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1. Diagnostic performance of point-of-care ubiquitin carboxy-terminal Hydrolase-L1 assay in distinguishing imaging abnormalities in traumatic brain injury: A TRACK-TBI cohort study

Author

Kevin K. Wang, Jennifer C. Munoz-Pareja, Lauren A. Lautenslager, J. Adrian Tyndall, Zhihui Yang, Maria R. Kerrigan, Ramon Diaz-Arrastia, Frederick K. Korley, David Okonkwo, Ava M. Puccio, John K. Yue, Sabrina R. Taylor, Pratik Mukherjee, Esther L. Yuh, Nancy R. Temkin, Claudia S. Robertson, Xiaoying Sun, Sonia Jain, Amy J. Markowitz, Geoffrey T. Manley, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, V Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Joseph Giacino, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J Claude Hemphill, Gillian Hotz, Joel Kramer, Natalie Kreitzer, Harvey Levin, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Lindsay Nelson, Laura Ngwenya, Eva Palacios, Daniel Perl, Miri Rabinowitz, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Arthur Toga, Alex Valadka, Mary Vassar, Paul Vespa, and Ross Zafonte

Subjects
TBI, Biomarkers, UCH-L1, Point of care, Mild TBI, NSE, Toxicology. Poisons, RA1190-1270, Biotechnology, TP248.13-248.65, Biology (General), QH301-705.5
Abstract

The use of UCH-L1 detection with point-of-care (POC) assay alone has not been characterized for clinical use. This study compares the accuracies of POC UCH-L1 and Neuron-Specific Enolase (NSE) Elecsys® levels for identifying TBI patients with structural abnormalities on neuroimaging.The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Phase 1 Cohort, enrolled 1375 TBI patients (GCS 3–15) presenting to one of 18 US Level I trauma centers within 24 h of injury who had an admission head CT; blood samples were collected, along with 122 orthopedic and 209 healthy controls. The TBI cohort consisted of 810 CT-negative (CT-) and 549 CT-positive (CT+) subjects. Of the CT- subjects who had MRIs, 121 were MRI-positive (MRI+) and 333 were MRI-negative (MRI-). UCH-L1 POC showed best diagnostic performance for CT + versus CT-, 0–8 h post-injury with an AUC of 0·779 [0·708–0.850] when compared to the 0–25 h interval, with an AUC of 0.684 [0.655–0.712]. NSE assay has an AUC of 0.695 [0.619–0.770] for the 0–8 h interval and 0.634 [0.603–0.665] for the 0–25 h interval. During the first 8 after injury, POC UCH-L1 outperforms NSE in identifying TBI patients with structural abnormalities on neuroimaging.

Published
2023
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2. Incidence, prevalence, and risk factors of infectious uveitis and scleritis in the United States: A claims-based analysis.

Author

Youning Zhang, Sarina Amin, Khristina I Lung, Seth Seabury, Narsing Rao, and Brian C Toy

Subjects
Medicine, Science
Abstract

BackgroundOcular inflammation causes significant visual morbidity in the United States, yet little is known about the epidemiology of infectious uveitis and scleritis. This study aims to evaluate the epidemiology of infectious uveitis/scleritis employing a large national medical claims database.MethodsThis was a retrospective, case-control study, employing Optum's de-identified Clinformatics® Data Mart Database, containing data from 21.5 million privately insured individuals with enrollment for at least 15 months within 2007-2015. Inclusion in the uveitis/scleritis sample required an index uveitis/scleritis diagnosis based on International Classification of Diseases, Ninth Revision (ICD-9) codes. Exclusion criteria included index date within 3 months after intraocular surgery. Rates for uveitis/scleritis were determined by anatomic site. Multivariable logistic regression analyses were performed to determine odds ratios for the incidence and prevalence of uveitis/scleritis by anatomic category.FindingsInfectious etiologies accounted for less than 20% of uveitis/scleritis, with mean rates of 18.9 (incidence) and 60.6 (prevalence) per 100,000 persons. The mean prevalences of infectious anterior, intermediate, posterior, panuveitis, and scleritis were 27.7, 0.17, 23.4, 4.4, and 4.6, per 100,000, respectively. Overall risk of prevalent infectious uveitis/scleritis increased with age (OR>3.3 for each decade over age 18, pConclusionsThe incidence and prevalence of infectious uveitis/scleritis in the United States were higher than previously reported estimates but remained lower than in developing countries. Rates varied by age, sex, race, and medical comorbidities, and may reflect differential susceptibility to various infectious agents with disparate geographic distributions within the United States.

Published
2020
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3. Lifetime benefits of early detection and treatment of diabetic kidney disease.

Author

Julia Thornton Snider, Jeffrey Sullivan, Emma van Eijndhoven, Michael K Hansen, Nobel Bellosillo, Cheryl Neslusan, Ellen O'Brien, Ralph Riley, Seth Seabury, and Bertram L Kasiske

Subjects
Medicine, Science
Abstract

ObjectivesDiabetic kidney disease (DKD) is a frequent complication of diabetes with potentially devastating consequences that may be prevented or delayed. This study aimed to estimate the health and economic benefit of earlier diagnosis and treatment of DKD.MethodsLife expectancy and medical spending for people with diabetes were modeled using The Health Economics Medical Innovation Simulation (THEMIS). THEMIS uses data from the Health and Retirement Study to model cohorts of individuals over age 50 to project population-level lifetime health and economic outcomes. DKD status was imputed based on diagnoses and laboratory values in the National Health and Nutrition Examination Survey. We simulated the implementation of a new biomarker identifying people with diabetes at an elevated risk of DKD and DKD patients at risk of rapid progression.ResultsCompared to baseline, the prevalence of DKD declined 5.1% with a novel prognostic biomarker test, while the prevalence of diabetes with stage 5 chronic kidney disease declined 3.0%. Consequently, people with diabetes gained 0.2 years in life expectancy, while per-capita annual medical spending fell by 0.3%. The estimated cost was $12,796 per life-year gained and $25,842 per quality-adjusted life-year.ConclusionsA biomarker test that allows earlier treatment reduces DKD prevalence and slows DKD progression, thereby increasing life expectancy among people with diabetes while raising healthcare spending by less than one percent.

Published
2019
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4. The quality of occupational healthcare for carpal tunnel syndrome, healthcare expenditures, and disability outcomes: A prospective observational study

Author

Teryl K. Nuckols, Michael Dworsky, Craig Conlon, Michael Robbins, Douglas Benner, Seth Seabury, and Steven M. Asch

Subjects
Adult, Occupational Diseases, Cellular and Molecular Neuroscience, Physiology, Physiology (medical), Humans, Workers' Compensation, Prospective Studies, Neurology (clinical), Health Expenditures, Carpal Tunnel Syndrome, Delivery of Health Care, Article
Abstract

INTRODUCTION/AIMS: In prior work, higher quality care for work-associated carpal tunnel syndrome (CTS) was associated with improved symptoms, functional status, and overall health. We sought to examine whether quality of care is associated with healthcare expenditures or disability. METHODS: Among 343 adults with workers’ compensation claims for CTS, we created patient-level aggregate quality scores for underuse (not receiving highly beneficial care) and overuse (receiving care for which risks exceed benefits). We assessed whether each aggregate quality score (0-100%, 100% = better care) was associated with healthcare expenditures (18-month expenditures, any anticipated need for future expenditures) or disability (days on temporary disability, permanent impairment rating at 18 months). RESULTS: Mean aggregate quality scores were 77.8% (standard deviation [S.D.] 16.5%) for underuse and 89.2% (S.D. 11.0%) for overuse. An underuse score of 100% was associated with higher risk-adjusted 18-month expenditures ($3,672; 95% CI $324 to $7,021) but not with future expenditures (−0.07 percentage points; 95% CI −0.48 to 0.34), relative to a score of 0%. An overuse score of 100% was associated with lower 18-month expenditures (−$4,549, 95% CI −$8,792 to −$306) and a modestly lower likelihood of future expenditures (−0.62 percentage points, 95% CI −1.23 to −0.02). Quality of care was not associated with disability. DISCUSSION: Improving quality of care could increase or lower short-term healthcare expenditures, depending on how often care is currently underused or overused. Future research is needed on quality of care in varied workers’ compensation contexts, as well as effective and economical strategies for improving quality.

