Leslie Mackler, MSLS

EVIDENCE SUMMARY
Troponin I and T proteins are specific to cardiac myocytes and, unlike CK-MB, aren’t elevated by damage to skeletal muscle.

Measuring troponin levels increased the number of patients diagnosed with AMI

A multinational prospective cohort study of patients with suspected ACS (N=10,719) found that measuring troponin levels in addition to CK-MB levels improved the diagnosis of AMI.¹ Investigators used elevation of any biomarker (CK, CK-MB, or troponin I or T) above the upper limit of normal as their diagnostic criterion. They found that measuring troponin increased the number of patients diagnosed with AMI by 10.4% over patients diagnosed using CK and CK-MB levels. Elevated troponin levels were associated with an inpatient mortality rate 1.5 to 3 times higher, regardless of the patient’s CK-MB status.

Troponin levels are more sensitive and specific than CK-MB

A prospective cohort study of 718 patients with suspected AMI calculated the area under curve (AUC) of the receiver operator curve—a measure of diagnostic accuracy in which an AUC value of 1 indicates 100% sensitivity and specificity—for troponin and CK-MB levels at initial presentation.² Two independent cardiologists reviewed all available medical records and made the final diagnosis. The AUCs for troponin levels ranged from 0.94 to 0.96 compared with 0.88 for CK-MB.

Troponin levels and odds of MI or death

A prospective study of 1852 patients with suspected ACS from 3 trial populations evaluated the prognostic value of increased troponin levels vs CK-MB levels at initial presentation, compared with a reference group with normal troponin and CK-MB levels.³ Patients with isolated troponin elevation had an increased odds of MI or death at 24 hours (odds ratio [OR]=5.2; 95% confidence interval [CI], 2.2-11.9) and 30 days (OR=2.1; 95% CI, 1.4-3.0), whereas patients with isolated CK-MB elevations didn't. At 30 days, patients with isolated CK-MB elevations equaled the reference group odds for MI and death (OR=1.0; 95% CI, 0.6-1.6).

Serial troponin assessment boosts diagnostic sensitivity

A prospective cohort study found that serial measurements of troponin increased the diagnostic sensitivity for AMI.⁴ Investigators evaluated 1818 consecutive patients with new onset chest pain in 3 German chest-pain units with troponin levels on admission and at 3 and 6 hours later. The gold standard was diagnosis of AMI by 2 independent cardiologists. Troponin measurement produced an AUC of 0.96 at admission, increasing to 0.98 and 0.99 at 3 and 6 hours after admission, respectively.

Recommendations
The American College of Cardiology and American Heart Association recommend measuring biomarkers of cardiac injury in all patients who present with chest discomfort consistent with ACS.⁵ A cardiac-specific troponin is the preferred marker and should be measured in all patients. If troponin is not available, CK-MB is the best alternative. Cardiac biomarkers should be repeated 6 to 9 hours after presentation and, in patients with a high clinical suspicion of AMI, at 12 to 24 hours.^6,7

EVIDENCE SUMMARY
Troponin I and T proteins are specific to cardiac myocytes and, unlike CK-MB, aren’t elevated by damage to skeletal muscle.

Measuring troponin levels increased the number of patients diagnosed with AMI

A multinational prospective cohort study of patients with suspected ACS (N=10,719) found that measuring troponin levels in addition to CK-MB levels improved the diagnosis of AMI.¹ Investigators used elevation of any biomarker (CK, CK-MB, or troponin I or T) above the upper limit of normal as their diagnostic criterion. They found that measuring troponin increased the number of patients diagnosed with AMI by 10.4% over patients diagnosed using CK and CK-MB levels. Elevated troponin levels were associated with an inpatient mortality rate 1.5 to 3 times higher, regardless of the patient’s CK-MB status.

Troponin levels are more sensitive and specific than CK-MB

A prospective cohort study of 718 patients with suspected AMI calculated the area under curve (AUC) of the receiver operator curve—a measure of diagnostic accuracy in which an AUC value of 1 indicates 100% sensitivity and specificity—for troponin and CK-MB levels at initial presentation.² Two independent cardiologists reviewed all available medical records and made the final diagnosis. The AUCs for troponin levels ranged from 0.94 to 0.96 compared with 0.88 for CK-MB.

Troponin levels and odds of MI or death

A prospective study of 1852 patients with suspected ACS from 3 trial populations evaluated the prognostic value of increased troponin levels vs CK-MB levels at initial presentation, compared with a reference group with normal troponin and CK-MB levels.³ Patients with isolated troponin elevation had an increased odds of MI or death at 24 hours (odds ratio [OR]=5.2; 95% confidence interval [CI], 2.2-11.9) and 30 days (OR=2.1; 95% CI, 1.4-3.0), whereas patients with isolated CK-MB elevations didn't. At 30 days, patients with isolated CK-MB elevations equaled the reference group odds for MI and death (OR=1.0; 95% CI, 0.6-1.6).

Serial troponin assessment boosts diagnostic sensitivity

A prospective cohort study found that serial measurements of troponin increased the diagnostic sensitivity for AMI.⁴ Investigators evaluated 1818 consecutive patients with new onset chest pain in 3 German chest-pain units with troponin levels on admission and at 3 and 6 hours later. The gold standard was diagnosis of AMI by 2 independent cardiologists. Troponin measurement produced an AUC of 0.96 at admission, increasing to 0.98 and 0.99 at 3 and 6 hours after admission, respectively.

Recommendations
The American College of Cardiology and American Heart Association recommend measuring biomarkers of cardiac injury in all patients who present with chest discomfort consistent with ACS.⁵ A cardiac-specific troponin is the preferred marker and should be measured in all patients. If troponin is not available, CK-MB is the best alternative. Cardiac biomarkers should be repeated 6 to 9 hours after presentation and, in patients with a high clinical suspicion of AMI, at 12 to 24 hours.^6,7

EVIDENCE SUMMARY
Troponin I and T proteins are specific to cardiac myocytes and, unlike CK-MB, aren’t elevated by damage to skeletal muscle.

