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When should we stop mammography screening for breast cancer in elderly women?
There is insufficient evidence to recommend for or against routine screening mammography beyond the age of 69 years. The best candidates to stop screening are elderly women who have significant comorbidities, poor functional status, low bone mineral density (BMD), little interest in preventive care, or an unwillingness to accept the potential harm of screening. (Grade of Recommendation: C, based on retrospective cohort studies.)
Recommendations from others
Guidelines from other groups regarding mammographic screening of older women are not consistent Table. Neither the American Academy of Family Physicians and the American College of Radiology make specific recommendations.
Evidence-based answer
Screening mammography for women aged up to 70 years is widely recommended. However, its role in older women is unclear, even the though average life expectancy of elderly women is lengthy (eg, 9 years at age 80). Patients with 3 or more major comorbidities (ie, hypertension, diabetes, arthritis, myocardial infarction, stroke, respiratory disease, or other cancers) are 20 times more likely to die of a cause other than breast cancer within 3 years.5 Although half of all cancers are diagnosed in women older than 65 years, screening these women poses some risks. For every 1000 women older than 70 years who are screened, 81 mammograms will show an abnormal result, requiring 79 follow-up tests and 26 biopsies to detect 11 cancers.6 The picture is further complicated by the possibility that these cancers may be less aggressive. Cancers may grow more slowly with age,7 and 25% of all tumors in elderly women are ductal carcinoma in situ, which are unlikely to cause morbidity or death within their life spans.8
Unfortunately, the randomized trials of screening mammography have enrolled few women aged 70 to 74 years and none older than 74. Two studies retrospectively compared cohorts of elderly women who did and did not have screening. Smith-Bindman and colleagues9 studied 690,000 Medicare beneficiaries in California and found a 43% reduction in the risk of metastatic breast cancer in the screened group. A 13-year Dutch study found a 20% breast cancer mortality reduction that first appeared 7 years after initiating screening. The cohorts were not randomly assigned in either study, leading to possible differences in baseline risk.
In a cost-effectiveness analysis, Kerlikowske and coworkers10 included BMD in the model, which is positively associated with breast cancer risk. They found a small benefit to screening for women with the highest quartile BMD (highest cancer risk) and virtually no benefit in screening the lowest quartile BMD. Mandeblatt and colleagues 11 incorporated comorbidities in another model and found a small benefit for women older than 69 years that gradually diminished as they approached the age of 85. This benefit was halved in the presence of a major comorbidity. Both of these models assumed that the efficacy of screening in younger women applies to older women.
Since there are no randomized trials in this age group, the true efficacy of screening is unknown. Therefore, other factors must be considered, including the patient’s age, comorbidities, and preferences. The evidence suggests that the best candidates to stop screening mammography are elderly women who have significant comorbidities, poor functional status, low BMD, little interest in preventive care, or an unwillingness to accept the potential harm of screening.
Henry Domke, MD
Family Care Associates Jefferson City, Missouri
The evidence reviewed and the recommendations presented fit my clinical experience. I focus particularly on the issue of patient preference, because many of my elderly patients would be insulted if I recommended not getting a screening mammogram. After a woman reaches 75 years of age I address mammography screening only if the patient initiates the topic.
1. National Guideline Clearinghouse Web site. Available at www.guideline.gov. Accessed December 6, 2000.
2. American College of Preventive Medicine (ACPM). Screening mammography for breast cancer: American College of Preventive Medicine practice policy statement. Am J Prev Med 1996;12:340-41.
3. American Geriatrics Society Clinical Practice Committee. Breast cancer screening in older women. JAGS 2000;48:842-44.
4. US Preventive Services Task Force (USPSTF). Screening for breast cancer. In: Guide to clinical preventive services. 2nd ed. Baltimore, Md: Williams & Wilkins; 1996;89-103
5. Satariano WA, Ragland DR. The effect of comorbidity on 3 year survival of women with primary breast cancer. Ann Intern Med 1994;120:104-10.
6. Welch HG. Diagnostic testing following screening mammography in the elderly. JNCI 1998;90:1389-92.
7. Peer PG, van Dijck JA, Hendriks JH, Holland R, Verbeek AL. Age-dependent growth rate of primary breast cancer. Cancer 1993;71:3547-51.
8. Kerlikowske KM, Grady D, Barclay J, Sickles EA, Eaton A, Ernster V. Positive predictive value of screening mammography by age and family history of breast cancer. JAMA 1993;270:2444-50.
9. Smith-Bindman R, Kerlikowski K, Gebretsadik T, Newman J. Is screening mammography effective in elderly women? AJM 2000;108:112-19.
10. Kerlikowske K, Salzmann P, Phillips KA, Cauley JA, Cummings SR. Continuing screening mammography in women aged 70 to 79 years: impact on life expectancy and cost-effectiveness. JAMA 1999;282:2156-63.
11. Mandelblatt JS, Wheat ME, Monane M, Moshief RD, Hollenberg JP, Tang J. Breast cancer screening for elderly women with and without comorbid conditions. Ann Intern Med 1992;116:722-30.
There is insufficient evidence to recommend for or against routine screening mammography beyond the age of 69 years. The best candidates to stop screening are elderly women who have significant comorbidities, poor functional status, low bone mineral density (BMD), little interest in preventive care, or an unwillingness to accept the potential harm of screening. (Grade of Recommendation: C, based on retrospective cohort studies.)
Recommendations from others
Guidelines from other groups regarding mammographic screening of older women are not consistent Table. Neither the American Academy of Family Physicians and the American College of Radiology make specific recommendations.
Evidence-based answer
Screening mammography for women aged up to 70 years is widely recommended. However, its role in older women is unclear, even the though average life expectancy of elderly women is lengthy (eg, 9 years at age 80). Patients with 3 or more major comorbidities (ie, hypertension, diabetes, arthritis, myocardial infarction, stroke, respiratory disease, or other cancers) are 20 times more likely to die of a cause other than breast cancer within 3 years.5 Although half of all cancers are diagnosed in women older than 65 years, screening these women poses some risks. For every 1000 women older than 70 years who are screened, 81 mammograms will show an abnormal result, requiring 79 follow-up tests and 26 biopsies to detect 11 cancers.6 The picture is further complicated by the possibility that these cancers may be less aggressive. Cancers may grow more slowly with age,7 and 25% of all tumors in elderly women are ductal carcinoma in situ, which are unlikely to cause morbidity or death within their life spans.8
Unfortunately, the randomized trials of screening mammography have enrolled few women aged 70 to 74 years and none older than 74. Two studies retrospectively compared cohorts of elderly women who did and did not have screening. Smith-Bindman and colleagues9 studied 690,000 Medicare beneficiaries in California and found a 43% reduction in the risk of metastatic breast cancer in the screened group. A 13-year Dutch study found a 20% breast cancer mortality reduction that first appeared 7 years after initiating screening. The cohorts were not randomly assigned in either study, leading to possible differences in baseline risk.
