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Do patients at high risk of Alzheimer’s disease benefit from early treatment?
Yes, but the extent of the benefit is unclear. Treating patients with early-stage Alzheimer’s disease yields statistically significant, though perhaps not clinically significant, improvement in cognition and global function (strength of recommendation [SOR]: A, consistent evidence from multiple randomized controlled trials [RCTs]). In a few cases, it may delay loss of function and need for long-term care.
Treating patients with mild cognitive impairment (MCI)—the most likely precursor to Alzheimer’s disease—with cholinesterase inhibitors seems to have an initial, but perhaps unsustained, benefit over no treatment (SOR: B, inconsistent results from few trials). Withdrawing anticholinergic drugs from patients taking them promises to reduce symptoms of MCI, but is unlikely to reduce rates of Alzheimer’s (SOR: C, well-designed observational study).
Remember nondrug interventions
Jaqueline Raetz, MD
Departments of Family Medicine and Long-Term Care, University of Washington School of Medicine, Seattle
Clinicians often forget the many nonpharmacologic treatments for dementia, including exercise, cognitive stimulation, increased socialization, addressing polypharmacy, and optimizing nutrition. Diagnosing and managing comorbidities such as depression and cardiovascular disease are also important. Primary care physicians who care for the frail elderly should advocate these interventions. In the very elderly, who are all at high risk of developing Alzheimer’s disease, these measures may help prevent functional decline and reduce clinically apparent disease.
All patients diagnosed with early-stage Alzheimer’s disease, and possibly patients with MCI, should be offered a trial of pharmacotherapy. However—given the high cost of drug therapy, the modest improvement it produces in patients with Alzheimer’s dementia, and the lack of definitive evidence that it benefits patients with MCI—I wouldn’t advocate medication for asymptomatic patients at high risk of developing dementia.
Evidence summary
Alzheimer’s disease is characterized by deficits in memory and at least 1 other cognitive domain (aphrasia, apraxia, agnosia, or loss of executive function) accompanied by impaired function. As the US population ages, Alzheimer’s disease is likely to increase substantially in prevalence and cost, from its current 4.5 million people affected and $100 billion per year in direct expenses.1
Because the definition of Alzheimer’s precludes asymptomatic disease, “early” treatment implies either treating a precursor condition or treating before cognitive and functional impairment force the patient and family to seek medical care. The literature identifies 2 possible prodromal conditions: MCI and personality change. Personality change is proposed as a prodrome based only on a small study that diagnosed Alzheimer’s disease at autopsy, so this Clinical Inquiry doesn’t address it further.2
Therapy for MCI: A look at 3 interventions
MCI is a measurable memory deficit, more severe than normal aging changes (slower learning of new material and difficulty retrieving names and places) but not meeting criteria for dementia.3 Researchers differ on a more precise definition; some subdivide MCI into “MCI-amnestic type” and “MCI-multiple cognitive deficits type.”4 MCI progresses to Alzheimer’s disease in anywhere from 10% to 56% of patients.4,5
Three interventions may benefit patients with MCI:
- cholinesterase inhibitors
- exercise
- discontinuation of anticholinergic drugs in patients taking them.
Two recent RCTs of donepezil6,7 and 1 of galantamine8 showed initial cognitive improvement in MCI patients. However, the only trial carried out for 3 years showed no persistent benefit at that time.6
Another study showed that moderate exercise—30 minutes 3 days a week—improves cognition in MCI patients.9
A longitudinal cohort study found that patients taking anticholinergic drugs had an 80% prevalence of MCI, compared with a 35% prevalence in a matched population of patients not using these drugs; yet Alzheimer’s disease hadn’t increased among the anticholinergic drug users at 8-year follow-up. Attributable risk for MCI from anticholinergic drug use was 19%. Stopping anticholinergic medications may reduce the prevalence of MCI.10
In established Alzheimer’s disease, cholinesterase inhibitors statistically benefit patients with early and moderate disease and probably benefit patients with severe disease.11,12 The treatment effect is small, however—3 points on a 70-point cognitive scale. Comparison studies show mixed results; no single agent appears to be most effective.12
Are cholinesterase inhibitors cost effective?
The relatively modest benefit of cholinesterase inhibitors—especially given their expense—has raised questions about cost effectiveness. When weighing the choice, consider that donepezil may delay nursing home placement,11,13 and the cholinesterase inhibitors may reduce caregiver burden.11 The medications are likely to be cost effective in patients showing a clinically significant response. More effective treatments would clearly be welcome.
Recommendations
The US Preventive Services Task Force (USPSTF) acknowledges that fair to good evidence supports a benefit from treatment of early-stage Alzheimer’s disease. However, routine screening for dementia in older adults receives an I-level recommendation (insufficient evidence), both because it’s unknown whether diagnosis would be as accurate and treatment as effective in primary care practices and because the benefit from screening is uncertain (coupled with a small treatment benefit).14
The task force reported finding no good data that treating MCI is beneficial. However, the USPSTF recommendation preceded publication of all 4 RCTs on treatment of MCI addressed in this Clinical Inquiry.
