalho, D. R., … Scalabrin, E. E. (2019). Process mining techniques and applications – A systematic mapping study. Expert Systems with Applications, 133, 260-295. doi:10.1016/j.eswa.2019.05.003Bhargava, A., Kim, T., Quine, D. B., & Hauser, R. G. (2019). A 20-Year Evaluation of LOINC in the United States’ Largest Integrated Health System. Archives of Pathology & Laboratory Medicine, 144(4), 478-484. doi:10.5858/arpa.2019-0055-oaLee, D., de Keizer, N., Lau, F., & Cornet, R. (2014). Literature review of SNOMED CT use. Journal of the American Medical Informatics Association, 21(e1), e11-e19. doi:10.1136/amiajnl-2013-001636TROTTI, A., COLEVAS, A., SETSER, A., RUSCH, V., JAQUES, D., BUDACH, V., … COLEMAN, C. (2003). CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Seminars in Radiation Oncology, 13(3), 176-181. doi:10.1016/s1053-4296(03)00031-6Daniel, C., & Kalra, D. (2019). Clinical Research Informatics: Contributions from 2018. Yearbook of Medical Informatics, 28(01), 203-205. doi:10.1055/s-0039-1677921Marco-Ruiz, L., Pedrinaci, C., Maldonado, J. A., Panziera, L., Chen, R., & Bellika, J. G. (2016). Publication, discovery and interoperability of Clinical Decision Support Systems: A Linked Data approach. Journal of Biomedical Informatics, 62, 243-264. doi:10.1016/j.jbi.2016.07.011Marcos, C., González-Ferrer, A., Peleg, M., & Cavero, C. (2015). Solving the interoperability challenge of a distributed complex patient guidance system: a data integrator based on HL7’s Virtual Medical Record standard. Journal of the American Medical Informatics Association, 22(3), 587-599. doi:10.1093/jamia/ocv003Wulff, A., Haarbrandt, B., Tute, E., Marschollek, M., Beerbaum, P., & Jack, T. (2018). An interoperable clinical decision-support system for early detection of SIRS in pediatric intensive care using openEHR. Artificial Intelligence in Medicine, 89, 10-23. doi:10.1016/j.artmed.2018.04.012Chen, C., Chen, K., Hsu, C.-Y., Chiu, W.-T., & Li, Y.-C. (Jack). (2010). A guideline-based decision support for pharmacological treatment can improve the quality of hyperlipidemia management. Computer Methods and Programs in Biomedicine, 97(3), 280-285. doi:10.1016/j.cmpb.2009.12.004Anani, N., Mazya, M. V., Chen, R., Prazeres Moreira, T., Bill, O., Ahmed, N., … Koch, S. (2017). Applying openEHR’s Guideline Definition Language to the SITS international stroke treatment registry: a European retrospective observational study. BMC Medical Informatics and Decision Making, 17(1). doi:10.1186/s12911-016-0401-5Eddy, D. M. (1982). Clinical Policies and the Quality of Clinical Practice. New England Journal of Medicine, 307(6), 343-347. doi:10.1056/nejm198208053070604Guyatt, G. H. (1990). Then-of-1 Randomized Controlled Trial: Clinical Usefulness. Annals of Internal Medicine, 112(4), 293. doi:10.7326/0003-4819-112-4-293CHALMERS, I. (1993). The Cochrane Collaboration: Preparing, Maintaining, and Disseminating Systematic Reviews of the Effects of Health Care. Annals of the New York Academy of Sciences, 703(1 Doing More Go), 156-165. doi:10.1111/j.1749-6632.1993.tb26345.xWoolf, S. H., Grol, R., Hutchinson, A., Eccles, M., & Grimshaw, J. (1999). Clinical guidelines: Potential benefits, limitations, and harms of clinical guidelines. BMJ, 318(7182), 527-530. doi:10.1136/bmj.318.7182.527Grading quality of evidence and strength of recommendations. (2004). BMJ, 328(7454), 1490. doi:10.1136/bmj.328.7454.1490Guyatt, G. H., Oxman, A. D., Vist, G. E., Kunz, R., Falck-Ytter, Y., Alonso-Coello, P., & Schünemann, H. J. (2008). GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ, 336(7650), 924-926. doi:10.1136/bmj.39489.470347.adHill, J., Bullock, I., & Alderson, P. (2011). A Summary of the Methods That the National Clinical Guideline Centre Uses to Produce Clinical Guidelines for the National Institute for Health and Clinical Excellence. Annals of Internal Medicine, 154(11), 752. doi:10.7326/0003-4819-154-11-201106070-00007Qaseem, A. (2012). Guidelines International Network: Toward International Standards for Clinical Practice Guidelines. Annals of Internal Medicine, 156(7), 525. doi:10.7326/0003-4819-156-7-201204030-00009Rosenfeld, R. M., Nnacheta, L. C., & Corrigan, M. D. (2015). Clinical Consensus Statement Development Manual. Otolaryngology–Head and Neck Surgery, 153(2_suppl), S1-S14. doi:10.1177/0194599815601394De Boeck, K., Castellani, C., & Elborn, J. S. (2014). Medical consensus, guidelines, and position papers: A policy for the ECFS. Journal of Cystic Fibrosis, 13(5), 495-498. doi:10.1016/j.jcf.2014.06.012Clinical Practical Guidelineshttp://www.openclinical.org/guidelines.htmlHaynes, A. B., Weiser, T. G., Berry, W. R., Lipsitz, S. R., Breizat, A.