Measuring troponin levels increased the number of patients diagnosed with AMI

A multinational prospective cohort study of patients with suspected ACS (N=10,719) found that measuring troponin levels in addition to CK-MB levels improved the diagnosis of AMI.¹ Investigators used elevation of any biomarker (CK, CK-MB, or troponin I or T) above the upper limit of normal as their diagnostic criterion. They found that measuring troponin increased the number of patients diagnosed with AMI by 10.4% over patients diagnosed using CK and CK-MB levels. Elevated troponin levels were associated with an inpatient mortality rate 1.5 to 3 times higher, regardless of the patient’s CK-MB status.

Troponin levels are more sensitive and specific than CK-MB

A prospective cohort study of 718 patients with suspected AMI calculated the area under curve (AUC) of the receiver operator curve—a measure of diagnostic accuracy in which an AUC value of 1 indicates 100% sensitivity and specificity—for troponin and CK-MB levels at initial presentation.² Two independent cardiologists reviewed all available medical records and made the final diagnosis. The AUCs for troponin levels ranged from 0.94 to 0.96 compared with 0.88 for CK-MB.

Troponin levels and odds of MI or death

A prospective study of 1852 patients with suspected ACS from 3 trial populations evaluated the prognostic value of increased troponin levels vs CK-MB levels at initial presentation, compared with a reference group with normal troponin and CK-MB levels.³ Patients with isolated troponin elevation had an increased odds of MI or death at 24 hours (odds ratio [OR]=5.2; 95% confidence interval [CI], 2.2-11.9) and 30 days (OR=2.1; 95% CI, 1.4-3.0), whereas patients with isolated CK-MB elevations didn't. At 30 days, patients with isolated CK-MB elevations equaled the reference group odds for MI and death (OR=1.0; 95% CI, 0.6-1.6).

Serial troponin assessment boosts diagnostic sensitivity

A prospective cohort study found that serial measurements of troponin increased the diagnostic sensitivity for AMI.⁴ Investigators evaluated 1818 consecutive patients with new onset chest pain in 3 German chest-pain units with troponin levels on admission and at 3 and 6 hours later. The gold standard was diagnosis of AMI by 2 independent cardiologists. Troponin measurement produced an AUC of 0.96 at admission, increasing to 0.98 and 0.99 at 3 and 6 hours after admission, respectively.

Recommendations
The American College of Cardiology and American Heart Association recommend measuring biomarkers of cardiac injury in all patients who present with chest discomfort consistent with ACS.⁵ A cardiac-specific troponin is the preferred marker and should be measured in all patients. If troponin is not available, CK-MB is the best alternative. Cardiac biomarkers should be repeated 6 to 9 hours after presentation and, in patients with a high clinical suspicion of AMI, at 12 to 24 hours.^6,7

EVIDENCE SUMMARY

Women with probable migraine with visual aura (PMVA) have an increased risk for ischemic stroke (odds ratio [OR]=2.1) but not hemorrhagic stroke.¹ Women with >12 PMVA episodes per year are at greatest risk (OR=2.2, compared with <12 PMVA episodes per year, OR=1.1).² Women taking oral contraceptive pills (OCPs) also have an increased risk for stroke, depending on the estrogen dose (OR=4.8 for 50 mcg; OR=2.7 for 30-40 mcg; OR=1.7 for 20 mcg; and OR=1.0 for progestin-only pills).³

Women with migraines who smoke and take OCPs have the highest risk

Four case-control studies evaluated the risk of ischemic stroke in women with migraines who take OCPs. The first study compared the OR among 135 women 15 to 49 years of age with PMVA and a first ischemic stroke with 614 controls (no history of stroke, matched for age and ethnicity).² Although women with PMVA overall had an increased risk of ischemic stroke (OR=1.5; 95% confidence interval [CI], 1.1-2.0), a subgroup of women with PMVA who also were taking OCPs didn’t have a significantly greater stroke risk than women with PMVA who were not taking OCPs (OR=1.6; 95% CI, not given but reported as not significant; P=.87). Investigators didn’t specify the type of OCPs.

Women with PMVA who smoked had a greater risk of ischemic stroke (OR=1.5; 95% CI, 1.1-2.3), and women with PMVA who both smoked and took OCPs had the highest risk of ischemic stroke (OR =7.0; 95% CI, 1.4-22.8).

In women younger than 45 years, OCPs are associated with higher stroke risk

The second study compared the odds ratio for ischemic stroke among 47 women younger than 45 years with PMVA who were taking combined OCPs with 63 controls.³ Most OCPs contained 30 to 40 mcg estrogen. Women with PMVA taking a combined OCP had a higher risk of ischemic stroke (OR=13.9; 95% CI, 5.5-35.1) than women with PMVA who didn’t take OCPs (OR=3.7; 95% CI, 1.5-9.1). Investigators didn’t report the number of PMVA episodes per year among the women.

The third study compared the odds ratio for ischemic stroke among 10 women 20 to 44 years of age with migraines who were taking combined OCPs with 23 controls.⁴ Investigators didn’t specify the type of migraine, although classic migraine was approximately twice as common as simple migraine among the women in the larger study population. Women with migraine taking OCPs were more likely to have an ischemic stroke overall (OR=16.9; 95% CI, 2.7-106), with the exception of those taking OCPs with <50 mcg estrogen (4 patients) (OR=0.59; 95 % CI, 0.79-54.8).