In a cost-effectiveness analysis, Kerlikowske and coworkers10 included BMD in the model, which is positively associated with breast cancer risk. They found a small benefit to screening for women with the highest quartile BMD (highest cancer risk) and virtually no benefit in screening the lowest quartile BMD. Mandeblatt and colleagues 11 incorporated comorbidities in another model and found a small benefit for women older than 69 years that gradually diminished as they approached the age of 85. This benefit was halved in the presence of a major comorbidity. Both of these models assumed that the efficacy of screening in younger women applies to older women.
Since there are no randomized trials in this age group, the true efficacy of screening is unknown. Therefore, other factors must be considered, including the patient’s age, comorbidities, and preferences. The evidence suggests that the best candidates to stop screening mammography are elderly women who have significant comorbidities, poor functional status, low BMD, little interest in preventive care, or an unwillingness to accept the potential harm of screening.
Henry Domke, MD
Family Care Associates Jefferson City, Missouri
The evidence reviewed and the recommendations presented fit my clinical experience. I focus particularly on the issue of patient preference, because many of my elderly patients would be insulted if I recommended not getting a screening mammogram. After a woman reaches 75 years of age I address mammography screening only if the patient initiates the topic.
There is insufficient evidence to recommend for or against routine screening mammography beyond the age of 69 years. The best candidates to stop screening are elderly women who have significant comorbidities, poor functional status, low bone mineral density (BMD), little interest in preventive care, or an unwillingness to accept the potential harm of screening. (Grade of Recommendation: C, based on retrospective cohort studies.)
Recommendations from others
Guidelines from other groups regarding mammographic screening of older women are not consistent Table. Neither the American Academy of Family Physicians and the American College of Radiology make specific recommendations.
Evidence-based answer
Screening mammography for women aged up to 70 years is widely recommended. However, its role in older women is unclear, even the though average life expectancy of elderly women is lengthy (eg, 9 years at age 80). Patients with 3 or more major comorbidities (ie, hypertension, diabetes, arthritis, myocardial infarction, stroke, respiratory disease, or other cancers) are 20 times more likely to die of a cause other than breast cancer within 3 years.5 Although half of all cancers are diagnosed in women older than 65 years, screening these women poses some risks. For every 1000 women older than 70 years who are screened, 81 mammograms will show an abnormal result, requiring 79 follow-up tests and 26 biopsies to detect 11 cancers.6 The picture is further complicated by the possibility that these cancers may be less aggressive. Cancers may grow more slowly with age,7 and 25% of all tumors in elderly women are ductal carcinoma in situ, which are unlikely to cause morbidity or death within their life spans.8
Unfortunately, the randomized trials of screening mammography have enrolled few women aged 70 to 74 years and none older than 74. Two studies retrospectively compared cohorts of elderly women who did and did not have screening. Smith-Bindman and colleagues9 studied 690,000 Medicare beneficiaries in California and found a 43% reduction in the risk of metastatic breast cancer in the screened group. A 13-year Dutch study found a 20% breast cancer mortality reduction that first appeared 7 years after initiating screening. The cohorts were not randomly assigned in either study, leading to possible differences in baseline risk.
In a cost-effectiveness analysis, Kerlikowske and coworkers10 included BMD in the model, which is positively associated with breast cancer risk. They found a small benefit to screening for women with the highest quartile BMD (highest cancer risk) and virtually no benefit in screening the lowest quartile BMD. Mandeblatt and colleagues 11 incorporated comorbidities in another model and found a small benefit for women older than 69 years that gradually diminished as they approached the age of 85. This benefit was halved in the presence of a major comorbidity. Both of these models assumed that the efficacy of screening in younger women applies to older women.
Since there are no randomized trials in this age group, the true efficacy of screening is unknown. Therefore, other factors must be considered, including the patient’s age, comorbidities, and preferences. The evidence suggests that the best candidates to stop screening mammography are elderly women who have significant comorbidities, poor functional status, low BMD, little interest in preventive care, or an unwillingness to accept the potential harm of screening.
Henry Domke, MD
Family Care Associates Jefferson City, Missouri
The evidence reviewed and the recommendations presented fit my clinical experience. I focus particularly on the issue of patient preference, because many of my elderly patients would be insulted if I recommended not getting a screening mammogram. After a woman reaches 75 years of age I address mammography screening only if the patient initiates the topic.
1. National Guideline Clearinghouse Web site. Available at www.guideline.gov. Accessed December 6, 2000.
2. American College of Preventive Medicine (ACPM). Screening mammography for breast cancer: American College of Preventive Medicine practice policy statement. Am J Prev Med 1996;12:340-41.
3. American Geriatrics Society Clinical Practice Committee. Breast cancer screening in older women. JAGS 2000;48:842-44.
4. US Preventive Services Task Force (USPSTF). Screening for breast cancer. In: Guide to clinical preventive services. 2nd ed. Baltimore, Md: Williams & Wilkins; 1996;89-103
5. Satariano WA, Ragland DR. The effect of comorbidity on 3 year survival of women with primary breast cancer. Ann Intern Med 1994;120:104-10.
6. Welch HG. Diagnostic testing following screening mammography in the elderly. JNCI 1998;90:1389-92.
7. Peer PG, van Dijck JA, Hendriks JH, Holland R, Verbeek AL. Age-dependent growth rate of primary breast cancer. Cancer 1993;71:3547-51.
8. Kerlikowske KM, Grady D, Barclay J, Sickles EA, Eaton A, Ernster V. Positive predictive value of screening mammography by age and family history of breast cancer. JAMA 1993;270:2444-50.
9. Smith-Bindman R, Kerlikowski K, Gebretsadik T, Newman J. Is screening mammography effective in elderly women? AJM 2000;108:112-19.