Published
2022
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5. Formulary Restrictions and Stroke Risk in Patients With Atrial Fibrillation

Author

Bo, Zhou, Seth, Seabury, Dana, Goldman, and Geoffrey, Joyce

Subjects
Stroke, Ischemic Attack, Transient, Health Policy, Atrial Fibrillation, Administration, Oral, Anticoagulants, Humans, Longitudinal Studies, Medicare, United States, Aged
Abstract

To determine the use of formulary restrictions (prior authorization and step therapy) on the use of non-vitamin K antagonist oral anticoagulants (NOACs) and their effect on health outcomes.Longitudinal cohort study. We identified a sample of Medicare beneficiaries with an incident diagnosis of atrial fibrillation (AF) in 2011 to 2015 and followed them until the end of 2016 or death. We compared anticoagulant use and health outcomes associated with Medicare Part D plan coverage of NOACs.The primary outcomes were composite rates of death, stroke, transient ischemic attack, and systemic embolism. We used Cox proportional hazards models to estimate the association between formulary restrictions and adverse health outcomes.Beneficiaries enrolled in Part D plans that restricted access to NOACs had a lower probability of NOAC use (30.2% vs 32.2%), worse adherence conditional on NOAC use (32.1% vs 34.3% adherent), and longer delays in filling an initial prescription (46% vs 55% filled within 30 days of AF diagnosis). Beneficiaries in restricted plans had higher aggregate risk of mortality/stroke/transient ischemic attack (adjusted HR, 1.098; 95% CI, 1.079-1.118).Limiting access to NOACs may exacerbate current underuse of anticoagulants and increase the risk of stroke among patients with newly diagnosed AF. Pharmacy benefit managers and Part D plans need to continuously review the appropriateness of formulary policies to ensure patient access to effective medications.

Published
2022
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6. The Broader Economic Value of Treatment for Diabetic Macular Edema

Author

Karen Mulligan, Jaehong Kim, Bryan Tysinger, Jill Blim, Geoffrey Emerson, Philip J. Ferrone, Judy E. Kim, Seth Seabury, and Paul Hahn

Subjects
Advanced and Specialized Nursing, Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract

OBJECTIVE To simulate economic outcomes for individuals with diabetic macular edema (DME) and estimate the economic value of direct and indirect benefits associated with DME treatment. RESEARCH DESIGN AND METHODS Our study pairs individual and cohort analyses to demonstrate the value of treatment for DME. We used a microsimulation model to simulate self-reported vision (SRV) and economic outcomes for individuals with DME. Four scenarios derived from clinical trial data were simulated and compared for a lifetime horizon: untreated, anti-VEGF therapy, laser, and steroid. To quantify the relative magnitude of costs and benefits of DME treatment in the U.S., we used a cohort-level analysis based on real-world treatment parameters derived from published data. RESULTS In the model, excellent/good SRV roughly corresponded to 20/40 or better visual acuity. A representative 51-year-old treated for DME would spend 30–35% additional years with excellent/good SRV and 29–32% fewer years with fair/poor SRV relative to being untreated. A treated individual would experience 4–5% greater life expectancy and 9–13% more quality-adjusted life-years. Indirect benefits from treatment included 6–9% more years working, 12–19% greater lifetime earnings, and 8–16% fewer years with disability. For the U.S. DME cohort (1.1. million people), total direct benefit was $63.0 billion over 20 years, and total indirect benefit was $4.8 billion. Net value (benefit − cost) of treatment ranged from $28.1 billion to $52.8 billion. CONCLUSIONS Treatment for DME provides economic value to patients and society through improved vision, life expectancy, and quality of life and indirectly through improved employment and disability outcomes.

Published
2023
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7. Assessing the Use of Data Systems to Estimate Return-on-Investment of Behavioral Healthcare Interventions: Opportunities and Barriers

Author

Hanke Heun-Johnson, Katiri V. Zuluaga, Michael Menchine, Shelley Starkey, Rebecca Farley David, and Seth Seabury

Subjects
Health (social science), Health Policy, Public Health, Environmental and Occupational Health
Abstract

To improve access to and quality of affordable behavioral healthcare, there is a need for more research to identify which interventions can generate long-term, societal return-on-investment (ROI). Barriers to ROI studies in the behavioral health sector were explored by conducting semi-structured interviews with individuals from key stakeholder groups at state and national behavioral health-related organizations. Limited operating budgets, state-based payer systems, the lack of financial support, privacy laws, and other unique experiences of behavioral health providers and patients were identified as important factors that affect the collection and utilization of data. To comprehensively assess ROI of interventions, it is necessary to improve standardization and data infrastructure across multiple health and non-health systems and clarify or address legal, regulatory, and commercial conflicts.

Published
2022
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8. A genome-wide association study of outcome from traumatic brain injury

