title: Effect of continuous deep sedation on survival in patients with advanced cancer (J-Proval): a propensity score-weighted analysis of a prospective cohort study.
abstract: BACKGROUND
  Continuous deep sedation (CDS) before death is a form of palliative sedation therapy that has become a focus of strong debate, especially with respect to whether it shortens survival. We aimed to examine whether CDS shortens patient survival using the propensity score-weighting method, and to explore the effect of artificial hydration during CDS on survival.
  
  
  METHODS
  This study was a secondary analysis of a large multicentre prospective cohort study that recruited and followed up patients between Sept 3, 2012, and April 30, 2014, from 58 palliative care institutions across Japan, including hospital palliative care settings, inpatient palliative care units, and home-based palliative care services. Adult patients (aged ≥ 20 years) with advanced cancer who received care through the participating palliative care services were eligible for this secondary analysis. Patients with missing data for outcome variables or who lived for more than 180 days were excluded. We compared survival after enrolment between patients who did and did not receive CDS. We used a propensity score-weighting method to control for patient characteristics, disease status, and symptom burden at enrolment.
  
  
  RESULTS
  Of 2426 enrolled patients with advanced cancer, we excluded 289 (12%) for living longer than 180 days and 310 (13%) with missing data, leaving an analysis population of 1827 patients. 269 (15%) of 1827 patients received CDS. Unweighted median survival was 27 days (95% CI 22-30) in the CDS group and 26 days (24-27) in the no CDS group (median difference -1 day [95% CI -5 to 4]; HR 0·92 [95% CI 0·81-1·05]; log-rank p=0·20). After propensity-score weighting, these values were 22 days (95% CI 21-24) and 26 days (24-27), respectively (median difference -1 day [95% CI -6 to 4]; HR 1·01 [95% CI 0·87-1·17]; log-rank p=0·91). Age (p(interaction)=0·67), sex (p(interaction)=0·26), performance status (p(interaction)=0·90), and volume of artificial hydration (p(interaction)=0·14) did not have an effect modification on the association between sedation and survival, although care setting did have a significant effect modification (p(interaction)=0·021).
  
  
  CONCLUSIONS
  CDS does not seem to be associated with a measurable shortening of life in patients with advanced cancer cared for by specialised palliative care services, and could be considered a viable option for palliative care in this setting.
  
  
  BACKGROUND
  Japanese National Cancer Center Research and Development Fund.
authors.affiliation: Department of Palliative Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: maeda@pm.med.osaka-u.ac.jp.
authors.forename: Isseki
authors.initials: I
authors.lastname: Maeda
authors.affiliation: Department of Palliative and Supportive Care, Palliative Care Team, Kita-ku, Hamamatsu, Shizuoka, Japan; Seirei Hospice, Seirei Mikatahara General Hospital, Kita-ku, Hamamatsu, Shizuoka, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Morita
authors.affiliation: Division of Biostatistics, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Seirei Hospice, Seirei Mikatahara General Hospital, Kita-ku, Hamamatsu, Shizuoka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Children's Hospice Hospital, Yodogawa Christian Hospital, Higashiyodogawa-ku, Osaka, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ikenaga
authors.affiliation: Department of Palliative Medicine, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Department of Pain and Palliative Care, Kameda Medical Center, Kamogawa, Chiba, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sekine
authors.affiliation: Department of Palliative Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Palliative Care, Mitui Memorial Hospital, Chiyoda-ku, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirohashi
authors.affiliation: Department of Palliative Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Tajima
authors.affiliation: Department of Palliative Medicine, Osaka City General Hospital, Miyakojima-ku, Osaka, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Tatara
authors.affiliation: Komaki City Hospital, Komaki, Aichi, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Palliative Care Team, and Palliative and Supportive Care, National Kyushu Cancer Center, Minami-ku, Fukuoka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Otani
authors.affiliation: Department of Palliative Care, KKR Sapporo Medical Center, Sapporo, Hokkaido, Japan.
authors.forename: Chizuko
authors.initials: C
authors.lastname: Takigawa
authors.affiliation: Department of Psychosomatic Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Matsuda
authors.affiliation: Department of Medical Social Service Center for Palliative Care, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Hiroka
authors.initials: H
authors.lastname: Nagaoka
authors.affiliation: Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Mori
authors.affiliation: Seirei Hospice, Seirei Mikatahara General Hospital, Kita-ku, Hamamatsu, Shizuoka, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Tei
authors.affiliation: Department of Oncology, Mitsubishi Kyoto Hospital, Nishikyoku, Kyoto, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kikuchi
authors.affiliation: Palliative Care Division, Saito Yukoukai Hospital, Ibaraki, Osaka, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Baba
authors.affiliation: Department of Palliative Medicine, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Kinoshita
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D054810:Deep Sedation; D005260:Female; D005440:Fluid Therapy; D006699:Home Care Services; D006738:Hospices; D006761:Hospitals; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality* / Q000628:therapy*; D010166:Palliative Care / Q000379:methods*; D057216:Propensity Score; D011446:Prospective Studies; D015996:Survival Rate; D013727:Terminal Care / Q000379:methods*