Dolores Zegar Judkins, MLS

Evidence summary

Although extensive in vitro and animal studies have analyzed the effect of curcumin on inflammation and inflammatory mediators (including inhibition of lipoxygenase, cyclooxygenase-2, leukotrienes, thromboxane, prostaglandins, and tumor necrosis factor),¹ few human studies have looked at patient-oriented outcomes.

Rheumatoid arthritis. One very small (N=18) double-blind crossover study showed a statistically significant improvement in morning stiffness, walking time, and joint swelling in rheumatoid arthritis patients taking curcumin.²

Psoriasis. A cohort study demonstrated that curcumin applied topically in a gel formulation to patients with psoriasis resulted in either resolution or reduction in psoriatic plaques after 8 weeks of treatment.³

IBS. Two studies have found curcumin to have a positive effect on patients with IBS. A cohort study (N=10) of patients with ulcerative colitis or Crohn’s disease demonstrated symptomatic improvement (more formed stools, less frequent bowel movements, and less abdominal pain and cramping) after consuming curcumin for 2 and 3 months, respectively.⁴ A randomized, double-blind, multicenter trial (N=89) showed that 6 months of daily curcumin improved the clinical activity index and maintained remission in patients with ulcerative colitis.⁵

Inflammatory eye diseases. A cohort study of 32 patients found that curcumin was as effective as corticosteroids for chronic anterior uveitis (as demonstrated by improved vision, decreased keratic precipitates, and a break of synechiae assessed by slit lamp examination).⁶ Another small cohort study (N=5) by the same authors showed that curcumin reduced or resolved inflammatory orbital pseudotumor (as evidenced by reduced ocular swelling, normal ocular movements, and absence of diplopia).⁷

Familial adenomatous polyposis. A small cohort study (N=5) demonstrated a decrease in size and number of adenomas in patients with familial adenomatous polyposis after a mean of 6 months of treatment with curcumin, although patients received quercetin concurrently during the treatment period.⁸

Kidney transplantation. A cohort study followed 43 dialysis-dependent cadaver kidney recipients who had taken curcumin for 1 month. Investigators observed reduced acute rejection and neurotoxicity over the course of 6 months.⁹

HIV. Curcumin didn’t reduce viral load or improve CD4 counts in 40 HIV patients in the single study identified in a Cochrane Review.¹⁰

Dosage and adverse effects.
Dosing varied across the studies reviewed in this Clinical Inquiry, but generally was 500 to 1000 mg, 1 to 3 times daily. Curcumin doses as high as 12,000 mg daily have been given in experimental settings without significant adverse events. Minor gastrointestinal side effects, including nausea and diarrhea, have been reported.¹¹

Recommendations

The National Center for Complementary and Alternative Medicine of the National Institutes of Health states that little reliable evidence exists to support the use of turmeric for any health condition because few clinical trials have been conducted. Preliminary findings from animal and laboratory studies suggest that curcumin may have anti-inflammatory and anticancer properties, but these findings have not been confirmed in people.¹²

Evidence summary

Although extensive in vitro and animal studies have analyzed the effect of curcumin on inflammation and inflammatory mediators (including inhibition of lipoxygenase, cyclooxygenase-2, leukotrienes, thromboxane, prostaglandins, and tumor necrosis factor),¹ few human studies have looked at patient-oriented outcomes.

Rheumatoid arthritis. One very small (N=18) double-blind crossover study showed a statistically significant improvement in morning stiffness, walking time, and joint swelling in rheumatoid arthritis patients taking curcumin.²

Psoriasis. A cohort study demonstrated that curcumin applied topically in a gel formulation to patients with psoriasis resulted in either resolution or reduction in psoriatic plaques after 8 weeks of treatment.³

IBS. Two studies have found curcumin to have a positive effect on patients with IBS. A cohort study (N=10) of patients with ulcerative colitis or Crohn’s disease demonstrated symptomatic improvement (more formed stools, less frequent bowel movements, and less abdominal pain and cramping) after consuming curcumin for 2 and 3 months, respectively.⁴ A randomized, double-blind, multicenter trial (N=89) showed that 6 months of daily curcumin improved the clinical activity index and maintained remission in patients with ulcerative colitis.⁵

Inflammatory eye diseases. A cohort study of 32 patients found that curcumin was as effective as corticosteroids for chronic anterior uveitis (as demonstrated by improved vision, decreased keratic precipitates, and a break of synechiae assessed by slit lamp examination).⁶ Another small cohort study (N=5) by the same authors showed that curcumin reduced or resolved inflammatory orbital pseudotumor (as evidenced by reduced ocular swelling, normal ocular movements, and absence of diplopia).⁷

Familial adenomatous polyposis. A small cohort study (N=5) demonstrated a decrease in size and number of adenomas in patients with familial adenomatous polyposis after a mean of 6 months of treatment with curcumin, although patients received quercetin concurrently during the treatment period.⁸

Kidney transplantation. A cohort study followed 43 dialysis-dependent cadaver kidney recipients who had taken curcumin for 1 month. Investigators observed reduced acute rejection and neurotoxicity over the course of 6 months.⁹

HIV. Curcumin didn’t reduce viral load or improve CD4 counts in 40 HIV patients in the single study identified in a Cochrane Review.¹⁰

Dosage and adverse effects.
Dosing varied across the studies reviewed in this Clinical Inquiry, but generally was 500 to 1000 mg, 1 to 3 times daily. Curcumin doses as high as 12,000 mg daily have been given in experimental settings without significant adverse events. Minor gastrointestinal side effects, including nausea and diarrhea, have been reported.¹¹

Recommendations

The National Center for Complementary and Alternative Medicine of the National Institutes of Health states that little reliable evidence exists to support the use of turmeric for any health condition because few clinical trials have been conducted. Preliminary findings from animal and laboratory studies suggest that curcumin may have anti-inflammatory and anticancer properties, but these findings have not been confirmed in people.¹²

Evidence summary

Although extensive in vitro and animal studies have analyzed the effect of curcumin on inflammation and inflammatory mediators (including inhibition of lipoxygenase, cyclooxygenase-2, leukotrienes, thromboxane, prostaglandins, and tumor necrosis factor),¹ few human studies have looked at patient-oriented outcomes.

Rheumatoid arthritis. One very small (N=18) double-blind crossover study showed a statistically significant improvement in morning stiffness, walking time, and joint swelling in rheumatoid arthritis patients taking curcumin.²

Psoriasis. A cohort study demonstrated that curcumin applied topically in a gel formulation to patients with psoriasis resulted in either resolution or reduction in psoriatic plaques after 8 weeks of treatment.³

IBS. Two studies have found curcumin to have a positive effect on patients with IBS. A cohort study (N=10) of patients with ulcerative colitis or Crohn’s disease demonstrated symptomatic improvement (more formed stools, less frequent bowel movements, and less abdominal pain and cramping) after consuming curcumin for 2 and 3 months, respectively.⁴ A randomized, double-blind, multicenter trial (N=89) showed that 6 months of daily curcumin improved the clinical activity index and maintained remission in patients with ulcerative colitis.⁵

Inflammatory eye diseases. A cohort study of 32 patients found that curcumin was as effective as corticosteroids for chronic anterior uveitis (as demonstrated by improved vision, decreased keratic precipitates, and a break of synechiae assessed by slit lamp examination).⁶ Another small cohort study (N=5) by the same authors showed that curcumin reduced or resolved inflammatory orbital pseudotumor (as evidenced by reduced ocular swelling, normal ocular movements, and absence of diplopia).⁷

Familial adenomatous polyposis. A small cohort study (N=5) demonstrated a decrease in size and number of adenomas in patients with familial adenomatous polyposis after a mean of 6 months of treatment with curcumin, although patients received quercetin concurrently during the treatment period.⁸

Kidney transplantation. A cohort study followed 43 dialysis-dependent cadaver kidney recipients who had taken curcumin for 1 month. Investigators observed reduced acute rejection and neurotoxicity over the course of 6 months.⁹

HIV. Curcumin didn’t reduce viral load or improve CD4 counts in 40 HIV patients in the single study identified in a Cochrane Review.¹⁰

Dosage and adverse effects.
Dosing varied across the studies reviewed in this Clinical Inquiry, but generally was 500 to 1000 mg, 1 to 3 times daily. Curcumin doses as high as 12,000 mg daily have been given in experimental settings without significant adverse events. Minor gastrointestinal side effects, including nausea and diarrhea, have been reported.¹¹

Recommendations

The National Center for Complementary and Alternative Medicine of the National Institutes of Health states that little reliable evidence exists to support the use of turmeric for any health condition because few clinical trials have been conducted. Preliminary findings from animal and laboratory studies suggest that curcumin may have anti-inflammatory and anticancer properties, but these findings have not been confirmed in people.¹²

Evidence summary

Our search retrieved no randomized controlled clinical trials evaluating the screening tests required to work-up a male with low testosterone. We therefore examined 2 consensus guidelines, 9 review articles, and disease-oriented evidence. The recommendations discussed here are based primarily on consensus guidelines and disease-oriented evidence.

Hypogonadism increases with age

Hypogonadism is a common endocrinologic disorder in men. Advancing age, increased life expectancy, and a rising prevalence of obesity and type 2 diabetes may increase the occurrence of hypogonadism.³ Many cases result from partial androgen deficiency in the aging male, because testosterone levels decline an estimated 1% to 2% per year in adult men.^1,3 A focused, cost-effective work-up will become ever more critical because an estimated 19% of men will be 65 years or older by 2050.⁴

TABLE
Causes of hypogonadism

Serum testosterone: The first-choice test

Serum testosterone measurements are considered the initial test of choice be-cause they’re reliable, inexpensive, and widely available. Testosterone levels vary from hour to hour and diurnally, so a repeat morning measurement is recommended to confirm subnormal levels.^3,5

In some cases—including patients with obesity, type 2 diabetes, or hypothyroidism—the total testosterone level can be misleading; tests for free testosterone and sex hormone-binding globulin levels should be ordered. These tests can also help evaluate men with low-normal total testosterone levels (200-400 ng/dL).^6,7

Is the patient pre- or postpubertal?