Author

Mart Kals, Kevin Kunzmann, Livia Parodi, Farid Radmanesh, Lindsay Wilson, Saef Izzy, Christopher D. Anderson, Ava M. Puccio, David O. Okonkwo, Nancy Temkin, Ewout W. Steyerberg, Murray B. Stein, Geoff T. Manley, Andrew I.R. Maas, Sylvia Richardson, Ramon Diaz-Arrastia, Aarno Palotie, Samuli Ripatti, Jonathan Rosand, David K. Menon, Cecilia Åkerlund, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Mark Coburn, Jonathan P. Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire DahyotFizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, GuyLoup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J.A. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Jiyao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Kornaropoulos, LarsOwe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Ana M. CastañoLeón, Marc Maegele, Marek Majdan, Alex Manara, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia F.J. Newcombe, Daan Nieboer, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Paul M. Parizel, JeanFrançois Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Dana Pisica, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Isabel Retel Helmrich, Jonathan Rhodes, Sophie Richter, Saulius Rocka, Cecilie Roe, Olav Roise, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan SanchezPorras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Mathieu van der Jagt, Gregory van der Steen, Joukje van der Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Ernest van Veen, Thijs Vande Vyvere, Roel P.J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Janek Frantzén, Ari Katila, Henna-Rikka Maanpää, Jussi Tallus, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Jason Barber, Yelena Bodien, Randall Chesnut, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Joseph Giacino, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, Claude Hemphill, Gillian Hotz, Sonia Jain, Dirk Keene, Frederick K. Korley, Joel Kramer, Natalie Kreitzer, Harvey Levin, Chris Lindsell, Joan Machamer, Christopher Madden, Geoffrey T. Manley, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Pratik Mukherjee, Lindsay Nelson, Laura B Ngwenya, Florence Noel, Amber Nolan, David Okonkwo, Eva Palacios, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Mark Sherer, Murray Stein, Sabrina Taylor, Arthur Toga, Alex Valadka, Mary Vassar, John K. Yue, Esther Yuh, Ross Zafonte, Public Health, Cell biology, Ragauskas, Arminas, Ročka, Saulius, Tamošuitis, Tomas, Vilcinis, Rimantas, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J. A., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Jiyao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, LarsOwe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I. R., CastañoLeón, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David K., Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia F. J., Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, JeanFrançois, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Raj, Rahul, Rambadagalla, Malinka, Helmrich, Isabel Retel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, SanchezPorras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Ao, Braden Te, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T. J. M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, van Veen, Ernest, Vyvere, Thijs Vande, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K. W., Åkerlund, Cecilia, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Amrein, Krisztina, Ziverte, Agate, Zoerle, Tommaso, Izzy, Saef, Radmanesh, Farid, Frantzén, Janek, Katila, Ari, Maanpää, Henna-Rikka, Tallus, Jussi, Adeoye, Opeolu, Badjatia, Neeraj, Andelic, Nada, Boase, Kim, Barber, Jason, Bodien, Yelena, Chesnut, Randall, Corrigan, John D., Crawford, Karen, Diaz-Arrastia, Ramon, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Andreassen, Lasse, Feeser, Ramana, Ferguson, Adam R., Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Giacino, Joseph, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Anke, Audny, Hemphill, Claude, Hotz, Gillian, Jain, Sonia, Keene, Dirk, Korley, Frederick K., Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Machamer, Joan, Antoni, Anna, Madden, Christopher, Manley, Geoffrey T., Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Mukherjee, Pratik, Nelson, Lindsay, Ngwenya, Laura B., Noel, Florence, Audibert, Gérard, Nolan, Amber, Okonkwo, David, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Azouvi, Philippe, Schnyer, David, Seabury, Seth, Sherer, Mark, Stein, Murray, Taylor, Sabrina, Temkin, Nancy, Toga, Arthur, Valadka, Alex, Vassar, Mary, Yue, John K., Azzolini, Maria Luisa, Yuh, Esther, Zafonte, Ross, Carroll, Ellen, Chatfield, Doris A., Coles, Jonathan P., Helmy, Adel, Manktelow, Anne, Outtrim, Joanne G., Bartels, Ronald, Takala, Rikka, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, DahyotFizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Corte, Francesco Della, Boogert, Hugo den, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, GuyLoup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Molecular Neuroscience and Ageing Research (MOLAR), Kals, M, Kunzmann, K, Parodi, L, Radmanesh, F, Wilson, L, Izzy, S, Anderson, C, Puccio, A, Okonkwo, D, Temkin, N, Steyerberg, E, Stein, M, Manley, G, Citerio, G, Genetic Associations In Neurotrauma (GAIN) Consortium, CENTER-TBI, CABI, MGB, TBIcare Studies, TRACK-TBI, „Elsevier Science' grupė, Menon, David [0000-0002-3228-9692], Apollo - University of Cambridge Repository, Institute for Molecular Medicine Finland, Complex Disease Genetics, Research Programs Unit, Centre of Excellence in Complex Disease Genetics, Genomics of Neurological and Neuropsychiatric Disorders, Faculty Common Matters (Faculty of Social Sciences), Department of Public Health, and Biostatistics Helsinki

Subjects
Traumatic, Physical Injury - Accidents and Adverse Effects, Clinical Sciences, LOCI, SUSCEPTIBILITY, Traumatic Brain Injury (TBI), Mannose-Binding Lectin, DISEASE, General Biochemistry, Genetics and Molecular Biology, Traumatic brain injury, Consortia, Recovery, Brain Injuries, Traumatic, Genetics, 2.1 Biological and endogenous factors, Humans, Prospective Studies, Aetiology, Traumatic Head and Spine Injury, Outcome, Human Genome, 3112 Neurosciences, Neurosciences, General Medicine, LECTIN, Brain Disorders, Good Health and Well Being, consortia, genome-wide association study, outcome, recovery, traumatic brain injury, Brain Injuries, Genetic Associations In Neurotrauma (GAIN) Consortium, Public Health and Health Services, Human medicine, Transcriptome, Genome-Wide association study
Abstract

EBioMedicine 77, 103933 (2022). doi:10.1016/j.ebiom.2022.103933, Published by Elsevier, Amsterdam [u.a.]

Published
2022
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9. Life After Mild Traumatic Brain Injury: Widespread Structural Brain Changes Associated With Psychological Distress Revealed With Multimodal Magnetic Resonance Imaging

Author

Francesca Sibilia, Rachel M. Custer, Andrei Irimia, Farshid Sepehrband, Arthur W. Toga, Ryan P. Cabeen, Opeolu Adeoye, Neeraj Badjatia, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Ramon Diaz-Arrastia, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, Frederick K. Korley, Joel Kramer, Natalie Kreitzer, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Randall Merchant, Laura B. Ngwenya, Florence Noel, David Okonkwo, Eva Palacios, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Sabrina Taylor, Arthur Toga, Alex Valadka, Mary Vassar, Paul Vespa, Kevin Wang, John K. Yue, and Ross Zafonte

Subjects
General Medicine
Published
2022
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10. Effect of frailty on 6-month outcome after traumatic brain injury: a multicentre cohort study with external validation

Author

Stefania Galimberti, Francesca Graziano, Andrew I R Maas, Giulia Isernia, Fiona Lecky, Sonia Jain, Xiaoying Sun, Raquel C Gardner, Sabrina R Taylor, Amy J Markowitz, Geoffrey T Manley, Maria Grazia Valsecchi, Giuseppe Bellelli, Giuseppe Citerio, Cecilia Ackerlund, Hadie Adams, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Ana M. Castaño-León, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Hans Clusmann, Mark Steven Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Covic, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Marc Maegele, Marek Majdan, Alex Manara, Hugues Maréchal, Costanza Martino, Julia Mattern, Charles McFadyen, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Matej Oresic, Fabrizio Ortolano, Olubukola Otesile, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Dana Pisica, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Veronika Rehorčíková, Isabel Retel Helmrich, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Ranjit D. Singh, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolijn Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Egils Valeinis, Shirley Vallance, Zoltán Vámos, Mathieu van der Jagt, Joukje van der Naalt, Gregory Van der Steen, Jeroen T.J.M. van Dijck, Inge A. van Erp, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Ernest van Veen, Roel van Wijk, Thijs Vande Vyvere, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Peter Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. Zeiler, Agate Ziverte, Tommaso Zoerle, Opeolu Adeoye, Neeraj Badjatia, Jason Barber, Michael Bergin, Kim Boase, Yelena Bodien, Randall Chesnut, John Corrigan, Karen Crawford, Ramon Diaz-Arrastia, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, Venkata Feeser, Adam R Ferguson, Brandon Foreman, Etienne Gaudette, Joseph Giacino, Luis Gonzalez, Shankar Gopinath, Ramesh Grandhi, Rao Gullapalli, Claude Hemphill, Gillian Hotz, Russell Huie, Ruchira Jha, C. Dirk Keene, Ryan Kitagawa, Frederick Korley, Joel Kramer, Natalie Kreitzer, Harvey Levin, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Pratik Mukherjee, Lindsay Nelson, Laura B. Ngwenya, Florence Noel, Amber Nolan, David Okonkwo, Eva Palacios, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Richard Ben Rodgers, Jonathan Rosand, Eric Rosenthal, Angelle Sander, Danielle Sandsmark, Gabriella Sugar, Andrea Schneider, David Schnyer, Seth Seabury, Mark Sherer, Murray Stein, Nancy Temkin, Arthur Toga, Abel Torres-Espin, Alex Valadka, Mary Vassar, Kevin Wang, Vincent Wang, John K. Yue, Esther Yuh, Ross Zafonte, Galimberti, S, Graziano, F, Maas, A, Isernia, G, Lecky, F, Jain, S, Sun, X, Gardner, R, Taylor, S, Markowitz, A, Manley, G, Valsecchi, M, Bellelli, G, Citerio, G, Ackerlund, C, Adams, H, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azouvi, P, Azzolini, M, Bartels, R, Barzo, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Beretta, L, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Buki, A, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Carbayo Lozano, G, Carbonara, M, Castano-Leon, A, Cavallo, S, Chevallard, G, Chieregato, A, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Covic, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, Dawes, H, De Keyser, V, Degos, V, Della Corte, F, den Boogert, H, Depreitere, B, Dilvesi, D, Dixit, A, Donoghue, E, Dreier, J, Duliere, G, Ercole, A, Esser, P, Ezer, E, Fabricius, M, Feigin, V, Foks, K, Frisvold, S, Furmanov, A, Gagliardo, P, Galanaud, D, Gantner, D, Gao, G, George, P, Ghuysen, A, Giga, L, Glocker, B, Golubovic, J, Gomez, P, Gratz, J, Gravesteijn, B, Grossi, F, Gruen, R, Gupta, D, Haagsma, J, Haitsma, I, Helbok, R, Helseth, E, Horton, L, Huijben, J, Hutchinson, P, Jacobs, B, Jankowski, S, Jarrett, M, Jiang, J, Johnson, F, Jones, K, Karan, M, Kolias, A, Kompanje, E, Kondziella, D, Koskinen, L, Kovacs, N, Kowark, A, Lagares, A, Lanyon, L, Laureys, S, Ledoux, D, Lefering, R, Legrand, V, Lejeune, A, Levi, L, Lightfoot, R, Lingsma, H, Maegele, M, Majdan, M, Manara, A, Marechal, H, Martino, C, Mattern, J, Mcfadyen, C, Mcmahon, C, Melegh, B, Menon, D, Menovsky, T, Mikolic, A, Misset, B, Muraleedharan, V, Murray, L, Negru, A, Nelson, D, Newcombe, V, Nieboer, D, Nyiradi, J, Oresic, M, Ortolano, F, Otesile, O, Palotie, A, Parizel, P, Payen, J, Perera, N, Perlbarg, V, Persona, P, Peul, W, Piippo-Karjalainen, A, Pirinen, M, Pisica, D, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Rehorcikova, V, Retel Helmrich, I, Rhodes, J, Richardson, S, Richter, S, Ripatti, S, Rocka, S, Roe, C, Roise, O, Rosenfeld, J, Rosenlund, C, Rosenthal, G, Rossaint, R, Rossi, S, Rueckert, D, Rusnak, M, Sahuquillo, J, Sakowitz, O, Sanchez-Porras, R, Sandor, J, Schafer, N, Schmidt, S, Schoechl, H, Schoonman, G, Schou, R, Schwendenwein, E, Sewalt, C, Singh, R, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Stevens, R, Stewart, W, Steyerberg, E, Stocchetti, N, Sundstrom, N, Takala, R, Tamas, V, Tamosuitis, T, Taylor, M, Te Ao, B, Tenovuo, O, Theadom, A, Thomas, M, Tibboel, D, Timmers, M, Tolias, C, Trapani, T, Tudora, C, Unterberg, A, Vajkoczy, P, Valeinis, E, Vallance, S, Vamos, Z, van der Jagt, M, van der Naalt, J, Van der Steen, G, van Dijck, J, van Erp, I, van Essen, T, Van Hecke, W, van Heugten, C, Van Praag, D, van Veen, E, van Wijk, R, Vande Vyvere, T, Vargiolu, A, Vega, E, Velt, K, Verheyden, J, Vespa, P, Vik, A, Vilcinis, R, Volovici, V, von Steinbuchel, N, Voormolen, D, Vulekovic, P, Wang, K, Wiegers, E, Williams, G, Wilson, L, Wolf, S, Yang, Z, Ylen, P, Younsi, A, Zeiler, F, Ziverte, A, Zoerle, T, Adeoye, O, Badjatia, N, Barber, J, Bergin, M, Boase, K, Bodien, Y, Chesnut, R, Corrigan, J, Crawford, K, Diaz-Arrastia, R, Dikmen, S, Duhaime, A, Ellenbogen, R, Feeser, V, Ferguson, A, Foreman, B, Gaudette, E, Giacino, J, Gonzalez, L, Gopinath, S, Grandhi, R, Gullapalli, R, Hemphill, C, Hotz, G, Huie, R, Jha, R, Keene, C, Kitagawa, R, Korley, F, Kramer, J, Kreitzer, N, Levin, H, Lindsell, C, Machamer, J, Madden, C, Martin, A, Mcallister, T, Mccrea, M, Merchant, R, Mukherjee, P, Nelson, L, Ngwenya, L, Noel, F, Nolan, A, Okonkwo, D, Palacios, E, Perl, D, Puccio, A, Rabinowitz, M, Robertson, C, Rodgers, R, Rosand, J, Rosenthal, E, Sander, A, Sandsmark, D, Sugar, G, Schneider, A, Schnyer, D, Seabury, S, Sherer, M, Stein, M, Temkin, N, Toga, A, Torres-Espin, A, Valadka, A, Vassar, M, Wang, V, Yue, J, Yuh, E, Zafonte, R, Molecular Neuroscience and Ageing Research (MOLAR), CENTER-TBI TRACK-TBI Participants and Investigators, Galimberti, S., Graziano, F., Maas, A. I. R., Isernia, G., Lecky, F., Jain, S., Sun, X., Gardner, R. C., Taylor, S. R., Markowitz, A. J., Manley, G. T., Valsecchi, M. G., Bellelli, G., Citerio, G., Ackerlund, C., Adams, H., Amrein, K., Andelic, N., Andreassen, L., Anke, A., Antoni, A., Audibert, G., Azouvi, P., Azzolini, M. L., Bartels, R., Barzo, P., Beauvais, R., Beer, R., Bellander, B. -M., Belli, A., Benali, H., Berardino, M., Beretta, L., Blaabjerg, M., Bragge, P., Brazinova, A., Brinck, V., Brooker, J., Brorsson, C., Buki, A., Bullinger, M., Cabeleira, M., Caccioppola, A., Calappi, E., Calvi, M. R., Cameron, P., Carbayo Lozano, G., Carbonara, M., Castano-Leon, A. M., Cavallo, S., Chevallard, G., Chieregato, A., Clusmann, H., Coburn, M. S., Coles, J., Cooper, J. D., Correia, M., Covic, A., Curry, N., Czeiter, E., Czosnyka, M., Dahyot-Fizelier, C., Dark, P., Dawes, H., De Keyser, V., Degos, V., Della Corte, F., den Boogert, H., Depreitere, B., Dilvesi, D., Dixit, A., Donoghue, E., Dreier, J., Duliere, G. -L., Ercole, A., Esser, P., Ezer, E., Fabricius, M., Feigin, V. L., Foks, K., Frisvold, S., Furmanov, A., Gagliardo, P., Galanaud, D., Gantner, D., Gao, G., George, P., Ghuysen, A., Giga, L., Glocker, B., Golubovic, J., Gomez, P. A., Gratz, J., Gravesteijn, B., Grossi, F., Gruen, R. L., Gupta, D., Haagsma, J. A., Haitsma, I., Helbok, R., Helseth, E., Horton, L., Huijben, J., Hutchinson, P. J., Jacobs, B., Jankowski, S., Jarrett, M., Jiang, J. -Y., Johnson, F., Jones, K., Karan, M., Kolias, A. G., Kompanje, E., Kondziella, D., Koskinen, L. -O., Kovacs, N., Kowark, A., Lagares, A., Lanyon, L., Laureys, S., Ledoux, D., Lefering, R., Legrand, V., Lejeune, A., Levi, L., Lightfoot, R., Lingsma, H., Maegele, M., Majdan, M., Manara, A., Marechal, H., Martino, C., Mattern, J., Mcfadyen, C., Mcmahon, C., Melegh, B., Menon, D., Menovsky, T., Mikolic, A., Misset, B., Muraleedharan, V., Murray, L., Negru, A., Nelson, D., Newcombe, V., Nieboer, D., Nyiradi, J., Oresic, M., Ortolano, F., Otesile, O., Palotie, A., Parizel, P. M., Payen, J. -F., Perera, N., Perlbarg, V., Persona, P., Peul, W., Piippo-Karjalainen, A., Pirinen, M., Pisica, D., Ples, H., Polinder, S., Pomposo, I., Posti, J. P., Puybasset, L., Radoi, A., Ragauskas, A., Raj, R., Rambadagalla, M., Rehorcikova, V., Retel Helmrich, I., Rhodes, J., Richardson, S., Richter, S., Ripatti, S., Rocka, S., Roe, C., Roise, O., Rosenfeld, J., Rosenlund, C., Rosenthal, G., Rossaint, R., Rossi, S., Rueckert, D., Rusnak, M., Sahuquillo, J., Sakowitz, O., Sanchez-Porras, R., Sandor, J., Schafer, N., Schmidt, S., Schoechl, H., Schoonman, G., Schou, R. F., Schwendenwein, E., Sewalt, C., Singh, R. D., Skandsen, T., Smielewski, P., Sorinola, A., Stamatakis, E., Stanworth, S., Stevens, R., Stewart, W., Steyerberg, E. W., Stocchetti, N., Sundstrom, N., Takala, R., Tamas, V., Tamosuitis, T., Taylor, M. S., Te Ao, B., Tenovuo, O., Theadom, A., Thomas, M., Tibboel, D., Timmers, M., Tolias, C., Trapani, T., Tudora, C. M., Unterberg, A., Vajkoczy, P., Valeinis, E., Vallance, S., Vamos, Z., van der Jagt, M., van der Naalt, J., Van der Steen, G., van Dijck, J. T. J. M., van Erp, I. A., van Essen, T. A., Van Hecke, W., van Heugten, C., Van Praag, D., van Veen, E., van Wijk, R., Vande Vyvere, T., Vargiolu, A., Vega, E., Velt, K., Verheyden, J., Vespa, P. M., Vik, A., Vilcinis, R., Volovici, V., von Steinbuchel, N., Voormolen, D., Vulekovic, P., Wang, K. K. W., Wiegers, E., Williams, G., Wilson, L., Wolf, S., Yang, Z., Ylen, P., Younsi, A., Zeiler, F. A., Ziverte, A., Zoerle, T., Adeoye, O., Badjatia, N., Barber, J., Bergin, M., Boase, K., Bodien, Y., Chesnut, R., Corrigan, J., Crawford, K., Diaz-Arrastia, R., Dikmen, S., Duhaime, A. -C., Ellenbogen, R., Feeser, V., Ferguson, A. R., Foreman, B., Gaudette, E., Giacino, J., Gonzalez, L., Gopinath, S., Grandhi, R., Gullapalli, R., Hemphill, C., Hotz, G., Huie, R., Jha, R., Keene, C. D., Kitagawa, R., Korley, F., Kramer, J., Kreitzer, N., Levin, H., Lindsell, C., Machamer, J., Madden, C., Martin, A., Mcallister, T., Mccrea, M., Merchant, R., Mukherjee, P., Nelson, L., Ngwenya, L. B., Noel, F., Nolan, A., Okonkwo, D., Palacios, E., Perl, D., Puccio, A., Rabinowitz, M., Robertson, C., Rodgers, R. B., Rosand, J., Rosenthal, E., Sander, A., Sandsmark, D., Sugar, G., Schneider, A., Schnyer, D., Seabury, S., Sherer, M., Stein, M., Temkin, N., Toga, A., Torres-Espin, A., Valadka, A., Vassar, M., Wang, K., Wang, V., Yue, J. K., Yuh, E., and Zafonte, R.