The fourth study compared the OR for ischemic stroke among 4 women 18 to 44 years old who had a history of migraine (type not specified) and used low-dose OCPs with 14 controls. Women with migraines taking OCPs had a higher risk of ischemic stroke (OR=2.08; 95% CI, 1.19-3.65).⁵

RECOMMENDATIONS

The American College of Obstetricians and Gynecologists says that combined OCPs are contraindicated for women with migraine with focal neurologic symptoms such as aura.⁶ Although strokes are rare in women with migraine taking OCPs, the impact of a stroke is so devastating that clinicians should consider progestin-only, intrauterine, or barrier contraceptives for these women. However, physicians may consider combined OCPs for women younger than 35 years with migraine if they don’t have focal neurologic signs, don’t smoke, and are otherwise healthy.

The World Health Organization and Centers for Disease Control and Prevention state that women with a history of migraine who use combined OCPs are 2 to 4 times more likely to have an ischemic stroke than nonusers and conclude that combined OCP use in women older than 35 years with migraine, or migraine with aura at any age, represents an unacceptable health risk. However, the advantages of using combined OCPs in women younger than 35 years with migraine generally outweigh the theoretical or proven risks.^7,8

EVIDENCE SUMMARY

Women with probable migraine with visual aura (PMVA) have an increased risk for ischemic stroke (odds ratio [OR]=2.1) but not hemorrhagic stroke.¹ Women with >12 PMVA episodes per year are at greatest risk (OR=2.2, compared with <12 PMVA episodes per year, OR=1.1).² Women taking oral contraceptive pills (OCPs) also have an increased risk for stroke, depending on the estrogen dose (OR=4.8 for 50 mcg; OR=2.7 for 30-40 mcg; OR=1.7 for 20 mcg; and OR=1.0 for progestin-only pills).³

Women with migraines who smoke and take OCPs have the highest risk

Four case-control studies evaluated the risk of ischemic stroke in women with migraines who take OCPs. The first study compared the OR among 135 women 15 to 49 years of age with PMVA and a first ischemic stroke with 614 controls (no history of stroke, matched for age and ethnicity).² Although women with PMVA overall had an increased risk of ischemic stroke (OR=1.5; 95% confidence interval [CI], 1.1-2.0), a subgroup of women with PMVA who also were taking OCPs didn’t have a significantly greater stroke risk than women with PMVA who were not taking OCPs (OR=1.6; 95% CI, not given but reported as not significant; P=.87). Investigators didn’t specify the type of OCPs.

Women with PMVA who smoked had a greater risk of ischemic stroke (OR=1.5; 95% CI, 1.1-2.3), and women with PMVA who both smoked and took OCPs had the highest risk of ischemic stroke (OR =7.0; 95% CI, 1.4-22.8).

In women younger than 45 years, OCPs are associated with higher stroke risk

The second study compared the odds ratio for ischemic stroke among 47 women younger than 45 years with PMVA who were taking combined OCPs with 63 controls.³ Most OCPs contained 30 to 40 mcg estrogen. Women with PMVA taking a combined OCP had a higher risk of ischemic stroke (OR=13.9; 95% CI, 5.5-35.1) than women with PMVA who didn’t take OCPs (OR=3.7; 95% CI, 1.5-9.1). Investigators didn’t report the number of PMVA episodes per year among the women.

The third study compared the odds ratio for ischemic stroke among 10 women 20 to 44 years of age with migraines who were taking combined OCPs with 23 controls.⁴ Investigators didn’t specify the type of migraine, although classic migraine was approximately twice as common as simple migraine among the women in the larger study population. Women with migraine taking OCPs were more likely to have an ischemic stroke overall (OR=16.9; 95% CI, 2.7-106), with the exception of those taking OCPs with <50 mcg estrogen (4 patients) (OR=0.59; 95 % CI, 0.79-54.8).

The fourth study compared the OR for ischemic stroke among 4 women 18 to 44 years old who had a history of migraine (type not specified) and used low-dose OCPs with 14 controls. Women with migraines taking OCPs had a higher risk of ischemic stroke (OR=2.08; 95% CI, 1.19-3.65).⁵

RECOMMENDATIONS

The American College of Obstetricians and Gynecologists says that combined OCPs are contraindicated for women with migraine with focal neurologic symptoms such as aura.⁶ Although strokes are rare in women with migraine taking OCPs, the impact of a stroke is so devastating that clinicians should consider progestin-only, intrauterine, or barrier contraceptives for these women. However, physicians may consider combined OCPs for women younger than 35 years with migraine if they don’t have focal neurologic signs, don’t smoke, and are otherwise healthy.

The World Health Organization and Centers for Disease Control and Prevention state that women with a history of migraine who use combined OCPs are 2 to 4 times more likely to have an ischemic stroke than nonusers and conclude that combined OCP use in women older than 35 years with migraine, or migraine with aura at any age, represents an unacceptable health risk. However, the advantages of using combined OCPs in women younger than 35 years with migraine generally outweigh the theoretical or proven risks.^7,8

EVIDENCE SUMMARY

Women with probable migraine with visual aura (PMVA) have an increased risk for ischemic stroke (odds ratio [OR]=2.1) but not hemorrhagic stroke.¹ Women with >12 PMVA episodes per year are at greatest risk (OR=2.2, compared with <12 PMVA episodes per year, OR=1.1).² Women taking oral contraceptive pills (OCPs) also have an increased risk for stroke, depending on the estrogen dose (OR=4.8 for 50 mcg; OR=2.7 for 30-40 mcg; OR=1.7 for 20 mcg; and OR=1.0 for progestin-only pills).³

Women with migraines who smoke and take OCPs have the highest risk

Four case-control studies evaluated the risk of ischemic stroke in women with migraines who take OCPs. The first study compared the OR among 135 women 15 to 49 years of age with PMVA and a first ischemic stroke with 614 controls (no history of stroke, matched for age and ethnicity).² Although women with PMVA overall had an increased risk of ischemic stroke (OR=1.5; 95% confidence interval [CI], 1.1-2.0), a subgroup of women with PMVA who also were taking OCPs didn’t have a significantly greater stroke risk than women with PMVA who were not taking OCPs (OR=1.6; 95% CI, not given but reported as not significant; P=.87). Investigators didn’t specify the type of OCPs.

Women with PMVA who smoked had a greater risk of ischemic stroke (OR=1.5; 95% CI, 1.1-2.3), and women with PMVA who both smoked and took OCPs had the highest risk of ischemic stroke (OR =7.0; 95% CI, 1.4-22.8).

In women younger than 45 years, OCPs are associated with higher stroke risk

The second study compared the odds ratio for ischemic stroke among 47 women younger than 45 years with PMVA who were taking combined OCPs with 63 controls.³ Most OCPs contained 30 to 40 mcg estrogen. Women with PMVA taking a combined OCP had a higher risk of ischemic stroke (OR=13.9; 95% CI, 5.5-35.1) than women with PMVA who didn’t take OCPs (OR=3.7; 95% CI, 1.5-9.1). Investigators didn’t report the number of PMVA episodes per year among the women.

The third study compared the odds ratio for ischemic stroke among 10 women 20 to 44 years of age with migraines who were taking combined OCPs with 23 controls.⁴ Investigators didn’t specify the type of migraine, although classic migraine was approximately twice as common as simple migraine among the women in the larger study population. Women with migraine taking OCPs were more likely to have an ischemic stroke overall (OR=16.9; 95% CI, 2.7-106), with the exception of those taking OCPs with <50 mcg estrogen (4 patients) (OR=0.59; 95 % CI, 0.79-54.8).

The fourth study compared the OR for ischemic stroke among 4 women 18 to 44 years old who had a history of migraine (type not specified) and used low-dose OCPs with 14 controls. Women with migraines taking OCPs had a higher risk of ischemic stroke (OR=2.08; 95% CI, 1.19-3.65).⁵

RECOMMENDATIONS

The American College of Obstetricians and Gynecologists says that combined OCPs are contraindicated for women with migraine with focal neurologic symptoms such as aura.⁶ Although strokes are rare in women with migraine taking OCPs, the impact of a stroke is so devastating that clinicians should consider progestin-only, intrauterine, or barrier contraceptives for these women. However, physicians may consider combined OCPs for women younger than 35 years with migraine if they don’t have focal neurologic signs, don’t smoke, and are otherwise healthy.

The World Health Organization and Centers for Disease Control and Prevention state that women with a history of migraine who use combined OCPs are 2 to 4 times more likely to have an ischemic stroke than nonusers and conclude that combined OCP use in women older than 35 years with migraine, or migraine with aura at any age, represents an unacceptable health risk. However, the advantages of using combined OCPs in women younger than 35 years with migraine generally outweigh the theoretical or proven risks.^7,8

Evidence summary

Pes planus has no universal radiographic or clinical definition, although it can be classified as rigid or flexible based on the mobility of the longitudinal arch. In the absence of an accepted definition, prevalence estimates vary widely.

An Austrian survey of 835 kindergartners ages 3 to 6 years found the prevalence of FFF to be 44%; the prevalence of pathologic flatfoot was less that 1%. Flatfoot was defined by clinical inspection and laser scanning. The study also found that prevalence decreases with age (54% at 3 years, 24% at 6 years) and that boys had a higher rate of FFF (52%) than girls (36%).¹

Flexible flatfoot doesn’t affect function
Ligament laxity is thought to be the primary cause of the abnormally low-lying longitudinal arch associated with weight bearing that characterizes FFF. A small (N=230) prospective cohort study showed that the foot shape of Australian military recruits was unrelated to pain, injury, and functioning during an 8-week basic training course.²

Another prospective cohort study of 246 male US Army recruits enrolled in a rigorous 12-week infantry training program found that trainees with low or flat arches actually had a lower risk of foot injury than trainees with high arches.³

Few studies evaluate FFF conservative treatment
Conservative therapies traditionally used to treat symptomatic FFF include physical therapy, orthotics, and corrective shoes. Few studies of their efficacy exist, however. Although we found no studies of adults or adolescents with symptomatic FFF, we did find a few studies of younger children with noticeably flat feet and concerned parents or physicians who referred them for therapy.

A prospective study followed 129 children with FFF (1-6 years old, mean age 29 months) who were referred by pediatricians to Texas Scottish Rite Hospital Flatfoot Clinic, which was set up entirely for the sake of the study, based on cosmetic appearance as well as functional symptoms. The children were randomized to 1 of 4 groups—controls, corrective orthopedic shoes, heel cups, and custom-molded inserts—and followed for 3 years.

The authors, who were blinded to group assignment, measured 14 outcomes related to foot shape and function. They quantified radiographic changes, not patients’ clinical or functional outcomes. All of the outcomes showed improvement in all 4 groups; no significant differences were noted between children who received active interventions and controls. Thirty-one patients were dropped from the study because of noncompliance and weren’t included in the final analysis.⁴

A small, randomized, single-blind controlled trial studied 160 Australian children between 7 and 11 years of age with bilateral flexible excess pronation (everted calcaneous and lowered medial transverse arch) associated with weight bearing. The investigators evaluated gross motor proficiency, self-perception, exercise efficiency, and pain over 12 months in 3 groups of children who received no treatment, noncustom orthoses, or custom-made orthoses. They found no significant difference in any outcomes measure among the groups after 3 and 12 months.⁵

Better results with heel cups than insoles
A small (N=30) retrospective study enrolled children (mean age 3.8 years) based on clinical and anatomical characteristics of FFF. The study found that a polyethylene “dynamic varus heel cup” worn for 14 months was superior to static insoles for treating severe pes planus, characterized by poor formation of the longitudinal arch and valgus deviation of the calcaneous. The study was not randomized or blinded, and the authors evaluated only physical examination features and radiographic findings, not patient symptoms or functional outcomes.⁶

Rigid flatfoot often causes symptoms

RFF is often symptomatic and is caused by underlying pathology.⁷ Tarsal coalition is the most common cause, but trauma, neoplasm, infection, and rheumatologic and neuromuscular disorders can all contribute. A very small retrospective study of 9 patients found that “children and adolescents with painful idiopathic rigid flatfeet…can have significant, persistent disability.”⁸

Surgical treatment depends on underlying pathology
No long-term studies similar to studies of FFF have compared surgery with conservative therapies for RFF. The type of surgical treatment used depends on the underlying pathology and which planes of the foot are affected.⁹ Surgery may include 1 or more of the following procedures, depending on clinical and radiographic evaluation:

• tendon transfers or lengthening
• tarsal arthrodeses or subtalar joint motion blockers
• calcaneal osteotomy.

Several small studies of different surgical treatments found varying degrees of radio-graphic and symptomatic improvement. None reported long-term outcome data, however.

Recommendations

A Cochrane review of interventions for pes planus is in process.

Recommendations from the Clinical Practice Guideline Pediatric Flatfoot Panel of the American College of Foot and Ankle Surgeons state that “most flexible flatfeet are physiologic, asymptomatic, and require no treatment. Physiologic flexible flatfoot follows a natural history of improvement over time. Periodic observation may be indicated to monitor for signs of progression. Treatment is generally not indicated.”⁹

If FFF is symptomatic, “initial treatment includes activity modifications (primarily avoiding painful activities), stretching, foot strengthening exercises, and orthoses. When all nonsurgical treatment options have been exhausted, surgical intervention can be considered.”⁹

Regarding RFF, the panel notes that the condition “can be symptomatic or asymptomatic. Most cases are associated with underlying primary pathology” and its treatment. “Surgical consideration should be given to those who fail to respond to nonsurgical treatment.”⁹ Tendon transfers and tendon lengthening are not recommended for children.

Evidence summary

Pes planus has no universal radiographic or clinical definition, although it can be classified as rigid or flexible based on the mobility of the longitudinal arch. In the absence of an accepted definition, prevalence estimates vary widely.

An Austrian survey of 835 kindergartners ages 3 to 6 years found the prevalence of FFF to be 44%; the prevalence of pathologic flatfoot was less that 1%. Flatfoot was defined by clinical inspection and laser scanning. The study also found that prevalence decreases with age (54% at 3 years, 24% at 6 years) and that boys had a higher rate of FFF (52%) than girls (36%).¹

Flexible flatfoot doesn’t affect function
Ligament laxity is thought to be the primary cause of the abnormally low-lying longitudinal arch associated with weight bearing that characterizes FFF. A small (N=230) prospective cohort study showed that the foot shape of Australian military recruits was unrelated to pain, injury, and functioning during an 8-week basic training course.²

Another prospective cohort study of 246 male US Army recruits enrolled in a rigorous 12-week infantry training program found that trainees with low or flat arches actually had a lower risk of foot injury than trainees with high arches.³

Few studies evaluate FFF conservative treatment
Conservative therapies traditionally used to treat symptomatic FFF include physical therapy, orthotics, and corrective shoes. Few studies of their efficacy exist, however. Although we found no studies of adults or adolescents with symptomatic FFF, we did find a few studies of younger children with noticeably flat feet and concerned parents or physicians who referred them for therapy.

A prospective study followed 129 children with FFF (1-6 years old, mean age 29 months) who were referred by pediatricians to Texas Scottish Rite Hospital Flatfoot Clinic, which was set up entirely for the sake of the study, based on cosmetic appearance as well as functional symptoms. The children were randomized to 1 of 4 groups—controls, corrective orthopedic shoes, heel cups, and custom-molded inserts—and followed for 3 years.

The authors, who were blinded to group assignment, measured 14 outcomes related to foot shape and function. They quantified radiographic changes, not patients’ clinical or functional outcomes. All of the outcomes showed improvement in all 4 groups; no significant differences were noted between children who received active interventions and controls. Thirty-one patients were dropped from the study because of noncompliance and weren’t included in the final analysis.⁴

A small, randomized, single-blind controlled trial studied 160 Australian children between 7 and 11 years of age with bilateral flexible excess pronation (everted calcaneous and lowered medial transverse arch) associated with weight bearing. The investigators evaluated gross motor proficiency, self-perception, exercise efficiency, and pain over 12 months in 3 groups of children who received no treatment, noncustom orthoses, or custom-made orthoses. They found no significant difference in any outcomes measure among the groups after 3 and 12 months.⁵

Better results with heel cups than insoles
A small (N=30) retrospective study enrolled children (mean age 3.8 years) based on clinical and anatomical characteristics of FFF. The study found that a polyethylene “dynamic varus heel cup” worn for 14 months was superior to static insoles for treating severe pes planus, characterized by poor formation of the longitudinal arch and valgus deviation of the calcaneous. The study was not randomized or blinded, and the authors evaluated only physical examination features and radiographic findings, not patient symptoms or functional outcomes.⁶

Rigid flatfoot often causes symptoms

RFF is often symptomatic and is caused by underlying pathology.⁷ Tarsal coalition is the most common cause, but trauma, neoplasm, infection, and rheumatologic and neuromuscular disorders can all contribute. A very small retrospective study of 9 patients found that “children and adolescents with painful idiopathic rigid flatfeet…can have significant, persistent disability.”⁸

Surgical treatment depends on underlying pathology
No long-term studies similar to studies of FFF have compared surgery with conservative therapies for RFF. The type of surgical treatment used depends on the underlying pathology and which planes of the foot are affected.⁹ Surgery may include 1 or more of the following procedures, depending on clinical and radiographic evaluation:

• tendon transfers or lengthening
• tarsal arthrodeses or subtalar joint motion blockers
• calcaneal osteotomy.

Several small studies of different surgical treatments found varying degrees of radio-graphic and symptomatic improvement. None reported long-term outcome data, however.

Recommendations

A Cochrane review of interventions for pes planus is in process.

Recommendations from the Clinical Practice Guideline Pediatric Flatfoot Panel of the American College of Foot and Ankle Surgeons state that “most flexible flatfeet are physiologic, asymptomatic, and require no treatment. Physiologic flexible flatfoot follows a natural history of improvement over time. Periodic observation may be indicated to monitor for signs of progression. Treatment is generally not indicated.”⁹

If FFF is symptomatic, “initial treatment includes activity modifications (primarily avoiding painful activities), stretching, foot strengthening exercises, and orthoses. When all nonsurgical treatment options have been exhausted, surgical intervention can be considered.”⁹

Regarding RFF, the panel notes that the condition “can be symptomatic or asymptomatic. Most cases are associated with underlying primary pathology” and its treatment. “Surgical consideration should be given to those who fail to respond to nonsurgical treatment.”⁹ Tendon transfers and tendon lengthening are not recommended for children.

Evidence summary

Pes planus has no universal radiographic or clinical definition, although it can be classified as rigid or flexible based on the mobility of the longitudinal arch. In the absence of an accepted definition, prevalence estimates vary widely.

An Austrian survey of 835 kindergartners ages 3 to 6 years found the prevalence of FFF to be 44%; the prevalence of pathologic flatfoot was less that 1%. Flatfoot was defined by clinical inspection and laser scanning. The study also found that prevalence decreases with age (54% at 3 years, 24% at 6 years) and that boys had a higher rate of FFF (52%) than girls (36%).¹

Flexible flatfoot doesn’t affect function
Ligament laxity is thought to be the primary cause of the abnormally low-lying longitudinal arch associated with weight bearing that characterizes FFF. A small (N=230) prospective cohort study showed that the foot shape of Australian military recruits was unrelated to pain, injury, and functioning during an 8-week basic training course.²

Another prospective cohort study of 246 male US Army recruits enrolled in a rigorous 12-week infantry training program found that trainees with low or flat arches actually had a lower risk of foot injury than trainees with high arches.³

Few studies evaluate FFF conservative treatment
Conservative therapies traditionally used to treat symptomatic FFF include physical therapy, orthotics, and corrective shoes. Few studies of their efficacy exist, however. Although we found no studies of adults or adolescents with symptomatic FFF, we did find a few studies of younger children with noticeably flat feet and concerned parents or physicians who referred them for therapy.

A prospective study followed 129 children with FFF (1-6 years old, mean age 29 months) who were referred by pediatricians to Texas Scottish Rite Hospital Flatfoot Clinic, which was set up entirely for the sake of the study, based on cosmetic appearance as well as functional symptoms. The children were randomized to 1 of 4 groups—controls, corrective orthopedic shoes, heel cups, and custom-molded inserts—and followed for 3 years.

The authors, who were blinded to group assignment, measured 14 outcomes related to foot shape and function. They quantified radiographic changes, not patients’ clinical or functional outcomes. All of the outcomes showed improvement in all 4 groups; no significant differences were noted between children who received active interventions and controls. Thirty-one patients were dropped from the study because of noncompliance and weren’t included in the final analysis.⁴

A small, randomized, single-blind controlled trial studied 160 Australian children between 7 and 11 years of age with bilateral flexible excess pronation (everted calcaneous and lowered medial transverse arch) associated with weight bearing. The investigators evaluated gross motor proficiency, self-perception, exercise efficiency, and pain over 12 months in 3 groups of children who received no treatment, noncustom orthoses, or custom-made orthoses. They found no significant difference in any outcomes measure among the groups after 3 and 12 months.⁵

Better results with heel cups than insoles
A small (N=30) retrospective study enrolled children (mean age 3.8 years) based on clinical and anatomical characteristics of FFF. The study found that a polyethylene “dynamic varus heel cup” worn for 14 months was superior to static insoles for treating severe pes planus, characterized by poor formation of the longitudinal arch and valgus deviation of the calcaneous. The study was not randomized or blinded, and the authors evaluated only physical examination features and radiographic findings, not patient symptoms or functional outcomes.⁶

Rigid flatfoot often causes symptoms

RFF is often symptomatic and is caused by underlying pathology.⁷ Tarsal coalition is the most common cause, but trauma, neoplasm, infection, and rheumatologic and neuromuscular disorders can all contribute. A very small retrospective study of 9 patients found that “children and adolescents with painful idiopathic rigid flatfeet…can have significant, persistent disability.”⁸

Surgical treatment depends on underlying pathology
No long-term studies similar to studies of FFF have compared surgery with conservative therapies for RFF. The type of surgical treatment used depends on the underlying pathology and which planes of the foot are affected.⁹ Surgery may include 1 or more of the following procedures, depending on clinical and radiographic evaluation:

• tendon transfers or lengthening
• tarsal arthrodeses or subtalar joint motion blockers
• calcaneal osteotomy.

Several small studies of different surgical treatments found varying degrees of radio-graphic and symptomatic improvement. None reported long-term outcome data, however.

Recommendations

A Cochrane review of interventions for pes planus is in process.

Recommendations from the Clinical Practice Guideline Pediatric Flatfoot Panel of the American College of Foot and Ankle Surgeons state that “most flexible flatfeet are physiologic, asymptomatic, and require no treatment. Physiologic flexible flatfoot follows a natural history of improvement over time. Periodic observation may be indicated to monitor for signs of progression. Treatment is generally not indicated.”⁹

If FFF is symptomatic, “initial treatment includes activity modifications (primarily avoiding painful activities), stretching, foot strengthening exercises, and orthoses. When all nonsurgical treatment options have been exhausted, surgical intervention can be considered.”⁹

Regarding RFF, the panel notes that the condition “can be symptomatic or asymptomatic. Most cases are associated with underlying primary pathology” and its treatment. “Surgical consideration should be given to those who fail to respond to nonsurgical treatment.”⁹ Tendon transfers and tendon lengthening are not recommended for children.

