Abstract
Most people with Alzheimer’s disease and other dementias do not receive ongoing, intentional medical management for these conditions, and effective coordination of medical and non-medical care is rare. Many published guidelines and consensus statements provide recommendations for identification, diagnosis and ongoing management of key issues, including cognitive decline, behavioral and psychiatric symptoms, depression, safety, family caregiver support and use of community services. These recommendations provide a strong basis for the development of disease management approaches that could improve medical outcomes and quality of life for people with these conditions and their families. In the US, a demonstration project (Chronic Care Networks for Alzheimer’s Disease) is testing an innovative model of coordinated medical and non-medical care that incorporates many of the recommendations.
Similar content being viewed by others
Notes
In the US, tacrine, a cholinesterase inhibitor, was approved for the treatment of Alzheimer’s disease in 1993. As of early 2002, three other cholinesterase inhibitors have also been approved for the treatment of Alzheimer’s disease: donepezil, rivastigmine and galantamine.
The telephone interviews were conducted by Roper Starch Worldwide, Inc., with funding from Janssen Pharmaceutica and Ortho-McNeil Pharmaceuticals. Some of the family members (222) were identified through a random digit dialing system that includes all telephone households in the US, both listed and unlisted. An additional 154 family members were selected from a national mail panel of more than 500 000 households that is screened periodically for various diseases. The physician sample was drawn from an AMA directory that lists all physicians (both members and non-members) in the US and their specialty and included only physicians with at least 10% of their patients aged 65 years or over and some patients with a diagnosis of Alzheimer’s disease
At least one study found lower rates of coexisting medical conditions[58] perhaps in part because of sample factors.
Available data indicate that 20 to 25% of people with Alzheimer’s disease and other dementias live alone.[71] US census data for 2000 show that among people aged 85 years and older, 59% of women live alone. Alzheimer’s disease and other dementias are most common in this age group, and it is likely that many very old people with Alzheimer’s disease, other dementias and other coexisting medical conditions are living alone.
The six CCN/AD sites are in Denver (Colorado), Minneapolis/St Paul (Minnesota), Philadelphia (Pennsylvania), San Francisco (California), Troy/Albany (New York), and the upstate New York service area of the US Department of Veterans Affairs.
References
Boise L, Camicioli R, Morgan D, et al. Diagnosing dementia: perspectives of primary care physicians. Gerontologist 1999; 39(4): 457–64.
Rait G, Walters K, Iliffe S. The diagnosis and management of dementia in primary care. Generations 1999; 23(3): 17–23.
National Institute of Aging. 2000 Progress Report on Alzheimer’s disease: taking the next steps. Rockville (MD): Department of Health and Human Services, Public Health Service, National Institutes of Health, 2000.
Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer’s disease in the United States and public health impact of delaying disease onset. Am J Public Health 1998; 88(9): 1337–42.
Evans DA, Scherr PA, Cook NR, et al. Estimated prevalence of Alzheimer’s disease in the United States. Milbank Q 1990; 66(2): 267–90.
Department of Commerce, Census Bureau. Profile of General Demographic Characteristics, 2000 [online]. Available from URL: http://www.census.gov/ [Accessed 2001 Jun].
Evans DA, Funkenstein HH, Albert MS, et al. Prevalence of Alzheimer’s disease in a community population of older persons. JAMA 1989; 262(18): 2551–6.
Small GW, Rabins PV, Barry PP, et al. Diagnosis and treatment of Alzheimer disease and related disorders: consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer’s Association, and the American Geriatrics Society. JAMA 1997; 278(16): 1363–71.
Barclay LL, Zemcov A, Blass JP, et al. Survival in Alzheimer’s disease and vascular dementias. Neurology 1985; 35: 834–40.
Jost B, Grossberg GT. The natural history of Alzheimer’s disease: a brain bank study. J Am Geriatr Soc 1995; 45: 1248–55.
Walsh JS, Welch HG, Larson EB. Survival of outpatients with Alzheimer’s-type dementia. Ann Intern Med 1990; 113(6): 429–34.
Wolfson C, Wolfson DB, Asgharian M, et al. A reevaluation of the duration of survival after the onset of dementia. N Engl J Med 2001; 344(15): 1111–6.
