Clinical Inquiries

Evidence summary

A recent systematic review found NSAIDs more effective than placebo for pain relief in patients with acute low back pain.¹ There is conflicting evidence regarding the effectiveness of NSAIDs versus acetaminophen or narcotics alone.

According to another systematic review, there is no difference in pain intensity at 3 weeks’ follow-up between active patients and patients for whom variable lengths of short-term bed rest for treatment of acute low back pain have been prescribed.² No consistent conclusions could be drawn regarding the effectiveness of epidural steroid injections for acute low back pain.³ This analysis was limited by the inclusion of all studies of patients with acute low back pain regardless of the underlying etiology and presence or absence of radicular symptoms. A systematic review of 12 trials reported inconsistent results of facet joint, epidural, and local corticosteroid injections; however, only 1 studied epidural injections.⁴

Cyclobenzaprine is more effective than placebo, according to a recent systematic review summary (odds ratio for improvement by day 10: 4.7 [2.7-8.1 95% CI]; number needed to treat [NNT] = 2.7 [2.0-4.2 95% CI]).⁵ There is no statistically significant difference in pain relief between patients using NSAIDs alone versus those using both NSAIDs and muscle relaxants.¹ The use of muscle relaxants was associated with more adverse reactions than placebo (53% vs 28%; number needed to harm [NNH] = 4).

Performance of specific flexion or extension exercises was no more effective than analgesics.⁶ In a randomized, controlled trial (n = 321) to assess the effectiveness of formal physical therapy for acute low back pain, patients referred to physical therapy were more satisfied with their care than were patients given handouts on back exercises, even though disability and pain scores were unchanged.⁷ Evidence is insufficient to support the use of spinal manipulation in patients with acute low back pain because of serious design flaws in the trials.⁸

Recommendations from others

The Institute for Clinical Systems Improvement recommends conservative treatment such as cold and heat therapies and over-the-counter anti-inflammatory or analgesic drugs as the first line of treatment. Patients with acute low back pain should stay active and continue routine activity within the limits permitted by the pain.⁹ The Agency for Health Care Policy and Research states that acetaminophen is the treatment of choice for low back pain and that NSAIDs should be used sparingly because of their potential side effects. Manipulation is safe and effective in the first month in patients who do not have radicular symptoms.¹⁰

Evidence summary

A recent systematic review found NSAIDs more effective than placebo for pain relief in patients with acute low back pain.¹ There is conflicting evidence regarding the effectiveness of NSAIDs versus acetaminophen or narcotics alone.

According to another systematic review, there is no difference in pain intensity at 3 weeks’ follow-up between active patients and patients for whom variable lengths of short-term bed rest for treatment of acute low back pain have been prescribed.² No consistent conclusions could be drawn regarding the effectiveness of epidural steroid injections for acute low back pain.³ This analysis was limited by the inclusion of all studies of patients with acute low back pain regardless of the underlying etiology and presence or absence of radicular symptoms. A systematic review of 12 trials reported inconsistent results of facet joint, epidural, and local corticosteroid injections; however, only 1 studied epidural injections.⁴

Cyclobenzaprine is more effective than placebo, according to a recent systematic review summary (odds ratio for improvement by day 10: 4.7 [2.7-8.1 95% CI]; number needed to treat [NNT] = 2.7 [2.0-4.2 95% CI]).⁵ There is no statistically significant difference in pain relief between patients using NSAIDs alone versus those using both NSAIDs and muscle relaxants.¹ The use of muscle relaxants was associated with more adverse reactions than placebo (53% vs 28%; number needed to harm [NNH] = 4).

Performance of specific flexion or extension exercises was no more effective than analgesics.⁶ In a randomized, controlled trial (n = 321) to assess the effectiveness of formal physical therapy for acute low back pain, patients referred to physical therapy were more satisfied with their care than were patients given handouts on back exercises, even though disability and pain scores were unchanged.⁷ Evidence is insufficient to support the use of spinal manipulation in patients with acute low back pain because of serious design flaws in the trials.⁸

Recommendations from others

The Institute for Clinical Systems Improvement recommends conservative treatment such as cold and heat therapies and over-the-counter anti-inflammatory or analgesic drugs as the first line of treatment. Patients with acute low back pain should stay active and continue routine activity within the limits permitted by the pain.⁹ The Agency for Health Care Policy and Research states that acetaminophen is the treatment of choice for low back pain and that NSAIDs should be used sparingly because of their potential side effects. Manipulation is safe and effective in the first month in patients who do not have radicular symptoms.¹⁰

Evidence summary

A recent systematic review found NSAIDs more effective than placebo for pain relief in patients with acute low back pain.¹ There is conflicting evidence regarding the effectiveness of NSAIDs versus acetaminophen or narcotics alone.

According to another systematic review, there is no difference in pain intensity at 3 weeks’ follow-up between active patients and patients for whom variable lengths of short-term bed rest for treatment of acute low back pain have been prescribed.² No consistent conclusions could be drawn regarding the effectiveness of epidural steroid injections for acute low back pain.³ This analysis was limited by the inclusion of all studies of patients with acute low back pain regardless of the underlying etiology and presence or absence of radicular symptoms. A systematic review of 12 trials reported inconsistent results of facet joint, epidural, and local corticosteroid injections; however, only 1 studied epidural injections.⁴

Cyclobenzaprine is more effective than placebo, according to a recent systematic review summary (odds ratio for improvement by day 10: 4.7 [2.7-8.1 95% CI]; number needed to treat [NNT] = 2.7 [2.0-4.2 95% CI]).⁵ There is no statistically significant difference in pain relief between patients using NSAIDs alone versus those using both NSAIDs and muscle relaxants.¹ The use of muscle relaxants was associated with more adverse reactions than placebo (53% vs 28%; number needed to harm [NNH] = 4).

Performance of specific flexion or extension exercises was no more effective than analgesics.⁶ In a randomized, controlled trial (n = 321) to assess the effectiveness of formal physical therapy for acute low back pain, patients referred to physical therapy were more satisfied with their care than were patients given handouts on back exercises, even though disability and pain scores were unchanged.⁷ Evidence is insufficient to support the use of spinal manipulation in patients with acute low back pain because of serious design flaws in the trials.⁸

Recommendations from others

The Institute for Clinical Systems Improvement recommends conservative treatment such as cold and heat therapies and over-the-counter anti-inflammatory or analgesic drugs as the first line of treatment. Patients with acute low back pain should stay active and continue routine activity within the limits permitted by the pain.⁹ The Agency for Health Care Policy and Research states that acetaminophen is the treatment of choice for low back pain and that NSAIDs should be used sparingly because of their potential side effects. Manipulation is safe and effective in the first month in patients who do not have radicular symptoms.¹⁰

Evidence summary

In studies that evaluated onetime softening in the office to ease or eliminate the need for irrigation, a presoak with docusate sodium (Colace) was most effective, although its effects were not compared with those of water.¹ Both triethanolamine (Cerumenex) and olive oil were the next most effective treatments.² Carbamide peroxide (Debrox, Murine Ear) was least effective (see Table and Table W1*).³ In 1 small, carefully done study of ear candles, more candle wax was added than earwax was removed in the 8 ears tested.⁴

