Mechanisms of dexamethasone-induced disturbed sleep and fatigue in paediatric patients receiving treatment for ALL.
Mechanisms of dexamethasone-induced disturbed sleep and fatigue in paediatric patients receiving treatment for ALL.
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DOI：
10.1016/j.ejca.2010.03.026
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发表时间：
2010-07
影响因子：
8.4
通讯作者：
Hinds, Pamela S.
中科院分区：
文献类型：
--
作者：
Vallance, Kelly;Liu, Wei;Mandrell, Belinda N.;Panetta, John C.;Gattuso, Jami S.;Hockenberry, Marilyn;Zupanec, Sue;Yang, Lei;Yang, Jie;Hinds, Pamela S.
关键词：
Dexamethasone contributes to high cure rates in pediatric acute lymphoblastic leukaemia (ALL) but significantly and adversely alters sleep and fatigue. Herein we explored three mechanisms (pharmacokinetics, serum albumin, and pharmacogenetics) through which dexamethasone may cause debilitating fatigue and disrupted sleep. We enrolled 100 patients on a 10-day study: 5 days of no dexamethasone (OFF DEX) followed by 5 days of dexamethasone (ON DEX) during continuation chemotherapy. Sleep variables were collected with continuous actigraphy on Days 1 through 5, both OFF DEX and ON DEX. On Days 2 and 5 of each 5-day period, parents and patients 7 years of age and older completed a sleep diary and Fatigue Scale questionnaire. Blood was collected at 0 (pre-dexamethasone), 1, 2, 4, and 8 hours after the first oral dexamethasone dose for pharmacokinetic analysis. Serum albumin concentration was retrospectively analyzed in stored samples. Patient DNA was genotyped for 99 polymorphic loci in candidate genes associated with glucocorticoid metabolism. Dexamethasone clearance was significantly greater in younger patients than in older ones and in lower risk patients. In multiple regression models, risk group was significantly related to pharmacokinetic parameters. We found that polymorphisms in three genes (AHSG, IL6, POLDIP3) were significantly associated with sleep measures but not fatigue. Risk group had the most significant relationship with disrupted sleep in patients while on dexamethasone. Serum albumin levels had neither a direct relationship with sleep or fatigue variables nor an indirect relationship through systemic exposure to dexamethasone. We identified candidate genes that may help explain the adverse events of disrupted sleep in pediatric patients receiving dexamethasone.
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DOI：
10.1186/1740-2557-5-3
发表时间：
2008-07-14
期刊：
Journal of autoimmune diseases
影响因子：
--
作者：
Avila, Julio;Acosta, Elisa;Martin-Vasallo, Pablo
通讯作者：
Martin-Vasallo, Pablo
影响因子：
2.6
作者：
Hinds, PS;Hockenberry-Eaton, M;Quargnenti, A
通讯作者：
Quargnenti, A
影响因子：
45.3
作者：
BALIS, FM;LESTER, CM;POPLACK, DG
通讯作者：
POPLACK, DG
影响因子：
6.2
作者：
Hoffmann, SC;Stanley, EM;Blair, PJ
通讯作者：
Blair, PJ
DOI：
10.1002/mpo.2950200104
发表时间：
1992-01-01
期刊：
MEDICAL AND PEDIATRIC ONCOLOGY
影响因子：
--
作者：
DRIGAN, R;SPIRITO, A;GELBER, RD
通讯作者：
GELBER, RD