Gorelick PB, Erkinjuntti T, Hofman A, et al. Prevention of vascular dementia. Alzheimer Dis Assoc Disord 1999; 13 Suppl. 3: S131–9.
Nyenhuis DL, Gorelick PB. Vascular dementia: a contemporary review of epidemiology, diagnosis, prevention, and treatment. J Am Geriatr Soc 1998; 46(11): 1437–48.
Alexopoulous GS, Silver JM, Kahn DA, et al. Treatment of agitation in older persons with dementia. Minneapolis (MN): McGraw-Hill Healthcare Information Group, 1998.
American Medical Association. Diagnosis, management, and treatment of dementia: a practical guide for primary care physicians. Chicago (IL): American Medical Association, 1999.
California Workgroup on Guidelines for Alzheimer’s Disease Management. Guidelines for Alzheimer’s disease management. Los Angeles (CA): Alzheimer’s Association, 1998.
Doody RS, Stevens JC, Beck RN, et al. Practice parameter: management of dementia (an evidence-based review): report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2001; 56: 1154–66.
Patterson CJS, Gauthier S, Bergman H, et al. Recognition, assessment and management of dementing disorders: conclusions from the Canadian consensus conference on dementia. CMAJ 1999; 160(12 Suppl.): S1–15.
Tangalos E, Burger SG, Cali T, et al. Dementia: clinical practice guideline. Washington (DC): American Medical Directors Association, 1998.
Work Group on Alzheimer’s Disease and Related Dementias. Practice guideline for the treatment of patients with Alzheimer’s disease and related dementias of late life. Am J Psychiatry 1997; 154(5 Suppl.): 1–39.
Beisecker AE, Chrisman SK, Wright LJ. Perceptions of family caregivers of persons with Alzheimer’s disease: communication with physicians. Am J Alzheimer’s Dis 1997; 12(2): 73–83.
Boise L, Morgan DL, Kaye J, et al. Delays in the diagnosis of dementia: perspectives of family caregivers. Am J Alzheimer’s Dis 1999; 14(1): 20–6.
Chenoweth B, Spencer B. Dementia: the experience of family caregivers. Gerontologist 1986; 26(3): 267–72.
Connell CM, Gallant M. P. Spouse caregivers’ attitudes toward obtaining a diagnosis of a dementing illness. J Am Geriatr Soc 1996; 44(8): 1003–9.
Glasser M, Rubin S, Dickover M. Caregiver views of help from the physician. Am J Alzheimer’s Care Relat Disord Res 1989; 4(4): 4–11.
Glosser G, Wexler D, Balmelli M. Physicians’ and families’ perspectives on the medical management of dementia. J Am Geriatr Soc 1985; 33(6): 383–91.
Haley WE, Clair JM, Saulsberry K. Family caregiver satisfaction with medical care of their demented relatives. Gerontologist 1992; 32(2): 219–26.
Rubin SM, Glasser ML, Werckle MA. The examination of physicians’ awareness of dementing disorders. J Am Geriatr Soc 1987; 35(12): 1051–8.
Glasser M. Alzheimer’s disease and dementing disorders: practices and experiences of rural physicians. Am J Alzheimer’s Care Relat Disord Res 1993; 8(4): 28–35.
Ardern M, Mayou R, Feldman F, et al. Cognitive impairment in the elderly medically ill: how often is it missed? Int J Geriatr Psychiatry 1993; 8: 929–7.
Boise L, Powers M. Dementia often undiagnosed in clinical settings: results from a Portland area study. Progress in Alzheimer’s Disease Research. Portland (OR): Alzheimer’s Research Alliance of Oregon, 1999.
Callahan DM, Hendrie HC, Tierney WM. Documentation and evaluation of cognitive impairment in elderly primary care patients. Ann Intern Med 1995; 122(6): 422–9.
O’Connor DW, Pollitt PA, Brook CPB, et al. Do general practitioners miss dementia in elderly patients? BMJ 1988; 297: 1107–10.
Torian L, Davidson E, Fulop G, et al. The effect of dementia on acute care in a geriatric medical unit. Int Psychogeriatr 1992; 4(2): 231–9.
