Abstract
Aging is a risk factor for developing obstructive sleep apnea (OSA) due, in part, to an increased collapsibility of the upper airways. As a result, the prevalence of sleep-disordered breathing is higher in the elderly than in the general population. The clinical characteristics of OSA in the elderly can be distinct from the typical presentation of middle-aged adults and can include nocturia, cognitive dysfunction, and mild hypersomnia. Obstructive sleep apnea can be observed in older patients with a normal body mass index and can increase the risk of stroke, but the effect of OSA on mortality is still controversial. Among the therapeutic options, CPAP therapy is considered the best modality, even in older patients, and can improve cognitive function, decrease the frequency of nocturia, and possibly slow cognitive deterioration in patients with dementia. CPAP therapy should not be withheld based on age, since it is well tolerated, even in moderately demented patients. Further studies are needed to determine whether CPAP therapy can affect outcomes in an older patient population.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Unruh ML, Redline S, An MW, Buysse DJ, Nieto FJ, Yeh JL, et al. Subjective and objective sleep quality and aging in the sleep heart health study. J Am Geriatr Soc. 2008;56:1218–27.
Neikrug AB, Ancoli-Israel S. Sleep disturbances in nursing homes. J Nutr Health Aging. 2010;14:207–11.
Feinsilver SH, Hertz G. Sleep in the elderly patient. Clin Chest Med. 1993;14:405–11.
Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The report of an american academy of sleep medicine task force. Sleep. 1999;22:667–689.
Moser NJ, Phillips BA, Berry DT, Harbison L. What is hypopnea, anyway? Chest. 1994;105: 426–8.
Gottlieb DJ, Whitney CW, Bonekat WH, Iber C, James GD, Lebowitz M, et al. Relation of sleepiness to respiratory disturbance index: the sleep heart health study. Am J Respir Crit Care Med. 1999;159:502–7.
Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328:1230–5.
Ancoli-Israel S, Kripke DF, Klauber MR, Mason WJ, Fell R, Kaplan O. Sleep-disordered breathing in community-dwelling elderly. Sleep. 1991;14:486–95.
Hoch CC, Reynolds 3rd CF, Monk TH, Buysse DJ, Yeager AL, Houck PR, et al. Comparison of sleep-disordered breathing among healthy elderly in the seventh, eighth, and ninth decades of life. Sleep. 1990;13:502–11.
Young T, Shahar E, Nieto FJ, Redline S, Newman AB, Gottlieb DJ, et al. Predictors of sleep-disordered breathing in community-dwelling adults: the sleep heart health study. Arch Intern Med. 2002;162:893–900.
Martin JL, Mory AK, Alessi CA. Nighttime oxygen desaturation and symptoms of sleep-disordered breathing in long-stay nursing home residents. J Gerontol A Biol Sci Med Sci. 2005;60:104–8.
Gehrman PR, Martin JL, Shochat T, Nolan S, Corey-Bloom J, Ancoli-Israel S. Sleep-disordered breathing and agitation in institutionalized adults with alzheimer disease. Am J Geriatr Psychiatry. 2003;11:426–33.
Krystal AD, Edinger J, Wohlgemuth W, Marsh GR. Sleep in peri-menopausal and post-menopausal women. Sleep Med Rev. 1998;2:243–53.
Dancey DR, Hanly PJ, Soong C, Lee B, Hoffstein V. Impact of menopause on the prevalence and severity of sleep apnea. Chest. 2001;120:151–5.
Ware JC, McBrayer RH, Scott JA. Influence of sex and age on duration and frequency of sleep apnea events. Sleep. 2000;23:165–70.
Zamarron C, Gude F, Otero Y, Alvarez JM, Golpe A, Rodriguez JR. Prevalence of sleep disordered breathing and sleep apnea in 50- to 70-year-old individuals. A survey. Respiration. 1999;66:317–22.
Strobel RJ, Rosen RC. Obesity and weight loss in obstructive sleep apnea: a critical review. Sleep. 1996;19:104–15.
Lopez PP, Stefan B, Schulman CI, Byers PM. Prevalence of sleep apnea in morbidly obese patients who presented for weight loss surgery evaluation: more evidence for routine screening for obstructive sleep apnea before weight loss surgery. Am Surg. 2008;74:834–8.
Peppard PE, Young T, Palta M, Dempsey J, Skatrud J. Longitudinal study of moderate weight change and sleep-disordered breathing. JAMA. 2000;284:3015–21.
Vgontzas AN, Papanicolaou DA, Bixler EO, Hopper K, Lotsikas A, Lin HM, et al. Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab. 2000;85:1151–8.
Simpson L, Mukherjee S, Cooper MN, Ward KL, Lee JD, Fedson AC, et al. Sex differences in the association of regional fat distribution with the severity of obstructive sleep apnea. Sleep. 2010;33:467–74.
Hughes VA, Frontera WR, Roubenoff R, Evans WJ, Singh MA. Longitudinal changes in body composition in older men and women: role of body weight change and physical activity. Am J Clin Nutr. 2002;76:473–81.
Zamboni M, Armellini F, Harris T, Turcato E, Micciolo R, Bergamo-Andreis IA, et al. Effects of age on body fat distribution and cardiovascular risk factors in women. Am J Clin Nutr. 1997;66:111–5.
Zamboni M, Mazzali G, Zoico E, Harris TB, Meigs JB, Di Francesco V, et al. Health consequences of obesity in the elderly: a review of four unresolved questions. Int J Obes (Lond). 2005;29:1011–29.
Sternfeld B, Wang H, Quesenberry Jr CP, Abrams B, Everson-Rose SA, Greendale GA, et al. Physical activity and changes in weight and waist circumference in midlife women: findings from the study of women’s health across the nation. Am J Epidemiol. 2004;160:912–22.
Ancoli-Israel S, Gehrman P, Kripke DF, Stepnowsky C, Mason W, Cohen-Zion M, et al. Long-term follow-up of sleep disordered breathing in older adults. Sleep Med. 2001;2: 511–6.
Carmelli D, Swan GE, Bliwise DL. Relationship of 30-year changes in obesity to sleep-disordered breathing in the western collaborative group study. Obes Res. 2000;8:632–7.
Bliwise DL, Colrain IM, Swan GE, Bliwise NG. Incident sleep disordered breathing in old age. J Gerontol A Biol Sci Med Sci. 2010;65:997–1003.
Conn DK, Madan R. Use of sleep-promoting medications in nursing home residents: risks versus benefits. Drugs Aging. 2006;23:271–87.
Cumming RG, Le Couteur DG. Benzodiazepines and risk of hip fractures in older people: a review of the evidence. CNS Drugs. 2003;17:825–37.
Guilleminault C. Benzodiazepines, breathing, and sleep. Am J Med. 1990;88:25S–8.
Glass J, Lanctot KL, Herrmann N, Sproule BA, Busto UE. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ. 2005;331:1169.
Shigeta Y, Ogawa T, Venturin J, Nguyen M, Clark GT, Enciso R. Gender- and age-based differences in computerized tomographic measurements of the orophaynx. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;106:563–70.
Martin SE, Mathur R, Marshall I, Douglas NJ. The effect of age, sex, obesity and posture on upper airway size. Eur Respir J. 1997;10:2087–90.
Malhotra A, Huang Y, Fogel R, Lazic S, Pillar G, Jakab M, et al. Aging influences on pharyngeal anatomy and physiology: the predisposition to pharyngeal collapse. Am J Med. 2006;119: 72.e79–14.
Burger CD, Stanson AW, Sheedy 2nd PF, Daniels BK, Shepard Jr JW. Fast-computed tomography evaluation of age-related changes in upper airway structure and function in normal men. Am Rev Respir Dis. 1992;145:846–52.
Klawe JJ, Tafil-Klawe M. Age-related response of the genioglossus muscle emg-activity to hypoxia in humans. J Physiol Pharmacol. 2003;54 Suppl 1:14–9.
van Lunteren E, Vafaie H, Salomone RJ. Comparative effects of aging on pharyngeal and diaphragm muscles. Respir Physiol. 1995;99:113–25.
Ray AD, Ogasa T, Magalang UJ, Krasney JA, Farkas GA. Aging increases upper airway collapsibility in fischer 344 rats. J Appl Physiol. 2008;105:1471–6.
Eikermann M, Jordan AS, Chamberlin NL, Gautam S, Wellman A, Lo YL, et al. The influence of aging on pharyngeal collapsibility during sleep. Chest. 2007;131:1702–9.
Veldi M, Vasar V, Vain A, Kull M. Obstructive sleep apnea and ageing myotonometry demonstrates changes in the soft palate and tongue while awake. Pathophysiology. 2004;11:159–65.
Riha RL. Clinical assessment of the obstructive sleep apnoea/hypopnoea syndrome. Ther Adv Respir Dis. 2010;4:83–91.
Chung S, Yoon IY, Lee CH, Kim JW. Effects of age on the clinical features of men with obstructive sleep apnea syndrome. Respiration. 2009;78:23–9.
Gottlieb DJ, Yao Q, Redline S, Ali T, Mahowald MW. Does snoring predict sleepiness independently of apnea and hypopnea frequency? Am J Respir Crit Care Med. 2000;162:1512–7.
Kezirian EJ, Harrison SL, Ancoli-Israel S, Redline S, Ensrud K, Goldberg AN, et al. Behavioral correlates of sleep-disordered breathing in older men. Sleep. 2009;32:253–61.
Endeshaw Y. Clinical characteristics of obstructive sleep apnea in community-dwelling older adults. J Am Geriatr Soc. 2006;54:1740–4.
Endeshaw YW, Johnson TM, Kutner MH, Ouslander JG, Bliwise DL. Sleep-disordered breathing and nocturia in older adults. J Am Geriatr Soc. 2004;52:957–60.
Aloia MS, Ilniczky N, Di Dio P, Perlis ML, Greenblatt DW, Giles DE. Neuropsychological changes and treatment compliance in older adults with sleep apnea. J Psychosom Res. 2003;54:71–6.
Dealberto MJ, Pajot N, Courbon D, Alperovitch A. Breathing disorders during sleep and cognitive performance in an older community sample: the eva study. J Am Geriatr Soc. 1996;44:1287–94.
Peters RW. Obstructive sleep apnea and cardiovascular disease. Chest. 2005;127:1–3.
Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342:1378–84.
Gami AS, Howard DE, Olson EJ, Somers VK. Day-night pattern of sudden death in obstructive sleep apnea. N Engl J Med. 2005;352:1206–14.
Peker Y, Kraiczi H, Hedner J, Loth S, Johansson A, Bende M. An independent association between obstructive sleep apnoea and coronary artery disease. Eur Respir J. 1999;14:179–84.
Mooe T, Franklin KA, Holmstrom K, Rabben T, Wiklund U. Sleep-disordered breathing and coronary artery disease: long-term prognosis. Am J Respir Crit Care Med. 2001;164: 1910–3.
Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005;353:2034–41.
Yim-Yeh S, Rahangdale S, Nguyen AT, Jordan AS, Novack V, Veves A, et al. Obstructive sleep apnea and aging effects on macrovascular and microcirculatory function. Sleep. 2010;33:1177–83.
Nieto FJ, Young TB, Lind BK, Shahar E, Samet JM, Redline S, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep heart health study. JAMA. 2000;283:1829–36.
Munoz R, Duran-Cantolla J, Martinez-Vila E, Gallego J, Rubio R, Aizpuru F, et al. Severe sleep apnea and risk of ischemic stroke in the elderly. Stroke. 2006;37:2317–21.
He J, Kryger MH, Zorick FJ, Conway W, Roth T. Mortality and apnea index in obstructive sleep apnea. Experience in 385 male patients. Chest. 1988;94:9–14.
Bliwise DL, Bliwise NG, Partinen M, Pursley AM, Dement WC. Sleep apnea and mortality in an aged cohort. Am J Public Health. 1988;78:544–7.
Ancoli-Israel S, Klauber MR, Kripke DF, Parker L, Cobarrubias M. Sleep apnea in female patients in a nursing home. Increased risk of mortality. Chest. 1989;96:1054–8.
Mant A, King M, Saunders NA, Pond CD, Goode E, Hewitt H. Four-year follow-up of mortality and sleep-related respiratory disturbance in non-demented seniors. Sleep. 1995;18:433–8.
Ancoli-Israel S, Kripke DF, Klauber MR, Fell R, Stepnowsky C, Estline E, et al. Morbidity, mortality and sleep-disordered breathing in community dwelling elderly. Sleep. 1996;19: 277–82.
Lavie P, Lavie L, Herer P. All-cause mortality in males with sleep apnoea syndrome: declining mortality rates with age. Eur Respir J. 2005;25:514–20.
Lavie P, Lavie L. Unexpected survival advantage in elderly people with moderate sleep apnoea. J Sleep Res. 2009;18:397–403.
Lavie L, Lavie P. Ischemic preconditioning as a possible explanation for the age decline relative mortality in sleep apnea. Med Hypotheses. 2006;66:1069–73.
Lavie L, Lavie P. Coronary collateral circulation in sleep apnea: a cardioprotective mechanism? Chest. 2010;137:511–2.
Cai Z, Manalo DJ, Wei G, Rodriguez ER, Fox-Talbot K, Lu H, et al. Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia-reperfusion injury. Circulation. 2003;108:79–85.
Malhotra RK, Desai AK. Healthy brain aging: what has sleep got to do with it? Clin Geriatr Med. 2010;26:45–56.
Ayalon L, Ancoli-Israel S, Aka AA, McKenna BS, Drummond SP. Relationship between obstructive sleep apnea severity and brain activation during a sustained attention task. Sleep. 2009;32:373–81.
Adams N, Strauss M, Schluchter M, Redline S. Relation of measures of sleep-disordered breathing to neuropsychological functioning. Am J Respir Crit Care Med. 2001;163: 1626–31.
Gozal D, Daniel JM, Dohanich GP. Behavioral and anatomical correlates of chronic episodic hypoxia during sleep in the rat. J Neurosci. 2001;21:2442–50.
Macey PM, Henderson LA, Macey KE, Alger JR, Frysinger RC, Woo MA, et al. Brain morphology associated with obstructive sleep apnea. Am J Respir Crit Care Med. 2002;166: 1382–7.
Singer T, Verhaeghen P, Ghisletta P, Lindenberger U, Baltes PB. The fate of cognition in very old age: six-year longitudinal findings in the Berlin aging study (base). Psychol Aging. 2003;18:318–31.
Gozal D, Row BW, Kheirandish L, Liu R, Guo SZ, Qiang F, et al. Increased susceptibility to intermittent hypoxia in aging rats: changes in proteasomal activity, neuronal apoptosis and spatial function. J Neurochem. 2003;86:1545–52.
Mathieu A, Mazza S, Decary A, Massicotte-Marquez J, Petit D, Gosselin N, et al. Effects of obstructive sleep apnea on cognitive function: a comparison between younger and older osas patients. Sleep Med. 2008;9:112–20.
Phillips BA, Berry DT, Schmitt FA, Harbison L, Lipke-Molby T. Sleep-disordered breathing in healthy aged persons: two- and three-year follow-up. Sleep. 1994;17:411–5.
Cohen-Zion M, Stepnowsky C, Johnson S, Marler M, Dimsdale JE, Ancoli-Israel S. Cognitive changes and sleep disordered breathing in elderly: differences in race. J Psychosom Res. 2004;56:549–53.
Alchanatis M, Zias N, Deligiorgis N, Liappas I, Chroneou A, Soldatos C, et al. Comparison of cognitive performance among different age groups in patients with obstructive sleep apnea. Sleep Breath. 2008;12:17–24.
Alchanatis M, Zias N, Deligiorgis N, Amfilochiou A, Dionellis G, Orphanidou D. Sleep apnea-related cognitive deficits and intelligence: an implication of cognitive reserve theory. J Sleep Res. 2005;14:69–75.
Ayalon L, Ancoli-Israel S, Drummond SP. Obstructive sleep apnea and age: a double insult to brain function? Am J Respir Crit Care Med. 2010;182:413–9.
Ancoli-Israel S, Klauber MR, Butters N, Parker L, Kripke DF. Dementia in institutionalized elderly: relation to sleep apnea. J Am Geriatr Soc. 1991;39:258–63.
Sun X, He G, Qing H, Zhou W, Dobie F, Cai F, et al. Hypoxia facilitates Alzheimer’s disease pathogenesis by up-regulating bace1 gene expression. Proc Natl Acad Sci USA. 2006;103: 18727–32.
Manini TM. Energy expenditure and aging. Ageing Res Rev. 2009;9:1–11.
Cartwright RD. Effect of sleep position on sleep apnea severity. Sleep. 1984;7:110–4.
Iber C, O’Brien C, Schluter J, Davies S, Leatherman J, Mahowald M. Single night studies in obstructive sleep apnea. Sleep. 1991;14:383–5.
McArdle N, Douglas NJ. Effect of continuous positive airway pressure on sleep architecture in the sleep apnea-hypopnea syndrome: a randomized controlled trial. Am J Respir Crit Care Med. 2001;164:1459–63.
Bardwell WA, Ancoli-Israel S, Berry CC, Dimsdale JE. Neuropsychological effects of one-week continuous positive airway pressure treatment in patients with obstructive sleep apnea: a placebo-controlled study. Psychosom Med. 2001;63:579–84.
Montserrat JM, Ferrer M, Hernandez L, Farre R, Vilagut G, Navajas D, et al. Effectiveness of cpap treatment in daytime function in sleep apnea syndrome: a randomized controlled study with an optimized placebo. Am J Respir Crit Care Med. 2001;164:608–13.
Sanner BM, Tepel M, Markmann A, Zidek W. Effect of continuous positive airway pressure therapy on 24-hour blood pressure in patients with obstructive sleep apnea syndrome. Am J Hypertens. 2002;15:251–7.
Javaheri S. Effects of continuous positive airway pressure on sleep apnea and ventricular irritability in patients with heart failure. Circulation. 2000;101:392–7.
Bahammam A, Delaive K, Ronald J, Manfreda J, Roos L, Kryger MH. Health care utilization in males with obstructive sleep apnea syndrome two years after diagnosis and treatment. Sleep. 1999;22:740–7.
Tarasiuk A, Greenberg-Dotan S, Simon-Tuval T, Oksenberg A, Reuveni H. The effect of obstructive sleep apnea on morbidity and health care utilization of middle-aged and older adults. J Am Geriatr Soc. 2008;56:247–54.
Frohnhofen H, Heuer HC, Pfundner N, Orth G. Cyclical nocturnal oxygen desaturation and impact on activities of daily living in elderly patients. J Physiol Pharmacol. 2007;58 Suppl 5:185–91.
Frohnhofen H, Heuer HC, Kanzia A, Firat A. Influence of type of treatment for sleep apnea on activities of daily living in a sample of elderly patients with severe sleep apnea. J Physiol Pharmacol. 2009;60 Suppl 5:51–5.
Canessa N, Castronovo V, Cappa SF, Aloia MS, Marelli S, Falini A, et al. Obstructive sleep apnea: brain structural changes and neurocognitive function before and after treatment. Am J Respir Crit Care Med. 2011;183(10):1292–4.
Margel D, Shochat T, Getzler O, Livne PM, Pillar G. Continuous positive airway pressure reduces nocturia in patients with obstructive sleep apnea. Urology. 2006;67:974–7.
Aihara K, Chin K, Oga T, Takahashi K, Hitomi T, Takegami M, et al. Long-term nasal continuous positive airway pressure treatment lowers blood pressure in patients with obstructive sleep apnea regardless of age. Hypertens Res. 2010;33:1025–31.
Kostikas K, Browne HA, Ghiassi R, Adams L, Simonds AK, Morrell MJ. The determinants of therapeutic levels of continuous positive airway pressure in elderly sleep apnea patients. Respir Med. 2006;100:1216–25.
Pelletier-Fleury N, Rakotonanahary D, Fleury B. The age and other factors in the evaluation of compliance with nasal continuous positive airway pressure for obstructive sleep apnea syndrome. A cox’s proportional hazard analysis. Sleep Med. 2001;2:225–32.
Russo-Magno P, O’Brien A, Panciera T, Rounds S. Compliance with cpap therapy in older men with obstructive sleep apnea. J Am Geriatr Soc. 2001;49:1205–11.
Aloia MS, Di Dio L, Ilniczky N, Perlis ML, Greenblatt DW, Giles DE. Improving compliance with nasal CPAP and vigilance in older adults with OAHS. Sleep Breath. 2001;5:13–21.
Frohnhofen H, Hoeltmann B, Orth G. Acceptance of NCPAP in a sample of patients admitted for geriatric rehabilitation. Eur J Med Res. 2009;14 Suppl 4:82–5.
Ayalon L, Ancoli-Israel S, Stepnowsky C, Marler M, Palmer BW, Liu L, et al. Adherence to continuous positive airway pressure treatment in patients with Alzheimer’s disease and obstructive sleep apnea. Am J Geriatr Psychiatry. 2006;14:176–80.
Ancoli-Israel S, Palmer BW, Cooke JR, Corey-Bloom J, Fiorentino L, Natarajan L, et al. Cognitive effects of treating obstructive sleep apnea in Alzheimer’s disease: a randomized controlled study. J Am Geriatr Soc. 2008;56:2076–81.
Cooke JR, Ayalon L, Palmer BW, Loredo JS, Corey-Bloom J, Natarajan L, et al. Sustained use of CPAP slows deterioration of cognition, sleep, and mood in patients with Alzheimer’s disease and obstructive sleep apnea: a preliminary study. J Clin Sleep Med. 2009;5:305–9.
Cooke JR, Ancoli-Israel S, Liu L, Loredo JS, Natarajan L, Palmer BS, et al. Continuous positive airway pressure deepens sleep in patients with Alzheimer’s disease and obstructive sleep apnea. Sleep Med. 2009;10:1101–6.
Kushida CA, Morgenthaler TI, Littner MR, Alessi CA, Bailey D, Coleman Jr J, et al. Practice parameters for the treatment of snoring and obstructive sleep apnea with oral appliances: an update for 2005. Sleep. 2006;29:240–3.
Petit FX, Pepin JL, Bettega G, Sadek H, Raphael B, Levy P. Mandibular advancement devices: rate of contraindications in 100 consecutive obstructive sleep apnea patients. Am J Respir Crit Care Med. 2002;166:274–8.
Bloom HG, Ahmed I, Alessi CA, Ancoli-Israel S, Buysse DJ, Kryger MH, et al. Evidence-based recommendations for the assessment and management of sleep disorders in older persons. J Am Geriatr Soc. 2009;57:761–89.
Nelogi S, Porwal A, Naveen H. Modified mandibular advancement appliance for an edentulous obstructive sleep apnea patient: a clinical report. J Prosthodont Res. 2011;55(3):179–83.
Caples SM, Rowley JA, Prinsell JR, Pallanch JF, Elamin MB, Katz SG, et al. Surgical modifications of the upper airway for obstructive sleep apnea in adults: a systematic review and meta-analysis. Sleep. 2010;33:1396–407.
Shochat T, Pillar G. Sleep apnoea in the older adult: pathophysiology, epidemiology, consequences and management. Drugs Aging. 2003;20:551–60.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Roux, F.J. (2012). Obstructive Sleep Apnea in Older Patients. In: Pisani, M. (eds) Aging and Lung Disease. Respiratory Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-727-3_8
Download citation
DOI: https://doi.org/10.1007/978-1-60761-727-3_8
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60761-726-6
Online ISBN: 978-1-60761-727-3
eBook Packages: MedicineMedicine (R0)