title: Prevention of Morbidity in sickle cell disease--qualitative outcomes, pain and quality of life in a randomised cross-over pilot trial of overnight supplementary oxygen and auto-adjusting continuous positive airways pressure (POMS2a): study protocol for a randomised controlled trial.
abstract: BACKGROUND
  Sickle cell anaemia (SCA) is an inherited disorder of haemoglobin. Patients experience long-term health care problems, affecting quality of life (QOL) including frequent acute pain, which is difficult to document in trials except as hospital admissions. Pilot data suggests that overnight respiratory support, either supplementary oxygen or auto-adjusting continuous positive airways pressure (APAP), is safe and may have clinical benefit. This pilot trial aims to determine which intervention is more acceptable to participants and whether there are other advantages of one over the other, e.g. in respiratory function or haematological parameters, before conducting the Phase 2 trial of overnight respiratory support funded by the National Institutes of Health Research.
  
  
  METHODS
  This is a pilot cross-over interventional trial with the order of interventions decided by simple randomization. Ten adults (age over 18 years) and 10 children (aged between 8 and 18 years) with homozygous sickle cell disease (haemoglobin SS, HbSS), recruited regardless of symptoms of sleep-disordered breathing, will undergo overnight pulse oximetry and will have two interventions, overnight oxygen and APAP, for a week each in randomised order with a washout week between interventions. Participants will complete online diaries via an iPad throughout the 29 days of the study and will complete QOL questionnaires and have measurement of haematology, biochemistry, spirometry and lung volumes (adults only) at 3 time points, at baseline and after each intervention, as well as in-depth semi-structured qualitative interviews after each intervention, carried out by an experienced psychologist. Both qualitative and statistical methods will be used to analyze the data. The primary outcome is qualitative data looking at participant experience from the transcribed interviews after each intervention. The participant's view on feasibility, acceptability and preference will specifically be explored. The QOL, laboratory and lung function data will be compared with baseline for each arm.
  
  
  CONCLUSIONS
  Patient and public involvement is an integral part of this trial and the key outcome is the qualitative result, which is dependent on obtaining good quality data to advise on participant feasibility, acceptability and preference. This is being addressed by using a standard interview. The development of a pain endpoint is another important outcome and collecting daily measurements is likely to be challenging. Research results will be used to inform design of the Phase 2 trial.
  
  
  BACKGROUND
  ISRCTN46078697 18 July 2014.
authors: Department of Haematology, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK. Jo.Howard@gstt.nhs.uk.
authors: Jo
authors: J
authors: Howard
authors: Evelina Children's Hospital, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK. Baba.Inusa@gstt.nhs.uk.
authors: Baba
authors: B
authors: Inusa
authors: University of Southampton, Southampton, UK. C.Liossi@soton.ac.uk.
authors: Christina
authors: C
authors: Liossi
authors: University of California Los Angeles, Los Angeles, CA, USA. eufemia@sonnet.ucla.edu.
authors: Eufemia
authors: E
authors: Jacob
authors: King's College London, London, UK. Patrick.b.murphy@kcl.ac.uk.|Lane Fox Respiratory Unit, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK. Patrick.b.murphy@kcl.ac.uk.
authors: Patrick B
authors: PB
authors: Murphy
authors: King's College London, London, UK. Nicholas.Hart@gstt.nhs.uk.|Lane Fox Respiratory Unit, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK. Nicholas.Hart@gstt.nhs.uk.
authors: Nicholas
authors: N
authors: Hart
authors: Department of Child Health, University Hospital Southampton, Southampton, UK. Johanna.Gavlak@uhs.nhs.uk.|Neurosciences Unit, University College London Institute of Child Health, London, UK. Johanna.Gavlak@uhs.nhs.uk.
authors: Johanna
authors: J
authors: Gavlak
authors: Department of Child Health, University Hospital Southampton, Southampton, UK. S.Sahota@ucl.ac.uk.
authors: Sati
authors: S
authors: Sahota
authors: Evelina Children's Hospital, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK. M.Chorozoglou@soton.ac.uk.
authors: Maria
authors: M
authors: Chorozoglou
authors: Sickle Cell and Young Stroke Survivors Charity, London, UK. Carolnwosu@scyss.org.
authors: Carol
authors: C
authors: Nwosu
authors: Sickle Cell and Young Stroke Survivors Charity, London, UK. maureengwam@hotmail.co.uk.
authors: Maureen
authors: M
authors: Gwam
authors: King's College hospital, London, UK. atulgupta1@nhs.net.
authors: Atul
authors: A
authors: Gupta
authors: King's College London, London, UK. David.Rees2@nhs.net.|King's College hospital, London, UK. David.Rees2@nhs.net.
authors: David C
authors: DC
authors: Rees
authors: King's College London, London, UK. sl.thein@kcl.ac.uk.|King's College hospital, London, UK. sl.thein@kcl.ac.uk.
authors: Swee Lay
authors: SL
authors: Thein
authors: University of Southampton, Southampton, UK. I.C.Reading@soton.ac.uk.|Research Design Service, University Hospital Southampton, Southampton, UK. I.C.Reading@soton.ac.uk.
authors: Isabel C
authors: IC
authors: Reading
authors: University of Southampton, Southampton, UK. Fenella.Kirkham@ucl.ac.uk.|Department of Child Health, University Hospital Southampton, Southampton, UK. Fenella.Kirkham@ucl.ac.uk.|Neurosciences Unit, University College London Institute of Child Health, London, UK. Fenella.Kirkham@ucl.ac.uk.
authors: Fenella J
authors: FJ
authors: Kirkham
authors: University of Southampton, Southampton, UK. M.Y.Cheng@soton.ac.uk.|Research Design Service, University Hospital Southampton, Southampton, UK. M.Y.Cheng@soton.ac.uk.
authors: Man Yeung Edith
authors: MY
authors: Cheng
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology / Q000523:psychology; D002648:Child; D002985:Clinical Protocols; D045422:Continuous Positive Airway Pressure / Q000009:adverse effects / Q000379:methods*; D018592:Cross-Over Studies; D004739:England; D005260:Female; D006801:Humans; D007407:Interviews as Topic; D008297:Male; D010092:Oximetry; D010102:Oxygen Inhalation Therapy / Q000009:adverse effects; D017060:Patient Satisfaction; D010865:Pilot Projects; D011788:Quality of Life; D012107:Research Design; D012129:Respiratory Function Tests; D012891:Sleep Apnea Syndromes / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult