Current Surgery Reports

, 5:30 | Cite as

Frailty in Trauma Patients: An Emerging Geriatric Syndrome

Trauma Surgery (J. Diaz, Section Editor)
Part of the following topical collections:
  1. Trauma Surgery

Abstract

Purpose of Review

In contrast to their younger counterparts, geriatric patients have a decreased physiological reserve. This age-related vulnerability poses unique challenges for clinical decision-making. Additionally, as the population of the United States (U.S.) continues to age at a rapid pace, an increasing number of elderly patients need trauma care. Accordingly, this review examines the relevance of the concept of frailty in trauma cases, as well as its role in identifying vulnerable trauma patients and improving patient care. Moreover, through a process of simplification, we made the fundamental concepts of frailty and Frailty Index clearer and more useful.

Recent Findings

Frailty is a state of decline in many physiological systems. It increases vulnerability to a poor resolution after a stressor event. More precisely, this cumulative depletion of the body’s reserves makes it more likely, that a stressor will trigger disproportionate changes in health. This being the case, investigators have developed several validated models of frailty that show the association between frailty and health outcomes in trauma.

Summary

Frailty can decisively impact a wide spectrum of a trauma patient care, including morbidity, mortality, hospital stay, discharge disposition from the hospital, and informed clinical decision-making. Therefore, especially given the increasing number of aging individuals in the U.S., the frailty of such patients must be considered to improve outcomes.

