Clinical Inquiries

Evidence summary

Since natural menopause is clinically defined as the final menstrual period, the best way to diagnose it is to retrospectively observe 12 consecutive months of amenorrhea. Several studies followed women longitudinally and found the characteristics that best predicted actual transition to menopause within 4 years were amenorrhea of between 3 and 12 months duration (sensitivity=0.16–0.32; specificity=0.98–1.0; positive likelihood ratio [LR+]=14.4–∞; negative likelihood ratio [LR–]=0.69–0.84), cycle irregularity within 12 months (sensitivity=0.65–0.66; specificity=0.77–0.85; LR+=2.84-4.17; LR–=0.42–0.84), and age≥50 years (sensitivity=0.35; specificity=0.98; LR+=15.4; LR–=0.66).^1-3 Change in the amount of flow is more sensitive but less specific (sensitivity=0.81; specificity=0.30; LR+=1.15; LR–=0.65).³ A woman’s global perception of being perimenopausal can also be useful for “rulingin” transition to menopause within the next several years (sensitivity=0.18; specificity=1; LR+=∞; LR–=0.82).^1,5 No studies were identified that prospectively studied the usefulness of laboratory or radiologic findings among perimenopausal women for predicting transition to postmenopausal state.

Because the perimenopause marks the entry into the menopausal transition, whether a woman has entered perimenopause is often the more relevant diagnosis to be made. Factors often used to diagnose perimenopause include age, maternal age at menopause, vasomotor and vaginal symptoms, FSH level, and a patient’s global perception of being perimenopausal. Other proposed methods include vaginal ultrasound to measure ovarian volume and number of antral follicles and assays for inhibins, but currently the test characteristics for these are inferior to less invasive and less costly methods.

Age alone can be a useful predictor for perimenopause; most women have either entered or completed the menopausal transition by age 50, and almost all by age 55.

The TABLE summarizes test characteristics for a variety of symptoms and lab assays to diagnose perimenopause. No one test is highly sensitive and specific. Typical symptoms of hot flashes, night sweats, and vaginal dryness are about as specific as laboratory tests, but are generally less sensitive.^1,4,6-7 Self-perceived menopausal status is moderately to highly sensitive, but the range of specificity estimates are wide. The LR+and LR–for FSH, which are of midhigh magnitude, would suggest it to be the best single diagnostic test.^4,6,7 However, because laboratory tests are usually ordered after some determination of pretest probability based on history and physical, FSH may be of less utility where the pretest probability for perimenopause is already high, such as the case of a 52-year-old woman seeking “confirmation” for perimenopausal symptoms. FSH levels are highly varied within individuals during perimenopause; and further variation due to body-mass index and ethnicity make defining diagnostic thresholds difficult.⁸

TABLE
Symptoms and laboratory tests for diagnosing perimenopause

Recommendations from others

The American Academy of Family Physicians, American College of Physicians, and American College of Obstetricians and Gynecologists do not address the diagnosis of menopause in any recommendations.

The North American Menopause Society states that estradiol and FSH are of limited value in confirming perimenopause due to extreme monthly fluctuations. They say perimenopausal women are not protected from unplanned pregnancy until amenorrhea of at least 1 year’s duration or consistently elevated FSH levels (>30 IU/L) are demonstrated. Confirmation of perimenopause relies on medical history and symptoms.

The American Association of Clinical Endocrinologists recommends a detailed history, exam, and measurement of FSH. The diagnosis of menopause is confirmed by FSH levels >40 IU/L; however, they note in perimenopause, FSH elevation is intermittent and not reliable for establishing the onset of menopause.

Evidence summary

Since natural menopause is clinically defined as the final menstrual period, the best way to diagnose it is to retrospectively observe 12 consecutive months of amenorrhea. Several studies followed women longitudinally and found the characteristics that best predicted actual transition to menopause within 4 years were amenorrhea of between 3 and 12 months duration (sensitivity=0.16–0.32; specificity=0.98–1.0; positive likelihood ratio [LR+]=14.4–∞; negative likelihood ratio [LR–]=0.69–0.84), cycle irregularity within 12 months (sensitivity=0.65–0.66; specificity=0.77–0.85; LR+=2.84-4.17; LR–=0.42–0.84), and age≥50 years (sensitivity=0.35; specificity=0.98; LR+=15.4; LR–=0.66).^1-3 Change in the amount of flow is more sensitive but less specific (sensitivity=0.81; specificity=0.30; LR+=1.15; LR–=0.65).³ A woman’s global perception of being perimenopausal can also be useful for “rulingin” transition to menopause within the next several years (sensitivity=0.18; specificity=1; LR+=∞; LR–=0.82).^1,5 No studies were identified that prospectively studied the usefulness of laboratory or radiologic findings among perimenopausal women for predicting transition to postmenopausal state.

Because the perimenopause marks the entry into the menopausal transition, whether a woman has entered perimenopause is often the more relevant diagnosis to be made. Factors often used to diagnose perimenopause include age, maternal age at menopause, vasomotor and vaginal symptoms, FSH level, and a patient’s global perception of being perimenopausal. Other proposed methods include vaginal ultrasound to measure ovarian volume and number of antral follicles and assays for inhibins, but currently the test characteristics for these are inferior to less invasive and less costly methods.

Age alone can be a useful predictor for perimenopause; most women have either entered or completed the menopausal transition by age 50, and almost all by age 55.

The TABLE summarizes test characteristics for a variety of symptoms and lab assays to diagnose perimenopause. No one test is highly sensitive and specific. Typical symptoms of hot flashes, night sweats, and vaginal dryness are about as specific as laboratory tests, but are generally less sensitive.^1,4,6-7 Self-perceived menopausal status is moderately to highly sensitive, but the range of specificity estimates are wide. The LR+and LR–for FSH, which are of midhigh magnitude, would suggest it to be the best single diagnostic test.^4,6,7 However, because laboratory tests are usually ordered after some determination of pretest probability based on history and physical, FSH may be of less utility where the pretest probability for perimenopause is already high, such as the case of a 52-year-old woman seeking “confirmation” for perimenopausal symptoms. FSH levels are highly varied within individuals during perimenopause; and further variation due to body-mass index and ethnicity make defining diagnostic thresholds difficult.⁸

TABLE
Symptoms and laboratory tests for diagnosing perimenopause

Recommendations from others

The American Academy of Family Physicians, American College of Physicians, and American College of Obstetricians and Gynecologists do not address the diagnosis of menopause in any recommendations.

The North American Menopause Society states that estradiol and FSH are of limited value in confirming perimenopause due to extreme monthly fluctuations. They say perimenopausal women are not protected from unplanned pregnancy until amenorrhea of at least 1 year’s duration or consistently elevated FSH levels (>30 IU/L) are demonstrated. Confirmation of perimenopause relies on medical history and symptoms.

The American Association of Clinical Endocrinologists recommends a detailed history, exam, and measurement of FSH. The diagnosis of menopause is confirmed by FSH levels >40 IU/L; however, they note in perimenopause, FSH elevation is intermittent and not reliable for establishing the onset of menopause.

Evidence summary

Since natural menopause is clinically defined as the final menstrual period, the best way to diagnose it is to retrospectively observe 12 consecutive months of amenorrhea. Several studies followed women longitudinally and found the characteristics that best predicted actual transition to menopause within 4 years were amenorrhea of between 3 and 12 months duration (sensitivity=0.16–0.32; specificity=0.98–1.0; positive likelihood ratio [LR+]=14.4–∞; negative likelihood ratio [LR–]=0.69–0.84), cycle irregularity within 12 months (sensitivity=0.65–0.66; specificity=0.77–0.85; LR+=2.84-4.17; LR–=0.42–0.84), and age≥50 years (sensitivity=0.35; specificity=0.98; LR+=15.4; LR–=0.66).^1-3 Change in the amount of flow is more sensitive but less specific (sensitivity=0.81; specificity=0.30; LR+=1.15; LR–=0.65).³ A woman’s global perception of being perimenopausal can also be useful for “rulingin” transition to menopause within the next several years (sensitivity=0.18; specificity=1; LR+=∞; LR–=0.82).^1,5 No studies were identified that prospectively studied the usefulness of laboratory or radiologic findings among perimenopausal women for predicting transition to postmenopausal state.

Because the perimenopause marks the entry into the menopausal transition, whether a woman has entered perimenopause is often the more relevant diagnosis to be made. Factors often used to diagnose perimenopause include age, maternal age at menopause, vasomotor and vaginal symptoms, FSH level, and a patient’s global perception of being perimenopausal. Other proposed methods include vaginal ultrasound to measure ovarian volume and number of antral follicles and assays for inhibins, but currently the test characteristics for these are inferior to less invasive and less costly methods.

Age alone can be a useful predictor for perimenopause; most women have either entered or completed the menopausal transition by age 50, and almost all by age 55.

The TABLE summarizes test characteristics for a variety of symptoms and lab assays to diagnose perimenopause. No one test is highly sensitive and specific. Typical symptoms of hot flashes, night sweats, and vaginal dryness are about as specific as laboratory tests, but are generally less sensitive.^1,4,6-7 Self-perceived menopausal status is moderately to highly sensitive, but the range of specificity estimates are wide. The LR+and LR–for FSH, which are of midhigh magnitude, would suggest it to be the best single diagnostic test.^4,6,7 However, because laboratory tests are usually ordered after some determination of pretest probability based on history and physical, FSH may be of less utility where the pretest probability for perimenopause is already high, such as the case of a 52-year-old woman seeking “confirmation” for perimenopausal symptoms. FSH levels are highly varied within individuals during perimenopause; and further variation due to body-mass index and ethnicity make defining diagnostic thresholds difficult.⁸

TABLE
Symptoms and laboratory tests for diagnosing perimenopause

Recommendations from others

The American Academy of Family Physicians, American College of Physicians, and American College of Obstetricians and Gynecologists do not address the diagnosis of menopause in any recommendations.

The North American Menopause Society states that estradiol and FSH are of limited value in confirming perimenopause due to extreme monthly fluctuations. They say perimenopausal women are not protected from unplanned pregnancy until amenorrhea of at least 1 year’s duration or consistently elevated FSH levels (>30 IU/L) are demonstrated. Confirmation of perimenopause relies on medical history and symptoms.

The American Association of Clinical Endocrinologists recommends a detailed history, exam, and measurement of FSH. The diagnosis of menopause is confirmed by FSH levels >40 IU/L; however, they note in perimenopause, FSH elevation is intermittent and not reliable for establishing the onset of menopause.

Evidence summary

Pulmonary embolism remains one of the leading causes of maternal mortality in developed nations. For nonpregnant populations, low-molecular-weight heparin has equal efficacy as unfractionated heparin with a lower overall mortality.^1,2

The only direct comparison of unfractionated with low-molecular-weight heparin for treatment of VTE in pregnancy was a prospective cohort study of 31 patients.³ For the initial week of treatment, the unfractionated heparin group received an IV bolus followed by infusion titrated to aPTT levels (goal 70–100s), while lowmolecular-weight heparin group received subcutaneous dalteparin 115 IU/kg twice daily adjusted to target antifactor Xa levels of 1 to 1.5 IU/mL 3 hours after injection. After 7 days, both groups received prophylactic doses of dalteparin throughout the remainder of pregnancy. There were no significant differences in outcome including bleeding or fetal effects. No cases of thrombocytopenia or pulmonary embolus were seen. There was 1 case of progressive thrombosis for a patient on low-molecular-weight heparin.

One randomized controlled trial compared unfractionated with low-molecular-weight heparin for VTE prophylaxis among 107 high-risk pregnant patients.⁴ The unfractionated heparin group received 7500 IU subcutaneously twice daily adjusted to aPTT levels, while the dalteparin group received weight-adjusted doses to target antifactor Xa levels >0.2 IU/mL at 3 hours. No thromboembolic complications occurred in either group (95% confidence interval, 0 to 2 in both groups). Minor bleeding complications were significantly more common with unfractionated heparin than with low-molecular-weight heparin. Two bleeds requiring transfusion and 2 lumbosacral compression fractures were also observed in the unfractionated heparin group, compared with none in the dalteparin group (difference not statistically significant).

Heparinoid metabolism appears to significantly alter in pregnancy. Several studies of low-molecular-weight heparin for the treatment of VTE in pregnancy used target antifactor Xa levels of 0.5 to 1.5 at 3 hours and found patients often need doses greater than those used for nonpregnant patients.^3,5-7 The only study of unfractionated heparin for the treatment of VTE in pregnancy used aPTT levels extrapolated from nonpregnant patients, with a mean heparin dose of 25,430 IU/d, similar to mean doses for nonpregnant patients.³

There are no studies of repeat lower extremity ultrasounds for pregnant patients; however, 1 study of nonpregnant patients revealed proximal extension of deep venous thrombosis despite anticoagulation predicted increased risk of pulmonary embolism.⁸

Recommendations from others

Both the American College of Obstetrics and Gynecologists⁹ and the American College of Chest Physicians¹⁰ recommends treating acute VTE in pregnancy with either weight-adjusted-dose low-molecular-weight heparin (goal antifactor Xa levels, 0.5–1.2) throughout pregnancy or full-dose intravenous unfractionated heparin, followed by adjusted-dose unfractionated or low-molecular-weight heparin, for the remainder of the pregnancy and at least 6 weeks postpartum.