10. Kerlikowske K, Salzmann P, Phillips KA, Cauley JA, Cummings SR. Continuing screening mammography in women aged 70 to 79 years: impact on life expectancy and cost-effectiveness. JAMA 1999;282:2156-63.
11. Mandelblatt JS, Wheat ME, Monane M, Moshief RD, Hollenberg JP, Tang J. Breast cancer screening for elderly women with and without comorbid conditions. Ann Intern Med 1992;116:722-30.
1. National Guideline Clearinghouse Web site. Available at www.guideline.gov. Accessed December 6, 2000.
2. American College of Preventive Medicine (ACPM). Screening mammography for breast cancer: American College of Preventive Medicine practice policy statement. Am J Prev Med 1996;12:340-41.
3. American Geriatrics Society Clinical Practice Committee. Breast cancer screening in older women. JAGS 2000;48:842-44.
4. US Preventive Services Task Force (USPSTF). Screening for breast cancer. In: Guide to clinical preventive services. 2nd ed. Baltimore, Md: Williams & Wilkins; 1996;89-103
5. Satariano WA, Ragland DR. The effect of comorbidity on 3 year survival of women with primary breast cancer. Ann Intern Med 1994;120:104-10.
6. Welch HG. Diagnostic testing following screening mammography in the elderly. JNCI 1998;90:1389-92.
7. Peer PG, van Dijck JA, Hendriks JH, Holland R, Verbeek AL. Age-dependent growth rate of primary breast cancer. Cancer 1993;71:3547-51.
8. Kerlikowske KM, Grady D, Barclay J, Sickles EA, Eaton A, Ernster V. Positive predictive value of screening mammography by age and family history of breast cancer. JAMA 1993;270:2444-50.
9. Smith-Bindman R, Kerlikowski K, Gebretsadik T, Newman J. Is screening mammography effective in elderly women? AJM 2000;108:112-19.
10. Kerlikowske K, Salzmann P, Phillips KA, Cauley JA, Cummings SR. Continuing screening mammography in women aged 70 to 79 years: impact on life expectancy and cost-effectiveness. JAMA 1999;282:2156-63.
11. Mandelblatt JS, Wheat ME, Monane M, Moshief RD, Hollenberg JP, Tang J. Breast cancer screening for elderly women with and without comorbid conditions. Ann Intern Med 1992;116:722-30.
Evidence-based answers from the Family Physicians Inquiries Network
Is surgery effective for reducing symptoms in adults with obstructive sleep apnea?
Current evidence is insufficient to recommend surgery for symptom relief for patients with obstructive sleep apnea. More convincing evidence exists supporting the use of Continuous Positive Airway Pressure (CPAP) or dental appliances for reducing symptoms of sleep apnea.
Grade of recommendation: C, based on case series and poor quality cohort and case-control studies
Recommendations from others
The Cochrane Database of Systematic Reviews reports, “In light of the current lack of good trial-based evidence, clinicians should consider restricting surgery for obstructive sleep apnoea to that carried out as part of clinical trials. Where practice is continued, patients should be informed of the experimental nature of the operations. Patients should be told that there is a lack of good trial-based evidence of the efficacy of surgery for obstructive sleep apnoea, a course of action that may restrict the use of these operations.”1
The American Sleep Disorders Association states, “The presence and severity of obstructive sleep apnea must be determined before initiating surgical therapy… because of the complexity of airway narrowing or collapse during sleep, any one surgical procedure may not eradicate a patient’s sleep apnea. A stepwise approach to surgical management is acceptable if the patient is advised at the onset of treatment about the likelihood of the success of each procedure and that multiple operations may be necessary. After the surgical site has healed, a follow-up evaluation, including an objective measure of respiration and quality of sleep, must be performed to ensure that the abnormalities noted in the original study are corrected.”2
Search strategy
The Cochrane Database of Systematic Reviews, the National Guideline Clearinghouse Database, the Turning Research Into Practice (TRIP) database, British National Health Service Health Technology Assessment Database (HTA), and DARE (Database of Abstracts and Reviews of Effectiveness) were searched, using the keywords “sleep” and “sleep apnea.”
MEDLINE search strategy: {(Sleep Apnea, Obstructive/su [Surgery], OR sleep apnea syndromes/su) AND (clinical trial.pt. OR exp treatment outcome/OR meta-analysis.pt)}
Evidence summary
Obstructive sleep apnea is a common and potentially serious condition. Good evidence now exists supporting the efficacy of CPAP in improving patient-oriented outcomes (eg, daytime sleepiness) and disease-oriented outcomes (eg, nocturnal hypoxia).3,4,5 However, CPAP is not tolerated by 20% to 30% of patients, not universally effective, and ineffective if not used regularly.5 Surgery has held promise as a potentially curative therapy, a promise not yet demonstrated in well-designed randomized controlled trials.
The Cochrane Airways Group performed an extensive review of this topic in October 1999 and found that none of the 594 potentially relevant articles reviewed were methodologically adequate.1 Our search found 2 randomized controlled trials: 1 apparently missed by the Cochrane review and 1 subsequent to it.
Lojander et al6 compared uvulopharyngopalatoplasty (UPPP) to conservative management (weight loss, smoking cessation, and alcohol avoidance advice) in 32 patients. Patients were excluded if they had asthma, obesity (body mass index >40), restless leg syndrome, hypothyroidism, chronic obstructive pulmonary disease, or intolerance of missed work because of somnolence. Remaining patients were selected as possible surgical candidates by a team of hospital-based experts then randomized to surgery or conservative therapy. At 1 year of follow-up, they found no change in nocturnal oxygen desaturation but some improvement in the mean score of a visual analog scale of daytime sleepiness and in the mean self-report of out-of-bed sleeping episodes. Unfortunately these subjective outcome measures have not been validated and are subject to bias. This, in addition to lack of intention-to-treat analysis, renders these results uninterpretable.
The other trial compared UPPP with dental appliances in late 1999 and found dental appliances superior to surgery for improving apnea scores.7
Current recommendations in favor of surgical therapy are based solely on case series, poorly designed trials, expert opinion or pathophysiologic reasoning.1 Although such literature is voluminous, the most optimistic review estimates that less than 50% of patients with obstructive sleep apnea will benefit from surgery.8 The nonrandomized design of such trials may overestimate treatment effects by more than 40%.9
Given how little is known about its effectiveness, compounded by potential iatrogenesis, surgery should be considered the last resort for patients with obstructive sleep apnea. Doctors should discuss CPAP (the most effective therapy) and condition-specific dental appliances (the best tolerated therapy) with their patients until more is known about the efficacy of surgery. All patients should be counseled regarding healthy lifestyle modification.
Alan R. Gill, MD
Tacoma Family Medicine Family Practice Residency Program
Sleep apnea is a difficult problem for the primary care physician. Uncertainty extends well beyond the efficacy of surgery. The literature associating sleep apnea and its proposed clinical consequences (such as pulmonary hypertension) is weak, and evidence that any current treatment alters long-term outcomes is even weaker. Clinicians can offer relief from daytime somnolence by recommending nightly CPAP, but they can promise little else. Our patients should understand the limits of our knowledge as we help them make lifestyle changes and choose appropriate therapy. Surgery remains an experimental approach for markedly symptomatic patients who do not respond to noninvasive therapies.
1. Bridgeman SA. Dunn KM and the Cochrane Airways Group. Surgery for obstructive sleep apnea. The Cochrane Database of Systematic Reviews, The Cochrane Library. Issue 3 1999.
2. Standards of Practice Committee of the American Sleep Disorders Association. Practice parameters for the treatment of obstructive sleep apnea in adults: The efficacy of surgical modifications of the upper airway. Sleep 1996;19:1996.-
3. Jenkinson C, Davies RJ, Mullins R, Strandling JR. Comparison of therapeutic and non-therapeutic nasal continuous positive airway pressure for obstructive sleep apnea: a randomised prospective parallel trial. Lancet. 1999;353:2100-5.
4. Engleman HM, Kingshott RN, Wraith PK, et al. Randomized placebo-controlled crossover trial of continuous positive airway pressure for mild sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med. 1999;159:461-7.
5. Wright J. White J and the Cochrane Airways Group. Continuous positive airways pressure for obstructive sleep apnoea. The Cochrane Database of Systematic Reviews, The Cochrane Library Issue 3 2000.
6. Lojander J, Maasilta P, Partinen M, Brander PE, Salmi T, Lehtonen H. Nasal-CPAP, surgery, and conservative management for treatment of obstructive sleep apnea syndrome. Chest 1996;110:114-119.
7. Wilhelmsson B, Tegelberg A, Walker-Engstrom ML, et al. A prospective randomized trial of dental appliance compared with uvulopalatopharyngoplasty in the treatment of obstructive sleep apnea. Acta Oto-laryngologica 1999;119:503-9.
8. Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper airway in adults with obstructive sleep apnea syndrome. Sleep 1996;19:156-77.
9. Bias. Bandolier 2000;80:2.-http://www.jr2.ox.ac.uk/bandolier/band80/b80-2.html
Current evidence is insufficient to recommend surgery for symptom relief for patients with obstructive sleep apnea. More convincing evidence exists supporting the use of Continuous Positive Airway Pressure (CPAP) or dental appliances for reducing symptoms of sleep apnea.
Grade of recommendation: C, based on case series and poor quality cohort and case-control studies
Recommendations from others
The Cochrane Database of Systematic Reviews reports, “In light of the current lack of good trial-based evidence, clinicians should consider restricting surgery for obstructive sleep apnoea to that carried out as part of clinical trials. Where practice is continued, patients should be informed of the experimental nature of the operations. Patients should be told that there is a lack of good trial-based evidence of the efficacy of surgery for obstructive sleep apnoea, a course of action that may restrict the use of these operations.”1
The American Sleep Disorders Association states, “The presence and severity of obstructive sleep apnea must be determined before initiating surgical therapy… because of the complexity of airway narrowing or collapse during sleep, any one surgical procedure may not eradicate a patient’s sleep apnea. A stepwise approach to surgical management is acceptable if the patient is advised at the onset of treatment about the likelihood of the success of each procedure and that multiple operations may be necessary. After the surgical site has healed, a follow-up evaluation, including an objective measure of respiration and quality of sleep, must be performed to ensure that the abnormalities noted in the original study are corrected.”2
Search strategy
The Cochrane Database of Systematic Reviews, the National Guideline Clearinghouse Database, the Turning Research Into Practice (TRIP) database, British National Health Service Health Technology Assessment Database (HTA), and DARE (Database of Abstracts and Reviews of Effectiveness) were searched, using the keywords “sleep” and “sleep apnea.”
MEDLINE search strategy: {(Sleep Apnea, Obstructive/su [Surgery], OR sleep apnea syndromes/su) AND (clinical trial.pt. OR exp treatment outcome/OR meta-analysis.pt)}
Evidence summary
Obstructive sleep apnea is a common and potentially serious condition. Good evidence now exists supporting the efficacy of CPAP in improving patient-oriented outcomes (eg, daytime sleepiness) and disease-oriented outcomes (eg, nocturnal hypoxia).3,4,5 However, CPAP is not tolerated by 20% to 30% of patients, not universally effective, and ineffective if not used regularly.5 Surgery has held promise as a potentially curative therapy, a promise not yet demonstrated in well-designed randomized controlled trials.
The Cochrane Airways Group performed an extensive review of this topic in October 1999 and found that none of the 594 potentially relevant articles reviewed were methodologically adequate.1 Our search found 2 randomized controlled trials: 1 apparently missed by the Cochrane review and 1 subsequent to it.
Lojander et al6 compared uvulopharyngopalatoplasty (UPPP) to conservative management (weight loss, smoking cessation, and alcohol avoidance advice) in 32 patients. Patients were excluded if they had asthma, obesity (body mass index >40), restless leg syndrome, hypothyroidism, chronic obstructive pulmonary disease, or intolerance of missed work because of somnolence. Remaining patients were selected as possible surgical candidates by a team of hospital-based experts then randomized to surgery or conservative therapy. At 1 year of follow-up, they found no change in nocturnal oxygen desaturation but some improvement in the mean score of a visual analog scale of daytime sleepiness and in the mean self-report of out-of-bed sleeping episodes. Unfortunately these subjective outcome measures have not been validated and are subject to bias. This, in addition to lack of intention-to-treat analysis, renders these results uninterpretable.
The other trial compared UPPP with dental appliances in late 1999 and found dental appliances superior to surgery for improving apnea scores.7
Current recommendations in favor of surgical therapy are based solely on case series, poorly designed trials, expert opinion or pathophysiologic reasoning.1 Although such literature is voluminous, the most optimistic review estimates that less than 50% of patients with obstructive sleep apnea will benefit from surgery.8 The nonrandomized design of such trials may overestimate treatment effects by more than 40%.9
Given how little is known about its effectiveness, compounded by potential iatrogenesis, surgery should be considered the last resort for patients with obstructive sleep apnea. Doctors should discuss CPAP (the most effective therapy) and condition-specific dental appliances (the best tolerated therapy) with their patients until more is known about the efficacy of surgery. All patients should be counseled regarding healthy lifestyle modification.
Alan R. Gill, MD
Tacoma Family Medicine Family Practice Residency Program
Sleep apnea is a difficult problem for the primary care physician. Uncertainty extends well beyond the efficacy of surgery. The literature associating sleep apnea and its proposed clinical consequences (such as pulmonary hypertension) is weak, and evidence that any current treatment alters long-term outcomes is even weaker. Clinicians can offer relief from daytime somnolence by recommending nightly CPAP, but they can promise little else. Our patients should understand the limits of our knowledge as we help them make lifestyle changes and choose appropriate therapy. Surgery remains an experimental approach for markedly symptomatic patients who do not respond to noninvasive therapies.
Current evidence is insufficient to recommend surgery for symptom relief for patients with obstructive sleep apnea. More convincing evidence exists supporting the use of Continuous Positive Airway Pressure (CPAP) or dental appliances for reducing symptoms of sleep apnea.
Grade of recommendation: C, based on case series and poor quality cohort and case-control studies
Recommendations from others
The Cochrane Database of Systematic Reviews reports, “In light of the current lack of good trial-based evidence, clinicians should consider restricting surgery for obstructive sleep apnoea to that carried out as part of clinical trials. Where practice is continued, patients should be informed of the experimental nature of the operations. Patients should be told that there is a lack of good trial-based evidence of the efficacy of surgery for obstructive sleep apnoea, a course of action that may restrict the use of these operations.”1
The American Sleep Disorders Association states, “The presence and severity of obstructive sleep apnea must be determined before initiating surgical therapy… because of the complexity of airway narrowing or collapse during sleep, any one surgical procedure may not eradicate a patient’s sleep apnea. A stepwise approach to surgical management is acceptable if the patient is advised at the onset of treatment about the likelihood of the success of each procedure and that multiple operations may be necessary. After the surgical site has healed, a follow-up evaluation, including an objective measure of respiration and quality of sleep, must be performed to ensure that the abnormalities noted in the original study are corrected.”2
Search strategy
The Cochrane Database of Systematic Reviews, the National Guideline Clearinghouse Database, the Turning Research Into Practice (TRIP) database, British National Health Service Health Technology Assessment Database (HTA), and DARE (Database of Abstracts and Reviews of Effectiveness) were searched, using the keywords “sleep” and “sleep apnea.”
MEDLINE search strategy: {(Sleep Apnea, Obstructive/su [Surgery], OR sleep apnea syndromes/su) AND (clinical trial.pt. OR exp treatment outcome/OR meta-analysis.pt)}
Evidence summary
Obstructive sleep apnea is a common and potentially serious condition. Good evidence now exists supporting the efficacy of CPAP in improving patient-oriented outcomes (eg, daytime sleepiness) and disease-oriented outcomes (eg, nocturnal hypoxia).3,4,5 However, CPAP is not tolerated by 20% to 30% of patients, not universally effective, and ineffective if not used regularly.5 Surgery has held promise as a potentially curative therapy, a promise not yet demonstrated in well-designed randomized controlled trials.
The Cochrane Airways Group performed an extensive review of this topic in October 1999 and found that none of the 594 potentially relevant articles reviewed were methodologically adequate.1 Our search found 2 randomized controlled trials: 1 apparently missed by the Cochrane review and 1 subsequent to it.
Lojander et al6 compared uvulopharyngopalatoplasty (UPPP) to conservative management (weight loss, smoking cessation, and alcohol avoidance advice) in 32 patients. Patients were excluded if they had asthma, obesity (body mass index >40), restless leg syndrome, hypothyroidism, chronic obstructive pulmonary disease, or intolerance of missed work because of somnolence. Remaining patients were selected as possible surgical candidates by a team of hospital-based experts then randomized to surgery or conservative therapy. At 1 year of follow-up, they found no change in nocturnal oxygen desaturation but some improvement in the mean score of a visual analog scale of daytime sleepiness and in the mean self-report of out-of-bed sleeping episodes. Unfortunately these subjective outcome measures have not been validated and are subject to bias. This, in addition to lack of intention-to-treat analysis, renders these results uninterpretable.
The other trial compared UPPP with dental appliances in late 1999 and found dental appliances superior to surgery for improving apnea scores.7
Current recommendations in favor of surgical therapy are based solely on case series, poorly designed trials, expert opinion or pathophysiologic reasoning.1 Although such literature is voluminous, the most optimistic review estimates that less than 50% of patients with obstructive sleep apnea will benefit from surgery.8 The nonrandomized design of such trials may overestimate treatment effects by more than 40%.9
Given how little is known about its effectiveness, compounded by potential iatrogenesis, surgery should be considered the last resort for patients with obstructive sleep apnea. Doctors should discuss CPAP (the most effective therapy) and condition-specific dental appliances (the best tolerated therapy) with their patients until more is known about the efficacy of surgery. All patients should be counseled regarding healthy lifestyle modification.
Alan R. Gill, MD
Tacoma Family Medicine Family Practice Residency Program
Sleep apnea is a difficult problem for the primary care physician. Uncertainty extends well beyond the efficacy of surgery. The literature associating sleep apnea and its proposed clinical consequences (such as pulmonary hypertension) is weak, and evidence that any current treatment alters long-term outcomes is even weaker. Clinicians can offer relief from daytime somnolence by recommending nightly CPAP, but they can promise little else. Our patients should understand the limits of our knowledge as we help them make lifestyle changes and choose appropriate therapy. Surgery remains an experimental approach for markedly symptomatic patients who do not respond to noninvasive therapies.
1. Bridgeman SA. Dunn KM and the Cochrane Airways Group. Surgery for obstructive sleep apnea. The Cochrane Database of Systematic Reviews, The Cochrane Library. Issue 3 1999.
2. Standards of Practice Committee of the American Sleep Disorders Association. Practice parameters for the treatment of obstructive sleep apnea in adults: The efficacy of surgical modifications of the upper airway. Sleep 1996;19:1996.-
3. Jenkinson C, Davies RJ, Mullins R, Strandling JR. Comparison of therapeutic and non-therapeutic nasal continuous positive airway pressure for obstructive sleep apnea: a randomised prospective parallel trial. Lancet. 1999;353:2100-5.
4. Engleman HM, Kingshott RN, Wraith PK, et al. Randomized placebo-controlled crossover trial of continuous positive airway pressure for mild sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med. 1999;159:461-7.
5. Wright J. White J and the Cochrane Airways Group. Continuous positive airways pressure for obstructive sleep apnoea. The Cochrane Database of Systematic Reviews, The Cochrane Library Issue 3 2000.
6. Lojander J, Maasilta P, Partinen M, Brander PE, Salmi T, Lehtonen H. Nasal-CPAP, surgery, and conservative management for treatment of obstructive sleep apnea syndrome. Chest 1996;110:114-119.
7. Wilhelmsson B, Tegelberg A, Walker-Engstrom ML, et al. A prospective randomized trial of dental appliance compared with uvulopalatopharyngoplasty in the treatment of obstructive sleep apnea. Acta Oto-laryngologica 1999;119:503-9.
8. Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper airway in adults with obstructive sleep apnea syndrome. Sleep 1996;19:156-77.
9. Bias. Bandolier 2000;80:2.-http://www.jr2.ox.ac.uk/bandolier/band80/b80-2.html
1. Bridgeman SA. Dunn KM and the Cochrane Airways Group. Surgery for obstructive sleep apnea. The Cochrane Database of Systematic Reviews, The Cochrane Library. Issue 3 1999.
2. Standards of Practice Committee of the American Sleep Disorders Association. Practice parameters for the treatment of obstructive sleep apnea in adults: The efficacy of surgical modifications of the upper airway. Sleep 1996;19:1996.-
3. Jenkinson C, Davies RJ, Mullins R, Strandling JR. Comparison of therapeutic and non-therapeutic nasal continuous positive airway pressure for obstructive sleep apnea: a randomised prospective parallel trial. Lancet. 1999;353:2100-5.
4. Engleman HM, Kingshott RN, Wraith PK, et al. Randomized placebo-controlled crossover trial of continuous positive airway pressure for mild sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med. 1999;159:461-7.
5. Wright J. White J and the Cochrane Airways Group. Continuous positive airways pressure for obstructive sleep apnoea. The Cochrane Database of Systematic Reviews, The Cochrane Library Issue 3 2000.
6. Lojander J, Maasilta P, Partinen M, Brander PE, Salmi T, Lehtonen H. Nasal-CPAP, surgery, and conservative management for treatment of obstructive sleep apnea syndrome. Chest 1996;110:114-119.
7. Wilhelmsson B, Tegelberg A, Walker-Engstrom ML, et al. A prospective randomized trial of dental appliance compared with uvulopalatopharyngoplasty in the treatment of obstructive sleep apnea. Acta Oto-laryngologica 1999;119:503-9.
8. Sher AE, Schechtman KB, Piccirillo JF. The efficacy of surgical modifications of the upper airway in adults with obstructive sleep apnea syndrome. Sleep 1996;19:156-77.
9. Bias. Bandolier 2000;80:2.-http://www.jr2.ox.ac.uk/bandolier/band80/b80-2.html
Evidence-based answers from the Family Physicians Inquiries Network
What is a reasonable initial approach to the patient with fatigue?
Half of all patients presenting with fatigue have a psychological cause. Patients with a history of anxiety or depression or those with a duration of symptoms for more than 3 months are more likely to remain symptomatic 6 months later. Physicians should perform a physical examination, take a thorough history, and screen patients for depression using a validated primary care instrument, such as the Beck Depression Inventory or Prime-MD. Physicians may also consider a directed laboratory evaluation with sedimentation rate, blood count, and glycohemoglobin and thyroid stimulating hormone (TSH) levels, particularly in older patients.
Grade of Recommendation: C, based on case series and expert opinion
Recommendations from others
A guideline developed by a group of family physicians1 provides the best overview of the topic. They recommend performing a detailed history and physical examination with further investigation reserved for patients with signs and symptoms of treatable causes of fatigue, such as anemia or hypothyroidism. They also recommend a somewhat more aggressive approach to investigation for patients older than 65 years.
Evidence summary
Before evaluating a patient presenting with fatigue, we must know the differential diagnosis in primary care practice for this complaint. Approximately 10% of patients visiting a primary care practice report fatigue of at least 1 month’s duration.2 Ridsdale identified 220 British patients presenting to a general practitioner with a chief complaint of fatigue. Physicians performed a thorough history and physical; took a complete blood count; tested the levels of blood or urine glucose, electrolytes, sedimentation rate, TSH, and urea; and tested for mononucleosis (if younger than 40). Only 19 (8%) were given a diagnosis based on the laboratory evaluation: 8 had anemia, 3 were hypothyroid, 3 had mononucleosis, 3 had other infections, 1 had diabetes, and 1 had carcinomatosis.3Table 1 shows results from 4 other series of fatigued patients.
Regarding prognosis, 59% of patients were still fatigued after 6 months.3 Patients with a previous diagnosis of anxiety or depression (odds ratio [OR] =3.0; 95% confidence interval [CI], 1.4 - 6.1), those with symptoms for more than 3 months (OR= 2.1, 95% CI, 1.1 - 4.1), and those with more education (OR=3.5; 95% CI, 3.2 - 3.8) were more likely to remain fatigued at follow-up.3,7
To summarize, of 100 patients presenting to a primary care physician with fatigue, approximately 25 will be depressed; 25 will have another psychiatric diagnosis, such as dysthymia or anxiety; 15 will have an infection, such as hepatitis, cytomegalovirus, or mononucleosis; 15 will have another physiological cause of fatigue, such as undiagnosed diabetes, anemia, or hypothyroidism; and 20 will remain undiagnosed.