Keywords

Frailty Geriatric trauma Geriatric syndrome Frailty Index Trauma outcomes 

Notes

Compliance with Ethics Guidelines

Conflict of interest

The authors declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Rhee P, Joseph B, Pandit V, Aziz H, Vercruysse G, Kulvatunyou N, et al. Increasing trauma deaths in the United States. Ann Surg. 2014;260(1):13–21.PubMedCrossRefGoogle Scholar
  2. 2.
    Rzepka SG, Malangoni MA, Rimm AA. Geriatric trauma hospitalization in the United States: a population-based study. J Clin Epidemiol. 2001;54(6):627–33.PubMedCrossRefGoogle Scholar
  3. 3.
    • Joseph B, Hassan A. Geriatric trauma patients: what is the difference? Curr Surg Rep. 2016;4(1):1. This paper denotes the importance of geriatric trauma and how management of geriatric trauma can be challenging.Google Scholar
  4. 4.
    Colby SL, Ortman JM. Projections of the size and composition of the US population: 2014 to 2060. Current population reports P25-1143. Washington, DC: US Census Bureau; 2015.Google Scholar
  5. 5.
    • Hashmi A, Ibrahim-Zada I, Rhee P, Aziz H, Fain MJ, Friese RS, et al. Predictors of mortality in geriatric trauma patients: a systematic review and meta-analysis. J Trauma Acute Care Surg. 2014;76(3):894–901. Sytemic review and meta-analysis demonstrating the predioctors of mortality in gariatric trauma patients.Google Scholar
  6. 6.
    Turrentine FE, Wang H, Simpson VB, Jones RS. Surgical risk factors, morbidity, and mortality in elderly patients. J Am Coll Surg. 2006;203(6):865–77.PubMedCrossRefGoogle Scholar
  7. 7.
    Jacobs DG, Plaisier BR, Barie PS, Hammond JS, Holevar MR, Sinclair KE, et al. Practice management guidelines for geriatric trauma: the EAST Practice Management Guidelines Work Group. J Trauma Acute Care Surg. 2003;54(2):391–416.CrossRefGoogle Scholar
  8. 8.
    Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, et al. A global clinical measure of fitness and frailty in elderly people. Can Med Assoc J. 2005;173(5):489–95.CrossRefGoogle Scholar
  9. 9.
    Rockwood K, Howlett SE, MacKnight C, Beattie BL, Bergman H, Hébert R, et al. Prevalence, attributes, and outcomes of fitness and frailty in community-dwelling older adults: report from the Canadian study of health and aging. J Gerontol A. 2004;59(12):1310–7.CrossRefGoogle Scholar
  10. 10.
    Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults evidence for a phenotype. J Gerontol A. 2001;56(3):M146–57.CrossRefGoogle Scholar
  11. 11.
    Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A. 2004;59(3):M255–63.CrossRefGoogle Scholar
  12. 12.
    Winograd CH. Targeting strategies: an overview of criteria and outcomes. J Am Geriatr Soc. 1991;39(S1):25S–35S.PubMedCrossRefGoogle Scholar
  13. 13.
    Campbell AJ, Buchner DM. Unstable disability and the fluctuations of frailty. Age Ageing. 1997;26(4):315–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Joseph B, Pandit V, Sadoun M, Zangbar B, Fain MJ, Friese RS, et al. Frailty in surgery. J Trauma Acute Care Surg. 2014;76(4):1151–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Lipsitz LA. Dynamics of stability: the physiologic basis of functional health and frailty. J Gerontol A. 2002;57(3):B115–25.CrossRefGoogle Scholar
  16. 16.
    Fried LP, Xue Q-L, Cappola AR, Ferrucci L, Chaves P, Varadhan R, et al. Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. J Gerontol A. 2009;64(10):1049–57.CrossRefGoogle Scholar
  17. 17.
    Chen X, Mao G, Leng SX. Frailty syndrome: an overview. Clin Interv Aging. 2014;9:433.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Newman AB, Gottdiener JS, McBurnie MA, Hirsch CH, Kop WJ, Tracy R, et al. Associations of subclinical cardiovascular disease with frailty. J Gerontol A. 2001;56(3):M158–66.CrossRefGoogle Scholar
  19. 19.
    Arai Y, Takayama M, Gondo Y, Inagaki H, Yamamura K, Nakazawa S, et al. Adipose endocrine function, insulin-like growth factor-1 axis, and exceptional survival beyond 100 years of age. J Gerontol A. 2008;63(11):1209–18.CrossRefGoogle Scholar
  20. 20.
    Reiner AP, Aragaki AK, Gray SL, Wactawski-Wende J, Cauley JA, Cochrane BB, et al. Inflammation and thrombosis biomarkers and incident frailty in postmenopausal women. Am J Med. 2009;122(10):947–54.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Lenz A, Franklin GA, Cheadle WG. Systemic inflammation after trauma. Injury. 2007;38(12):1336–45. doi: 10.1016/j.injury.2007.10.003.PubMedCrossRefGoogle Scholar
  22. 22.
