title: Therapeutic Drug Monitoring of Corticosteroids/β2-agonists in Hair in Asthmatic Patients: an Open-label Feasibility Study

acronym: CorticHair

summary:
This feasibility study will be open-label with two dose groups: patients receiving budesonide/formoterol Turbuhaler® at a total daily dose [400 to 800 µg[ (group 1) and patients receiving a total daily dose ≥800 µg/day (group 2) to investigate whether there is a relationship between dose and hair concentration.

The objective of this feasibility study is to determine if the product administered to the patient is detectable and quantifiable in hair in order to have a mean to monitor adherence to the treatment. This study does not in any way evaluate the efficacy or safety of the medicinal product, which will be used in accordance with its marketing authorization.

ReferenceCitation: Al-Jahdali H, Ahmed A, Al-Harbi A, Khan M, Baharoon S, Bin Salih S, Halwani R, Al-Muhsen S. Improper inhaler technique is associated with poor asthma control and frequent emergency department visits. Allergy Asthma Clin Immunol. 2013 Mar 6;9(1):8. doi: 10.1186/1710-1492-9-8.

ReferenceCitation: Alonso L, Fuchs E. The hair cycle. J Cell Sci. 2006 Feb 1;119(Pt 3):391-3. doi: 10.1242/jcs.02793. No abstract available.

ReferenceCitation: Alvarez JC, Abe E, Etting I, Le Guen M, Devillier P, Grassin-Delyle S. Quantification of remifentanil and propofol in human plasma: a LC-MS/MS assay validated according to the EMA guideline. Bioanalysis. 2015;7(13):1675-84. doi: 10.4155/bio.15.89.

ReferenceCitation: Alvarez JC, Charbit B, Grassin-Delyle S, Demolis JL, Funck-Brentano C, Abe E. Human plasma quantification of droperidol and ondansetron used in preventing postoperative nausea and vomiting with a LC/ESI/MS/MS method. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Jan 15;879(2):186-90. doi: 10.1016/j.jchromb.2010.12.001. Epub 2010 Dec 16.

ReferenceCitation: Auchus RJ. Steroid assays and endocrinology: best practices for basic scientists. Endocrinology. 2014 Jun;155(6):2049-51. doi: 10.1210/en.2014-7534. No abstract available.

ReferenceCitation: Baxi SM, Greenblatt RM, Bacchetti P, Jin C, French AL, Keller MJ, Augenbraun MH, Gange SJ, Liu C, Mack WJ, Gandhi M; Women's Interagency HIV Study (WIHS). Nevirapine Concentration in Hair Samples Is a Strong Predictor of Virologic Suppression in a Prospective Cohort of HIV-Infected Patients. PLoS One. 2015 Jun 8;10(6):e0129100. doi: 10.1371/journal.pone.0129100. eCollection 2015.

ReferenceCitation: Bevalot F, Gaillard Y, Lhermitte MA, Pepin G. Analysis of corticosteroids in hair by liquid chromatography-electrospray ionization mass spectrometry. J Chromatogr B Biomed Sci Appl. 2000 Apr 14;740(2):227-36. doi: 10.1016/s0378-4347(00)00085-2.

ReferenceCitation: Borges NC, Astigarraga RB, Sverdloff CE, Borges BC, Paiva TR, Galvinas PR, Moreno RA. Budesonide quantification by HPLC coupled to atmospheric pressure photoionization (APPI) tandem mass spectrometry. Application to a comparative systemic bioavailability of two budesonide formulations in healthy volunteers. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Feb 1;879(3-4):236-42. doi: 10.1016/j.jchromb.2010.12.003. Epub 2010 Dec 13.

ReferenceCitation: Buscher BA, Jagfeldt H, Sandman H, Brust-van Schaik R, van Schaik F, Brull LP. The determination of budesonide and fluticasone in human sputum samples collected from COPD patients using LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Jan 1;880(1):6-11. doi: 10.1016/j.jchromb.2011.10.029. Epub 2011 Nov 16.

ReferenceCitation: Capron A, Antunes MV, Wagner SC, Mattevi VS, Vieira N, Leite R, Reginato F, Capra M, Fogliatto L, Wallemacq P, Linden R. First report of imatinib measurement in hair: Method development and preliminary evaluation of the relation between hair and plasma concentrations with therapeutic response in chronic myeloid leukemia. Clin Chim Acta. 2016 Jan 30;453:42-7. doi: 10.1016/j.cca.2015.11.032. Epub 2015 Dec 3.

ReferenceCitation: Chalmers GW, Macleod KJ, Little SA, Thomson LJ, McSharry CP, Thomson NC. Influence of cigarette smoking on inhaled corticosteroid treatment in mild asthma. Thorax. 2002 Mar;57(3):226-30. doi: 10.1136/thorax.57.3.226.

ReferenceCitation: Chèze, M. and Gaulier, J.-M. (2014). Chapter 8 - Drugs Involved in Drug-Facilitated Crimes (DFC): Analytical Aspects: 2-Hair A2 - Kintz, Pascal. Toxicological Aspects of Drug-Facilitated Crimes. Oxford, Academic Press: 181-222.

ReferenceCitation: Choi HI, Choi GI, Kim EK, Choi YJ, Sohn KC, Lee Y, Kim CD, Yoon TJ, Sohn HJ, Han SH, Kim S, Lee JH, Lee YH. Hair greying is associated with active hair growth. Br J Dermatol. 2011 Dec;165(6):1183-9. doi: 10.1111/j.1365-2133.2011.10625.x.

ReferenceCitation: Cirimele V, Kintz P, Dumestre V, Goulle JP, Ludes B. Identification of ten corticosteroids in human hair by liquid chromatography-ionspray mass spectrometry. Forensic Sci Int. 2000 Jan 10;107(1-3):381-8. doi: 10.1016/s0379-0738(99)00180-2.

ReferenceCitation: Cirimele V, Tracqui A, Kintz P, Ludes B. First identification of prednisone in human hair by liquid chromatography-ionspray mass spectrometry. J Anal Toxicol. 1999 May-Jun;23(3):225-6. doi: 10.1093/jat/23.3.225. No abstract available.

ReferenceCitation: Cochrane MG, Bala MV, Downs KE, Mauskopf J, Ben-Joseph RH. Inhaled corticosteroids for asthma therapy: patient compliance, devices, and inhalation technique. Chest. 2000 Feb;117(2):542-50. doi: 10.1378/chest.117.2.542.

ReferenceCitation: Cone EJ. Mechanisms of drug incorporation into hair. Ther Drug Monit. 1996 Aug;18(4):438-43. doi: 10.1097/00007691-199608000-00022.

ReferenceCitation: Cooper GA, Kronstrand R, Kintz P; Society of Hair Testing. Society of Hair Testing guidelines for drug testing in hair. Forensic Sci Int. 2012 May 10;218(1-3):20-4. doi: 10.1016/j.forsciint.2011.10.024. Epub 2011 Nov 15.

ReferenceCitation: Cuypers E, Flinders B, Bosman IJ, Lusthof KJ, Van Asten AC, Tytgat J, Heeren RMA. Hydrogen peroxide reactions on cocaine in hair using imaging mass spectrometry. Forensic Sci Int. 2014 Sep;242:103-110. doi: 10.1016/j.forsciint.2014.06.035. Epub 2014 Jul 7.

ReferenceCitation: Dalby C, Polanowski T, Larsson T, Borgstrom L, Edsbacker S, Harrison TW. The bioavailability and airway clearance of the steroid component of budesonide/formoterol and salmeterol/fluticasone after inhaled administration in patients with COPD and healthy subjects: a randomized controlled trial. Respir Res. 2009 Oct 31;10(1):104. doi: 10.1186/1465-9921-10-104.

ReferenceCitation: DAVIS BK. Phases of the hair-growth cycle. Nature. 1962 May 19;194:694. doi: 10.1038/194694a0. No abstract available.

ReferenceCitation: Deventer K, Mikulcikova P, Van Hoecke H, Van Eenoo P, Delbeke FT. Detection of budesonide in human urine after inhalation by liquid chromatography-mass spectrometry. J Pharm Biomed Anal. 2006 Oct 11;42(4):474-9. doi: 10.1016/j.jpba.2006.05.016. Epub 2006 Jul 12.

ReferenceCitation: Deventer K, Pozo OJ, Delbeke FT, Van Eenoo P. Quantitative detection of inhaled formoterol in human urine and relevance to doping control analysis. Drug Test Anal. 2012 Jun;4(6):449-54. doi: 10.1002/dta.418. Epub 2012 Mar 22.

ReferenceCitation: Dimova H, Wang Y, Pommery S, Moellmann H, Hochhaus G. SPE/RIA vs LC/MS for measurement of low levels of budesonide in plasma. Biomed Chromatogr. 2003 Jan;17(1):14-20. doi: 10.1002/bmc.204.

ReferenceCitation: Duvivier WF, Peeters RJ, van Beek TA, Nielen MW. Evidence based decontamination protocols for the removal of external Delta9-tetrahydrocannabinol (THC) from contaminated hair. Forensic Sci Int. 2016 Feb;259:110-8. doi: 10.1016/j.forsciint.2015.12.014. Epub 2015 Dec 19.

ReferenceCitation: Fabresse, N. (2015). Mise au point et validation d'une méthode de dosage des anabolisants stéroïdiens dans le sang et les cheveux par spectrométrie de masse haute résolution Orbitrap Application à deux cas médico-légaux, http://www.sudoc.fr/188207155: 93.

ReferenceCitation: Fabresse N, Grassin-Delyle S, Etting I, Alvarez JC. Detection and quantification of 12 anabolic steroids and analogs in human whole blood and 20 in hair using LC-HRMS/MS: application to real cases. Int J Legal Med. 2017 Jul;131(4):989-999. doi: 10.1007/s00414-017-1552-3. Epub 2017 Feb 24.

ReferenceCitation: FDA.

ReferenceCitation: Foster JM, Usherwood T, Smith L, Sawyer SM, Xuan W, Rand CS, Reddel HK. Inhaler reminders improve adherence with controller treatment in primary care patients with asthma. J Allergy Clin Immunol. 2014 Dec;134(6):1260-1268.e3. doi: 10.1016/j.jaci.2014.05.041. Epub 2014 Jul 22.

ReferenceCitation: Gaillard Y, Vayssette F, Pepin G. Compared interest between hair analysis and urinalysis in doping controls. Results for amphetamines, corticosteroids and anabolic steroids in racing cyclists. Forensic Sci Int. 2000 Jan 10;107(1-3):361-79. doi: 10.1016/s0379-0738(99)00179-6.

ReferenceCitation: Gamble J, Stevenson M, McClean E, Heaney LG. The prevalence of nonadherence in difficult asthma. Am J Respir Crit Care Med. 2009 Nov 1;180(9):817-22. doi: 10.1164/rccm.200902-0166OC. Epub 2009 Jul 30.

ReferenceCitation: Gandhi M, Ameli N, Bacchetti P, Anastos K, Gange SJ, Minkoff H, Young M, Milam J, Cohen MH, Sharp GB, Huang Y, Greenblatt RM. Atazanavir concentration in hair is the strongest predictor of outcomes on antiretroviral therapy. Clin Infect Dis. 2011 May;52(10):1267-75. doi: 10.1093/cid/cir131.

ReferenceCitation: Gandhi M, Greenblatt RM, Bacchetti P, Jin C, Huang Y, Anastos K, Cohen M, Dehovitz JA, Sharp GB, Gange SJ, Liu C, Hanson SC, Aouizerat B; Women's Interagency HIV Study. A single-nucleotide polymorphism in CYP2B6 leads to >3-fold increases in efavirenz concentrations in plasma and hair among HIV-infected women. J Infect Dis. 2012 Nov;206(9):1453-61. doi: 10.1093/infdis/jis508. Epub 2012 Aug 20.

