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• Recovered and the patient returned to baseline status • Recovered with permanent sequelae • Symptoms persist 10.2.3 Time Period for Adverse Events Adverse events will be recorded from the time of randomization and will continue through 28 days after randomization, hospital discharge, or death, whichever occurs earlie...
protocol.txt
bfc71952-593d-4fc3-8aca-4a15452dadb8
events will not be recorded for subjects who are in the observational cohorts, since there is no study intervention nor randomization event. 10.2.4 Data Collection Procedures for Adverse Events Subjects who have been randomized to study drug will undergo daily screening for adverse events from the first day of study dr...
protocol.txt
f9e4412b-a281-4e51-9337-370eff5a782f
discharge, or death, whichever happens first. This screening will include review of all vital signs, all clinically-ordered laboratory data and imaging studies, physical exam findings (as documented in the medical record by the clinical team), and clinical progress and procedure notes since the time of the prior day’s ...
protocol.txt
3bd95b6e-4266-4a77-b390-e84e5081a9f4
that documents clinical, laboratory, and radiographic abnormalities that are present prior to the start of study drug. Any medical condition or laboratory abnormality that is present prior to randomization, which remains unchanged or improves (unless the clinician feels it is clinically relevant), will not be recorded ...
protocol.txt
6f52e725-ab25-4933-8018-48600ed4c025
ing of a medical condition that was present at the time of randomization will be considered a new adverse event and reported. After patient randomization all adverse events (including serious adverse events) will be recorded according to relatedness, severity, and expectedness, as well as their duration and
protocol.txt
d06e1ab7-d5e9-4570-9e5f-ea63c224dd37
any treatment prescribed. Abnormal laboratory values that are clinically significant will be recorded as adverse events and the site investigator will assess the relationship to the study and expectedness. Adverse events will be coded using the MedDRA coding vocabulary. Coding will be done centrally at the Data Coordin...
protocol.txt
762aabd7-7a95-4053-9029-629d20f56e5b
Common Terminology for Criteria for Adverse Events (CTCAE) scoring system. PRECISE Protocol Version 1.07 Protocol Version Date: June 16, 2023 The Collaborative Pediatric Critical Care Research NetworkProtocol 90 (Hall, Zuppa and Mourani) Page 61 of 76 10.2.5 Unanticipated Problems (UP) Unanticipated problems (UP) are d...
protocol.txt
fd6561f9-e268-486b-8937-b0c6820da96d
pected, related or possibly related to participation in the study, and suggest that the research places subjects at a greater risk of harm than was previously known or recognized. The site investigator will report unanticipated problems to the Data Coordinating Center within 24 hours of becoming aware of the event. A d...
protocol.txt
2c5e9c16-ecad-4121-ad18-8ca14b85b900
Data Coordinating Center within 3 working days of the event. After receipt of the complete report, the Data Coordinating Center will report these unanticipated problems to the NICHD Project Officer in an expedited manner (as close to 24 hours as possible). The medical monitor (Section 10.2.6) for the study will assess ...
protocol.txt
02693a57-9fc9-4d4f-aab9-5a471bed36c0
acting as the single IRB for the study, may be required. In addition, dependent on the nature of the unanticipated problem, all participating institutions may require notification. In the event that the medical monitor believes that such an event warrants emergent suspension of enrollment in the trial, and NICHD staff ...
protocol.txt
60592feb-39b2-48aa-8993-38902117c328
will notify the study investigators (Drs. Hall, Zuppa and Mourani) and all site investigators to cease enrollment in the trial. Resumption of enrollment will not occur without consent of the NICHD staff after discussion with the DSMB. 10.2.6 Monitoring Serious Adverse Events A qualified physician will be designated to ...
protocol.txt
3eabc37d-7918-4960-9937-516eba126c6c
study. Site investigators and/or research coordinators will report serious adverse events to the Data Coordinating Center within 24 hours of becoming aware of the event. A detailed completed report will be required to be sent to the Data Coordinating Center within 3 working days of the event, and the medical monitor wi...