Subjects
Male, Traumatic/therapy, Frailty, Brain Injuries, Traumatic/therapy, traumatic brain injury, Reproducibility of Results, Middle Aged, Cohort Studies, Brain Injuries, Brain Injuries, Traumatic, outcome, Humans, Glasgow Coma Scale, Neurology (clinical), Human medicine, Prospective Studies, Aged
Abstract

Background: Frailty is known to be associated with poorer outcomes in individuals admitted to hospital for medical conditions requiring intensive care. However, little evidence is available for the effect of frailty on patients’ outcomes after traumatic brain injury. Many frailty indices have been validated for clinical practice and show good performance to predict clinical outcomes. However, each is specific to a particular clinical context. We aimed to develop a frailty index to predict 6-month outcomes in patients after a traumatic brain injury. Methods: A cumulative deficit approach was used to create a novel frailty index based on 30 items dealing with disease states, current medications, and laboratory values derived from data available from CENTER-TBI, a prospective, longitudinal observational study of patients with traumatic brain injury presenting within 24 h of injury and admitted to a ward or an intensive care unit at 65 centres in Europe between Dec 19, 2014, and Dec 17, 2017. From the individual cumulative CENTER-TBI frailty index (range 0–30), we obtained a standardised value (range 0–1), with high scores indicating higher levels of frailty. The effect of frailty on 6-month outcome evaluated with the extended Glasgow Outcome Scale (GOSE) was assessed through a proportional odds logistic model adjusted for known outcome predictors. An unfavourable outcome was defined as death or severe disability (GOSE score ≤4). External validation was performed on data from TRACK-TBI, a prospective observational study co-designed with CENTER-TBI, which enrolled patients with traumatic brain injury at 18 level I trauma centres in the USA from Feb 26, 2014, to July 27, 2018. CENTER-TBI is registered with ClinicalTrials.gov, NCT02210221; TRACK-TBI is registered at ClinicalTrials.gov, NCT02119182. Findings: 2993 participants (median age was 51 years [IQR 30–67], 2058 [69%] were men) were included in this analysis. The overall median CENTER-TBI frailty index score was 0·07 (IQR 0·03–0·15), with a median score of 0·17 (0·08–0·27) in older adults (aged ≥65 years). The CENTER-TBI frailty index score was significantly associated with the probability of an increasingly unfavourable outcome (cumulative odds ratio [OR] 1·03, 95% CI 1·02–1·04; p

Published
2022
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11. Biomarkers for Traumatic Brain Injury: Data Standards and Statistical Considerations