-H. S., Dellinger, E. P., … Gawande, A. A. (2009). A Surgical Safety Checklist to Reduce Morbidity and Mortality in a Global Population. New England Journal of Medicine, 360(5), 491-499. doi:10.1056/nejmsa0810119Grigg, E. (2015). Smarter Clinical Checklists. Anesthesia & Analgesia, 121(2), 570-573. doi:10.1213/ane.0000000000000352Hales, B., Terblanche, M., Fowler, R., & Sibbald, W. (2007). Development of medical checklists for improved quality of patient care. International Journal for Quality in Health Care, 20(1), 22-30. doi:10.1093/intqhc/mzm062Greenfield, S. (2017). Clinical Practice Guidelines. JAMA, 317(6), 594. doi:10.1001/jama.2016.19969Vegting, I. L., van Beneden, M., Kramer, M. H. H., Thijs, A., Kostense, P. J., & Nanayakkara, P. W. B. (2012). How to save costs by reducing unnecessary testing: Lean thinking in clinical practice. European Journal of Internal Medicine, 23(1), 70-75. doi:10.1016/j.ejim.2011.07.003Drummond, M. (2016). Clinical Guidelines: A NICE Way to Introduce Cost-Effectiveness Considerations? Value in Health, 19(5), 525-530. doi:10.1016/j.jval.2016.04.020Prior, M., Guerin, M., & Grimmer-Somers, K. (2008). The effectiveness of clinical guideline implementation strategies - a synthesis of systematic review findings. Journal of Evaluation in Clinical Practice, 14(5), 888-897. doi:10.1111/j.1365-2753.2008.01014.xWatts, C. G., Dieng, M., Morton, R. L., Mann, G. J., Menzies, S. W., & Cust, A. E. (2014). Clinical practice guidelines for identification, screening and follow-up of individuals at high risk of primary cutaneous melanoma: a systematic review. British Journal of Dermatology, 172(1), 33-47. doi:10.1111/bjd.13403Woolf, S., Schünemann, H. J., Eccles, M. P., Grimshaw, J. M., & Shekelle, P. (2012). Developing clinical practice guidelines: types of evidence and outcomes; values and economics, synthesis, grading, and presentation and deriving recommendations. Implementation Science, 7(1). doi:10.1186/1748-5908-7-61Legido-Quigley, H., Panteli, D., Brusamento, S., Knai, C., Saliba, V., Turk, E., … Busse, R. (2012). Clinical guidelines in the European Union: Mapping the regulatory basis, development, quality control, implementation and evaluation across member states. Health Policy, 107(2-3), 146-156. doi:10.1016/j.healthpol.2012.08.004Rashidian, A., Eccles, M. P., & Russell, I. (2008). Falling on stony ground? A qualitative study of implementation of clinical guidelines’ prescribing recommendations in primary care. Health Policy, 85(2), 148-161. doi:10.1016/j.healthpol.2007.07.011Yang, W.-S., & Hwang, S.-Y. (2006). A process-mining framework for the detection of healthcare fraud and abuse. Expert Systems with Applications, 31(1), 56-68. doi:10.1016/j.eswa.2005.09.003Kose, I., Gokturk, M., & Kilic, K. (2015). An interactive machine-learning-based electronic fraud and abuse detection system in healthcare insurance. Applied Soft Computing, 36, 283-299. doi:10.1016/j.asoc.2015.07.018Pryor, T. A., Gardner, R. M., Clayton, P. D., & Warner, H. R. (1983). The HELP system. Journal of Medical Systems, 7(2), 87-102. doi:10.1007/bf00995116Shahar, Y., Miksch, S., & Johnson, P. (1998). The Asgaard project: a task-specific framework for the application and critiquing of time-oriented clinical guidelines. Artificial Intelligence in Medicine, 14(1-2), 29-51. doi:10.1016/s0933-3657(98)00015-3Boxwala, A. A., Peleg, M., Tu, S., Ogunyemi, O., Zeng, Q. T., Wang, D., … Shortliffe, E. H. (2004). GLIF3: a representation format for sharable computer-interpretable clinical practice guidelines. Journal of Biomedical Informatics, 37(3), 147-161. doi:10.1016/j.jbi.2004.04.002Terenziani, P., Molino, G., & Torchio, M. (2001). A modular approach for representing and executing clinical guidelines. Artificial Intelligence in Medicine, 23(3), 249-276. doi:10.1016/s0933-3657(01)00087-2Sutton, D. R., & Fox, J. (2003). The Syntax and Semantics of the PROformaGuideline Modeling Language. Journal