The American College of Physicians and American Academy of Family Physicians published a joint clinical practice guideline in March 2008 that questioned whether the slight benefit of cholinesterase inhibitors surpassed the harm of adverse effects and cost. They recommend counseling each patient about the likely benefits and harms.15
1. Geldmacher DS. Cost-effective recognition and diagnosis of dementia. Semin Neurol. 2002;22:63-70.
2. Balsis S, Carpenter BD, Storandt M. Personality change precedes clinical diagnosis of dementia of the Alzheimer type. J Gerontol B Psychol Sci Soc Sci. 2005;60:P98-P101.
3. Warner J, Butler R, Wuntakal B. What are the effects of treatments on cognitive symptoms of dementia? BMJ Clin Evid. 2008;01:1001-1028.
4. Lopez OL, Jagust WJ, DeKoskey ST, et al. Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1. Arch Neurol. 2003;60:1385-1389.
5. Petersen RC, Smith GE, Waring SC, et al. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56:303-308.
6. Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352:2379-2388.
7. Olazaran J, Muñiz R, Reisberg B, et al. Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease. Neurology. 2004;63:2348-2353.
8. Koontz J, Baskys A. Effects of galantamine on working memory and global functioning in patients with mild cognitive impairment: a double-blind placebo-controlled study. Am J Alzheimers Dis Other Demen. 2005;20:295-302.
9. Larson EB, Wang L, Bowen JD, et al. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med. 2006;144:73-81.
10. Ancelin ML, Artero S, Portet F, et al. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ. 2006;332:455-459.
11. Lanctot KL, Herrmann N, Yau KK, et al. Efficacy and safety of cholinesterase inhibitors in Alzheimer’s disease: a meta-analysis. CMAJ. 2003;169:557-564.
12. Santaguida PS, Raina P, Booker L, et al. Pharmacological treatment of dementia. Evidence Report/Technology Assessment No. 97 (prepared by McMaster University Evidence-based Practice Center under Contract No. 290-02-0020). AHRQ Publication No. 04-E019-2. Rockville, MD: Agency for Healthcare Research and Quality; April 2004.
13. Geldmacher DS, Provenzano G, McRae T, et al. Done-pezil is associated with delayed nursing home placement in patients with Alzheimer’s disease. J Am Geriatr Soc. 2003;51:937-944.
14. Boustani M, Peterson B, Hanson L, et al. Screening for dementia in primary care: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2003;138:927-937.
15. Qaseem A, Snow V, Cross JT, Jr, et al. Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2008;148:370-378.
Yes, but the extent of the benefit is unclear. Treating patients with early-stage Alzheimer’s disease yields statistically significant, though perhaps not clinically significant, improvement in cognition and global function (strength of recommendation [SOR]: A, consistent evidence from multiple randomized controlled trials [RCTs]). In a few cases, it may delay loss of function and need for long-term care.
Treating patients with mild cognitive impairment (MCI)—the most likely precursor to Alzheimer’s disease—with cholinesterase inhibitors seems to have an initial, but perhaps unsustained, benefit over no treatment (SOR: B, inconsistent results from few trials). Withdrawing anticholinergic drugs from patients taking them promises to reduce symptoms of MCI, but is unlikely to reduce rates of Alzheimer’s (SOR: C, well-designed observational study).
Remember nondrug interventions
Jaqueline Raetz, MD
Departments of Family Medicine and Long-Term Care, University of Washington School of Medicine, Seattle
Clinicians often forget the many nonpharmacologic treatments for dementia, including exercise, cognitive stimulation, increased socialization, addressing polypharmacy, and optimizing nutrition. Diagnosing and managing comorbidities such as depression and cardiovascular disease are also important. Primary care physicians who care for the frail elderly should advocate these interventions. In the very elderly, who are all at high risk of developing Alzheimer’s disease, these measures may help prevent functional decline and reduce clinically apparent disease.
All patients diagnosed with early-stage Alzheimer’s disease, and possibly patients with MCI, should be offered a trial of pharmacotherapy. However—given the high cost of drug therapy, the modest improvement it produces in patients with Alzheimer’s dementia, and the lack of definitive evidence that it benefits patients with MCI—I wouldn’t advocate medication for asymptomatic patients at high risk of developing dementia.
Evidence summary
Alzheimer’s disease is characterized by deficits in memory and at least 1 other cognitive domain (aphrasia, apraxia, agnosia, or loss of executive function) accompanied by impaired function. As the US population ages, Alzheimer’s disease is likely to increase substantially in prevalence and cost, from its current 4.5 million people affected and $100 billion per year in direct expenses.1
Because the definition of Alzheimer’s precludes asymptomatic disease, “early” treatment implies either treating a precursor condition or treating before cognitive and functional impairment force the patient and family to seek medical care. The literature identifies 2 possible prodromal conditions: MCI and personality change. Personality change is proposed as a prodrome based only on a small study that diagnosed Alzheimer’s disease at autopsy, so this Clinical Inquiry doesn’t address it further.2
Therapy for MCI: A look at 3 interventions
MCI is a measurable memory deficit, more severe than normal aging changes (slower learning of new material and difficulty retrieving names and places) but not meeting criteria for dementia.3 Researchers differ on a more precise definition; some subdivide MCI into “MCI-amnestic type” and “MCI-multiple cognitive deficits type.”4 MCI progresses to Alzheimer’s disease in anywhere from 10% to 56% of patients.4,5
Three interventions may benefit patients with MCI:
- cholinesterase inhibitors
- exercise
- discontinuation of anticholinergic drugs in patients taking them.
Two recent RCTs of donepezil6,7 and 1 of galantamine8 showed initial cognitive improvement in MCI patients. However, the only trial carried out for 3 years showed no persistent benefit at that time.6
Another study showed that moderate exercise—30 minutes 3 days a week—improves cognition in MCI patients.9
A longitudinal cohort study found that patients taking anticholinergic drugs had an 80% prevalence of MCI, compared with a 35% prevalence in a matched population of patients not using these drugs; yet Alzheimer’s disease hadn’t increased among the anticholinergic drug users at 8-year follow-up. Attributable risk for MCI from anticholinergic drug use was 19%. Stopping anticholinergic medications may reduce the prevalence of MCI.10
In established Alzheimer’s disease, cholinesterase inhibitors statistically benefit patients with early and moderate disease and probably benefit patients with severe disease.11,12 The treatment effect is small, however—3 points on a 70-point cognitive scale. Comparison studies show mixed results; no single agent appears to be most effective.12
Are cholinesterase inhibitors cost effective?
The relatively modest benefit of cholinesterase inhibitors—especially given their expense—has raised questions about cost effectiveness. When weighing the choice, consider that donepezil may delay nursing home placement,11,13 and the cholinesterase inhibitors may reduce caregiver burden.11 The medications are likely to be cost effective in patients showing a clinically significant response. More effective treatments would clearly be welcome.
Recommendations
The US Preventive Services Task Force (USPSTF) acknowledges that fair to good evidence supports a benefit from treatment of early-stage Alzheimer’s disease. However, routine screening for dementia in older adults receives an I-level recommendation (insufficient evidence), both because it’s unknown whether diagnosis would be as accurate and treatment as effective in primary care practices and because the benefit from screening is uncertain (coupled with a small treatment benefit).14
The task force reported finding no good data that treating MCI is beneficial. However, the USPSTF recommendation preceded publication of all 4 RCTs on treatment of MCI addressed in this Clinical Inquiry.
The American College of Physicians and American Academy of Family Physicians published a joint clinical practice guideline in March 2008 that questioned whether the slight benefit of cholinesterase inhibitors surpassed the harm of adverse effects and cost. They recommend counseling each patient about the likely benefits and harms.15
Yes, but the extent of the benefit is unclear. Treating patients with early-stage Alzheimer’s disease yields statistically significant, though perhaps not clinically significant, improvement in cognition and global function (strength of recommendation [SOR]: A, consistent evidence from multiple randomized controlled trials [RCTs]). In a few cases, it may delay loss of function and need for long-term care.
Treating patients with mild cognitive impairment (MCI)—the most likely precursor to Alzheimer’s disease—with cholinesterase inhibitors seems to have an initial, but perhaps unsustained, benefit over no treatment (SOR: B, inconsistent results from few trials). Withdrawing anticholinergic drugs from patients taking them promises to reduce symptoms of MCI, but is unlikely to reduce rates of Alzheimer’s (SOR: C, well-designed observational study).
Remember nondrug interventions
Jaqueline Raetz, MD
Departments of Family Medicine and Long-Term Care, University of Washington School of Medicine, Seattle
Clinicians often forget the many nonpharmacologic treatments for dementia, including exercise, cognitive stimulation, increased socialization, addressing polypharmacy, and optimizing nutrition. Diagnosing and managing comorbidities such as depression and cardiovascular disease are also important. Primary care physicians who care for the frail elderly should advocate these interventions. In the very elderly, who are all at high risk of developing Alzheimer’s disease, these measures may help prevent functional decline and reduce clinically apparent disease.
All patients diagnosed with early-stage Alzheimer’s disease, and possibly patients with MCI, should be offered a trial of pharmacotherapy. However—given the high cost of drug therapy, the modest improvement it produces in patients with Alzheimer’s dementia, and the lack of definitive evidence that it benefits patients with MCI—I wouldn’t advocate medication for asymptomatic patients at high risk of developing dementia.
Evidence summary
Alzheimer’s disease is characterized by deficits in memory and at least 1 other cognitive domain (aphrasia, apraxia, agnosia, or loss of executive function) accompanied by impaired function. As the US population ages, Alzheimer’s disease is likely to increase substantially in prevalence and cost, from its current 4.5 million people affected and $100 billion per year in direct expenses.1
Because the definition of Alzheimer’s precludes asymptomatic disease, “early” treatment implies either treating a precursor condition or treating before cognitive and functional impairment force the patient and family to seek medical care. The literature identifies 2 possible prodromal conditions: MCI and personality change. Personality change is proposed as a prodrome based only on a small study that diagnosed Alzheimer’s disease at autopsy, so this Clinical Inquiry doesn’t address it further.2
Therapy for MCI: A look at 3 interventions
MCI is a measurable memory deficit, more severe than normal aging changes (slower learning of new material and difficulty retrieving names and places) but not meeting criteria for dementia.3 Researchers differ on a more precise definition; some subdivide MCI into “MCI-amnestic type” and “MCI-multiple cognitive deficits type.”4 MCI progresses to Alzheimer’s disease in anywhere from 10% to 56% of patients.4,5
Three interventions may benefit patients with MCI:
- cholinesterase inhibitors
- exercise
- discontinuation of anticholinergic drugs in patients taking them.
Two recent RCTs of donepezil6,7 and 1 of galantamine8 showed initial cognitive improvement in MCI patients. However, the only trial carried out for 3 years showed no persistent benefit at that time.6
Another study showed that moderate exercise—30 minutes 3 days a week—improves cognition in MCI patients.9
A longitudinal cohort study found that patients taking anticholinergic drugs had an 80% prevalence of MCI, compared with a 35% prevalence in a matched population of patients not using these drugs; yet Alzheimer’s disease hadn’t increased among the anticholinergic drug users at 8-year follow-up. Attributable risk for MCI from anticholinergic drug use was 19%. Stopping anticholinergic medications may reduce the prevalence of MCI.10
In established Alzheimer’s disease, cholinesterase inhibitors statistically benefit patients with early and moderate disease and probably benefit patients with severe disease.11,12 The treatment effect is small, however—3 points on a 70-point cognitive scale. Comparison studies show mixed results; no single agent appears to be most effective.12
Are cholinesterase inhibitors cost effective?
The relatively modest benefit of cholinesterase inhibitors—especially given their expense—has raised questions about cost effectiveness. When weighing the choice, consider that donepezil may delay nursing home placement,11,13 and the cholinesterase inhibitors may reduce caregiver burden.11 The medications are likely to be cost effective in patients showing a clinically significant response. More effective treatments would clearly be welcome.
Recommendations
The US Preventive Services Task Force (USPSTF) acknowledges that fair to good evidence supports a benefit from treatment of early-stage Alzheimer’s disease. However, routine screening for dementia in older adults receives an I-level recommendation (insufficient evidence), both because it’s unknown whether diagnosis would be as accurate and treatment as effective in primary care practices and because the benefit from screening is uncertain (coupled with a small treatment benefit).14
The task force reported finding no good data that treating MCI is beneficial. However, the USPSTF recommendation preceded publication of all 4 RCTs on treatment of MCI addressed in this Clinical Inquiry.
The American College of Physicians and American Academy of Family Physicians published a joint clinical practice guideline in March 2008 that questioned whether the slight benefit of cholinesterase inhibitors surpassed the harm of adverse effects and cost. They recommend counseling each patient about the likely benefits and harms.15
1. Geldmacher DS. Cost-effective recognition and diagnosis of dementia. Semin Neurol. 2002;22:63-70.
2. Balsis S, Carpenter BD, Storandt M. Personality change precedes clinical diagnosis of dementia of the Alzheimer type. J Gerontol B Psychol Sci Soc Sci. 2005;60:P98-P101.
3. Warner J, Butler R, Wuntakal B. What are the effects of treatments on cognitive symptoms of dementia? BMJ Clin Evid. 2008;01:1001-1028.
4. Lopez OL, Jagust WJ, DeKoskey ST, et al. Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1. Arch Neurol. 2003;60:1385-1389.
5. Petersen RC, Smith GE, Waring SC, et al. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56:303-308.
6. Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352:2379-2388.
7. Olazaran J, Muñiz R, Reisberg B, et al. Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease. Neurology. 2004;63:2348-2353.
8. Koontz J, Baskys A. Effects of galantamine on working memory and global functioning in patients with mild cognitive impairment: a double-blind placebo-controlled study. Am J Alzheimers Dis Other Demen. 2005;20:295-302.
9. Larson EB, Wang L, Bowen JD, et al. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med. 2006;144:73-81.
10. Ancelin ML, Artero S, Portet F, et al. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ. 2006;332:455-459.
11. Lanctot KL, Herrmann N, Yau KK, et al. Efficacy and safety of cholinesterase inhibitors in Alzheimer’s disease: a meta-analysis. CMAJ. 2003;169:557-564.
12. Santaguida PS, Raina P, Booker L, et al. Pharmacological treatment of dementia. Evidence Report/Technology Assessment No. 97 (prepared by McMaster University Evidence-based Practice Center under Contract No. 290-02-0020). AHRQ Publication No. 04-E019-2. Rockville, MD: Agency for Healthcare Research and Quality; April 2004.
13. Geldmacher DS, Provenzano G, McRae T, et al. Done-pezil is associated with delayed nursing home placement in patients with Alzheimer’s disease. J Am Geriatr Soc. 2003;51:937-944.
14. Boustani M, Peterson B, Hanson L, et al. Screening for dementia in primary care: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2003;138:927-937.
15. Qaseem A, Snow V, Cross JT, Jr, et al. Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2008;148:370-378.
1. Geldmacher DS. Cost-effective recognition and diagnosis of dementia. Semin Neurol. 2002;22:63-70.
2. Balsis S, Carpenter BD, Storandt M. Personality change precedes clinical diagnosis of dementia of the Alzheimer type. J Gerontol B Psychol Sci Soc Sci. 2005;60:P98-P101.
3. Warner J, Butler R, Wuntakal B. What are the effects of treatments on cognitive symptoms of dementia? BMJ Clin Evid. 2008;01:1001-1028.
4. Lopez OL, Jagust WJ, DeKoskey ST, et al. Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1. Arch Neurol. 2003;60:1385-1389.
5. Petersen RC, Smith GE, Waring SC, et al. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56:303-308.
6. Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352:2379-2388.
7. Olazaran J, Muñiz R, Reisberg B, et al. Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease. Neurology. 2004;63:2348-2353.
8. Koontz J, Baskys A. Effects of galantamine on working memory and global functioning in patients with mild cognitive impairment: a double-blind placebo-controlled study. Am J Alzheimers Dis Other Demen. 2005;20:295-302.
9. Larson EB, Wang L, Bowen JD, et al. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med. 2006;144:73-81.
10. Ancelin ML, Artero S, Portet F, et al. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ. 2006;332:455-459.
11. Lanctot KL, Herrmann N, Yau KK, et al. Efficacy and safety of cholinesterase inhibitors in Alzheimer’s disease: a meta-analysis. CMAJ. 2003;169:557-564.
12. Santaguida PS, Raina P, Booker L, et al. Pharmacological treatment of dementia. Evidence Report/Technology Assessment No. 97 (prepared by McMaster University Evidence-based Practice Center under Contract No. 290-02-0020). AHRQ Publication No. 04-E019-2. Rockville, MD: Agency for Healthcare Research and Quality; April 2004.
13. Geldmacher DS, Provenzano G, McRae T, et al. Done-pezil is associated with delayed nursing home placement in patients with Alzheimer’s disease. J Am Geriatr Soc. 2003;51:937-944.
14. Boustani M, Peterson B, Hanson L, et al. Screening for dementia in primary care: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2003;138:927-937.
15. Qaseem A, Snow V, Cross JT, Jr, et al. Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2008;148:370-378.
Evidence-based answers from the Family Physicians Inquiries Network
Should a nylon brush be used for Pap smears from pregnant women?
Use of a nylon brush (Cytobrush and others) with spatula to obtain Papanicolaou (Pap) smears from pregnant women is more likely to obtain sufficient endocervical cells, without adverse consequence for the mother or for the fetus. This method is also most likely to be cost-effective. However, current evidence does not support any superiority of the nylon brush with spatula for any patient-oriented outcomes (eg, fewer procedures, less cancer, etc) during or after pregnancy (strength of recommendation: A; based on multiple randomized controlled trials).
Evidence summary
A Cochrane review of Pap smear sampling devices for nonpregnant women concludes that the cervical brush with spatula is more effective at collecting endocervical cells and producing adequate Pap smears.1 Based on more limited evidence, the higher rate of adequate smears is associated with the detection of more cytologic abnormalities. However, the manufacturer of Cytobrush (Medscand) recommends that the device not be used after the first 10 weeks of pregnancy, raising issues of both effectiveness and safety in this population.
Upon review of the literature, these concerns appear to be unfounded. In multiple studies involving more than 25,000 pregnant and nonpregnant patients, the brush was consistently shown to be the method obtaining the highest rate of adequate smears—ie, those containing endocervical cells.2-10 Furthermore, in studies including about 1900 pregnant patients, the brush with spatula caused no significantly increased risk of serious adverse outcomes, nor any trend in that direction.5-7,9-11 The device did cause a slight increase in self-limited vaginal spotting.
In theory, a more accurate Pap smear could lead to patient-oriented outcomes, such as less need for procedures to diagnose and treat cervical cytologic abnormalities, reduced incidence of invasive cervical cancer, and fewer patient deaths from cervical cancer. No data on these outcomes is available. Some studies did look for differences in the detection of cytologic abnormalities between the brush with spatula and the swab with spatula methods. Most small studies and a meta-analysis showed no difference.2,3,8,9 One study showed a trend towards improved yield; in another study, the brush with spatula significantly improved the ability to detect cytologic abnormalities in pregnant patients.7,10
Three studies addressed cost-effectiveness of the brush in pregnancy.3,9,12 Especially when including the cost of repeat Pap smears for inadequate specimens, the brush with spatula was rated most cost-effective in all 3 studies.
Comparison of the use of conventional Pap smear collection techniques with newer liquid-based cytology or human papilloma virus (HPV) typing has not yet been addressed in the literature.
Recommendations from others
“The Working Group’s Recommendations for Women in Low Risk Pregnancy” through the Veterans Health Administration lists use of a nylon cervical brush—no type is specified—as the appropriate sampling device in the late first trimester of pregnancy.13 No recommendations specific to the Cytobrush were found.
The following organizations have made no recommendations for or against the use of the Cytobrush in pregnancy: US Preventive Services Task Force, American College of Obstetricians and Gynecologists, American Academy of Family Physicians, or the American Academy of Nurse-Midwives.
Use the spatula and brush for Pap smears from pregnant women
Julia Fashner, MD
St. Joseph Regional Medical Center, South Bend, Ind
The evidence for safety and efficacy supports the use of the spatula and brush for obtaining Pap smears from pregnant women. You will have fewer inadequate smears that need to be repeated, but you will need to warn the patient of spotting that may occur after the specimen is obtained. For ThinPrep Pap smears, remember to follow the same recommendations as for nonpregnant women—turn the spatula the full 360° in contact with the cervix and only turn the brush a half-turn. Being overly aggressive to collect endocervical cells by twirling the brush may cause more bleeding.
1. Martin-Hirsch P, Jarvis G, Kitchener H, Lilford R. Collection devices for obtaining cervical cytology samples. Cochrane Gynaecological Cancer Group. Cochrane Database Syst Rev 2005; 1.
2. Bauman BJ. Use of a cervical brush for Papanicolaou smears collection. J Nurse Midwifery 1993;38:267-275.
3. McCord ML, Stovall TG, Meric JL, Summitt RL, Coleman SA. Cervical cytology: A randomized comparison of four sampling methods. Am J Obstet Gynecol 1992;166:1772-1779.
4. Curtis P, Mintzer M, Morrell D, Resnick J, Hendrix S, Qaqish B. Characteristics and quality of Papanicolaou smears obtained by primary care clinicians using a single commercial laboratory. Arch Fam Med 1999;8:407-413.
5. Paraiso MF, Brady K, Helmchen R, Roat T. Evaluation of the endocervical Cytobrush and cervix-brush in pregnant women. Obstet Gynecol 1994;84:539-543.
6. Foster JC, Smith HL. Use of the Cytobrush for Papanicolaou smear screens in pregnant women. J Nurse Midwifery 1996;41:211-217.
7. Orr JW, Barrett JM, Orr PF, Holloway RW, Holimon JL. The efficacy and safety of the Cytobrush during pregnancy. Gynecol Oncol 1992;44:260-262.
8. Rivlin ME, Woodliff JM, Bowlin RB, et al. Comparison of Cytobrush and cotton swab for Papanicolaou smears in pregnancy. J Reprod Med 1993;38:147-150.
9. Smith-Levitin M, Hernandez E, Anderson L, Heller P. Safety, efficacy and cost of three cervical cytology sampling devices in a prenatal clinic. J Reprod Med 1996;41:749-753.
10. Stillson T, Knight AL, Elswick RK. The effectiveness and safety of two cervical cytologic techniques during pregnancy. J Fam Pract 1997;45:159-164.
11. Grossman JH, Rivlin ME, Morrison JC. Cytobrush versus swab endocervical sampling for the detection of obstetric chlamydial infection. Am J Perinatol 1993;10:76-78.
12. Harrison DD, Hernandez E, Dunton CJ. Endocervical brush versus cotton swab for obtaining cervical smears at a clinic: A cost comparison. J Reprod Med 1993;38:285-288.
13. National Guidelines Clearinghouse. Veterans Health Administration, Department of Defense. DoD/VA clinical practice guideline for the management of uncomplicated pregnancy (in “The Working Group’s Recommendations for Women in Low Risk Pregnancy”). Washington, DC: Department of Veteran Affairs; 2002.
Use of a nylon brush (Cytobrush and others) with spatula to obtain Papanicolaou (Pap) smears from pregnant women is more likely to obtain sufficient endocervical cells, without adverse consequence for the mother or for the fetus. This method is also most likely to be cost-effective. However, current evidence does not support any superiority of the nylon brush with spatula for any patient-oriented outcomes (eg, fewer procedures, less cancer, etc) during or after pregnancy (strength of recommendation: A; based on multiple randomized controlled trials).
Evidence summary
A Cochrane review of Pap smear sampling devices for nonpregnant women concludes that the cervical brush with spatula is more effective at collecting endocervical cells and producing adequate Pap smears.1 Based on more limited evidence, the higher rate of adequate smears is associated with the detection of more cytologic abnormalities. However, the manufacturer of Cytobrush (Medscand) recommends that the device not be used after the first 10 weeks of pregnancy, raising issues of both effectiveness and safety in this population.
Upon review of the literature, these concerns appear to be unfounded. In multiple studies involving more than 25,000 pregnant and nonpregnant patients, the brush was consistently shown to be the method obtaining the highest rate of adequate smears—ie, those containing endocervical cells.2-10 Furthermore, in studies including about 1900 pregnant patients, the brush with spatula caused no significantly increased risk of serious adverse outcomes, nor any trend in that direction.5-7,9-11 The device did cause a slight increase in self-limited vaginal spotting.
In theory, a more accurate Pap smear could lead to patient-oriented outcomes, such as less need for procedures to diagnose and treat cervical cytologic abnormalities, reduced incidence of invasive cervical cancer, and fewer patient deaths from cervical cancer. No data on these outcomes is available. Some studies did look for differences in the detection of cytologic abnormalities between the brush with spatula and the swab with spatula methods. Most small studies and a meta-analysis showed no difference.2,3,8,9 One study showed a trend towards improved yield; in another study, the brush with spatula significantly improved the ability to detect cytologic abnormalities in pregnant patients.7,10
Three studies addressed cost-effectiveness of the brush in pregnancy.3,9,12 Especially when including the cost of repeat Pap smears for inadequate specimens, the brush with spatula was rated most cost-effective in all 3 studies.
Comparison of the use of conventional Pap smear collection techniques with newer liquid-based cytology or human papilloma virus (HPV) typing has not yet been addressed in the literature.
Recommendations from others
“The Working Group’s Recommendations for Women in Low Risk Pregnancy” through the Veterans Health Administration lists use of a nylon cervical brush—no type is specified—as the appropriate sampling device in the late first trimester of pregnancy.13 No recommendations specific to the Cytobrush were found.
The following organizations have made no recommendations for or against the use of the Cytobrush in pregnancy: US Preventive Services Task Force, American College of Obstetricians and Gynecologists, American Academy of Family Physicians, or the American Academy of Nurse-Midwives.
Use the spatula and brush for Pap smears from pregnant women
Julia Fashner, MD
St. Joseph Regional Medical Center, South Bend, Ind
The evidence for safety and efficacy supports the use of the spatula and brush for obtaining Pap smears from pregnant women. You will have fewer inadequate smears that need to be repeated, but you will need to warn the patient of spotting that may occur after the specimen is obtained. For ThinPrep Pap smears, remember to follow the same recommendations as for nonpregnant women—turn the spatula the full 360° in contact with the cervix and only turn the brush a half-turn. Being overly aggressive to collect endocervical cells by twirling the brush may cause more bleeding.
Use of a nylon brush (Cytobrush and others) with spatula to obtain Papanicolaou (Pap) smears from pregnant women is more likely to obtain sufficient endocervical cells, without adverse consequence for the mother or for the fetus. This method is also most likely to be cost-effective. However, current evidence does not support any superiority of the nylon brush with spatula for any patient-oriented outcomes (eg, fewer procedures, less cancer, etc) during or after pregnancy (strength of recommendation: A; based on multiple randomized controlled trials).
Evidence summary
A Cochrane review of Pap smear sampling devices for nonpregnant women concludes that the cervical brush with spatula is more effective at collecting endocervical cells and producing adequate Pap smears.1 Based on more limited evidence, the higher rate of adequate smears is associated with the detection of more cytologic abnormalities. However, the manufacturer of Cytobrush (Medscand) recommends that the device not be used after the first 10 weeks of pregnancy, raising issues of both effectiveness and safety in this population.
Upon review of the literature, these concerns appear to be unfounded. In multiple studies involving more than 25,000 pregnant and nonpregnant patients, the brush was consistently shown to be the method obtaining the highest rate of adequate smears—ie, those containing endocervical cells.2-10 Furthermore, in studies including about 1900 pregnant patients, the brush with spatula caused no significantly increased risk of serious adverse outcomes, nor any trend in that direction.5-7,9-11 The device did cause a slight increase in self-limited vaginal spotting.
In theory, a more accurate Pap smear could lead to patient-oriented outcomes, such as less need for procedures to diagnose and treat cervical cytologic abnormalities, reduced incidence of invasive cervical cancer, and fewer patient deaths from cervical cancer. No data on these outcomes is available. Some studies did look for differences in the detection of cytologic abnormalities between the brush with spatula and the swab with spatula methods. Most small studies and a meta-analysis showed no difference.2,3,8,9 One study showed a trend towards improved yield; in another study, the brush with spatula significantly improved the ability to detect cytologic abnormalities in pregnant patients.7,10
Three studies addressed cost-effectiveness of the brush in pregnancy.3,9,12 Especially when including the cost of repeat Pap smears for inadequate specimens, the brush with spatula was rated most cost-effective in all 3 studies.
Comparison of the use of conventional Pap smear collection techniques with newer liquid-based cytology or human papilloma virus (HPV) typing has not yet been addressed in the literature.
Recommendations from others
“The Working Group’s Recommendations for Women in Low Risk Pregnancy” through the Veterans Health Administration lists use of a nylon cervical brush—no type is specified—as the appropriate sampling device in the late first trimester of pregnancy.13 No recommendations specific to the Cytobrush were found.
The following organizations have made no recommendations for or against the use of the Cytobrush in pregnancy: US Preventive Services Task Force, American College of Obstetricians and Gynecologists, American Academy of Family Physicians, or the American Academy of Nurse-Midwives.
Use the spatula and brush for Pap smears from pregnant women
Julia Fashner, MD
St. Joseph Regional Medical Center, South Bend, Ind
The evidence for safety and efficacy supports the use of the spatula and brush for obtaining Pap smears from pregnant women. You will have fewer inadequate smears that need to be repeated, but you will need to warn the patient of spotting that may occur after the specimen is obtained. For ThinPrep Pap smears, remember to follow the same recommendations as for nonpregnant women—turn the spatula the full 360° in contact with the cervix and only turn the brush a half-turn. Being overly aggressive to collect endocervical cells by twirling the brush may cause more bleeding.
1. Martin-Hirsch P, Jarvis G, Kitchener H, Lilford R. Collection devices for obtaining cervical cytology samples. Cochrane Gynaecological Cancer Group. Cochrane Database Syst Rev 2005; 1.