    Cappola AR, Xue Q-L, Ferrucci L, Guralnik JM, Volpato S, Fried LP. Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women. J Clin Endocrinol Metab. 2003;88(5):2019–25.PubMedCrossRefGoogle Scholar
  23. 23.
    Kacey DJ, Perez-Tamayo A. Principles and practice of geriatric surgery. JAMA. 2012;307(18):1981.CrossRefGoogle Scholar
  24. 24.
    Sternberg S, Levin R, Dkaidek S, Edelman S, Resnick T, Menczel J. Frailty and osteoporosis in older women—a prospective study. Osteoporos Int. 2014;25(2):763–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–62.PubMedCrossRefGoogle Scholar
  26. 26.
    • Joseph B, Pandit V, Rhee P, Aziz H, Sadoun M, Wynne J, et al. Predicting hospital discharge disposition in geriatric trauma patients: is frailty the answer? J Trauma Acute Care Surg. 2014;76(1):196–200. This study demonstrates the importance of frailty index in predicting unfavourable dishcarge disposition, and how it should be an integral part of tool to determine discharge disposition.Google Scholar
  27. 27.
    • Joseph B, Pandit V, Zangbar B, Kulvatunyou N, Tang A, O’Keeffe T, et al. Validating trauma-specific frailty index for geriatric trauma patients: a prospective analysis. J Am Coll Surg. 2014;219(1):10–7.e1. An important paper in validating the trauma specific frailty index, which is most extensively used frailty assessment tool in trauma population.Google Scholar
  28. 28.
    Brown M, Sinacore DR, Binder EF, Kohrt WM. Physical and performance measures for the identification of mild to moderate frailty. J Gerontol A. 2000;55(6):M350–5.CrossRefGoogle Scholar
  29. 29.
    Rikli RE, Jones CJ. Development and validation of a functional fitness test for community-residing older adults. J Aging Phys Act. 1999;7(2):129–61.CrossRefGoogle Scholar
  30. 30.
    Sudarsky L. Gait disorders: prevalence, morbidity, and etiology. Adv Neurol. 2001;87:111.PubMedGoogle Scholar
  31. 31.
    Salzman B. Gait and balance disorders in older adults. Am Fam Physician. 2010;82(1):61–8.PubMedGoogle Scholar
  32. 32.
    • Toosizadeh N, Joseph B, Heusser MR, Jokar TO, Mohler J, Phelan HA, et al. Assessing upper-extremity motion: an innovative, objective method to identify frailty in older bed-bound trauma patients. J Am Coll Surg. 2016;223(2):240–8. A more objective tool to measure frailty status, Upper Extremity Frailty assessment tool.Google Scholar
  33. 33.
    Maxwell CA, Dietrich MS, Minnick AF, Mion LC. Preinjury physical function and frailty in injured older adults: self-versus proxy responses. J Am Geriatr Soc. 2015;63(7):1443–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Maxwell CA, Mion LC, Mukherjee K, Dietrich MS, Minnick A, May A, et al. Feasibility of screening for preinjury frailty in hospitalized injured older adults. J Trauma Acute Care Surg. 2015;78(4):844–51.PubMedCrossRefGoogle Scholar
  35. 35.
    Maxwell CA, Mion LC, Mukherjee K, Dietrich MS, Minnick A, May A, et al. Preinjury physical frailty and cognitive impairment among geriatric trauma patients determine postinjury functional recovery and survival. J Trauma Acute Care Surg. 2016;80(2):195–203.PubMedCrossRefGoogle Scholar
  36. 36.
    Saliba D, Elliott M, Rubenstein LZ, Solomon DH, Young RT, Kamberg CJ, et al. The vulnerable elders survey: a tool for identifying vulnerable older people in the community. J Am Geriatr Soc. 2001;49(12):1691–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Collin C, Wade D, Davies S, Horne V. The Barthel ADL Index: a reliability study. Int Disabilit Stud. 1988;10(2):61–3.CrossRefGoogle Scholar
  38. 38.
    Portegijs E, Iwarsson S, Rantakokko M, Viljanen A, Rantanen T. Life-space mobility assessment in older people in Finland; measurement properties in winter and spring. BMC Res Notes. 2014;7(1):323.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Chow WB, Rosenthal RA, Merkow RP, Ko CY, Esnaola NF. Optimal preoperative assessment of the geriatric surgical patient: a best practices guideline from the American College of Surgeons National Surgical Quality Improvement Program and the American Geriatrics Society. J Am Coll Surg. 2012;215(4):453–66.PubMedCrossRefGoogle Scholar
  40. 40.
    Roubenoff R. Sarcopenia: a major modifiable cause of frailty in the elderly. J Nutr Health Aging. 2000;4(3):140–2.PubMedGoogle Scholar
  41. 41.
    Cooper C, Dere W, Evans W, Kanis J, Rizzoli R, Sayer AA, et al. Frailty and sarcopenia: definitions and outcome parameters. Osteoporos Int. 2012;23(7):1839–48.PubMedCrossRefGoogle Scholar
  42. 42.
    Cook AC, Joseph B, Inaba K, Nakonezny PA, Bruns BR, Kerby JD, et al. Multicenter external validation of the Geriatric Trauma Outcome Score: a study by the Prognostic Assessment of Life and Limitations After Trauma in the Elderly (PALLIATE) consortium. J Trauma Acute Care Surg. 2016;80(2):204–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Khan M, O’Keeffe T, Jehan F, Kulvatunyou N, Kattaa A, Gries L, et al. The impact of Glasgow Coma Scale—age prognosis score on geriatric traumatic brain injury outcomes. J Surg Res. 2017;216:109–14.PubMedCrossRefGoogle Scholar
  44. 44.
    Obeid NM, Azuh O, Reddy S, Webb S, Reickert C, Velanovich V, et al. Predictors of critical care-related complications in colectomy patients using the National Surgical Quality Improvement Program: exploring frailty and aggressive laparoscopic approaches. J Trauma Acute Care Surg. 2012;72(4):878–83.PubMedCrossRefGoogle Scholar
  45. 45.
    Andersson RE. Short and long-term mortality after appendectomy in Sweden 1987 to 2006. Influence of appendectomy diagnosis, sex, age, co-morbidity, surgical method, hospital volume, and time period. A national population-based cohort study. World J Surg. 2013;37(5):974–81.PubMedCrossRefGoogle Scholar
  46. 46.
    Finegold JA, Asaria P, Francis DP. Mortality from ischaemic heart disease by country, region, and age: statistics from World Health Organisation and United Nations. Int J Cardiol. 2013;168(2):934–45.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Yazdi-Ravandi S, Taslimi Z, Saberi H, Shams J, Osanlo S, Nori G, et al. The role of resilience and age on quality of life in patients with pain disorders. Basic Clin Neurosci. 2013;4(1):24.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Bobay KL, Jerofke TA, Weiss ME, Yakusheva O. Age-related differences in perception of quality of discharge teaching and readiness for hospital discharge. Geriatr Nurs. 2010;31(3):178–87.PubMedCrossRefGoogle Scholar
  49. 49.
    Ringburg AN, Polinder S, van Ierland MCP, Steyerberg EW, van Lieshout EM, Patka P, et al. Prevalence and prognostic factors of disability after major trauma. J Trauma Acute Care Surg. 2011;70(4):916–22.CrossRefGoogle Scholar
  50. 50.
    Finelli FC, Jonsson J, Champion HR, Morelli S, Fouty WJ. A case control study for major trauma in geriatric patients. J Trauma Acute Care Surg. 1989;29(5):541–8.CrossRefGoogle Scholar
  51. 51.
    Joseph B, Pandit V, Khalil M, Kulvatunyou N, Zangbar B, Friese RS, et al. Managing older adults with ground-level falls admitted to a trauma service: the effect of frailty. J Am Geriatr Soc. 2015;63(4):745–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Hewitt J, Moug SJ, Middleton M, Chakrabarti M, Stechman MJ, McCarthy K, et al. Prevalence of frailty and its association with mortality in general surgery. Am J Surg. 2015;209(2):254–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Revenig LM, Canter DJ, Taylor MD, Tai C, Sweeney JF, Sarmiento JM, et al. Too frail for surgery? Initial results of a large multidisciplinary prospective study examining preoperative variables predictive of poor surgical outcomes. J Am Coll Surg. 2013;217(4):665–70.e1.Google Scholar
  54. 54.
    Green P, Woglom AE, Genereux P, Daneault B, Paradis J-M, Schnell S, et al. The impact of frailty status on survival after transcatheter aortic valve replacement in older adults with severe aortic stenosis: a single-center experience. JACC Cardiovasc Interv. 2012;5(9):974–81.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Ali R, Schwalb JM, Nerenz DR, Antoine HJ, Rubinfeld I. Use of the modified frailty index to predict 30-day morbidity and mortality from spine surgery. J Neurosurg Spine. 2016;25(4):537–41.PubMedCrossRefGoogle Scholar
  56. 56.
    Dasgupta M, Rolfson DB, Stolee P, Borrie MJ, Speechley M. Frailty is associated with postoperative complications in older adults with medical problems. Arch Gerontol Geriatr. 2009;48(1):78–83.PubMedCrossRefGoogle Scholar
  57. 57.
    • Joseph B, Pandit V, Zangbar B, Kulvatunyou N, Hashmi A, Green DJ, et al. Superiority of frailty over age in predicting outcomes among geriatric trauma patients: a prospective analysis. JAMA Surg. 2014;149(8):766–72. A break through study about frailty in trauma, the development of frailty index in trauma population using the 50 variable frailty index from canadian study of health and aging.Google Scholar
  58. 58.
    • Joseph B, Phelan H, Hassan A, Jokar TO, O’keeffe T, Azim A, et al. The impact of frailty on failure-to-rescue in geriatric trauma patients: A prospective study. J Trauma Acute Care Surg. 2016;81(6):1150–55. An important analysis of impact of frailty on failure to rescue, which is considered an index for quality of measure.Google Scholar
  59. 59.
    • Joseph B, Jokar TO, Hassan A, Azim A, Mohler MJ, Kulvatunyou N, et al. Redefining the association between old age and poor outcomes after trauma: the impact of frailty syndrome. J Trauma Acute Care Surg. 2017;82(3):575–81. An important analysis of impact of railty in both short and long-term outcomes.Google Scholar
  60. 60.
    Makary MA, Segev DL, Pronovost PJ, Syin D, Bandeen-Roche K, Patel P, et al. Frailty as a predictor of surgical outcomes in older patients. J Am Coll Surg. 2010;210(6):901–8.PubMedCrossRefGoogle Scholar
  61. 61.
    Garonzik-Wang JM, Govindan P, Grinnan JW, Liu M, Ali HM, Chakraborty A, et al. Frailty and delayed graft function in kidney transplant recipients. Arch Surg. 2012;147(2):190–3.PubMedCrossRefGoogle Scholar
  62. 62.
    Pol R, Van Leeuwen B, Visser L, Izaks G, Van den Dungen J, Tielliu I, et al. Standardised frailty indicator as predictor for postoperative delirium after vascular surgery: a prospective cohort study. Eur J Vasc Endovasc Surg. 2011;42(6):824–30.PubMedCrossRefGoogle Scholar
  63. 63.
    Kasotakis G, Schmidt U, Perry D, Grosse-Sundrup M, Benjamin J, Ryan C, et al. The surgical intensive care unit optimal mobility score predicts mortality and length of stay. Crit Care Med. 2012;40(4):1122–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Robinson TN, Eiseman B, Wallace JI, Church SD, McFann KK, Pfister SM, et al. Redefining geriatric preoperative assessment using frailty, disability and co-morbidity. Ann Surg. 2009;250(3):449–55.PubMedGoogle Scholar
  65. 65.
    Masud D, Norton S, Smailes S, Shelley O, Philp B, Dziewulski P. The use of a frailty scoring system for burns in the elderly. Burns. 2013;39(1):30–6.PubMedCrossRefGoogle Scholar
  66. 66.
    Robinson TN, Wallace JI, Wu DS, Wiktor A, Pointer LF, Pfister SM, et al. Accumulated frailty characteristics predict postoperative discharge institutionalization in the geriatric patient. J Am Coll Surg. 2011;213(1):37–42.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Lee TH, Marcantonio ER, Mangione CM, Thomas EJ, Polanczyk CA, Cook EF, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation. 1999;100(10):1043–9.PubMedCrossRefGoogle Scholar
  68. 68.
    Silber JH, Williams SV, Krakauer H, Schwartz JS. Hospital and patient characteristics associated with death after surgery: a study of adverse occurrence and failure to rescue. Med Care. 1992;30:615–29.PubMedCrossRefGoogle Scholar
  69. 69.
    Silber JH, Williams SV, Krakauer H, Schwartz JS. Hospital and patient characteristics associated with death after surgery. A study of adverse occurrence and failure to rescue. Med Care. 1992;30(7):615–29.PubMedCrossRefGoogle Scholar
  70. 70.
    Glance LG, Dick AW, Meredith JW, Mukamel DB. Variation in hospital complication rates and failure-to-rescue for trauma patients. Ann Surg. 2011;253(4):811–6.PubMedCrossRefGoogle Scholar
  71. 71.
    Waits SA, Sheetz KH, Campbell DA, Ghaferi AA, Englesbe MJ, Eliason JL, et al. Failure to rescue and mortality following repair of abdominal aortic aneurysm. J Vasc Surg. 2014;59(4):909–14.e1.Google Scholar
  72. 72.
    Ghaferi AA, Birkmeyer JD, Dimick JB. Variation in hospital mortality associated with inpatient surgery. N Engl J Med. 2009;361(14):1368–75.PubMedCrossRefGoogle Scholar
  73. 73.
    Bagshaw SM, Stelfox HT, McDermid RC, Rolfson DB, Tsuyuki RT, Baig N, et al. Association between frailty and short-and long-term outcomes among critically ill patients: a multicentre prospective cohort study. Can Med Assoc J. 2014;186(2):E95–102.CrossRefGoogle Scholar
  74. 74.
    Barlow J, Singh D, Bayer S, Curry R. A systematic review of the benefits of home telecare for frail elderly people and those with long-term conditions. J Telemed Telecare. 2007;13(4):172–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Rockwood K, Mitnitski A, Song X, Steen B, Skoog I. Long-term risks of death and institutionalization of elderly people in relation to deficit accumulation at age 70. J Am Geriatr Soc. 2006;54(6):975–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Masel MC, Graham JE, Reistetter TA, Markides KS, Ottenbacher KJ. Frailty and health related quality of life in older Mexican Americans. Health Qual Life Outcomes. 2009;7(1):70.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Chang Y-W, Chen W-L, Lin F-G, Fang W-H, Yen M-Y, Hsieh C-C, et al. Frailty and its impact on health-related quality of life: a cross-sectional study on elder community-dwelling preventive health service users. PLoS ONE. 2012;7(5):e38079.