Exercise interventions to improve sleep in cancer patients: A systematic review and meta-analysis

Sleep Medicine Reviews

Volumn 36, Issue , 2017, Pages 43-56

  Mercier, Joanie ^a,b   Savard, Josée ^a,b   Bernard, Paquito ^a,b  

^a UNIVERSITÉ LAVAL   (Canada)

^b LAVAL UNIVERSITY   (Canada)

Author keywords

Cancer; Exercise; Insomnia; Physical activity; Sleep

Indexed keywords

AEROBIC EXERCISE; BREAST CANCER; CANCER PATIENT; CLINICAL EFFECTIVENESS; EVIDENCE BASED MEDICINE; HEALTH PROGRAM; HOME CARE; HUMAN; KINESIOTHERAPY; META ANALYSIS; MOTOR ACTIVITY; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SLEEP DISORDER; SPORT; SYSTEMATIC REVIEW; WALKING; CLINICAL TRIAL (TOPIC); NEOPLASM; PROCEDURES; PSYCHOLOGY; QUALITY OF LIFE;

CLINICAL TRIALS AS TOPIC; EXERCISE THERAPY; HUMANS; NEOPLASMS; QUALITY OF LIFE; SLEEP WAKE DISORDERS;

EID: 85008191077     PISSN: 10870792     EISSN: 15322955     Source Type: Journal    
DOI: 10.1016/j.smrv.2016.11.001     Document Type: Review

References (102)