Author

J. Russell Huie, Stefania Mondello, Christopher J. Lindsell, Luca Antiga, Esther L. Yuh, Elisa R. Zanier, Serge Masson, Bedda L. Rosario, Adam R. Ferguson, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Ramon Diaz-Arrastia, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Joseph Giacino, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, Sonia Jain, Frederick Korley, Joel Kramer, Natalie Kreitzer, Harvey Levin, Joan Machamer, Christopher Madden, Geoffrey T. Manley, Alastair Martin, Thomas McAllister, Michael McCrea, Randall Merchant, Pratik Mukherjee, Lindsay Nelson, Laura B. Ngwenya, Florence Noel, David Okonkwo, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Jonathan Rosand, Angelle Sander, David Schnyer, Seth Seabury, Murray Stein, Sabrina Taylor, Nancy Temkin, Arthur Toga, Alex Valadka, Mary Vassar, Paul Vespa, Kevin Wang, John K. Yue, Ross Zafonte, Cecilia Ackerlund, Hadie Adams, Vanni Agnoletti, Judith Allanson, Krisztina Amrein, Norberto Andaluz, Nada Andelic, Lasse Andreassen, Audny Anke, Azasevac Antun, Anna Antoni, Hilko Ardon, Kaspars Auslands, Philippe Azouvi, Maria Luisa Azzolini, Camelia Baciu, Rafael Badenes, Ronald Bartels, Pál Barzó, Ursula Bauerfeind, Romuald Beauvais, Ronny Beer, Francisco Javier Belda, Bo Michael Bellander, Antonio Belli, Rémy Bellier, Habib Benali, Thierry Benard, Maurizio Berardino, Luigi Beretta, Christopher Beynon, Federico Bilotta, Harald Binder, Erta Biqiri, Morten Blaabjerg, Hugo den Boogert, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Lozano Guillermo Carbayo, Marco Carbonara, Elsa Carise, K. Carpenter, Ana M. Castaño León, Francesco Causin, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Maryse Cnossen, Mark Coburn, Jonathan Coles, Lizzie Coles-Kemp, Johnny Collett, Jamie D. Cooper, Marta Correia, Amra Covic, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot Fizelier, François Damas, Pierre Damas, Helen Dawes, Véronique De Keyser, Francesco Della Corte, Bart Depreitere, Godard C.W. de Ruiter, Dula Dilvesi, Shenghao Ding, Diederik Dippel, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy Loup Dulière, Heiko Engemann, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Junfeng Feng, Kelly Foks, Francesca Fossi, Gilles Francony, Ulderico Freo, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Karin Geleijns, Pradeep George, Alexandre Ghuysen, Lelde Giga, Benoit Giraud, Ben Glocker, Jagos Golubovic, Pedro A. Gomez, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Asta Kristine Håberg, Bram Jacobs, Iain Haitsma, Jed A. Hartings, Raimund Helbok, Eirik Helseth, Daniel Hertle, Astrid Hoedemaekers, Stefan Hoefer, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Stefan Jankowski, Mike Jarrett, Bojan Jelaca, Ji yao Jiang, Kelly Jones, Konstantinos Kamnitsas, Mladen Karan, Ari Katila, Maija Kaukonen, Thomas Kerforne, Riku Kivisaari, Angelos G. Kolias, Bálint Kolumbán, Erwin Kompanje, Ksenija Kolundzija, Daniel Kondziella, Lars Owe Koskinen, Noémi Kovács, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Christian Ledig, Rolf Lefering, Valerie Legrand, Jin Lei, Leon Levi, Roger Lightfoot, Hester Lingsma, Dirk Loeckx, Angels Lozano, Andrew I.R. Maas, Stephen MacDonald, Marc Maegele, Majdan Marek, Sebastian Major, Alex Manara, Geoffrey Manley, Didier Martin, Leon Francisco Martin, Costanza Martino, Hugues Maréchal, Armando Maruenda, Alessandro Masala, Julia Mattern, Charles McFadyen, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Cristina Morganti Kossmann, Davide Mulazzi, Holger Mühlan, Visakh Muraleedharan, Lynnette Murray, Nandesh Nair, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, Quentin Noirhomme, József Nyirádi, Mauro Oddo, Annemarie Oldenbeuving, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Adriana Patruno, Jean François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Floury Sébastien Pili, Matti Pirinen, Horia Ples, Maria Antonia Poca, Suzanne Polinder, Inigo Pomposo, Jussi Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Ruben Real, Veronika Rehorčíková, Jonathan Rhodes, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Gerwin Roks, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Marco Sacchi, Barbara Sahakian, Juan Sahuquillo, Oliver Sakowitz, Francesca Sala, Renan Sanchez Porras, Janos Sandor, Edgar Santos, Luminita Sasu, Davide Savo, Nadine Schäffer, Inger Schipper, Barbara Schlößer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Michael Schöll, Charlie Sewalt, Özcan Sir, Toril Skandsen, Lidwien Smakman, Dirk Smeets, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Nicole Steinbüchel, Ana Stevanovic, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Anneliese Synnot, Fabio Silvio Taccone, Riikka Takala, Viktória Tamás, Päivi Tanskanen, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Ralph Telgmann, Guido Teodorani, Alice Theadom, Matt Thomas, Dick Tibboel, Christos Tolias, Jean Flory Luaba Tshibanda, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Gregory Van der Steen, Mathieu van der Jagt, JV de Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Julia Van Waesberghe, Audrey Vanhaudenhuyse, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Giacinta Vizzino, Carmen Vleggeert Lankamp, Victor Volovici, Daphne Voormolen, Peter Vulekovic, Zoltán Vámos, Derick Wade, Kevin K.W. Wang, Lei Wang, Lars Wessels, Eveline Wiegers, Eno Wildschut, Guy Williams, Lindsay Wilson, Maren K.L. Winkler, Stefan Wolf, Peter Ylén, Alexander Younsi, Menashe Zaaroor, Frederik Zeiler, Yang Zhihui, Agate Ziverte, Fabrizio Zumbo, Huie, J Russell, Mondello, Stefania, Lindsell, Christopher J, Antiga, Luca, Yuh, Esther L, Zanier, Elisa R, Masson, Serge, Rosario, Bedda L, Ferguson, Adam R (Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Participants and Investigators), Beretta, Luigi, Huie, J, Mondello, S, Lindsell, C, Antiga, L, Yuh, E, Zanier, E, Masson, S, Rosario, B, Ferguson, A, Citerio, G, and Molecular Neuroscience and Ageing Research (MOLAR)

Subjects
Traumatic, 030506 rehabilitation, Data Interpretation, Data management, data sharing, TERMINAL HYDROLASE-L1, Big data, Poison control, 0302 clinical medicine, Brain Injuries, Traumatic, TBI, Medicine, Biomarker discovery, Common Data Elements, traumatic brain injury, Injuries and accidents, Statistical, Reference Standards, NET RECLASSIFICATION INDEX, Data Interpretation, Statistical, Biomarker (medicine), biomarker, 0305 other medical science, Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators, CT, The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators, medicine.medical_specialty, Physical Injury - Accidents and Adverse Effects, Clinical Sciences, Context (language use), Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], Traumatic Brain Injury (TBI), Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Participants and Investigators, 03 medical and health sciences, MICROARRAY, Special Section: Statistical Methods in Tbi Research, Humans, biomarkers, Intensive care medicine, Traumatic Head and Spine Injury, Neurology & Neurosurgery, business.industry, Information Dissemination, OUTCOME PREDICTION, Neurosciences, COMMON DATA ELEMENTS, Precision medicine, Brain Disorders, DIFFUSE AXONAL INJURY, Data sharing, Good Health and Well Being, Brain Injuries, DISCOVERY, TRACK, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Contains fulltext : 238746.pdf (Publisher’s version ) (Closed access) Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.

Published
2021

12. Pathological Computed Tomography Features Associated with Adverse Outcomes after Mild Traumatic Brain Injury

Author

Esther L. Yuh, Sonia Jain, Xiaoying Sun, Dana Pisicǎ, Mark H. Harris, Sabrina R. Taylor, Amy J. Markowitz, Pratik Mukherjee, Jan Verheyden, Joseph T. Giacino, Harvey S. Levin, Michael McCrea, Murray B. Stein, Nancy R. Temkin, Ramon Diaz-Arrastia, Claudia S. Robertson, H.F. (Hester) Lingsma, David O. Okonkwo, Andrew I.R. Maas, Geoffrey T. Manley, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, C. Dirk Keene, Joel Kramer, Natalie Kreitzer, Chris Lindsell, Joan MacHamer, Christopher Madden, Alastair Martin, Thomas McAllister, Randall Merchant, Lindsay Nelson, Laura B. Ngwenya, Florence Noel, Amber Nolan, Eva Palacios, Daniel Perl, Miri Rabinowitz, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Arthur W. Toga, Alex Valadka, Mary Vassar, Ross Zafonte, Esther L. Yuh, Sonia Jain, Xiaoying Sun, Dana Pisicǎ, Mark H. Harris, Sabrina R. Taylor, Amy J. Markowitz, Pratik Mukherjee, Jan Verheyden, Joseph T. Giacino, Harvey S. Levin, Michael McCrea, Murray B. Stein, Nancy R. Temkin, Ramon Diaz-Arrastia, Claudia S. Robertson, H.F. (Hester) Lingsma, David O. Okonkwo, Andrew I.R. Maas, Geoffrey T. Manley, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, John D. Corrigan, Karen Crawford, Sureyya Dikmen, Ann Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, C. Dirk Keene, Joel Kramer, Natalie Kreitzer, Chris Lindsell, Joan MacHamer, Christopher Madden, Alastair Martin, Thomas McAllister, Randall Merchant, Lindsay Nelson, Laura B. Ngwenya, Florence Noel, Amber Nolan, Eva Palacios, Daniel Perl, Miri Rabinowitz, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Arthur W. Toga, Alex Valadka, Mary Vassar, and Ross Zafonte