Assessment of low testosterone should distinguish between pre- and postpubertal males. In prepubertal males, chromosomal analysis is indicated because hypothalamic-pituitary-gonadal axis defects are common—especially Klinefelter syndrome (1 in 500 males).^6,8

Men with very low testosterone levels (<150 ng/dL) or signs and symptoms suggesting pituitary pathology warrant pituitary imaging and measurement of thyroxine, cortisol, and prolactin levels.⁶ Both pre- and postpubertal males with low testosterone should have FSH, LH, and prolactin levels tested to differentiate primary from secondary hypogonadism.^6,9

Be alert for hemochromatosis and low bone density

Order biopsy or ultrasound examination of testicular masses and iron studies if hemochromatosis is suspected. Hemochromatosis is the most common single gene disorder of Caucasian Americans (1 in 250-300 are homozygous; 1 in 10 are heterozygous) and is associated with hypogonadotrophic hypogonadism.^5,10 In a series of 3 studies, 30% (26 of 89) of men with hemochromatosis had hypogonadism.¹¹ The prevalence of hemochromatosis in males with hypogonadism hasn’t been reported.

Because chronic hypogonadism leads to low bone density and increased risk of fracture, baseline bone densitometry may be prudent.¹² A chart review study of nursing home residents found that 66% of men with hip fractures and 20% of men with vertebral fractures had low testosterone.¹³ Notably, 50% of men in their 80s have testosterone levels in the hypogonadal range (<300 ng/dL), compared with 12% of men <50 years.^1,14

Recommendations

Scant guidance is available concerning what screening tests to order for a male with low testosterone. The United States Preventive Services Task Force and Canadian Task Force on Preventive Health Care make no recommendations; the Cochrane collaboration has no reviews on the topic. The American Association of Clinical Endocrinologists’ (AACE) guidelines are based on expert opinion.³

The AACE consensus guideline used peer review for validation and didn’t specify the method used to assess the quality and strength of the evidence used to write the statement. The AACE guideline recommends a history and physical exam, obtaining repeat morning testosterone levels, prolactin, FSH, LH, bone densitometry, and a semen analysis if fertility is an issue.

In acquired hypogonadism, pituitary imaging is recommended along with thyroid, adrenal, and growth hormone axis testing. Prepubertal males should undergo chromosome analysis, and men with a suspected mass should have a testicular ultrasound examination.

Evidence summary

Our search retrieved no randomized controlled clinical trials evaluating the screening tests required to work-up a male with low testosterone. We therefore examined 2 consensus guidelines, 9 review articles, and disease-oriented evidence. The recommendations discussed here are based primarily on consensus guidelines and disease-oriented evidence.

Hypogonadism increases with age

Hypogonadism is a common endocrinologic disorder in men. Advancing age, increased life expectancy, and a rising prevalence of obesity and type 2 diabetes may increase the occurrence of hypogonadism.³ Many cases result from partial androgen deficiency in the aging male, because testosterone levels decline an estimated 1% to 2% per year in adult men.^1,3 A focused, cost-effective work-up will become ever more critical because an estimated 19% of men will be 65 years or older by 2050.⁴

TABLE
Causes of hypogonadism

Serum testosterone: The first-choice test

Serum testosterone measurements are considered the initial test of choice be-cause they’re reliable, inexpensive, and widely available. Testosterone levels vary from hour to hour and diurnally, so a repeat morning measurement is recommended to confirm subnormal levels.^3,5

In some cases—including patients with obesity, type 2 diabetes, or hypothyroidism—the total testosterone level can be misleading; tests for free testosterone and sex hormone-binding globulin levels should be ordered. These tests can also help evaluate men with low-normal total testosterone levels (200-400 ng/dL).^6,7

Is the patient pre- or postpubertal?

Assessment of low testosterone should distinguish between pre- and postpubertal males. In prepubertal males, chromosomal analysis is indicated because hypothalamic-pituitary-gonadal axis defects are common—especially Klinefelter syndrome (1 in 500 males).^6,8

Men with very low testosterone levels (<150 ng/dL) or signs and symptoms suggesting pituitary pathology warrant pituitary imaging and measurement of thyroxine, cortisol, and prolactin levels.⁶ Both pre- and postpubertal males with low testosterone should have FSH, LH, and prolactin levels tested to differentiate primary from secondary hypogonadism.^6,9

Be alert for hemochromatosis and low bone density

Order biopsy or ultrasound examination of testicular masses and iron studies if hemochromatosis is suspected. Hemochromatosis is the most common single gene disorder of Caucasian Americans (1 in 250-300 are homozygous; 1 in 10 are heterozygous) and is associated with hypogonadotrophic hypogonadism.^5,10 In a series of 3 studies, 30% (26 of 89) of men with hemochromatosis had hypogonadism.¹¹ The prevalence of hemochromatosis in males with hypogonadism hasn’t been reported.

Because chronic hypogonadism leads to low bone density and increased risk of fracture, baseline bone densitometry may be prudent.¹² A chart review study of nursing home residents found that 66% of men with hip fractures and 20% of men with vertebral fractures had low testosterone.¹³ Notably, 50% of men in their 80s have testosterone levels in the hypogonadal range (<300 ng/dL), compared with 12% of men <50 years.^1,14

Recommendations

Scant guidance is available concerning what screening tests to order for a male with low testosterone. The United States Preventive Services Task Force and Canadian Task Force on Preventive Health Care make no recommendations; the Cochrane collaboration has no reviews on the topic. The American Association of Clinical Endocrinologists’ (AACE) guidelines are based on expert opinion.³

The AACE consensus guideline used peer review for validation and didn’t specify the method used to assess the quality and strength of the evidence used to write the statement. The AACE guideline recommends a history and physical exam, obtaining repeat morning testosterone levels, prolactin, FSH, LH, bone densitometry, and a semen analysis if fertility is an issue.

In acquired hypogonadism, pituitary imaging is recommended along with thyroid, adrenal, and growth hormone axis testing. Prepubertal males should undergo chromosome analysis, and men with a suspected mass should have a testicular ultrasound examination.

Evidence summary

Our search retrieved no randomized controlled clinical trials evaluating the screening tests required to work-up a male with low testosterone. We therefore examined 2 consensus guidelines, 9 review articles, and disease-oriented evidence. The recommendations discussed here are based primarily on consensus guidelines and disease-oriented evidence.

Hypogonadism increases with age

Hypogonadism is a common endocrinologic disorder in men. Advancing age, increased life expectancy, and a rising prevalence of obesity and type 2 diabetes may increase the occurrence of hypogonadism.³ Many cases result from partial androgen deficiency in the aging male, because testosterone levels decline an estimated 1% to 2% per year in adult men.^1,3 A focused, cost-effective work-up will become ever more critical because an estimated 19% of men will be 65 years or older by 2050.⁴

TABLE
Causes of hypogonadism

Serum testosterone: The first-choice test

Serum testosterone measurements are considered the initial test of choice be-cause they’re reliable, inexpensive, and widely available. Testosterone levels vary from hour to hour and diurnally, so a repeat morning measurement is recommended to confirm subnormal levels.^3,5

In some cases—including patients with obesity, type 2 diabetes, or hypothyroidism—the total testosterone level can be misleading; tests for free testosterone and sex hormone-binding globulin levels should be ordered. These tests can also help evaluate men with low-normal total testosterone levels (200-400 ng/dL).^6,7

Is the patient pre- or postpubertal?

Assessment of low testosterone should distinguish between pre- and postpubertal males. In prepubertal males, chromosomal analysis is indicated because hypothalamic-pituitary-gonadal axis defects are common—especially Klinefelter syndrome (1 in 500 males).^6,8

Men with very low testosterone levels (<150 ng/dL) or signs and symptoms suggesting pituitary pathology warrant pituitary imaging and measurement of thyroxine, cortisol, and prolactin levels.⁶ Both pre- and postpubertal males with low testosterone should have FSH, LH, and prolactin levels tested to differentiate primary from secondary hypogonadism.^6,9

Be alert for hemochromatosis and low bone density

Order biopsy or ultrasound examination of testicular masses and iron studies if hemochromatosis is suspected. Hemochromatosis is the most common single gene disorder of Caucasian Americans (1 in 250-300 are homozygous; 1 in 10 are heterozygous) and is associated with hypogonadotrophic hypogonadism.^5,10 In a series of 3 studies, 30% (26 of 89) of men with hemochromatosis had hypogonadism.¹¹ The prevalence of hemochromatosis in males with hypogonadism hasn’t been reported.

Because chronic hypogonadism leads to low bone density and increased risk of fracture, baseline bone densitometry may be prudent.¹² A chart review study of nursing home residents found that 66% of men with hip fractures and 20% of men with vertebral fractures had low testosterone.¹³ Notably, 50% of men in their 80s have testosterone levels in the hypogonadal range (<300 ng/dL), compared with 12% of men <50 years.^1,14

Recommendations

Scant guidance is available concerning what screening tests to order for a male with low testosterone. The United States Preventive Services Task Force and Canadian Task Force on Preventive Health Care make no recommendations; the Cochrane collaboration has no reviews on the topic. The American Association of Clinical Endocrinologists’ (AACE) guidelines are based on expert opinion.³

The AACE consensus guideline used peer review for validation and didn’t specify the method used to assess the quality and strength of the evidence used to write the statement. The AACE guideline recommends a history and physical exam, obtaining repeat morning testosterone levels, prolactin, FSH, LH, bone densitometry, and a semen analysis if fertility is an issue.

In acquired hypogonadism, pituitary imaging is recommended along with thyroid, adrenal, and growth hormone axis testing. Prepubertal males should undergo chromosome analysis, and men with a suspected mass should have a testicular ultrasound examination.

Evidence summary

Clinical diagnosis of scabies begins with pruritus, typical lesions in a distribution consistent with scabies—finger webs, wrists, axillae, elbows, buttocks, genitalia of men, breasts of women—and possible exposure. Clinical diagnosis can be confirmed by skin scrapings from characteristic lesions, such as burrows. When these scrapings are examined under light microscopy, they can show mites, eggs, or feces from the mites (FIGURE). However, this technique depends greatly on operator experience and skill, and a lack of light microscopy findings does not rule out scabies.¹

The only study we found that investigated the sensitivity of clinical features in diagnosing scabies was done in sub-Saharan Africa.² In this study, the presence of diffuse itching, plus lesions in at least 2 locations typical with scabies or a household member with itch, had 100% sensitivity and 96.9% specificity for scabies infection. This study used the evaluation of a dermatologist as a gold standard. The authors propose that treatment based on clinical findings with or without microscopic confirmation is appropriate; however, it is not clear how these data translate to a primary care population with a lower prevalence of scabies.