of the American Medical Informatics Association, 10(5), 433-443. doi:10.1197/jamia.m1264Musen, M. A., Tu, S. W., Das, A. K., & Shahar, Y. (1996). EON: A Component-Based Approach to Automation of Protocol-Directed Therapy. Journal of the American Medical Informatics Association, 3(6), 367-388. doi:10.1136/jamia.1996.97084511Ciccarese, P., Caffi, E., Quaglini, S., & Stefanelli, M. (2005). Architectures and tools for innovative Health Information Systems: The Guide Project. International Journal of Medical Informatics, 74(7-8), 553-562. doi:10.1016/j.ijmedinf.2005.02.001Shiffman, R. N., & Greenes, R. A. (1994). Improving Clinical Guidelines with Logic and Decision-table Techniques. Medical Decision Making, 14(3), 245-254. doi:10.1177/0272989x9401400306Peleg, M., Tu, S., Bury, J., Ciccarese, P., Fox, J., Greenes, R. A., … Stefanelli, M. (2003). Comparing Computer-interpretable Guideline Models: A Case-study Approach. Journal of the American Medical Informatics Association, 10(1), 52-68. doi:10.1197/jamia.m1135Karadimas, H., Ebrahiminia, V., & Lepage, E. (2018). User-defined functions in the Arden Syntax: An extension proposal. Artificial Intelligence in Medicine, 92, 103-110. doi:10.1016/j.artmed.2015.11.003Peleg, M., Keren, S., & Denekamp, Y. (2008). Mapping computerized clinical guidelines to electronic medical records: Knowledge-data ontological mapper (KDOM). Journal of Biomedical Informatics, 41(1), 180-201. doi:10.1016/j.jbi.2007.05.003German, E., Leibowitz, A., & Shahar, Y. (2009). An architecture for linking medical decision-support applications to clinical databases and its evaluation. Journal of Biomedical Informatics, 42(2), 203-218. doi:10.1016/j.jbi.2008.10.007Marcos, M., Maldonado, J. A., Martínez-Salvador, B., Boscá, D., & Robles, M. (2013). Interoperability of clinical decision-support systems and electronic health records using archetypes: A case study in clinical trial eligibility. Journal of Biomedical Informatics, 46(4), 676-689. doi:10.1016/j.jbi.2013.05.004Marco-Ruiz, L., Moner, D., Maldonado, J. A., Kolstrup, N., & Bellika, J. G. (2015). Archetype-based data warehouse environment to enable the reuse of electronic health record data. International Journal of Medical Informatics, 84(9), 702-714. doi:10.1016/j.ijmedinf.2015.05.016Gooch, P., & Roudsari, A. (2011). Computerization of workflows, guidelines, and care pathways: a review of implementation challenges for process-oriented health information systems. Journal of the American Medical Informatics Association, 18(6), 738-748. doi:10.1136/amiajnl-2010-000033Quaglini, S., Stefanelli, M., Cavallini, A., Micieli, G., Fassino, C., & Mossa, C. (2000). Guideline-based careflow systems. Artificial Intelligence in Medicine, 20(1), 5-22. doi:10.1016/s0933-3657(00)00050-6Schadow, G., Russler, D. C., & McDonald, C. J. (2001). Conceptual alignment of electronic health record data with guideline and workflow knowledge. International Journal of Medical Informatics, 64(2-3), 259-274. doi:10.1016/s1386-5056(01)00196-4González-Ferrer, A., ten Teije, A., Fdez-Olivares, J., & Milian, K. (2013). Automated generation of patient-tailored electronic care pathways by translating computer-interpretable guidelines into hierarchical task networks. Artificial Intelligence in Medicine, 57(2), 91-109. doi:10.1016/j.artmed.2012.08.008Shabo, A., Parimbelli, E., Quaglini, S., Napolitano, C., & Peleg, M. (2016). Interplay between Clinical Guidelines and Organizational Workflow Systems. Methods of Information in Medicine, 55(06), 488-494. doi:10.3414/me16-01-0006Mulyar, N., van der Aalst, W. M. P., & Peleg, M. (2007). A Pattern-based Analysis of Clinical Computer-interpretable Guideline Modeling Languages. Journal of the American Medical Informatics Association, 14(6), 781-787. doi:10.1197/jamia.m2389Grando, M. A., Glasspool, D., & Fox, J. (2012). A formal approach to the analysis of clinical computer-interpretable guideline modeling languages. Artificial Intelligence in Medicine, 54(1), 1-13. doi:10.1016/j.artmed.2011.07.001Kaiser, K., & Marcos, M. (2015). Leveraging workflow control patterns in the domain of clinical practice guidelines. BMC Medical Informatics and Decision Making, 16(1). doi:10.1186/s12911-016-0253-zMartínez-Salvador, B., & Marcos, M. (2016). Supporting the Refinement of Clinical