Abstract

Importance: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood. Objective: To identify pathological CT features associated with adverse outcomes after mTBI. Design, Setting, and Participants: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021. Exposures: Acute nonpenetrating head trauma. Main Outcomes and Measures: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months. Results: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; int

Published
2021
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13. Smaller Regional Brain Volumes Predict Posttraumatic Stress Disorder at 3 Months after Mild Traumatic Brain Injury

Author

Murray B. Stein, Esther Yuh, Sonia Jain, David O. Okonkwo, Christine L. Mac Donald, Harvey Levin, Joseph T. Giacino, Sureyya Dikmen, Mary J. Vassar, Ramon Diaz-Arrastia, Claudia S. Robertson, Lindsay D. Nelson, Michael McCrea, Xiaoying Sun, Nancy Temkin, Sabrina R. Taylor, Amy J. Markowitz, Geoffrey T. Manley, Pratik Mukherjee, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Jason Barber, Yelena Bodien, M. Ross Bullock, Randall Chesnut, John D. Corrigan, Karen Crawford, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel Gardner, Etienne Gaudette, Dana Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, C. Dirk Keene, Frederick K. Korley, Joel Kramer, Natalie Kreitzer, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair Martin, Thomas McAllister, Randall Merchant, Laura B. Ngwenya, Florence Noel, Amber Nolan, Eva Palacios, Daniel Perl, Ava Puccio, Miri Rabinowitz, Claudia Robertson, Jonathan Rosand, Angelle Sander, Gabriella Satris, David Schnyer, Seth Seabury, Arthur Toga, Alex Valadka, Paul Vespa, Kevin Wang, John K. Yue, and Ross Zafonte

Subjects
Traumatic brain injury, Cognitive Neuroscience, Hippocampus, behavioral disciplines and activities, Amygdala, 050105 experimental psychology, Article, Stress Disorders, Post-Traumatic, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Biological Psychiatry, Brain Concussion, Cognitive reserve, medicine.diagnostic_test, business.industry, 05 social sciences, Glasgow Coma Scale, Brain, Magnetic resonance imaging, Emergency department, medicine.disease, medicine.anatomical_structure, Anesthesia, Neurology (clinical), business, Insula, 030217 neurology & neurosurgery
Abstract

Background Brain volumes in regions such as the hippocampus and amygdala have been associated with risk for the development of posttraumatic stress disorder (PTSD). The objective of this study was to determine whether a set of regional brain volumes, measured by magnetic resonance imaging at 2 weeks following mild traumatic brain injury, were predictive of PTSD at 3 and 6 months after injury. Methods Using data from TRACK-TBI (Transforming Research and Clinical Knowledge in TBI), we included patients (N = 421) with Glasgow Coma Scale scores 13–15 assessed after evaluation in the emergency department and at 2 weeks, 3 months, and 6 months after injury. Probable PTSD diagnosis (PTSD Checklist for DSM-5 score, ≥33) was the outcome. FreeSurfer 6.0 was used to perform volumetric analysis of three-dimensional T1-weighted magnetic resonance images at 3T obtained 2 weeks post injury. Brain regions selected a priori for volumetric analyses were insula, hippocampus, amygdala, superior frontal cortex, rostral and caudal anterior cingulate, and lateral and medial orbitofrontal cortices. Results Overall, 77 (18.3%) and 70 (16.6%) patients had probable PTSD at 3 and 6 months. A composite volume derived as the first principal component incorporating 73.8% of the variance in insula, superior frontal cortex, and rostral and caudal cingulate contributed to the prediction of 3-month (but not 6-month) PTSD in multivariable models incorporating other established risk factors. Conclusions Results, while needing replication, provide support for a brain reserve hypothesis of PTSD and proof of principle for how prediction of at-risk individuals might be accomplished to enhance prognostic accuracy and enrich clinical prevention trials for individuals at the highest risk of PTSD following mild traumatic brain injury.

Published
2020

14. Risk of Posttraumatic Stress Disorder and Major Depression in Civilian Patients After Mild Traumatic Brain Injury: A TRACK-TBI Study

Author

Murray B, Stein, Sonia, Jain, Joseph T, Giacino, Harvey, Levin, Sureyya, Dikmen, Lindsay D, Nelson, Mary J, Vassar, David O, Okonkwo, Ramon, Diaz-Arrastia, Claudia S, Robertson, Pratik, Mukherjee, Michael, McCrea, Christine L, Mac Donald, John K, Yue, Esther, Yuh, Xiaoying, Sun, Laura, Campbell-Sills, Nancy, Temkin, Geoffrey T, Manley, Opeolu, Adeoye, Neeraj, Badjatia, Kim, Boase, Yelena, Bodien, M Ross, Bullock, Randall, Chesnut, John D, Corrigan, Karen, Crawford, Ann-Christine, Duhaime, Richard, Ellenbogen, V Ramana, Feeser, Adam, Ferguson, Brandon, Foreman, Raquel, Gardner, Etienne, Gaudette, Luis, Gonzalez, Shankar, Gopinath, Rao, Gullapalli, J Claude, Hemphill, Gillian, Hotz, Frederick, Korley, Joel, Kramer, Natalie, Kreitzer, Chris, Lindsell, Joan, Machamer, Christopher, Madden, Alastair, Martin, Thomas, McAllister, Randall, Merchant, Florence, Noel, Eva, Palacios, Daniel, Perl, Ava, Puccio, Miri, Rabinowitz, Jonathan, Rosand, Angelle, Sander, Gabriela, Satris, David, Schnyer, Seth, Seabury, Mark, Sherer, Sabrina, Taylor, Arthur, Toga, Alex, Valadka, Paul, Vespa, Kevin, Wang, and Ross, Zafonte

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Traumatic brain injury, Comorbidity, behavioral disciplines and activities, Stress Disorders, Post-Traumatic, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Risk Factors, mental disorders, Brain Injuries, Traumatic, Prevalence, Medicine, Humans, Glasgow Coma Scale, Longitudinal Studies, Prospective Studies, Young adult, Psychiatry, Prospective cohort study, Depression (differential diagnoses), Original Investigation, Depressive Disorder, Major, business.industry, Emergency department, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Case-Control Studies, Major depressive disorder, Female, business, Emergency Service, Hospital, 030217 neurology & neurosurgery
Abstract

IMPORTANCE: Traumatic brain injury (TBI) has been associated with adverse mental health outcomes, such as posttraumatic stress disorder (PTSD) and major depressive disorder (MDD), but little is known about factors that modify risk for these psychiatric sequelae, particularly in the civilian sector. OBJECTIVE: To ascertain prevalence of and risk factors for PTSD and MDD among patients evaluated in the emergency department for mild TBI (mTBI). DESIGN, SETTING, AND PARTICIPANTS: Prospective longitudinal cohort study (February 2014 to May 2018). Posttraumatic stress disorder and MDD symptoms were assessed using the PTSD Checklist for DSM-5 and the Patient Health Questionnaire-9 Item. Risk factors evaluated included preinjury and injury characteristics. Propensity score weights-adjusted multivariable logistic regression models were performed to assess associations with PTSD and MDD. A total of 1155 patients with mTBI (Glasgow Coma Scale score, 13-15) and 230 patients with nonhead orthopedic trauma injuries 17 years and older seen in 11 US hospitals with level 1 trauma centers were included in this study. MAIN OUTCOMES AND MEASURES: Probable PTSD (PTSD Checklist for DSM-5 score, ≥33) and MDD (Patient Health Questionnaire-9 Item score, ≥15) at 3, 6, and 12 months postinjury. RESULTS: Participants were 1155 patients (752 men [65.1%]; mean [SD] age, 40.5 [17.2] years) with mTBI and 230 patients (155 men [67.4%]; mean [SD] age, 40.4 [15.6] years) with nonhead orthopedic trauma injuries. Weights-adjusted prevalence of PTSD and/or MDD in the mTBI vs orthopedic trauma comparison groups at 3 months was 20.0% (SE, 1.4%) vs 8.7% (SE, 2.2%) (P

Published
2019

15. Medical Care Spending and Labor Market Outcomes: Evidence from Workers’ Compensation Reforms*

Author

Seth Seabury and David Powell

Subjects
Health Care Reform, Insurance, Disability, Back Injuries, Humans, Workers' Compensation, Health Expenditures, health care economics and organizations, Article, California, Forecasting
Abstract

Medical care represents an important component of workers' compensation benefits with the potential to improve health and post-injury labor outcomes, but little is known about the relationship between medical care spending and the labor outcomes of injured workers. We exploit the 2003--2004 California workers' compensation reforms which reduced medical spending disproportionately for workers incurring low back injuries. We link administrative claims data to earnings records for injured workers and their uninjured coworkers. We find that workers with low back injuries experienced a 7.6 percent post-reform decline in medical care, and an 8.1 percent drop in post-injury earnings relative to other injured workers.

Published
2018

16. Quality of Care and Patient-reported Outcomes in Carpal Tunnel Syndrome: A Prospective Observational Study

Author

Teryl K, Nuckols, Craig, Conlon, Michael, Robbins, Michael, Dworsky, Julie, Lai, Carol P, Roth, Barbara, Levitan, Seth, Seabury, Rachana, Seelam, Douglas, Benner, and Steven M, Asch

Subjects
Adult, Male, Middle Aged, Health Surveys, Carpal Tunnel Syndrome, Article, Patient Satisfaction, Surveys and Questionnaires, Humans, Female, Patient Reported Outcome Measures, Prospective Studies, Aged, Quality of Health Care
Abstract

Higher quality care for carpal tunnel syndrome (CTS) may be associated with better outcomes.This prospective observational study recruited adults diagnosed with CTS from 30 occupational health centers, evaluated physicians' adherence to recommended care processes, and assessed results of the Boston Carpal Tunnel Questionnaire (BCTQ) and Short Form Health Survey version 2 (SF-12v2) at recruitment and at 18 months.Among 343 individuals, receiving better care (80th vs. 20th percentile for adherence) was associated with greater improvements in BCTQ Symptom Severity scores (-0.18, 95% confidence interval [CI] -0.32 to -0.05), BCTQ Functional Status scores (-0.21, 95% CI -0.34 to -0.08), and SF12-v2 Physical Component scores (1.75, 95% CI 0.33-3.16). Symptoms improved more when physicians assessed and managed activity, patients underwent necessary surgery, and employers adjusted job tasks.Efforts should be made to ensure that patients with CTS receive essential care processes including necessary surgery and activity assessment and management. Muscle Nerve 57: 896-904, 2018.

Published
2018

17. The option value of innovative treatments for non-small cell lung cancer and renal cell carcinoma

Author

Julia, Thornton Snider, Katharine, Batt, Yanyu, Wu, Mahlet Gizaw, Tebeka, and Seth, Seabury

Subjects
Male, Lung Neoplasms, Cost-Benefit Analysis, Antibodies, Monoclonal, Antineoplastic Agents, Middle Aged, Survival Analysis, Kidney Neoplasms, Life Expectancy, Nivolumab, Carcinoma, Non-Small-Cell Lung, Humans, Female, Neoplasm Metastasis, Carcinoma, Renal Cell, Aged, SEER Program
Abstract

To develop a model of the option value a therapy provides by enabling patients to live to see subsequent innovations and to apply the model to the case of nivolumab in renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC).A model of the option value of nivolumab in RCC and NSCLC was developed and estimated.Data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry and published clinical trial results were used to estimate survival curves for metastatic cancer patients with RCC, squamous NSCLC, or nonsquamous NSCLC. To estimate the conventional value of nivolumab, survival with the pre-nivolumab standard of care was compared with survival with nivolumab assuming no future innovation. To estimate the option value of nivolumab, long-term survival trends in RCC and squamous and nonsquamous NSCLC were measured in SEER to forecast mortality improvements that nivolumab patients may live to see.Compared with the previous standard of care, nivolumab extended life expectancy by 6.3 months in RCC, 7.5 months in squamous NSCLC, and 4.5 months in nonsquamous NSCLC, according to conventional methods. Accounting for expected future mortality trends, nivolumab patients are likely to gain an additional 1.2 months in RCC, 0.4 months in squamous NSCLC, and 0.5 months in nonsquamous NSCLC. These option values correspond to 18%, 5%, and 10% of the conventional value of nivolumab, respectively.Option value is important when valuing therapies like nivolumab that extend life in a rapidly evolving area of care.

Published
2017

19. Impact of type 2 diabetes medication cost sharing on patient outcomes and health plan costs

Author

Julia, Thornton Snider, Seth, Seabury, Janice, Lopez, Scott, McKenzie, and Dana P, Goldman

Subjects
Adult, Male, Insurance, Health, Databases, Factual, Health Care Costs, Middle Aged, Insurance, Pharmaceutical Services, Drug Costs, United States, Cohort Studies, Hospitalization, Insurance Claim Review, Diabetes Mellitus, Type 2, Linear Models, Humans, Female, Cost Sharing, Aged, Retrospective Studies
Abstract

To study the association between cost sharing for diabetes medications, adherence, hospitalization rates, and healthcare costs, with relationship to patient risk.A retrospective claims analysis of data from 35 large, private, self-insured employers (2004 to 2012).We examined outcomes for 92,410 patients aged 18 to 64 years with a type 2 diabetes (T2D) diagnosis who filled at least 1 T2D prescription. First, we examined the relationship between adherence, measured as the proportion of days covered, and cost sharing, measured as the out-of-pocket cost to purchase a pre-specified bundle of T2D prescriptions. We then examined the association between adherence and hospital days. Simulations showed the effect of increased cost sharing on adherence and inpatient utilization.A $10 increase in out-of-pocket cost was associated with a 1.9% reduction in adherence (P.01). In turn, a 10% reduction in adherence was associated with a 15% increase in per-patient hospital days (0.17 days; P.01). For the average plan, switching from low to high cost sharing reduced per-patient medication costs by $242 and increased per-patient hospitalization costs by $342, for a net increase of $100 in plan costs. Increases in per-patient costs were greater for high-risk patients, such as those with heart failure ($1328).Increased cost sharing for T2D medication was associated with reductions in pharmacy costs, but higher total costs for patients with T2D. This problem is particularly acute for patients with 1 or more cardiovascular comorbidities. The results suggest that increased diabetes cost sharing may hamper efforts to lower the total cost of diabetes care.

Published
2016

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