ReferenceCitation: Shen HH, Du XF, Ying SM. [Comparison of Chinese guideline for asthma managment and prevention (2016 update) and global initiative for asthma (2017 update)]. Zhonghua Jie He He Hu Xi Za Zhi. 2018 Mar 12;41(3):166-168. doi: 10.3760/cma.j.issn.1001-0939.2018.03.003. No abstract available. Chinese.

ReferenceCitation: Grassin Delyle S, Abe E, Batisse A, Tremey B, Fischler M, Devillier P, Alvarez JC. A validated assay for the quantitative analysis of tranexamic acid in human serum by liquid chromatography coupled with electrospray ionization mass spectrometry. Clin Chim Acta. 2010 Mar;411(5-6):438-43. doi: 10.1016/j.cca.2010.01.005. Epub 2010 Jan 11.

ReferenceCitation: Grassin Delyle S, Abe E, Devillier P, Alvarez JC. Determination of rimonabant in human plasma and hair by liquid chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Sep 1;872(1-2):115-20. doi: 10.1016/j.jchromb.2008.07.041. Epub 2008 Aug 5.

ReferenceCitation: Handelsman DJ, Wartofsky L. Requirement for mass spectrometry sex steroid assays in the Journal of Clinical Endocrinology and Metabolism. J Clin Endocrinol Metab. 2013 Oct;98(10):3971-3. doi: 10.1210/jc.2013-3375. No abstract available.

ReferenceCitation: He G, Lu J, Wang X, Xu Y, Wu Y, Dong Y, Shen L, He Z, Zhao J, Yuan H. An improved liquid chromatography-tandem mass spectrometric method to quantify formoterol in human urine. J Chromatogr Sci. 2014 Sep;52(8):848-51. doi: 10.1093/chromsci/bmt127. Epub 2013 Sep 12.

ReferenceCitation: Hoelzle C, Scheufler F, Uhl M, Sachs H, Thieme D. Application of discriminant analysis to differentiate between incorporation of cocaine and its congeners into hair and contamination. Forensic Sci Int. 2008 Mar 21;176(1):13-8. doi: 10.1016/j.forsciint.2007.07.020. Epub 2007 Dec 11.

ReferenceCitation: Josefsson M, Sabanovic A. Sample preparation on polymeric solid phase extraction sorbents for liquid chromatographic-tandem mass spectrometric analysis of human whole blood--a study on a number of beta-agonists and beta-antagonists. J Chromatogr A. 2006 Jul 7;1120(1-2):1-12. doi: 10.1016/j.chroma.2006.03.013. Epub 2006 Apr 4.

ReferenceCitation: Juniper EF, O'Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of a questionnaire to measure asthma control. Eur Respir J. 1999 Oct;14(4):902-7. doi: 10.1034/j.1399-3003.1999.14d29.x.

ReferenceCitation: Juniper EF, Svensson K, Mork AC, Stahl E. Measurement properties and interpretation of three shortened versions of the asthma control questionnaire. Respir Med. 2005 May;99(5):553-8. doi: 10.1016/j.rmed.2004.10.008. Epub 2004 Nov 26.

ReferenceCitation: Jurado C, Kintz P, Menendez M, Repetto M. Influence of the cosmetic treatment of hair on drug testing. Int J Legal Med. 1997;110(3):159-63. doi: 10.1007/s004140050056.

ReferenceCitation: Kintz P. Value of the concept of minimal detectable dosage in human hair. Forensic Sci Int. 2012 May 10;218(1-3):28-30. doi: 10.1016/j.forsciint.2011.10.018. Epub 2011 Oct 20.

ReferenceCitation: Kintz P, Alvarez JC, Deveaux M, Dumestre V, Gaillard Y, Gaulier JM. Conflicting hair testing results can have an impact in courts: interpretation of single exposure to zolpidem. J Anal Toxicol. 2014 Jun;38(5):304-5. doi: 10.1093/jat/bku014. Epub 2014 Mar 11. No abstract available.

ReferenceCitation: Kintz P, Cirimele V, Ludes B. Pharmacological criteria that can affect the detection of doping agents in hair. Forensic Sci Int. 2000 Jan 10;107(1-3):325-34. doi: 10.1016/s0379-0738(99)00176-0.

ReferenceCitation: Kintz P, Dumestre-Toulet V, Jamey C, Cirimele V, Ludes B. Doping control for beta-adrenergic compounds through hair analysis. J Forensic Sci. 2000 Jan;45(1):170-4.

ReferenceCitation: Kronkvist K, Gustavsson M, Wendel AK, Jaegfeldt H. Automated sample preparation for the determination of budesonide in plasma samples by liquid chromatography and tandem mass spectrometry. J Chromatogr A. 1998 Oct 9;823(1-2):401-9. doi: 10.1016/s0021-9673(98)00592-5.

ReferenceCitation: Kronstrand R, Ahlner J, Dizdar N, Larson G. Quantitative analysis of desmethylselegiline, methamphetamine, and amphetamine in hair and plasma from Parkinson patients on long-term selegiline medication. J Anal Toxicol. 2003 Apr;27(3):135-41. doi: 10.1093/jat/27.3.135.

ReferenceCitation: Kronstrand R, Roman M, Hedman M, Ahlner J, Dizdar N. Dose-hair concentration relationship and pigmentation effects in patients on low-dose clozapine. Forensic Sci Med Pathol. 2007 Jun;3(2):107-14. doi: 10.1007/s12024-007-0010-9. Epub 2007 May 9.

ReferenceCitation: LeBeau MA, Montgomery MA, Brewer JD. The role of variations in growth rate and sample collection on interpreting results of segmental analyses of hair. Forensic Sci Int. 2011 Jul 15;210(1-3):110-6. doi: 10.1016/j.forsciint.2011.02.015. Epub 2011 Mar 6.

ReferenceCitation: Lee KM, Kim HJ, Son J, Park JH, Kwon OS, Lee J. Simple quantitation of formoterol and 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid in human urine by liquid chromatography-tandem mass spectrometry in doping control. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Sep 15;967:8-12. doi: 10.1016/j.jchromb.2014.07.009. Epub 2014 Jul 14.

ReferenceCitation: Lemaire-Hurtel, A.-S., Durand-Maugard, C., Berquin, P., Antonios, M., Hary, L., Andrejak, M., Masson, H., Manaouil, C., Abe, E. and Alvarez, J.-C. (2010).

ReferenceCitation: Li N, Tattam B, Brow KF, Seale JP. Quantification of epimeric budesonide and fluticasone propionate in human plasma by liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry. J Chromatogr B Biomed Sci Appl. 2001 Sep 25;761(2):177-85. doi: 10.1016/s0378-4347(01)00329-2.

ReferenceCitation: Li YN, Tattam B, Brown KF, Seale JP. Determination of epimers 22R and 22S of budesonide in human plasma by high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry. J Chromatogr B Biomed Appl. 1996 Aug 30;683(2):259-68. doi: 10.1016/0378-4347(96)00111-9.

ReferenceCitation: Lindberg C, Blomqvist A, Paulson J. Determination of (22R,S)budesonide in human plasma by automated liquid chromatography/thermospray mass spectrometry. Biol Mass Spectrom. 1992 Nov;21(11):525-33. doi: 10.1002/bms.1200211102.

ReferenceCitation: Liu AY, Yang Q, Huang Y, Bacchetti P, Anderson PL, Jin C, Goggin K, Stojanovski K, Grant R, Buchbinder SP, Greenblatt RM, Gandhi M. Strong relationship between oral dose and tenofovir hair levels in a randomized trial: hair as a potential adherence measure for pre-exposure prophylaxis (PrEP). PLoS One. 2014 Jan 8;9(1):e83736. doi: 10.1371/journal.pone.0083736. eCollection 2014.

ReferenceCitation: Loussouarn G, Lozano I, Panhard S, Collaudin C, El Rawadi C, Genain G. Diversity in human hair growth, diameter, colour and shape. An in vivo study on young adults from 24 different ethnic groups observed in the five continents. Eur J Dermatol. 2016 Apr 1;26(2):144-54. doi: 10.1684/ejd.2015.2726.

ReferenceCitation: Lu Y, Sun Z, Zhang Y, Chen X, Zhong D. Simultaneous quantification of 22R and 22S epimers of budesonide in human plasma by ultra-high-performance liquid chromatography-tandem mass spectrometry: application in a stereoselective pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Mar 15;921-922:27-34. doi: 10.1016/j.jchromb.2013.01.015. Epub 2013 Jan 28.

ReferenceCitation: Mancebo, M., Grassin-Delyle, S., Essid, A., Bataille, J., Guérard, P., Delyle, A. G. and Alvarez, J.-C. (2011).

ReferenceCitation: Mascher DG, Zech K, Nave R, Kubesch KM, Mascher HJ. Ultra-sensitive determination of Formoterol in human serum by high performance liquid chromatography and electrospray tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Jan 2;830(1):25-34. doi: 10.1016/j.jchromb.2005.10.022. Epub 2005 Nov 7.

ReferenceCitation: Mazzarino M, de la Torre X, Fiacco I, Pompei C, Calabrese F, Botre F. A simplified procedure for the analysis of formoterol in human urine by liquid chromatography-electrospray tandem mass spectrometry: application to the characterization of the metabolic profile and stability of formoterol in urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Jul 15;931:75-83. doi: 10.1016/j.jchromb.2013.05.021. Epub 2013 May 28.

ReferenceCitation: Millar SE. Molecular mechanisms regulating hair follicle development. J Invest Dermatol. 2002 Feb;118(2):216-25. doi: 10.1046/j.0022-202x.2001.01670.x.

ReferenceCitation: Miller-Larsson A, Mattsson H, Hjertberg E, Dahlback M, Tunek A, Brattsand R. Reversible fatty acid conjugation of budesonide. Novel mechanism for prolonged retention of topically applied steroid in airway tissue. Drug Metab Dispos. 1998 Jul;26(7):623-30.

ReferenceCitation: Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available.

ReferenceCitation: Miramont S, Alvarez JC, Bourgogne E, Cheron G. [Passive cocaine inhalation by a 25-month-old child]. Arch Pediatr. 2013 Jun;20(6):654-6. doi: 10.1016/j.arcped.2013.03.006. Epub 2013 Apr 19. French.

ReferenceCitation: Mortimer KJ, Harrison TW, Tang Y, Wu K, Lewis S, Sahasranaman S, Hochhaus G, Tattersfield AE. Plasma concentrations of inhaled corticosteroids in relation to airflow obstruction in asthma. Br J Clin Pharmacol. 2006 Oct;62(4):412-9. doi: 10.1111/j.1365-2125.2006.02712.x.

ReferenceCitation: Nilsson K, Andersson M, Beck O. Phospholipid removal combined with a semi-automated 96-well SPE application for determination of budesonide in human plasma with LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Nov 1;970:31-5. doi: 10.1016/j.jchromb.2014.08.035. Epub 2014 Sep 6.

ReferenceCitation: Noppe G, de Rijke YB, Dorst K, van den Akker EL, van Rossum EF. LC-MS/MS-based method for long-term steroid profiling in human scalp hair. Clin Endocrinol (Oxf). 2015 Aug;83(2):162-6. doi: 10.1111/cen.12781. Epub 2015 Apr 27.

ReferenceCitation: Pecoraro, V. and Astore, I. P. L. (1990). Measurements of hair growth under physiological conditions. Hair and Hair Diseases. C. E. Orfanos and R. Happle. Berlin, Heidelberg, Springer Berlin Heidelberg: 237-254.

ReferenceCitation: Potsch L. A discourse on human hair fibers and reflections on the conservation of drug molecules. Int J Legal Med. 1996;108(6):285-93. doi: 10.1007/BF02432122.

ReferenceCitation: Pragst F, Balikova MA. State of the art in hair analysis for detection of drug and alcohol abuse. Clin Chim Acta. 2006 Aug;370(1-2):17-49. doi: 10.1016/j.cca.2006.02.019. Epub 2006 Mar 6.

ReferenceCitation: Pritchett JS, Phinney KW. Influence of chemical straightening on the stability of drugs of abuse in hair. J Anal Toxicol. 2015 Jan-Feb;39(1):13-6. doi: 10.1093/jat/bku106. Epub 2014 Oct 8.

ReferenceCitation: Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Eur Respir J. 1993 Mar;6 Suppl 16:5-40. doi: 10.1183/09041950.005s1693. No abstract available.

ReferenceCitation: Ray A, Raundhal M, Oriss TB, Ray P, Wenzel SE. Current concepts of severe asthma. J Clin Invest. 2016 Jul 1;126(7):2394-403. doi: 10.1172/JCI84144. Epub 2016 Jul 1.

ReferenceCitation: Ribot M, Polito A, Grassin-Delyle S, Annane D, Alvarez JC. Human plasma quantification of fludrocortisone using liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometry after low-dosage administration. Clin Chim Acta. 2013 May;420:109-13. doi: 10.1016/j.cca.2012.11.026. Epub 2012 Dec 7.

ReferenceCitation: Ricard F, Abe E, Duverneuil-Mayer C, Charlier P, de la Grandmaison G, Alvarez JC. Measurement of atropine and scopolamine in hair by LC-MS/MS after Datura stramonium chronic exposure. Forensic Sci Int. 2012 Nov 30;223(1-3):256-60. doi: 10.1016/j.forsciint.2012.09.015. Epub 2012 Oct 22.

ReferenceCitation: Roberts JK, Cook SF, Stockmann C, Rollins DE, Wilkins DG, Sherwin CM. A Population Pharmacokinetic Analysis of Dextroamphetamine in the Plasma and Hair of Healthy Adults. Clin Drug Investig. 2015 Oct;35(10):633-43. doi: 10.1007/s40261-015-0323-5.

ReferenceCitation: Rohrich J, Zorntlein S, Potsch L, Skopp G, Becker J. Effect of the shampoo Ultra Clean on drug concentrations in human hair. Int J Legal Med. 2000;113(2):102-6. doi: 10.1007/pl00007707.

ReferenceCitation: Rollins DE, Wilkins DG, Krueger GG, Augsburger MP, Mizuno A, O'Neal C, Borges CR, Slawson MH. The effect of hair color on the incorporation of codeine into human hair. J Anal Toxicol. 2003 Nov-Dec;27(8):545-51. doi: 10.1093/jat/27.8.545.

ReferenceCitation: Baque CS, Zhou J, Gu W, Collaudin C, Kravtchenko S, Kempf JY, Saint-Leger D. Relationships between hair growth rate and morphological parameters of human straight hair: a same law above ethnical origins? Int J Cosmet Sci. 2012 Apr;34(2):111-6. doi: 10.1111/j.1468-2494.2011.00687.x. Epub 2011 Oct 21.

ReferenceCitation: Salomone A, Tsanaclis L, Agius R, Kintz P, Baumgartner MR. European guidelines for workplace drug and alcohol testing in hair. Drug Test Anal. 2016 Oct;8(10):996-1004. doi: 10.1002/dta.1999. Epub 2016 Jul 12.

ReferenceCitation: Sardela VF, Deventer K, Pereira HM, de Aquino Neto FR, Van Eenoo P. Development and validation of a ultra high performance liquid chromatography-tandem mass spectrometric method for the direct detection of formoterol in human urine. J Pharm Biomed Anal. 2012 Nov;70:471-5. doi: 10.1016/j.jpba.2012.06.042. Epub 2012 Jul 7.

ReferenceCitation: Skopp G, Potsch L, Moeller MR. On cosmetically treated hair--aspects and pitfalls of interpretation. Forensic Sci Int. 1997 Jan 17;84(1-3):43-52. doi: 10.1016/s0379-0738(96)02047-6.

ReferenceCitation: Streel B, Cahay B, Klinkenberg R. Using total error concept for the validation of a liquid chromatography-tandem mass spectrometry method for the determination of budesonide epimers in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Aug 1;877(23):2290-300. doi: 10.1016/j.jchromb.2009.02.004. Epub 2009 Feb 11.

ReferenceCitation: Sullivan SD, Rasouliyan L, Russo PA, Kamath T, Chipps BE; TENOR Study Group. Extent, patterns, and burden of uncontrolled disease in severe or difficult-to-treat asthma. Allergy. 2007 Feb;62(2):126-33. doi: 10.1111/j.1398-9995.2006.01254.x.

ReferenceCitation: Szeitz A, Manji J, Riggs KW, Thamboo A, Javer AR. Validated assay for the simultaneous determination of cortisol and budesonide in human plasma using ultra high performance liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2014 Mar;90:198-206. doi: 10.1016/j.jpba.2013.12.006. Epub 2013 Dec 16.

ReferenceCitation: Taylor RL, Grebe SK, Singh RJ. Quantitative, highly sensitive liquid chromatography-tandem mass spectrometry method for detection of synthetic corticosteroids. Clin Chem. 2004 Dec;50(12):2345-52. doi: 10.1373/clinchem.2004.033605. Epub 2004 Oct 14.

ReferenceCitation: Thevis M, Opfermann G, Schanzer W. Liquid chromatography/electrospray ionization tandem mass spectrometric screening and confirmation methods for beta2-agonists in human or equine urine. J Mass Spectrom. 2003 Nov;38(11):1197-206. doi: 10.1002/jms.542.

ReferenceCitation: Thomas A, Geyer H, Schanzer W, Crone C, Kellmann M, Moehring T, Thevis M. Sensitive determination of prohibited drugs in dried blood spots (DBS) for doping controls by means of a benchtop quadrupole/Orbitrap mass spectrometer. Anal Bioanal Chem. 2012 May;403(5):1279-89. doi: 10.1007/s00216-011-5655-2. Epub 2012 Jan 10.

ReferenceCitation: Thorsson L, Edsbacker S, Conradson TB. Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered-dose inhaler P-MDI. Eur Respir J. 1994 Oct;7(10):1839-44. doi: 10.1183/09031936.94.07101839.

ReferenceCitation: Tosi A, Misciali C, Piraccini BM, Peluso AM, Bardazzi F. Drug-induced hair loss and hair growth. Incidence, management and avoidance. Drug Saf. 1994 Apr;10(4):310-7. doi: 10.2165/00002018-199410040-00005.

ReferenceCitation: Tsanaclis L, Nutt J, Bagley K, Bevan S, Wicks J. Differentiation between consumption and external contamination when testing for cocaine and cannabis in hair samples. Drug Test Anal. 2014 Jun;6 Suppl 1:37-41. doi: 10.1002/dta.1623.

ReferenceCitation: van den Brink KI, Boorsma M, Staal-van den Brekel AJ, Edsbacker S, Wouters EF, Thorsson L. Evidence of the in vivo esterification of budesonide in human airways. Br J Clin Pharmacol. 2008 Jul;66(1):27-35. doi: 10.1111/j.1365-2125.2008.03164.x. Epub 2008 Apr 1.

ReferenceCitation: Van Neste D. Thickness, medullation and growth rate of female scalp hair are subject to significant variation according to pigmentation and scalp location during ageing. Eur J Dermatol. 2004 Jan-Feb;14(1):28-32.

ReferenceCitation: Van Neste D. Why care about linear hair growth rates (LHGR)? a study using in vivo imaging and computer assisted image analysis after manual processing (CAIAMP) in unaffected male controls and men with male pattern hair loss (MPHL). Eur J Dermatol. 2014 Sep-Oct;24(5):568-76. doi: 10.1684/ejd.2014.2428.

ReferenceCitation: Van Neste DJ, Rushton DH. Gender differences in scalp hair growth rates are maintained but reduced in pattern hair loss compared to controls. Skin Res Technol. 2016 Aug;22(3):363-9. doi: 10.1111/srt.12274. Epub 2015 Nov 3.

ReferenceCitation: van Zyl GU, van Mens TE, McIlleron H, Zeier M, Nachega JB, Decloedt E, Malavazzi C, Smith P, Huang Y, van der Merwe L, Gandhi M, Maartens G. Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting. J Acquir Immune Defic Syndr. 2011 Apr;56(4):333-9. doi: 10.1097/QAI.0b013e31820dc0cc.

ReferenceCitation: Wang Y, Tang Y, Moellmann H, Hochhaus G. Simultaneous quantification of budesonide and its two metabolites, 6beta-hydroxybudesonide and 16alpha-hydroxyprednisolone, in human plasma by liquid chromatography negative electrospray ionization tandem mass spectrometry. Biomed Chromatogr. 2003 Mar-Apr;17(2-3):158-64. doi: 10.1002/bmc.233.

ReferenceCitation: Wenzel SE. Complex phenotypes in asthma: current definitions. Pulm Pharmacol Ther. 2013 Dec;26(6):710-5. doi: 10.1016/j.pupt.2013.07.003. Epub 2013 Jul 20.

ReferenceCitation: Williams J, Patsalos PN, Mei Z, Schapel G, Wilson JF, Richens A. Relation between dosage of carbamazepine and concentration in hair and plasma samples from a compliant inpatient epileptic population. Ther Drug Monit. 2001 Feb;23(1):15-20. doi: 10.1097/00007691-200102000-00004.

ReferenceCitation: Yegles M, Marson Y, Wennig R. Influence of bleaching on stability of benzodiazepines in hair. Forensic Sci Int. 2000 Jan 10;107(1-3):87-92. doi: 10.1016/s0379-0738(99)00152-8.


type: Other Identifier

title: Prevention of Cognitive Decline in Older Adults With Low Dha/Epa Index in Red Blood Cells

acronym: LO-MAPT

summary: LO MAPT is an 18-month, phase III, multicenter, randomized, placebo-controlled, 2 parallel groups trial, followed by a 18-month open-label extension phase, to evaluate the efficacy of omega-3 supplementation on cognitive decline in older adults with low DHA/EPA status and subjective memory complaints or family history of Alzheimer disease.

study_start_date_type: Actual

status: Completed

study_completion_date_type: Actual

study_type: Interventional

design_allocation: Randomized

primary_purpose: Prevention

enrollment_type: Actual

ipd_sharing: No

lead_sponsor: University Hospital, Toulouse

intervention_type: Drug

lead_sponsor_type: academique

status_simplified: Completed


title: A Retrospective Study of Obstetrical and Neonatal Complications in Hereditary Haemorrhagic Telangiectasia (HHT)

acronym: CONCERTO

summary:
Hereditary Haemorrhagic Telangiectasia (HHT) is a rare inherited genetic disease of autosomal dominant inheritance with a prevalence of about 1/5000. It is manifested by haemorrhage, mucocutaneous telangiectasia and visceral arteriovenous malformations (AVMs) (lung, liver and nervous system).

Severe complications during pregnancy in HHT are rare but considered high risk. Intracranial or pulmonary haemorrhage, stroke and heart failure have been reported in some women with HHT during pregnancy. These complications occur most often in the second and third trimesters when maternal physiological changes such as peripheral vasodilatation and increased cardiac output are at their peak.

Previous retrospective studies were conducted with numbers ranging from 40 to 97 patients and highlighted the importance of early screening of complications and specific management.

The aim of this study is to describe, on a larger number of patients, the obstetric and neonatal complications in patients with HHT and followed in the French Reference Center for HHT.

study_type: Observational

time_perspective: Prospective

lead_sponsor: Hospices Civils de Lyon

location_facility: Centre de Référence pour la maladie de Rendu-Osler Service Génétique Clinique Bâtiment A1 - Hôpital Femme-Mère-Enfant - Hospices Civils de Lyon

intervention_type: Other


title: A Prospective Study Evaluating the Effect of Ocrelizumab on Brain Innate Immune Microglial Cells Activation in Multiple Sclerosis Using PET-MRI With 18F-DPA714

acronym: INN-MS

summary: Ocrelizumab is a humanized anti-CD20 monoclonal antibody that showed in phase III trials a powerful effect on relapse rate and lesion load accumulation in the relapsing form of multiple sclerosis (RMS). This therapeutic agent also showed for the first time a significant reduction of disability progression in Primary Progressive Multiple Sclerosis (PPMS) patients, whereas all other anti-inflammatory drugs had failed to do so in well-conducted studies. This raises the possibility that ocrelizumab, beyond its effects on the adaptive immune system activation underlying white matter lesions and clinical relapses, could beneficially influence other mechanisms involved in the progressive phase of the disease, such as the innate immune microglial cells activation, that has been described to persist in a diffuse manner in the Central Nervous system (CNS). To date the activation of these cells is not accessible to classical Magnetic Resonance Imaging (MRI) techniques, impeding the full investigation of the therapeutic efficacy of drugs such as ocrelizumab.

status: Recruiting

study_completion_date_type: Anticipated

primary_purpose: Treatment

enrollment_type: Anticipated

lead_sponsor: Assistance Publique - Hôpitaux de Paris

collaborators: Institut du Cerveau et de la Moelle épinière

location_facility: Hôpital Saint-Antoine - Service de Neurologie

status_simplified: Ongoing


title: Infraorbital Nerve Involvement on Magnetic Resonance Imaging in European Patients With IgG4-related Ophthalmic Disease

summary: Infraorbital nerve enlargement (IONE) on magnetic resonance imaging is known to be a possible consequence of IgG4-related ophthalmic disease. However this imaging sign can also be found in other conditions causing orbital inflammation. This study aims at comparing the frequency of IONE in patients suffering from IgG4-related ophthalmic disease (IgG4-ROD) versus patients suffering from non-IgG4-related ophthalmic disease (non-IgG4-ROD)

time_perspective: Retrospective

lead_sponsor: Fondation Ophtalmologique Adolphe de Rothschild

location_facility: Fondation Ophtalmologique A. de Rotchschild

lead_sponsor_type: industriel


title: Long-term Outcome of AIDS-related Primary Central Nervous System Lymphoma Treated With High Dose Methotrexate and Combined Antiretroviral Therapy

acronym: LCPVIH

summary: This study aims at describing survival rates over time (Kaplan-Meier estimator) in patients suffering from AIDS-related primary central nervous system lymphoma who were diagnosed from 1996 to 2014 and treated with infusions of high-dose methotrexate and combined antiretroviral therapy.

sponsor_collaborators: Fondation Ophtalmologique Adolphe de Rothschild


title: Medical Imaging Characteristics of Patient With Unclassified Acute Cervical Pain

acronym: RetroTIPIC

summary:
Some cases of acute antero-lateral cervical pain cannot be accurately classified by medical imaging (ultrasound and/or magnetic resonance imaging and/or CT-scan) : imaging rules out carotid dissection, carotid occlusion or vasculitis as well as musculoskeletal causes and thus the pain is considered "of unknown origin".

The investigators hypothesize that in such cases perivascular inflammation of the carotid may be involved.

This study aims at systematically reviewing medical files (including imaging) of patients suffering from acute cervical pain in which carotid dissection, carotid occlusion or vasculitis as well as musculoskeletal causes have been ruled out by ultrasound and/or magnetic resonance imaging and/or CT-scan


title: Use of Metabolomics for the Identification of Endometrial Biomarkers for Recurrent Pregnancy Loss and Reccurent Implantation Failure Following in Vitro Fertilization.

acronym: ENDOMETAB

summary:
It is a case-control study composed of 3 groups : 2 cases groups (RIF and IRPL) already composed as part of a pre-existing research project and 1 control group including patients undergoing ART for male factor infertility.

The purpose of this study is to compare the 2 case group with the control group to identify metabolomics signatures.

study_start_date_type: Anticipated

status: Unknown status

design_allocation: Non-Randomized

primary_purpose: Other

ipd_sharing: Yes

lead_sponsor: University Hospital, Angers

status_simplified: Unknown


title: Assessment of the Knowledge and Needs of Patients With AMD Before a Therapeutic Patient Education Program is Put in Place

acronym: DEMELE

summary:
Age-related macular degeneration (AMD) is a disease that blurs the sharp, central vision you need for "straight-ahead" activities such as reading, sewing, and driving. AMD affects the macula, the part of the eye that allows you to see fine detail

The purpose of the study is to describe in patients with AMD and depending on the nature of their pathology (neovascular or atrophic):

(i) knowledge about their pathology (risk factors, symptoms, treatments, self-monitoring tool), (ii) their needs and (iii) impact on their daily lives

This study is to make an inventory of the knowledge of patients with AMD about their disease and risk factors using a questionnaire (Appendix 1) and to identify their needs, the impact of the disease on their daily lives during individual interviews by raising the recurrent data and confronting them during the focus group. The information gathered will enable the construction of a therapeutic education program for better patient care and to strengthen the patient's capacities so that he becomes an actor in his change throughout his care project.

This a 3 steps study:

200 patients will be enrolled and answer a questionnaire on knowledge of the disease
Two groups of 20 patients will be selected to participate to a semi-structured individual interviews
Two focus groups of 10 patients will be organized to assess needs, expectations, satisfactions or to better understand opinions, motivations or behaviors.

primary_purpose: Supportive Care

lead_sponsor: University Hospital, Limoges

intervention_type: Behavioral


title: Study Programmed Intermittent Epidural Bolus (PIEB) vs PIEB: the Dose is it Variable According to the Patients

acronym: DOPABIEB

summary: the main objective of this study is to compare the effectiveness of three groups of epidurals with three different programmed intermittent epidural bolus (PIEB)settings.

lead_sponsor: Rennes University Hospital

location_facility: Centre Hospitalier Universitaire de Rennes


title: Development of the Purification of Human Cardiac Mitochondria, Characterization of These Organelles and Validation of the Model in Acute Endocarditis and Obesity

acronym: MITHOM

summary: Data about human cardiac mitochondria are cruelly lacking in the literature. However, damages of the activity of these organelles are often the source of abnormal cardiac function in several pathologies. The purpose of this study is to develop a model of purified human cardiac mitochondria, to verify the purity of these organelles and to validate the authenticity of their function in acute endocarditis and obesity, two situations known to alter their activity. Animal studies have shown that microbial infection reduced mitochondrial metabolism whereas obesity increases it. The investigator's hypotheses are the following: 1) acute endocarditis, a form of cardiac microbial infection, reduces the function of human cardiac mitochondria; 2) obesity (body mass index > 30) activates the metabolism of human cardiac mitochondria.

ReferenceType: background

ReferenceCitation: Mourmoura E, Rigaudiere JP, Couturier K, Hininger I, Laillet B, Malpuech-Brugere C, Azarnoush K, Demaison L. Long-term abdominal adiposity activates several parameters of cardiac energy function. J Physiol Biochem. 2016 Sep;72(3):525-37. doi: 10.1007/s13105-015-0427-7. Epub 2015 Aug 10.

lead_sponsor: University Hospital, Clermont-Ferrand

collaborators: Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement


title: Nice Human Immunodeficiency Virus (HIV) Cohort

summary: Historically, the database on the HIV was organized within the framework of the medico-economic file of the human immunodeficiency (DMI-2), introduced jointly by the Direction of Hospitals (Mission AIDS) and the INSERM at the end of the 80s. Today this database is fed via the computerized medical record NADIS. Most part of the research works on the theme of the HIV take support on this database (DAD, EuroAIDS, Neuradapt).

lead_sponsor: Centre Hospitalier Universitaire de Nice


title: Value of Tomosynthesis for Detection of Sacro-iliitis: a Prospective Comparative Study

acronym: TOMOS SI

summary:
Spondyloarthropathies (SpAs) are chronic inflammatory diseases encompassing ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthropathy, and undifferentiated SpA.

In 2001, the estimated prevalence of SpA was 1.5% worldwide. Sacroiliitis is a condition caused by inflammation within the sacroiliac joint. It is the most frequent damage of SpA depicted at imaging evaluation.

Conventional radiography (X-ray) is usually used to depict the structural changes associated with sacroiliitis.

However further evaluation often requires additionnal computed tomography (CT).

Tomosynthesis is an Xray-based imaging technology which allows reconstruction of multiple section images from a set of projection images acquired as the x-ray tube moves along a prescribed path. The advantagee of tomosynthesis is the significant reduction of radiation dose exposure compared to CT Tomosynthesis is currently used in the field of breast imaging and pneumology. Very few studies have examined the value of tomosynthesis for osteoarticular imaging.

The study aims at evaluating the diagnostic performances of tomosynthesis as compared to standard X-ray and CT, in patients with a clinical suspicion of sacroiliitis.

the investigators hypothesize that tomosynthesis is superior to conventional radiography for detection of sacroiliitis and is at least equal to CT with lower irradiation.

primary_purpose: Diagnostic

lead_sponsor: University Hospital, Montpellier

sponsor_collaborators:
University Hospital, Montpellier
DMS Apelem
Thales
Digisens
Medecom
BPIfrance
European Regional Development Fund

intervention_type: Device


title: Evaluation of Physical Activity Practice (AP) After Cerebral Vascular Stroke (Stroke)

acronym: QAP-AVC

summary:
Physical activity is defined by any movement produced by the skeletal muscles responsible for an increase in energy expenditure.

The Stroke Council of the American Heart Association (AHA) recommends, in prevention after the occurrence of a first stroke, the practice of moderate to intense physical activity for 40 minutes a day, three to four times a week (Lackland et al., 2014). The World Health Organization (WHO) also recommends the practice of at least 150 minutes of moderate-intensity endurance activity or at least 75 minutes of endurance activity of sustained intensity per week, adapted to the possibilities of the patient (World Health Organization 2010). Unfortunately, the majority of stroke patients have activity below recommendation (Rand et al., 2009).

The main hypothesis of this work is that the amount of AP, measured by self-questionnaire, is insufficient, and below current recommendations in patients with stroke, after return home.

Given the multiple physical, psychological, social, and economic benefits of PA practice, it is also important to identify the habits and challenges that patients experience with PA, so that they can be better informed. advise and guide them to reach AP stroke recommendations.

lead_sponsor: Centre Hospitalier Universitaire, Amiens


type: EudraCT Number

title: Interest of the T2 * Sequence in MRI for the Diagnosis of Migraine Aura in the Acute Phase.

acronym: MARIE

summary: investigators hypothesize that T2 * vein abnormalities are frequent and are specific to the migraine aura.

location_facility: Hôpital Pierre Paul Riquet - CHU de Toulouse

intervention_type: Diagnostic Test


title: High Flow Oxygen During Spontaneous Breathing Trial in Patients With High Weaning Risk Failure: Impact on the Weaning Course at D7 From the First Spontaneous Breathing Trial. A Pilot Randomized Controlled Trial

acronym: ObiWEAN

summary:
In intensive care unit (ICU), mechanical ventilation (MV) is part of routine care.

Weaning phase is a daily preoccupation for the caregivers. Prolonged MV can lead to many complications. Failing the weaning phase expose the patient to the need for reintubation, that improves the mortality.

The caregiver faces a major problem, in one hand the need to wean properly and quickly and on the other the risk of reintubation.

In order to help the clinician making the good choice, the spontaneous breathing trial (SBT) is a key tool. The international literature provides the investigators many ways to perform the SBT. The most common is the T-piece; the patient is disconnected from the ventilator and connected to a T-piece that can provide supplemental oxygen. Another one is the Support pressure trial, the patient is still connected to the ventilator, but the setups are changed to recreate the T-piece conditions.

In many French ICU's, the SBT is performed by using a heat humidifier filter that is directly connected to the endotracheal tube, this filter allows the clinician to provide supplemental oxygen in accordance with the patient need.

In high risk for reintubation patients, the SBT can create physical stress, that lead to prolonged MV.

In our ICU, for those patients, the investigators perform the SBT by connecting the patient to a device that provides high flow oxygen trough endotracheal connector for tracheotomy.

The investigators hypothesis that high flow oxygen SBT, will allow the high risk for reintubation patients to succeed the SBT.

ReferenceCitation: Thille AW, Richard JC, Brochard L. The decision to extubate in the intensive care unit. Am J Respir Crit Care Med. 2013 Jun 15;187(12):1294-302. doi: 10.1164/rccm.201208-1523CI.

oa_host_type: closed

repositories_concat: closed

publisher_dissemination: American Thoracic Society

ReferenceCitation: Ladeira MT, Vital FM, Andriolo RB, Andriolo BN, Atallah AN, Peccin MS. Pressure support versus T-tube for weaning from mechanical ventilation in adults. Cochrane Database Syst Rev. 2014 May 27;2014(5):CD006056. doi: 10.1002/14651858.CD006056.pub2.

ReferenceCitation: Brochard L, Rauss A, Benito S, Conti G, Mancebo J, Rekik N, Gasparetto A, Lemaire F. Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation. Am J Respir Crit Care Med. 1994 Oct;150(4):896-903. doi: 10.1164/ajrccm.150.4.7921460.

lead_sponsor: Centre Hospitalier Régional d'Orléans

intervention_type: Procedure


title: Volumetric Imaging Follow up of Patients With Liver Metastases of Small Intestinal Neuroendocrine Tumors (NETs).

acronym: VOLUNET

summary:
More than 50% of intestinal NETs are metastatic at the time of diagnosis, the liver being the main affected organ in 50-90% of cases.

Initial liver tumor burden and slope of the tumor growth rate are two major prognostic factors in patients with intestinal NETs, followed by tumor grade at pathology. They are used in routine practice by oncologists to adapt patient treatment.

Unlike other tumors, most NETs metastases are slow-growing tumors. Previous studies have shown that approximately half of the patients diagnosed with liver metastases showed no progression over a period of 3 to 6 months.

The aim of this non randomised retrospective cohort study is to investigate whether the volumetric monitoring of the total tumor burden compared to the RECIST 1.1 criteria (used in routine practice by radiologists) at baseline and early follow-up (3 to 6 months) is more suitable for NETs, making possible to predict the prognosis at the onset of the disease, and also allowing a better adaptation of the treatment.

The secondary objectives are to evaluate if the initial volume of the liver tumor is a prognostic factor of time to progression, to correlate the initial liver tumor volume and the number of liver lesions to the blood concentration of Chromogranin A (CgA), the presence of extra-abdominal disease and to correlate the tumor growth rate (TGR) and KI 67 (%) at base-line.

location_facility: Service de radiologie-Pavillon B-Cellule Recherche imagerie - Hôpital Edouard Herriot


acronym: NEUPERSART

summary:
Background:

Chemotherapy induced peripheral neuropathy (CIPN) is often painful, and is caused by neurotoxic chemotherapy including vincristine. It is a cause of significant impairment in quality of life in patients surviving to a solid cancer or malignant lymphoma. The only recognized prevention is based on pre-existing neuropathy and early detection of neuropathic signs and symptoms in individuals subjected to neurotoxic chemotherapy, justifying sometimes a change in the therapeutic strategy when other molecules are available. It seems obvious that to identify early markers of CIPN and to develop preventive therapeutic strategies, are priorities for improving patients' quality of life and enable them to follow optimal treatment.

Purpose:

To describe in patients treated for non-Hodgkin's type B malignant lymphoma with multidrug therapy containing vincristine, the impact of candesartan on the occurrence of neuropathy measured by the variation of TNSc (Total Neuropathy Score clinical version, evaluating clinical signs of neuropathy)

status: Terminated

title: Pilot Study, Single-blind, Candesartan Versus Usual Care of Peripheral Neuropathy Development Induced by Vincristine (PNIV) in Patients Treated for Lymphoma B

source: euctr


title: Effects of Emotion on Episodic Memory in Typically Developing Children and Children With Williams-Beuren Syndrome

acronym: EEM-TAdev

summary: It's well established in the literature that emotional events are more likely to be remembered than neutral events. Although this Emotional Enhancement of Memory (EEM) has been well demonstrated in the adult literature, little is known about EEM for typically developing children and children with Williams-Beuren syndrome (WBS). In this study, two investigations will be conducted concomitantly: one of EEM in typically developing children and the other of EEM in children with WBS. For this purpose, three behavioral experiments will be established to investigate EEM in this two populations, with the first experiment also including electroencephalography measures. Performances of typically developing children will be compared to young adults, and performances of children with WBS will be compared to control children matched for mental age. Finally, this study aims to bring new knowledge about the interactions between emotion and memory in children, and to better understand cognitive functioning in children with WBS.

lead_sponsor: Hôpital le Vinatier


title: The Value of Post-operative Antibiotic Therapy After Laparoscopic Appendectomy for Complicated Acute Appendicitis (Other Than for Generalized Peritonitis): a Prospective, Randomized, Placebo-controlled Phase III Study

acronym: ABAP

summary:
Around 30% of appendectomies are performed for complicated acute appendicitis (CAA, i.e. cases with perforated appendicitis, extraluminal fecaliths, abscesses, or local or generalized peritonitis). The treatment of these complicated forms involves the following steps: initiation of antibiotic treatment at the time of the diagnosis, appendectomy and post-operative antibiotic therapy that continues for 3 days for localized forms of CAA and for 5 days for generalized peritonitis (according to the guidelines issued by the French Society for Anaesthesia and Critical Care Medicine (SFAR)). The results of a Cochrane meta-analysis published in 2005 suggested that the post-operative infection rate was lower in patients having receiving antibiotic therapy after surgery for AA. When only cases of CAA were considered, the difference was no longer significant. However, it should be noted that the studies included in the meta-analysis are now rather old (published before 1995, with open procedures) and no longer provide valid data for answering this question because most appendectomies (80%) are now performed using laparoscopy. Furthermore, a recent cohort study compared a short (3-day) course of antibiotics with a long course (at least 5 days) in patients with CAA having undergone laparoscopic or open appendectomy. There was no significant intergroup difference in the post-operative complication rate. One can thus legitimately question whether post-operative antibiotic therapy is required after laparoscopic appendectomy for CAA.

The purpose of the present study is to evaluate the impact of the absence of post-operative antibiotic therapy on the organ space surgical site infection (SSI) rate in patients presenting with CAA (other than cases of generalized peritonitis) by comparing a group of patients having undergone a conventional strategy of post-operative antibiotic therapy for three days after appendectomy for CAA (the control group) with a group of patients having received a post-operative placebo for three days after appendectomy for CAA (the experimental group). The primary endpoint will be evaluated at one month after randomization.

ReferenceType: derived

ReferenceCitation: Sabbagh C, Siembida N, Dupont H, Diouf M, Schmit JL, Boddaert S, Regimbeau JM. The value of post-operative antibiotic therapy after laparoscopic appendectomy for complicated acute appendicitis: a prospective, randomized, double-blinded, placebo-controlled phase III study (ABAP study). Trials. 2020 Jun 1;21(1):451. doi: 10.1186/s13063-020-04411-1.

oa_colors: green gold

oa_host_type: publisher;repository

evidence: oa journal (via doaj)

host_type: publisher

license: cc-by

license_normalized: cc-by

version: publishedVersion

evidence: oa repository (via OAI-PMH doi match)

host_type: repository

repository_institution: PubMed Central - Europe PMC

repository_normalized: PubMed Central

evidence: oa repository (via pmcid lookup)

license_normalized: no license

repositories_concat: PubMed Central

unpaywall_oa_status: gold

publisher_dissemination: Springer-Nature

sponsor_collaborators: Centre Hospitalier Universitaire, Amiens

appel_a_projets: PHRCN

region: Hauts-de-France

nom_etablissement: CHU AMIENS PICARDIE

type_etablissement: CH

acronyme: ABAP

titre: Intérêt de l'antibiothérapie post-opératoire après appendicectomie sous coelioscopie pour appendicite aiguë compliquée (en dehors des péritonites généralisées) : étude prospective randomisée de phase III contre placebo

discipline_principale: chirurgie viscérale et digestive

nom_porteur: REGIMBEAU

prenom_porteur: Jean Marc


title: Determination of the Minimal Effective Concentration (EC90) of Ropivacaine in Axillary Brachial Plexus Block With Intravenous Dexamethasone or Saline Injection

acronym: AxiRopiDexa

summary: Prospective up and down sequential evaluation of the minimal effective concentration of perineural ropivacaine for 90% success in axillary brachial plexus block with the injection of intravenous dexamethasone or saline placebo during regional anesthesia performance

ipd_sharing: Undecided

ipd_sharing_description: IPD sharing in progress in the institution

lead_sponsor: Centre Hospitalier Universitaire de Besancon

location_facility: Centre Hospitalier Universitaire de Besançon


title: In-hospital Falls and Hemorrhagic Complications : a Descriptive Analysis in Rennes University Hospital

acronym: HEMO-CIH

summary:
Anticoagulant and antiplatelet treatments have well defined indactions, with a clearly proved benefit, respectivly for prevention of arterial and venous emblism and for prevention of athermo-related arterial thrombosis.

Bleeding risk represents the main adverse effect of these antithrombotic medications. Then benefit-risk ratio is sometimes difficult to evaluate, especially for elderly patients prone to fall (incidence of falls estimated to 30% per year for patients over 65), exposed on the one hand to thromboembolic risk and on the other hand to bleeding risk.

Associations between falls and antithrombotic-related bleeding risk had already been evaluated in several studies :

Concerning anticoagulant treatments in patients at high risk of falls, retrospective studies shown a overrated risk of intracranial hemorrhage and mortality, but those results remain discordant wtih 3 major prospective studies on larger populations.
Concerning antiplatelet treatments in patients at high risk of falls, majority of retrospective studies reported an overrated risk of major bleeding, intracranial bleeding and mortality, but datas remain fewer than for anticoagulant and results are as well discordant with prospective studies.
No difference of morbi-mortality is clearly estalblished depending of antithrombotic treatment class (anticoagulant versus antiplatelet), however there is a cumulative risk in case of association of both anticoagulant and antiplatelet.
Main factors associated with fall-related bleeding for patients on anticoagulant include age, female sex, anemia, chronic kidney disease, dementia and polymedication.

Thus, the purpose of this study is to specify whether occurrence of falls justify to reconsider prescription of antithrombotic treatments in patients having an indication of antiplatelet or anticoagulant therapy.


title: Immunological and Functional Characterization of Cellular Population CD45+ Infiltrating Human Glioblastoma

acronym: GLIOBLASTOMES

summary: Despite advances in neurosurgery , radiotherapy and chemotherapy, the median survival in GBM patients is only 15 months from diagnosis. Immunotherapy by checkpoint inhibitors (PD1 /PDL-1) appears as a promising treatment for many cancers. However, first clinical results are disappointing for GBM. An hypothesis is the immunosuppressive activity from infiltrating non-tumor cells. Conversion of non-tumor cells from an immunosuppressive to an immuno-activating phenotype could be attempted in a therapeutic perspective.


title: Importance of Exploring Feasibility and Acceptability in Application of EEG Neurofeedback in Older Adults With Mild Cognitive Impairment

acronym: Neurofeedel

summary: This is a non-pharmacological study evaluating the feasibility of a neurofeedback training program in elderly with mild cognitive impairment (MCI) according to recruitment, retention, attendance, acceptability data.

lead_sponsor: Fabienne Marlats


title: Effect of Oral Administration of Memantine in Pre and Post-surgery in the Prevention of Post-mastectomy Neuropathic Pain

acronym: CLEMANTINE

summary: The aim of this study is to evaluate if memantine administered for four weeks starting two weeks before surgery induces a decrease in pain intensity at 3 months post-mastectomy.


title: Acceptability Study SMARTphone to Collect Clinical Data Using the Memind App by Patients and Medical Satff.

acronym: MeMind

summary: The study goal is to determine the feasbility and interest of monitoring mental health and non mental health related simptoms in Outpatients in order to prevent suicide.

lead_sponsor: University Hospital, Brest


title: Costs of the Patient's Stay Under ExtraCorporeal Membrane Oxygenation From the Hospital Point of View: a Pilot Study at the Rennes University Hospital Center

acronym: ECMONOMY

summary: The objective of this study is to determine the average cost of stay of a patient supported by ExtraCorporeal Membrane Oxygenation from the point of view of the hospital facility, during the hospitalization in which the ECMO was implanted.


title: Myocardial Function of the Setonis Aortic Valve Before and Beyond Valve

acronym: AOMYOC

summary: Study the consequences on heart muscle of the stenosis aortic valve before and after the replacement procedure, the repercussion on heart. Study the impact on the heart of "sick" valve can affect on "well-being" and prognosis in the year following the surgery.


title: Evaluation of Pain Following Scoliosis Surgery.- RACHIDOL

acronym: RACHIDOL

summary: The main objective of this study was to evaluate acute pain following scoliosis surgery in adolescent.


title: Evaluation of Renal Angioplasty on Atherosclerotic Stenosis Since 2010

acronym: PARAS

summary:
The interest of renal angioplasty in the nosological framework of atherosclerotic stenosis has been significantly challenged by STAR and ASTRAL clinical trials in 2009, confirmed by the CORAL study in 2014.

These studies did not show any benefit of the gesture on renal function, morbidity and cardiovascular mortality or the tension control. The aim of the study is to evaluate renal angioplasty on atherosclerotic stenosis.


title: Institut Paoli Calmettes Hepatic Surgery Database

acronym: BDD CHIRHEP

summary: Database of patients who undergo hepatic surgery for: benign diseases, primary or secondary liver cancer at Institut Paoli-Calmettes

lead_sponsor: Institut Paoli-Calmettes


title: NUCLEAR LAMINA, OVARIAN AGE AND MEDICAL ASSISTANCE TO PROCREATION

summary:
The nuclear lamina (LN) consists of a network of proteins interposed between the chromatin and the internal nucleic membrane, to which it is closely associated. LN consists essentially of lamins encoded by the LMNA (Lamines A / C), LMNB1 and LMNB2 genes (BI, B2, B3 lamins). Malfunctions of the A / C-type laminates causing the production of a toxic isoform called progerin are directly responsible for various serious pathologies such as Progeria Hutchingson-Gilford. This rare disease is characterized by accelerated pathological aging. Moreover, it is known that progerin is produced in the absence of any mutation of the gene LMNA is involved in the physiological aging of tissus.

The ovarian reserve of a woman is a parameter that changes with age. Although this progressive loss is inevitable in the course of life, the kinetics of this ovarian exhaustion appear variable according to the women, sometimes leading to an accelerated loss causing a discordance between the female age and the ovarian age. But ovarian age becomes a major prognostic parameter to be taken into account during any attempt at medical assistance to procreation (AMP) and is often incriminated in the failures of MPAs. There are currently few markers to predict the quality of ovarian response of women to ovarian stimulation, let alone the quality of the oocytes retrieved. However, their quality directly influences their ability to give an evolving embryo and therefore a pregnancy Our team has previously shown that type B laminates are involved in human spermiogenesis, and highlighted the human B3 isoform. These very encouraging results obtained on human spermatogenesis, have prompted us to also look at the potential interest of the exploration of the nuclear lamina within the human ovary.

The aim of this project is therefore to continue the exploration of the nuclear lamina and its potential role on the quality of human gametes, by studying the follicular ovarian cells surrounding the oocyte. These cells express A / C type lamins and sometime progerin Investigators want to conduct a prospective pilot study in a cohort of 40 women in MPA, aged between 20 and 42 years. The main objective is to compare the levels of expression of the A / C, B and progerin laminae in the follicular cells of 2 groups of women: a group of infertile patients managed to induce ovulation in order to Intraconjugal AMP and a group of women managed to induce ovulation to give their oocytes. For this purpose, investigators will analyze the expression of the A / C and B lamins in RT-PCR, the localization of the lamins and progerin in immunofluorescence, and will look for quantitative variations in the production of A / C and / or progerin lamins by western- blot, depending on the age of the patients.

This pilot study will allow investigators to characterize for the first time the LN of human follicular cells. They should highlight variations in the expression and / or localization of lamins and possibly progerin in patients tested according to their age and / or ovarian reserve. The team preliminary results showed that this track deserves to be explored. This is an excellent opportunity to bring new insights into the understanding of the mechanisms responsible for alteration of ovarian reserve in women and the prognosis of MPA attempts.

Finally, this approach could serve as a basis for a larger, multicenter study. These markers could represent new diagnostic markers to be taken into account to evaluate the chances of pregnancy of each woman in AMP.

lead_sponsor: Assistance Publique Hopitaux De Marseille

location_facility: Assistance Publique Hôpitaux de Marseille


title: Efficacy of Light Therapy Device LUMINETTE® in Major Depressive Disorder(LUMIDEP)

acronym: LUMIDEP

summary: This study evaluates the addition of light therapy with LUMINETTE device to usual treatment (antidepressant drug and psychotherapy) in the treatment of Major Depressive Disorder (MDD). Half of the participants will receive active light therapy with LUMINETTE device while the other half will receive placebo light therapy with LUMINETTE placebo device.

ReferenceCitation: Schwitzer T, Le Cam S, Cosker E, Vinsard H, Leguay A, Angioi-Duprez K, Laprevote V, Ranta R, Schwan R, Dorr VL. Retinal electroretinogram features can detect depression state and treatment response in adults: A machine learning approach. J Affect Disord. 2022 Jun 1;306:208-214. doi: 10.1016/j.jad.2022.03.025. Epub 2022 Mar 15.

oa_host_type: publisher

evidence: open (via crossref license, author manuscript)

license: publisher-specific-oa

license_normalized: publisher-specific

version: acceptedVersion

unpaywall_oa_status: hybrid

publisher_dissemination: Elsevier

ReferenceCitation: Cosker E, Moulard M, Schmitt S, Angioi-Duprez K, Baumann C, Laprevote V, Schwan R, Schwitzer T. Portable light therapy in the treatment of unipolar non-seasonal major depressive disorder: study protocol for the LUMIDEP randomised controlled trial. BMJ Open. 2021 Jul 9;11(7):e049331. doi: 10.1136/bmjopen-2021-049331.

license: cc-by-nc

license_normalized: cc-by-nc

publisher_dissemination: British Medical Journal

lead_sponsor: Centre Psychothérapique de Nancy

sponsor_collaborators:
Centre Psychothérapique de Nancy
LUCIMED


title: Impact of Histologic Concordance Between Biopsies and the Endoscopic Resection Specimen, in the Treatment of Barrett's Esophagus in Dysplasia, on the Recurrence of Dysplasia

acronym: PatheBarett

summary:
Influence of histological concordance on the risk of recurrence:

the histological concordance being the comparison between the biopsies and the endoscopic resection piece and its concordant response rate.

ReferenceType: result

ReferenceCitation: Godat S, Caillol F, Autret A, Bories E, Pesenti C, Ratone JP, De Cassan C, Poizat F, Giovannini M. Endotherapy in case of relapse of neoplastic Barrett's esophagus after successful initial endoscopic resection. Surg Endosc. 2017 Sep;31(9):3703-3710. doi: 10.1007/s00464-016-5409-5. Epub 2017 Jan 11.


title: Randomized, Double-blind, Placebo Controlled Trial of Effect of ANACA3 Slimming Gel on Loss of Abdominal and Thigh Circumferences in Healthy Volunteers

summary:
Overweight and obesity is defined, according to the World Health Organization (WHO), by abnormal or excessive accumulation of adipose or fatty tissue that may be harmful to health.

Overweight and obesity are therefore important determinants of health, which expose people to many pathologies whose consequences for individuals are not only health, but also social: stigma, prejudice, discrimination.

Indeed, most overweight people have a bad image of themselves. For some people, overweight can trigger stress, malaise and disgust.

To break free from this malaise and satisfy the growing desire of women to take care of their body, many products are present in the slimming beauty market.

EFFANACA3GEL is a prospective, randomized, double-blind, placebo controlled study. 208 healthy volunteers will be followed for 2 months during which they will use ANACA3 slimming gel. The aim of this study is to evaluate the effects of ANACA3 slimming gel on hip and waist circumferences.

lead_sponsor: Nutravalia

sponsor_collaborators:
Nutravalia
Slb Pharma


title: Decolonization of Patients Carrying S. Aureus Before Cardiac Surgery: Study of the Risk Factors Associated With Failure

acronym: STAdécol

summary: Staphylococcus aureus nasal carriage is a well-known risk factor for S. aureus surgical site infections (SSI). According to a recent study demonstrating 60% reduction risk of SSI due this bacterium after patients' screening and decolonization, recent French and WHO guidelines recommend in cardiac surgery the decolonization of nasal S. aureus carriers before surgery. In practice the decolonization procedures are not well-defined according notably to the duration and time of delivery before surgery and doses of topical antimicrobial drugs. The aim of the proposed study is to investigate the factors associated with failures of S. aureus decolonization: carriage state, compliance with treatment, S. aureus capacity of internalization in nasal epithelial cells, resistance to antimicrobial drugs used. This study will allow (i) to measure the frequency of patients with residual S. aureus carriage just before surgery, whatever they have been decolonized or not, (ii) to characterize the S. aureus nasal carriage state of patients before surgery, and (iii) to investigate the adding value of mupirocin dosage in the nose and urines of decolonized patients as a marker of compliance and efficacy of the decolonization process.

lead_sponsor: Centre Hospitalier Universitaire de Saint Etienne


title: Association Between Renal and Right Cardiac Functions After Urinary Sodium Depletion Following Cardiac Surgery: a Prospective Observational Study

acronym: DECONGEST

summary: Following cardiac surgery, right ventricular function may be altered leading to increase central venous pressure and decrease in renal blood flow. The investigator's standard care includes use of diuretic to avoid interstitial fluid accumulation. The aim of the study is to assess cardiac and renal function before and after depletion by using diuretics


title: Rehabilitation by Effort for Patients With Advanced Bronchial Cancer

acronym: RehabKBP

summary:
Bronchopulmonary cancers or mesothelioma are associated with effort deconditioning due to pathology (chronic inflammation) and also to treatments (surgery, radiotherapy, chemotherapy); it's considerably alters patients quality of life.

Investigators want to ensured the feasibility of rehabilitation by effort for these patients.

lead_sponsor: University Hospital, Toulouse


title: Comparative Analysis of Filmed Sequences for the Assessment of Discomfort in Atopic Dermatitis of Infants Under 6 Months of Age

acronym: PRURINEO

summary:
Atopic dermatitis (AD) is an frequent chronic and itchy inflammatory dermatitis which concern about 20% of pediatric population with a revelation usually toward 3-6 months of live. However, there are very few data about the prevalence of pruritus of young infants and about the discomfort linked with it. While the skin and the nervous system of young infants (Under 6 month) are competent in pruritus experiment, the acquisition of conscious and deliberate motor ability allowing specific scratching of the body parts which are affected is possible only from 6 month. Thus, the diagnosis of AD intensity and the assesment of the potential associated discomfort are hard. At the present time, the diagnosis and the assesment of pruritus of children are based on a hetero-assesment via scales which are not applicable for infants under 6 month. The visual scale "Numeric Rating Scale" validated in adult population seems to be the most specific to assess AD severity. In pediatric population, the use of "Eppendorf Itch Questionnaire" and the american version of "Childhood Atopic Dermatitis Impact Scale" are recommended. Alternatives to clinic and subjective scoring of pruritus severity are described via actigraphy. Thus, a strong statistic correlation have been demonstrated between a nocturne measure of motor activity of wrist, as a reflect of the intensity of pruritus, and infra-red video analysis. But, once again, the technic is not adapted to young infants because of the absence of conscious and oriented motor ability and as a result of less organised sleep/wake cycle.