Process Models to Computer-Interpretable Guideline Models. Business & Information Systems Engineering, 58(5), 355-366. doi:10.1007/s12599-016-0443-3Decision Model and Notation Version 1.0https://www.omg.org/spec/DMN/1.0Ghasemi, M., & Amyot, D. (2016). Process mining in healthcare: a systematised literature review. International Journal of Electronic Healthcare, 9(1), 60. doi:10.1504/ijeh.2016.078745Rebuge, Á., & Ferreira, D. R. (2012). Business process analysis in healthcare environments: A methodology based on process mining. Information Systems, 37(2), 99-116. doi:10.1016/j.is.2011.01.003Rovani, M., Maggi, F. M., de Leoni, M., & van der Aalst, W. M. P. (2015). Declarative process mining in healthcare. Expert Systems with Applications, 42(23), 9236-9251. doi:10.1016/j.eswa.2015.07.040Rojas, E., Munoz-Gama, J., Sepúlveda, M., & Capurro, D. (2016). Process mining in healthcare: A literature review. Journal of Biomedical Informatics, 61, 224-236. doi:10.1016/j.jbi.2016.04.007Lenkowicz, J., Gatta, R., Masciocchi, C., Casà, C., Cellini, F., Damiani, A., … Valentini, V. (2018). Assessing the conformity to clinical guidelines in oncology. Management Decision, 56(10), 2172-2186. doi:10.1108/md-09-2017-0906Fernández-Llatas, C., Benedi, J.-M., García-Gómez, J., & Traver, V. (2013). Process Mining for Individualized Behavior Modeling Using Wireless Tracking in Nursing Homes. Sensors, 13(11), 15434-15451. doi:10.3390/s131115434Qu, G., Liu, Z., Cui, S., & Tang, J. (2013). Study on Self-Adaptive Clinical Pathway Decision Support System Based on Case-Based Reasoning. Frontier and Future Development of Information Technology in Medicine and Education, 969-978. doi:10.1007/978-94-007-7618-0_95Van de Velde, S., Roshanov, P., Kortteisto, T., Kunnamo, I., Aertgeerts, B., Vandvik, P. O., & Flottorp, S. (2015). Tailoring implementation strategies for evidence-based recommendations using computerised clinical decision support systems: protocol for the development of the GUIDES tools. Implementation Science, 11(1). doi:10.1186/s13012-016-0393-

Comparative effectiveness of intracranial hypertension management guided by ventricular versus intraparenchymal pressure monitoring:a CENTER-TBI study

Objective: To compare outcomes between patients with primary external ventricular device (EVD)–driven treatment of intracranial hypertension and those with primary intraparenchymal monitor (IP)–driven treatment. Methods: The CENTER-TBI study is a prospective, multicenter, longitudinal observational cohort study that enrolled patients of all TBI severities from 62 participating centers (mainly level I trauma centers) across Europe between 2015 and 2017. Functional outcome was assessed at 6 months and a year. We used multivariable adjusted instrumental variable (IV) analysis with “center” as instrument and logistic regression with covariate adjustment to determine the effect estimate of EVD on 6-month functional outcome. Results: A total of 878 patients of all TBI severities with an indication for intracranial pressure (ICP) monitoring were included in the present study, of whom 739 (84%) patients had an IP monitor and 139 (16%) an EVD. Patients included were predominantly male (74% in the IP monitor and 76% in the EVD group), with a median age of 46 years in the IP group and 48 in the EVD group. Six-month GOS-E was similar between IP and EVD patients (adjusted odds ratio (aOR) and 95% confidence interval [CI] OR 0.74 and 95% CI [0.36–1.52], adjusted IV analysis). The length of intensive care unit stay was greater in the EVD group than in the IP group (adjusted rate ratio [95% CI] 1.70 [1.34–2.12], IV analysis). One hundred eighty-seven of the 739 patients in the IP group (25%) required an EVD due to refractory ICPs. Conclusion: We found no major differences in outcomes of patients with TBI when comparing EVD-guided and IP monitor–guided ICP management. In our cohort, a quarter of patients that initially received an IP monitor required an EVD later for ICP control. The prevalence of complications was higher in the EVD group. Protocol: The core study is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (RRID: SCR_015582).</p

The burden of traumatic brain injury from low-energy falls among patients from 18 countries in the CENTER-TBI Registry: A comparative cohort study.

BACKGROUND: Traumatic brain injury (TBI) is an important global public health burden, where those injured by high-energy transfer (e.g., road traffic collisions) are assumed to have more severe injury and are prioritised by emergency medical service trauma triage tools. However recent studies suggest an increasing TBI disease burden in older people injured through low-energy falls. We aimed to assess the prevalence of low-energy falls among patients presenting to hospital with TBI, and to compare their characteristics, care pathways, and outcomes to TBI caused by high-energy trauma. METHODS AND FINDINGS: We conducted a comparative cohort study utilising the CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) Registry, which recorded patient demographics, injury, care pathway, and acute care outcome data in 56 acute trauma receiving hospitals across 18 countries (17 countries in Europe and Israel). Patients presenting with TBI and indications for computed tomography (CT) brain scan between 2014 to 2018 were purposively sampled. The main study outcomes were (i) the prevalence of low-energy falls causing TBI within the overall cohort and (ii) comparisons of TBI patients injured by low-energy falls to TBI patients injured by high-energy transfer-in terms of demographic and injury characteristics, care pathways, and hospital mortality. In total, 22,782 eligible patients were enrolled, and study outcomes were analysed for 21,681 TBI patients with known injury mechanism; 40% (95% CI 39% to 41%) (8,622/21,681) of patients with TBI were injured by low-energy falls. Compared to 13,059 patients injured by high-energy transfer (HE cohort), the those injured through low-energy falls (LE cohort) were older (LE cohort, median 74 [IQR 56 to 84] years, versus HE cohort, median 42 [IQR 25 to 60] years; p < 0.001), more often female (LE cohort, 50% [95% CI 48% to 51%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001), more frequently taking pre-injury anticoagulants or/and platelet aggregation inhibitors (LE cohort, 44% [95% CI 42% to 45%], versus HE cohort, 13% [95% CI 11% to 14%]; p < 0.001), and less often presenting with moderately or severely impaired conscious level (LE cohort, 7.8% [95% CI 5.6% to 9.8%], versus HE cohort, 10% [95% CI 8.7% to 12%]; p < 0.001), but had similar in-hospital mortality (LE cohort, 6.3% [95% CI 4.2% to 8.3%], versus HE cohort, 7.0% [95% CI 5.3% to 8.6%]; p = 0.83). The CT brain scan traumatic abnormality rate was 3% lower in the LE cohort (LE cohort, 29% [95% CI 27% to 31%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001); individuals in the LE cohort were 50% less likely to receive critical care (LE cohort, 12% [95% CI 9.5% to 13%], versus HE cohort, 24% [95% CI 23% to 26%]; p < 0.001) or emergency interventions (LE cohort, 7.5% [95% CI 5.4% to 9.5%], versus HE cohort, 13% [95% CI 12% to 15%]; p < 0.001) than patients injured by high-energy transfer. The purposive sampling strategy and censorship of patient outcomes beyond hospital discharge are the main study limitations. CONCLUSIONS: We observed that patients sustaining TBI from low-energy falls are an important component of the TBI disease burden and a distinct demographic cohort; further, our findings suggest that energy transfer may not predict intracranial injury or acute care mortality in patients with TBI presenting to hospital. This suggests that factors beyond energy transfer level may be more relevant to prehospital and emergency department TBI triage in older people. A specific focus to improve prevention and care for patients sustaining TBI from low-energy falls is required.CENTER-TBI was supported by the European Union 7th Framework program (EC grant 602150), recipient A.I.R. Maas. Additional funding was obtained from the Hannelore Kohl Stiftung (Germany) - recipient A.I.R. Maas, from OneMind (USA) - recipient A.I.R. Maas and from Integra LifeSciences Corporation (USA) - recipient A.I.R. Maas. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript