title: Blinded Patient Preference for Morphine Compared to Placebo in the Setting of Chronic Refractory Breathlessness--An Exploratory Study.
abstract: BACKGROUND
  Patients' preference for morphine therapy has received little attention in the setting of chronic refractory breathlessness. However, this is one important factor in considering longer term therapy.
  
  
  OBJECTIVE
  The aim of this secondary analysis was to explore blinded patient preference of morphine compared to placebo for this indication and to define any predictors of preference.
  
  
  METHODS
  Data were pooled from three randomized, double-blind, crossover, placebo-controlled studies of morphine (four days each) in chronic refractory breathlessness. Blinded patient preferences were chosen at the end of each study. A multivariable regression model was used to establish patient predictors of preference.
  
  
  RESULTS
  Sixty-five participants provided sufficient data (60 men; median age 74 years; heart failure 55%, chronic obstructive pulmonary disease 45%; median Eastern Cooperative Oncology Group performance status 2). Forty-three percent of participants preferred morphine (32% placebo and 25% no preference). Morphine preference and younger age were strongly associated: odds ratio = 0.85, 95% confidence interval 0.78-0.93; P < 0.001). There was also an inverse association between morphine preference and sedation (odds ratio = 0.77, 95% confidence interval 0.60-0.99; P < 0.05). An inverse association was also seen between nausea and morphine preference in the univariate model only (P < 0.05). No association was seen between morphine preference and breathlessness intensity, either at baseline or change from baseline.
  
  
  CONCLUSIONS
  Participants preferred morphine over placebo for the relief of chronic refractory breathlessness. Morphine offers clinically important improvement, but net benefit can be easily outweighed by side effects, reducing net benefits. Side effects require aggressive management to allow more patients to realize benefits.
authors.affiliation: Department of Internal Medicine, Hospital de Egas Moniz-CHLO, Lisbon, Portugal; Department of Medical Oncology, Portuguese Institute of Oncology (IPO) of Lisbon Francisco Gentil EPE, Lisbon, Portugal.
authors.forename: Diana H
authors.initials: DH
authors.lastname: Ferreira
authors.affiliation: Department of Internal Medicine, Hospital de Egas Moniz-CHLO, Lisbon, Portugal; Department of Medical Oncology, Portuguese Institute of Oncology (IPO) of Lisbon Francisco Gentil EPE, Lisbon, Portugal. Electronic address: jospais@gmail.com.
authors.forename: José P
authors.initials: JP
authors.lastname: Silva
authors.affiliation: School of Medicine, Flinders University, Bedford Park, South Australia, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Quinn
authors.affiliation: Discipline, Palliative and Supportive Services, Flinders University, Bedford Park, South Australia, Australia; Department of Medicine, Duke University Medical Centre, Durham, North Carolina, USA.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Abernethy
authors.affiliation: Palliative Medicine, Hull York Medical School, University of Hull, Hull, United Kingdom.
authors.forename: Miriam J
authors.initials: MJ
authors.lastname: Johnson
authors.affiliation: Kirkwood Hospice, Huddersfield, United Kingdom.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Oxberry
authors.affiliation: Discipline, Palliative and Supportive Services, Flinders University, Bedford Park, South Australia, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Currow
mesh_terms: D000367:Age Factors; D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology / Q000523:psychology; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D006801:Humans; D008297:Male; D009020:Morphine / Q000009:adverse effects / Q000627:therapeutic use*; D015999:Multivariate Analysis; D009325:Nausea / Q000150:complications / Q000503:physiopathology / Q000523:psychology; D010166:Palliative Care / Q000379:methods / Q000523:psychology / Q000706:statistics & numerical data; D057240:Patient Preference / Q000523:psychology / Q000706:statistics & numerical data; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine
keywords: COPD; Patient preference; breathlessness; morphine; palliative care; randomized controlled trial