FIGURE
The “Oh, wow!” test

It is reassuring to know that evidence exists for opting to treat without confirmation. It also saves the patient the cost of the skin scraping and microscopy—important for the increasing numbers of cash-paying, uninsured patients.
—Barbara Walker, Do

Long stretches without symptoms play role in treatment

To date, no controlled trials address whether empiric treatment of asymptomatic contacts or family members of those with scabies decreases its spread. However, it is known that an initial infestation with scabies will not lead to pruritus for up to 4 to 6 weeks.¹ Asymptomatic contacts can be infected with scabies, and can transmit this infection to others before symptoms even occur.

Given the long period of asymptomatic infestation, prevention of epidemics in institutions such as hospitals, nursing homes, and residential facilities is of particular importance. One case-control study, performed at a large tertiary-care teaching hospital, demonstrated that health care workers on a service having a patient with undiagnosed scabies were 5.3 times more likely to develop a pruritic rash than those in other units.³

Health care workers with more skin-to-skin contact with the patients (nurses, nursing students, and physical therapists) were 4.5 times more likely to develop scabies compared with those in less physical contact (physicians, medical students, and occupational therapists). Among the symptomatic health care workers, 17% of their household contacts developed scabies, too.

Permethrin vs lindane? Which is better?

A 2000 Cochrane review, updated in 2002, concluded that permethrin was superior to lindane for topical treatment of scabies.^4,5 Combining 4 trials with 718 patients, permethrin 5% appeared better than lindane 1% (odds ratio=0.66; 95% confidence interval, 0.46–0.95). However, there was significant heterogeneity between the studies, and the largest trial (n=467) found no difference.

Oral ivermectin, though costly, is an effective alternative for those who do not tolerate topical treatment. See the TABLE for a summary of treatment recommendations.

TABLE
Recommended treatment for scabies infection

Recommendations from others

Guidelines released by the Centers for Disease Control and Prevention in 2002 regarding the treatment of sexually transmitted diseases state that both sexual and close personal or household contacts of patients diagnosed with scabies within the preceding month should be examined and treated.⁶

Another guideline, developed by the British Association of Sexual Health and HIV, recommends empiric treatment of sexual, household, and institutional contacts of those with scabies. This guideline recommends treating those who were in contact with the scabies patient within 2 months of his diagnosis; this time frame, though, is arbitrary.⁷ No evidence grading was given for these recommendations, which are based on expert opinion.

Evidence summary

Clinical diagnosis of scabies begins with pruritus, typical lesions in a distribution consistent with scabies—finger webs, wrists, axillae, elbows, buttocks, genitalia of men, breasts of women—and possible exposure. Clinical diagnosis can be confirmed by skin scrapings from characteristic lesions, such as burrows. When these scrapings are examined under light microscopy, they can show mites, eggs, or feces from the mites (FIGURE). However, this technique depends greatly on operator experience and skill, and a lack of light microscopy findings does not rule out scabies.¹

The only study we found that investigated the sensitivity of clinical features in diagnosing scabies was done in sub-Saharan Africa.² In this study, the presence of diffuse itching, plus lesions in at least 2 locations typical with scabies or a household member with itch, had 100% sensitivity and 96.9% specificity for scabies infection. This study used the evaluation of a dermatologist as a gold standard. The authors propose that treatment based on clinical findings with or without microscopic confirmation is appropriate; however, it is not clear how these data translate to a primary care population with a lower prevalence of scabies.

FIGURE
The “Oh, wow!” test

It is reassuring to know that evidence exists for opting to treat without confirmation. It also saves the patient the cost of the skin scraping and microscopy—important for the increasing numbers of cash-paying, uninsured patients.
—Barbara Walker, Do

Long stretches without symptoms play role in treatment

To date, no controlled trials address whether empiric treatment of asymptomatic contacts or family members of those with scabies decreases its spread. However, it is known that an initial infestation with scabies will not lead to pruritus for up to 4 to 6 weeks.¹ Asymptomatic contacts can be infected with scabies, and can transmit this infection to others before symptoms even occur.

Given the long period of asymptomatic infestation, prevention of epidemics in institutions such as hospitals, nursing homes, and residential facilities is of particular importance. One case-control study, performed at a large tertiary-care teaching hospital, demonstrated that health care workers on a service having a patient with undiagnosed scabies were 5.3 times more likely to develop a pruritic rash than those in other units.³

Health care workers with more skin-to-skin contact with the patients (nurses, nursing students, and physical therapists) were 4.5 times more likely to develop scabies compared with those in less physical contact (physicians, medical students, and occupational therapists). Among the symptomatic health care workers, 17% of their household contacts developed scabies, too.

Permethrin vs lindane? Which is better?

A 2000 Cochrane review, updated in 2002, concluded that permethrin was superior to lindane for topical treatment of scabies.^4,5 Combining 4 trials with 718 patients, permethrin 5% appeared better than lindane 1% (odds ratio=0.66; 95% confidence interval, 0.46–0.95). However, there was significant heterogeneity between the studies, and the largest trial (n=467) found no difference.

Oral ivermectin, though costly, is an effective alternative for those who do not tolerate topical treatment. See the TABLE for a summary of treatment recommendations.

TABLE
Recommended treatment for scabies infection

Recommendations from others

Guidelines released by the Centers for Disease Control and Prevention in 2002 regarding the treatment of sexually transmitted diseases state that both sexual and close personal or household contacts of patients diagnosed with scabies within the preceding month should be examined and treated.⁶

Another guideline, developed by the British Association of Sexual Health and HIV, recommends empiric treatment of sexual, household, and institutional contacts of those with scabies. This guideline recommends treating those who were in contact with the scabies patient within 2 months of his diagnosis; this time frame, though, is arbitrary.⁷ No evidence grading was given for these recommendations, which are based on expert opinion.

Evidence summary

Clinical diagnosis of scabies begins with pruritus, typical lesions in a distribution consistent with scabies—finger webs, wrists, axillae, elbows, buttocks, genitalia of men, breasts of women—and possible exposure. Clinical diagnosis can be confirmed by skin scrapings from characteristic lesions, such as burrows. When these scrapings are examined under light microscopy, they can show mites, eggs, or feces from the mites (FIGURE). However, this technique depends greatly on operator experience and skill, and a lack of light microscopy findings does not rule out scabies.¹

The only study we found that investigated the sensitivity of clinical features in diagnosing scabies was done in sub-Saharan Africa.² In this study, the presence of diffuse itching, plus lesions in at least 2 locations typical with scabies or a household member with itch, had 100% sensitivity and 96.9% specificity for scabies infection. This study used the evaluation of a dermatologist as a gold standard. The authors propose that treatment based on clinical findings with or without microscopic confirmation is appropriate; however, it is not clear how these data translate to a primary care population with a lower prevalence of scabies.

FIGURE
The “Oh, wow!” test

It is reassuring to know that evidence exists for opting to treat without confirmation. It also saves the patient the cost of the skin scraping and microscopy—important for the increasing numbers of cash-paying, uninsured patients.
—Barbara Walker, Do

Long stretches without symptoms play role in treatment

To date, no controlled trials address whether empiric treatment of asymptomatic contacts or family members of those with scabies decreases its spread. However, it is known that an initial infestation with scabies will not lead to pruritus for up to 4 to 6 weeks.¹ Asymptomatic contacts can be infected with scabies, and can transmit this infection to others before symptoms even occur.

Given the long period of asymptomatic infestation, prevention of epidemics in institutions such as hospitals, nursing homes, and residential facilities is of particular importance. One case-control study, performed at a large tertiary-care teaching hospital, demonstrated that health care workers on a service having a patient with undiagnosed scabies were 5.3 times more likely to develop a pruritic rash than those in other units.³

Health care workers with more skin-to-skin contact with the patients (nurses, nursing students, and physical therapists) were 4.5 times more likely to develop scabies compared with those in less physical contact (physicians, medical students, and occupational therapists). Among the symptomatic health care workers, 17% of their household contacts developed scabies, too.

Permethrin vs lindane? Which is better?

A 2000 Cochrane review, updated in 2002, concluded that permethrin was superior to lindane for topical treatment of scabies.^4,5 Combining 4 trials with 718 patients, permethrin 5% appeared better than lindane 1% (odds ratio=0.66; 95% confidence interval, 0.46–0.95). However, there was significant heterogeneity between the studies, and the largest trial (n=467) found no difference.

Oral ivermectin, though costly, is an effective alternative for those who do not tolerate topical treatment. See the TABLE for a summary of treatment recommendations.

TABLE
Recommended treatment for scabies infection

Recommendations from others

Guidelines released by the Centers for Disease Control and Prevention in 2002 regarding the treatment of sexually transmitted diseases state that both sexual and close personal or household contacts of patients diagnosed with scabies within the preceding month should be examined and treated.⁶

Another guideline, developed by the British Association of Sexual Health and HIV, recommends empiric treatment of sexual, household, and institutional contacts of those with scabies. This guideline recommends treating those who were in contact with the scabies patient within 2 months of his diagnosis; this time frame, though, is arbitrary.⁷ No evidence grading was given for these recommendations, which are based on expert opinion.

TABLE
Summary of HSV test characteristics

Evidence summary

Our literature search failed to find any randomized controlled trials comparing diagnostic tests for HSV-2 infection among asymptomatic populations. Data from cross-sectional studies, however, are available.

Glycoprotein G ELISA has better specificity

Using the Western blot technique as the gold standard, a total of 158 serum samples from patients with either HSV-1 or HSV-2 infection—without mention of symptomatology—were used to compare the performance of several commercially available ELISA assays.¹ The glycoprotein G and non–glycoprotein G ELISA tests were both found to have sensitivities >90%, but the non–glycoprotein G ELISA tests had specificities under 90%.

In 47% to 82% of the samples tested with non–glycoprotein G ELISA, there was cross-reactivity between HSV-1 and HSV-2 antibodies.¹ The College of American Pathologists found that 46% to 84% of laboratories using non–glycoprotein G ELISA tests incorrectly identified an HSV-1 sample as being HSV-2. All laboratories reporting use of glycoprotein G ELISA tests correctly identified the sample as containing only HSV-1 antibodies.² Neither study included controls, delineated symptom status, or measured patient-oriented outcomes.

Genital culture has poor sensitivity

A prospective cohort study compared the viral shedding by Western blot among 52 asymptomatic seropositive patients with 90 seropositive and symptomatic patients.³ Daily genital swabs were done for 3 months for each patient. The asymptomatic individuals had HSV-2 positive cultures on 3% of culture days.³ Genital culture appears to have a very poor sensitivity (5%) for diagnosis of HSV-2 infection among asymptomatic individuals.

We found no studies that measured patient-oriented harms or benefits arising from testing asymptomatic individuals for HSV-2 infection.

Recommendations from others

The USPSTF recommends against routine serological screening for HSV in asymptomatic adolescents and adults (D recommendation, fair or good evidence that the service is ineffective or that the harms outweigh the benefits).⁴ The California Sexually Transmitted Diseases Controllers Association recommends that serologic testing is likely to benefit HIV-infected patients, those whose sexual partners have genital herpes, and those at high risk of STDs motivated to reduce their sexual risk behavior.⁵

TABLE
Summary of HSV test characteristics

Evidence summary

Our literature search failed to find any randomized controlled trials comparing diagnostic tests for HSV-2 infection among asymptomatic populations. Data from cross-sectional studies, however, are available.

Glycoprotein G ELISA has better specificity

Using the Western blot technique as the gold standard, a total of 158 serum samples from patients with either HSV-1 or HSV-2 infection—without mention of symptomatology—were used to compare the performance of several commercially available ELISA assays.¹ The glycoprotein G and non–glycoprotein G ELISA tests were both found to have sensitivities >90%, but the non–glycoprotein G ELISA tests had specificities under 90%.

In 47% to 82% of the samples tested with non–glycoprotein G ELISA, there was cross-reactivity between HSV-1 and HSV-2 antibodies.¹ The College of American Pathologists found that 46% to 84% of laboratories using non–glycoprotein G ELISA tests incorrectly identified an HSV-1 sample as being HSV-2. All laboratories reporting use of glycoprotein G ELISA tests correctly identified the sample as containing only HSV-1 antibodies.² Neither study included controls, delineated symptom status, or measured patient-oriented outcomes.

Genital culture has poor sensitivity

A prospective cohort study compared the viral shedding by Western blot among 52 asymptomatic seropositive patients with 90 seropositive and symptomatic patients.³ Daily genital swabs were done for 3 months for each patient. The asymptomatic individuals had HSV-2 positive cultures on 3% of culture days.³ Genital culture appears to have a very poor sensitivity (5%) for diagnosis of HSV-2 infection among asymptomatic individuals.

We found no studies that measured patient-oriented harms or benefits arising from testing asymptomatic individuals for HSV-2 infection.

Recommendations from others

The USPSTF recommends against routine serological screening for HSV in asymptomatic adolescents and adults (D recommendation, fair or good evidence that the service is ineffective or that the harms outweigh the benefits).⁴ The California Sexually Transmitted Diseases Controllers Association recommends that serologic testing is likely to benefit HIV-infected patients, those whose sexual partners have genital herpes, and those at high risk of STDs motivated to reduce their sexual risk behavior.⁵

TABLE
Summary of HSV test characteristics

Evidence summary

Our literature search failed to find any randomized controlled trials comparing diagnostic tests for HSV-2 infection among asymptomatic populations. Data from cross-sectional studies, however, are available.

Glycoprotein G ELISA has better specificity

Using the Western blot technique as the gold standard, a total of 158 serum samples from patients with either HSV-1 or HSV-2 infection—without mention of symptomatology—were used to compare the performance of several commercially available ELISA assays.¹ The glycoprotein G and non–glycoprotein G ELISA tests were both found to have sensitivities >90%, but the non–glycoprotein G ELISA tests had specificities under 90%.

In 47% to 82% of the samples tested with non–glycoprotein G ELISA, there was cross-reactivity between HSV-1 and HSV-2 antibodies.¹ The College of American Pathologists found that 46% to 84% of laboratories using non–glycoprotein G ELISA tests incorrectly identified an HSV-1 sample as being HSV-2. All laboratories reporting use of glycoprotein G ELISA tests correctly identified the sample as containing only HSV-1 antibodies.² Neither study included controls, delineated symptom status, or measured patient-oriented outcomes.

Genital culture has poor sensitivity

A prospective cohort study compared the viral shedding by Western blot among 52 asymptomatic seropositive patients with 90 seropositive and symptomatic patients.³ Daily genital swabs were done for 3 months for each patient. The asymptomatic individuals had HSV-2 positive cultures on 3% of culture days.³ Genital culture appears to have a very poor sensitivity (5%) for diagnosis of HSV-2 infection among asymptomatic individuals.

We found no studies that measured patient-oriented harms or benefits arising from testing asymptomatic individuals for HSV-2 infection.

Recommendations from others

The USPSTF recommends against routine serological screening for HSV in asymptomatic adolescents and adults (D recommendation, fair or good evidence that the service is ineffective or that the harms outweigh the benefits).⁴ The California Sexually Transmitted Diseases Controllers Association recommends that serologic testing is likely to benefit HIV-infected patients, those whose sexual partners have genital herpes, and those at high risk of STDs motivated to reduce their sexual risk behavior.⁵

Evidence summary

Our search for articles that examined patient- and primary care–oriented PID diagnostic tests resulted in 2 systematic reviews, no randomized controlled trials, 4 data analyses, and 5 cohort studies, all of which were fair- to good-quality.

Systematic reviews don’t show consistent results

One systematic review of 12 fair- to good-quality studies, based in Europe and the US, included urban populations treated in Ob/Gyn departments, emergency rooms, and sexually transmitted disease clinics. This review supports a thorough evaluation when more severe disease is suspected and the use of sensitive diagnostic tests for suspected mild disease—eg, CRP (74%–93% sensitivity) and ESR (64%–81% sensitivity for value >20 or 15 mm/h).³

Another systematic review of 19 fair-to good-quality cohort studies found a sensitivity of only 64% for laparoscopy, 50% to 87% for endometrial biopsy, and up to 80% for microbiological tests. Results were not consistent for the reported sensitivity of WBC, ESR, or CRP.⁴

Multivariate analyses of Swedish data come to different conclusions

We identified no randomized controlled trials that addressed the diagnosis of PID. Two multivariate analyses of the same Swedish data from the 1960s came to different conclusions.

The Lund analysis includes data collected between 1960 and 1969 at Lund University Hospital in Sweden on women with suspected PID, with about 625 cases included for these analyses. Simms et al⁵ found insufficient evidence from these data for any existing diagnostic criteria.

Looking at the same data, Hagdu et al proposed the use of a clinical criteria model including low abdominal pain and 2 or more of the following other criteria: vaginal discharge, temperature greater than 38°C, vomiting, irregular menses, urologic or proctitis symptoms, pelvic tenderness, adnexal mass or swelling, and ESR ≥15.⁶ This model had a reported sensitivity of 87%, specificity of 52.5%, and false-positive and false-negative rates of 21.2% and 33.3%, respectively.

Looking at adnexal tenderness aids sensitivity of other tests

Cross-sectional analysis of a multisite US randomized treatment trial supported using adnexal tenderness as a minimum clinical criterion to increase sensitivity.¹ Further analysis of that trial suggests that some asymptomatic women are at equivalent risk of developing sequelae compared with symptomatic women diagnosed with PID. Those asymptomatic women who met diagnostic criteria with a positive endometrial biopsy were more likely to have pelvic tenderness than asymptomatic women who were not diagnosed.²

Symptoms >1 week and elevated WBC also helpful

Two small, fair-quality cohort studies (N=61 and 176, respectively) investigated the use of clinical diagnostic criteria for PID. The smaller study compared clinical criteria to several reference standards (laparoscopy, histology, microbiological markers, and transvaginal ultrasound) and found clinical criteria, specifically adnexal tenderness, most sensitive (87%), and laparoscopy most specific (100%).⁷

In the second study, the authors evaluated 176 consecutive admissions for clinically diagnosed PID, 76% of which were laparoscopically confirmed. Reviewing clinical indicators, they found that a combination of adnexal tenderness, symptoms for <1 week, and elevated WBC was the most sensitive set of predictors (sensitivity 86.6%, specificity 45.7%) with positive predictive value of 0.84 and negative predictive value of 0.52.⁸

Useful lab indicators: C-reactive protein, serum CA-125

Three small cohort studies (N=50–152) of fair-quality evaluated various laboratory indicators in the diagnosis of PID. Each used a different reference standard: clinical criteria, laparoscopy, and endometrial biopsy, respectively.

One study found CRP >10 to be 93% sensitive and 83% specific in a cohort of women admitted to the emergency department with an acute gynecological disorder.⁹ This population had a high baseline incidence of PID, pregnancy, and intrauterine device use.

A study of serum CA-125 levels showed a predictive value of 97% for values >16 U/mL in diagnosing salpingitis. This test might therefore be useful in confirming peritoneal involvement when PID is suspected clinically.¹⁰

Another study developed a model using vaginal WBC (the single most sensitive factor at 78%), serum WBC (the single most specific factor at 88%), CRP, and ESR. The model was 100% sensitive if the diagnosis only required 1 positive test, although the specificity was only 18%. The positive predictive value was 65%. If all 4 were positive, specificity was 95%, with 29% sensitivity, a positive predictive value of 90%, and a negative predictive value of 47%. Prevalence was 60% in the group studied.¹¹

Recommendations from others

The CDC recommends empiric treatment of women with lower abdominal or pelvic pain who are at risk for sexually transmitted diseases with uterine, adnexal, or cervical motion tenderness and no other identifiable cause.¹²

Clinical Evidence found no RCTs that compared empiric treatment of suspected PID with waiting for microbiological test results for guidance.¹³

The Agency for Healthcare Research and Quality recommends requiring the presence of lower abdominal, adnexal and cervical tenderness, without alternative diagnosis, for the diagnosis of PID. Temperature >101°F, cervical or vaginal discharge, elevated ESR, and positive gonococcal or chlamydia cultures all increase specificity of diagnosis.¹⁴

The United Kingdom’s national guideline recommends maintaining a low threshold for empirical treatment, citing a lack of definitive diagnostic criteria and potential for sequelae, but does recommend testing for gonorrhea and chlamydia.¹⁵

Evidence summary

Our search for articles that examined patient- and primary care–oriented PID diagnostic tests resulted in 2 systematic reviews, no randomized controlled trials, 4 data analyses, and 5 cohort studies, all of which were fair- to good-quality.

