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Is St. John’s wort an effective treatment for major depression?
BACKGROUND: A meta-analysis of 23 randomized trials published in 1996 found St. John’s wort (SJW) to be effective for treating depressive disorders. However, the trials have been criticized for such flaws as lack of standard diagnostic criteria, short duration, wide dose variation, failure to blind, lack of placebo use, and suboptimal doses of comparison antidepressants. This trial aimed to address those concerns.
POPULATION STUDIED: Patients with major depressive disorder according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition were recruited from 11 academic medical centers’ psychiatry outpatient clinics, and 200 met criteria for randomization. Treatment and control groups were similar, with a mean age of 41.4 years, 64% women, and 85% white. This was the first episode of major depression for 35% of the sample. Patients were excluded for risk of suicide, psychotropic medicine use, history of treatment-resistant depression, or recent enrollment in psychotherapy. Other conditions that led to exclusion were cognitive disorders, posttraumatic stress disorder, eating disorders, substance use disorder, panic disorder, bipolar or psychotic disorders, and borderline, antisocial, or schizotypal personality disorders.
STUDY DESIGN AND VALIDITY: This study was a multisite placebo-controlled trial. Allocation of assignment was concealed. The taste and smell of SJW were masked by using an odorless SJW extract. All patients received placebo for 1 week, and 16 patients were excluded either because they experienced a 25% improvement on the Hamilton Rating Scale for Depression (HAM-D) while taking placebo or had very low HAM-D scores after 1 week. Patients were then randomized to receive either 300 mg of SJW extract or an identical placebo tablet 3 times daily. At 4 weeks the dose increased to 4 times daily if no improvement occurred. The subjects were followed up for 8 weeks. The researchers addressed many of the concerns about previous studies by using standard diagnostic techniques and a standardized drug dose. The use of a placebo run-in period decreases the overall response rate of both groups. Therefore, it should not affect statistical significance in comparing the 2 groups, but the response rate may appear lower than the results seen in clinical practice. This study had the power to detect a 17.5% difference in response between SJW and placebo. Smaller differences may exist but may not be clinically meaningful.
OUTCOMES MEASURED: The researchers measured efficacy of treatment using standard assessment tools. The primary measure of efficacy was the difference in the rate of improvement between SJW and placebo on total HAM-D scores over 8 weeks. The researchers also looked for differences in response (50% improvement in HAM-D scores) and remission (a HAM-D score of ≤7 and a clinical global impression score of 1-2), and they did a subgroup analysis of patients with mild depression (HAM-D scores <23).
RESULTS: Of the 98 patients completing the placebo run-in and randomized to SJW, 80 completed the trial compared with 87 of 100 placebo-assigned patients. Both intention-to-treat and completer analysis were performed for all measures of effect. The rate of improvement over time was not significantly different between SJW and placebo (P=.58). The 26.5% clinical response for SJW was not significantly better at 8 weeks than the 18.6% response for placebo (P=.15). Remission rates were significantly higher for SJW compared with placebo in the intention-to-treat analysis (14.3%; 95% confidence interval [CI], 8.6%-22.8% vs 4.9%; 95% CI, 2.0%-11.3%, P=.02; number needed to treat=11). The only significant adverse outcome was headache, which occurred in 41% of patients taking SJW (number needed to harm=7).
This well-designed study did not find a significant benefit of SJW in the treatment of major depression. The study did not address treatment of dysthymia or minor depression. Patients treated with SJW did not respond better than those taking placebo. Although remission rates were significantly better than those in the placebo group, these rates were very low for both groups. Given the seriousness of major depression and the availability of effective alternatives, SJW should not be used as first-line therapy for major depression.
BACKGROUND: A meta-analysis of 23 randomized trials published in 1996 found St. John’s wort (SJW) to be effective for treating depressive disorders. However, the trials have been criticized for such flaws as lack of standard diagnostic criteria, short duration, wide dose variation, failure to blind, lack of placebo use, and suboptimal doses of comparison antidepressants. This trial aimed to address those concerns.
POPULATION STUDIED: Patients with major depressive disorder according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition were recruited from 11 academic medical centers’ psychiatry outpatient clinics, and 200 met criteria for randomization. Treatment and control groups were similar, with a mean age of 41.4 years, 64% women, and 85% white. This was the first episode of major depression for 35% of the sample. Patients were excluded for risk of suicide, psychotropic medicine use, history of treatment-resistant depression, or recent enrollment in psychotherapy. Other conditions that led to exclusion were cognitive disorders, posttraumatic stress disorder, eating disorders, substance use disorder, panic disorder, bipolar or psychotic disorders, and borderline, antisocial, or schizotypal personality disorders.