A recent systematic review of case-finding instruments for depression in primary care found that most instruments are similar in accuracy (84% sensitive, 72% specific).8 If applied to a group of fatigued patients with a 25% probability of depression, 50% of patients with an abnormal result on one of these case-finding instruments would be depressed compared with only 7% who had a normal or negative result. A primary care physician’s clinical impression based on their interview of a patient has not been formally evaluated for its accuracy in the diagnosis of depression. A 2-question screen has good sensitivity but poor specificity (43% of nondepressed patients will be labeled as depressed by this instrument).9
Jeffery L. Belden, MD
Family Health Care (private practice) Columbia, Missouri
E-mail: [email protected]
The evidence reviewed and the recommendations fit fairly well with my clinical impressions and approach to patients presenting with fatigue. However, I find that a substantial proportion have sleep deprivation, lack of adequate exercise, or their life is in some way out of balance (too much work, stress, or busyness with inadequate play, replenishment, or spiritual reflection and renewal). I am not convinced of the value of a routine sedimentation rate test unless the patient is elderly, has some other historical factor suggesting its utility, or has absolutely no other explanation for their symptoms. I seldom use depression-screening instruments since I simply take a history focused on depressive symptoms. Use of a depression screen before I enter the room would help focus and shorten the visit, and detect cases of depression I might otherwise miss. I will consider implementing such a practice for patients who present with fatigue or insomnia.
1. Godwin M, Delva D, Miller K, et al. Investigating fatigue of less than 6 month’s duration: Guidelines for family physicians. Can Fam Phys 1999;45:373-9.
2. David A, Pelosi A, McDonald E, et al. Tired, weak, or in need of rest: fatigue among general practice attenders. BMJ 1990;301:1199-202.
3. Ridsdale L, Evans A, Jerrett W, et al. Patients with fatigue in general practice: a prospective study. BMJ 1993;307:103-6.
4. Morrison JD. Fatigue as a presenting complain in family practice. J Fam Pract 1980;10:795-801.
5. Sugarman JR, Berg AO. Evaluation of fatigue in a family practice. J Fam Pract 1984;19:643-7.
6. Elnicki M, Shockcor WT, Brick E, Beynon D. Evaluating the compliant of fatigue in primary care: diagnoses and outcomes. Am J Med 1992;93:303-6.
7. Valdini AF, Steinhardt S, Valicenti J, Jaffe A. A one-year follow-up of fatigued patients. J Fam Pract 1988;26:33-8.
8. Mulrow CD, Williams JW, Gerety MB, et al. Case-finding instruments for depression in primary care settings. Ann Intern Med 1995;123:913-21.
9. Case-finding instruments for depression. Two questions are as good as many. J Gen Intern Med. 1997;12:439-45.
Half of all patients presenting with fatigue have a psychological cause. Patients with a history of anxiety or depression or those with a duration of symptoms for more than 3 months are more likely to remain symptomatic 6 months later. Physicians should perform a physical examination, take a thorough history, and screen patients for depression using a validated primary care instrument, such as the Beck Depression Inventory or Prime-MD. Physicians may also consider a directed laboratory evaluation with sedimentation rate, blood count, and glycohemoglobin and thyroid stimulating hormone (TSH) levels, particularly in older patients.
Grade of Recommendation: C, based on case series and expert opinion
Recommendations from others
A guideline developed by a group of family physicians1 provides the best overview of the topic. They recommend performing a detailed history and physical examination with further investigation reserved for patients with signs and symptoms of treatable causes of fatigue, such as anemia or hypothyroidism. They also recommend a somewhat more aggressive approach to investigation for patients older than 65 years.
Evidence summary
Before evaluating a patient presenting with fatigue, we must know the differential diagnosis in primary care practice for this complaint. Approximately 10% of patients visiting a primary care practice report fatigue of at least 1 month’s duration.2 Ridsdale identified 220 British patients presenting to a general practitioner with a chief complaint of fatigue. Physicians performed a thorough history and physical; took a complete blood count; tested the levels of blood or urine glucose, electrolytes, sedimentation rate, TSH, and urea; and tested for mononucleosis (if younger than 40). Only 19 (8%) were given a diagnosis based on the laboratory evaluation: 8 had anemia, 3 were hypothyroid, 3 had mononucleosis, 3 had other infections, 1 had diabetes, and 1 had carcinomatosis.3Table 1 shows results from 4 other series of fatigued patients.
Regarding prognosis, 59% of patients were still fatigued after 6 months.3 Patients with a previous diagnosis of anxiety or depression (odds ratio [OR] =3.0; 95% confidence interval [CI], 1.4 - 6.1), those with symptoms for more than 3 months (OR= 2.1, 95% CI, 1.1 - 4.1), and those with more education (OR=3.5; 95% CI, 3.2 - 3.8) were more likely to remain fatigued at follow-up.3,7
To summarize, of 100 patients presenting to a primary care physician with fatigue, approximately 25 will be depressed; 25 will have another psychiatric diagnosis, such as dysthymia or anxiety; 15 will have an infection, such as hepatitis, cytomegalovirus, or mononucleosis; 15 will have another physiological cause of fatigue, such as undiagnosed diabetes, anemia, or hypothyroidism; and 20 will remain undiagnosed.
A recent systematic review of case-finding instruments for depression in primary care found that most instruments are similar in accuracy (84% sensitive, 72% specific).8 If applied to a group of fatigued patients with a 25% probability of depression, 50% of patients with an abnormal result on one of these case-finding instruments would be depressed compared with only 7% who had a normal or negative result. A primary care physician’s clinical impression based on their interview of a patient has not been formally evaluated for its accuracy in the diagnosis of depression. A 2-question screen has good sensitivity but poor specificity (43% of nondepressed patients will be labeled as depressed by this instrument).9
Jeffery L. Belden, MD
Family Health Care (private practice) Columbia, Missouri
E-mail: [email protected]
The evidence reviewed and the recommendations fit fairly well with my clinical impressions and approach to patients presenting with fatigue. However, I find that a substantial proportion have sleep deprivation, lack of adequate exercise, or their life is in some way out of balance (too much work, stress, or busyness with inadequate play, replenishment, or spiritual reflection and renewal). I am not convinced of the value of a routine sedimentation rate test unless the patient is elderly, has some other historical factor suggesting its utility, or has absolutely no other explanation for their symptoms. I seldom use depression-screening instruments since I simply take a history focused on depressive symptoms. Use of a depression screen before I enter the room would help focus and shorten the visit, and detect cases of depression I might otherwise miss. I will consider implementing such a practice for patients who present with fatigue or insomnia.