Systematic reviews don’t show consistent results

One systematic review of 12 fair- to good-quality studies, based in Europe and the US, included urban populations treated in Ob/Gyn departments, emergency rooms, and sexually transmitted disease clinics. This review supports a thorough evaluation when more severe disease is suspected and the use of sensitive diagnostic tests for suspected mild disease—eg, CRP (74%–93% sensitivity) and ESR (64%–81% sensitivity for value >20 or 15 mm/h).³

Another systematic review of 19 fair-to good-quality cohort studies found a sensitivity of only 64% for laparoscopy, 50% to 87% for endometrial biopsy, and up to 80% for microbiological tests. Results were not consistent for the reported sensitivity of WBC, ESR, or CRP.⁴

Multivariate analyses of Swedish data come to different conclusions

We identified no randomized controlled trials that addressed the diagnosis of PID. Two multivariate analyses of the same Swedish data from the 1960s came to different conclusions.

The Lund analysis includes data collected between 1960 and 1969 at Lund University Hospital in Sweden on women with suspected PID, with about 625 cases included for these analyses. Simms et al⁵ found insufficient evidence from these data for any existing diagnostic criteria.

Looking at the same data, Hagdu et al proposed the use of a clinical criteria model including low abdominal pain and 2 or more of the following other criteria: vaginal discharge, temperature greater than 38°C, vomiting, irregular menses, urologic or proctitis symptoms, pelvic tenderness, adnexal mass or swelling, and ESR ≥15.⁶ This model had a reported sensitivity of 87%, specificity of 52.5%, and false-positive and false-negative rates of 21.2% and 33.3%, respectively.

Looking at adnexal tenderness aids sensitivity of other tests

Cross-sectional analysis of a multisite US randomized treatment trial supported using adnexal tenderness as a minimum clinical criterion to increase sensitivity.¹ Further analysis of that trial suggests that some asymptomatic women are at equivalent risk of developing sequelae compared with symptomatic women diagnosed with PID. Those asymptomatic women who met diagnostic criteria with a positive endometrial biopsy were more likely to have pelvic tenderness than asymptomatic women who were not diagnosed.²

Symptoms >1 week and elevated WBC also helpful

Two small, fair-quality cohort studies (N=61 and 176, respectively) investigated the use of clinical diagnostic criteria for PID. The smaller study compared clinical criteria to several reference standards (laparoscopy, histology, microbiological markers, and transvaginal ultrasound) and found clinical criteria, specifically adnexal tenderness, most sensitive (87%), and laparoscopy most specific (100%).⁷

In the second study, the authors evaluated 176 consecutive admissions for clinically diagnosed PID, 76% of which were laparoscopically confirmed. Reviewing clinical indicators, they found that a combination of adnexal tenderness, symptoms for <1 week, and elevated WBC was the most sensitive set of predictors (sensitivity 86.6%, specificity 45.7%) with positive predictive value of 0.84 and negative predictive value of 0.52.⁸

Useful lab indicators: C-reactive protein, serum CA-125

Three small cohort studies (N=50–152) of fair-quality evaluated various laboratory indicators in the diagnosis of PID. Each used a different reference standard: clinical criteria, laparoscopy, and endometrial biopsy, respectively.

One study found CRP >10 to be 93% sensitive and 83% specific in a cohort of women admitted to the emergency department with an acute gynecological disorder.⁹ This population had a high baseline incidence of PID, pregnancy, and intrauterine device use.

A study of serum CA-125 levels showed a predictive value of 97% for values >16 U/mL in diagnosing salpingitis. This test might therefore be useful in confirming peritoneal involvement when PID is suspected clinically.¹⁰

Another study developed a model using vaginal WBC (the single most sensitive factor at 78%), serum WBC (the single most specific factor at 88%), CRP, and ESR. The model was 100% sensitive if the diagnosis only required 1 positive test, although the specificity was only 18%. The positive predictive value was 65%. If all 4 were positive, specificity was 95%, with 29% sensitivity, a positive predictive value of 90%, and a negative predictive value of 47%. Prevalence was 60% in the group studied.¹¹

Recommendations from others

The CDC recommends empiric treatment of women with lower abdominal or pelvic pain who are at risk for sexually transmitted diseases with uterine, adnexal, or cervical motion tenderness and no other identifiable cause.¹²

Clinical Evidence found no RCTs that compared empiric treatment of suspected PID with waiting for microbiological test results for guidance.¹³

The Agency for Healthcare Research and Quality recommends requiring the presence of lower abdominal, adnexal and cervical tenderness, without alternative diagnosis, for the diagnosis of PID. Temperature >101°F, cervical or vaginal discharge, elevated ESR, and positive gonococcal or chlamydia cultures all increase specificity of diagnosis.¹⁴

The United Kingdom’s national guideline recommends maintaining a low threshold for empirical treatment, citing a lack of definitive diagnostic criteria and potential for sequelae, but does recommend testing for gonorrhea and chlamydia.¹⁵

Evidence summary

Our search for articles that examined patient- and primary care–oriented PID diagnostic tests resulted in 2 systematic reviews, no randomized controlled trials, 4 data analyses, and 5 cohort studies, all of which were fair- to good-quality.

Systematic reviews don’t show consistent results

One systematic review of 12 fair- to good-quality studies, based in Europe and the US, included urban populations treated in Ob/Gyn departments, emergency rooms, and sexually transmitted disease clinics. This review supports a thorough evaluation when more severe disease is suspected and the use of sensitive diagnostic tests for suspected mild disease—eg, CRP (74%–93% sensitivity) and ESR (64%–81% sensitivity for value >20 or 15 mm/h).³

Another systematic review of 19 fair-to good-quality cohort studies found a sensitivity of only 64% for laparoscopy, 50% to 87% for endometrial biopsy, and up to 80% for microbiological tests. Results were not consistent for the reported sensitivity of WBC, ESR, or CRP.⁴

Multivariate analyses of Swedish data come to different conclusions

We identified no randomized controlled trials that addressed the diagnosis of PID. Two multivariate analyses of the same Swedish data from the 1960s came to different conclusions.

The Lund analysis includes data collected between 1960 and 1969 at Lund University Hospital in Sweden on women with suspected PID, with about 625 cases included for these analyses. Simms et al⁵ found insufficient evidence from these data for any existing diagnostic criteria.

Looking at the same data, Hagdu et al proposed the use of a clinical criteria model including low abdominal pain and 2 or more of the following other criteria: vaginal discharge, temperature greater than 38°C, vomiting, irregular menses, urologic or proctitis symptoms, pelvic tenderness, adnexal mass or swelling, and ESR ≥15.⁶ This model had a reported sensitivity of 87%, specificity of 52.5%, and false-positive and false-negative rates of 21.2% and 33.3%, respectively.

Looking at adnexal tenderness aids sensitivity of other tests

Cross-sectional analysis of a multisite US randomized treatment trial supported using adnexal tenderness as a minimum clinical criterion to increase sensitivity.¹ Further analysis of that trial suggests that some asymptomatic women are at equivalent risk of developing sequelae compared with symptomatic women diagnosed with PID. Those asymptomatic women who met diagnostic criteria with a positive endometrial biopsy were more likely to have pelvic tenderness than asymptomatic women who were not diagnosed.²

Symptoms >1 week and elevated WBC also helpful

Two small, fair-quality cohort studies (N=61 and 176, respectively) investigated the use of clinical diagnostic criteria for PID. The smaller study compared clinical criteria to several reference standards (laparoscopy, histology, microbiological markers, and transvaginal ultrasound) and found clinical criteria, specifically adnexal tenderness, most sensitive (87%), and laparoscopy most specific (100%).⁷

In the second study, the authors evaluated 176 consecutive admissions for clinically diagnosed PID, 76% of which were laparoscopically confirmed. Reviewing clinical indicators, they found that a combination of adnexal tenderness, symptoms for <1 week, and elevated WBC was the most sensitive set of predictors (sensitivity 86.6%, specificity 45.7%) with positive predictive value of 0.84 and negative predictive value of 0.52.⁸

Useful lab indicators: C-reactive protein, serum CA-125

Three small cohort studies (N=50–152) of fair-quality evaluated various laboratory indicators in the diagnosis of PID. Each used a different reference standard: clinical criteria, laparoscopy, and endometrial biopsy, respectively.

One study found CRP >10 to be 93% sensitive and 83% specific in a cohort of women admitted to the emergency department with an acute gynecological disorder.⁹ This population had a high baseline incidence of PID, pregnancy, and intrauterine device use.

A study of serum CA-125 levels showed a predictive value of 97% for values >16 U/mL in diagnosing salpingitis. This test might therefore be useful in confirming peritoneal involvement when PID is suspected clinically.¹⁰

Another study developed a model using vaginal WBC (the single most sensitive factor at 78%), serum WBC (the single most specific factor at 88%), CRP, and ESR. The model was 100% sensitive if the diagnosis only required 1 positive test, although the specificity was only 18%. The positive predictive value was 65%. If all 4 were positive, specificity was 95%, with 29% sensitivity, a positive predictive value of 90%, and a negative predictive value of 47%. Prevalence was 60% in the group studied.¹¹

Recommendations from others

The CDC recommends empiric treatment of women with lower abdominal or pelvic pain who are at risk for sexually transmitted diseases with uterine, adnexal, or cervical motion tenderness and no other identifiable cause.¹²

Clinical Evidence found no RCTs that compared empiric treatment of suspected PID with waiting for microbiological test results for guidance.¹³

The Agency for Healthcare Research and Quality recommends requiring the presence of lower abdominal, adnexal and cervical tenderness, without alternative diagnosis, for the diagnosis of PID. Temperature >101°F, cervical or vaginal discharge, elevated ESR, and positive gonococcal or chlamydia cultures all increase specificity of diagnosis.¹⁴

The United Kingdom’s national guideline recommends maintaining a low threshold for empirical treatment, citing a lack of definitive diagnostic criteria and potential for sequelae, but does recommend testing for gonorrhea and chlamydia.¹⁵

Evidence Summary

Our comprehensive literature search found no studies that provide direct evidence for or against continuing to monitor microalbuminuria among patients with diabetes already on ACE inhibitor or ARB therapy. We reviewed and included indirect evidence and expert opinion to answer this clinical question.

Diabetes mellitus is the leading cause of end-stage renal disease in the Western world.¹ The prevalence of diabetic nephropathy continues to rise along with the rapidly rising prevalence of obesity and diabetes, with 40% of patients with diabetes at risk of developing nephropathy. One study that followed 5097 patients with type 2 diabetes over a median of 10.4 years found that 2% of patients progressed from normal levels of urinary protein to microalbuminuria; 2.8% changed from microalbuminuria to macroalbuminuria (urine albumin >300 mg in a 24-hour period); and 2.3% progressed to chronic renal disease (creatinine ≥2 mg/dL) from macroalbuminuria per year.² Chronic renal disease is more likely to occur in those patients whose hypertension or hyperglycemia is poorly controlled.