In studies that evaluated 3 to 14 days of home ceruminolysis to obviate or ease irritation, 5% urea hydrogen peroxide in glycerol was most effective.⁵ Sterile water, sodium bicarbonate in glycerol, 2% acetic acid (VoSoL, Domeboro), ethylene oxide polyoxypropylene (Addax), and acpd (arachis oil, chlorobutanol, p-dichlorobenzene [Cerumenol]) were all of equal efficacy.^6-8 All were more effective than no treatment. Notably, 5% of cases resolved completely and 26% became moderately clear after 5 days of no treatment (Table W2*).⁶

No direct comparisons exist of same-day in-office softening followed by irrigation or disimpaction against home softening followed by irrigation and manual disimpaction. Until more placebo-controlled data are generated, recommendations should be based on relative safety and on the direct comparison trials within each strategy. Complications of irrigation include otitis externa, perforation, canal trauma, pain, cough, tinnitus, vertigo, otitis media, treatment failure, and time consumption.⁹ Harm done by wax softeners is minimal.

TABLE
EVIDENCE SUMMARY FOR IN-OFFICE CERUMEN REMOVAL

Recommendations from others

The 5-Minute Clinical Consult 2001 recommends Cerumenex followed by irrigation in office. Clinical Evidence 2001 reports that clinically accepted standards are ear syringing and manual disimpaction, although no randomized clinical trials addressing benefit or harm have been conducted. No specific recommendation made because of inconsistent, unclear study design or undefined terms (eg, impaction).

Evidence summary

In studies that evaluated onetime softening in the office to ease or eliminate the need for irrigation, a presoak with docusate sodium (Colace) was most effective, although its effects were not compared with those of water.¹ Both triethanolamine (Cerumenex) and olive oil were the next most effective treatments.² Carbamide peroxide (Debrox, Murine Ear) was least effective (see Table and Table W1*).³ In 1 small, carefully done study of ear candles, more candle wax was added than earwax was removed in the 8 ears tested.⁴

In studies that evaluated 3 to 14 days of home ceruminolysis to obviate or ease irritation, 5% urea hydrogen peroxide in glycerol was most effective.⁵ Sterile water, sodium bicarbonate in glycerol, 2% acetic acid (VoSoL, Domeboro), ethylene oxide polyoxypropylene (Addax), and acpd (arachis oil, chlorobutanol, p-dichlorobenzene [Cerumenol]) were all of equal efficacy.^6-8 All were more effective than no treatment. Notably, 5% of cases resolved completely and 26% became moderately clear after 5 days of no treatment (Table W2*).⁶

No direct comparisons exist of same-day in-office softening followed by irrigation or disimpaction against home softening followed by irrigation and manual disimpaction. Until more placebo-controlled data are generated, recommendations should be based on relative safety and on the direct comparison trials within each strategy. Complications of irrigation include otitis externa, perforation, canal trauma, pain, cough, tinnitus, vertigo, otitis media, treatment failure, and time consumption.⁹ Harm done by wax softeners is minimal.

TABLE
EVIDENCE SUMMARY FOR IN-OFFICE CERUMEN REMOVAL

Recommendations from others

The 5-Minute Clinical Consult 2001 recommends Cerumenex followed by irrigation in office. Clinical Evidence 2001 reports that clinically accepted standards are ear syringing and manual disimpaction, although no randomized clinical trials addressing benefit or harm have been conducted. No specific recommendation made because of inconsistent, unclear study design or undefined terms (eg, impaction).

Evidence summary

In studies that evaluated onetime softening in the office to ease or eliminate the need for irrigation, a presoak with docusate sodium (Colace) was most effective, although its effects were not compared with those of water.¹ Both triethanolamine (Cerumenex) and olive oil were the next most effective treatments.² Carbamide peroxide (Debrox, Murine Ear) was least effective (see Table and Table W1*).³ In 1 small, carefully done study of ear candles, more candle wax was added than earwax was removed in the 8 ears tested.⁴

In studies that evaluated 3 to 14 days of home ceruminolysis to obviate or ease irritation, 5% urea hydrogen peroxide in glycerol was most effective.⁵ Sterile water, sodium bicarbonate in glycerol, 2% acetic acid (VoSoL, Domeboro), ethylene oxide polyoxypropylene (Addax), and acpd (arachis oil, chlorobutanol, p-dichlorobenzene [Cerumenol]) were all of equal efficacy.^6-8 All were more effective than no treatment. Notably, 5% of cases resolved completely and 26% became moderately clear after 5 days of no treatment (Table W2*).⁶

No direct comparisons exist of same-day in-office softening followed by irrigation or disimpaction against home softening followed by irrigation and manual disimpaction. Until more placebo-controlled data are generated, recommendations should be based on relative safety and on the direct comparison trials within each strategy. Complications of irrigation include otitis externa, perforation, canal trauma, pain, cough, tinnitus, vertigo, otitis media, treatment failure, and time consumption.⁹ Harm done by wax softeners is minimal.

TABLE
EVIDENCE SUMMARY FOR IN-OFFICE CERUMEN REMOVAL

Recommendations from others

The 5-Minute Clinical Consult 2001 recommends Cerumenex followed by irrigation in office. Clinical Evidence 2001 reports that clinically accepted standards are ear syringing and manual disimpaction, although no randomized clinical trials addressing benefit or harm have been conducted. No specific recommendation made because of inconsistent, unclear study design or undefined terms (eg, impaction).

Evidence summary

The value of screening with PSA in any population is uncertain. This issue will remain controversial at least until the first of 2 well-designed randomized controlled trials reports results in 2004.^2,3 However, higher-risk subgroups merit special attention. Screening the 3 groups mentioned above would improve the positive predictive value of PSA, but crucial data to determine whether this will improve outcomes are lacking. Using average estimates, if 3300 African American men (aged 50 to 65 years) were screened, 100 would have cancer. After subsequent radical prostatectomy, 1 screened man would die from the procedure, 60 would become impotent, and 20 would be incontinent.⁴

If current therapies for localized therapy do not decrease morbidity or mortality, screening higher-risk groups merely puts them at increased risk for potentially harmful interventions. Biopsies cannot reliably predict which cancers will progress and which will lie indolent. The 30% incidence of CaP on autopsy means that more people die with CaP than from it. Using estimates of the prevalence and natural history of the disease, decision analyses report varying years saved by screening compared with watchful waiting (ranging from a gain of 2.5 quality-adjusted life years (QALYs) to an actual decrease in QALYs, depending primarily on the rate of progression to metastatic disease and efficacy of treatment.^5,6 Another decision analysis, using quality-of-life measures, concluded that men would favor screening only if the prevalence of CaP were greater than any current estimate.⁷ Since the mean expected survival at age 70 is slightly more than 10 years, PSA screening for men 70 years or older to detect cancers with a 10-year survival rate of approximately 90% makes little sense.