1. Savard, J., Morin, C.M., Insomnia in the context of cancer: a review of a neglected problem. J Clin Oncol 19:3 (2001 Feb 1), 895–908.
2. Savard, J., Simard, S., Blanchet, J., Ivers, H., Morin, C.M., Prevalence, clinical characteristics, and risk factors for insomnia in the context of breast cancer. Sleep 24:5 (2001 Aug 1), 583–590.
3. Savard, J., Villa, J., Ivers, H., Simard, S., Morin, C.M., Prevalence, natural course, and risk factors of insomnia comorbid with cancer over a 2-month period. J Clin Oncol 27:31 (2009 Nov 1), 5233–5239.
4. Berger, A.M., Update on the state of the science: sleep-wake disturbances in adult patients with cancer. Oncol Nurs forum 36:4 (2009 Jul), E165–E177.
5. Davidson, J.R., MacLean, A.W., Brundage, M.D., Schulze, K., Sleep disturbance in cancer patients. Soc Sci Med (1982) 54:9 (2002 May), 1309–1321.
6. Savard, J., Ivers, H., Villa, J., Caplette-Gingras, A., Morin, C.M., Natural course of insomnia comorbid with cancer: an 18-month longitudinal study. J Clin Oncol 29:26 (2011 Sep 10), 3580–3586.
7. Palesh, O.G., Roscoe, J.A., Mustian, K.M., Roth, T., Savard, J., Ancoli-Israel, S., et al. Prevalence, demographics, and psychological associations of sleep disruption in patients with cancer: University of Rochester Cancer Center-Community Clinical Oncology Program. J Clin Oncol 28:2 (2010 Jan 10), 292–298.
8. Ancoli-Israel, S., Liu, L., Marler, M.R., Parker, B.A., Jones, V., Sadler, G.R., et al. Fatigue, sleep, and circadian rhythms prior to chemotherapy for breast cancer. Support Care Cancer 14:3 (2006 Mar), 201–209.
9. Ancoli-Israel, S., Moore, P.J., Jones, V., The relationship between fatigue and sleep in cancer patients: a review. Eur J Cancer care 10:4 (2001 Dec), 245–255.
10. Berger, A.M., Farr, L.A., Kuhn, B.R., Fischer, P., Agrawal, S., Values of sleep/wake, activity/rest, circadian rhythms, and fatigue prior to adjuvant breast cancer chemotherapy. J Pain Symptom Manag 33:4 (2007 Apr), 398–409.
11. Roscoe, J.A., Kaufman, M.E., Matteson-Rusby, S.E., Palesh, O.G., Ryan, J.L., Kohli, S., et al. Cancer-related fatigue and sleep disorders. Oncol 12:Suppl. 1 (2007), 35–42.
12. Berger, A.M., Parker, K.P., Young-McCaughan, S., Mallory, G.A., Barsevick, A.M., Beck, S.L., et al. Sleep wake disturbances in people with cancer and their caregivers: state of the science. Oncol Nurs forum 32:6 (2005 Nov), E98–E126.
13. Fiorentino, L., Ancoli-Israel, S., Sleep dysfunction in patients with cancer. Curr Treat Options Neurol 9:5 (2007 Sep), 337–346.
14. O'Donnell, J.F., Insomnia in cancer patients. Clin cornerstone 6:Suppl. 1D (2004), S6–S14.
15. Otte, J.L., Carpenter, J.S., Theories, models, and frameworks related to sleep-wake disturbances in the context of cancer. Cancer Nurs 32:2 (2009 Mar-Apr), 90–104 quiz 5–6.
16. Sateia, M.J., Lang, B.J., Sleep and cancer: recent developments. Curr Oncol Rep 10:4 (2008 Jul), 309–318.
17. Theobald, D.E., Cancer pain, fatigue, distress, and insomnia in cancer patients. Clin Cornerstone 6:Suppl. 1D (2004), S15–S21.
18. Engstrom, C.A., Strohl, R.A., Rose, L., Lewandowski, L., Stefanek, M.E., Sleep alterations in cancer patients. Cancer Nurs 22:2 (1999 Apr), 143–148.
19. Caplette-Gingras, A., Savard, J., Savard, M.H., Ivers, H., Is insomnia associated with cognitive impairments in breast cancer patients?. Behav Sleep Med 11 (2013), 239–257.
20. Lee, K., Cho, M., Miaskowski, C., Dodd, M., Impaired sleep and rhythms in persons with cancer. Sleep Med Rev 8:3 (2004 Jun), 199–212.
21. Ruel, S., Savard, J., Ivers, H., Insomnia and self-reported infections in cancer patients: an 18-month longitudinal study. Health Psychol 34:10 (2015 Oct), 983–991.
22. Daley, M., Morin, C.M., LeBlanc, M., Gregoire, J.P., Savard, J., The economic burden of insomnia: direct and indirect costs for individuals with insomnia syndrome, insomnia symptoms, and good sleepers. Sleep 32:1 (2009 Jan), 55–64.
23. Wickwire, E.M., Shaya, F.T., Scharf, S.M., Health economics of insomnia treatments: the return on investment for a good night's sleep. Sleep Med Rev 30 (2015 Nov 28), 72–82.
24. Donovan, K.A., Jacobsen, P.B., Fatigue, depression, and insomnia: evidence for a symptom cluster in cancer. Semin Oncol Nurs 23:2 (2007 May), 127–135.
25. Graci, G., Pathogenesis and management of cancer-related insomnia. J Support Oncol 3:5 (2005 Sep-Oct), 349–359.
26. Casault, L., Savard, J., Ivers, H., Savard, M.H., Simard, S., Utilization of hypnotic medication in the context of cancer: predictors and frequency of use. Support Care Cancer 20:6 (2011), 1203–1210.
27. Derogatis, L.R., Feldstein, M., Morrow, G., Schmale, A., Schmitt, M., Gates, C., et al. A survey of psychotropic drug prescriptions in an oncology population. Cancer 44:5 (1979 Nov), 1919–1929.
28. Guo, Y., Young, B.L., Hainley, S., Palmer, J.L., Bruera, E., Evaluation and pharmacologic management of symptoms in cancer patients undergoing acute rehabilitation in a comprehensive cancer center. Arch Phys Med Rehabil 88:7 (2007 Jul), 891–895.
29. Moore, T.A., Berger, A.M., Dizona, P., Sleep aid use during and following breast cancer adjuvant chemotherapy. Psycho-oncology 20:3 (2011 Mar), 321–325.
30. Paltiel, O., Marzec-Boguslawska, A., Soskolne, V., Massalha, S., Avitzour, M., Pfeffer, R., et al. Use of tranquilizers and sleeping pills among cancer patients is associated with a poorer quality of life. Qual Life Res 13:10 (2004 Dec), 1699–1706.
31. Fiorentino, L., Ancoli-Israel, S., Insomnia and its treatment in women with breast cancer. Sleep Med Rev 10:6 (2006 Dec), 419–429.
32. Holbrook, A.M., Crowther, R., Lotter, A., Cheng, C., King, D., Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ 162:2 (2000 Jan 25), 225–233.
33. National Institute of Health, National Institutes of Health State of the Science Conference statement on manifestations and management of chronic insomnia in adults, June 13–15, 2005. Sleep, Sep 2005, 1049–1057.
34. Courneya, K.S., Exercise in cancer survivors: an overview of research. Med Sci Sports Exerc 35:11 (2003 Nov), 1846–1852.
35. Courneya, K.S., Friedenreich, C.M., Physical activity and cancer: an introduction. Recent Results Cancer Res Fortschritte der Krebsforschung 186 (2011), 1–10.
36. Ferrer, R.A., Huedo-Medina, T.B., Johnson, B.T., Ryan, S., Pescatello, L.S., Exercise interventions for cancer survivors: a meta-analysis of quality of life outcomes. Ann Behav Med 41:1 (2011 Feb), 32–47.
37. Schmitz, K.H., Courneya, K.S., Matthews, C., Demark-Wahnefried, W., Galvao, D.A., Pinto, B.M., et al. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc 42:7 (2010 Jul), 1409–1426.
38. Speck, R.M., Courneya, K.S., Masse, L.C., Duval, S., Schmitz, K.H., An update of controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. J Cancer Surviv 4:2 (2009 Jun), 87–100.
39. Sprod, L.K., Hsieh, C.C., Hayward, R., Schneider, C.M., Three versus six months of exercise training in breast cancer survivors. Breast Cancer Res Treat 121:2 (2010 Jun), 413–419.
40. Pinto, B.M., Rabin, C., Abdow, S., Papandonatos, G.D., A pilot study on disseminating physical activity promotion among cancer survivors: a brief report. Psycho-oncology 17:5 (2008 May), 517–521.
41. Schwartz, A.L., Physical activity. Semin Oncol Nurs 24:3 (2008 Aug), 164–170.
42. Physical Activity and Cancer, National Cancer Institute of the National Institute of Health. 2015 www.cancer.gov.
43. Physical activity, Canadian Cancer Society. 2015 www.cancer.ca.
44. Driver, H.S., Taylor, S.R., Exercise and sleep. Sleep Med Rev 4:4 (2000 Aug), 387–402.
45. Kredlow, M.A., Capozzoli, M.C., Hearon, B.A., Calkins, A.W., Otto, M.W., The effects of physical activity on sleep: a meta-analytic review. J Behav Med 38:3 (2015), 427–449.
46. O'Connor, P.J., Youngstedt, S.D., Influence of exercise on human sleep. Exerc Sport Sci Rev 23 (1995), 105–134.
47. Sherrill, D.L., Kotchou, K., Quan, S.F., Association of physical activity and human sleep disorders. Arch Intern Med 158:17 (1998 Sep 28), 1894–1898.
48. Vuori, I., Urponen, H., Hasan, J., Partinen, M., Epidemiology of exercise effects on sleep. Acta Physiol Scand 574 (1988), 3–7.
49. Youngstedt, S.D., Kline, C.E., Epidemiology of exercise and sleep. Sleep Biol Rhythms 4 (2006), 215–221.
50. Mishra, S.I., Scherer, R.W., Snyder, C., Geigle, P.M., Berlanstein, D.R., Topaloglu, O., Exercise interventions on health-related quality of life for people with cancer during active treatment. Cochrane Database Syst Rev, 8, 2012, CD008465.
51. Tomlinson, D., Diorio, C., Beyene, J., Sung, L., Effect of exercise on cancer-related fatigue: a meta-analysis. Am J Phys Med Rehabil 93:8 (2014 Aug), 675–686.
52. Chiu, H.Y., Huang, H.C., Chen, P.Y., Hou, W.H., Tsai, P.S., Walking improves sleep in individuals with cancer: a meta-analysis of randomized, controlled trials. Oncol Nurs Forum 42:2 (2015 Mar), E54–E62.
53. Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med, 6(7), 2009 Jul 21, e1000097.
54. Landis, J.R., Koch, G.G., An application of hierarchical kappa-type statistics in the assessment of majority agreement among multiple observers. Biometrics 33:2 (1977 Jun), 363–374.
55. Lipsey, M.W., Wilson, D.B., Practical meta-analysis. 2001, Sage Publications, Thousand Oaks, CA, US.
56. Higgins, J.P., Thompson, S.G., Deeks, J.J., Altman, D.G., Measuring inconsistency in meta-analyses. BMJ 327:7414 (2003 Sep 6), 557–560.
57. Cohen, J., Statistical power analysis for the behavioral science. 2nd ed., 1988, Lawrence Erlbaum Associates, New-Jersey.
58. Viechtbauer, W., Conducting meta-analyses in R with the metafor Package. J Stat Softw 36:3 (2010), 1–48.
59. Courneya, K.S., Segal, R.J., Mackey, J.R., Gelmon, K., Friedenreich, C.M., Yasui, Y., et al. Effects of exercise dose and type on sleep quality in breast cancer patients receiving chemotherapy: a multicenter randomized trial. Breast Cancer Res Treat 144:2 (2014), 361–369.
60. Dodd, M.J., Cho, M.H., Miaskowski, C., Painter, P.L., Paul, S.M., Cooper, B.A., et al. A randomized controlled trial of home-based exercise for cancer-related fatigue in women during and after chemotherapy with or without radiation therapy. Cancer Nurs 33:4 (2010 Jul-Aug), 245–257.
61. Kampshoff, C.S., Chinapaw, M.J., Brug, J., Twisk, J.W., Schep, G., Nijziel, M.R., et al. Randomized controlled trial of the effects of high intensity and low-to-moderate intensity exercise on physical fitness and fatigue in cancer survivors: results of the Resistance and Endurance exercise after ChemoTherapy (REACT) study. BMC Med, 13, 2015, 275.
62. van Waart, H., Stuiver, M.M., van Harten, W.H., Geleijn, E., Kieffer, J.M., Buffart, L.M., et al. Effect of low-intensity physical activity and moderate- to high-intensity physical exercise during adjuvant chemotherapy on physical fitness, fatigue, and chemotherapy completion rates: results of the PACES randomized clinical trial. J Clin Oncol 33:17 (2015 Jun 10), 1918–1927.
63. Rabin, C., Pinto, B., Dunsiger, S., Nash, J., Trask, P., Exercise and relaxation intervention for breast cancer survivors: feasibility, acceptability and effects. Psycho-oncology 18:3 (2009 Mar), 258–266.
64. Rajotte, E.J., Yi, J.C., Baker, K.S., Gregerson, L., Leiserowitz, A., Syrjala, K.L., Community-based exercise program effectiveness and safety for cancer survivors. J Cancer Surviv 6:2 (2012 Jun), 219–228.
65. Young-McCaughan, S., Mays, M.Z., Arzola, S.M., Yoder, L.H., Dramiga, S.A., Leclerc, K.M., et al. Research and commentary: Change in exercise tolerance, activity and sleep patterns, and quality of life in patients with cancer participating in a structured exercise program. Oncol Nurs Forum 30:3 (2003 May-Jun), 441–454 discussion -54.
66. Kröz, M., Fink, M., Reif, M., Grobbecker, S., Zerm, R., Quetz, M., et al. Multimodal therapy concept and aerobic training in breast cancer patients with chronic cancer-related fatigue. Integr Cancer Ther 12:4 (2013 Jul), 301–311.
67. Courneya, K.S., Sellar, C.M., Trinh, L., Forbes, C.C., Stevinson, C., McNeely, M.L., et al. A randomized trial of aerobic exercise and sleep quality in lymphoma patients receiving chemotherapy or no treatments. Cancer Epidemiol Biomarkers Prev 21:6 (2012 Jun), 887–894.
68. Donnelly, C.M., Blaney, J.M., Lowe-Strong, A., Rankin, J.P., Campbell, A., McCrum-Gardner, E., et al. A randomised controlled trial testing the feasibility and efficacy of a physical activity behavioural change intervention in managing fatigue with gynaecological cancer survivors. Gynecol Oncol 122:3 (2011), 618–624.
69. Rogers, L.Q., Fogleman, A., Trammell, R., Hopkins-Price, P., Spenner, A., Vicari, S., et al. Inflammation and psychosocial factors mediate exercise effects on sleep quality in breast cancer survivors: pilot randomized controlled trial. Psycho-oncology 24:3 (2015 Mar), 302–310.
70. Tang, M.F., Liou, T.H., Lin, C.C., Improving sleep quality for cancer patients: benefits of a home-based exercise intervention. Support Care Cancer 18:10 (2010 Oct), 1329–1339.
71. Buysse, D.J., Reynolds, C.F. 3rd, Monk, T.H., Berman, S.R., Kupfer, D.J., The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 28:2 (1989 May), 193–213.
72. Payne, J.K., Held, J., Thorpe, J., Shaw, H., Effect of exercise on biomarkers, fatigue, sleep disturbances, and depressive symptoms in older women with breast cancer receiving hormonal therapy. Oncol Nurs Forum 35:4 (2008 Jul), 635–642.
73. Rogers, L.Q., Hopkins-Price, P., Vicari, S., Pamenter, R., Courneya, K.S., Markwell, S., et al. A randomized trial to increase physical activity in breast cancer survivors. Med Sci Sports Exerc 41:4 (2009 Apr), 935–946.
74. Rogers, L.Q., Fogleman, A., Trammell, R., Hopkins-Price, P., Vicari, S., Rao, K., et al. Effects of a physical activity behavior change intervention on inflammation and related health outcomes in breast cancer survivors: pilot randomized trial. Integr Cancer Ther 12:4 (2013), 323–335.
75. Sprod, L.K., Palesh, O.G., Janelsins, M.C., Peppone, L.J., Heckler, C.E., Jacob Adams, M., et al. Exercise, sleep quality, and mediators of sleep in breast and prostate cancer patients receiving radiation therapy. Community Oncol 7:10 (2010), 463–471.
76. Wang, Y.J., Boehmke, M., Wu, Y.W., Dickerson, S.S., Fisher, N., Effects of a 6-week walking program on Taiwanese women newly diagnosed with early-stage breast cancer. Cancer Nurs, 34(2), 2011 Mar-Apr E1-13.
77. Wenzel, J.A., Griffith, K.A., Shang, J., Thompson, C.B., Hedlin, H., Stewart, K.J., et al. Impact of a home-based walking intervention on outcomes of sleep quality, emotional distress, and fatigue in patients undergoing treatment for solid tumors. Oncologist 18:4 (2013), 476–484.
78. Naraphong, W., Lane, A., Schafer, J., Whitmer, K., Wilson, B.R., Exercise intervention for fatigue-related symptoms in Thai women with breast cancer: a pilot study. Nurs Health Sci 17:1 (2015), 33–41.
79. Buysse, D.J., Ancoli-Israel, S., Edinger, J.D., Lichstein, K.L., Morin, C.M., Recommendations for a standard research assessment of insomnia. Sleep 29:9 (2006 Sep), 1155–1173.
80. Morin, C.M., Insomnia: psychological assessment and management. 1993, Guilford Press, New York.
81. Savard, M.H., Savard, J., Simard, S., Ivers, H., Empirical validation of the insomnia severity index in cancer patients. Psycho-oncology 14:6 (2005 Jun), 429–441.
82. Rogers, L.Q., McAuley, E., Anton, P.M., Courneya, K.S., Vicari, S., Hopkins-Price, P., et al. Better exercise adherence after treatment for cancer (BEAT Cancer) study: rationale, design, and methods. Contemp Clin Trials 33:1 (2012), 124–137.
83. Coleman, E.A., Coon, S., Hall-Barrow, J., Richards, K., Gaylor, D., Stewart, B., Feasibility of exercise during treatment for multiple myeloma. Cancer Nurs 26:5 (2003), 410–419.
84. Coleman, E.A., Goodwin, J.A., Kennedy, R., Coon, S.K., Richards, K., Enderlin, C., et al. Effects of exercise on fatigue, sleep, and performance: a randomized trial. Oncol Nurs Forum 39:5 (2012 Sep), 468–477.
85. Rogers, L.Q., Hopkins-Price, P., Vicari, S., Markwell, S., Pamenter, R., Courneya, K.S., et al. Physical activity and health outcomes three months after completing a physical activity behavior change intervention: persistent and delayed effects. Cancer Epidemiol Biomarkers Prev 18:5 (2009), 1410–1418.
86. Savard, J., Ivers, H., Savard, M.H., Morin, C.M., Cancer treatments and their side effects are associated with aggravation of insomnia: results of a longitudinal study. Cancer 121:10 (2015 May 15), 1703–1711.
87. Savard, J., Ganz, P.A., Subjective or objective measures of cognitive functioning-what's more important?. JAMA Oncol 2:10 (2016), 1263–1264.
88. Kay, D.B., Buysse, D.J., Germain, A., Hall, M., Monk, T.H., Subjective-objective sleep discrepancy among older adults: associations with insomnia diagnosis and insomnia treatment. J Sleep Res 24:1 (2015 Feb), 32–39.
89. Morin, C.M., The nature of insomnia and the need to refine our diagnostic criteria. Psychosom Med 62:4 (2000 Jul-Aug), 483–485.
90. Association, A.P., (eds.) Diagnostic and statistical manual of mental disorders (DSM-5), 5e éd, 2013, Washington American Psychiatric Association Publishing.
91. Langford, D.J., Lee, K., Miaskowski, C., Sleep disturbance interventions in oncology patients and family caregivers: a comprehensive review and meta-analysis. Sleep Med Rev 16:5 (2012 Oct), 397–414.
92. Courneya, K.S., Friedenreich, C.M., Quinney, H.A., Fields, A.L., Jones, L.W., Fairey, A.S., Predictors of adherence and contamination in a randomized trial of exercise in colorectal cancer survivors. Psycho-oncology 13:12 (2004 Dec), 857–866.
93. Mock, V., Frangakis, C., Davidson, N.E., Ropka, M.E., Pickett, M., Poniatowski, B., et al. Exercise manages fatigue during breast cancer treatment: a randomized controlled trial. Psycho-oncology 14:6 (2005 Jun), 464–477.
94. Shang, J., Wenzel, J., Krumm, S., Griffith, K., Stewart, K., Who will drop out and who will drop in: exercise adherence in a randomized clinical trial among patients receiving active cancer treatment. Cancer Nurs 35:4 (2012 Jul-Aug), 312–322.
95. Savard, J., Savard, M.H., Insomnia and cancer: prevalence, nature, and nonpharmacologic treatment. Sleep Med Clin 8:3 (2013), 373–387.
96. Buman, M.P., King, A.C., Exercise as a treatment to enhance sleep. Am J Lifestyle Med 4:6 (2010), 500–514.
97. Leger, D., Horloge biologique et rythme veille/sommeil. Médecine et nutrition. Conférence, Paris, FRANCE: Centre du Sommeil et de la Vigilance, Hôtel-Dieu de Paris; 2005, 01–2005.
98. Monteleone, P., Maj, M., Circadian rhythm disturbances in depression: implications for treatment and quality of remission. Medicographia 31:2 (2009), 132–139.
99. Espie, C.A., Fleming, L., Cassidy, J., Samuel, L., Taylor, L.M., White, C.A., et al. Randomized controlled clinical effectiveness trial of cognitive behavior therapy compared with treatment as usual for persistent insomnia in patients with cancer. J Clin Oncol 26:28 (2008 Oct 1), 4651–4658.
100. Garland, S.N., Johnson, J.A., Savard, J., Gehrman, P., Perlis, M., Carlson, L., et al. Sleeping well with cancer: a systematic review of cognitive behavioral therapy for insomnia in cancer patients. Neuropsychiatr Dis Treat 10 (2014), 1113–1124.
101. Roscoe, J.A., Garland, S.N., Heckler, C.E., Perlis, M.L., Peoples, A.R., Shayne, M., et al. Randomized placebo-controlled trial of cognitive behavioral therapy and armodafinil for insomnia after cancer treatment. J Clin Oncol 33:2 (2015 Jan 10), 165–171.
102. Savard, J., Simard, S., Ivers, H., Morin, C.M., Randomized study on the efficacy of cognitive-behavioral therapy for insomnia secondary to breast cancer, part I: sleep and psychological effects. J Clin Oncol 23:25 (2005 Sep 1), 6083–6096.