For patients with diabetes who develop microalbuminuria, the evidence is good for starting ACE inhibitors or ARBs for renal protection.^3,4 The American Diabetes Association (ADA) also recommends that patients with diabetes and hypertension and those aged >55 years with other cardiovascular risk factors (history of cardiovascular disease, dyslipidemia, or tobacco use) be started on ACE inhibitors or ARBs.¹ There is also good evidence that screening for microalbuminuria can identify those who might benefit from treatments that delay the onset of nephropathy.⁵

Recent studies have raised the possibility of further benefit in prevention and treatment of diabetic nephropathy by maximizing doses of ACE inhibitors or ARBs, and even from the dual blockade attained from using both. For example, during a 2-year trial—in which 590 patients with diabetes and microalbuminuria were randomized to receive placebo, 150 mg irbesartan, or 300 mg irbesartan—14.9% of the placebo group, 9.7% of the 150-mg group, and only 5.2% of the 300-mg group progressed to overt nephropathy.⁶ In very small randomized trial of 20 patients with type 2 diabetes, adding 16 mg of candesartan to the maximal dose of an ACE inhibitor decreased albuminuria an additional 28%.⁷

Experts argue that it may benefit patients to continue regular surveillance for the presence or progression of microalbuminuria even if they are already taking an ACE inhibitor or ARB so that therapy can be maximized.^1,8 However, no direct evidence supports this recommendation.

Recommendations from others

The ADA suggests that clinicians perform a test each year for microalbuminuria among patients with type 1 diabetes of ≥5 years duration, and in all patients with type 2 diabetes at diagnosis and during pregnancy. They also recommend continued surveillance of proteinuria to assess both response to therapy and progression of disease.¹

The National Kidney Foundation recommends continued surveillance of microalbuminuria to assess progression of chronic kidney disease and response to therapy.⁸

Evidence Summary

Our comprehensive literature search found no studies that provide direct evidence for or against continuing to monitor microalbuminuria among patients with diabetes already on ACE inhibitor or ARB therapy. We reviewed and included indirect evidence and expert opinion to answer this clinical question.

Diabetes mellitus is the leading cause of end-stage renal disease in the Western world.¹ The prevalence of diabetic nephropathy continues to rise along with the rapidly rising prevalence of obesity and diabetes, with 40% of patients with diabetes at risk of developing nephropathy. One study that followed 5097 patients with type 2 diabetes over a median of 10.4 years found that 2% of patients progressed from normal levels of urinary protein to microalbuminuria; 2.8% changed from microalbuminuria to macroalbuminuria (urine albumin >300 mg in a 24-hour period); and 2.3% progressed to chronic renal disease (creatinine ≥2 mg/dL) from macroalbuminuria per year.² Chronic renal disease is more likely to occur in those patients whose hypertension or hyperglycemia is poorly controlled.

For patients with diabetes who develop microalbuminuria, the evidence is good for starting ACE inhibitors or ARBs for renal protection.^3,4 The American Diabetes Association (ADA) also recommends that patients with diabetes and hypertension and those aged >55 years with other cardiovascular risk factors (history of cardiovascular disease, dyslipidemia, or tobacco use) be started on ACE inhibitors or ARBs.¹ There is also good evidence that screening for microalbuminuria can identify those who might benefit from treatments that delay the onset of nephropathy.⁵

Recent studies have raised the possibility of further benefit in prevention and treatment of diabetic nephropathy by maximizing doses of ACE inhibitors or ARBs, and even from the dual blockade attained from using both. For example, during a 2-year trial—in which 590 patients with diabetes and microalbuminuria were randomized to receive placebo, 150 mg irbesartan, or 300 mg irbesartan—14.9% of the placebo group, 9.7% of the 150-mg group, and only 5.2% of the 300-mg group progressed to overt nephropathy.⁶ In very small randomized trial of 20 patients with type 2 diabetes, adding 16 mg of candesartan to the maximal dose of an ACE inhibitor decreased albuminuria an additional 28%.⁷

Experts argue that it may benefit patients to continue regular surveillance for the presence or progression of microalbuminuria even if they are already taking an ACE inhibitor or ARB so that therapy can be maximized.^1,8 However, no direct evidence supports this recommendation.

Recommendations from others

The ADA suggests that clinicians perform a test each year for microalbuminuria among patients with type 1 diabetes of ≥5 years duration, and in all patients with type 2 diabetes at diagnosis and during pregnancy. They also recommend continued surveillance of proteinuria to assess both response to therapy and progression of disease.¹

The National Kidney Foundation recommends continued surveillance of microalbuminuria to assess progression of chronic kidney disease and response to therapy.⁸

Evidence Summary

Our comprehensive literature search found no studies that provide direct evidence for or against continuing to monitor microalbuminuria among patients with diabetes already on ACE inhibitor or ARB therapy. We reviewed and included indirect evidence and expert opinion to answer this clinical question.

Diabetes mellitus is the leading cause of end-stage renal disease in the Western world.¹ The prevalence of diabetic nephropathy continues to rise along with the rapidly rising prevalence of obesity and diabetes, with 40% of patients with diabetes at risk of developing nephropathy. One study that followed 5097 patients with type 2 diabetes over a median of 10.4 years found that 2% of patients progressed from normal levels of urinary protein to microalbuminuria; 2.8% changed from microalbuminuria to macroalbuminuria (urine albumin >300 mg in a 24-hour period); and 2.3% progressed to chronic renal disease (creatinine ≥2 mg/dL) from macroalbuminuria per year.² Chronic renal disease is more likely to occur in those patients whose hypertension or hyperglycemia is poorly controlled.

For patients with diabetes who develop microalbuminuria, the evidence is good for starting ACE inhibitors or ARBs for renal protection.^3,4 The American Diabetes Association (ADA) also recommends that patients with diabetes and hypertension and those aged >55 years with other cardiovascular risk factors (history of cardiovascular disease, dyslipidemia, or tobacco use) be started on ACE inhibitors or ARBs.¹ There is also good evidence that screening for microalbuminuria can identify those who might benefit from treatments that delay the onset of nephropathy.⁵

Recent studies have raised the possibility of further benefit in prevention and treatment of diabetic nephropathy by maximizing doses of ACE inhibitors or ARBs, and even from the dual blockade attained from using both. For example, during a 2-year trial—in which 590 patients with diabetes and microalbuminuria were randomized to receive placebo, 150 mg irbesartan, or 300 mg irbesartan—14.9% of the placebo group, 9.7% of the 150-mg group, and only 5.2% of the 300-mg group progressed to overt nephropathy.⁶ In very small randomized trial of 20 patients with type 2 diabetes, adding 16 mg of candesartan to the maximal dose of an ACE inhibitor decreased albuminuria an additional 28%.⁷

Experts argue that it may benefit patients to continue regular surveillance for the presence or progression of microalbuminuria even if they are already taking an ACE inhibitor or ARB so that therapy can be maximized.^1,8 However, no direct evidence supports this recommendation.

Recommendations from others

The ADA suggests that clinicians perform a test each year for microalbuminuria among patients with type 1 diabetes of ≥5 years duration, and in all patients with type 2 diabetes at diagnosis and during pregnancy. They also recommend continued surveillance of proteinuria to assess both response to therapy and progression of disease.¹

The National Kidney Foundation recommends continued surveillance of microalbuminuria to assess progression of chronic kidney disease and response to therapy.⁸

Evidence Summary

Heart rate varies by age; however, tachycardia in adults is usually defined as a rate exceeding 100 beats/minute.¹ Tachycardia at rest requires a diagnostic evaluation. However, our search found no systematic reviews, randomized trials, or prospective cohort studies relevant to this question. The highest level of evidence we located was an international practice guideline developed by the American College of Cardiology, the American Heart Association Task Force on Practice Guidelines, and the European Society of Cardiology Committee for Practice Guidelines.¹

This joint guideline recommends that the diagnostic evaluation of a hemodynamically stable patient should begin with a clinical history, physical examination with relevant labs, and 12-lead ECG.¹ Many patients with tachycardia are asymptomatic; however, common symptoms and complaints include palpitations, fatigue, lightheadedness, chest discomfort, dyspnea, presyncope, or syncope.¹ If the patient has experienced symptoms, it is of crucial importance to obtain a clinical history describing the pattern in terms of the number of episodes, duration, frequency, mode of onset, and possible triggers.¹

The main goals of the physical examination, labs, and the 12-lead ECG are to determine if the patient has a sinus or non-sinus tachycardia and to look for other findings that may suggest either a cause for the tachycardia or any complications resulting from the tachycardia.

First, determine if the patient’s heartbeat is regular or irregular. Atrial flutter and atrial fibrillation are common causes of an irregular heartbeat that can easily be diagnosed with a 12-lead ECG. Second, determine the width of the QRS interval: narrow QRS complex tachycardias are supraventricular (from the sinus node, the atria, and the atrioventricular junction) in origin, and wide QRS complex tachycardias are usually ventricular (from all sites below the AV junction).^2,3 If an irregular heartbeat or wide-complex tachycardia is detected, appropriate management (including possible urgent referrals) should begin immediately.¹ A stable patient with a regular rhythm and a narrow QRS complex can be further investigated at a more relaxed pace.

Refer to the TABLE for a listing of common secondary causes for sinus tachycardia, which should direct lab investigations. If no secondary cause is easily identifiable, a 24-hour monitor is recommended as the next step.

TABLE
Potential secondary causes of resting sinus tachycardia^5-7

Recommendations from others

Textbook chapters and other review articles regarding this topic describe a similar initial evaluation and provide further details about interpreting the 12-lead ECG.^2-7 The most relevant and recent review article suggests that further investigation of narrow QRS complex tachycardias with a regular rate currently involves 4 diagnostic categories: normal sinus tachycardia (ie, secondary cause can be identified), inappropriate sinus tachycardia (IST), postural orthostatic tachycardia syndrome (POTS), and sinus node reentry tachycardia (SNRT).⁴

If a secondary cause is identified, it should be treated appropriately. If no underlying cause is discovered, a 24-hour Holter monitor is recommended.

Persistent sinus tachycardia (sometimes with nocturnal normalization of heart rate) is diagnosed as IST.⁴ If the monitor shows paroxysmal episodes of sinus tachycardia, determine if they are triggered by orthostasis and relieved by recumbency (confirm with head upright tilt test) to make the diagnosis of POTS. If it is not POTS, the recordings from the 24-hour Holter monitor help make the diagnosis of SNRT, which consists of sudden, paroxysmal, and usually nonsustained tachycardia.⁴ The FIGURE shows an algorithm of one common diagnostic strategy for evaluation of tachycardia.^2-7

FIGURE
Diagnostic algorithm for evaluating tachycardias⁴

Evidence Summary

Heart rate varies by age; however, tachycardia in adults is usually defined as a rate exceeding 100 beats/minute.¹ Tachycardia at rest requires a diagnostic evaluation. However, our search found no systematic reviews, randomized trials, or prospective cohort studies relevant to this question. The highest level of evidence we located was an international practice guideline developed by the American College of Cardiology, the American Heart Association Task Force on Practice Guidelines, and the European Society of Cardiology Committee for Practice Guidelines.¹

This joint guideline recommends that the diagnostic evaluation of a hemodynamically stable patient should begin with a clinical history, physical examination with relevant labs, and 12-lead ECG.¹ Many patients with tachycardia are asymptomatic; however, common symptoms and complaints include palpitations, fatigue, lightheadedness, chest discomfort, dyspnea, presyncope, or syncope.¹ If the patient has experienced symptoms, it is of crucial importance to obtain a clinical history describing the pattern in terms of the number of episodes, duration, frequency, mode of onset, and possible triggers.¹

The main goals of the physical examination, labs, and the 12-lead ECG are to determine if the patient has a sinus or non-sinus tachycardia and to look for other findings that may suggest either a cause for the tachycardia or any complications resulting from the tachycardia.

First, determine if the patient’s heartbeat is regular or irregular. Atrial flutter and atrial fibrillation are common causes of an irregular heartbeat that can easily be diagnosed with a 12-lead ECG. Second, determine the width of the QRS interval: narrow QRS complex tachycardias are supraventricular (from the sinus node, the atria, and the atrioventricular junction) in origin, and wide QRS complex tachycardias are usually ventricular (from all sites below the AV junction).^2,3 If an irregular heartbeat or wide-complex tachycardia is detected, appropriate management (including possible urgent referrals) should begin immediately.¹ A stable patient with a regular rhythm and a narrow QRS complex can be further investigated at a more relaxed pace.

Refer to the TABLE for a listing of common secondary causes for sinus tachycardia, which should direct lab investigations. If no secondary cause is easily identifiable, a 24-hour monitor is recommended as the next step.

TABLE
Potential secondary causes of resting sinus tachycardia^5-7

Recommendations from others

Textbook chapters and other review articles regarding this topic describe a similar initial evaluation and provide further details about interpreting the 12-lead ECG.^2-7 The most relevant and recent review article suggests that further investigation of narrow QRS complex tachycardias with a regular rate currently involves 4 diagnostic categories: normal sinus tachycardia (ie, secondary cause can be identified), inappropriate sinus tachycardia (IST), postural orthostatic tachycardia syndrome (POTS), and sinus node reentry tachycardia (SNRT).⁴

If a secondary cause is identified, it should be treated appropriately. If no underlying cause is discovered, a 24-hour Holter monitor is recommended.

Persistent sinus tachycardia (sometimes with nocturnal normalization of heart rate) is diagnosed as IST.⁴ If the monitor shows paroxysmal episodes of sinus tachycardia, determine if they are triggered by orthostasis and relieved by recumbency (confirm with head upright tilt test) to make the diagnosis of POTS. If it is not POTS, the recordings from the 24-hour Holter monitor help make the diagnosis of SNRT, which consists of sudden, paroxysmal, and usually nonsustained tachycardia.⁴ The FIGURE shows an algorithm of one common diagnostic strategy for evaluation of tachycardia.^2-7

FIGURE
Diagnostic algorithm for evaluating tachycardias⁴

Evidence Summary

Heart rate varies by age; however, tachycardia in adults is usually defined as a rate exceeding 100 beats/minute.¹ Tachycardia at rest requires a diagnostic evaluation. However, our search found no systematic reviews, randomized trials, or prospective cohort studies relevant to this question. The highest level of evidence we located was an international practice guideline developed by the American College of Cardiology, the American Heart Association Task Force on Practice Guidelines, and the European Society of Cardiology Committee for Practice Guidelines.¹

This joint guideline recommends that the diagnostic evaluation of a hemodynamically stable patient should begin with a clinical history, physical examination with relevant labs, and 12-lead ECG.¹ Many patients with tachycardia are asymptomatic; however, common symptoms and complaints include palpitations, fatigue, lightheadedness, chest discomfort, dyspnea, presyncope, or syncope.¹ If the patient has experienced symptoms, it is of crucial importance to obtain a clinical history describing the pattern in terms of the number of episodes, duration, frequency, mode of onset, and possible triggers.¹

The main goals of the physical examination, labs, and the 12-lead ECG are to determine if the patient has a sinus or non-sinus tachycardia and to look for other findings that may suggest either a cause for the tachycardia or any complications resulting from the tachycardia.

First, determine if the patient’s heartbeat is regular or irregular. Atrial flutter and atrial fibrillation are common causes of an irregular heartbeat that can easily be diagnosed with a 12-lead ECG. Second, determine the width of the QRS interval: narrow QRS complex tachycardias are supraventricular (from the sinus node, the atria, and the atrioventricular junction) in origin, and wide QRS complex tachycardias are usually ventricular (from all sites below the AV junction).^2,3 If an irregular heartbeat or wide-complex tachycardia is detected, appropriate management (including possible urgent referrals) should begin immediately.¹ A stable patient with a regular rhythm and a narrow QRS complex can be further investigated at a more relaxed pace.

Refer to the TABLE for a listing of common secondary causes for sinus tachycardia, which should direct lab investigations. If no secondary cause is easily identifiable, a 24-hour monitor is recommended as the next step.

TABLE
Potential secondary causes of resting sinus tachycardia^5-7

Recommendations from others

Textbook chapters and other review articles regarding this topic describe a similar initial evaluation and provide further details about interpreting the 12-lead ECG.^2-7 The most relevant and recent review article suggests that further investigation of narrow QRS complex tachycardias with a regular rate currently involves 4 diagnostic categories: normal sinus tachycardia (ie, secondary cause can be identified), inappropriate sinus tachycardia (IST), postural orthostatic tachycardia syndrome (POTS), and sinus node reentry tachycardia (SNRT).⁴

If a secondary cause is identified, it should be treated appropriately. If no underlying cause is discovered, a 24-hour Holter monitor is recommended.

Persistent sinus tachycardia (sometimes with nocturnal normalization of heart rate) is diagnosed as IST.⁴ If the monitor shows paroxysmal episodes of sinus tachycardia, determine if they are triggered by orthostasis and relieved by recumbency (confirm with head upright tilt test) to make the diagnosis of POTS. If it is not POTS, the recordings from the 24-hour Holter monitor help make the diagnosis of SNRT, which consists of sudden, paroxysmal, and usually nonsustained tachycardia.⁴ The FIGURE shows an algorithm of one common diagnostic strategy for evaluation of tachycardia.^2-7

FIGURE
Diagnostic algorithm for evaluating tachycardias⁴

Evidence summary

Critically ill patients are at increased risk of bleeding from stress-induced gastroduodenal ulceration. Decades ago, ICUs began using pharmacologic prophylaxis on most patients to prevent gastrointestinal bleeding, which had a mortality rate as high as 80%. Before the advent of prophylaxis, the incidence of upper gastro-intestinal bleeding was 6% to 25%.⁴ Since then, improvements in ICU management have decreased this incidence to 0% to 2.8%.⁵ Recent studies suggest that only ICU patients with certain risk factors benefit from ulcer prophylaxis (TABLE).¹

Our search retrieved 20 randomized controlled trials and 6 systematic reviews with meta-analyses from the Medline database since 1990. It was difficult to find a consensus on the matter of stress ulcer prophylaxis because of inconsistencies in the outcomes measured in these studies. We focused on studies examining clinically important bleeding, but even in these studies definitions and measurements vary. Few studies addressed mortality or length of stay; those that did reported no significant difference in either outcome with prophylaxis.

Medications used to prevent gastrointestinal bleeding have included antacids, sucralfate, H2RAs, and PPIs. Sucralfate and H2RAs have been studied most frequently, and both agents significantly reduce the incidence of clinically important bleeding in high-risk patients. Compared with placebo, the odds ratio for clinically important bleeding was 0.44 with ranitidine (95% confidence interval [CI], 0.22–0.88) and 0.58 with sucralfate (95% CI, 0.34–0.99).⁶ In a population with a clinically important bleeding incidence of 3% to 6%, a range consistent with the most recent studies we reviewed, the number needed to treat to prevent 1 bleeding episode is 30 to 60 for ranitidine and 40 to 79 for sucralfate.

Some studies suggest that pharmacologic prophylaxis may increase the incidence of aspiration pneumonia in ventilator-dependent patients. The largest randomized trial addressing this issue (N=1200) found no significant difference between H2RAs and sucralfate in ventilator-associated pneumonia.³ Improved ICU management, such as frequent suctioning, upright positioning, and use of enteral nutrition may help prevent nosocomial pneumonia due to aspiration.

TABLE
Risk factors for stress ulcers

Recommendation from others

In the American Journal of Health-System Pharmacy, Allen et al⁵ state “the frequency of clinically important bleeding is low … the majority of recently published prospective studies and meta-analyses have been unable to demonstrate a reduction in clinically important bleeding with pharmacologic agents.” A 2001 Agency for Healthcare Research and Quality evidence report⁷ states that the evidence is not conclusive that all intensive care patients benefit from stress ulcer prophylaxis and that clinicians “may consider use of prophylactic agents in very high risk patients.”

Evidence summary

Critically ill patients are at increased risk of bleeding from stress-induced gastroduodenal ulceration. Decades ago, ICUs began using pharmacologic prophylaxis on most patients to prevent gastrointestinal bleeding, which had a mortality rate as high as 80%. Before the advent of prophylaxis, the incidence of upper gastro-intestinal bleeding was 6% to 25%.⁴ Since then, improvements in ICU management have decreased this incidence to 0% to 2.8%.⁵ Recent studies suggest that only ICU patients with certain risk factors benefit from ulcer prophylaxis (TABLE).¹

Our search retrieved 20 randomized controlled trials and 6 systematic reviews with meta-analyses from the Medline database since 1990. It was difficult to find a consensus on the matter of stress ulcer prophylaxis because of inconsistencies in the outcomes measured in these studies. We focused on studies examining clinically important bleeding, but even in these studies definitions and measurements vary. Few studies addressed mortality or length of stay; those that did reported no significant difference in either outcome with prophylaxis.