In order to improve young infants' (Under 6 month) care, the analysis of their behaviours with AD seems to be necessary to better identify a discomfort of these patients.


title: Stroke Observatory of Caen-Normandie Metropole

acronym: NORMANDYSTROKE

summary: Stroke Observatory of Caen-Normandy Metropole provides epidemiological data in prospective collection. The primary objective is to determinate incidence of Stroke in this area. Several data sources will be crossed to allow an exhaustive identification of the cases. No intervention will be carried. The data collected will correspond to those obtained in current practice. The number of participants is estimated at 800 per year. This Observatory aims to become a qualified population register after three years, according to requirement of the french registry evaluation committee.

lead_sponsor: University Hospital, Caen


title: Satisfaction Assessment of Patients With Local Breast Cancer When Using Cosmetics During Chemotherapy and Post-treatment Thermal Cure

acronym: COSMIK

summary: The purpose of this study is to assess the satisfaction, the observance, the intolerance, the qualitative appreciation and the expectations of the patients related to the use of the cosmetic products ("Tendre Caresse au cold cream" body cream and "Crème de douche" face and body cleanser from Cosmétosource) during chemotherapy and post-treatment thermal cure

lead_sponsor: Centre Jean Perrin


title: Inflammatory Response to Paramyxovirus Infection in an Ex-vivo Model of Bronchial Epithelial Cells in Allogeneic Hematopoietic Stem Cell Recipients

acronym: ALLOVIRO

summary:
Introduction. Chronic graft-versus-host-disease (GVHD) is the main late noninfectious complication after allogeneic hematopoietic stem cell transplantation (HSCT) that can affect several organs. Bronchiolitis obliterans syndrome (BOS) is recognized as pulmonary chronic GVHD. A diagnosis of a lower respiratory tract infection in the first 100 days following transplant has been associated to the development of BOS. One hypothesis is that the first stage driving to BOS is a previous aggression of bronchial epithelial cells by various factors such as chemotherapy and radiotherapy. Thereafter, data suggest that viral infections, in particular Parainfluenza viruses could be a trigger for BOS. The alloimmune reaction activated by the respiratory virus could lead to the fibrosis process. Our hypothesis is that the bronchial epithelium of allogeneic HSCT recipients has phenotypic specificities that are associated with a specific response to the viral respiratory infections (in particular paramyxovirus) leading to the development of BOS.

Main objective. To characterize and compare the inflammatory response after infection with Parainfluenza 3 virus in an ex-vivo model of bronchial epithelial cells obtained from allogeneic HSCT recipients and controls.

Objective secondary. To characterize the phenotypic specificities of allogeneic HSCT recipients' bronchial epithelium.

Methodology, and experimental plan. Prospective, monocentric research. Bronchial biopsies obtained from patients, will be completely differentiated after 21 days of culture. Epithelial cells will be infected by the virus strain Parainfluenza 3. Transcriptome of the cells from both allogeneic HSCT patients and controls, infected and non-infected will be analyzed 48 hours after infection.

lead_sponsor: Assistance Publique - Hôpitaux de Paris


title: Population Pharmacokinetics Modeling : a Priori Optimization of Amikacin First Dose in Critically Ill Patients Using a Nomogram

acronym: PIC-AMI

summary: The aim of this study is to elaborate nomograms to optimize amikacine first dosing in critically ill patients, using a population pharmacokinetics model elaborated with multicentric data.

ReferenceCitation: Roger C, Nucci B, Louart B, Friggeri A, Knani H, Evrard A, Lavigne JP, Allaouchiche B, Lefrant JY, Roberts JA, Muller L. Impact of 30 mg/kg amikacin and 8 mg/kg gentamicin on serum concentrations in critically ill patients with severe sepsis. J Antimicrob Chemother. 2016 Jan;71(1):208-12. doi: 10.1093/jac/dkv291. Epub 2015 Oct 1.

lead_sponsor: Nantes University Hospital

collaborators: Centre Hospitalier Universitaire de Nīmes


title: Antibiotic De-escalation in Onco-hematology Patients for Sepsis or Septic Shock

acronym: DéPOH

summary:
De-escalation aims at reducing the use of broad-spectrum antibiotics and therefore the emergence of multidrug-resistant (MDR) pathogens.

Observational studies suggested that this strategy seems to be safe. However, there is no adequate, direct evidence showing de-escalation of antimicrobial agents to be effective and safe for onco-hematology patients with sepsis or septic shock. Thus, randomized clinical trials are needed for testing the safety and efficiency of de-escalation of antimicrobial therapy.

The investigator's hypothesis is that de-escalation of empirical antimicrobial therapy in onco-hematology patients with sepsis or septic shock is noninferior to the continuation of empirical antimicrobial therapy.

The first aim of the study is to demonstrate that de-escalation is noninferior to the continuation of broad-spectrum antibiotics in terms of hospital mortality.

The secondary aims are to compare the two strategies in terms of mortality, duration of antimicrobial therapy, durations of mechanical ventilation, vasopressor use, numbers of superinfections, organ failure.

Antimicrobial de-escalation (ADE) of antimicrobial therapy is a strategy proposed to allow for the rational use of broad-spectrum antimicrobial therapy as the empiric treatment for infections and minimize the overall exposure to these broad-spectrum agents. The need for prompt, effective antimicrobial therapy for patients with known or suspected infections is widely accepted. This principle leads to the use of very broad-spectrum antimicrobial therapy to increase the odds that all suspected potential pathogens are adequately treated. However, the potential drawback is selection of multidrug-resistant (MDR) organisms.

ADE is widely recommended in the management of antimicrobial therapy in intensive care unit (ICU) patients. The Surviving Sepsis Campaign guidelines describe and recommend the process for selecting antimicrobial therapy as commencement of antimicrobials within the first hour, antimicrobial therapy broad enough to cover all likely pathogens, and daily reassessment for potential ADE.

To date, no randomized study assessing this strategy is available for this specific population of cancer critically ill patients. In a recent systematic review based on 13 observational studies and one randomized controlled trial, the authors conclude that the equipoise remains and a large randomized trial is required to assess the effect of the antibiotics de-escalation strategy on the bacterial ecosystem, on MDR carriage, and on patient outcomes.

appel_a_projets: PHRCK

region: Provence-Alpes-Côte d'Azur

nom_etablissement: INSTITUT PAOLI CALMETTES

type_etablissement: CLCC

acronyme: DePOH

titre: DéPOH-DESESCALADE ANTIBIOTIQUE CHEZ LE PATIENT D'ONCO-HEMATOLOGIE ADMIS EN REANIMATION POUR SEPSIS SEVERE OU CHOC SEPTIQUE

discipline_principale: cancer

nom_porteur: MOKART

prenom_porteur: Djamel


title: Early and Comprehensive Care Bundle in Elderly for Acute Heart Failure: a Stepped Wedge Cluster Randomized Trial

acronym: ELISABETH

summary: This is a prospective multicentre (N=15), stepped-wedge randomized trial that aims to evaluate the benefit of a protocolised comprehensive care bundle for early management of acute heart failure in the ED.

ReferenceCitation: Freund Y, Cachanado M, Delannoy Q, Laribi S, Yordanov Y, Gorlicki J, Chouihed T, Feral-Pierssens AL, Truchot J, Desmettre T, Occelli C, Bobbia X, Khellaf M, Ganansia O, Bokobza J, Balen F, Beaune S, Bloom B, Simon T, Mebazaa A. Effect of an Emergency Department Care Bundle on 30-Day Hospital Discharge and Survival Among Elderly Patients With Acute Heart Failure: The ELISABETH Randomized Clinical Trial. JAMA. 2020 Nov 17;324(19):1948-1956. doi: 10.1001/jama.2020.19378.

oa_colors: green other

evidence: open (via free pdf)

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Diderot

repository_normalized: HAL

version: submittedVersion

repositories:
HAL
PubMed Central

repositories_concat: HAL;PubMed Central

unpaywall_oa_status: bronze

publisher_dissemination: American Medical Association

ReferenceCitation: Freund Y, Gorlicki J, Cachanado M, Salhi S, Lemaitre V, Simon T, Mebazaa A. Early and comprehensive care bundle in the elderly for acute heart failure in the emergency department: study protocol of the ELISABETH stepped-wedge cluster randomized trial. Trials. 2019 Jan 31;20(1):95. doi: 10.1186/s13063-019-3188-8.

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Inria

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - IN2P3

evidence: oa repository (via page says license)

repository_normalized: Research Square

repositories:
HAL
PubMed Central
Research Square

repositories_concat: HAL;PubMed Central;Research Square

location_facility: Emergency department Hospital Pitié-Salpêtrière

region: Île-de-France

nom_etablissement: ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS

type_etablissement: CHUR

acronyme: ELISABETH

titre: Evaluation d'une prise en charge précoce du syndrome d'insuffisance cardiaque aiguë du sujet âgé aux urgences : une étude randomisée en cluster de type stepped wedge

discipline_principale: médecine d'urgence

nom_porteur: Mebazaa

prenom_porteur: Alexandre


title: Diagnostic Suspicion of Primitive Syndrome Sjögren's : Brest Cohort

acronym: DIApSS

summary: This study aims to evaluate the diagnosis performance of several item used for the classification, the diagnosis and the prognostic of pSS (primary Sjogren syndrome)


title: Indication to Transplant Patients With High Risk B Cells Lymphoma in Metabolic Complete Remission After 2 Cycles of Chemotherapy ?

summary:
The autograft of patients with prognostically unfavourable B-cells lymphoma cells in first remission remains controversial, in particular since the association of Rituximab with chemotherapy. Even though many randomized and non-randomized studies have been conducted, their is still no standard procedure . Recently, the use of early TEP (positron emission topography) answer, after 2 in 3 cures of chemotherapy allowed to select the poor-responder patients who remain candidate to autograft in front-line. Nevertheless, in good-responder patients, the benefits of an intensification therapy ins term of long-lasting disease control remains discussion.

This institutional retrospective study aims at comparing the outcome of early metabolic responder patients who received an intensification treatment to those who received a standard chemotherapy.


title: Multi-center Register for the Use of the Cor-Knot® Automated Knotting System in Heart Valve Surgery

acronym: RECORVA

summary: The Cor-Knot® device is an automated knotting system for valve sutures and prosthetic rings used for more than a year during valve replacements and annuloplasties in cardiac surgery. It reduces the time spent knotting the threads fixing the prosthesis and thus reduces aortic clamping and extracorporeal circulation times. The originality of the project is based on the absence of national multi-rate data collection on the effectiveness and safety of the Cor-Knot® knotting device.

lead_sponsor: Centre Hospitalier Universitaire Dijon


title: Exploration of Glutamatergic System With PET Radiotracer in Gilles de la Tourette Patients: Pilot Study (GlutaTour)

acronym: GlutaTour

summary: Gilles de la Tourette syndrome is a neuropsychiatric disorder characterized by motor and vocal tics often associated with psychiatric comorbidities (obsessive compulsive disorder, anxiety and depressive syndrome, impulsivity). The pathophysiology of Gilles de la Tourette syndrome remains unclear.

location_facility: Hôpital Pierre-Paul Riquet - CHU Toulouse


title: Evaluation of the Risks and Benefits of Abdominal Massage Treatment in Neonatalogy in Premature Children

acronym: PREMASS

summary:
Premature birth creates difficulties for the child in starting his diet and digestion. The immaturity of the major vital functions complicates the abdominal transit. The initial diet, essentially parenteral in the central way, decreases progressively according to the digestive tolerance allowing the increase of the enteral feedings to optimize the growth. To ensure this transition, nurses nurses in Neonatology service, through their knowledge and expertise, practice a daily gesture: abdominal massage-care. This prevents or remedies a slowing of transit. The paramedical clinical examination of the child, determines the realization of this care. Several studies have proved the benefit of massage on the weight gain of premature babies. These stimulate peristalsis, decrease the duration of intestinal transit and the sensations of discomfort and pain related to it. Currently in Neonatology, developmental care (NIDCAP) is an approach to individualized care for the premature to improve its evolution. The fine observation of his behavior allows us to adapt our care and to ensure the respect of his pace. However, the first sensory capacity developed in the fetus, the touch can also be a source of over-stimulation for the premature baby. Moreover, the greater the prematurity, the greater the risk of occurrence of digestive complications. Can the abdominal care-massage in premature babies be harmful or risk increasing existing symptoms? The abdominal care-massage is neither described nor referenced in the nomenclature of nursing, neither taught nor subject to medical prescription.