Cattel C, Gambassi G, Sgadari A, et al. Correlates of delayed referral for the diagnosis of dementia in an outpatient population. J Gerontol A Biol Sci Med Sci 2000; 55A(2): M98–102.
Knopman D, Donohue JA, Gutterman EM. Patterns of care in the early stages of Alzheimer’s disease: impediments to timely diagnosis. J Am Geriatr Soc 2000; 48(3): 300–4.
Cheok AS, Cohen CA, Zucchero CA. Diagnosing and managing dementia patients: practice patterns of family physicians. Can Fam Physician 1997; 43: 477–82.
Fortinsky RH, Leighton A, Wasson JH. Primary care physicians’ diagnostic, management, and referral practices for older persons and families affected by dementia. Res Aging 1995; 17(2): 124–48.
Fortinsky RH, Wasson JH. How do physicians diagnose dementia? Evidence from clinical vignette responses. Am J Alzheimer’s Dis 1997; 12(2): 51–61.
Gifford DR, Holloway RG, Frankel MR. Improving adherence to dementia guidelines through education and opinion leaders. Ann Intern Med 1999; 131(4): 237–46.
Somerfield MR, Weisman CS, Ury W, et al. Physician practices in the diagnosis of dementing disorders. J Am Geriatr Soc 1991; 39(2): 172–5.
Vickery BG, Gifford DR, Belin TR, et al. Practice styles of UK compared to US neurologists. Neurology 1998; 319: 1220–2.
Alzheimer’s Association. Alzheimer’s Disease Study: communication gaps between PCPs and caregivers. Washington (DC): Alzheimer’s Association, 2001 Jun.
Biegel DE, Bass DM, Schulz R, et al. Predictors of in-home and out-of-home service use by family caregivers of Alzheimer’s disease patients. J Aging Health 1993; 5(4): 419–38.
Cotrell V. Respite use by dementia caregivers: preferences and reasons for initial use. J Gerontol Soc Work 1996; 26(3/4): 35–55.
Fortinsky RH, Hathaway TJ. Information and service needs among active and former family caregivers of persons with Alzheimer’s disease. Gerontologist 1990; 30(5): 604–9.
Gill CE, Hinrichsen GA, DiGiuseppe R. Factors associated with formal service use by family members of patients with dementia. J Appl Gerontol 1998; 7(1): 38–52.
Hamilton EM, Braun JW, Kerber P, et al. Factors associated with family caregivers’ choice not to use services. Am J Alzheimer’s Dis 1996; 11(5): 29–38.
Fortinsky RH. How linked are physicians to community support services for their patients with dementia. J Applied Gerontol 1998; 17(4): 480–98.
Newcomer R, Millier R, Clay T, et al. Effect of the Medicare Alzheimer’s Disease Demonstration on Medicare Expenditures. Health Care Finan Rev 1999; 20(4): 45–65.
Albert SM, Costa R, Merchant C, et al. Hospitalization and Alzheimer’s disease: results from a community-based study. J Gerontol 1999; 54A(5): M267–71.
Doraiswamy PM, Leon J, Cummings JL, et al. Prevalence and impact of medical comorbidity in Alzheimer’s disease. J Gerontology 2002; 57A(3): M173–7.
Gutterman EM, Markowitz JS, Lewis B, et al. Cost of Alzheimer’s disease and related dementia in managed-Medicare. J Am Geriatr Soc 1999; 47(9): 1065–71.
Hill JW, Futterman R, Duttagupta S, et al. Alzheimer’s disease and related dementias increase costs of comorbidities in managed Medicare. Neurology 2002; 58: 62–70.
Weiner M, Powe NR, Weiler WE, et al. Alzheimer’s disease under managed care: implications from Medicare utilization and expenditure patterns. J Am Geriatr Soc 1998; 46(6): 762–70.
Larson EB, Reifler BV, Featherstone HJ, et al. Dementia in elderly outpatients: a prospective study. Ann Intern Med 1984; 100: 417–23.
Wolf-Klein GP, Silverstone FA, Brod MS, et al. Are Alzheimer’s patients healthier? J Am Geriatr Soc 1988; 36(3): 219–24.