STUDY DESIGN AND VALIDITY: This study was a multisite placebo-controlled trial. Allocation of assignment was concealed. The taste and smell of SJW were masked by using an odorless SJW extract. All patients received placebo for 1 week, and 16 patients were excluded either because they experienced a 25% improvement on the Hamilton Rating Scale for Depression (HAM-D) while taking placebo or had very low HAM-D scores after 1 week. Patients were then randomized to receive either 300 mg of SJW extract or an identical placebo tablet 3 times daily. At 4 weeks the dose increased to 4 times daily if no improvement occurred. The subjects were followed up for 8 weeks. The researchers addressed many of the concerns about previous studies by using standard diagnostic techniques and a standardized drug dose. The use of a placebo run-in period decreases the overall response rate of both groups. Therefore, it should not affect statistical significance in comparing the 2 groups, but the response rate may appear lower than the results seen in clinical practice. This study had the power to detect a 17.5% difference in response between SJW and placebo. Smaller differences may exist but may not be clinically meaningful.
OUTCOMES MEASURED: The researchers measured efficacy of treatment using standard assessment tools. The primary measure of efficacy was the difference in the rate of improvement between SJW and placebo on total HAM-D scores over 8 weeks. The researchers also looked for differences in response (50% improvement in HAM-D scores) and remission (a HAM-D score of ≤7 and a clinical global impression score of 1-2), and they did a subgroup analysis of patients with mild depression (HAM-D scores <23).
RESULTS: Of the 98 patients completing the placebo run-in and randomized to SJW, 80 completed the trial compared with 87 of 100 placebo-assigned patients. Both intention-to-treat and completer analysis were performed for all measures of effect. The rate of improvement over time was not significantly different between SJW and placebo (P=.58). The 26.5% clinical response for SJW was not significantly better at 8 weeks than the 18.6% response for placebo (P=.15). Remission rates were significantly higher for SJW compared with placebo in the intention-to-treat analysis (14.3%; 95% confidence interval [CI], 8.6%-22.8% vs 4.9%; 95% CI, 2.0%-11.3%, P=.02; number needed to treat=11). The only significant adverse outcome was headache, which occurred in 41% of patients taking SJW (number needed to harm=7).
This well-designed study did not find a significant benefit of SJW in the treatment of major depression. The study did not address treatment of dysthymia or minor depression. Patients treated with SJW did not respond better than those taking placebo. Although remission rates were significantly better than those in the placebo group, these rates were very low for both groups. Given the seriousness of major depression and the availability of effective alternatives, SJW should not be used as first-line therapy for major depression.
BACKGROUND: A meta-analysis of 23 randomized trials published in 1996 found St. John’s wort (SJW) to be effective for treating depressive disorders. However, the trials have been criticized for such flaws as lack of standard diagnostic criteria, short duration, wide dose variation, failure to blind, lack of placebo use, and suboptimal doses of comparison antidepressants. This trial aimed to address those concerns.
POPULATION STUDIED: Patients with major depressive disorder according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition were recruited from 11 academic medical centers’ psychiatry outpatient clinics, and 200 met criteria for randomization. Treatment and control groups were similar, with a mean age of 41.4 years, 64% women, and 85% white. This was the first episode of major depression for 35% of the sample. Patients were excluded for risk of suicide, psychotropic medicine use, history of treatment-resistant depression, or recent enrollment in psychotherapy. Other conditions that led to exclusion were cognitive disorders, posttraumatic stress disorder, eating disorders, substance use disorder, panic disorder, bipolar or psychotic disorders, and borderline, antisocial, or schizotypal personality disorders.
STUDY DESIGN AND VALIDITY: This study was a multisite placebo-controlled trial. Allocation of assignment was concealed. The taste and smell of SJW were masked by using an odorless SJW extract. All patients received placebo for 1 week, and 16 patients were excluded either because they experienced a 25% improvement on the Hamilton Rating Scale for Depression (HAM-D) while taking placebo or had very low HAM-D scores after 1 week. Patients were then randomized to receive either 300 mg of SJW extract or an identical placebo tablet 3 times daily. At 4 weeks the dose increased to 4 times daily if no improvement occurred. The subjects were followed up for 8 weeks. The researchers addressed many of the concerns about previous studies by using standard diagnostic techniques and a standardized drug dose. The use of a placebo run-in period decreases the overall response rate of both groups. Therefore, it should not affect statistical significance in comparing the 2 groups, but the response rate may appear lower than the results seen in clinical practice. This study had the power to detect a 17.5% difference in response between SJW and placebo. Smaller differences may exist but may not be clinically meaningful.
OUTCOMES MEASURED: The researchers measured efficacy of treatment using standard assessment tools. The primary measure of efficacy was the difference in the rate of improvement between SJW and placebo on total HAM-D scores over 8 weeks. The researchers also looked for differences in response (50% improvement in HAM-D scores) and remission (a HAM-D score of ≤7 and a clinical global impression score of 1-2), and they did a subgroup analysis of patients with mild depression (HAM-D scores <23).
RESULTS: Of the 98 patients completing the placebo run-in and randomized to SJW, 80 completed the trial compared with 87 of 100 placebo-assigned patients. Both intention-to-treat and completer analysis were performed for all measures of effect. The rate of improvement over time was not significantly different between SJW and placebo (P=.58). The 26.5% clinical response for SJW was not significantly better at 8 weeks than the 18.6% response for placebo (P=.15). Remission rates were significantly higher for SJW compared with placebo in the intention-to-treat analysis (14.3%; 95% confidence interval [CI], 8.6%-22.8% vs 4.9%; 95% CI, 2.0%-11.3%, P=.02; number needed to treat=11). The only significant adverse outcome was headache, which occurred in 41% of patients taking SJW (number needed to harm=7).
This well-designed study did not find a significant benefit of SJW in the treatment of major depression. The study did not address treatment of dysthymia or minor depression. Patients treated with SJW did not respond better than those taking placebo. Although remission rates were significantly better than those in the placebo group, these rates were very low for both groups. Given the seriousness of major depression and the availability of effective alternatives, SJW should not be used as first-line therapy for major depression.
At what age do patients no longer need colorectal cancer screening?
Good evidence supports fecal occult blood testing (FOBT) for patients up to age 75 (grade of recommendation: A, based on systematic review of randomized controlled trials). There is insufficient evidence to recommend for or against colorectal cancer (CRC) screening after age 75 (grade of recommendation: D, based on expert opinion). CRC screening may be discontinued between ages 75 and 80, preferably after at least 1 negative screening examination result. Unusually healthy individuals may choose to continue screening until a later age.
Evidence summary
FOBT is the only CRC screening tool with evidence of efficacy from randomized controlled trials.1 A meta-analysis of 4 trials showed that 1173 patients would need to be screened for 10 years on a biennial basis to prevent 1 death from CRC. The upper age limits of patients were 75,2 64,3 74,4 and 80 years.5 In the one study that included subjects to age 80, only 13% were older than 70 years. One case control study of FOBT showed a significant reduction in risk of mortality from CRC for individuals younger than 75 years, but not for patients older than 75; however, confidence intervals were wide.6
Evidence for screening with flexible sigmoidoscopy and colonoscopy comes primarily from case-control studies, and little information about appropriate upperage limits is available.7-9 However, average time from onset of polyp to carcinoma is 10 to 15 years.10 Furthermore, cancers, large polyps (>1 cm), or dysplastic polyps were not found in any patient examined a mean of 3.4 years after normal flexible sigmoidoscopy,11 and subsequent cancer is a rare early event after endoscopy, even in patients who have had polyps removed.12 This suggests the cessation of endoscopic screening would miss few cancers in the very old.
While CRC incidence approximately doubles with each decade from age 40 to 80,13 the average life expectancy is 11.2 years at age 75 and 8.5 years at age 80.14 Given the slow progression from polyp to carcinoma, such patients may not live long enough to achieve any screening benefits. Similar reasoning suggests that even high-risk patients (eg, those with a family history of CRC) with repeatedly normal endoscopic examination results may be able to discontinue screening between ages 75 and 80, unless they are unusually healthy.
Risks of screening include discomfort from endoscopic examinations and complications relating to the many false-positive results of FOBT (98% in Minnesota study).5 A meta-analysis found that patients experience 1 perforation or hemorrhage for every 2.5 to 4.7 lives saved.1 The risk of death is only about 1 in 50,000 for colonoscopy at the Mayo Clinic.15 Other complications include worry, perforation, and complications of treatment.
Recommendations from others
The USPSTF, AAFP, American Gastroenterology Association, and the American Cancer Society recommend screening adults 50 years of age and older for colon cancer; none sets an upper limit.16-20 The USPSTF specifically states, “the appropriate age to discontinue screening has not been determined.”16 The American Geriatrics Society recommends that patients with short life expectancy or patients who could not undergo colonoscopy or barium enema plus sigmoidoscopy should not be screened.21
Brian Easton, MD
Highlands Family Medicine Lebanon, Virginia
Knowing the average time from onset of polyp to carcinoma and the life expectancy at 75 and 80 years old is very helpful. This gives support to using endoscopy in addition to FOBT instead of FOBT alone, especially during the period before the cessation of routine screening. A negative sigmoidoscopy result would “insure” the next 3 to 5 years and colonoscopy the next 10 years. After explaining the benefits of screening, I tell my patients that when they complete a FOBT each year, they have a 10% to 40% chance of having a colonoscopy, and if they have this follow-up procedure, they have a 0.3% or less chance of having a perforation or hemorrhage as a complication.1-5 Most of my patients older than 75 years choose not to continue screening.
1. Towler BP, Irwig L, Glasziou P, Weller D, Kewenter J. Screening for colorectal cancer using the fecal occult blood test, Hemoccult (Cochrane Review). The Cochrane Library. Oxford, UK: Update Software; 2001.
2. Kronborg O, Fenger C, Olsen J, Jorgensen OD, Sondergaard O. Randomised study of screening for colorectal cancer with fecal occult blood test. Lancet 1996;348:1467-71.
3. Kewenter J, Brevinge H, Engaras B, Haglind E, Ahren C. Results of screening, rescreening, and follow-up in a prospective randomized study for detection of colorectal cancer by fecal occult blood testing. Results for 68,308 subjects. Scand J Gastroenterol. 1994;29:468-73.
4. Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomised controlled trial of fecal-occult-blood screening for colorectal cancer. Lancet 1996;348:1472-77.
5. Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993;328:1365-71.
6. Lazovich D, Weiss NS, Stevens NG, White E, McKnight B, Wagner EH. A case-control study to evaluate efficacy of screening for fecal occult blood. J Med Screen 1995;2:84-9.
7. Newcomb PA, Norfleet RG, Storer BE, Surawicz TS, Marcus PM. Screening sigmoidoscopy and colorectal cancer mortality. J Natl Cancer Inst 1992;84:1572-75.
8. Muller AD, Sonnenberg A. Protection by endoscopy against death from colorectal cancer. A case-control study among veterans. Arch Intern Med 1995;155:1741-48.
9. Selby JV, Friedman GD, Quesenberry CP, Jr, Weiss NS. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 1992;326:653-57.
10. Scholefield JH. ABC of colorectal cancer—screening. BMJ 2000;321:1004-06.
11. Rex DK, Lehman GA, Ulbright TM, Smith JJ, Hawes RH. The yield of a second screening flexible sigmoidoscopy in average-risk persons after one negative examination. Gastroenterology 1994;106:593-95.
12. Atkin WS, Morson BC, Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N Engl J Med 1992;326:658-62.
13. Mulcahy HE, Farthing MJ, O’Donoghue DP. Screening for asymptomatic colorectal cancer. BMJ 1997;314:285-91.
14. Anderson RN. United States life tables, 1997. National Vital Statistics Reports 1999;47:1-37.
15. Anderson ML, Pasha TM, Leighton JA. Endoscopic perforation of the colon: lessons from a 10 year study. Am J Gastroenterol 2000;95:3418-22.
16. US Preventive Services Task Force Screening for colorectal cancer. Guide to clinical preventive services: report of the US Preventive Services Task Force. Baltimore, MD: Williams & Wilkins; 1996;89-103.
17. Periodic health examinations: summary of AAFP policy recommendations and age charts Positive recommendations: general population standards. Last updated 2000. Accessed on 12-6-2000.
18. Winawer SJ, Flehinger BJ, Schottenfeld D, Miller DG. Screening for colorectal cancer with fecal occult blood testing and sigmoidoscopy. J Natl Cancer Inst 1993;85:1311-18.
19. Byers T, Levin B, Rothenberger D, Dodd GD, Smith RA. American Cancer Society guidelines for screening and surveillance for early detection of colorectal polyps and cancer: update 1997. American Cancer Society Detection and Treatment Advisory Group on Colorectal Cancer. CA Cancer J Clin 1997;47:154-160.
20. Colorectal Cancer Screening: Clinical Guidelines and Rationale. Gastroenterology 1997;112:594-642.
21. Colon cancer screening (USPSTF recommendation). US Preventive Services Task Force. J Am Geriatr Soc 2000;48:333-35.
Good evidence supports fecal occult blood testing (FOBT) for patients up to age 75 (grade of recommendation: A, based on systematic review of randomized controlled trials). There is insufficient evidence to recommend for or against colorectal cancer (CRC) screening after age 75 (grade of recommendation: D, based on expert opinion). CRC screening may be discontinued between ages 75 and 80, preferably after at least 1 negative screening examination result. Unusually healthy individuals may choose to continue screening until a later age.
Evidence summary
FOBT is the only CRC screening tool with evidence of efficacy from randomized controlled trials.1 A meta-analysis of 4 trials showed that 1173 patients would need to be screened for 10 years on a biennial basis to prevent 1 death from CRC. The upper age limits of patients were 75,2 64,3 74,4 and 80 years.5 In the one study that included subjects to age 80, only 13% were older than 70 years. One case control study of FOBT showed a significant reduction in risk of mortality from CRC for individuals younger than 75 years, but not for patients older than 75; however, confidence intervals were wide.6
Evidence for screening with flexible sigmoidoscopy and colonoscopy comes primarily from case-control studies, and little information about appropriate upperage limits is available.7-9 However, average time from onset of polyp to carcinoma is 10 to 15 years.10 Furthermore, cancers, large polyps (>1 cm), or dysplastic polyps were not found in any patient examined a mean of 3.4 years after normal flexible sigmoidoscopy,11 and subsequent cancer is a rare early event after endoscopy, even in patients who have had polyps removed.12 This suggests the cessation of endoscopic screening would miss few cancers in the very old.
While CRC incidence approximately doubles with each decade from age 40 to 80,13 the average life expectancy is 11.2 years at age 75 and 8.5 years at age 80.14 Given the slow progression from polyp to carcinoma, such patients may not live long enough to achieve any screening benefits. Similar reasoning suggests that even high-risk patients (eg, those with a family history of CRC) with repeatedly normal endoscopic examination results may be able to discontinue screening between ages 75 and 80, unless they are unusually healthy.
Risks of screening include discomfort from endoscopic examinations and complications relating to the many false-positive results of FOBT (98% in Minnesota study).5 A meta-analysis found that patients experience 1 perforation or hemorrhage for every 2.5 to 4.7 lives saved.1 The risk of death is only about 1 in 50,000 for colonoscopy at the Mayo Clinic.15 Other complications include worry, perforation, and complications of treatment.
Recommendations from others
The USPSTF, AAFP, American Gastroenterology Association, and the American Cancer Society recommend screening adults 50 years of age and older for colon cancer; none sets an upper limit.16-20 The USPSTF specifically states, “the appropriate age to discontinue screening has not been determined.”16 The American Geriatrics Society recommends that patients with short life expectancy or patients who could not undergo colonoscopy or barium enema plus sigmoidoscopy should not be screened.21
Brian Easton, MD
Highlands Family Medicine Lebanon, Virginia
Knowing the average time from onset of polyp to carcinoma and the life expectancy at 75 and 80 years old is very helpful. This gives support to using endoscopy in addition to FOBT instead of FOBT alone, especially during the period before the cessation of routine screening. A negative sigmoidoscopy result would “insure” the next 3 to 5 years and colonoscopy the next 10 years. After explaining the benefits of screening, I tell my patients that when they complete a FOBT each year, they have a 10% to 40% chance of having a colonoscopy, and if they have this follow-up procedure, they have a 0.3% or less chance of having a perforation or hemorrhage as a complication.1-5 Most of my patients older than 75 years choose not to continue screening.
Good evidence supports fecal occult blood testing (FOBT) for patients up to age 75 (grade of recommendation: A, based on systematic review of randomized controlled trials). There is insufficient evidence to recommend for or against colorectal cancer (CRC) screening after age 75 (grade of recommendation: D, based on expert opinion). CRC screening may be discontinued between ages 75 and 80, preferably after at least 1 negative screening examination result. Unusually healthy individuals may choose to continue screening until a later age.
Evidence summary
FOBT is the only CRC screening tool with evidence of efficacy from randomized controlled trials.1 A meta-analysis of 4 trials showed that 1173 patients would need to be screened for 10 years on a biennial basis to prevent 1 death from CRC. The upper age limits of patients were 75,2 64,3 74,4 and 80 years.5 In the one study that included subjects to age 80, only 13% were older than 70 years. One case control study of FOBT showed a significant reduction in risk of mortality from CRC for individuals younger than 75 years, but not for patients older than 75; however, confidence intervals were wide.6
Evidence for screening with flexible sigmoidoscopy and colonoscopy comes primarily from case-control studies, and little information about appropriate upperage limits is available.7-9 However, average time from onset of polyp to carcinoma is 10 to 15 years.10 Furthermore, cancers, large polyps (>1 cm), or dysplastic polyps were not found in any patient examined a mean of 3.4 years after normal flexible sigmoidoscopy,11 and subsequent cancer is a rare early event after endoscopy, even in patients who have had polyps removed.12 This suggests the cessation of endoscopic screening would miss few cancers in the very old.
While CRC incidence approximately doubles with each decade from age 40 to 80,13 the average life expectancy is 11.2 years at age 75 and 8.5 years at age 80.14 Given the slow progression from polyp to carcinoma, such patients may not live long enough to achieve any screening benefits. Similar reasoning suggests that even high-risk patients (eg, those with a family history of CRC) with repeatedly normal endoscopic examination results may be able to discontinue screening between ages 75 and 80, unless they are unusually healthy.
Risks of screening include discomfort from endoscopic examinations and complications relating to the many false-positive results of FOBT (98% in Minnesota study).5 A meta-analysis found that patients experience 1 perforation or hemorrhage for every 2.5 to 4.7 lives saved.1 The risk of death is only about 1 in 50,000 for colonoscopy at the Mayo Clinic.15 Other complications include worry, perforation, and complications of treatment.
Recommendations from others
The USPSTF, AAFP, American Gastroenterology Association, and the American Cancer Society recommend screening adults 50 years of age and older for colon cancer; none sets an upper limit.16-20 The USPSTF specifically states, “the appropriate age to discontinue screening has not been determined.”16 The American Geriatrics Society recommends that patients with short life expectancy or patients who could not undergo colonoscopy or barium enema plus sigmoidoscopy should not be screened.21
Brian Easton, MD
Highlands Family Medicine Lebanon, Virginia
Knowing the average time from onset of polyp to carcinoma and the life expectancy at 75 and 80 years old is very helpful. This gives support to using endoscopy in addition to FOBT instead of FOBT alone, especially during the period before the cessation of routine screening. A negative sigmoidoscopy result would “insure” the next 3 to 5 years and colonoscopy the next 10 years. After explaining the benefits of screening, I tell my patients that when they complete a FOBT each year, they have a 10% to 40% chance of having a colonoscopy, and if they have this follow-up procedure, they have a 0.3% or less chance of having a perforation or hemorrhage as a complication.1-5 Most of my patients older than 75 years choose not to continue screening.
1. Towler BP, Irwig L, Glasziou P, Weller D, Kewenter J. Screening for colorectal cancer using the fecal occult blood test, Hemoccult (Cochrane Review). The Cochrane Library. Oxford, UK: Update Software; 2001.
2. Kronborg O, Fenger C, Olsen J, Jorgensen OD, Sondergaard O. Randomised study of screening for colorectal cancer with fecal occult blood test. Lancet 1996;348:1467-71.
3. Kewenter J, Brevinge H, Engaras B, Haglind E, Ahren C. Results of screening, rescreening, and follow-up in a prospective randomized study for detection of colorectal cancer by fecal occult blood testing. Results for 68,308 subjects. Scand J Gastroenterol. 1994;29:468-73.
4. Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomised controlled trial of fecal-occult-blood screening for colorectal cancer. Lancet 1996;348:1472-77.
5. Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993;328:1365-71.
6. Lazovich D, Weiss NS, Stevens NG, White E, McKnight B, Wagner EH. A case-control study to evaluate efficacy of screening for fecal occult blood. J Med Screen 1995;2:84-9.
7. Newcomb PA, Norfleet RG, Storer BE, Surawicz TS, Marcus PM. Screening sigmoidoscopy and colorectal cancer mortality. J Natl Cancer Inst 1992;84:1572-75.
8. Muller AD, Sonnenberg A. Protection by endoscopy against death from colorectal cancer. A case-control study among veterans. Arch Intern Med 1995;155:1741-48.
9. Selby JV, Friedman GD, Quesenberry CP, Jr, Weiss NS. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 1992;326:653-57.
10. Scholefield JH. ABC of colorectal cancer—screening. BMJ 2000;321:1004-06.
11. Rex DK, Lehman GA, Ulbright TM, Smith JJ, Hawes RH. The yield of a second screening flexible sigmoidoscopy in average-risk persons after one negative examination. Gastroenterology 1994;106:593-95.
12. Atkin WS, Morson BC, Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N Engl J Med 1992;326:658-62.
13. Mulcahy HE, Farthing MJ, O’Donoghue DP. Screening for asymptomatic colorectal cancer. BMJ 1997;314:285-91.
14. Anderson RN. United States life tables, 1997. National Vital Statistics Reports 1999;47:1-37.
15. Anderson ML, Pasha TM, Leighton JA. Endoscopic perforation of the colon: lessons from a 10 year study. Am J Gastroenterol 2000;95:3418-22.
16. US Preventive Services Task Force Screening for colorectal cancer. Guide to clinical preventive services: report of the US Preventive Services Task Force. Baltimore, MD: Williams & Wilkins; 1996;89-103.
17. Periodic health examinations: summary of AAFP policy recommendations and age charts Positive recommendations: general population standards. Last updated 2000. Accessed on 12-6-2000.
18. Winawer SJ, Flehinger BJ, Schottenfeld D, Miller DG. Screening for colorectal cancer with fecal occult blood testing and sigmoidoscopy. J Natl Cancer Inst 1993;85:1311-18.
19. Byers T, Levin B, Rothenberger D, Dodd GD, Smith RA. American Cancer Society guidelines for screening and surveillance for early detection of colorectal polyps and cancer: update 1997. American Cancer Society Detection and Treatment Advisory Group on Colorectal Cancer. CA Cancer J Clin 1997;47:154-160.
20. Colorectal Cancer Screening: Clinical Guidelines and Rationale. Gastroenterology 1997;112:594-642.
21. Colon cancer screening (USPSTF recommendation). US Preventive Services Task Force. J Am Geriatr Soc 2000;48:333-35.
1. Towler BP, Irwig L, Glasziou P, Weller D, Kewenter J. Screening for colorectal cancer using the fecal occult blood test, Hemoccult (Cochrane Review). The Cochrane Library. Oxford, UK: Update Software; 2001.
2. Kronborg O, Fenger C, Olsen J, Jorgensen OD, Sondergaard O. Randomised study of screening for colorectal cancer with fecal occult blood test. Lancet 1996;348:1467-71.
3. Kewenter J, Brevinge H, Engaras B, Haglind E, Ahren C. Results of screening, rescreening, and follow-up in a prospective randomized study for detection of colorectal cancer by fecal occult blood testing. Results for 68,308 subjects. Scand J Gastroenterol. 1994;29:468-73.
4. Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomised controlled trial of fecal-occult-blood screening for colorectal cancer. Lancet 1996;348:1472-77.
5. Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993;328:1365-71.
6. Lazovich D, Weiss NS, Stevens NG, White E, McKnight B, Wagner EH. A case-control study to evaluate efficacy of screening for fecal occult blood. J Med Screen 1995;2:84-9.
7. Newcomb PA, Norfleet RG, Storer BE, Surawicz TS, Marcus PM. Screening sigmoidoscopy and colorectal cancer mortality. J Natl Cancer Inst 1992;84:1572-75.
8. Muller AD, Sonnenberg A. Protection by endoscopy against death from colorectal cancer. A case-control study among veterans. Arch Intern Med 1995;155:1741-48.
9. Selby JV, Friedman GD, Quesenberry CP, Jr, Weiss NS. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 1992;326:653-57.
10. Scholefield JH. ABC of colorectal cancer—screening. BMJ 2000;321:1004-06.
11. Rex DK, Lehman GA, Ulbright TM, Smith JJ, Hawes RH. The yield of a second screening flexible sigmoidoscopy in average-risk persons after one negative examination. Gastroenterology 1994;106:593-95.
12. Atkin WS, Morson BC, Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N Engl J Med 1992;326:658-62.
13. Mulcahy HE, Farthing MJ, O’Donoghue DP. Screening for asymptomatic colorectal cancer. BMJ 1997;314:285-91.
14. Anderson RN. United States life tables, 1997. National Vital Statistics Reports 1999;47:1-37.
15. Anderson ML, Pasha TM, Leighton JA. Endoscopic perforation of the colon: lessons from a 10 year study. Am J Gastroenterol 2000;95:3418-22.
16. US Preventive Services Task Force Screening for colorectal cancer. Guide to clinical preventive services: report of the US Preventive Services Task Force. Baltimore, MD: Williams & Wilkins; 1996;89-103.
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Evidence-based answers from the Family Physicians Inquiries Network
Which venous leg ulcers will heal using limb compression bandages?
BACKGROUND: Limb compression bandages, such as Unna boots, successfully treat 30% to 60% of venous leg ulcers. The authors of this study attempted to create a simple model to predict which patients’ ulcers will heal using this therapy.
POPULATION STUDIED: All patients were drawn from a dermatology skin ulcer clinic. A training group of 260 consecutive patients with chronic venous leg ulcers was used to develop predictive models. Venous ulcers were defined as wounds in the “gaiter area” of the limb from the mid-calf to 1 inch below the malleolus. All patients had lower leg edema and cutaneous evidence of venous disease. second group of 219 patients enrolled in the control arm of 2 randomized controlled trials testing skin allograft versus compression was used to validate the rule. Ulcers in this study were at least 4 weeks old and between 0.5 and 200 cm2 in area.
STUDY DESIGN AND VALIDITY: This was a cohort study for developing and validating a clinical decision rule. Prognostic models were created with 10 risk factors and statistically analyzed for their ability to correctly predict wound healing. The models were simplified by dropping prognostic factors one by one from the model, as long as the ability to predict healing was not affected. All of the models were evaluated by measuring the area under the receiver-operating characteristic (ROC) curve. By definition, an area closer to 1 indicates a better ability to distinguish which ulcers will heal. An area of 0.5 indicates a worthless test or rule. The most accurate model from the training group was evaluated using the validation group.
OUTCOMES MEASURED: The primary outcome measure was the ability of a model to predict wound healing within 24 weeks as measured by the area under the ROC curve.
RESULTS: Overall, 65% of ulcers from the training group and 56% of ulcers from the validation group healed by 24 weeks. All of the candidate models had areas under the ROC curve greater than 0.80, meaning that the model discriminated between ulcers that did and did not heal more than 80% of the time. The simplest model, which gave a score of 1 point for a wound area greater than 5 cm2 (measured by a template) and 1 point for wound age greater than 6 months, correctly predicted healing 87% of the time. Ulcers with a score of 0 healed in 95% of the validation group, while ulcers with a score of 1 healed in 73% of the validation group.
This simple rule accurately predicts which venous stasis ulcers will heal in 6 months using compression bandages. Score 1 point for a wound older than 6 months and 1 point if the area of the wound is greater than 5 cm2 as measured by a template. Ulcers with a score of 0 are 95% likely to heal, while those with a score of 2 are only 37% likely to heal. Patients whose ulcers rate a score of 0 can be treated with compression bandages and are unlikely to need referral. Whether newer therapies will add benefit for patients with a score of 1 or 2 is unknown. Early referral of patients with ulcers with a score of 2 will likely depend on local practice.
BACKGROUND: Limb compression bandages, such as Unna boots, successfully treat 30% to 60% of venous leg ulcers. The authors of this study attempted to create a simple model to predict which patients’ ulcers will heal using this therapy.
POPULATION STUDIED: All patients were drawn from a dermatology skin ulcer clinic. A training group of 260 consecutive patients with chronic venous leg ulcers was used to develop predictive models. Venous ulcers were defined as wounds in the “gaiter area” of the limb from the mid-calf to 1 inch below the malleolus. All patients had lower leg edema and cutaneous evidence of venous disease. second group of 219 patients enrolled in the control arm of 2 randomized controlled trials testing skin allograft versus compression was used to validate the rule. Ulcers in this study were at least 4 weeks old and between 0.5 and 200 cm2 in area.
STUDY DESIGN AND VALIDITY: This was a cohort study for developing and validating a clinical decision rule. Prognostic models were created with 10 risk factors and statistically analyzed for their ability to correctly predict wound healing. The models were simplified by dropping prognostic factors one by one from the model, as long as the ability to predict healing was not affected. All of the models were evaluated by measuring the area under the receiver-operating characteristic (ROC) curve. By definition, an area closer to 1 indicates a better ability to distinguish which ulcers will heal. An area of 0.5 indicates a worthless test or rule. The most accurate model from the training group was evaluated using the validation group.
OUTCOMES MEASURED: The primary outcome measure was the ability of a model to predict wound healing within 24 weeks as measured by the area under the ROC curve.
RESULTS: Overall, 65% of ulcers from the training group and 56% of ulcers from the validation group healed by 24 weeks. All of the candidate models had areas under the ROC curve greater than 0.80, meaning that the model discriminated between ulcers that did and did not heal more than 80% of the time. The simplest model, which gave a score of 1 point for a wound area greater than 5 cm2 (measured by a template) and 1 point for wound age greater than 6 months, correctly predicted healing 87% of the time. Ulcers with a score of 0 healed in 95% of the validation group, while ulcers with a score of 1 healed in 73% of the validation group.
This simple rule accurately predicts which venous stasis ulcers will heal in 6 months using compression bandages. Score 1 point for a wound older than 6 months and 1 point if the area of the wound is greater than 5 cm2 as measured by a template. Ulcers with a score of 0 are 95% likely to heal, while those with a score of 2 are only 37% likely to heal. Patients whose ulcers rate a score of 0 can be treated with compression bandages and are unlikely to need referral. Whether newer therapies will add benefit for patients with a score of 1 or 2 is unknown. Early referral of patients with ulcers with a score of 2 will likely depend on local practice.
BACKGROUND: Limb compression bandages, such as Unna boots, successfully treat 30% to 60% of venous leg ulcers. The authors of this study attempted to create a simple model to predict which patients’ ulcers will heal using this therapy.
POPULATION STUDIED: All patients were drawn from a dermatology skin ulcer clinic. A training group of 260 consecutive patients with chronic venous leg ulcers was used to develop predictive models. Venous ulcers were defined as wounds in the “gaiter area” of the limb from the mid-calf to 1 inch below the malleolus. All patients had lower leg edema and cutaneous evidence of venous disease. second group of 219 patients enrolled in the control arm of 2 randomized controlled trials testing skin allograft versus compression was used to validate the rule. Ulcers in this study were at least 4 weeks old and between 0.5 and 200 cm2 in area.
STUDY DESIGN AND VALIDITY: This was a cohort study for developing and validating a clinical decision rule. Prognostic models were created with 10 risk factors and statistically analyzed for their ability to correctly predict wound healing. The models were simplified by dropping prognostic factors one by one from the model, as long as the ability to predict healing was not affected. All of the models were evaluated by measuring the area under the receiver-operating characteristic (ROC) curve. By definition, an area closer to 1 indicates a better ability to distinguish which ulcers will heal. An area of 0.5 indicates a worthless test or rule. The most accurate model from the training group was evaluated using the validation group.
OUTCOMES MEASURED: The primary outcome measure was the ability of a model to predict wound healing within 24 weeks as measured by the area under the ROC curve.
RESULTS: Overall, 65% of ulcers from the training group and 56% of ulcers from the validation group healed by 24 weeks. All of the candidate models had areas under the ROC curve greater than 0.80, meaning that the model discriminated between ulcers that did and did not heal more than 80% of the time. The simplest model, which gave a score of 1 point for a wound area greater than 5 cm2 (measured by a template) and 1 point for wound age greater than 6 months, correctly predicted healing 87% of the time. Ulcers with a score of 0 healed in 95% of the validation group, while ulcers with a score of 1 healed in 73% of the validation group.
This simple rule accurately predicts which venous stasis ulcers will heal in 6 months using compression bandages. Score 1 point for a wound older than 6 months and 1 point if the area of the wound is greater than 5 cm2 as measured by a template. Ulcers with a score of 0 are 95% likely to heal, while those with a score of 2 are only 37% likely to heal. Patients whose ulcers rate a score of 0 can be treated with compression bandages and are unlikely to need referral. Whether newer therapies will add benefit for patients with a score of 1 or 2 is unknown. Early referral of patients with ulcers with a score of 2 will likely depend on local practice.