title: PHEDRE trial protocol - observational study of the prevalence of problematic use of Equimolar Mixture of Oxygen and Nitrous Oxide (EMONO) and analgesics in the French sickle-cell disease population.
abstract: BACKGROUND
  The use of analgesics can lead to cases of drug abuse and dependence. It can also cause pseudo-addiction in patients suffering from pain. What is the actual situation in patients suffering from severe sickle-cell disease, exposed to acute pain during vaso-occlusive crises? Evaluation of the use of analgesics, on the basis of Diagnostic and Statistical Manual of Mental Disorders criteria for substance abuse and dependence, makes it possible to differentiate the symptoms occurring only in a context of pain, in the aim of managing the pain, and thus describing pseudo-addiction, from symptoms also occurring when there is no pain, and more in favour of true addiction. Currently there is no data available in France on this problem, and no studies have been carried out in children or adolescents with sickle-cell disease. The purpose of the study is to evaluate the prevalence of problematic use of equimolar mixture of oxygen and nitrous oxide and other analgesic drugs in a population of subjects with severe sickle-cell disease in France.
  
  
  METHODS
  PHEDRE (Pharmacodépendance Et DREpanocytose-drug dependence and sickle-cell disease) is an observational, descriptive and transversal study. Patients under the age of 26 with sickle-cell disease are included in the study by the doctors looking after them in sickle-cell disease centres. The patients are then contacted by a trained researcher for a telephone interview, including an evaluation of the Diagnostic and Statistical Manual of Mental Disorders criteria for abuse and dependence to equimolar mixture of oxygen and nitrous oxide and for each of the analgesic drugs taken by the patient. The data are also completed using the subject's medical record.
  
  
  CONCLUSIONS
  This study will make it possible to provide an initial quantitative and qualitative evaluation of problematic use of equimolar mixture of oxygen and nitrous oxide and analgesic drugs in the sickle-cell disease population. The results will be used firstly to provide additional data essential for monitoring the risk of overdose, abuse, dependence and misuse of these products, and to begin awareness-raising and to provide information for health care professionals, in order to significantly improve the management of sickle-cell disease-related pain.
  
  
  BACKGROUND
  Clinical Trials.gov ID: NCT02580565 registered 16 October 2015 Unique Protocol ID: RC14_0344.
authors.affiliation: Clinical Pharmacology Department, Nantes University Hospital, Institut de Biologie, 9 quai Moncousu, 44093, Nantes Cedex 1, France. marie.gerardin@chu-nantes.fr.|EA 4275 SPHERE « bioStatistics, Pharmacoepidemiology and Human sciEnces REsearch, Faculties of Medicine and Pharmaceutical Sciences, Nantes University, Nantes, France. marie.gerardin@chu-nantes.fr.
authors.forename: Marie
authors.initials: M
authors.lastname: Gérardin
authors.affiliation: Paediatric Haematology Department, Nantes University Hospital, 7 quai Moncousu, 44093, Nantes Cedex 1, France. marielaure.couec@chu-nantes.fr.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Couec
authors.affiliation: EA 4275 SPHERE « bioStatistics, Pharmacoepidemiology and Human sciEnces REsearch, Faculties of Medicine and Pharmaceutical Sciences, Nantes University, Nantes, France. marie.bronnec@chu-nantes.fr.|Addictology and Psychiatry Department, Nantes University Hospital, 85 rue de Saint-Jacques, 44093, Nantes Cedex 1, France. marie.bronnec@chu-nantes.fr.
authors.forename: Marie
authors.initials: M
authors.lastname: Grall-Bronnec
authors.affiliation: EA 4275 SPHERE « bioStatistics, Pharmacoepidemiology and Human sciEnces REsearch, Faculties of Medicine and Pharmaceutical Sciences, Nantes University, Nantes, France. fanny.feuillet@univ-nantes.fr.|Biometry Platform, Nantes University Hospital, Nantes, France. fanny.feuillet@univ-nantes.fr.
authors.forename: Fanny
authors.initials: F
authors.lastname: Feuillet
authors.affiliation: Clinical Pharmacology Department, Nantes University Hospital, Institut de Biologie, 9 quai Moncousu, 44093, Nantes Cedex 1, France. laura.wainstein@hotmail.com.
authors.forename: Laura
authors.initials: L
authors.lastname: Wainstein
authors.affiliation: Clinical Pharmacology Department, Nantes University Hospital, Institut de Biologie, 9 quai Moncousu, 44093, Nantes Cedex 1, France. morgane.rousselet@chu-nantes.fr.|EA 4275 SPHERE « bioStatistics, Pharmacoepidemiology and Human sciEnces REsearch, Faculties of Medicine and Pharmaceutical Sciences, Nantes University, Nantes, France. morgane.rousselet@chu-nantes.fr.|Addictology and Psychiatry Department, Nantes University Hospital, 85 rue de Saint-Jacques, 44093, Nantes Cedex 1, France. morgane.rousselet@chu-nantes.fr.
authors.forename: Morgane
authors.initials: M
authors.lastname: Rousselet
authors.affiliation: Clinical Pharmacology Department, Nantes University Hospital, Institut de Biologie, 9 quai Moncousu, 44093, Nantes Cedex 1, France. marie-lyne.pinot@chu-nantes.fr.
authors.forename: Marie-Lyne
authors.initials: ML
authors.lastname: Pinot
authors.affiliation: Clinical Pharmacology Department, Nantes University Hospital, Institut de Biologie, 9 quai Moncousu, 44093, Nantes Cedex 1, France. fanny.perrouin@chu-nantes.fr.
authors.forename: Fanny
authors.initials: F
authors.lastname: Perrouin
authors.affiliation: Child and Adolescent Psychiatry Department, Nantes University Hospital, 7 quai Moncousu, 44093, Nantes Cedex 1, France. olivier.bonnot@chu-nantes.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bonnot
authors.affiliation: Paediatric Oncology and Haematology Department, Nantes University Hospital, 7 quai Moncousu, 44093, Nantes Cedex 1, France. mariehelene.drouineau@chu-nantes.fr.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Drouineau
authors.affiliation: Clinical Pharmacology Department, Nantes University Hospital, Institut de Biologie, 9 quai Moncousu, 44093, Nantes Cedex 1, France. pascale.jolliet@univ-nantes.fr.|EA 4275 SPHERE « bioStatistics, Pharmacoepidemiology and Human sciEnces REsearch, Faculties of Medicine and Pharmaceutical Sciences, Nantes University, Nantes, France. pascale.jolliet@univ-nantes.fr.
authors.forename: Pascale
authors.initials: P
authors.lastname: Jolliet
authors.affiliation: Clinical Pharmacology Department, Nantes University Hospital, Institut de Biologie, 9 quai Moncousu, 44093, Nantes Cedex 1, France. caroline.vigneau@chu-nantes.fr.|EA 4275 SPHERE « bioStatistics, Pharmacoepidemiology and Human sciEnces REsearch, Faculties of Medicine and Pharmaceutical Sciences, Nantes University, Nantes, France. caroline.vigneau@chu-nantes.fr.
authors.forename: Caroline
authors.initials: C
authors.lastname: Victorri-Vigneau
mesh_terms: D000293:Adolescent; D000328:Adult; D000700:Analgesics / Q000008:administration & dosage*; D000755:Anemia, Sickle Cell / Q000188:drug therapy*; D002648:Child; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D009609:Nitrous Oxide / Q000008:administration & dosage*; D010100:Oxygen / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D019966:Substance-Related Disorders / Q000150:complications; D055815:Young Adult
chemical_list: D000700:Analgesics; D009609:Nitrous Oxide; D010100:Oxygen