Few publications exist on this subject, no large-scale research has been reported. On the other hand, the perception of our empirical practice seems to show that the abdominal massage-care is an important aid to the smooth transit of the premature newborn. Transmitted orally by professionals to newcomers to Neonatology, this treatment is carried out in a heterogeneous manner according to professionals. Convinced of its effectiveness, carers wonder about their practice: is there an optimal technique without risk for the child? Determining the absence of risk and the effectiveness of the abdominal care-massage suggests a wider benefit for the well-being and progress of the premature child until he leaves the hospital. This validated practice could be disseminated on a larger scale in other neonatal departments.

ipd_sharing_description: Publication


title: How to Give Back the Pleasure of Eating to the Dependent elderly_observational Study

acronym: Petit-dejeuner

summary:
Many public health recommendations and policies aim to combat malnutrition in the elderly. It must be noted that levels of malnutrition are high in the elderly with more than 70% of the dependent population at home or in institutions and 30 to 70% of elderly people in hospitals.

In hospitals, the collective catering system and the "medicalisation" of meals (diets, medicines, etc.) force patients to change their eating habits, and they are often faced with a lack of choice and a less pleasurable experience. These organizational constraints are particularly harmful for elderly patients who tend to be malnourished or at risk of malnutrition and who are often polypathological and polymedicated.

If eating is one of the only pleasures sometimes left to this fragile population, breakfast is one of the most appreciated meals of the day (after a fasting time >10h). It tends to follow the habits acquired at home and is mostly oriented towards sweet foods. However, it is not known whether different and more varied choices could change dietary directions and intakes.

Offering sweet and savoury foods can upset medical prescriptions, cultural habits and can go against what remains a patient need: the pleasure of eating.

Although some work in the medico-social field has been successfully carried out and has reported changes in dietary behaviour in a choice situation (buffet type) at breakfast, scientific studies have not yet been done in a retirement home environment. The objective of this project is to emphasize the sensory pleasure and commensality of breakfast. During this buffet meal, sweet and savoury foods will be offered. The idea is to detect if the variety will naturally direct individual choices towards the savory and/or sweet flavours and if it encourages an increase in caloric and protein intakes. Several studies have shown that sensory changes in the elderly can lead to changes in behaviour and food preferences. The decrease in the pleasure only accentuates the causes of malnutrition. Moreover, preconceived ideas reinforce the association between the elderly and a preference for sweet foods. However, no study has shown that the elderly find less pleasure in savory than sweet foods, especially at breakfast.

The research will be organized as follows:

Phase 1: follow-up of breakfast consumption by food weighing. This is a prospective study that will be carried out at Dijon University Hospital within the retirement home.

The consumption of each meal will be measured the day of the breakfast with savory and sweet options, and then two days after in usual conditions in the individual's room. The distribution, service and consumption methods will be consistent with the habits of the units where the investigation is taking place.

For each resident, food consumption will be recorded three times, at one month intervals over 2 non-consecutive days.

Phase 2: observations at breakfast time Pleasure evaluation - Feasibility - commensality - conviviality A SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis will be conducted for each type of environment and meals offered. This analysis will be done using established grids and semi-directive interviews with resource persons who are working in the field (the professionals involved), and with research support units. The professionals will be asked to complete various scales, of the Likert type, before and after the breakfasts included in the study.


title: Pharmacokinetics of Levosimendan, OR1855 and OR1896 in Neonates and Children With or Without Extracorporeal Membrane Oxygenation

acronym: PALMAréa

summary: To describe pharmacokinetics of levosimendan in neonates and children supported or not with extracorporeal circulation devices (ECMO, CRRT)

ReferenceCitation: Kivikko M, Antila S, Eha J, Lehtonen L, Pentikainen PJ. Pharmacokinetics of levosimendan and its metabolites during and after a 24-hour continuous infusion in patients with severe heart failure. Int J Clin Pharmacol Ther. 2002 Oct;40(10):465-71. doi: 10.5414/cpp40465.


title: Methods for Fertility Preservation: Impact of Vitrification on in Vitro Matured Oocytes

acronym: OVOMIV

summary:
During the last decades, there was an improvement of the cancer treatments of the woman and the teenagers. Therefore higher survival rate is described. However, cancer treatments can alter the reproduction functions and reduce considerably the window of the fertility to the adulthood. Therefore, it is recommended to proceed to a fertility preservation by oocytes vitrification when it is possible. The vitrification is a freezing technique allowing high survival rate and similar results by assisted reproductive technologies compared with the use of fresh oocytes. An innovative method of automated vitrification was recently developed. The usual protocol consist to vitrify mature oocytes. However, this strategy cannot be used for hormone -sensitive cancer or when ovarian stimulation is not possible. In these situations, immature oocytes can be collected. It is also necessary to realize an in vitro maturation step for a use by assisted reproductive technology.

According to the recent data of the literature, it remains unclear whether the vitrification of ovocytes must be performed before or after in vitro maturation (IVM). Therefore the aim of this study is to study the impact on structure and functions of ovocytes when vitrification is performed before or after IVM. The vitrification will be performed by a semi-automatic method which is an innovative method.

lead_sponsor: University Hospital, Clermont-Ferrand


title: sCD160 in Sera and Intra-ocular Fluids: Association With Ischaemic Retinopathies

summary:
CD160 represents a new angiogenic factor as its specific engagement by an agonist monoclonal antibody directed against human CD160 reduced angiogenesis of endothelial cells with a distinct mechanism from current angiogenic therapies that target the VEGF/VEGF-R pathway. A soluble form of CD160, sCD160, has been found to be highly expressed in the vitreous and the sera of patients with severe diabetic retinopathies, and can now be dosed with help of an ELISA test.

The investigators aim to evaluate the association between ischaemic retinopathies (patients with or without) and sCD160 concentrations in the vitreous, the aqueous humour and the serum.

lead_sponsor: CHU de Reims


title: Phase II Study Evaluating Adaptive Radiation Therapy in Pre-operative or Exclusive Radiation Therapy for Limb Soft Tissues Sarcomas

acronym: ADAPTO-SARC

summary:
Soft tissue sarcomas (STS) is generally treated by surgery, followed or preceded by radiotherapy and chemotherapy. Preoperative irradiation has been shown to be effective in a randomized trial, and is often indicated in locally advanced Soft tissue sarcomas of the limbs, in order to reach R0 resection, or in case of rapid tumor growth despite first chemotherapy. For inoperable sarcomas, radiotherapy is an efficient palliative treatment, increasing local control.

Adaptive radiotherapy is defined as the set of procedures leading to the modification of a treatment plan based on the individual variations observed during irradiation. The place of this technique is increasing since the development of image-guided-radiotherapy allowing the visualization of daily variations in position, shape or volume of the tumor and organs at risk. Its implementation in current practice however remains limited because of the cumbersome processes involved (new delineation, new dose calculation, or even re-optimization) and resources to commit, especially in human time.

Irradiation of soft tissue sarcomas always begins with a planning CT scan, where the target-volumes and organ at risk are delineated, and dosimetric calculations are performed prior to radiotherapy initiation. During the radiotherapy, the variations leading to a mismatch between the planned dose and the dose delivered are multiple. These may be due to positioning errors or morphological changes in the patient (weight loss), or in the tumor or organs at risk (modifications in shape, size or position). The volume of soft tissue sarcomas changes also during radiotherapy (response, progression or pseudo- progression of the tumor).

However, to date, few data are available in the literature both on the volume variation of soft tissue sarcomas during preoperative radiotherapy, and on the interest of adaptive radiotherapy in the management of these tumors. It is therefore necessary to evaluate whether modifications of growth or macroscopic tumor volume are observed during the treatment, and to evaluate dosimetric impact on the target volume coverage that could impact the results of the treatment.

This a prospective multicentric phase II trial conducted to evaluate the interest of adaptive radiotherapy in the preoperative or exclusive management of limb sarcomas Patients will be treated by preoperative or definitive radiotherapy for a limb soft tissue sarcomas, using an intensity-modulated conformal irradiation (with a static or dynamic technic), over 5 to 7 consecutive weeks. The total dose delivered will be of 50 Gray (preoperative radiation therapy), or 60 to 70 Gray (exclusive radiation therapy). The delineation of growth or macroscopic tumor volume,clinical target volume, and planning target volume, as well as healthy surrounding tissues will be carried out in each of the centers, and under the responsibility of the radiotherapist, on The simulation CT-scan, used for dosimetry, and 3 CT scan performed on day 1 of radiotherapy (d1), at a dose of 30Gy (d30Gy) and 50Gy (d50GY). The dosimetric re-planning according to the variations of the volume of the planning target volume will be done in case of significant variation of the target volume according to de definition mentionned in the main and secondary objectives.

Main objective: The aim of this study is to evaluate the interest of adaptive radiotherapy in the preoperative or exclusive management of limb sarcomas.

This is the first prospective trial focused on the evaluation of the volume variation of soft tissue sarcomas during preoperative radiotherapy, and also on the interest of adaptive radiotherapy in the management of these tumors, whereas indications of preoperative and/or exclusive radiation therapy are very frequent.

intervention_type: Radiation


title: Interest of Training in Procedural Simulation of Nurses in Reducing Complications Related to Arteriovenous Fistula Puncture in Chronic Hemodialysis Patients

acronym: SIMFAV

summary: Interest of training in procedural simulation of nurses in the reduction of complications related to arteriovenous fistula puncture in hemodialysis patients


title: Single-center Trial for the Validation of High-resolution Transrectal Ultrasound (Exact Imaging Scanner ExactVu) for the Detection of Prostate Cancer

acronym: EXACTVU

summary: The primary objective of this study is to evaluate the performance of HR-TRUS in detection of prostate cancer lesions relative to whole mount section after radical prostatectomy as the reference.

ReferenceCitation: Pavlovich CP, Cornish TC, Mullins JK, Fradin J, Mettee LZ, Connor JT, Reese AC, Askin FB, Luck R, Epstein JI, Burke HB. High-resolution transrectal ultrasound: pilot study of a novel technique for imaging clinically localized prostate cancer. Urol Oncol. 2014 Jan;32(1):34.e27-32. doi: 10.1016/j.urolonc.2013.01.006. Epub 2013 Apr 2.

ReferenceCitation: Walz J, Marcy M, Maubon T, Brunelle S, Laroche J, Gravis G, Salem N, Bladou F. [Real time elastography in the diagnosis of prostate cancer: comparison of preoperative imaging and histology after radical prostatectomy]. Prog Urol. 2011 Dec;21(13):925-31. doi: 10.1016/j.purol.2011.04.006. Epub 2011 Jun 2. French.

ReferenceCitation: Ghai S, Eure G, Fradet V, Hyndman ME, McGrath T, Wodlinger B, Pavlovich CP. Assessing Cancer Risk on Novel 29 MHz Micro-Ultrasound Images of the Prostate: Creation of the Micro-Ultrasound Protocol for Prostate Risk Identification. J Urol. 2016 Aug;196(2):562-9. doi: 10.1016/j.juro.2015.12.093. Epub 2016 Jan 12.

ReferenceCitation: Boehm K, Salomon G, Beyer B, Schiffmann J, Simonis K, Graefen M, Budaeus L. Shear wave elastography for localization of prostate cancer lesions and assessment of elasticity thresholds: implications for targeted biopsies and active surveillance protocols. J Urol. 2015 Mar;193(3):794-800. doi: 10.1016/j.juro.2014.09.100. Epub 2014 Sep 28.

ReferenceCitation: Villers A, Puech P, Mouton D, Leroy X, Ballereau C, Lemaitre L. Dynamic contrast enhanced, pelvic phased array magnetic resonance imaging of localized prostate cancer for predicting tumor volume: correlation with radical prostatectomy findings. J Urol. 2006 Dec;176(6 Pt 1):2432-7. doi: 10.1016/j.juro.2006.08.007.

sponsor_collaborators:
Institut Paoli-Calmettes
Exact Imaging