protocol.txt
b23602ac-bea6-4124-9e33-2864a2e4239c
For each of these serious adverse events, the site investigator will provide sufficient medical history and clinical details for a safety assessment to be made with regard to continuation of the trial. The medical monitor will sign off on each SAE report after review. All SAE reports will be retained at the Data Coordi...
protocol.txt
19e1994d-40c2-4f95-9290-ac31d5a1135e
DSMB members and NICHD staff. The SAE reporting process may be incorporated into the Electronic Data Capture (EDC) System in use for the study. In the unlikely event that the medical monitor believes an unexpected and study-related SAE warrants emergent cessation of enrollment in the trial, NICHD staff and the DSMB cha...
protocol.txt
9e34edf5-dff3-478c-b07d-1c532b7d016e
will be immediately consulted. If these individuals concur with the judgment of the medical monitor, or if the NICHD staff and the DSMB chairperson cannot be reached expeditiously, the PRECISE Protocol Version 1.07 Protocol Version Date: June 16, 2023 The Collaborative Pediatric Critical Care Research NetworkPage 62 of...
protocol.txt
796fb092-cb7f-4f35-9a98-22f421ba53de
Data Coordinating Center will notify the study investigators (Drs. Hall, Zuppa and Mourani) and all site investigators to cease enrollment in the trial. Resumption of enrollment will not occur without consent of the NICHD staff after discussion with the DSMB. The IRB in Utah will be notified, and each site investigator...
protocol.txt
b1131a35-e373-46e9-9381-cb5de6f71897
program of the trial suspension. Criteria for halting enrollment in the TRIPS trial pending a formal safety review include: • The death of a randomized subject in whom the cause of death is judged to be probably or definitely related to the study drug. • The occurrence, in any subject, of a life-threatening SAE whose c...
protocol.txt
606b9d0d-6053-4865-b3f8-47470220eb37
• Two (2) occurrences of Grade 3 or higher toxicities that are judged to be probably or definitely related to the study drug. • Two (2) occurrences of a clinically significant Grade 3 or higher laboratory abnormality that are judged to be probably or definitely related to study drug. After notification of the NICHD Pro...
protocol.txt
9b55c060-7ece-4427-9689-7e01954c034d
son, of serious, unexpected, and study-related adverse events or unanticipated problems (UP), decisions will be made whether to continue the study without change, and whether to convene the entire DSMB for an emergent meeting. If a decision is made to suspend enrollment in the trial, this will be reported to the study ...
protocol.txt
39398f19-d813-4b11-8306-8b5fbe3d7362
clinical investigators, who will be instructed to report this to their local IRB. The DSMB will review all adverse events (not necessarily serious, unexpected, and study- related) during scheduled DSMB meetings which will occur at least twice annually. The Data Coordinating Center will prepare a Summary Report of Adver...
protocol.txt
decb55c7-dbd8-49b8-97c5-c2833a928338
DRA coding system, for the DSMB meetings, including the proportion of subjects experiencing treatment-emergent adverse events. The occurrence of any adverse event will be considered as a dichotomous outcome and compared between arms using a chi-squared test. Cumulative data on treatment-emergent adverse events will be ...
protocol.txt
dcddf2cf-fc2a-496f-a7dd-102b725a867f
manuscript at the conclusion of the trial. 10.2.7 Individual Subject Stopping Rules for TRIPS Trial The administration of study drug will be discontinued in individual subjects if they develop: PRECISE Protocol Version 1.07 Protocol Version Date: June 16, 2023 The Collaborative Pediatric Critical Care Research NetworkP...
protocol.txt
0fe20597-a704-4d14-9b72-f90050109c5c
• A new, unexpected, serious adverse event that is determined to be probably related to study drug. • A new reduction in absolute neutrophil count to <1,000 cells/mm3 on two consecutive days while receiving study drug. 10.2.8 Follow-up of Serious, Unexpected and Related Adverse Events All serious, unexpected and relate...
protocol.txt
97094798-e3bc-4adf-ba8d-1228b53ee52f
patient’s termination from the study or discharge from the hospital, will be followed by the site investigators until the events are resolved, subject is lost to follow-up, the adverse event is otherwise explained or has stabilized, and continuity of care with a responsible clinical team has been assured. 10.2.9 Report...