Medications used to prevent gastrointestinal bleeding have included antacids, sucralfate, H2RAs, and PPIs. Sucralfate and H2RAs have been studied most frequently, and both agents significantly reduce the incidence of clinically important bleeding in high-risk patients. Compared with placebo, the odds ratio for clinically important bleeding was 0.44 with ranitidine (95% confidence interval [CI], 0.22–0.88) and 0.58 with sucralfate (95% CI, 0.34–0.99).⁶ In a population with a clinically important bleeding incidence of 3% to 6%, a range consistent with the most recent studies we reviewed, the number needed to treat to prevent 1 bleeding episode is 30 to 60 for ranitidine and 40 to 79 for sucralfate.

Some studies suggest that pharmacologic prophylaxis may increase the incidence of aspiration pneumonia in ventilator-dependent patients. The largest randomized trial addressing this issue (N=1200) found no significant difference between H2RAs and sucralfate in ventilator-associated pneumonia.³ Improved ICU management, such as frequent suctioning, upright positioning, and use of enteral nutrition may help prevent nosocomial pneumonia due to aspiration.

TABLE
Risk factors for stress ulcers

Recommendation from others

In the American Journal of Health-System Pharmacy, Allen et al⁵ state “the frequency of clinically important bleeding is low … the majority of recently published prospective studies and meta-analyses have been unable to demonstrate a reduction in clinically important bleeding with pharmacologic agents.” A 2001 Agency for Healthcare Research and Quality evidence report⁷ states that the evidence is not conclusive that all intensive care patients benefit from stress ulcer prophylaxis and that clinicians “may consider use of prophylactic agents in very high risk patients.”

Evidence summary

Critically ill patients are at increased risk of bleeding from stress-induced gastroduodenal ulceration. Decades ago, ICUs began using pharmacologic prophylaxis on most patients to prevent gastrointestinal bleeding, which had a mortality rate as high as 80%. Before the advent of prophylaxis, the incidence of upper gastro-intestinal bleeding was 6% to 25%.⁴ Since then, improvements in ICU management have decreased this incidence to 0% to 2.8%.⁵ Recent studies suggest that only ICU patients with certain risk factors benefit from ulcer prophylaxis (TABLE).¹

Our search retrieved 20 randomized controlled trials and 6 systematic reviews with meta-analyses from the Medline database since 1990. It was difficult to find a consensus on the matter of stress ulcer prophylaxis because of inconsistencies in the outcomes measured in these studies. We focused on studies examining clinically important bleeding, but even in these studies definitions and measurements vary. Few studies addressed mortality or length of stay; those that did reported no significant difference in either outcome with prophylaxis.

Medications used to prevent gastrointestinal bleeding have included antacids, sucralfate, H2RAs, and PPIs. Sucralfate and H2RAs have been studied most frequently, and both agents significantly reduce the incidence of clinically important bleeding in high-risk patients. Compared with placebo, the odds ratio for clinically important bleeding was 0.44 with ranitidine (95% confidence interval [CI], 0.22–0.88) and 0.58 with sucralfate (95% CI, 0.34–0.99).⁶ In a population with a clinically important bleeding incidence of 3% to 6%, a range consistent with the most recent studies we reviewed, the number needed to treat to prevent 1 bleeding episode is 30 to 60 for ranitidine and 40 to 79 for sucralfate.

Some studies suggest that pharmacologic prophylaxis may increase the incidence of aspiration pneumonia in ventilator-dependent patients. The largest randomized trial addressing this issue (N=1200) found no significant difference between H2RAs and sucralfate in ventilator-associated pneumonia.³ Improved ICU management, such as frequent suctioning, upright positioning, and use of enteral nutrition may help prevent nosocomial pneumonia due to aspiration.

TABLE
Risk factors for stress ulcers

Recommendation from others

In the American Journal of Health-System Pharmacy, Allen et al⁵ state “the frequency of clinically important bleeding is low … the majority of recently published prospective studies and meta-analyses have been unable to demonstrate a reduction in clinically important bleeding with pharmacologic agents.” A 2001 Agency for Healthcare Research and Quality evidence report⁷ states that the evidence is not conclusive that all intensive care patients benefit from stress ulcer prophylaxis and that clinicians “may consider use of prophylactic agents in very high risk patients.”

Evidence summary

A 2002 Agency for Healthcare Research and Quality systematic review on the diagnosis and treatment of allergic rhinitis found no RCTs comparing antihistamines or nasal corticosteroids with immunotherapy.² Our literature review found 4 studies not included in this report that compared immunotherapy with nasal steroids or oral antihistamines.^3-6 Only 2 of these examined patient-oriented outcomes and both are of poor quality.^3,6 One study reported that inhaled nasal steroid therapy was superior to a nonstandard immunotherapy for ragweed pollen–induced rhinitis.³ The second study allowed patients to choose a treatment arm; it found that immunotherapy was superior to treatment with antihistamines and nasal steroids for patients who chose it.⁶

For patients requiring medication, studies comparing antihistamines with nasal corticosteroids have documented the superiority of intranasal steroids for symptom control of allergic rhinitis.^2,7

The effectiveness of immunotherapy has been documented in more than 40 placebo-controlled trials. However, the patients involved in these trials were often concurrently treated with allergy medications.⁸ In standard practice, immunotherapy is not recommended for most patients with seasonal allergic rhinitis unless avoidance measures and symptomatic therapy are ineffective, have adverse effects, or are not feasible.⁹ Studies indicate that immunotherapy is effective for several years after treatment is discontinued.¹⁰

A review of recent placebo-controlled trials indicates that the risk of developing asthma among patients with allergic rhinoconjunctivitis is significantly reduced when patients receive specific immunotherapy.¹¹ However, allergy immunotherapy presents risk of systemic reactions, with one study reporting a 0.5% risk of systemic reactions per year of therapy.¹²

Recommendations from others

The American College of Allergy, Asthma, and Immunology recommends that effective management of allergic rhinitis may require combinations of medications—antihistamines, decongestants, nasal corticosteroids, and anticholinergic agents as well as aggressive avoidance of rhinitis triggers. Consider allergen immunotherapy in carefully selected patients in consultation with an allergist-immunologist.¹⁰

Evidence summary

A 2002 Agency for Healthcare Research and Quality systematic review on the diagnosis and treatment of allergic rhinitis found no RCTs comparing antihistamines or nasal corticosteroids with immunotherapy.² Our literature review found 4 studies not included in this report that compared immunotherapy with nasal steroids or oral antihistamines.^3-6 Only 2 of these examined patient-oriented outcomes and both are of poor quality.^3,6 One study reported that inhaled nasal steroid therapy was superior to a nonstandard immunotherapy for ragweed pollen–induced rhinitis.³ The second study allowed patients to choose a treatment arm; it found that immunotherapy was superior to treatment with antihistamines and nasal steroids for patients who chose it.⁶

For patients requiring medication, studies comparing antihistamines with nasal corticosteroids have documented the superiority of intranasal steroids for symptom control of allergic rhinitis.^2,7

The effectiveness of immunotherapy has been documented in more than 40 placebo-controlled trials. However, the patients involved in these trials were often concurrently treated with allergy medications.⁸ In standard practice, immunotherapy is not recommended for most patients with seasonal allergic rhinitis unless avoidance measures and symptomatic therapy are ineffective, have adverse effects, or are not feasible.⁹ Studies indicate that immunotherapy is effective for several years after treatment is discontinued.¹⁰

A review of recent placebo-controlled trials indicates that the risk of developing asthma among patients with allergic rhinoconjunctivitis is significantly reduced when patients receive specific immunotherapy.¹¹ However, allergy immunotherapy presents risk of systemic reactions, with one study reporting a 0.5% risk of systemic reactions per year of therapy.¹²

Recommendations from others

The American College of Allergy, Asthma, and Immunology recommends that effective management of allergic rhinitis may require combinations of medications—antihistamines, decongestants, nasal corticosteroids, and anticholinergic agents as well as aggressive avoidance of rhinitis triggers. Consider allergen immunotherapy in carefully selected patients in consultation with an allergist-immunologist.¹⁰

Evidence summary

A 2002 Agency for Healthcare Research and Quality systematic review on the diagnosis and treatment of allergic rhinitis found no RCTs comparing antihistamines or nasal corticosteroids with immunotherapy.² Our literature review found 4 studies not included in this report that compared immunotherapy with nasal steroids or oral antihistamines.^3-6 Only 2 of these examined patient-oriented outcomes and both are of poor quality.^3,6 One study reported that inhaled nasal steroid therapy was superior to a nonstandard immunotherapy for ragweed pollen–induced rhinitis.³ The second study allowed patients to choose a treatment arm; it found that immunotherapy was superior to treatment with antihistamines and nasal steroids for patients who chose it.⁶

For patients requiring medication, studies comparing antihistamines with nasal corticosteroids have documented the superiority of intranasal steroids for symptom control of allergic rhinitis.^2,7

The effectiveness of immunotherapy has been documented in more than 40 placebo-controlled trials. However, the patients involved in these trials were often concurrently treated with allergy medications.⁸ In standard practice, immunotherapy is not recommended for most patients with seasonal allergic rhinitis unless avoidance measures and symptomatic therapy are ineffective, have adverse effects, or are not feasible.⁹ Studies indicate that immunotherapy is effective for several years after treatment is discontinued.¹⁰

A review of recent placebo-controlled trials indicates that the risk of developing asthma among patients with allergic rhinoconjunctivitis is significantly reduced when patients receive specific immunotherapy.¹¹ However, allergy immunotherapy presents risk of systemic reactions, with one study reporting a 0.5% risk of systemic reactions per year of therapy.¹²

Recommendations from others

The American College of Allergy, Asthma, and Immunology recommends that effective management of allergic rhinitis may require combinations of medications—antihistamines, decongestants, nasal corticosteroids, and anticholinergic agents as well as aggressive avoidance of rhinitis triggers. Consider allergen immunotherapy in carefully selected patients in consultation with an allergist-immunologist.¹⁰