Evidence summary

Pulmonary embolism remains one of the leading causes of maternal mortality in developed nations. For nonpregnant populations, low-molecular-weight heparin has equal efficacy as unfractionated heparin with a lower overall mortality.^1,2

The only direct comparison of unfractionated with low-molecular-weight heparin for treatment of VTE in pregnancy was a prospective cohort study of 31 patients.³ For the initial week of treatment, the unfractionated heparin group received an IV bolus followed by infusion titrated to aPTT levels (goal 70–100s), while lowmolecular-weight heparin group received subcutaneous dalteparin 115 IU/kg twice daily adjusted to target antifactor Xa levels of 1 to 1.5 IU/mL 3 hours after injection. After 7 days, both groups received prophylactic doses of dalteparin throughout the remainder of pregnancy. There were no significant differences in outcome including bleeding or fetal effects. No cases of thrombocytopenia or pulmonary embolus were seen. There was 1 case of progressive thrombosis for a patient on low-molecular-weight heparin.

One randomized controlled trial compared unfractionated with low-molecular-weight heparin for VTE prophylaxis among 107 high-risk pregnant patients.⁴ The unfractionated heparin group received 7500 IU subcutaneously twice daily adjusted to aPTT levels, while the dalteparin group received weight-adjusted doses to target antifactor Xa levels >0.2 IU/mL at 3 hours. No thromboembolic complications occurred in either group (95% confidence interval, 0 to 2 in both groups). Minor bleeding complications were significantly more common with unfractionated heparin than with low-molecular-weight heparin. Two bleeds requiring transfusion and 2 lumbosacral compression fractures were also observed in the unfractionated heparin group, compared with none in the dalteparin group (difference not statistically significant).

Heparinoid metabolism appears to significantly alter in pregnancy. Several studies of low-molecular-weight heparin for the treatment of VTE in pregnancy used target antifactor Xa levels of 0.5 to 1.5 at 3 hours and found patients often need doses greater than those used for nonpregnant patients.^3,5-7 The only study of unfractionated heparin for the treatment of VTE in pregnancy used aPTT levels extrapolated from nonpregnant patients, with a mean heparin dose of 25,430 IU/d, similar to mean doses for nonpregnant patients.³

There are no studies of repeat lower extremity ultrasounds for pregnant patients; however, 1 study of nonpregnant patients revealed proximal extension of deep venous thrombosis despite anticoagulation predicted increased risk of pulmonary embolism.⁸

Recommendations from others

Both the American College of Obstetrics and Gynecologists⁹ and the American College of Chest Physicians¹⁰ recommends treating acute VTE in pregnancy with either weight-adjusted-dose low-molecular-weight heparin (goal antifactor Xa levels, 0.5–1.2) throughout pregnancy or full-dose intravenous unfractionated heparin, followed by adjusted-dose unfractionated or low-molecular-weight heparin, for the remainder of the pregnancy and at least 6 weeks postpartum.

Evidence summary

Pulmonary embolism remains one of the leading causes of maternal mortality in developed nations. For nonpregnant populations, low-molecular-weight heparin has equal efficacy as unfractionated heparin with a lower overall mortality.^1,2

The only direct comparison of unfractionated with low-molecular-weight heparin for treatment of VTE in pregnancy was a prospective cohort study of 31 patients.³ For the initial week of treatment, the unfractionated heparin group received an IV bolus followed by infusion titrated to aPTT levels (goal 70–100s), while lowmolecular-weight heparin group received subcutaneous dalteparin 115 IU/kg twice daily adjusted to target antifactor Xa levels of 1 to 1.5 IU/mL 3 hours after injection. After 7 days, both groups received prophylactic doses of dalteparin throughout the remainder of pregnancy. There were no significant differences in outcome including bleeding or fetal effects. No cases of thrombocytopenia or pulmonary embolus were seen. There was 1 case of progressive thrombosis for a patient on low-molecular-weight heparin.

One randomized controlled trial compared unfractionated with low-molecular-weight heparin for VTE prophylaxis among 107 high-risk pregnant patients.⁴ The unfractionated heparin group received 7500 IU subcutaneously twice daily adjusted to aPTT levels, while the dalteparin group received weight-adjusted doses to target antifactor Xa levels >0.2 IU/mL at 3 hours. No thromboembolic complications occurred in either group (95% confidence interval, 0 to 2 in both groups). Minor bleeding complications were significantly more common with unfractionated heparin than with low-molecular-weight heparin. Two bleeds requiring transfusion and 2 lumbosacral compression fractures were also observed in the unfractionated heparin group, compared with none in the dalteparin group (difference not statistically significant).

Heparinoid metabolism appears to significantly alter in pregnancy. Several studies of low-molecular-weight heparin for the treatment of VTE in pregnancy used target antifactor Xa levels of 0.5 to 1.5 at 3 hours and found patients often need doses greater than those used for nonpregnant patients.^3,5-7 The only study of unfractionated heparin for the treatment of VTE in pregnancy used aPTT levels extrapolated from nonpregnant patients, with a mean heparin dose of 25,430 IU/d, similar to mean doses for nonpregnant patients.³

There are no studies of repeat lower extremity ultrasounds for pregnant patients; however, 1 study of nonpregnant patients revealed proximal extension of deep venous thrombosis despite anticoagulation predicted increased risk of pulmonary embolism.⁸

Recommendations from others

Both the American College of Obstetrics and Gynecologists⁹ and the American College of Chest Physicians¹⁰ recommends treating acute VTE in pregnancy with either weight-adjusted-dose low-molecular-weight heparin (goal antifactor Xa levels, 0.5–1.2) throughout pregnancy or full-dose intravenous unfractionated heparin, followed by adjusted-dose unfractionated or low-molecular-weight heparin, for the remainder of the pregnancy and at least 6 weeks postpartum.

Evidence summary

A Cochrane review conducted a meta-analysis looking only at FOBT for colorectal cancer screening. This review, based on published and unpublished data from 5 controlled trials, demonstrated that 3-card home FOBT conferred a reduction in colorectal cancer mortality of 16% (relative risk [RR]=0.84; 95% confidence interval [CI], 0.77–0.92) and a number needed to screen of 1173 (95% CI, 741–2807) to prevent 1 death from colon cancer over a 10-year period.¹ If adjusted for adherence to screening, the reduction in mortality increased to 23% (RR=0.77; 95% CI, 0.57–0.89).

In addition, long-term follow up of one of the RCTs in the review showed a continued reduction in colorectal cancer mortality of 34% (RR=0.66; 95% CI, 0.54–0.81) in subjects adhering to the FOBT screening protocol over a 13-year interval.² Overall mortality did not differ between the screened and unscreened groups.

A systematic review performed for the US Preventive Services Task Force (USPSTF) incorporated more recent data on colorectal cancer screening including colonoscopy.³ This review reached similar conclusions as above. This review also looked at office FOBT performed after digital rectal exam. It is important to note that a single office FOBT has a lower sensitivity than 3-card home FOBT and its effectiveness for reducing colorectal cancer mortality was unknown at the time of the systematic review. A subsequent 2005 Veterans Affairs prospective cohort study found that the sensitivity for detecting advanced neoplasia was only 4.9% for digital FOBT, and negative results did not decrease the likelihood of advanced neoplasia.⁴

The USPSTF review did not find any screening trials of colonoscopy but analyzed data from the National Polyp Study and a case-control study to draw its conclusions.³ The review reported an odds ratio for colorectal cancer mortality for patients who had colonoscopy to be 0.43 (95% CI, 0.30–63).

The USPSTF review also looked at the sensitivity and adverse effects of FOBT compared to colonoscopy. One-time 3-card home FOBT had a sensitivity of 30% to 40% for detecting cancer. The sensitivity of one-time colonoscopy was difficult to determine since it was the criterion standard examination, but it was estimated to be greater than 90%, with a risk of perforation of 1/2000.

The USPSTF review found both screening strategies cost-effective (<$30,000 per additional life-year gained) compared to no screening. FOBT had a cost per life-year saved of $5691 to $17,805 compared with $9038 to $22,012 for colonoscopy performed every 10 years.⁵

Recommendations from others

The USPSTF found strong evidence to recommend screening in this age group beginning at age 50 but found insufficient evidence to determine a preferred strategy. The evidence reviewed here does not apply to patients at higher risk for colorectal cancer based on personal history, family history or symptoms.

The TABLE details the American Cancer Society and the US Multisociety Task Force on Colorectal Cancer’s 2003 updates recommending options for screening average-risk individuals for colorectal cancer beginning at age 50.^6,7

TABLE

Recommended options for screening average-risk individuals for colorectal cancer

Evidence summary

A Cochrane review conducted a meta-analysis looking only at FOBT for colorectal cancer screening. This review, based on published and unpublished data from 5 controlled trials, demonstrated that 3-card home FOBT conferred a reduction in colorectal cancer mortality of 16% (relative risk [RR]=0.84; 95% confidence interval [CI], 0.77–0.92) and a number needed to screen of 1173 (95% CI, 741–2807) to prevent 1 death from colon cancer over a 10-year period.¹ If adjusted for adherence to screening, the reduction in mortality increased to 23% (RR=0.77; 95% CI, 0.57–0.89).

In addition, long-term follow up of one of the RCTs in the review showed a continued reduction in colorectal cancer mortality of 34% (RR=0.66; 95% CI, 0.54–0.81) in subjects adhering to the FOBT screening protocol over a 13-year interval.² Overall mortality did not differ between the screened and unscreened groups.

A systematic review performed for the US Preventive Services Task Force (USPSTF) incorporated more recent data on colorectal cancer screening including colonoscopy.³ This review reached similar conclusions as above. This review also looked at office FOBT performed after digital rectal exam. It is important to note that a single office FOBT has a lower sensitivity than 3-card home FOBT and its effectiveness for reducing colorectal cancer mortality was unknown at the time of the systematic review. A subsequent 2005 Veterans Affairs prospective cohort study found that the sensitivity for detecting advanced neoplasia was only 4.9% for digital FOBT, and negative results did not decrease the likelihood of advanced neoplasia.⁴

The USPSTF review did not find any screening trials of colonoscopy but analyzed data from the National Polyp Study and a case-control study to draw its conclusions.³ The review reported an odds ratio for colorectal cancer mortality for patients who had colonoscopy to be 0.43 (95% CI, 0.30–63).

The USPSTF review also looked at the sensitivity and adverse effects of FOBT compared to colonoscopy. One-time 3-card home FOBT had a sensitivity of 30% to 40% for detecting cancer. The sensitivity of one-time colonoscopy was difficult to determine since it was the criterion standard examination, but it was estimated to be greater than 90%, with a risk of perforation of 1/2000.

The USPSTF review found both screening strategies cost-effective (<$30,000 per additional life-year gained) compared to no screening. FOBT had a cost per life-year saved of $5691 to $17,805 compared with $9038 to $22,012 for colonoscopy performed every 10 years.⁵

Recommendations from others

The USPSTF found strong evidence to recommend screening in this age group beginning at age 50 but found insufficient evidence to determine a preferred strategy. The evidence reviewed here does not apply to patients at higher risk for colorectal cancer based on personal history, family history or symptoms.

The TABLE details the American Cancer Society and the US Multisociety Task Force on Colorectal Cancer’s 2003 updates recommending options for screening average-risk individuals for colorectal cancer beginning at age 50.^6,7

TABLE

Recommended options for screening average-risk individuals for colorectal cancer

Evidence summary

A Cochrane review conducted a meta-analysis looking only at FOBT for colorectal cancer screening. This review, based on published and unpublished data from 5 controlled trials, demonstrated that 3-card home FOBT conferred a reduction in colorectal cancer mortality of 16% (relative risk [RR]=0.84; 95% confidence interval [CI], 0.77–0.92) and a number needed to screen of 1173 (95% CI, 741–2807) to prevent 1 death from colon cancer over a 10-year period.¹ If adjusted for adherence to screening, the reduction in mortality increased to 23% (RR=0.77; 95% CI, 0.57–0.89).

In addition, long-term follow up of one of the RCTs in the review showed a continued reduction in colorectal cancer mortality of 34% (RR=0.66; 95% CI, 0.54–0.81) in subjects adhering to the FOBT screening protocol over a 13-year interval.² Overall mortality did not differ between the screened and unscreened groups.