protocol.txt
0155bf60-809f-44d4-9684-afa5ba7eda1d
Serious, unexpected and related adverse events will be reported to the FDA in an expedited manner consistent with FDA requirements. The Data Coordinating Center will prepare the report for submission by the principal investigator, Dr. Hall, who holds the IND. 11 Study Training A formal training program for investigator...
protocol.txt
01db6da4-68e3-443a-b7f1-9402867daf0c
of enrollment. The training program will cover regulatory topics and Good Clinical Practice. The training will also provide in depth explanations regarding study procedures, clinical care, adverse event reporting, data entry procedures, quality assurance, site monitoring, and the informed consent process. No site will ...
protocol.txt
185d5f47-7c10-4165-96b8-21ab583d3133
fulfilled by the site investigators and research staff. A manual of operations will be provided to each investigator prior to the start of enrollment. The manual will detail specific information about the study procedures, regulatory informa- tion, safety reporting, and other necessary information. Updates and revision...
protocol.txt
cdbf002f-9845-4c18-acd9-e08737ddaf97
will be made available electronically. The Data Coordinating Center, in collaboration with the study investigators (Drs. Hall, Zuppa and Mourani), will be the main contact for study questions. Each participating clinical site that has not previously participated in CPCCRN studies using the TNFαresponse assay will under...
protocol.txt
43b2cbbf-efeb-42e5-bd02-7bce8ceb69ba
familiarity with clinical and laboratory procedures required for immune phenotyping. In the PRECISE Protocol Version 1.07 Protocol Version Date: June 16, 2023 The Collaborative Pediatric Critical Care Research NetworkPage 64 of 76 Protocol 90 (Hall, Zuppa and Mourani) event that this is not possible (e.g., due to COVID...
protocol.txt
9d050378-3e1a-4ac2-ab0f-1dd4ea1a4f57
virtually, including video documentation of pharmacy and laboratory capabilities. 12 Regulatory Considerations 12.1 Food and Drug Administration This trial is being conducted under an Investigational New Drug application approved by the Food and Drug Administration. The clinical investigator at each participating site ...
protocol.txt
73bdf767-2c59-4c82-b513-804a582e38b6
12.2 Health Insurance Portability and Accountability Act Data elements collected include the date of birth and date of admission. Prior to statistical analyses, dates will be used to calculate patient age at the time of the study events. Data elements for race, ethnicity, and gender are also being collected. These demo...
protocol.txt
2cac3de6-5723-4669-9402-f411ac97d596
data are required for Federal reporting purposes to delineate subject accrual by race, ethnicity, and gender. For purposes of the DCC handling potential protected health information (PHI) and pro- ducing the de–identified research data sets that will be used for analyses, all study sites have been offered a Business As...
protocol.txt
e12a6877-3a90-4088-9ffe-063c707bc66c
Business Associate Agreements are maintained at the DCC. 12.3 Inclusion of Women and Minorities There will be no exclusion of patients based on gender, race, or ethnicity. 12.4 Clinical Trial Registration Requirements The GRACE-2 and TRIPS trials will be separately registered at https://clinicaltrials. gov in accordanc...
protocol.txt
8a05e0a3-7e33-427e-a1bd-2bb4b33986ad
For federally funded studies subject to the Common Rule, records relating to the research conducted shall be retained for at least 3 years after completion of the research. Completion of PRECISE Protocol Version 1.07 Protocol Version Date: June 16, 2023 The Collaborative Pediatric Critical Care Research NetworkProtocol...
protocol.txt
68531e6a-c296-4d7f-969b-020e822220cd
the research for this protocol should be anticipated to include planned primary and secondary analyses, as well as subsequent derivative analyses. Completion of the research also entails completion of all publications relating to the research. All records shall be accessible for inspection and copying by authorized rep...
protocol.txt
23987f41-aa73-48bc-b3db-91abe40125f8
times and in a reasonable manner [45 CFR §46.115(b)]. 12.6 Public Use Data Set After subject enrollment and follow up have been completed, the DCC will prepare a final study database for analysis. A releasable database will be produced and completely de-identified in accordance with the definitions provided in the Heal...
protocol.txt
e4264574-5593-454e-8ff4-b462a6b2e31c
Act (HIPAA). Namely, all identifiers specified in HIPAA will be recoded in a manner that will make it impossible to deduce or impute the specific identity of any patient. The database will not contain any institutional identifiers. The DCC will also prepare a data dictionary that provides a concise definition of every ...
protocol.txt
b3142ee8-5407-4cc0-b27a-64bd4f28f6b4
element included in the database. If specific data elements have idiosyncrasies that might affect interpretation or analysis, this will be discussed in the dictionary document. In accordance with policies determined by the investigators and funding sponsors, the releasable database will be provided to users in electron...
protocol.txt
63072572-fa9b-4bb0-9549-a256d0d22d8e
[1] E. Abraham, A. Anzueto, G. Gutierrez, S. Tessler, G. San Pedro, R. Wunderink, A. Dal Nogare, S. Nasraway, S. Berman, R. Cooney, H. Levy, R. Baughman, M. Rumbak, R. B. Light, L. Poole, R. Allred, J. Constant, J. Pennington, and S. Porter. Double-blind randomised controlled trial of monoclonal antibody to human tumou...
protocol.txt
505e4efc-dce8-4e6d-ad41-4b35da2784f4
treatment of septic shock. NORASEPT II Study Group. Lancet, 351(9107):929–33, 1998. [2] E. Abraham, M. P. Glauser, T. Butler, J. Garbino, D. Gelmont, P. F. Laterre, K. Kudsk, H. A. Bruining, C. Otto, E. Tobin, C. Zwingelstein, W. Lesslauer, and A. Leighton. p55 Tumor necrosis factor receptor fusion protein in the treat...
protocol.txt
ce482106-effc-43d3-a33f-f0a3273c9bf1
and septic shock. a randomized controlled multicenter trial. Ro 45-2081 Study Group. JAMA, 277(19):1531–8, 1997. PRECISE Protocol Version 1.07 Protocol Version Date: June 16, 2023 The Collaborative Pediatric Critical Care Research NetworkPage 66 of 76 Protocol 90 (Hall, Zuppa and Mourani) [3] C. E. Allen, X. Yu, C. A. ...
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6b908ddb-1d94-4ab7-991b-c4f4beab127c
the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer, 50(6):1227– 35, 2008. [4] F. Barkas, S. F. Ntekouan, M. Kosmidou, E. Liberopoulos, A. Liontos, and H. Milio- nis. Anakinra in hospitalized non-intubated patients with Coronavirus Disease 2019: a systematic review and meta-analysis. Rheumatology ...
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b215fcbc-04cf-4af2-b4c7-f7b26d9400a0
[5] J. Borgermann, I. Friedrich, R. Scheubel, O. Kuss, S. Lendemans, R. E. Silber, E. Kreuzfelder, and S. Flohe. Granulocyte-macrophage colony-stimulating factor (GM- CSF) restores decreased monocyte HLA-DR expression after cardiopulmonary bypass. Thorac Cardiovasc Surg, 55(1):24–31, 2007. [6] D. S. Bundschuh, J. Barsi...
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16475512-7b69-4062-8088-bc845c0af38c
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[8] J. A. Carcillo, R. A. Berg, D. Wessel, M. Pollack, K. Meert, M. Hall, C. Newth, J. C. Lin, A. Doctor, T. Shanley, T. Cornell, R. E. Harrison, A. F. Zuppa, R. W. Reeder, R. Banks, J. A. Kellum, R. Holubkov, D. A. Notterman, J. M. Dean, H. Eunice Kennedy Shriver National Institute of Child, and N. Human Development C...
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e8ad0bcb-9565-4e16-9113-d057d9ce40e4
Care Research. A multicenter network assessment of three inflammation phenotypes in pediatric sepsis-induced multiple organ failure. Pediatr Crit Care Med, 20(12):1137–1146, December 2019. [9] J. A. Carcillo, E. S. Halstead, M. W. Hall, T. C. Nguyen, R. Reeder, R. Aneja, B. Shakoory, D. Simon, H. Eunice Kennedy Shriver...