Evidence summary

Significant renal artery stenosis (RAS) is defined anatomically as >50% stenosis of the lumen by renal angiography; stenosis is considered hemodynamically significant (potentially causing renovascular hypertension) if it exceeds 75%.¹

The prevalence of renovascular hypertension among the general hypertensive population varies from 1% to 5%. The prevalence increases to 20% to 40% in the presence of certain clinical criteria:

• hypertension in patients <30 years
• worsening or sudden onset of hypertension in patients >50 years
• hypertension refractory to multiple medications
• malignant hypertension
• worsening renal function after starting an angiotensin-converting enzyme inhibitor (ACE-I).^2,3 (Worsening renal function is defined as >30% decline in estimated glomerular filtration rate or >30% increase in serum creatinine during the first 2 months of ACE-I therapy.¹)

Refractory hypertension associated with generalized atherosclerosis is the most predictive risk factor for RAS.

MRA is usually best, but don’t overlook ultrasound

Among the primary diagnostic tests for RAS (see TABLE W1 on page 216a), MRA is the most consistently accurate⁴ and least operator dependent—which makes it the best choice in most situations. One rare but serious concern with MRA is that contrast agents may cause nephrogenic systemic fibrosis (NSF), a debilitating and sometimes fatal diffuse disease affecting the skin, muscle, and internal organs. In 2006, 25 cases of NSF after exposure to gadolinium-based contrast agents were reported, prompting an FDA warning.⁵

Kidney duplex Doppler ultrasound can rival MRA and CTA in accuracy, but is highly operator dependent. If access to highly skilled, experienced technicians is available, this safe and less expensive option can be considered, especially for patients with chronic kidney disease.

TABLE W1
Diagnostic tests for renovascular hypertension

Recommendations

The American College of Radiology recommends stratifying patients into 3 groups:

• high index of suspicion with normal renal function
• high index of suspicion with diminished renal function
• low index of suspicion.

Recommendations include:

• MRA or CTA for high suspicion with normal renal function
• MRA or ultrasonography for high suspicion with impaired renal function
• All methods equally inappropriate if suspicion is low.³

Cost-effectiveness was not evaluated in the meta-analysis used to derive the guidelines.

The National Kidney Foundation recommends MRA and CTA as accurate, noninvasive, and consistent means of diagnosing RAS. The foundation also recommends duplex ultrasonography as a less invasive and less expensive alternative when local expertise is available. The guidelines include a moderately predictive rule for identifying patients who should be screened for renovascular hypertension—that is, patients with intermediate or high pretest probability (www.kidney.org/professionals/kdoqi/guidelines_bp/guide_4.htm).¹

The American College of Cardiology and the American Heart Association list advantages and disadvantages of each diagnostic method and recommend choosing the one that is best suited to the patient.⁶

Acknowledgements

The opinions and assertions contained herein are the private view of the authors and are not to be construed as official, or as reflecting the view of the US Air Force Medical service or the US Air Force at large.

Evidence summary

Significant renal artery stenosis (RAS) is defined anatomically as >50% stenosis of the lumen by renal angiography; stenosis is considered hemodynamically significant (potentially causing renovascular hypertension) if it exceeds 75%.¹

The prevalence of renovascular hypertension among the general hypertensive population varies from 1% to 5%. The prevalence increases to 20% to 40% in the presence of certain clinical criteria:

• hypertension in patients <30 years
• worsening or sudden onset of hypertension in patients >50 years
• hypertension refractory to multiple medications
• malignant hypertension
• worsening renal function after starting an angiotensin-converting enzyme inhibitor (ACE-I).^2,3 (Worsening renal function is defined as >30% decline in estimated glomerular filtration rate or >30% increase in serum creatinine during the first 2 months of ACE-I therapy.¹)

Refractory hypertension associated with generalized atherosclerosis is the most predictive risk factor for RAS.

MRA is usually best, but don’t overlook ultrasound

Among the primary diagnostic tests for RAS (see TABLE W1 on page 216a), MRA is the most consistently accurate⁴ and least operator dependent—which makes it the best choice in most situations. One rare but serious concern with MRA is that contrast agents may cause nephrogenic systemic fibrosis (NSF), a debilitating and sometimes fatal diffuse disease affecting the skin, muscle, and internal organs. In 2006, 25 cases of NSF after exposure to gadolinium-based contrast agents were reported, prompting an FDA warning.⁵

Kidney duplex Doppler ultrasound can rival MRA and CTA in accuracy, but is highly operator dependent. If access to highly skilled, experienced technicians is available, this safe and less expensive option can be considered, especially for patients with chronic kidney disease.

TABLE W1
Diagnostic tests for renovascular hypertension

Recommendations

The American College of Radiology recommends stratifying patients into 3 groups:

• high index of suspicion with normal renal function
• high index of suspicion with diminished renal function
• low index of suspicion.

Recommendations include:

• MRA or CTA for high suspicion with normal renal function
• MRA or ultrasonography for high suspicion with impaired renal function
• All methods equally inappropriate if suspicion is low.³

Cost-effectiveness was not evaluated in the meta-analysis used to derive the guidelines.

The National Kidney Foundation recommends MRA and CTA as accurate, noninvasive, and consistent means of diagnosing RAS. The foundation also recommends duplex ultrasonography as a less invasive and less expensive alternative when local expertise is available. The guidelines include a moderately predictive rule for identifying patients who should be screened for renovascular hypertension—that is, patients with intermediate or high pretest probability (www.kidney.org/professionals/kdoqi/guidelines_bp/guide_4.htm).¹

The American College of Cardiology and the American Heart Association list advantages and disadvantages of each diagnostic method and recommend choosing the one that is best suited to the patient.⁶

Acknowledgements

The opinions and assertions contained herein are the private view of the authors and are not to be construed as official, or as reflecting the view of the US Air Force Medical service or the US Air Force at large.