A systematic review performed for the US Preventive Services Task Force (USPSTF) incorporated more recent data on colorectal cancer screening including colonoscopy.³ This review reached similar conclusions as above. This review also looked at office FOBT performed after digital rectal exam. It is important to note that a single office FOBT has a lower sensitivity than 3-card home FOBT and its effectiveness for reducing colorectal cancer mortality was unknown at the time of the systematic review. A subsequent 2005 Veterans Affairs prospective cohort study found that the sensitivity for detecting advanced neoplasia was only 4.9% for digital FOBT, and negative results did not decrease the likelihood of advanced neoplasia.⁴

The USPSTF review did not find any screening trials of colonoscopy but analyzed data from the National Polyp Study and a case-control study to draw its conclusions.³ The review reported an odds ratio for colorectal cancer mortality for patients who had colonoscopy to be 0.43 (95% CI, 0.30–63).

The USPSTF review also looked at the sensitivity and adverse effects of FOBT compared to colonoscopy. One-time 3-card home FOBT had a sensitivity of 30% to 40% for detecting cancer. The sensitivity of one-time colonoscopy was difficult to determine since it was the criterion standard examination, but it was estimated to be greater than 90%, with a risk of perforation of 1/2000.

The USPSTF review found both screening strategies cost-effective (<$30,000 per additional life-year gained) compared to no screening. FOBT had a cost per life-year saved of $5691 to $17,805 compared with $9038 to $22,012 for colonoscopy performed every 10 years.⁵

Recommendations from others

The USPSTF found strong evidence to recommend screening in this age group beginning at age 50 but found insufficient evidence to determine a preferred strategy. The evidence reviewed here does not apply to patients at higher risk for colorectal cancer based on personal history, family history or symptoms.

The TABLE details the American Cancer Society and the US Multisociety Task Force on Colorectal Cancer’s 2003 updates recommending options for screening average-risk individuals for colorectal cancer beginning at age 50.^6,7

TABLE

Recommended options for screening average-risk individuals for colorectal cancer

Evidence summary

Eighteen percent of all women report migraines.¹ As estrogen levels increase early in pregnancy, many women report an increase in headache or new-onset headache. As estrogen levels stabilize in the second and third trimester, 60% to 70% of women with migraine report reduction in symptoms.^1,2

Nonpharmacologic treatment. A small case series of electromyograph (EMG) biofeedback and relaxation techniques on 5 pregnant women showed that 4 became headache-free.³ It is impossible to say whether it was the intervention, natural disease progression, or the attention received from the therapist that produced this result. Two studies were published together evaluating thermal biofeedback, relaxation training, and physical therapy exercises. The first, a cohort study, showed decrease in symptoms for 15 of 19 women. The second, a small randomized controlled trial, compared 11 women using the combination treatment with 14 control women who received attention from the therapist but no other intervention. More than 72% of the treatment arm improved, compared with nearly 29% of the attention control group.⁴ Interpretation of these studies is limited by small sample size and testing in settings with specialized resources that are not found in every community.

Sumatriptan and other agents. Six studies have evaluated sumatriptan use in pregnancy.⁵ All were designed to evaluate teratogenicity and harm. None evaluated treatment efficacy in pregnancy. One prospective controlled cohort study showed an increase in miscarriage rates that did not reach statistical significance.⁶ No trials showed an increased risk in birth defects compared with the general population.

A single case report on the use of intravenous magnesium sulfate and prochlorperazine reported that the combination was effective for aborting a prolonged (6-day) migraine with aura for a pregnant woman.⁷

Safety in pregnancy. The US Food and Drug Administration (FDA) assigns fetal risk categories to all drugs based on controlled studies in humans, animal reproduction studies, and surveillance studies.⁸ Though no data exist on the effectiveness of other medications for migraine in pregnancy, it is reasonable to select drugs for both effectiveness for nonpregnant patients and established safety as determined by the FDA’s fetal risk summary. The TABLE shows commonly used drugs for acute migraine and their pregnancy risk category classification.

TABLE
Pregnancy risk category of abortive drugs for migraine

Recommendations from others

Practice guidelines published by the American Academy of Neurology recommend acetaminophen as first-line therapy based on its established safety in surveillance studies, although it is of questionable efficacy for nonpregnant patients. They also recommend nonpharmacologic treatment as an acceptable option in pregnancy.⁹ Most review articles also recommend acetaminophen alone or in combination with codeine as the treatment of first choice.^1,10

Evidence summary

Eighteen percent of all women report migraines.¹ As estrogen levels increase early in pregnancy, many women report an increase in headache or new-onset headache. As estrogen levels stabilize in the second and third trimester, 60% to 70% of women with migraine report reduction in symptoms.^1,2

Nonpharmacologic treatment. A small case series of electromyograph (EMG) biofeedback and relaxation techniques on 5 pregnant women showed that 4 became headache-free.³ It is impossible to say whether it was the intervention, natural disease progression, or the attention received from the therapist that produced this result. Two studies were published together evaluating thermal biofeedback, relaxation training, and physical therapy exercises. The first, a cohort study, showed decrease in symptoms for 15 of 19 women. The second, a small randomized controlled trial, compared 11 women using the combination treatment with 14 control women who received attention from the therapist but no other intervention. More than 72% of the treatment arm improved, compared with nearly 29% of the attention control group.⁴ Interpretation of these studies is limited by small sample size and testing in settings with specialized resources that are not found in every community.

Sumatriptan and other agents. Six studies have evaluated sumatriptan use in pregnancy.⁵ All were designed to evaluate teratogenicity and harm. None evaluated treatment efficacy in pregnancy. One prospective controlled cohort study showed an increase in miscarriage rates that did not reach statistical significance.⁶ No trials showed an increased risk in birth defects compared with the general population.

A single case report on the use of intravenous magnesium sulfate and prochlorperazine reported that the combination was effective for aborting a prolonged (6-day) migraine with aura for a pregnant woman.⁷

Safety in pregnancy. The US Food and Drug Administration (FDA) assigns fetal risk categories to all drugs based on controlled studies in humans, animal reproduction studies, and surveillance studies.⁸ Though no data exist on the effectiveness of other medications for migraine in pregnancy, it is reasonable to select drugs for both effectiveness for nonpregnant patients and established safety as determined by the FDA’s fetal risk summary. The TABLE shows commonly used drugs for acute migraine and their pregnancy risk category classification.

TABLE
Pregnancy risk category of abortive drugs for migraine

Recommendations from others

Practice guidelines published by the American Academy of Neurology recommend acetaminophen as first-line therapy based on its established safety in surveillance studies, although it is of questionable efficacy for nonpregnant patients. They also recommend nonpharmacologic treatment as an acceptable option in pregnancy.⁹ Most review articles also recommend acetaminophen alone or in combination with codeine as the treatment of first choice.^1,10

Evidence summary

Eighteen percent of all women report migraines.¹ As estrogen levels increase early in pregnancy, many women report an increase in headache or new-onset headache. As estrogen levels stabilize in the second and third trimester, 60% to 70% of women with migraine report reduction in symptoms.^1,2

Nonpharmacologic treatment. A small case series of electromyograph (EMG) biofeedback and relaxation techniques on 5 pregnant women showed that 4 became headache-free.³ It is impossible to say whether it was the intervention, natural disease progression, or the attention received from the therapist that produced this result. Two studies were published together evaluating thermal biofeedback, relaxation training, and physical therapy exercises. The first, a cohort study, showed decrease in symptoms for 15 of 19 women. The second, a small randomized controlled trial, compared 11 women using the combination treatment with 14 control women who received attention from the therapist but no other intervention. More than 72% of the treatment arm improved, compared with nearly 29% of the attention control group.⁴ Interpretation of these studies is limited by small sample size and testing in settings with specialized resources that are not found in every community.

Sumatriptan and other agents. Six studies have evaluated sumatriptan use in pregnancy.⁵ All were designed to evaluate teratogenicity and harm. None evaluated treatment efficacy in pregnancy. One prospective controlled cohort study showed an increase in miscarriage rates that did not reach statistical significance.⁶ No trials showed an increased risk in birth defects compared with the general population.

A single case report on the use of intravenous magnesium sulfate and prochlorperazine reported that the combination was effective for aborting a prolonged (6-day) migraine with aura for a pregnant woman.⁷

Safety in pregnancy. The US Food and Drug Administration (FDA) assigns fetal risk categories to all drugs based on controlled studies in humans, animal reproduction studies, and surveillance studies.⁸ Though no data exist on the effectiveness of other medications for migraine in pregnancy, it is reasonable to select drugs for both effectiveness for nonpregnant patients and established safety as determined by the FDA’s fetal risk summary. The TABLE shows commonly used drugs for acute migraine and their pregnancy risk category classification.

TABLE
Pregnancy risk category of abortive drugs for migraine

Recommendations from others

Practice guidelines published by the American Academy of Neurology recommend acetaminophen as first-line therapy based on its established safety in surveillance studies, although it is of questionable efficacy for nonpregnant patients. They also recommend nonpharmacologic treatment as an acceptable option in pregnancy.⁹ Most review articles also recommend acetaminophen alone or in combination with codeine as the treatment of first choice.^1,10

Evidence summary

A validating cohort study looked at 5 clinical warning criteria (TABLE) for patients seen in an emergency department for headache; 70 adults with acute headache as the chief complaint were included. All patients received computed tomography (CT) scanning as part of their evaluation. Abrupt onset and focal neurologic findings most strongly predicted intracranial lesions. Overall, 36% of the patients (25/70) had significant pathology.¹

A retrospective study reviewed records of 111 patients seen in an emergency department with headache and who had undergone neuroimaging (CT or magnetic resonance imaging [MRI]). Three symptoms predicted a lesion: decreased level of consciousness (sensitivity=23%; positive likelihood ratio [LR+]=3.8), paralysis (sensitivity=25%; LR+=3.5), and papilledema (numbers not reported). In this study, 35% (39/111) of those receiving neuroimaging had intracranial pathology.²

A case-control study reviewed hospital records of 468 patients evaluated in the emergency department for nontraumatic headache. Neuroimaging (CT scan or cerebral angiogram) was performed for 160 of these patients. Final diagnosis and outcome was obtained at 6 months. The symptoms and their ability to predict intracranial pathology are as follows: abnormal neurologic examination (sensitivity=39%; LR+=19.5), location of headache (sensitivity=78%; LR+=4.87), age of patient (sensitivity=61%; LR+=2.26), multiple associated symptoms (sensitivity=61%; LR+=2.26), mode of onset of headache (sensitivity=78%; LR+=2.23), and presence of associated symptoms (sensitivity=89%; LR+=1.41). Again, abnormal neurologic examination was the most significant indicator for imaging. This study did not define associated symptoms nor did it specify what determined which patients were imaged.³

Information concerning the workup of headache in the ambulatory setting is limited. In actual practice, only about 3% of patients who present with a new headache in the office setting have neuroimaging ordered.⁴ When neuroimaging is performed, about 4% of CT scans find a significant and treatable lesion (in one sample of 293 CT scans, there were 12 true-positive scans and 2 false-positive scans).⁵ Expert guidelines regarding headaches among ambulatory patients recommend neuroimaging for migraine patients only in the presence of persistent focal abnormal neurological findings. They note insufficient evidence for recommendations concerning neuroimaging for patients with tension-type headaches. They also note insufficient evidence for or against neuroimaging when headache occurs in the presence or absence of nonfocal symptoms: dizziness, syncope, nausea, lack of coordination, the “worst headache ever,” headache that awakens the patient from sleep, and increasing frequency of headaches.⁶

TABLE
Five clinical warning criteria for headache

Recommendations from others

Rosen’s Emergency Medicine and Mettler: Essentials of Radiology add the following indications for imaging in headache: signs and symptoms of elevated intracranial pressure (eg, papilledema); meningismus; partial seizure; nocturnal headaches that awaken the patient from sleep; increase in pain with coughing, sneezing or change in body position; sudden onset headaches that reach maximum intensity in 2 to 3 minutes; headache associated with mental status changes or decreased alertness; any new headache in an HIV-positive patient.^7,8

Evidence summary

A validating cohort study looked at 5 clinical warning criteria (TABLE) for patients seen in an emergency department for headache; 70 adults with acute headache as the chief complaint were included. All patients received computed tomography (CT) scanning as part of their evaluation. Abrupt onset and focal neurologic findings most strongly predicted intracranial lesions. Overall, 36% of the patients (25/70) had significant pathology.¹

A retrospective study reviewed records of 111 patients seen in an emergency department with headache and who had undergone neuroimaging (CT or magnetic resonance imaging [MRI]). Three symptoms predicted a lesion: decreased level of consciousness (sensitivity=23%; positive likelihood ratio [LR+]=3.8), paralysis (sensitivity=25%; LR+=3.5), and papilledema (numbers not reported). In this study, 35% (39/111) of those receiving neuroimaging had intracranial pathology.²

A case-control study reviewed hospital records of 468 patients evaluated in the emergency department for nontraumatic headache. Neuroimaging (CT scan or cerebral angiogram) was performed for 160 of these patients. Final diagnosis and outcome was obtained at 6 months. The symptoms and their ability to predict intracranial pathology are as follows: abnormal neurologic examination (sensitivity=39%; LR+=19.5), location of headache (sensitivity=78%; LR+=4.87), age of patient (sensitivity=61%; LR+=2.26), multiple associated symptoms (sensitivity=61%; LR+=2.26), mode of onset of headache (sensitivity=78%; LR+=2.23), and presence of associated symptoms (sensitivity=89%; LR+=1.41). Again, abnormal neurologic examination was the most significant indicator for imaging. This study did not define associated symptoms nor did it specify what determined which patients were imaged.³

Information concerning the workup of headache in the ambulatory setting is limited. In actual practice, only about 3% of patients who present with a new headache in the office setting have neuroimaging ordered.⁴ When neuroimaging is performed, about 4% of CT scans find a significant and treatable lesion (in one sample of 293 CT scans, there were 12 true-positive scans and 2 false-positive scans).⁵ Expert guidelines regarding headaches among ambulatory patients recommend neuroimaging for migraine patients only in the presence of persistent focal abnormal neurological findings. They note insufficient evidence for recommendations concerning neuroimaging for patients with tension-type headaches. They also note insufficient evidence for or against neuroimaging when headache occurs in the presence or absence of nonfocal symptoms: dizziness, syncope, nausea, lack of coordination, the “worst headache ever,” headache that awakens the patient from sleep, and increasing frequency of headaches.⁶

TABLE
Five clinical warning criteria for headache

Recommendations from others

Rosen’s Emergency Medicine and Mettler: Essentials of Radiology add the following indications for imaging in headache: signs and symptoms of elevated intracranial pressure (eg, papilledema); meningismus; partial seizure; nocturnal headaches that awaken the patient from sleep; increase in pain with coughing, sneezing or change in body position; sudden onset headaches that reach maximum intensity in 2 to 3 minutes; headache associated with mental status changes or decreased alertness; any new headache in an HIV-positive patient.^7,8

Evidence summary

A validating cohort study looked at 5 clinical warning criteria (TABLE) for patients seen in an emergency department for headache; 70 adults with acute headache as the chief complaint were included. All patients received computed tomography (CT) scanning as part of their evaluation. Abrupt onset and focal neurologic findings most strongly predicted intracranial lesions. Overall, 36% of the patients (25/70) had significant pathology.¹

A retrospective study reviewed records of 111 patients seen in an emergency department with headache and who had undergone neuroimaging (CT or magnetic resonance imaging [MRI]). Three symptoms predicted a lesion: decreased level of consciousness (sensitivity=23%; positive likelihood ratio [LR+]=3.8), paralysis (sensitivity=25%; LR+=3.5), and papilledema (numbers not reported). In this study, 35% (39/111) of those receiving neuroimaging had intracranial pathology.²

A case-control study reviewed hospital records of 468 patients evaluated in the emergency department for nontraumatic headache. Neuroimaging (CT scan or cerebral angiogram) was performed for 160 of these patients. Final diagnosis and outcome was obtained at 6 months. The symptoms and their ability to predict intracranial pathology are as follows: abnormal neurologic examination (sensitivity=39%; LR+=19.5), location of headache (sensitivity=78%; LR+=4.87), age of patient (sensitivity=61%; LR+=2.26), multiple associated symptoms (sensitivity=61%; LR+=2.26), mode of onset of headache (sensitivity=78%; LR+=2.23), and presence of associated symptoms (sensitivity=89%; LR+=1.41). Again, abnormal neurologic examination was the most significant indicator for imaging. This study did not define associated symptoms nor did it specify what determined which patients were imaged.³

Information concerning the workup of headache in the ambulatory setting is limited. In actual practice, only about 3% of patients who present with a new headache in the office setting have neuroimaging ordered.⁴ When neuroimaging is performed, about 4% of CT scans find a significant and treatable lesion (in one sample of 293 CT scans, there were 12 true-positive scans and 2 false-positive scans).⁵ Expert guidelines regarding headaches among ambulatory patients recommend neuroimaging for migraine patients only in the presence of persistent focal abnormal neurological findings. They note insufficient evidence for recommendations concerning neuroimaging for patients with tension-type headaches. They also note insufficient evidence for or against neuroimaging when headache occurs in the presence or absence of nonfocal symptoms: dizziness, syncope, nausea, lack of coordination, the “worst headache ever,” headache that awakens the patient from sleep, and increasing frequency of headaches.⁶

TABLE
Five clinical warning criteria for headache

Recommendations from others

Rosen’s Emergency Medicine and Mettler: Essentials of Radiology add the following indications for imaging in headache: signs and symptoms of elevated intracranial pressure (eg, papilledema); meningismus; partial seizure; nocturnal headaches that awaken the patient from sleep; increase in pain with coughing, sneezing or change in body position; sudden onset headaches that reach maximum intensity in 2 to 3 minutes; headache associated with mental status changes or decreased alertness; any new headache in an HIV-positive patient.^7,8

Evidence summary

Medicare adapted the National Hospice Organization guidelines to determine patients’ eligibility for hospice care.¹ Recent studies, however, have identified additional prognostic criteria that may better predict survival of less than 6 months in select populations (TABLE).

Schonwetter and colleagues¹ conducted a retrospective chart audit of 165 patients, and a subsequent prospective cohort study of 80 patients at comparable stages of progressive dementia who were consecutively admitted to a community-based hospice program. These patients had estimated life expectancy of less than 6 months, as certified by the attending and the hospice medical director, without use of explicit guidelines. The survival curves for patients who, in retrospect, did and did not meet Medicare guidelines were similarie, the Medicare guidelines were not statistically better at predicting 6-month survival than the clinical impressions of the attending and hospice medical director.

In the 139 patients from the retrospective cohort included in the Cox regression analysis, 108 patients died within 6 months. Of those, 83 (77%) met Medicare criteria and 25 (23%) did not. Of the 31 who lived longer than 6 months, 22 (71%) met Medicare criteria and 9 (29%) did not. In the prospective cohort, of the 61 patients who died within 6 months, 39 (64%) met Medicare criteria and 22 (36%) did not; of the 18 who lived longer than 6 months, 9 met Medicare criteria (50%) and 9 did not.¹

More recent studies have looked at the FAST, MDS, and Global Deterioration Scale (GDS) to identify criteria for predicting 6-month mortality. The FAST rating is based on the lowest level of function on a scale ranging from 1 (normal) to 7f (unable to hold up head). The GDS is similar to the FAST, and also ranges from 1 to 7. A rating of 5 is given to people with moderately severe cognitive decline; 6 is severe cognitive decline.

Two prospective cohort studies followed 47 and 45 patients enrolled in hospice over 2 years; these studies demonstrated that patients who reach FAST stage 7c (inability to walk without assistance) in an stepwise fashion are likely to live less than 6 months.^2,3 In 1 of the 2 studies, patients who reached stage 7c ordinally had a mean survival time of 4.1 months; 71% died within 6 months of enrollment. For the large subset of patients who met 7c but not in an ordinal fashion (ie, they met criteria for 7c, but perhaps not 7a or 7b), only 30% died within 6 months, with median survival time 10.7 months.

Use of antibiotics did not make a statistically significant difference in survival, and use of Foley catheters was associated with shorter survival times (3.6 months vs 9 months; P<.03.)³ In the other study, however, less aggressive care plans resulted in shorter survival times (P<.01).²

In a retrospective cohort study of 11,430 nursing home residents with advanced dementia (defined as a score of 5 or 6 on the Cognitive Performance Score, which is itself based on MDS data, a prognostic summary score was developed using 12 variables from the MDS, a federally mandated assessment completed by nursing home staff at the time of admission.⁴ A high score predicted 6-month mortality more accurately than using an MDS correlate of FAST stage 7c. In the derivation cohort (n=6799), 28.3% (n=1922) died within 6 months; in the validation cohort (n=4631), 35.1% (n=1626) died within 6 months. The FAST 7c correlate was found to have a positive predictive value of only 38.5% and a sensitivity of 22% in predicting death within 6 months in this population. In contrast, using the MDS variables, a higher threshold for the prognostic summary score resulted in a positive predictive value of 80%, negative predictive value of 73%, specificity of 99%, but sensitivity of only 6%. A lower cutoff yielded better sensitivity (23%), and still had good specificity (96%) and negative predictive value (76%), though the positive predictive value was slightly lower (67%).

Morrison and Siu conducted a prospective cohort study of consecutive patients admitted with hip fracture or pneumonia to a single New York hospital over an 18-month period.⁵ Survival rates of 118 advanced dementia patients, defined by a GDS score of 6 or 7, were compared with survival rates of 98 patients without dementia. At 6 months, 42 (53%) of 80 pneumonia patients with end-stage dementia had died, compared with 5 (13%) of 39 cognitively intact patients with pneumonia (adjusted hazard ratio=4.6 [95% CI, 1.8–11.8]). At 6 months, 21 (55%) of 38 hip fracture patients with end-stage dementia had died, compared with 7 (12%) of 59 cognitively intact patients with hip fracture (adjusted hazard ratio=5.8 [95% CI, 1.7–20.4]). Of note, the end-stage dementia patients with hip fracture or pneumonia were 6 and 4 years older, respectively, than cognitively intact patients. In addition, the dementia patients were more likely to reside in nursing homes (82% vs 5% with hip fracture, 63% vs 5% with pneumonia). A palliative care plan was not identified for any of these patients during the admission.

TABLE
Prognostic factors and accuracy for 6-month survival in Alzheimer’s dementia

Recommendations from others

Guidelines for Medicare reimbursement for hospice care of demented patients is outlined in the see first row of the TABLE.⁶

Evidence summary

Medicare adapted the National Hospice Organization guidelines to determine patients’ eligibility for hospice care.¹ Recent studies, however, have identified additional prognostic criteria that may better predict survival of less than 6 months in select populations (TABLE).

Schonwetter and colleagues¹ conducted a retrospective chart audit of 165 patients, and a subsequent prospective cohort study of 80 patients at comparable stages of progressive dementia who were consecutively admitted to a community-based hospice program. These patients had estimated life expectancy of less than 6 months, as certified by the attending and the hospice medical director, without use of explicit guidelines. The survival curves for patients who, in retrospect, did and did not meet Medicare guidelines were similarie, the Medicare guidelines were not statistically better at predicting 6-month survival than the clinical impressions of the attending and hospice medical director.

In the 139 patients from the retrospective cohort included in the Cox regression analysis, 108 patients died within 6 months. Of those, 83 (77%) met Medicare criteria and 25 (23%) did not. Of the 31 who lived longer than 6 months, 22 (71%) met Medicare criteria and 9 (29%) did not. In the prospective cohort, of the 61 patients who died within 6 months, 39 (64%) met Medicare criteria and 22 (36%) did not; of the 18 who lived longer than 6 months, 9 met Medicare criteria (50%) and 9 did not.¹

More recent studies have looked at the FAST, MDS, and Global Deterioration Scale (GDS) to identify criteria for predicting 6-month mortality. The FAST rating is based on the lowest level of function on a scale ranging from 1 (normal) to 7f (unable to hold up head). The GDS is similar to the FAST, and also ranges from 1 to 7. A rating of 5 is given to people with moderately severe cognitive decline; 6 is severe cognitive decline.

Two prospective cohort studies followed 47 and 45 patients enrolled in hospice over 2 years; these studies demonstrated that patients who reach FAST stage 7c (inability to walk without assistance) in an stepwise fashion are likely to live less than 6 months.^2,3 In 1 of the 2 studies, patients who reached stage 7c ordinally had a mean survival time of 4.1 months; 71% died within 6 months of enrollment. For the large subset of patients who met 7c but not in an ordinal fashion (ie, they met criteria for 7c, but perhaps not 7a or 7b), only 30% died within 6 months, with median survival time 10.7 months.

Use of antibiotics did not make a statistically significant difference in survival, and use of Foley catheters was associated with shorter survival times (3.6 months vs 9 months; P<.03.)³ In the other study, however, less aggressive care plans resulted in shorter survival times (P<.01).²

In a retrospective cohort study of 11,430 nursing home residents with advanced dementia (defined as a score of 5 or 6 on the Cognitive Performance Score, which is itself based on MDS data, a prognostic summary score was developed using 12 variables from the MDS, a federally mandated assessment completed by nursing home staff at the time of admission.⁴ A high score predicted 6-month mortality more accurately than using an MDS correlate of FAST stage 7c. In the derivation cohort (n=6799), 28.3% (n=1922) died within 6 months; in the validation cohort (n=4631), 35.1% (n=1626) died within 6 months. The FAST 7c correlate was found to have a positive predictive value of only 38.5% and a sensitivity of 22% in predicting death within 6 months in this population. In contrast, using the MDS variables, a higher threshold for the prognostic summary score resulted in a positive predictive value of 80%, negative predictive value of 73%, specificity of 99%, but sensitivity of only 6%. A lower cutoff yielded better sensitivity (23%), and still had good specificity (96%) and negative predictive value (76%), though the positive predictive value was slightly lower (67%).

Morrison and Siu conducted a prospective cohort study of consecutive patients admitted with hip fracture or pneumonia to a single New York hospital over an 18-month period.⁵ Survival rates of 118 advanced dementia patients, defined by a GDS score of 6 or 7, were compared with survival rates of 98 patients without dementia. At 6 months, 42 (53%) of 80 pneumonia patients with end-stage dementia had died, compared with 5 (13%) of 39 cognitively intact patients with pneumonia (adjusted hazard ratio=4.6 [95% CI, 1.8–11.8]). At 6 months, 21 (55%) of 38 hip fracture patients with end-stage dementia had died, compared with 7 (12%) of 59 cognitively intact patients with hip fracture (adjusted hazard ratio=5.8 [95% CI, 1.7–20.4]). Of note, the end-stage dementia patients with hip fracture or pneumonia were 6 and 4 years older, respectively, than cognitively intact patients. In addition, the dementia patients were more likely to reside in nursing homes (82% vs 5% with hip fracture, 63% vs 5% with pneumonia). A palliative care plan was not identified for any of these patients during the admission.

TABLE
Prognostic factors and accuracy for 6-month survival in Alzheimer’s dementia

Recommendations from others

Guidelines for Medicare reimbursement for hospice care of demented patients is outlined in the see first row of the TABLE.⁶

Evidence summary

Medicare adapted the National Hospice Organization guidelines to determine patients’ eligibility for hospice care.¹ Recent studies, however, have identified additional prognostic criteria that may better predict survival of less than 6 months in select populations (TABLE).

Schonwetter and colleagues¹ conducted a retrospective chart audit of 165 patients, and a subsequent prospective cohort study of 80 patients at comparable stages of progressive dementia who were consecutively admitted to a community-based hospice program. These patients had estimated life expectancy of less than 6 months, as certified by the attending and the hospice medical director, without use of explicit guidelines. The survival curves for patients who, in retrospect, did and did not meet Medicare guidelines were similarie, the Medicare guidelines were not statistically better at predicting 6-month survival than the clinical impressions of the attending and hospice medical director.

In the 139 patients from the retrospective cohort included in the Cox regression analysis, 108 patients died within 6 months. Of those, 83 (77%) met Medicare criteria and 25 (23%) did not. Of the 31 who lived longer than 6 months, 22 (71%) met Medicare criteria and 9 (29%) did not. In the prospective cohort, of the 61 patients who died within 6 months, 39 (64%) met Medicare criteria and 22 (36%) did not; of the 18 who lived longer than 6 months, 9 met Medicare criteria (50%) and 9 did not.¹

More recent studies have looked at the FAST, MDS, and Global Deterioration Scale (GDS) to identify criteria for predicting 6-month mortality. The FAST rating is based on the lowest level of function on a scale ranging from 1 (normal) to 7f (unable to hold up head). The GDS is similar to the FAST, and also ranges from 1 to 7. A rating of 5 is given to people with moderately severe cognitive decline; 6 is severe cognitive decline.

Two prospective cohort studies followed 47 and 45 patients enrolled in hospice over 2 years; these studies demonstrated that patients who reach FAST stage 7c (inability to walk without assistance) in an stepwise fashion are likely to live less than 6 months.^2,3 In 1 of the 2 studies, patients who reached stage 7c ordinally had a mean survival time of 4.1 months; 71% died within 6 months of enrollment. For the large subset of patients who met 7c but not in an ordinal fashion (ie, they met criteria for 7c, but perhaps not 7a or 7b), only 30% died within 6 months, with median survival time 10.7 months.

Use of antibiotics did not make a statistically significant difference in survival, and use of Foley catheters was associated with shorter survival times (3.6 months vs 9 months; P<.03.)³ In the other study, however, less aggressive care plans resulted in shorter survival times (P<.01).²

In a retrospective cohort study of 11,430 nursing home residents with advanced dementia (defined as a score of 5 or 6 on the Cognitive Performance Score, which is itself based on MDS data, a prognostic summary score was developed using 12 variables from the MDS, a federally mandated assessment completed by nursing home staff at the time of admission.⁴ A high score predicted 6-month mortality more accurately than using an MDS correlate of FAST stage 7c. In the derivation cohort (n=6799), 28.3% (n=1922) died within 6 months; in the validation cohort (n=4631), 35.1% (n=1626) died within 6 months. The FAST 7c correlate was found to have a positive predictive value of only 38.5% and a sensitivity of 22% in predicting death within 6 months in this population. In contrast, using the MDS variables, a higher threshold for the prognostic summary score resulted in a positive predictive value of 80%, negative predictive value of 73%, specificity of 99%, but sensitivity of only 6%. A lower cutoff yielded better sensitivity (23%), and still had good specificity (96%) and negative predictive value (76%), though the positive predictive value was slightly lower (67%).

Morrison and Siu conducted a prospective cohort study of consecutive patients admitted with hip fracture or pneumonia to a single New York hospital over an 18-month period.⁵ Survival rates of 118 advanced dementia patients, defined by a GDS score of 6 or 7, were compared with survival rates of 98 patients without dementia. At 6 months, 42 (53%) of 80 pneumonia patients with end-stage dementia had died, compared with 5 (13%) of 39 cognitively intact patients with pneumonia (adjusted hazard ratio=4.6 [95% CI, 1.8–11.8]). At 6 months, 21 (55%) of 38 hip fracture patients with end-stage dementia had died, compared with 7 (12%) of 59 cognitively intact patients with hip fracture (adjusted hazard ratio=5.8 [95% CI, 1.7–20.4]). Of note, the end-stage dementia patients with hip fracture or pneumonia were 6 and 4 years older, respectively, than cognitively intact patients. In addition, the dementia patients were more likely to reside in nursing homes (82% vs 5% with hip fracture, 63% vs 5% with pneumonia). A palliative care plan was not identified for any of these patients during the admission.

TABLE
Prognostic factors and accuracy for 6-month survival in Alzheimer’s dementia

Recommendations from others

Guidelines for Medicare reimbursement for hospice care of demented patients is outlined in the see first row of the TABLE.⁶

Evidence summary

Nocturnal enuresis is an involuntary loss of urine at night in the absence of congenital or acquired central nervous system defect among children over 5 years of age.^1-4 Approximately 15% of children aged >5years wet their bed at night.⁵ The spontaneous resolution rate is about 15% per year.⁵ Before primary care treatment, indications for urological referral should be excluded, including daytime wetting, abnormal voiding (unusual posturing, discomfort, straining, or poor urine stream), recurrent urinary tract infections, neurological and anatomical anomalies, and urgency symptoms.⁴

The Cochrane Incontinence Group Trials demonstrated that enuresis alarms led to nearly 4 fewer wet nights per week compared with no treatment or placebo (weighted mean difference [WMD]=–3.65; 95% confidence interval [CI], –4.52 to –2.78).¹ The relative risk of failure was 0.36 compared with placebo (95% CI, 0.26 to 0.40). The number needed to treat (NNT) to achieve 14 consecutive dry nights is 2. About half the children relapse after stopping treatment, compared with nearly all children after control interventions (55% vs 99%). Evidence is insufficient to say whether the addition of dry bed training (scheduled awakenings, cleanliness training, social reinforcement, positive practice) improves the outcomes. Alarms that wake the child immediately (vs a time delay) and alarms that wake the child (instead of the parents) were slightly more effective.

A meta-analysis also showed that desmopressin (10-60 μg) at bedtime reduced bedwetting by 1 to 2 nights per week compared with placebo (WMD=1.34; 95% CI, -1.57 to –1.11 with a dose of 20 μg).⁶ The NNT to achieve 14 consecutive dry nights is 7. However, the data suggest once treatment stops, there is little difference between desmopressin and placebo. Some evidence suggested that a higher dose was more likely to decrease the number of wet nights; however, there was no difference in cure rates. Evidence comparing intranasal with oral administration is insufficient.²

In the Cochrane review, children treated with desmopressin had 1.7 fewer wet nights (WMD=1.7; 95% CI, –2.95 to –0.45) in the first week compared with children treated with alarms.⁶ However, at the end of 3 months, alarms were associated with 1.4 fewer wet nights per week than children treated with desmopressin (WMD=1.4; 95% CI, 0.14 to 2.66).

Evidence is conflicting for increased efficacy for combining desmopressin with enuresis alarms. There is some limited evidence that children receiving combination treatment with desmopressin and alarms had fewer wet nights than children treated with alarms and placebo.⁶ This combination treatment did not show a benefit with failure rates (not attaining 14 consecutive dry nights) or a statistically significant difference in failure and relapse rates once treatment stopped. In addition, one RCT in which desmopressin nonresponders were supplemented with alarms showed no added benefit in remission rates compared with conditioning alarms plus placebo (51% vs 48% in achieving 28 dry nights).⁷ Neither was there added benefit in relapse rates once treatment stopped.

Children treated with tricyclic drugs compared with those treated with placebo had approximately 1 less night of enuresis per week (WMD=1.19; 95% CI, –1.56 to-0.82).8 More children achieved 14 dry nights while on imipramine compared with placebo (21% vs 5%; NNT=6); however, this advantage was not sustained once treatment finished (96% vs 97% relapsed). Little evidence exists to compare desmopressin with tricyclic drugs.^2,8

Simple behavior methods may be more effective than no treatment, but there is little evidence for how these methods compare with one another, or with more successful means of treatment.⁹ Behavior techniques include lifting (taking a sleeping child to urinate in the bath-room), waking, rewards, and evening fluid restriction.

Dry bed training refers to comprehensive regimes, including enuresis alarms, waking routines, positive practice, cleanliness training, and bladder training in various combinations. A meta-analysis examining dry bed training including an enuresis alarm showed children had fewer wet nights compared with children receiving no treatment (relative risk [RR] of failure=0.17; 95% CI, 0.11-0.28).^2,10 Additionally, more children remained dry after treatment stopped (RR of relapse=0.25; 95% CI, 0.16-0.39). However, evidence was not sufficient to show a remission benefit for dry bed training without an alarm (RR of failure=0.82; 95% CI, 0.6-1.02), highlighting the key role for alarm therapy. On the other hand, dry bed training including bed alarms may reduce the relapse rate compared with alarm monotherapy (RR for failure or relapse=0.5; 95% CI, 0.31-0.8)

TABLE
Nocturnal enuresis treatments and efficacy

Recommendations from others

A recent evidence-based practice parameter from the American Academy of Child and Adolescent Psychiatry states once the history and physical suggest primary nocturnal enuresis, treatment should include education demystification and withholding punishment.⁴ Although insufficient evidence exists to recommend behavioral interventions such as journal keeping, fluid restrictions, and night awakenings, these supportive approaches are acceptable, benign starting points. Conditioning with an enuresis alarm and overlearning, which involves giving extra fluids at bedtime after successfully becoming dry and intermittent reinforcement before ending treatment, is a highly effective first-line management approach. Medication choices include desmopressin and imipramine, although relapse rates are high. Short-term use of desmopressin may be used for sleepovers or camping trips.

Evidence summary

Nocturnal enuresis is an involuntary loss of urine at night in the absence of congenital or acquired central nervous system defect among children over 5 years of age.^1-4 Approximately 15% of children aged >5years wet their bed at night.⁵ The spontaneous resolution rate is about 15% per year.⁵ Before primary care treatment, indications for urological referral should be excluded, including daytime wetting, abnormal voiding (unusual posturing, discomfort, straining, or poor urine stream), recurrent urinary tract infections, neurological and anatomical anomalies, and urgency symptoms.⁴

The Cochrane Incontinence Group Trials demonstrated that enuresis alarms led to nearly 4 fewer wet nights per week compared with no treatment or placebo (weighted mean difference [WMD]=–3.65; 95% confidence interval [CI], –4.52 to –2.78).¹ The relative risk of failure was 0.36 compared with placebo (95% CI, 0.26 to 0.40). The number needed to treat (NNT) to achieve 14 consecutive dry nights is 2. About half the children relapse after stopping treatment, compared with nearly all children after control interventions (55% vs 99%). Evidence is insufficient to say whether the addition of dry bed training (scheduled awakenings, cleanliness training, social reinforcement, positive practice) improves the outcomes. Alarms that wake the child immediately (vs a time delay) and alarms that wake the child (instead of the parents) were slightly more effective.

A meta-analysis also showed that desmopressin (10-60 μg) at bedtime reduced bedwetting by 1 to 2 nights per week compared with placebo (WMD=1.34; 95% CI, -1.57 to –1.11 with a dose of 20 μg).⁶ The NNT to achieve 14 consecutive dry nights is 7. However, the data suggest once treatment stops, there is little difference between desmopressin and placebo. Some evidence suggested that a higher dose was more likely to decrease the number of wet nights; however, there was no difference in cure rates. Evidence comparing intranasal with oral administration is insufficient.²

In the Cochrane review, children treated with desmopressin had 1.7 fewer wet nights (WMD=1.7; 95% CI, –2.95 to –0.45) in the first week compared with children treated with alarms.⁶ However, at the end of 3 months, alarms were associated with 1.4 fewer wet nights per week than children treated with desmopressin (WMD=1.4; 95% CI, 0.14 to 2.66).

Evidence is conflicting for increased efficacy for combining desmopressin with enuresis alarms. There is some limited evidence that children receiving combination treatment with desmopressin and alarms had fewer wet nights than children treated with alarms and placebo.⁶ This combination treatment did not show a benefit with failure rates (not attaining 14 consecutive dry nights) or a statistically significant difference in failure and relapse rates once treatment stopped. In addition, one RCT in which desmopressin nonresponders were supplemented with alarms showed no added benefit in remission rates compared with conditioning alarms plus placebo (51% vs 48% in achieving 28 dry nights).⁷ Neither was there added benefit in relapse rates once treatment stopped.

Children treated with tricyclic drugs compared with those treated with placebo had approximately 1 less night of enuresis per week (WMD=1.19; 95% CI, –1.56 to-0.82).8 More children achieved 14 dry nights while on imipramine compared with placebo (21% vs 5%; NNT=6); however, this advantage was not sustained once treatment finished (96% vs 97% relapsed). Little evidence exists to compare desmopressin with tricyclic drugs.^2,8

Simple behavior methods may be more effective than no treatment, but there is little evidence for how these methods compare with one another, or with more successful means of treatment.⁹ Behavior techniques include lifting (taking a sleeping child to urinate in the bath-room), waking, rewards, and evening fluid restriction.

Dry bed training refers to comprehensive regimes, including enuresis alarms, waking routines, positive practice, cleanliness training, and bladder training in various combinations. A meta-analysis examining dry bed training including an enuresis alarm showed children had fewer wet nights compared with children receiving no treatment (relative risk [RR] of failure=0.17; 95% CI, 0.11-0.28).^2,10 Additionally, more children remained dry after treatment stopped (RR of relapse=0.25; 95% CI, 0.16-0.39). However, evidence was not sufficient to show a remission benefit for dry bed training without an alarm (RR of failure=0.82; 95% CI, 0.6-1.02), highlighting the key role for alarm therapy. On the other hand, dry bed training including bed alarms may reduce the relapse rate compared with alarm monotherapy (RR for failure or relapse=0.5; 95% CI, 0.31-0.8)

TABLE
Nocturnal enuresis treatments and efficacy

Recommendations from others

A recent evidence-based practice parameter from the American Academy of Child and Adolescent Psychiatry states once the history and physical suggest primary nocturnal enuresis, treatment should include education demystification and withholding punishment.⁴ Although insufficient evidence exists to recommend behavioral interventions such as journal keeping, fluid restrictions, and night awakenings, these supportive approaches are acceptable, benign starting points. Conditioning with an enuresis alarm and overlearning, which involves giving extra fluids at bedtime after successfully becoming dry and intermittent reinforcement before ending treatment, is a highly effective first-line management approach. Medication choices include desmopressin and imipramine, although relapse rates are high. Short-term use of desmopressin may be used for sleepovers or camping trips.

Evidence summary

Nocturnal enuresis is an involuntary loss of urine at night in the absence of congenital or acquired central nervous system defect among children over 5 years of age.^1-4 Approximately 15% of children aged >5years wet their bed at night.⁵ The spontaneous resolution rate is about 15% per year.⁵ Before primary care treatment, indications for urological referral should be excluded, including daytime wetting, abnormal voiding (unusual posturing, discomfort, straining, or poor urine stream), recurrent urinary tract infections, neurological and anatomical anomalies, and urgency symptoms.⁴

The Cochrane Incontinence Group Trials demonstrated that enuresis alarms led to nearly 4 fewer wet nights per week compared with no treatment or placebo (weighted mean difference [WMD]=–3.65; 95% confidence interval [CI], –4.52 to –2.78).¹ The relative risk of failure was 0.36 compared with placebo (95% CI, 0.26 to 0.40). The number needed to treat (NNT) to achieve 14 consecutive dry nights is 2. About half the children relapse after stopping treatment, compared with nearly all children after control interventions (55% vs 99%). Evidence is insufficient to say whether the addition of dry bed training (scheduled awakenings, cleanliness training, social reinforcement, positive practice) improves the outcomes. Alarms that wake the child immediately (vs a time delay) and alarms that wake the child (instead of the parents) were slightly more effective.

A meta-analysis also showed that desmopressin (10-60 μg) at bedtime reduced bedwetting by 1 to 2 nights per week compared with placebo (WMD=1.34; 95% CI, -1.57 to –1.11 with a dose of 20 μg).⁶ The NNT to achieve 14 consecutive dry nights is 7. However, the data suggest once treatment stops, there is little difference between desmopressin and placebo. Some evidence suggested that a higher dose was more likely to decrease the number of wet nights; however, there was no difference in cure rates. Evidence comparing intranasal with oral administration is insufficient.²

In the Cochrane review, children treated with desmopressin had 1.7 fewer wet nights (WMD=1.7; 95% CI, –2.95 to –0.45) in the first week compared with children treated with alarms.⁶ However, at the end of 3 months, alarms were associated with 1.4 fewer wet nights per week than children treated with desmopressin (WMD=1.4; 95% CI, 0.14 to 2.66).

Evidence is conflicting for increased efficacy for combining desmopressin with enuresis alarms. There is some limited evidence that children receiving combination treatment with desmopressin and alarms had fewer wet nights than children treated with alarms and placebo.⁶ This combination treatment did not show a benefit with failure rates (not attaining 14 consecutive dry nights) or a statistically significant difference in failure and relapse rates once treatment stopped. In addition, one RCT in which desmopressin nonresponders were supplemented with alarms showed no added benefit in remission rates compared with conditioning alarms plus placebo (51% vs 48% in achieving 28 dry nights).⁷ Neither was there added benefit in relapse rates once treatment stopped.

Children treated with tricyclic drugs compared with those treated with placebo had approximately 1 less night of enuresis per week (WMD=1.19; 95% CI, –1.56 to-0.82).8 More children achieved 14 dry nights while on imipramine compared with placebo (21% vs 5%; NNT=6); however, this advantage was not sustained once treatment finished (96% vs 97% relapsed). Little evidence exists to compare desmopressin with tricyclic drugs.^2,8

Simple behavior methods may be more effective than no treatment, but there is little evidence for how these methods compare with one another, or with more successful means of treatment.⁹ Behavior techniques include lifting (taking a sleeping child to urinate in the bath-room), waking, rewards, and evening fluid restriction.

Dry bed training refers to comprehensive regimes, including enuresis alarms, waking routines, positive practice, cleanliness training, and bladder training in various combinations. A meta-analysis examining dry bed training including an enuresis alarm showed children had fewer wet nights compared with children receiving no treatment (relative risk [RR] of failure=0.17; 95% CI, 0.11-0.28).^2,10 Additionally, more children remained dry after treatment stopped (RR of relapse=0.25; 95% CI, 0.16-0.39). However, evidence was not sufficient to show a remission benefit for dry bed training without an alarm (RR of failure=0.82; 95% CI, 0.6-1.02), highlighting the key role for alarm therapy. On the other hand, dry bed training including bed alarms may reduce the relapse rate compared with alarm monotherapy (RR for failure or relapse=0.5; 95% CI, 0.31-0.8)

TABLE
Nocturnal enuresis treatments and efficacy

Recommendations from others

A recent evidence-based practice parameter from the American Academy of Child and Adolescent Psychiatry states once the history and physical suggest primary nocturnal enuresis, treatment should include education demystification and withholding punishment.⁴ Although insufficient evidence exists to recommend behavioral interventions such as journal keeping, fluid restrictions, and night awakenings, these supportive approaches are acceptable, benign starting points. Conditioning with an enuresis alarm and overlearning, which involves giving extra fluids at bedtime after successfully becoming dry and intermittent reinforcement before ending treatment, is a highly effective first-line management approach. Medication choices include desmopressin and imipramine, although relapse rates are high. Short-term use of desmopressin may be used for sleepovers or camping trips.

Evidence summary

Concussion, as defined by the American Association of Neurologists, is “a trauma-induced alteration in mental status that may or may not involve loss of consciousness.”¹ There are approximately 300,000 sports-related concussions sustained each season in the US, although many athletes do not recognize the symptoms of concussion or may under-report them.

While concussions usually result in no long-term sequela, persistent neurocognitive deficits and psychiatric illnesses, including depression, may result. Case reports exist of fatal brain swelling in athletes who suffer a second head injury while still recovering from a first one, although more recently the existence of a “second impact syndrome” has been disputed.²

A large prospective cohort study of 2900 US college football players found that players with 1 previous concussion had a 40% increased risk of future concussion, and those with 3 previous concussions had a three-fold increase in risk.³ High school students with concussions are 3 to 4 days slower in recovering memory function than college students,^4-6 and women with concussions are 1.7 times more likely to have cognitive impairment than men.⁷

Concussions are often accompanied by symptoms and cognitive problems that can be overlooked if not carefully and systematically assessed. A prospective study of high-school athletes demonstrated that neuropsychological dysfunction takes a week or longer to resolve in “ding” concussions (defined as no loss of consciousness and overt symptoms resolved within 15 minutes).⁸ A prospective cohort study of boxers at the US Military Academy found that it takes 3 to 7 days for recovery of neurocognitive function.⁹ Another cohort study of US college football players found that while postural stability commonly returns in just a day or 2, cognitive recovery often takes 3 to 5 days, and symptoms last over 7 days post-injury for 1 of 8 concussed athletes.¹⁰

Sport concussion assessments should include testing for cognition, postural stability, and self-reported symptoms. Results can then be compared with each individual’s preseason baseline. Examples of screening instruments include SCAT (the Sideline Concussion Assessment Tool),¹¹ SAC (the Standardized Assessment of Concussion), BESS (the Balance Error Scoring System), as well as ImPACT or other neurocognitive tests, to evaluate and document memory, brain processing speed, reaction time, and postconcussive symptoms.^10-12 SCAT, SAC, and BESS can be used on the sidelines, and each can be employed for baseline and follow up testing.

Results from these tests should be interpreted in light of all other aspects of the injury (physical exam, age, sex, history of previous concussion, etc) to guide the decision on returning to play.^11,12 After neurological and balance symptoms have resolved, noncontact exercise may be allowed. When neuropsychological testing has returned to preseason baseline, full contact may be permitted.

Athletes, their families, trainers, and coaches should be educated about concussions so that they are better equipped to both identify and report symptoms. Care for injured athletes should also include education about the long-term effects of multiple concussions.¹²

Recommendations from others

The 2nd International Conference on Concussion in Sport, Prague 2004¹¹ (emphasis added) recommended the following stages of recovery from a concussion:

1. No activity, complete rest. Once asymptomatic, proceed to level 2
2. Light aerobic exercise such as walking or stationary cycling, no resistance training
3. Sport-specific exercise (eg, skating in hockey, running in soccer), progressive addition of resistance training at steps 3 or 4
4. Noncontact training drills
5. Full contact training after medical clearance
6. Game play.

The National Athletic Training Association recommendations are:¹²

• Increase in education of staff working directly with athletes
• Increase in documentation about events surrounding and subsequent to the concussion
• Initial baseline testing for high-risk sports
• No single test should be use exclusively for return to play, as concussions can present in different ways
• Evaluations by athletic trainers or team physician after concussion Q 5 minutes
• Athletes symptomatic at rest and after exertion for 20 minutes (sprinting, push-ups) should be disqualified for that event
• Pediatric patients should have more strict/prolonged recovery periods.
• Wake athletes from sleep at home only if there has been loss of consciousness, prolonged amnesia, or significant symptoms

Evidence summary

Concussion, as defined by the American Association of Neurologists, is “a trauma-induced alteration in mental status that may or may not involve loss of consciousness.”¹ There are approximately 300,000 sports-related concussions sustained each season in the US, although many athletes do not recognize the symptoms of concussion or may under-report them.

While concussions usually result in no long-term sequela, persistent neurocognitive deficits and psychiatric illnesses, including depression, may result. Case reports exist of fatal brain swelling in athletes who suffer a second head injury while still recovering from a first one, although more recently the existence of a “second impact syndrome” has been disputed.²

A large prospective cohort study of 2900 US college football players found that players with 1 previous concussion had a 40% increased risk of future concussion, and those with 3 previous concussions had a three-fold increase in risk.³ High school students with concussions are 3 to 4 days slower in recovering memory function than college students,^4-6 and women with concussions are 1.7 times more likely to have cognitive impairment than men.⁷

Concussions are often accompanied by symptoms and cognitive problems that can be overlooked if not carefully and systematically assessed. A prospective study of high-school athletes demonstrated that neuropsychological dysfunction takes a week or longer to resolve in “ding” concussions (defined as no loss of consciousness and overt symptoms resolved within 15 minutes).⁸ A prospective cohort study of boxers at the US Military Academy found that it takes 3 to 7 days for recovery of neurocognitive function.⁹ Another cohort study of US college football players found that while postural stability commonly returns in just a day or 2, cognitive recovery often takes 3 to 5 days, and symptoms last over 7 days post-injury for 1 of 8 concussed athletes.¹⁰

Sport concussion assessments should include testing for cognition, postural stability, and self-reported symptoms. Results can then be compared with each individual’s preseason baseline. Examples of screening instruments include SCAT (the Sideline Concussion Assessment Tool),¹¹ SAC (the Standardized Assessment of Concussion), BESS (the Balance Error Scoring System), as well as ImPACT or other neurocognitive tests, to evaluate and document memory, brain processing speed, reaction time, and postconcussive symptoms.^10-12 SCAT, SAC, and BESS can be used on the sidelines, and each can be employed for baseline and follow up testing.

Results from these tests should be interpreted in light of all other aspects of the injury (physical exam, age, sex, history of previous concussion, etc) to guide the decision on returning to play.^11,12 After neurological and balance symptoms have resolved, noncontact exercise may be allowed. When neuropsychological testing has returned to preseason baseline, full contact may be permitted.

Athletes, their families, trainers, and coaches should be educated about concussions so that they are better equipped to both identify and report symptoms. Care for injured athletes should also include education about the long-term effects of multiple concussions.¹²

Recommendations from others

The 2nd International Conference on Concussion in Sport, Prague 2004¹¹ (emphasis added) recommended the following stages of recovery from a concussion:

1. No activity, complete rest. Once asymptomatic, proceed to level 2
2. Light aerobic exercise such as walking or stationary cycling, no resistance training
3. Sport-specific exercise (eg, skating in hockey, running in soccer), progressive addition of resistance training at steps 3 or 4
4. Noncontact training drills
5. Full contact training after medical clearance
6. Game play.

The National Athletic Training Association recommendations are:¹²

• Increase in education of staff working directly with athletes
• Increase in documentation about events surrounding and subsequent to the concussion
• Initial baseline testing for high-risk sports
• No single test should be use exclusively for return to play, as concussions can present in different ways
• Evaluations by athletic trainers or team physician after concussion Q 5 minutes
• Athletes symptomatic at rest and after exertion for 20 minutes (sprinting, push-ups) should be disqualified for that event
• Pediatric patients should have more strict/prolonged recovery periods.
• Wake athletes from sleep at home only if there has been loss of consciousness, prolonged amnesia, or significant symptoms

Evidence summary

Concussion, as defined by the American Association of Neurologists, is “a trauma-induced alteration in mental status that may or may not involve loss of consciousness.”¹ There are approximately 300,000 sports-related concussions sustained each season in the US, although many athletes do not recognize the symptoms of concussion or may under-report them.

While concussions usually result in no long-term sequela, persistent neurocognitive deficits and psychiatric illnesses, including depression, may result. Case reports exist of fatal brain swelling in athletes who suffer a second head injury while still recovering from a first one, although more recently the existence of a “second impact syndrome” has been disputed.²

A large prospective cohort study of 2900 US college football players found that players with 1 previous concussion had a 40% increased risk of future concussion, and those with 3 previous concussions had a three-fold increase in risk.³ High school students with concussions are 3 to 4 days slower in recovering memory function than college students,^4-6 and women with concussions are 1.7 times more likely to have cognitive impairment than men.⁷

Concussions are often accompanied by symptoms and cognitive problems that can be overlooked if not carefully and systematically assessed. A prospective study of high-school athletes demonstrated that neuropsychological dysfunction takes a week or longer to resolve in “ding” concussions (defined as no loss of consciousness and overt symptoms resolved within 15 minutes).⁸ A prospective cohort study of boxers at the US Military Academy found that it takes 3 to 7 days for recovery of neurocognitive function.⁹ Another cohort study of US college football players found that while postural stability commonly returns in just a day or 2, cognitive recovery often takes 3 to 5 days, and symptoms last over 7 days post-injury for 1 of 8 concussed athletes.¹⁰

Sport concussion assessments should include testing for cognition, postural stability, and self-reported symptoms. Results can then be compared with each individual’s preseason baseline. Examples of screening instruments include SCAT (the Sideline Concussion Assessment Tool),¹¹ SAC (the Standardized Assessment of Concussion), BESS (the Balance Error Scoring System), as well as ImPACT or other neurocognitive tests, to evaluate and document memory, brain processing speed, reaction time, and postconcussive symptoms.^10-12 SCAT, SAC, and BESS can be used on the sidelines, and each can be employed for baseline and follow up testing.

Results from these tests should be interpreted in light of all other aspects of the injury (physical exam, age, sex, history of previous concussion, etc) to guide the decision on returning to play.^11,12 After neurological and balance symptoms have resolved, noncontact exercise may be allowed. When neuropsychological testing has returned to preseason baseline, full contact may be permitted.

Athletes, their families, trainers, and coaches should be educated about concussions so that they are better equipped to both identify and report symptoms. Care for injured athletes should also include education about the long-term effects of multiple concussions.¹²

Recommendations from others

The 2nd International Conference on Concussion in Sport, Prague 2004¹¹ (emphasis added) recommended the following stages of recovery from a concussion:

1. No activity, complete rest. Once asymptomatic, proceed to level 2
2. Light aerobic exercise such as walking or stationary cycling, no resistance training
3. Sport-specific exercise (eg, skating in hockey, running in soccer), progressive addition of resistance training at steps 3 or 4
4. Noncontact training drills
5. Full contact training after medical clearance
6. Game play.

The National Athletic Training Association recommendations are:¹²

• Increase in education of staff working directly with athletes
• Increase in documentation about events surrounding and subsequent to the concussion
• Initial baseline testing for high-risk sports
• No single test should be use exclusively for return to play, as concussions can present in different ways
• Evaluations by athletic trainers or team physician after concussion Q 5 minutes
• Athletes symptomatic at rest and after exertion for 20 minutes (sprinting, push-ups) should be disqualified for that event
• Pediatric patients should have more strict/prolonged recovery periods.
• Wake athletes from sleep at home only if there has been loss of consciousness, prolonged amnesia, or significant symptoms

Evidence summary

An expert guideline recommends a history and physical examination to determine whether an elevated SPL is due to physiologic, pharmacologic, or pathologic causes (TABLE).¹ The fasting morning SPL is least variable and correlates best with a disease state.¹ Clinical correlation is necessary to reveal false positives (due to biologically inactive forms of prolactin) or false negatives (due to very high SPLs that exceed the ability of the assay). If an elevated SPL is suspected despite a normal laboratory report, retesting with serum diluted 1:100 can identify a false-negative value.²

A detailed drug history is important since drug-induced elevated SPL is common.¹ Laboratory evaluation includes thyroid-stimulating hormone, blood urea nitrogen, and creatinine, as well as pregnancy testing when applicable. If no cause of elevated SPL is identified by initial clinical evaluation or if the SPL is greater than 200 ng/mL, experts recommend imaging of the sella turcica with computed tomography or magnetic resonance imaging.¹

Physiologic causes. For patients with a mildly elevated SPL due to a physiologic cause, experts recommend expectant management. Patients should be monitored for symptoms of hypogonadism (amenorrhea, infertility, or sexual dysfunction) and have SPL measured at 6- to 12-month intervals.¹ In cohort studies, treatment of the underlying cause of elevated SPL reverses secondary physiologic changes of low estrogen or testosterone, and hypogonadism.^3-5

Pharmacologic causes. Eliminating a pharmacologic cause may lead to normalization of SPL, although experts recommend psychiatric consultation before discontinuing neuroleptic medications.¹

Pathologic causes. Experts advise treating the underlying cause of a pathologic elevation of SPL. Patients with microadenoma should have SPLs monitored to prevent complications of decreased bone mineral density and sexual dysfunction due to persistently elevated SPL. Patients with a macroadenoma (>1 cm) are at risk for tumor growth and require serial imaging studies in addition to treatment of SPL, according to expert opinion.^1-3

Medical therapy. Medical therapy with a dopamine agonist is indicated for patients with either symptoms of hypogonadism due to elevated SPL, or neurologic symptoms due to the size of a macroadenoma.¹ In a review of 13 cohort studies, bromocriptine improved symptoms and reduced SPLs to normal for 229 of 280 women (82%).⁶ A cohort study of 27 patients with macroadenomas treated with bromocriptine found 10% to 50% reductions of tumor size.⁷ A randomized controlled trial treating 459 women having hyperprolactinemic amenorrhea with either cabergoline or bromocriptine achieved a stable normal SPL in 83% and 59%, respectively (P<.001). Adverse effects were common but were less common with cabergoline (68% vs 78%) and resulted in fewer discontinuations (3% vs 12%).⁸

Surgical therapy. Surgery is indicated for patients unresponsive to or intolerant of medical therapy, or who have visual field loss, cranial nerve palsy, or headache due to macroadenoma.¹ A retrospective review of patients who underwent surgical resection found a 40% recurrence rate.⁹

Recommendations from others

Williams Textbook of Endocrinology includes the recommendations above and advises seeking consultation for patients with mass effects of macroadenomas such as visual field loss, cranial nerve palsy, or headaches; for patients with progressive elevation of SPL despite medical treatment; and for pregnant women.⁴ Conventional antipsychotic agents are commonly associated with elevated prolactin due to dopamine agonist activity. Some atypical antipsychotics may lead to lower levels of elevated prolactin, transient elevations or marked elevations.¹⁰ Experts recommend following serial SPLs, if antipsychotics are truly needed. Psychiatric consultation may assist in making decisions about medication selection. Patients with symptoms (galactorrhea, amenorrhea, headaches, visual disturbances, sexual dysfunction) or levels of 200 or more, should undergo an MRI or CT. Experts recommend monitoring levels every 1 to 3 months.¹

TABLE
Physiologic, pharmacologic, and pathologic causes of an elevated serum prolactin level¹

Evidence summary

An expert guideline recommends a history and physical examination to determine whether an elevated SPL is due to physiologic, pharmacologic, or pathologic causes (TABLE).¹ The fasting morning SPL is least variable and correlates best with a disease state.¹ Clinical correlation is necessary to reveal false positives (due to biologically inactive forms of prolactin) or false negatives (due to very high SPLs that exceed the ability of the assay). If an elevated SPL is suspected despite a normal laboratory report, retesting with serum diluted 1:100 can identify a false-negative value.²

A detailed drug history is important since drug-induced elevated SPL is common.¹ Laboratory evaluation includes thyroid-stimulating hormone, blood urea nitrogen, and creatinine, as well as pregnancy testing when applicable. If no cause of elevated SPL is identified by initial clinical evaluation or if the SPL is greater than 200 ng/mL, experts recommend imaging of the sella turcica with computed tomography or magnetic resonance imaging.¹

Physiologic causes. For patients with a mildly elevated SPL due to a physiologic cause, experts recommend expectant management. Patients should be monitored for symptoms of hypogonadism (amenorrhea, infertility, or sexual dysfunction) and have SPL measured at 6- to 12-month intervals.¹ In cohort studies, treatment of the underlying cause of elevated SPL reverses secondary physiologic changes of low estrogen or testosterone, and hypogonadism.^3-5

Pharmacologic causes. Eliminating a pharmacologic cause may lead to normalization of SPL, although experts recommend psychiatric consultation before discontinuing neuroleptic medications.¹

Pathologic causes. Experts advise treating the underlying cause of a pathologic elevation of SPL. Patients with microadenoma should have SPLs monitored to prevent complications of decreased bone mineral density and sexual dysfunction due to persistently elevated SPL. Patients with a macroadenoma (>1 cm) are at risk for tumor growth and require serial imaging studies in addition to treatment of SPL, according to expert opinion.^1-3

Medical therapy. Medical therapy with a dopamine agonist is indicated for patients with either symptoms of hypogonadism due to elevated SPL, or neurologic symptoms due to the size of a macroadenoma.¹ In a review of 13 cohort studies, bromocriptine improved symptoms and reduced SPLs to normal for 229 of 280 women (82%).⁶ A cohort study of 27 patients with macroadenomas treated with bromocriptine found 10% to 50% reductions of tumor size.⁷ A randomized controlled trial treating 459 women having hyperprolactinemic amenorrhea with either cabergoline or bromocriptine achieved a stable normal SPL in 83% and 59%, respectively (P<.001). Adverse effects were common but were less common with cabergoline (68% vs 78%) and resulted in fewer discontinuations (3% vs 12%).⁸

Surgical therapy. Surgery is indicated for patients unresponsive to or intolerant of medical therapy, or who have visual field loss, cranial nerve palsy, or headache due to macroadenoma.¹ A retrospective review of patients who underwent surgical resection found a 40% recurrence rate.⁹

Recommendations from others

Williams Textbook of Endocrinology includes the recommendations above and advises seeking consultation for patients with mass effects of macroadenomas such as visual field loss, cranial nerve palsy, or headaches; for patients with progressive elevation of SPL despite medical treatment; and for pregnant women.⁴ Conventional antipsychotic agents are commonly associated with elevated prolactin due to dopamine agonist activity. Some atypical antipsychotics may lead to lower levels of elevated prolactin, transient elevations or marked elevations.¹⁰ Experts recommend following serial SPLs, if antipsychotics are truly needed. Psychiatric consultation may assist in making decisions about medication selection. Patients with symptoms (galactorrhea, amenorrhea, headaches, visual disturbances, sexual dysfunction) or levels of 200 or more, should undergo an MRI or CT. Experts recommend monitoring levels every 1 to 3 months.¹

TABLE
Physiologic, pharmacologic, and pathologic causes of an elevated serum prolactin level¹

Evidence summary

An expert guideline recommends a history and physical examination to determine whether an elevated SPL is due to physiologic, pharmacologic, or pathologic causes (TABLE).¹ The fasting morning SPL is least variable and correlates best with a disease state.¹ Clinical correlation is necessary to reveal false positives (due to biologically inactive forms of prolactin) or false negatives (due to very high SPLs that exceed the ability of the assay). If an elevated SPL is suspected despite a normal laboratory report, retesting with serum diluted 1:100 can identify a false-negative value.²

A detailed drug history is important since drug-induced elevated SPL is common.¹ Laboratory evaluation includes thyroid-stimulating hormone, blood urea nitrogen, and creatinine, as well as pregnancy testing when applicable. If no cause of elevated SPL is identified by initial clinical evaluation or if the SPL is greater than 200 ng/mL, experts recommend imaging of the sella turcica with computed tomography or magnetic resonance imaging.¹

Physiologic causes. For patients with a mildly elevated SPL due to a physiologic cause, experts recommend expectant management. Patients should be monitored for symptoms of hypogonadism (amenorrhea, infertility, or sexual dysfunction) and have SPL measured at 6- to 12-month intervals.¹ In cohort studies, treatment of the underlying cause of elevated SPL reverses secondary physiologic changes of low estrogen or testosterone, and hypogonadism.^3-5

Pharmacologic causes. Eliminating a pharmacologic cause may lead to normalization of SPL, although experts recommend psychiatric consultation before discontinuing neuroleptic medications.¹

Pathologic causes. Experts advise treating the underlying cause of a pathologic elevation of SPL. Patients with microadenoma should have SPLs monitored to prevent complications of decreased bone mineral density and sexual dysfunction due to persistently elevated SPL. Patients with a macroadenoma (>1 cm) are at risk for tumor growth and require serial imaging studies in addition to treatment of SPL, according to expert opinion.^1-3

Medical therapy. Medical therapy with a dopamine agonist is indicated for patients with either symptoms of hypogonadism due to elevated SPL, or neurologic symptoms due to the size of a macroadenoma.¹ In a review of 13 cohort studies, bromocriptine improved symptoms and reduced SPLs to normal for 229 of 280 women (82%).⁶ A cohort study of 27 patients with macroadenomas treated with bromocriptine found 10% to 50% reductions of tumor size.⁷ A randomized controlled trial treating 459 women having hyperprolactinemic amenorrhea with either cabergoline or bromocriptine achieved a stable normal SPL in 83% and 59%, respectively (P<.001). Adverse effects were common but were less common with cabergoline (68% vs 78%) and resulted in fewer discontinuations (3% vs 12%).⁸

Surgical therapy. Surgery is indicated for patients unresponsive to or intolerant of medical therapy, or who have visual field loss, cranial nerve palsy, or headache due to macroadenoma.¹ A retrospective review of patients who underwent surgical resection found a 40% recurrence rate.⁹

Recommendations from others

Williams Textbook of Endocrinology includes the recommendations above and advises seeking consultation for patients with mass effects of macroadenomas such as visual field loss, cranial nerve palsy, or headaches; for patients with progressive elevation of SPL despite medical treatment; and for pregnant women.⁴ Conventional antipsychotic agents are commonly associated with elevated prolactin due to dopamine agonist activity. Some atypical antipsychotics may lead to lower levels of elevated prolactin, transient elevations or marked elevations.¹⁰ Experts recommend following serial SPLs, if antipsychotics are truly needed. Psychiatric consultation may assist in making decisions about medication selection. Patients with symptoms (galactorrhea, amenorrhea, headaches, visual disturbances, sexual dysfunction) or levels of 200 or more, should undergo an MRI or CT. Experts recommend monitoring levels every 1 to 3 months.¹

TABLE
Physiologic, pharmacologic, and pathologic causes of an elevated serum prolactin level¹

Evidence summary

Studies evaluating whether menopausal women experience fatigue at higher rates than pre-or perimenopausal women are of variable quality and yield conflicting results.¹ Though several studies suggest an association between fatigue among menopausal women and disease states, poor methodology limits the strength of their findings.

In an Internet-based survey, 448 middle-aged women who reported being either perimenopausal or menopausal responded to questions about their symptoms.² Feeling tired and lacking energy were the 2 most frequently reported symptoms, in 380 (89%) and 355 (83%) of respondents, respectively. These self-selected respondents probably do not represent the menopausal population of women at large.

A prospective cohort study, using a 1-page questionnaire that included 2 fatigue scales, identified 276 (24%) of 1159 primary care patients who indicated fatigue as a major problem.³ The mean age of patients was 57 years and 66% were women. Extensive laboratory testing was not helpful in determining the cause of fatigue. The Beck Depression Inventory, the Modified Somatic Perception Questionnaire, and the Social Readjustment Rating Scale identified depression or anxiety in 80% of patients with fatigue and 12% of controls. There are no similar studies for strictly menopausal women.

The prevalence of obstructive sleep apnea and sleep-disordered breathing increases at the time of menopause and peaks at age 65.^4,5 In a retrospective chart review of patients referred for evaluation of snoring, 22 (91%) of the women with studies) were more likely to report daytime fatigue as a presenting symptom than were the 44 (55%) of men with obstructive sleep apnea (P<.01).⁶ Most striking was a sub-group (40%) of women with documented obstructive sleep apnea who reported only fatigue and morning headache but did not note apnea or restless sleep.

Coronary heart disease is the primary cause of death for women in the United States. A retrospective study of 515 women 4 to 6 months after a myocardial infarction explored self-reported symptoms.⁷ The mean age was 66±12 years and 93% were white. Unusual fatigue was the most frequent prodromal symptom experienced by 70.7% of women 1 month before a myocardial infarction, with 42.9% reporting fatigue in the acute setting. Though this retrospective study is limited both by its methodological quality and by the narrow population studied, the results suggest a gender difference between men and women in their report of symptoms of coronary artery disease.

A review of 15 studies from 1989 to 2002 reported that some studies found women were more likely to seek medical care for extreme fatigue and dyspnea than they were for chest pain. In acute coronary syndromes, 18% of women (compared with 9% of men) reported fatigue as a presenting symptom (P<.05). This review was limited by small sample sizes, retrospective chart review designs, and lack of explicitly stated critical appraisal criteria.⁸

Recommendations from others

No recommendations were identified.

Evidence summary

Studies evaluating whether menopausal women experience fatigue at higher rates than pre-or perimenopausal women are of variable quality and yield conflicting results.¹ Though several studies suggest an association between fatigue among menopausal women and disease states, poor methodology limits the strength of their findings.

In an Internet-based survey, 448 middle-aged women who reported being either perimenopausal or menopausal responded to questions about their symptoms.² Feeling tired and lacking energy were the 2 most frequently reported symptoms, in 380 (89%) and 355 (83%) of respondents, respectively. These self-selected respondents probably do not represent the menopausal population of women at large.

A prospective cohort study, using a 1-page questionnaire that included 2 fatigue scales, identified 276 (24%) of 1159 primary care patients who indicated fatigue as a major problem.³ The mean age of patients was 57 years and 66% were women. Extensive laboratory testing was not helpful in determining the cause of fatigue. The Beck Depression Inventory, the Modified Somatic Perception Questionnaire, and the Social Readjustment Rating Scale identified depression or anxiety in 80% of patients with fatigue and 12% of controls. There are no similar studies for strictly menopausal women.

The prevalence of obstructive sleep apnea and sleep-disordered breathing increases at the time of menopause and peaks at age 65.^4,5 In a retrospective chart review of patients referred for evaluation of snoring, 22 (91%) of the women with studies) were more likely to report daytime fatigue as a presenting symptom than were the 44 (55%) of men with obstructive sleep apnea (P<.01).⁶ Most striking was a sub-group (40%) of women with documented obstructive sleep apnea who reported only fatigue and morning headache but did not note apnea or restless sleep.

Coronary heart disease is the primary cause of death for women in the United States. A retrospective study of 515 women 4 to 6 months after a myocardial infarction explored self-reported symptoms.⁷ The mean age was 66±12 years and 93% were white. Unusual fatigue was the most frequent prodromal symptom experienced by 70.7% of women 1 month before a myocardial infarction, with 42.9% reporting fatigue in the acute setting. Though this retrospective study is limited both by its methodological quality and by the narrow population studied, the results suggest a gender difference between men and women in their report of symptoms of coronary artery disease.

A review of 15 studies from 1989 to 2002 reported that some studies found women were more likely to seek medical care for extreme fatigue and dyspnea than they were for chest pain. In acute coronary syndromes, 18% of women (compared with 9% of men) reported fatigue as a presenting symptom (P<.05). This review was limited by small sample sizes, retrospective chart review designs, and lack of explicitly stated critical appraisal criteria.⁸

Recommendations from others

No recommendations were identified.

Evidence summary

Studies evaluating whether menopausal women experience fatigue at higher rates than pre-or perimenopausal women are of variable quality and yield conflicting results.¹ Though several studies suggest an association between fatigue among menopausal women and disease states, poor methodology limits the strength of their findings.

In an Internet-based survey, 448 middle-aged women who reported being either perimenopausal or menopausal responded to questions about their symptoms.² Feeling tired and lacking energy were the 2 most frequently reported symptoms, in 380 (89%) and 355 (83%) of respondents, respectively. These self-selected respondents probably do not represent the menopausal population of women at large.

A prospective cohort study, using a 1-page questionnaire that included 2 fatigue scales, identified 276 (24%) of 1159 primary care patients who indicated fatigue as a major problem.³ The mean age of patients was 57 years and 66% were women. Extensive laboratory testing was not helpful in determining the cause of fatigue. The Beck Depression Inventory, the Modified Somatic Perception Questionnaire, and the Social Readjustment Rating Scale identified depression or anxiety in 80% of patients with fatigue and 12% of controls. There are no similar studies for strictly menopausal women.

The prevalence of obstructive sleep apnea and sleep-disordered breathing increases at the time of menopause and peaks at age 65.^4,5 In a retrospective chart review of patients referred for evaluation of snoring, 22 (91%) of the women with studies) were more likely to report daytime fatigue as a presenting symptom than were the 44 (55%) of men with obstructive sleep apnea (P<.01).⁶ Most striking was a sub-group (40%) of women with documented obstructive sleep apnea who reported only fatigue and morning headache but did not note apnea or restless sleep.

Coronary heart disease is the primary cause of death for women in the United States. A retrospective study of 515 women 4 to 6 months after a myocardial infarction explored self-reported symptoms.⁷ The mean age was 66±12 years and 93% were white. Unusual fatigue was the most frequent prodromal symptom experienced by 70.7% of women 1 month before a myocardial infarction, with 42.9% reporting fatigue in the acute setting. Though this retrospective study is limited both by its methodological quality and by the narrow population studied, the results suggest a gender difference between men and women in their report of symptoms of coronary artery disease.

A review of 15 studies from 1989 to 2002 reported that some studies found women were more likely to seek medical care for extreme fatigue and dyspnea than they were for chest pain. In acute coronary syndromes, 18% of women (compared with 9% of men) reported fatigue as a presenting symptom (P<.05). This review was limited by small sample sizes, retrospective chart review designs, and lack of explicitly stated critical appraisal criteria.⁸

Recommendations from others

No recommendations were identified.