Moroney JT, Tseng CL, Paik MC, et al. Treatment for the secondary prevention of stroke in older patients: the influence of dementia status. J Am Geriatr Soc 1999; 47(7): 824–9.
Morrison RS, Siu AL. Survival in end-stage dementia following acute illness. JAMA 2000; (10): 47–52.
Brauner DJ, Muir JC, Sachs GA. Treating nondementia illnesses in patients with dementia. JAMA 2000; 283(24): 3230–5.
Post S, Whitehouse PJ. Fairhill guidelines on ethics of care of people with Alzheimer’s disease: a clinical summary. J Am Geriatr Soc 1995; 43(12): 1423–9.
Sachs GA. Dementia and the goals of care. J Am Geriatr Soc 1998; 46(6): 782–3.
Cook AK, Niven CA, Downs MG. Assessing the pain of people With cognitive impairment. Int J Geriatr Psychiatry 1999; 14: 421–5.
Feldt KS, Ryden MB, Miles S. Treatment of pain in cognitively impaired compared with cognitively intact older patients with hip-fracture. J Am Geriatr Soc 1998; 46(9): 1079–85.
Huffman JC, Kunik ME. Assessment and understanding of pain in patients with dementia. Gerontologist 2000; 40(5): 574–81.
Krulewitch H, London MR, Skakel VJ, et al. Assessment of pain in cognitively impaired older adults: a comparison of pain assessment tools and their use by nonprofessional caregivers. J Am Geriatr Soc 2000; 48(12): 1607–11.
Schmader KE, Hanlan JT, Fillenbaum GC, et al. Medication use patterns among demented, cognitively impaired, and cognitively intact community-dwelling elderly people. Age Ageing 1998; 27: 493–501.
Sengstaken EA, King SA. The problems of pain and its detection among geriatric nursing home residents. J Am Geriatr Soc 1993; 41(5): 541–4.
Larson EB. Management of Alzheimer’s disease in a primary care setting. Am J Geriatry Psychiatry 1998; 6(2 Suppl. 1): S34–40.
U.S. Office of Technology Assessment. Confused minds, burdened families: finding help for people with alzheimer’s and other dementias. Washington (DC): U.S. Government Printing Office, 1990.
Dellasaga C, Stricklin ML. Cognitive impairment in elderly home health clients. Home Health Care Serv Q 1993; 14(1): 81–92.
Ganguli M, Seaberg E, Belle S. Cognitive impairment and the use of health services in an elderly rural population: the MoVIES project. J Am Geriatr Soc 1993; 41(10): 1065–70.
Taylor DH, Sloan FA. How much do persons with Alzheimer’s disease cost Medicare? J Am Geriatr Soc 2000; 48(6): 639–46.
Weiler PG, Lubben JE, Chi I. Cognitive impairment and hospital use. Am J Public Health 1991; 81(9): 1153–7.
Leibson C, Owens T, O’Brien P, et al. Use of physician and acute care services by persons with and without Alzheimer’s disease: a population-based comparison. J Am Geriatr Soc 1999; 47(7): 864–9.
McCormick WC, Kukull WA, Van Belle G, et al. The effect of diagnosing Alzheimer’s disease on frequency of physician visits: a case-control study. J Gen Intern Med 1995; 10: 187–93.
Lyketsos CG, Sheppard JE, Rabins PV. Dementia in elderly persons in a general hospital. Am J Psychiatr 2000; 157(5): 704–7.
Inouye SK, Viscoli CM, Horwitz RI, et al. A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics. Ann Intern Med 1993; 119: 1348–53.
Colenda CC, Schoedel K, Hamer R. The delivery of health services to demented patients at a university hospital: a pilot study. Gerontologist 1988; 28(5): 659–62.
Day N, Musallam K, Wells M. Observed behaviors of patients with probable Alzheimer’s disease who are hospitalized for diagnostic tests. J Gerontol Nurs 1999; 25(11): 35–9.
Shedd PP, Kobokovich LJ, Slattery MJ. Confused patients in the acute care setting: prevalence, interventions, and outcomes. J Gerontol Nurs 1995; 21(4): 5–12.
Gill TM, Williams CS, Tinetti ME. The combined effects of baseline vulnerability and acute hospital events on the development of functional dependence among community-living older persons. J Gerontol A Biol Sci Med Sci 1999; 54A(7): M377–83.
Sager MA, Franke T, Inouye SK, et al. Functional outcomes of acute medical illness and hospitalization in older persons. Arch Intern Med 1996; 156: 645–52.
Wu AW, Yasui Y, Alzola C, et al. Predicting functional status outcomes in hospitalized patients aged 80 years and older. J Am Geriatr Soc 2000; 48(5): S6–15.
Sager MA, Rudberg MA, Jalaluddin M, et al. Hospital Admission Risk Profile (HARP): identifying older patients at risk for functional decline following acute medical illness and hospitalization. J Am Geriatr Soc 1996; 44(3): 251–7.
Ernst RL, Hay JW. Economic research on Alzheimer disease: a review of the literature. Alzheimer Dis Assoc Disord 1997; 11 Suppl. 6: 135–45.
Knapp M, Wilkinson D, Wigglesworth R. The economic consequences of Alzheimer’s disease in the context of new drug developments. Int J Geriatr Psychiatr 1998; 13: 531–43.
Wimo A, Ljunggren G, Winblad B. Costs of dementia and dementia care: a review. Int J Geriatr Psychiatry 1997; 12: 841–56.
Eppig FJ, Poisal JA. Mental health of Medicare beneficiaries: 1995. Health Care Financ Rev 1997; 18(3): 207–10.
Fishman P, Von Korff M, Lozano P, et al. Chronic care costs in managed care. Health Aff 1997; 16(3): 239–47.
Newcomer R, Clay T, Luxenberg JS, et al. Misclassification and selection bias when identifying Alzheimer’s disease solely from Medicare claims records. J Am Geriatr Soc 1999; 47(2): 215–9.
Costa PT, Williams TF, Somerfield M, et al. Recognition and initial assessment of Alzheimer’s disease and related dementias: clinical practice guideline. Rockville (MD): US Department of Health and Human Services, Agency for Health Care Policy and Research, 1996.
Brodaty H, Clarke J, Ganguli M, et al. Screening for cognitive impairment in general practice: toward a consensus. Alzheimer Dis Assoc Disord 1998; 12(1): 1–13.
Peterson RC, Stevens JC, Ganguli M, et al. Practice parameter: early detection of dementia (an evidence-based review): report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2001; 56: 1133–42.
Beck C, Cody M, Souder E, et al. Dementia diagnostic guidelines: methodologies, results, and implementation costs. J Am Geriatr Soc 2000; 48(10): 1195–203.
McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group. Neurology 1984; 34(7): 939–44.
National Institutes of Health. Differential diagnosis of dementing diseases: consensus statement. JAMA 1987; 258: 3411–6.
Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter for diagnosis and evaluation of dementia: summary statement. Neurology 1994; 44: 2203–6.
Veterans Health Administration. Dementia identification and assessment: guidelines for primary care practitioners. Washington (DC): U.S. Department of Veterans Affairs, 1997.
Wallin A, Brun A, Gustafson L. Swedish consensus on dementia diseases. Acta Neurol Scand 1994; 90 Suppl. 157: 1–31.
College Committee on Geriatrics, Royal College of Physicians. Organic mental impairment in the elderly: implications for research, education and the provision of services. J R Coll Physicians Lond 1981; 15(3): 141–67.
Ballard E, Cook GM, Gwyther LP, et al. Alzheimer’s disease: the physician’s role. Durham (NC): Duke University Medical Center, 1996.
Cefalu C, Grossberg GT. Diagnosis and management of dementia. Leawood (KS): American Academy of Family Physicians, 2001.
Clarfield AM, Bass MJ, Cohen C, et al. Assessing dementia: the Canadian consensus. CMAJ 1991; 144(7): 851–3.
North of England Evidence Based Guidelines Development Project. Evidence based guideline for the primary care management of dementia. Newcastle Upon Tyne: Centre for Health Services Research, 1998.
Robinson BE, Barry PP. Memory loss: evaluation in primary practice. New York (NY): John A. Hartford Foundation and the American Geriatrics Society, 1999.