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5aa7996e-1a40-48f0-8c03-49766e0c2cff
velopment Collaborative Pediatric Critical Care Research Network. Three hypothetical inflammation pathobiology phenotypes and pediatric sepsis-induced multiple organ failure outcome. Pediatr Crit Care Med, 18(6):513–523, 2017. [10] J. A. Carcillo, K. K. Kernan, C. M. Horvat, D. W. Simon, and R. K. Aneja. Why and how
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029fa367-6f5a-4a26-8249-b332e1a6bd03
is hyperferritinemic sepsis different from sepsis without hyperferritinemia? Pediatr Crit Care Med, 21(5):509–512, 2020. [11] G. Cavalli, G. De Luca, C. Campochiaro, E. Della-Torre, M. Ripa, D. Canetti, C. Oltolini, B. Castiglioni, C. Tassan Din, N. Boffini, A. Tomelleri, N. Farina, A. Ruggeri, P. Rovere- Querini, G. D...
protocol.txt
5eeafd02-2e1d-4cf8-ad7b-d269333565b2
PRECISE Protocol Version 1.07 Protocol Version Date: June 16, 2023 The Collaborative Pediatric Critical Care Research NetworkProtocol 90 (Hall, Zuppa and Mourani) Page 67 of 76 A. Zangrillo, P. Scarpellini, and L. Dagna. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distres...
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240a5510-e782-4490-8810-008740d20f6f
a retrospective cohort study. Lancet Rheumatol, 2(6):e325–e331, 2020. [12] G. Cavalli, A. Larcher, A. Tomelleri, C. Campochiaro, E. Della-Torre, G. De Luca, N. Farina, N. Boffini, A. Ruggeri, A. Poli, P. Scarpellini, P. Rovere-Querini, M. Tresoldi, A. Salonia, F. Montorsi, G. Landoni, A. Castagna, F. Ciceri, A. Zangril...
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52d8aece-6878-4779-bc59-81fab8d76716
Interleukin-1 and interleukin-6 inhibition compared with standard management in patients with COVID-19 and hyperinflammation: a cohort study. Lancet Rheumatol, 2021. [13] G. Ceneviva, J. A. Paschall, F. Maffei, and J. A. Carcillo. Hemodynamic support in fluid-refractory pediatric septic shock. Pediatrics, 102(2):e19, 1...
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fca3fd91-e6b9-4395-b8e8-abf40b31507e
[14] J. E. G. Charlesworth, S. Wilson, A. Qureshi, E. Blanco, A. Mitchell, S. Segal, D. Kelly, J. Weitz, D. O’Shea, K. Bailey, and A. Kavirayani. Continuous intravenous anakinra for treating severe secondary haemophagocytic lymphohistiocytosis/macrophage activation syndrome in critically ill children. Pediatr Blood Can...
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ea702ea8-5222-4a6d-bc5b-cdc4f4a44289
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therapy in inflammatory bowel disease. Front Med (Lausanne), 7:8, 2020. [17] E. Della-Torre, M. Lanzillotta, C. Campochiaro, G. Cavalli, G. De Luca, A. Tomelleri, N. Boffini, R. De Lorenzo, A. Ruggeri, P. Rovere-Querini, A. Castagna, G. Landoni, M. Tresoldi, F. Ciceri, A. Zangrillo, and L. Dagna. Respiratory impairment...
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0430d6aa-5e6d-47ab-b0ca-a0624a192be6
response to IL-1 and IL-6 blockade in COVID-19 patients with severe pneumonia and hyper-inflammation. Front Immunol, 12:675678, 2021. [18] K. J. Downes, J. C. Fitzgerald, E. Schriver, C. L. K. Boge, M. E. Russo, S. L. Weiss, F. Balamuth, S. E. Kubis, P. Tolomeo, W. B. Bilker, J. H. Han, E. Lautenbach, S. E. Coffin,
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a98a315f-fc51-4c6b-b15a-191cf7cd9bfc
and J. S. Gerber. Implementation of a pragmatic biomarker-driven algorithm to guide antibiotic use in the pediatric intensive care unit: the Optimizing Antibiotic Strategies in Sepsis (OASIS) II Study. J Pediatric Infect Dis Soc, 9(1):36–43, 2020. [19] H. C. Emsley, C. J. Smith, R. F. Georgiou, A. Vail, S. J. Hopkins, ...
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c5f06516-650f-4eb9-bdd2-9489557ac7eb
Tyrrell, and I. Acute Stroke. A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients. J Neurol Neurosurg Psychiatry, 76(10):1366–72, 2005. PRECISE Protocol Version 1.07 Protocol Version Date: June 16, 2023 The Collaborative Pediatric Critical Care Research NetworkPage 68 of 76 Protoco...
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9f254f6b-f20e-4e14-8c16-730207d4e343
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d93f4f07-918d-47ac-be6e-d7d9c0a4df88
[23] J. Fisher, C. J., J. F. Dhainaut, S. M. Opal, J. P. Pribble, R. A. Balk, G. J. Slotman, T. J. Iberti, E. C. Rackow, M. J. Shapiro, R. L. Greenman, and et al. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. results from a randomized, double-blind, placebo-contr...
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51ce9a44-8386-497b-963e-a59a3e7eea16
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a9d65f51-769f-4a9d-9544-b6e9d9541ec3
[25] S. Flohe, S. Lendemans, C. Selbach, C. Waydhas, M. Ackermann, F. U. Schade, and E. Kreuzfelder. Effect of granulocyte-macrophage colony-stimulating factor on the immune response of circulating monocytes after severe trauma. Crit Care Med, 31(10):2462–9, 2003. [26] M. Franzetti, A. Forastieri, N. Borsa, A. Pandolfo...
protocol.txt
bc8cab57-8193-4445-aca3-eda7f51d0242
G. Evasi, L. Guiotto, M. Erba, U. Pozzetti, A. Ronchetti, L. Valsecchi, G. Castaldo, E. Longoni, D. Colombo, M. Soncini, S. Crespi, S. Maggiolini, D. Guzzon, and S. Piconi. IL-1 receptor antagonist anakinra in the treatment of COVID-19 acute respiratory distress syndrome: A retrospective, observational study. J Immunol...
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29933c22-2ccb-4f9c-87e2-c66435e53e07
[27] J. Galea, K. Ogungbenro, S. Hulme, H. Patel, S. Scarth, M. Hoadley, K. Illingworth, C. J. McMahon, N. Tzerakis, A. T. King, A. Vail, S. J. Hopkins, N. Rothwell, and P. Tyrrell. PRECISE Protocol Version 1.07 Protocol Version Date: June 16, 2023 The Collaborative Pediatric Critical Care Research NetworkProtocol 90 (...
protocol.txt
9b3595be-654f-4388-b754-93381ad31d8a
Reduction of inflammation after administration of interleukin-1 receptor antagonist follow- ing aneurysmal subarachnoid hemorrhage: results of the Subcutaneous Interleukin-1Ra in SAH (SCIL-SAH) study. J Neurosurg, 128(2):515–523, 2018. [28] C. A. Gogos, E. Drosou, H. P. Bassaris, and A. Skoutelis. Pro- versus anti-infl...
protocol.txt
d8fd0f37-87f1-450a-89f5-5e3b6e4c3449
cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis, 181(1):176–80, 2000. [29] R. Goldbach-Mansky, N. J. Dailey, S. W. Canna, A. Gelabert, J. Jones, B. I. Rubin, H. J. Kim, C. Brewer, C. Zalewski, E. Wiggs, S. Hill, M. L. Turner, B. I. Karp, I. Aksentijev...
protocol.txt
5da3c9bc-5fa2-4788-ac8c-4bc1f1fdc3b3
F. Pucino, S. R. Penzak, M. H. Haverkamp, L. Stein, B. S. Adams, T. L. Moore, R. C. Fuhlbrigge, B. Shaham, J. N. Jarvis, K. O’Neil, R. K. Vehe, L. O. Beitz, G. Gardner, W. P. Hannan, R. W. Warren, W. Horn, J. L. Cole, S. M. Paul, P. N. Hawkins, T. H. Pham, C. Snyder, R. A. Wesley, S. C. Hoffmann, S. M. Holland, J. A. B...
protocol.txt
eec86f3b-aea4-4484-8d77-bc5d2421db79
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