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Ellis G, Whitehead MA, Robinson D, O’Neill D, Langhorne P. Comprehensive geriatric assessment for older adults admitted to hospital: meta-analysis of randomised controlled trials. BMJ. 2011;343:d6553.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Beswick AD, Rees K, Dieppe P, Ayis S, Gooberman-Hill R, Horwood J, et al. Complex interventions to improve physical function and maintain independent living in elderly people: a systematic review and meta-analysis. Lancet. 2008;371(9614):725–35.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Stuck AE, Egger M, Hammer A, Minder CE, Beck JC. Home visits to prevent nursing home admission and functional decline in elderly people: systematic review and meta-regression analysis. JAMA. 2002;287(8):1022–8.PubMedCrossRefGoogle Scholar
  81. 81.
    Barber SE, Clegg AP, Young JB. Is there a role for physical activity in preventing cognitive decline in people with mild cognitive impairment? Age Ageing. 2011;41(1):5–8.PubMedCrossRefGoogle Scholar
  82. 82.
    Handschin C, Spiegelman BM. The role of exercise and PGC1α in inflammation and chronic disease. Nature. 2008;454(7203):463–9.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Gleeson M, McFarlin B, Flynn M. Exercise and Toll-like receptors. Exerc Immunol Rev. 2006;12(1):34–53.PubMedGoogle Scholar
  84. 84.
    Van Praag H. Exercise and the brain: something to chew on. Trends Neurosci. 2009;32(5):283–90.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    De Vries N, Van Ravensberg C, Hobbelen J, Rikkert MO, Staal J, Nijhuis-van der Sanden M. Effects of physical exercise therapy on mobility, physical functioning, physical activity and quality of life in community-dwelling older adults with impaired mobility, physical disability and/or multi-morbidity: a meta-analysis. Ageing Res Rev. 2012;11(1):136–49.PubMedCrossRefGoogle Scholar
  86. 86.
    Theou O, Stathokostas L, Roland KP, Jakobi JM, Patterson C, Vandervoort AA, et al. The effectiveness of exercise interventions for the management of frailty: a systematic review. J Aging Res. 2011;2011:569194.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Clegg AP, Barber SE, Young JB, Forster A, Iliffe SJ. Do home-based exercise interventions improve outcomes for frail older people? Findings from a systematic review. Rev Clin Gerontol. 2012;22(1):68–78.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Forster A, Lambley R, Hardy J, Young J, Smith J, Green J, et al. Rehabilitation for older people in long-term care. Cochrane Database Syst Rev. 2009;1:CD004294.Google Scholar
  89. 89.
    Fiatarone MA, O’Neill EF, Ryan ND, Clements KM, Solares GR, Nelson ME, et al. Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med. 1994;330(25):1769–75.PubMedCrossRefGoogle Scholar
  90. 90.
    Onder G, Penninx BW, Balkrishnan R, Fried LP, Chaves PH, Williamson J, et al. Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study. Lancet. 2002;359(9310):926–30.PubMedCrossRefGoogle Scholar
  91. 91.
    Sumukadas D, Witham MD, Struthers AD, McMurdo ME. Effect of perindopril on physical function in elderly people with functional impairment: a randomized controlled trial. Can Med Assoc J. 2007;177(8):867–74.CrossRefGoogle Scholar
  92. 92.
    Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363(2):109–22.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Puts MT, Visser M, Twisk JW, Deeg DJ, Lips P. Endocrine and inflammatory markers as predictors of frailty. Clin Endocrinol. 2005;63(4):403–11.CrossRefGoogle Scholar
  94. 94.
    Wicherts IS, van Schoor NM, Boeke AJP, Visser M, Deeg DJ, Smit J, et al. Vitamin D status predicts physical performance and its decline in older persons. J Clin Endocrinol Metab. 2007;92(6):2058–65.PubMedCrossRefGoogle Scholar
  95. 95.
    Gillespie LD, Robertson MC, Gillespie WJ, Lamb SE, Gates S, Cumming RG, et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2009;2(2):CD007146.Google Scholar
  96. 96.
    Avenell A, Gillespie WJ, Gillespie LD, O’Connell D. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev. 2009;2(2):CD000227.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Division of Trauma, Critical Care, Emergency Surgery, and Burns, Department of SurgeryUniversity of ArizonaTucsonUSA
  2. 2.Division of Trauma, Critical Care, and Emergency Surgery, Department of SurgeryUniversity of ArizonaTucsonUSA

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