Half of all patients presenting with fatigue have a psychological cause. Patients with a history of anxiety or depression or those with a duration of symptoms for more than 3 months are more likely to remain symptomatic 6 months later. Physicians should perform a physical examination, take a thorough history, and screen patients for depression using a validated primary care instrument, such as the Beck Depression Inventory or Prime-MD. Physicians may also consider a directed laboratory evaluation with sedimentation rate, blood count, and glycohemoglobin and thyroid stimulating hormone (TSH) levels, particularly in older patients.
Grade of Recommendation: C, based on case series and expert opinion
Recommendations from others
A guideline developed by a group of family physicians1 provides the best overview of the topic. They recommend performing a detailed history and physical examination with further investigation reserved for patients with signs and symptoms of treatable causes of fatigue, such as anemia or hypothyroidism. They also recommend a somewhat more aggressive approach to investigation for patients older than 65 years.
Evidence summary
Before evaluating a patient presenting with fatigue, we must know the differential diagnosis in primary care practice for this complaint. Approximately 10% of patients visiting a primary care practice report fatigue of at least 1 month’s duration.2 Ridsdale identified 220 British patients presenting to a general practitioner with a chief complaint of fatigue. Physicians performed a thorough history and physical; took a complete blood count; tested the levels of blood or urine glucose, electrolytes, sedimentation rate, TSH, and urea; and tested for mononucleosis (if younger than 40). Only 19 (8%) were given a diagnosis based on the laboratory evaluation: 8 had anemia, 3 were hypothyroid, 3 had mononucleosis, 3 had other infections, 1 had diabetes, and 1 had carcinomatosis.3Table 1 shows results from 4 other series of fatigued patients.
Regarding prognosis, 59% of patients were still fatigued after 6 months.3 Patients with a previous diagnosis of anxiety or depression (odds ratio [OR] =3.0; 95% confidence interval [CI], 1.4 - 6.1), those with symptoms for more than 3 months (OR= 2.1, 95% CI, 1.1 - 4.1), and those with more education (OR=3.5; 95% CI, 3.2 - 3.8) were more likely to remain fatigued at follow-up.3,7
To summarize, of 100 patients presenting to a primary care physician with fatigue, approximately 25 will be depressed; 25 will have another psychiatric diagnosis, such as dysthymia or anxiety; 15 will have an infection, such as hepatitis, cytomegalovirus, or mononucleosis; 15 will have another physiological cause of fatigue, such as undiagnosed diabetes, anemia, or hypothyroidism; and 20 will remain undiagnosed.
A recent systematic review of case-finding instruments for depression in primary care found that most instruments are similar in accuracy (84% sensitive, 72% specific).8 If applied to a group of fatigued patients with a 25% probability of depression, 50% of patients with an abnormal result on one of these case-finding instruments would be depressed compared with only 7% who had a normal or negative result. A primary care physician’s clinical impression based on their interview of a patient has not been formally evaluated for its accuracy in the diagnosis of depression. A 2-question screen has good sensitivity but poor specificity (43% of nondepressed patients will be labeled as depressed by this instrument).9
Jeffery L. Belden, MD
Family Health Care (private practice) Columbia, Missouri
E-mail: [email protected]
The evidence reviewed and the recommendations fit fairly well with my clinical impressions and approach to patients presenting with fatigue. However, I find that a substantial proportion have sleep deprivation, lack of adequate exercise, or their life is in some way out of balance (too much work, stress, or busyness with inadequate play, replenishment, or spiritual reflection and renewal). I am not convinced of the value of a routine sedimentation rate test unless the patient is elderly, has some other historical factor suggesting its utility, or has absolutely no other explanation for their symptoms. I seldom use depression-screening instruments since I simply take a history focused on depressive symptoms. Use of a depression screen before I enter the room would help focus and shorten the visit, and detect cases of depression I might otherwise miss. I will consider implementing such a practice for patients who present with fatigue or insomnia.
1. Godwin M, Delva D, Miller K, et al. Investigating fatigue of less than 6 month’s duration: Guidelines for family physicians. Can Fam Phys 1999;45:373-9.
2. David A, Pelosi A, McDonald E, et al. Tired, weak, or in need of rest: fatigue among general practice attenders. BMJ 1990;301:1199-202.
3. Ridsdale L, Evans A, Jerrett W, et al. Patients with fatigue in general practice: a prospective study. BMJ 1993;307:103-6.
4. Morrison JD. Fatigue as a presenting complain in family practice. J Fam Pract 1980;10:795-801.
5. Sugarman JR, Berg AO. Evaluation of fatigue in a family practice. J Fam Pract 1984;19:643-7.
6. Elnicki M, Shockcor WT, Brick E, Beynon D. Evaluating the compliant of fatigue in primary care: diagnoses and outcomes. Am J Med 1992;93:303-6.
7. Valdini AF, Steinhardt S, Valicenti J, Jaffe A. A one-year follow-up of fatigued patients. J Fam Pract 1988;26:33-8.
8. Mulrow CD, Williams JW, Gerety MB, et al. Case-finding instruments for depression in primary care settings. Ann Intern Med 1995;123:913-21.
9. Case-finding instruments for depression. Two questions are as good as many. J Gen Intern Med. 1997;12:439-45.
1. Godwin M, Delva D, Miller K, et al. Investigating fatigue of less than 6 month’s duration: Guidelines for family physicians. Can Fam Phys 1999;45:373-9.
2. David A, Pelosi A, McDonald E, et al. Tired, weak, or in need of rest: fatigue among general practice attenders. BMJ 1990;301:1199-202.
3. Ridsdale L, Evans A, Jerrett W, et al. Patients with fatigue in general practice: a prospective study. BMJ 1993;307:103-6.
4. Morrison JD. Fatigue as a presenting complain in family practice. J Fam Pract 1980;10:795-801.
5. Sugarman JR, Berg AO. Evaluation of fatigue in a family practice. J Fam Pract 1984;19:643-7.
6. Elnicki M, Shockcor WT, Brick E, Beynon D. Evaluating the compliant of fatigue in primary care: diagnoses and outcomes. Am J Med 1992;93:303-6.
7. Valdini AF, Steinhardt S, Valicenti J, Jaffe A. A one-year follow-up of fatigued patients. J Fam Pract 1988;26:33-8.
8. Mulrow CD, Williams JW, Gerety MB, et al. Case-finding instruments for depression in primary care settings. Ann Intern Med 1995;123:913-21.
9. Case-finding instruments for depression. Two questions are as good as many. J Gen Intern Med. 1997;12:439-45.