Recommendations from others

The US Preventive Services Task Force in 1996 recommended against performing routine screening, stating that there was fair evidence to exclude the test. The American Cancer Society (ACS) and the American Urological Association (AUA) recommend that PSA be offered annually, beginning at patient age 50, to men with a life expectancy of more than 10 years. The same recommendation extends to younger African American men (age 40 years [AUA] or 45 years [ACS]) and men with 1 (AUA) or 2 (ACS) affected first-degree relatives. The American College of Physicians and the American Academy of Family Physicians (AAFP) recommend a discussion of the benefits and harms of screening, diagnosis and treatment, and individualizing the decision to screen.

Evidence summary

The value of screening with PSA in any population is uncertain. This issue will remain controversial at least until the first of 2 well-designed randomized controlled trials reports results in 2004.^2,3 However, higher-risk subgroups merit special attention. Screening the 3 groups mentioned above would improve the positive predictive value of PSA, but crucial data to determine whether this will improve outcomes are lacking. Using average estimates, if 3300 African American men (aged 50 to 65 years) were screened, 100 would have cancer. After subsequent radical prostatectomy, 1 screened man would die from the procedure, 60 would become impotent, and 20 would be incontinent.⁴

If current therapies for localized therapy do not decrease morbidity or mortality, screening higher-risk groups merely puts them at increased risk for potentially harmful interventions. Biopsies cannot reliably predict which cancers will progress and which will lie indolent. The 30% incidence of CaP on autopsy means that more people die with CaP than from it. Using estimates of the prevalence and natural history of the disease, decision analyses report varying years saved by screening compared with watchful waiting (ranging from a gain of 2.5 quality-adjusted life years (QALYs) to an actual decrease in QALYs, depending primarily on the rate of progression to metastatic disease and efficacy of treatment.^5,6 Another decision analysis, using quality-of-life measures, concluded that men would favor screening only if the prevalence of CaP were greater than any current estimate.⁷ Since the mean expected survival at age 70 is slightly more than 10 years, PSA screening for men 70 years or older to detect cancers with a 10-year survival rate of approximately 90% makes little sense.

Recommendations from others

The US Preventive Services Task Force in 1996 recommended against performing routine screening, stating that there was fair evidence to exclude the test. The American Cancer Society (ACS) and the American Urological Association (AUA) recommend that PSA be offered annually, beginning at patient age 50, to men with a life expectancy of more than 10 years. The same recommendation extends to younger African American men (age 40 years [AUA] or 45 years [ACS]) and men with 1 (AUA) or 2 (ACS) affected first-degree relatives. The American College of Physicians and the American Academy of Family Physicians (AAFP) recommend a discussion of the benefits and harms of screening, diagnosis and treatment, and individualizing the decision to screen.

Evidence summary

The value of screening with PSA in any population is uncertain. This issue will remain controversial at least until the first of 2 well-designed randomized controlled trials reports results in 2004.^2,3 However, higher-risk subgroups merit special attention. Screening the 3 groups mentioned above would improve the positive predictive value of PSA, but crucial data to determine whether this will improve outcomes are lacking. Using average estimates, if 3300 African American men (aged 50 to 65 years) were screened, 100 would have cancer. After subsequent radical prostatectomy, 1 screened man would die from the procedure, 60 would become impotent, and 20 would be incontinent.⁴

If current therapies for localized therapy do not decrease morbidity or mortality, screening higher-risk groups merely puts them at increased risk for potentially harmful interventions. Biopsies cannot reliably predict which cancers will progress and which will lie indolent. The 30% incidence of CaP on autopsy means that more people die with CaP than from it. Using estimates of the prevalence and natural history of the disease, decision analyses report varying years saved by screening compared with watchful waiting (ranging from a gain of 2.5 quality-adjusted life years (QALYs) to an actual decrease in QALYs, depending primarily on the rate of progression to metastatic disease and efficacy of treatment.^5,6 Another decision analysis, using quality-of-life measures, concluded that men would favor screening only if the prevalence of CaP were greater than any current estimate.⁷ Since the mean expected survival at age 70 is slightly more than 10 years, PSA screening for men 70 years or older to detect cancers with a 10-year survival rate of approximately 90% makes little sense.

Recommendations from others

The US Preventive Services Task Force in 1996 recommended against performing routine screening, stating that there was fair evidence to exclude the test. The American Cancer Society (ACS) and the American Urological Association (AUA) recommend that PSA be offered annually, beginning at patient age 50, to men with a life expectancy of more than 10 years. The same recommendation extends to younger African American men (age 40 years [AUA] or 45 years [ACS]) and men with 1 (AUA) or 2 (ACS) affected first-degree relatives. The American College of Physicians and the American Academy of Family Physicians (AAFP) recommend a discussion of the benefits and harms of screening, diagnosis and treatment, and individualizing the decision to screen.

Evidence summary

Because of a lack of uniformity in the definition of shoulder disorders and a wide variation in outcomes assessed in clinical trials, there is limited opportunity to compare and pool the results of individual trials. Even when studies define the disorders and outcomes similarly, the heterogeneity of the interventions, timing of outcome assessment, inadequate reporting of results, and small sample sizes limit the inference of specific therapeutic recommendations for shoulder pain.

A recent Cochrane Review concluded that there is little evidence to either support or refute the efficacy of most common interventions for shoulder pain.¹ The pooled analyses of 2 studies of rotator cuff tendinitis suggested that NSAIDs may be superior to placebo in improving the range of abduction, but there was no significant weighted difference between pain scores.^2,3 Another randomized controlled trial⁴ found 14-day treatment with oral NSAIDs superior to placebo for relieving acute shoulder pain (86% vs 56%; absolute risk reduction 30%; 95% confidence interval, 10%-50%).

A randomized single-blind study of primary care patients reported superiority of manipulative therapy over classic physiotherapy in the treatment of shoulder pain (70% vs 10% cure rate at 5 weeks).⁵ Manipulative therapy as performed by general practitioners or physiotherapists included mobilization and manipulation of the upper spine and ribs, acromioclavicular joint, and the glenohumeral joint. Classic physiotherapy as performed by physiotherapists included only exercise therapy, massage, and physical applications. For the patients with synovial pain, intra-articular corticosteroid injection was superior to both manipulative therapy and classic physiotherapy (cure rates of 75% vs 40% and 20%, respectively, at 5 weeks), yet many primary care physicians may not have enough experience to specifically diagnose synovial pain.

Recommendations from others

We identified no other published recommendations or guidelines from professional organizations.

Evidence summary

Because of a lack of uniformity in the definition of shoulder disorders and a wide variation in outcomes assessed in clinical trials, there is limited opportunity to compare and pool the results of individual trials. Even when studies define the disorders and outcomes similarly, the heterogeneity of the interventions, timing of outcome assessment, inadequate reporting of results, and small sample sizes limit the inference of specific therapeutic recommendations for shoulder pain.

A recent Cochrane Review concluded that there is little evidence to either support or refute the efficacy of most common interventions for shoulder pain.¹ The pooled analyses of 2 studies of rotator cuff tendinitis suggested that NSAIDs may be superior to placebo in improving the range of abduction, but there was no significant weighted difference between pain scores.^2,3 Another randomized controlled trial⁴ found 14-day treatment with oral NSAIDs superior to placebo for relieving acute shoulder pain (86% vs 56%; absolute risk reduction 30%; 95% confidence interval, 10%-50%).

A randomized single-blind study of primary care patients reported superiority of manipulative therapy over classic physiotherapy in the treatment of shoulder pain (70% vs 10% cure rate at 5 weeks).⁵ Manipulative therapy as performed by general practitioners or physiotherapists included mobilization and manipulation of the upper spine and ribs, acromioclavicular joint, and the glenohumeral joint. Classic physiotherapy as performed by physiotherapists included only exercise therapy, massage, and physical applications. For the patients with synovial pain, intra-articular corticosteroid injection was superior to both manipulative therapy and classic physiotherapy (cure rates of 75% vs 40% and 20%, respectively, at 5 weeks), yet many primary care physicians may not have enough experience to specifically diagnose synovial pain.

Recommendations from others

We identified no other published recommendations or guidelines from professional organizations.

Evidence summary

Because of a lack of uniformity in the definition of shoulder disorders and a wide variation in outcomes assessed in clinical trials, there is limited opportunity to compare and pool the results of individual trials. Even when studies define the disorders and outcomes similarly, the heterogeneity of the interventions, timing of outcome assessment, inadequate reporting of results, and small sample sizes limit the inference of specific therapeutic recommendations for shoulder pain.

A recent Cochrane Review concluded that there is little evidence to either support or refute the efficacy of most common interventions for shoulder pain.¹ The pooled analyses of 2 studies of rotator cuff tendinitis suggested that NSAIDs may be superior to placebo in improving the range of abduction, but there was no significant weighted difference between pain scores.^2,3 Another randomized controlled trial⁴ found 14-day treatment with oral NSAIDs superior to placebo for relieving acute shoulder pain (86% vs 56%; absolute risk reduction 30%; 95% confidence interval, 10%-50%).

A randomized single-blind study of primary care patients reported superiority of manipulative therapy over classic physiotherapy in the treatment of shoulder pain (70% vs 10% cure rate at 5 weeks).⁵ Manipulative therapy as performed by general practitioners or physiotherapists included mobilization and manipulation of the upper spine and ribs, acromioclavicular joint, and the glenohumeral joint. Classic physiotherapy as performed by physiotherapists included only exercise therapy, massage, and physical applications. For the patients with synovial pain, intra-articular corticosteroid injection was superior to both manipulative therapy and classic physiotherapy (cure rates of 75% vs 40% and 20%, respectively, at 5 weeks), yet many primary care physicians may not have enough experience to specifically diagnose synovial pain.

Recommendations from others

We identified no other published recommendations or guidelines from professional organizations.

Evidence summary

The Cochrane Database of Systemic Reviews^1,2 reported 72 placebo-controlled trials of topical agents that yielded the following cure rates: undecenoic acid, 72%; allylamines (terbinafine, naftifine, butenafine), 70%; tolnaftate, 64%; azoles (miconazole, clotrimazole, ketoconazole, econazole, oxiconazole), 47%. A meta-analysis of 11 RCTs suggests that allylamines are slightly more effective than azoles.

Orally administered antifungal agents are expensive and can have systemic side effects. Griseofulvin and ketoconazole are approved for oral therapy, but product labels clearly state that they should be used only after topical agents have failed. Griseofulvin has been used for more than 30 years, is well tolerated, and efficacious in treating dermatomycoses in the range of 60%.³ Ketoconazole’s cure rate is similar, but its use in cutaneous infections is limited by multiple drug interactions and serious side effects. Three placebo-controlled RCTs of itraconazole of varying doses and duration of treatment suggested favorable clinical cure of moccasin-type tinea pedis (51%-85%) . The most effective itraconazole regimen was 200 mg twice daily for 1 week. In a large double-blind multicenter study of all forms of tinea pedis, De Keyser et al⁴ compared 2 weeks of terbinafine at 250 mg/day to 2 weeks of itraconazole at 100 mg/day. After 8 weeks they found terbinafine superior to itraconazole for clinical cure (94.1% vs 72.4%). In a single multicenter open study the cure rate for fluconazole 150 mg was 77% when used once weekly for 3 weeks. See Table 1 for summary.

TABLE
RECOMMENDED TOPICAL TREATMENTS FOR TINEA PEDIS

Recommendations from others

American Academy of Dermatology Guidelines⁵ recommend topical therapy for initial treatment of tinea pedis. Oral therapy may be required to treat patients with hyperkeratotic soles, disabling or extensive disease, topical therapy failure, chronic infection, or immunosuppression. Surgical therapy is not indicated.

Evidence summary

The Cochrane Database of Systemic Reviews^1,2 reported 72 placebo-controlled trials of topical agents that yielded the following cure rates: undecenoic acid, 72%; allylamines (terbinafine, naftifine, butenafine), 70%; tolnaftate, 64%; azoles (miconazole, clotrimazole, ketoconazole, econazole, oxiconazole), 47%. A meta-analysis of 11 RCTs suggests that allylamines are slightly more effective than azoles.

Orally administered antifungal agents are expensive and can have systemic side effects. Griseofulvin and ketoconazole are approved for oral therapy, but product labels clearly state that they should be used only after topical agents have failed. Griseofulvin has been used for more than 30 years, is well tolerated, and efficacious in treating dermatomycoses in the range of 60%.³ Ketoconazole’s cure rate is similar, but its use in cutaneous infections is limited by multiple drug interactions and serious side effects. Three placebo-controlled RCTs of itraconazole of varying doses and duration of treatment suggested favorable clinical cure of moccasin-type tinea pedis (51%-85%) . The most effective itraconazole regimen was 200 mg twice daily for 1 week. In a large double-blind multicenter study of all forms of tinea pedis, De Keyser et al⁴ compared 2 weeks of terbinafine at 250 mg/day to 2 weeks of itraconazole at 100 mg/day. After 8 weeks they found terbinafine superior to itraconazole for clinical cure (94.1% vs 72.4%). In a single multicenter open study the cure rate for fluconazole 150 mg was 77% when used once weekly for 3 weeks. See Table 1 for summary.

TABLE
RECOMMENDED TOPICAL TREATMENTS FOR TINEA PEDIS

Recommendations from others

American Academy of Dermatology Guidelines⁵ recommend topical therapy for initial treatment of tinea pedis. Oral therapy may be required to treat patients with hyperkeratotic soles, disabling or extensive disease, topical therapy failure, chronic infection, or immunosuppression. Surgical therapy is not indicated.

Evidence summary

The Cochrane Database of Systemic Reviews^1,2 reported 72 placebo-controlled trials of topical agents that yielded the following cure rates: undecenoic acid, 72%; allylamines (terbinafine, naftifine, butenafine), 70%; tolnaftate, 64%; azoles (miconazole, clotrimazole, ketoconazole, econazole, oxiconazole), 47%. A meta-analysis of 11 RCTs suggests that allylamines are slightly more effective than azoles.

Orally administered antifungal agents are expensive and can have systemic side effects. Griseofulvin and ketoconazole are approved for oral therapy, but product labels clearly state that they should be used only after topical agents have failed. Griseofulvin has been used for more than 30 years, is well tolerated, and efficacious in treating dermatomycoses in the range of 60%.³ Ketoconazole’s cure rate is similar, but its use in cutaneous infections is limited by multiple drug interactions and serious side effects. Three placebo-controlled RCTs of itraconazole of varying doses and duration of treatment suggested favorable clinical cure of moccasin-type tinea pedis (51%-85%) . The most effective itraconazole regimen was 200 mg twice daily for 1 week. In a large double-blind multicenter study of all forms of tinea pedis, De Keyser et al⁴ compared 2 weeks of terbinafine at 250 mg/day to 2 weeks of itraconazole at 100 mg/day. After 8 weeks they found terbinafine superior to itraconazole for clinical cure (94.1% vs 72.4%). In a single multicenter open study the cure rate for fluconazole 150 mg was 77% when used once weekly for 3 weeks. See Table 1 for summary.

TABLE
RECOMMENDED TOPICAL TREATMENTS FOR TINEA PEDIS

Recommendations from others

American Academy of Dermatology Guidelines⁵ recommend topical therapy for initial treatment of tinea pedis. Oral therapy may be required to treat patients with hyperkeratotic soles, disabling or extensive disease, topical therapy failure, chronic infection, or immunosuppression. Surgical therapy is not indicated.

Evidence summary

The accuracy of ABPM has been validated for use in the adult, pediatric, and pregnant populations.¹ Community-based cohort studies have consistently shown ABPM to be more reproducible than office blood pressure measurements.^2,3 Also, ABPM correlates better with disease-oriented outcomes, such as left ventricular mass, retinopathy, and microalbuminuria than does office measurement.^4,5

ABPM also has a better correlation with several patient-oriented outcomes. A cohort study of 1076 patients found that an elevation in ABPM was a better predictor of cardiovascular events and overall mortality than office measurements.⁶ Another cohort study of 1464 patients found ABPM was linearly related to stroke risk and more predictive of a cerebrovascular event than was screening blood pressure over an average of 6.4 years.⁷

In a randomized parallel-group trial, 419 untreated patients were followed up using either ABPM or conventional office measurements to initiate and adjust antihypertensive therapy.⁸ When compared with standard office measurement, management with ABPM led to less intensive antihypertensive drug therapy without loss of blood pressure control. Evidence from these and other studies indicates that ABPM can be useful for risk stratification of patients in whom the diagnosis of hypertension is not clear.⁹ However, trials studying the long-term outcomes of the treatment of ambulatory blood pressure levels are still lacking.

Recommendations from others

An ad hoc committee of the American Society of Hypertension, the Canadian Hypertension Society, and the British Hypertension Society all agree that ABPM is useful in excluding the diagnosis of white-coat hypertension and evaluating resistant hypertension or episodic hypertension.¹ The sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension and the National High Blood Pressure Education Program working group on ambulatory blood pressure monitoring add that ABPM plays a limited role in the routine evaluation of patients with suspected hypertension.¹

Evidence summary

The accuracy of ABPM has been validated for use in the adult, pediatric, and pregnant populations.¹ Community-based cohort studies have consistently shown ABPM to be more reproducible than office blood pressure measurements.^2,3 Also, ABPM correlates better with disease-oriented outcomes, such as left ventricular mass, retinopathy, and microalbuminuria than does office measurement.^4,5

ABPM also has a better correlation with several patient-oriented outcomes. A cohort study of 1076 patients found that an elevation in ABPM was a better predictor of cardiovascular events and overall mortality than office measurements.⁶ Another cohort study of 1464 patients found ABPM was linearly related to stroke risk and more predictive of a cerebrovascular event than was screening blood pressure over an average of 6.4 years.⁷

In a randomized parallel-group trial, 419 untreated patients were followed up using either ABPM or conventional office measurements to initiate and adjust antihypertensive therapy.⁸ When compared with standard office measurement, management with ABPM led to less intensive antihypertensive drug therapy without loss of blood pressure control. Evidence from these and other studies indicates that ABPM can be useful for risk stratification of patients in whom the diagnosis of hypertension is not clear.⁹ However, trials studying the long-term outcomes of the treatment of ambulatory blood pressure levels are still lacking.

Recommendations from others

An ad hoc committee of the American Society of Hypertension, the Canadian Hypertension Society, and the British Hypertension Society all agree that ABPM is useful in excluding the diagnosis of white-coat hypertension and evaluating resistant hypertension or episodic hypertension.¹ The sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension and the National High Blood Pressure Education Program working group on ambulatory blood pressure monitoring add that ABPM plays a limited role in the routine evaluation of patients with suspected hypertension.¹

Evidence summary

The accuracy of ABPM has been validated for use in the adult, pediatric, and pregnant populations.¹ Community-based cohort studies have consistently shown ABPM to be more reproducible than office blood pressure measurements.^2,3 Also, ABPM correlates better with disease-oriented outcomes, such as left ventricular mass, retinopathy, and microalbuminuria than does office measurement.^4,5

ABPM also has a better correlation with several patient-oriented outcomes. A cohort study of 1076 patients found that an elevation in ABPM was a better predictor of cardiovascular events and overall mortality than office measurements.⁶ Another cohort study of 1464 patients found ABPM was linearly related to stroke risk and more predictive of a cerebrovascular event than was screening blood pressure over an average of 6.4 years.⁷

In a randomized parallel-group trial, 419 untreated patients were followed up using either ABPM or conventional office measurements to initiate and adjust antihypertensive therapy.⁸ When compared with standard office measurement, management with ABPM led to less intensive antihypertensive drug therapy without loss of blood pressure control. Evidence from these and other studies indicates that ABPM can be useful for risk stratification of patients in whom the diagnosis of hypertension is not clear.⁹ However, trials studying the long-term outcomes of the treatment of ambulatory blood pressure levels are still lacking.

Recommendations from others

An ad hoc committee of the American Society of Hypertension, the Canadian Hypertension Society, and the British Hypertension Society all agree that ABPM is useful in excluding the diagnosis of white-coat hypertension and evaluating resistant hypertension or episodic hypertension.¹ The sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension and the National High Blood Pressure Education Program working group on ambulatory blood pressure monitoring add that ABPM plays a limited role in the routine evaluation of patients with suspected hypertension.¹

Evidence Summary

Many trials report bone mineral density (BMD) as their primary outcome, which may or may not be associated with fracture rates. Relatively few studies have reported patient-oriented outcomes, such as vertebral or nonvertebral fracture.

Alendronate and risedronate have both reduced vertebral and nonvertebral fractures and increased BMD in clinical trials. The pooled risk estimates for alendronate’s antifracture effect are 48% to 53% vertebral and hip fracture reduction and 30% reduction of all clinical fractures (relative risk [RR] = 0.70; 95% confidence interval [CI], 0.59-0.82).1 Risedronate reduced hip fractures in osteoporotic women aged 70 to 79 years (RR = 0.6; 95% CI, 0.4-0.9), but women 80 years and older with nonskeletal risk factors did not benefit.² One alendronate trial in 241 osteoporotic men demonstrated increased spine and hip BMD and a decreased incidence of vertebral fractures.³

HRT has been associated with increased BMD in RCTs, fewer fractures in observational studies, and fewer fractures in a recent meta-analysis of RCTs. HRT had the greatest benefit among women younger than 60 years (RR = 0.67; 95% CI, 0.56-0.94).4 For women older than 60 years, a nonsignificant trend toward benefit was found (RR = 0.88, 95% CI, 0.71-1.08). However, in a large RCT of postmenopausal women, 85% without osteoporotic BMD, 4 years of HRT did not reduce fracture incidence.⁵ Testosterone replacement in men is less studied; some small studies demonstrate increased BMD, but long-term benefits are unknown.⁶

Raloxifene and calcitonin have some supporting evidence as well. In a large 4-year placebo-controlled trial, raloxifene decreased vertebral fracture risk (RR = 0.7; 95% CI, 0.5-0.8) but had no effect on hip fracture and a threefold increase in thromboembolic risk (RR = 3.1; 95% CI, 1.5-6.2).7 Regarding calcitonin, one RCT compared 3 doses of intranasal calcitonin and placebo in osteoporotic women and showed an increase in lumbar spine BMD in treated groups.8 Over the 5-year study (59% of participants were lost to follow-up), there was a 39% reduction in risk of radiologic deformities (P=.03) only for women taking 200 IU.

Many subjects also used vitamin D and calcium, but effective doses of both agents are still in question. Combined calcium and vitamin D supplements have decreased fracture risk using 700 to 800 IU of vitamin D and 500 to 1200 mg of calcium daily,9 but a systematic review of vitamin D without calcium found no clear benefit.10 A meta-analysis showed that exercise training programs may play a preventive role, potentially preventing or reversing 1% of bone loss annually among women.11 Smoking cessation may also increase bone density.¹²

Recommendations From Others

The Royal College of Physician Guidelines on Osteoporosis Prevention and Treatment gives HRT an A grade of recommendation for preventing spinal fractures and a B grade for nonvertebral fracture prevention, while alendronate and risedronate received an A grade for both vertebral and nonvertebral fracture prevention. The American Association of Clinical Endocrinologists (AACE) states that HRT is the standard of care for preventing and treating postmenopausal bone loss but supports the use of bisphosphonates as an alternative. The US Preventive Services Task Force emphasizes smoking cessation, regular exercise, and adequate calcium intake, and recommends discussion with patients of the risks and benefits of HRT.

Evidence Summary

Many trials report bone mineral density (BMD) as their primary outcome, which may or may not be associated with fracture rates. Relatively few studies have reported patient-oriented outcomes, such as vertebral or nonvertebral fracture.

Alendronate and risedronate have both reduced vertebral and nonvertebral fractures and increased BMD in clinical trials. The pooled risk estimates for alendronate’s antifracture effect are 48% to 53% vertebral and hip fracture reduction and 30% reduction of all clinical fractures (relative risk [RR] = 0.70; 95% confidence interval [CI], 0.59-0.82).1 Risedronate reduced hip fractures in osteoporotic women aged 70 to 79 years (RR = 0.6; 95% CI, 0.4-0.9), but women 80 years and older with nonskeletal risk factors did not benefit.² One alendronate trial in 241 osteoporotic men demonstrated increased spine and hip BMD and a decreased incidence of vertebral fractures.³

HRT has been associated with increased BMD in RCTs, fewer fractures in observational studies, and fewer fractures in a recent meta-analysis of RCTs. HRT had the greatest benefit among women younger than 60 years (RR = 0.67; 95% CI, 0.56-0.94).4 For women older than 60 years, a nonsignificant trend toward benefit was found (RR = 0.88, 95% CI, 0.71-1.08). However, in a large RCT of postmenopausal women, 85% without osteoporotic BMD, 4 years of HRT did not reduce fracture incidence.⁵ Testosterone replacement in men is less studied; some small studies demonstrate increased BMD, but long-term benefits are unknown.⁶

Raloxifene and calcitonin have some supporting evidence as well. In a large 4-year placebo-controlled trial, raloxifene decreased vertebral fracture risk (RR = 0.7; 95% CI, 0.5-0.8) but had no effect on hip fracture and a threefold increase in thromboembolic risk (RR = 3.1; 95% CI, 1.5-6.2).7 Regarding calcitonin, one RCT compared 3 doses of intranasal calcitonin and placebo in osteoporotic women and showed an increase in lumbar spine BMD in treated groups.8 Over the 5-year study (59% of participants were lost to follow-up), there was a 39% reduction in risk of radiologic deformities (P=.03) only for women taking 200 IU.

Many subjects also used vitamin D and calcium, but effective doses of both agents are still in question. Combined calcium and vitamin D supplements have decreased fracture risk using 700 to 800 IU of vitamin D and 500 to 1200 mg of calcium daily,9 but a systematic review of vitamin D without calcium found no clear benefit.10 A meta-analysis showed that exercise training programs may play a preventive role, potentially preventing or reversing 1% of bone loss annually among women.11 Smoking cessation may also increase bone density.¹²

Recommendations From Others

The Royal College of Physician Guidelines on Osteoporosis Prevention and Treatment gives HRT an A grade of recommendation for preventing spinal fractures and a B grade for nonvertebral fracture prevention, while alendronate and risedronate received an A grade for both vertebral and nonvertebral fracture prevention. The American Association of Clinical Endocrinologists (AACE) states that HRT is the standard of care for preventing and treating postmenopausal bone loss but supports the use of bisphosphonates as an alternative. The US Preventive Services Task Force emphasizes smoking cessation, regular exercise, and adequate calcium intake, and recommends discussion with patients of the risks and benefits of HRT.

Evidence Summary

Many trials report bone mineral density (BMD) as their primary outcome, which may or may not be associated with fracture rates. Relatively few studies have reported patient-oriented outcomes, such as vertebral or nonvertebral fracture.

Alendronate and risedronate have both reduced vertebral and nonvertebral fractures and increased BMD in clinical trials. The pooled risk estimates for alendronate’s antifracture effect are 48% to 53% vertebral and hip fracture reduction and 30% reduction of all clinical fractures (relative risk [RR] = 0.70; 95% confidence interval [CI], 0.59-0.82).1 Risedronate reduced hip fractures in osteoporotic women aged 70 to 79 years (RR = 0.6; 95% CI, 0.4-0.9), but women 80 years and older with nonskeletal risk factors did not benefit.² One alendronate trial in 241 osteoporotic men demonstrated increased spine and hip BMD and a decreased incidence of vertebral fractures.³

HRT has been associated with increased BMD in RCTs, fewer fractures in observational studies, and fewer fractures in a recent meta-analysis of RCTs. HRT had the greatest benefit among women younger than 60 years (RR = 0.67; 95% CI, 0.56-0.94).4 For women older than 60 years, a nonsignificant trend toward benefit was found (RR = 0.88, 95% CI, 0.71-1.08). However, in a large RCT of postmenopausal women, 85% without osteoporotic BMD, 4 years of HRT did not reduce fracture incidence.⁵ Testosterone replacement in men is less studied; some small studies demonstrate increased BMD, but long-term benefits are unknown.⁶

Raloxifene and calcitonin have some supporting evidence as well. In a large 4-year placebo-controlled trial, raloxifene decreased vertebral fracture risk (RR = 0.7; 95% CI, 0.5-0.8) but had no effect on hip fracture and a threefold increase in thromboembolic risk (RR = 3.1; 95% CI, 1.5-6.2).7 Regarding calcitonin, one RCT compared 3 doses of intranasal calcitonin and placebo in osteoporotic women and showed an increase in lumbar spine BMD in treated groups.8 Over the 5-year study (59% of participants were lost to follow-up), there was a 39% reduction in risk of radiologic deformities (P=.03) only for women taking 200 IU.

Many subjects also used vitamin D and calcium, but effective doses of both agents are still in question. Combined calcium and vitamin D supplements have decreased fracture risk using 700 to 800 IU of vitamin D and 500 to 1200 mg of calcium daily,9 but a systematic review of vitamin D without calcium found no clear benefit.10 A meta-analysis showed that exercise training programs may play a preventive role, potentially preventing or reversing 1% of bone loss annually among women.11 Smoking cessation may also increase bone density.¹²

Recommendations From Others

The Royal College of Physician Guidelines on Osteoporosis Prevention and Treatment gives HRT an A grade of recommendation for preventing spinal fractures and a B grade for nonvertebral fracture prevention, while alendronate and risedronate received an A grade for both vertebral and nonvertebral fracture prevention. The American Association of Clinical Endocrinologists (AACE) states that HRT is the standard of care for preventing and treating postmenopausal bone loss but supports the use of bisphosphonates as an alternative. The US Preventive Services Task Force emphasizes smoking cessation, regular exercise, and adequate calcium intake, and recommends discussion with patients of the risks and benefits of HRT.

Evidence Summary

Good evidence has existed for some time that treatment of obstructive sleep apnea (OSA) improves disease-oriented findings, such as disturbed sleep, oxygen desaturation, apneas, and hypopneas. However, evidence that supports patient-oriented improvement is less plentiful. A problem with evaluating benefits of treatment has been an abundance of case studies indicating good response to treatment but a lack of support for these studies by RCTs.

The Cochrane Database of Systematic Reviews includes treatment of OSA using surgery, lifestyle modifications, and continuous positive airways pressure (CPAP). Only a small portion of the available literature on OSA fits the stringent criteria for inclusion in this database. The review for treatment with CPAP indicates significant improvements in several quality-of-life and depression measures.¹ Some newer RCTs evaluating CPAP and oral devices are available that show more benefit.

A multicenter RCT comparing real and sham CPAP in patients without daytime sleepiness found no improvements in a variety of patient-oriented outcomes.² CPAP treatment has been shown in an RCT to improve subjective and objective sleepiness. For 73% of treated subjects, the sleepiness scores returned to normal (number needed to treat = 1.4). The CPAP users with the best compliance had the most improvement.³ In a crossover RCT of CPAP in patients with mild OSA, CPAP was shown to improve symptoms, cognitive function, psychologic wellbeing, and quality of life.⁴

CPAP has been shown to cause small decreases in blood pressure in normotensive patients. Systolic pressure fell most in those with more than 20 4% desaturations per hour, falling 4.0 mm Hg systolic and 5.0 mm Hg diastolic.⁵

Recommendations From Others

The Cochrane Database recommends that surgery be restricted to that carried out as part of clinical trials because of the lack of evidence for benefit from surgery for OSA. CPAP is regarded as the therapy with the most benefits, but oral appliances are best tolerated by patients. All patients should receive instruction and encouragement in lifestyle modification. Benefits of treatment are sufficient that patients prefer active treatment with its multiple hassles and expense over placebo.¹

Evidence Summary

Good evidence has existed for some time that treatment of obstructive sleep apnea (OSA) improves disease-oriented findings, such as disturbed sleep, oxygen desaturation, apneas, and hypopneas. However, evidence that supports patient-oriented improvement is less plentiful. A problem with evaluating benefits of treatment has been an abundance of case studies indicating good response to treatment but a lack of support for these studies by RCTs.

The Cochrane Database of Systematic Reviews includes treatment of OSA using surgery, lifestyle modifications, and continuous positive airways pressure (CPAP). Only a small portion of the available literature on OSA fits the stringent criteria for inclusion in this database. The review for treatment with CPAP indicates significant improvements in several quality-of-life and depression measures.¹ Some newer RCTs evaluating CPAP and oral devices are available that show more benefit.

A multicenter RCT comparing real and sham CPAP in patients without daytime sleepiness found no improvements in a variety of patient-oriented outcomes.² CPAP treatment has been shown in an RCT to improve subjective and objective sleepiness. For 73% of treated subjects, the sleepiness scores returned to normal (number needed to treat = 1.4). The CPAP users with the best compliance had the most improvement.³ In a crossover RCT of CPAP in patients with mild OSA, CPAP was shown to improve symptoms, cognitive function, psychologic wellbeing, and quality of life.⁴

CPAP has been shown to cause small decreases in blood pressure in normotensive patients. Systolic pressure fell most in those with more than 20 4% desaturations per hour, falling 4.0 mm Hg systolic and 5.0 mm Hg diastolic.⁵

Recommendations From Others

The Cochrane Database recommends that surgery be restricted to that carried out as part of clinical trials because of the lack of evidence for benefit from surgery for OSA. CPAP is regarded as the therapy with the most benefits, but oral appliances are best tolerated by patients. All patients should receive instruction and encouragement in lifestyle modification. Benefits of treatment are sufficient that patients prefer active treatment with its multiple hassles and expense over placebo.¹

Evidence Summary

Good evidence has existed for some time that treatment of obstructive sleep apnea (OSA) improves disease-oriented findings, such as disturbed sleep, oxygen desaturation, apneas, and hypopneas. However, evidence that supports patient-oriented improvement is less plentiful. A problem with evaluating benefits of treatment has been an abundance of case studies indicating good response to treatment but a lack of support for these studies by RCTs.

The Cochrane Database of Systematic Reviews includes treatment of OSA using surgery, lifestyle modifications, and continuous positive airways pressure (CPAP). Only a small portion of the available literature on OSA fits the stringent criteria for inclusion in this database. The review for treatment with CPAP indicates significant improvements in several quality-of-life and depression measures.¹ Some newer RCTs evaluating CPAP and oral devices are available that show more benefit.

A multicenter RCT comparing real and sham CPAP in patients without daytime sleepiness found no improvements in a variety of patient-oriented outcomes.² CPAP treatment has been shown in an RCT to improve subjective and objective sleepiness. For 73% of treated subjects, the sleepiness scores returned to normal (number needed to treat = 1.4). The CPAP users with the best compliance had the most improvement.³ In a crossover RCT of CPAP in patients with mild OSA, CPAP was shown to improve symptoms, cognitive function, psychologic wellbeing, and quality of life.⁴

CPAP has been shown to cause small decreases in blood pressure in normotensive patients. Systolic pressure fell most in those with more than 20 4% desaturations per hour, falling 4.0 mm Hg systolic and 5.0 mm Hg diastolic.⁵

Recommendations From Others

The Cochrane Database recommends that surgery be restricted to that carried out as part of clinical trials because of the lack of evidence for benefit from surgery for OSA. CPAP is regarded as the therapy with the most benefits, but oral appliances are best tolerated by patients. All patients should receive instruction and encouragement in lifestyle modification. Benefits of treatment are sufficient that patients prefer active treatment with its multiple hassles and expense over placebo.¹

Evidence Summary

There have been 3 RCTs of tamoxifen for primary prevention of cancer. The best, by Fisher and colleagues,² reported a 49% (P <.001) reduction in incidence of invasive breast cancer and 50% in noninvasive breast cancer (P <.002) among women with a 5-year risk of breast cancer Ž 1.66% based on the Gail Risk Index (http://bcra.nci.nih.gov/brc/). Estrogen receptor (ER)-negative breast cancers were unaffected. See the Table 1 for summary of risks and benefits.

Veronesi and coworkers³ reported no overall benefit from treatment with tamoxifen in low-risk hysterectomized women, but the trial was underpowered, had a high dropout rate in the first year, and allowed hormone replacement therapy (HRT).

Powles and colleagues⁴ reported no benefit from tamoxifen in young women with at least one first-degree relative with breast cancer. HRT was allowed, and the study had 90% power to detect a reduction of 50% in breast cancer incidence. Authors estimated that 36% of participants and 60% of women who developed breast cancer had a greater than 80% chance of having a breast cancer predisposition gene. Breast cancers in women with the Breast Cancer 1 gene (BRCA1) are more likely to be ER negative.

The optimal duration of treatment for primary prevention has not been determined. Fisher and coworkers⁵ reported that women given tamoxifen for only 5 years for ER-positive breast cancer with negative nodes had improved disease-free survival compared with women randomized to continue tamoxifen more than 5 years (92% vs 86% respectively, P=.003).

Recommendations from Others

Canadian Task Force on Preventive Health Care and the Canadian Breast Cancer Initiatives Steering Committee on Clinical Practice Guidelines: Evidence supports counseling women at high risk (Ž 1.66% over 5 years) on the potential benefits and harms. There is fair evidence to recommend against the use of tamoxifen to reduce the risk of breast cancer in women at low or normal risk of disease (Grade D recommendation).”⁴

Evidence Summary

There have been 3 RCTs of tamoxifen for primary prevention of cancer. The best, by Fisher and colleagues,² reported a 49% (P <.001) reduction in incidence of invasive breast cancer and 50% in noninvasive breast cancer (P <.002) among women with a 5-year risk of breast cancer Ž 1.66% based on the Gail Risk Index (http://bcra.nci.nih.gov/brc/). Estrogen receptor (ER)-negative breast cancers were unaffected. See the Table 1 for summary of risks and benefits.

Veronesi and coworkers³ reported no overall benefit from treatment with tamoxifen in low-risk hysterectomized women, but the trial was underpowered, had a high dropout rate in the first year, and allowed hormone replacement therapy (HRT).

Powles and colleagues⁴ reported no benefit from tamoxifen in young women with at least one first-degree relative with breast cancer. HRT was allowed, and the study had 90% power to detect a reduction of 50% in breast cancer incidence. Authors estimated that 36% of participants and 60% of women who developed breast cancer had a greater than 80% chance of having a breast cancer predisposition gene. Breast cancers in women with the Breast Cancer 1 gene (BRCA1) are more likely to be ER negative.

The optimal duration of treatment for primary prevention has not been determined. Fisher and coworkers⁵ reported that women given tamoxifen for only 5 years for ER-positive breast cancer with negative nodes had improved disease-free survival compared with women randomized to continue tamoxifen more than 5 years (92% vs 86% respectively, P=.003).

Recommendations from Others

Canadian Task Force on Preventive Health Care and the Canadian Breast Cancer Initiatives Steering Committee on Clinical Practice Guidelines: Evidence supports counseling women at high risk (Ž 1.66% over 5 years) on the potential benefits and harms. There is fair evidence to recommend against the use of tamoxifen to reduce the risk of breast cancer in women at low or normal risk of disease (Grade D recommendation).”⁴

Evidence Summary

There have been 3 RCTs of tamoxifen for primary prevention of cancer. The best, by Fisher and colleagues,² reported a 49% (P <.001) reduction in incidence of invasive breast cancer and 50% in noninvasive breast cancer (P <.002) among women with a 5-year risk of breast cancer Ž 1.66% based on the Gail Risk Index (http://bcra.nci.nih.gov/brc/). Estrogen receptor (ER)-negative breast cancers were unaffected. See the Table 1 for summary of risks and benefits.

Veronesi and coworkers³ reported no overall benefit from treatment with tamoxifen in low-risk hysterectomized women, but the trial was underpowered, had a high dropout rate in the first year, and allowed hormone replacement therapy (HRT).

Powles and colleagues⁴ reported no benefit from tamoxifen in young women with at least one first-degree relative with breast cancer. HRT was allowed, and the study had 90% power to detect a reduction of 50% in breast cancer incidence. Authors estimated that 36% of participants and 60% of women who developed breast cancer had a greater than 80% chance of having a breast cancer predisposition gene. Breast cancers in women with the Breast Cancer 1 gene (BRCA1) are more likely to be ER negative.

The optimal duration of treatment for primary prevention has not been determined. Fisher and coworkers⁵ reported that women given tamoxifen for only 5 years for ER-positive breast cancer with negative nodes had improved disease-free survival compared with women randomized to continue tamoxifen more than 5 years (92% vs 86% respectively, P=.003).

Recommendations from Others

Canadian Task Force on Preventive Health Care and the Canadian Breast Cancer Initiatives Steering Committee on Clinical Practice Guidelines: Evidence supports counseling women at high risk (Ž 1.66% over 5 years) on the potential benefits and harms. There is fair evidence to recommend against the use of tamoxifen to reduce the risk of breast cancer in women at low or normal risk of disease (Grade D recommendation).”⁴

EVIDENCE-BASED ANSWER

Patients diagnosed with HCV should have serum liver function tests and get a baseline HCV RNA level (viral load), since treatment decisions are affected by these laboratory values.^{additional clinical commentary and an algorithm for the treatment of HCV.}

EVIDENCE-BASED ANSWER

Patients diagnosed with HCV should have serum liver function tests and get a baseline HCV RNA level (viral load), since treatment decisions are affected by these laboratory values.^{additional clinical commentary and an algorithm for the treatment of HCV.}

EVIDENCE-BASED ANSWER

Patients diagnosed with HCV should have serum liver function tests and get a baseline HCV RNA level (viral load), since treatment decisions are affected by these laboratory values.^{additional clinical commentary and an algorithm for the treatment of HCV.}