2. Bauman BJ. Use of a cervical brush for Papanicolaou smears collection. J Nurse Midwifery 1993;38:267-275.
3. McCord ML, Stovall TG, Meric JL, Summitt RL, Coleman SA. Cervical cytology: A randomized comparison of four sampling methods. Am J Obstet Gynecol 1992;166:1772-1779.
4. Curtis P, Mintzer M, Morrell D, Resnick J, Hendrix S, Qaqish B. Characteristics and quality of Papanicolaou smears obtained by primary care clinicians using a single commercial laboratory. Arch Fam Med 1999;8:407-413.
5. Paraiso MF, Brady K, Helmchen R, Roat T. Evaluation of the endocervical Cytobrush and cervix-brush in pregnant women. Obstet Gynecol 1994;84:539-543.
6. Foster JC, Smith HL. Use of the Cytobrush for Papanicolaou smear screens in pregnant women. J Nurse Midwifery 1996;41:211-217.
7. Orr JW, Barrett JM, Orr PF, Holloway RW, Holimon JL. The efficacy and safety of the Cytobrush during pregnancy. Gynecol Oncol 1992;44:260-262.
8. Rivlin ME, Woodliff JM, Bowlin RB, et al. Comparison of Cytobrush and cotton swab for Papanicolaou smears in pregnancy. J Reprod Med 1993;38:147-150.
9. Smith-Levitin M, Hernandez E, Anderson L, Heller P. Safety, efficacy and cost of three cervical cytology sampling devices in a prenatal clinic. J Reprod Med 1996;41:749-753.
10. Stillson T, Knight AL, Elswick RK. The effectiveness and safety of two cervical cytologic techniques during pregnancy. J Fam Pract 1997;45:159-164.
11. Grossman JH, Rivlin ME, Morrison JC. Cytobrush versus swab endocervical sampling for the detection of obstetric chlamydial infection. Am J Perinatol 1993;10:76-78.
12. Harrison DD, Hernandez E, Dunton CJ. Endocervical brush versus cotton swab for obtaining cervical smears at a clinic: A cost comparison. J Reprod Med 1993;38:285-288.
13. National Guidelines Clearinghouse. Veterans Health Administration, Department of Defense. DoD/VA clinical practice guideline for the management of uncomplicated pregnancy (in “The Working Group’s Recommendations for Women in Low Risk Pregnancy”). Washington, DC: Department of Veteran Affairs; 2002.
1. Martin-Hirsch P, Jarvis G, Kitchener H, Lilford R. Collection devices for obtaining cervical cytology samples. Cochrane Gynaecological Cancer Group. Cochrane Database Syst Rev 2005; 1.
2. Bauman BJ. Use of a cervical brush for Papanicolaou smears collection. J Nurse Midwifery 1993;38:267-275.
3. McCord ML, Stovall TG, Meric JL, Summitt RL, Coleman SA. Cervical cytology: A randomized comparison of four sampling methods. Am J Obstet Gynecol 1992;166:1772-1779.
4. Curtis P, Mintzer M, Morrell D, Resnick J, Hendrix S, Qaqish B. Characteristics and quality of Papanicolaou smears obtained by primary care clinicians using a single commercial laboratory. Arch Fam Med 1999;8:407-413.
5. Paraiso MF, Brady K, Helmchen R, Roat T. Evaluation of the endocervical Cytobrush and cervix-brush in pregnant women. Obstet Gynecol 1994;84:539-543.
6. Foster JC, Smith HL. Use of the Cytobrush for Papanicolaou smear screens in pregnant women. J Nurse Midwifery 1996;41:211-217.
7. Orr JW, Barrett JM, Orr PF, Holloway RW, Holimon JL. The efficacy and safety of the Cytobrush during pregnancy. Gynecol Oncol 1992;44:260-262.
8. Rivlin ME, Woodliff JM, Bowlin RB, et al. Comparison of Cytobrush and cotton swab for Papanicolaou smears in pregnancy. J Reprod Med 1993;38:147-150.
9. Smith-Levitin M, Hernandez E, Anderson L, Heller P. Safety, efficacy and cost of three cervical cytology sampling devices in a prenatal clinic. J Reprod Med 1996;41:749-753.
10. Stillson T, Knight AL, Elswick RK. The effectiveness and safety of two cervical cytologic techniques during pregnancy. J Fam Pract 1997;45:159-164.
11. Grossman JH, Rivlin ME, Morrison JC. Cytobrush versus swab endocervical sampling for the detection of obstetric chlamydial infection. Am J Perinatol 1993;10:76-78.
12. Harrison DD, Hernandez E, Dunton CJ. Endocervical brush versus cotton swab for obtaining cervical smears at a clinic: A cost comparison. J Reprod Med 1993;38:285-288.
13. National Guidelines Clearinghouse. Veterans Health Administration, Department of Defense. DoD/VA clinical practice guideline for the management of uncomplicated pregnancy (in “The Working Group’s Recommendations for Women in Low Risk Pregnancy”). Washington, DC: Department of Veteran Affairs; 2002.
Evidence-based answers from the Family Physicians Inquiries Network