New York State. Guidelines for the diagnosis of Alzheimer’s disease and other dementias. New York (NY): New York State, 1990 July 20.
Warshaw GA, Gwyther LP, Phillips L, et al. Alzheimer’s disease: an overview for primary care. Tucson (AZ): University of Arizona Health Sciences Center, 1996.
Wisconsin Alzheimer’s Association Chapter Network. Physician’s reference: diagnosis and treatment of Alzheimer’s disease and other related dementias. Green Bay (WI): Wisconsin Alzheimer’s Association Chapter Network, 1998.
Knopman DS, DeKosky ST, Cummings JL, et al. Practice parameter: diagnosis of dementia (an evidence-based review): report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2001; 56: 1143–53.
Fillit H, Cummings J. Practice guidelines for the diagnosis and treatment of Alzheimer’s disease in a managed care setting: part 1. Early detection and diagnosis. Manag Care Interface 1999; 13(1): 51–6.
Fillit H, Knopman D, Cummings J, et al. Opportunities for improving managed care for individuals with dementia: part 2. A framework for care. Am J Manag Care 1999; 5(3): 317–24.
Pharmacy Benefits Management Strategic Healthcare Group and the Medical Advisory Panel. The pharmacologic management of cognitive changes in Alzheimer’s disease. Washington (DC): Veterans Health Administration, Department of Veterans Affairs, 1999: Pub. No. 99–0013.
Janicki MP, Heller T, Seltzer GB, et al. Practice guidelines for the clinical assessment and care management of Alzheimer and other dementias among adults with mental retardation: report of the AAMR-IASSID workgroup on practice guidelines for care management of Alzheimer’s disease. Washington (DC): American Association on Mental Retardation, 1995.
California Workgroup on Guidelines for Alzheimer’s Disease Management. Guidelines for Alzheimer’s management: final report. Los Angeles (CA): Alzheimer’s’ Association, 1999.
Janicki MP, Heller T, Seltzer GB, et al. Practice guidelines for the clinical assessment and care management of Alzheimer’s disease and other dementias among adults with intellectual disability. J Intellect Disabil Res 1996; 40(4): 374–82.
Corey-Bloom J, Thal LJ, Galasko D, et al. Diagnosis and evaluation of dementia. Neurology 1995; 45: 211–8.
Eccles M, Clarke J, Livingstone M, et al. North of England evidence based guidelines development project: guideline for the primary care management of dementia. BMJ 1998; 317: 802–8.
Kahn DA, Alexopoulos GS, Silver JM, et al. Treatment of agitation in elderly persons with dementia: a summary of the expert consensus guidelines. J Pract Psychiatry Behav Health 1998; 5: 265–76.
Hall GR. Research-based protocol: Alzheimer’s disease and chronic dementing illnesses. Iowa City (IA): University of Iowa Gerontological Nursing Interventions Research Center, 1996.
Marquette University College of Nursing and the Palliative Care Program at the Medical College of Wisconsin. Improving management of physical pain and affective discomfort for people with dementia in long-term care. Milwaukee (WI): Marquette University College of Nursing, 1999.
Fillit H, Knopman D, Cummings J, et al. Opportunities for improving managed care for individuals with dementia: part 1. Issues of care. Am J Manag Care 1999; 5(3): 309–15.
Fillit H, Cummings J. Practice guidelines for the diagnosis and treatment of Alzheimer’s disease in a managed care setting: part II: pharmacologic therapy. Manag Care Interface 1999; 12(12): 53–61.
Bass DM, Looman WJ, McCarthy CA, et al. The Cleveland Alzheimer’s managed care demonstration: caregiver outcomes and patient service use after 12 months of implementation [poster]. 54th Annual Meeting of the Gerontological Society of America; 2001 Nov 15–8, Chicago (IL).
Acknowledgements
No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Maslow, K., Selstad, J. & Denman, S.J. Guidelines and Care Management Issues for People with Alzheimer’s Disease and Other Dementias. Dis-Manage-Health-Outcomes 10, 693–706 (2002). https://doi.org/10.2165/00115677-200210110-00003
Published:
Issue Date:
DOI: https://doi.org/10.2165/00115677-200210110-00003