Evidence summary

Significant renal artery stenosis (RAS) is defined anatomically as >50% stenosis of the lumen by renal angiography; stenosis is considered hemodynamically significant (potentially causing renovascular hypertension) if it exceeds 75%.¹

The prevalence of renovascular hypertension among the general hypertensive population varies from 1% to 5%. The prevalence increases to 20% to 40% in the presence of certain clinical criteria:

• hypertension in patients <30 years
• worsening or sudden onset of hypertension in patients >50 years
• hypertension refractory to multiple medications
• malignant hypertension
• worsening renal function after starting an angiotensin-converting enzyme inhibitor (ACE-I).^2,3 (Worsening renal function is defined as >30% decline in estimated glomerular filtration rate or >30% increase in serum creatinine during the first 2 months of ACE-I therapy.¹)

Refractory hypertension associated with generalized atherosclerosis is the most predictive risk factor for RAS.

MRA is usually best, but don’t overlook ultrasound

Among the primary diagnostic tests for RAS (see TABLE W1 on page 216a), MRA is the most consistently accurate⁴ and least operator dependent—which makes it the best choice in most situations. One rare but serious concern with MRA is that contrast agents may cause nephrogenic systemic fibrosis (NSF), a debilitating and sometimes fatal diffuse disease affecting the skin, muscle, and internal organs. In 2006, 25 cases of NSF after exposure to gadolinium-based contrast agents were reported, prompting an FDA warning.⁵

Kidney duplex Doppler ultrasound can rival MRA and CTA in accuracy, but is highly operator dependent. If access to highly skilled, experienced technicians is available, this safe and less expensive option can be considered, especially for patients with chronic kidney disease.

TABLE W1
Diagnostic tests for renovascular hypertension

Recommendations

The American College of Radiology recommends stratifying patients into 3 groups:

• high index of suspicion with normal renal function
• high index of suspicion with diminished renal function
• low index of suspicion.

Recommendations include:

• MRA or CTA for high suspicion with normal renal function
• MRA or ultrasonography for high suspicion with impaired renal function
• All methods equally inappropriate if suspicion is low.³

Cost-effectiveness was not evaluated in the meta-analysis used to derive the guidelines.

The National Kidney Foundation recommends MRA and CTA as accurate, noninvasive, and consistent means of diagnosing RAS. The foundation also recommends duplex ultrasonography as a less invasive and less expensive alternative when local expertise is available. The guidelines include a moderately predictive rule for identifying patients who should be screened for renovascular hypertension—that is, patients with intermediate or high pretest probability (www.kidney.org/professionals/kdoqi/guidelines_bp/guide_4.htm).¹

The American College of Cardiology and the American Heart Association list advantages and disadvantages of each diagnostic method and recommend choosing the one that is best suited to the patient.⁶

Acknowledgements

The opinions and assertions contained herein are the private view of the authors and are not to be construed as official, or as reflecting the view of the US Air Force Medical service or the US Air Force at large.

Evidence summary

Ten percent of preeclampsia occurs in pregnancies at less than 34 weeks of gestation. Traditionally, physicians often recommended bed rest to preterm, preeclamptic patients in the belief that it would improve neonatal outcomes.

RCTs find no difference between bed rest and ad lib movement

A single-center RCT investigated bed rest treatment for 105 patients with preeclampsia and gestational ages between 26 to 38 weeks. Patients were assigned to either strict bed rest with bathroom privileges in the hospital until delivery, or to bed rest with the ability to move freely around the hospital. Outcome assessors were not blinded to patient treatment allocation. There was no statistical difference between the 2 groups in perinatal or neonatal mortality, or in the neonatal morbidities of preterm births, endotracheal intubations, or NICU admissions.¹

Similarly, a small, unblinded RCT of 40 preeclamptic patients treated in the hospital with strict bed confinement or without restrictions found no significant difference in fetal or perinatal mortality.² No power calculations were reported for detecting differences in neonatal outcome rates in either of these studies.

Studies in nonproteinuric hypertension were no different

In addition to the studies in patients with preeclampsia, 2 RCTs measured neonatal outcomes with bed rest compared with normal activity in pregnancies complicated by nonproteinuric hypertension. These studies also found that bed rest did not improve neonatal outcomes.

The first trial was a multicenter RCT involving 218 patients between 28 to 38 weeks gestation with nonproteinuric hypertension (blood pressure >140/90 mm Hg). The patients were randomized to 2 groups: bed rest in the hospital but allowed to move around the ward, and normal activity at home without restrictions. The outcomes were measured by masked assessors. There were no statistical differences in perinatal or neonatal mortality, or in the neonatal morbidities of preterm birth, newborns small for their gestational age, or NICU admissions between the 2 groups.³

A second RCT of 135 nonproteinuric but hypertensive pregnant patients with diastolic blood pressures between 90 and 109 mm Hg also demonstrated no difference between patients treated with bed rest and sedation or normal activity in fetal or neonatal outcomes.⁴

Recommendations from others

An American College of Obstetrics and Gynecology practice bulletin on diagnosis and management of preeclampsia and eclampsia does not mention bed rest.⁵ The Canadian Hypertension Society Consensus Conference in 1997 stated that a “policy of hospital admission and strict bed rest is not advised for gestational hypertension with or without proteinuria.”⁶

Evidence summary

Ten percent of preeclampsia occurs in pregnancies at less than 34 weeks of gestation. Traditionally, physicians often recommended bed rest to preterm, preeclamptic patients in the belief that it would improve neonatal outcomes.

RCTs find no difference between bed rest and ad lib movement

A single-center RCT investigated bed rest treatment for 105 patients with preeclampsia and gestational ages between 26 to 38 weeks. Patients were assigned to either strict bed rest with bathroom privileges in the hospital until delivery, or to bed rest with the ability to move freely around the hospital. Outcome assessors were not blinded to patient treatment allocation. There was no statistical difference between the 2 groups in perinatal or neonatal mortality, or in the neonatal morbidities of preterm births, endotracheal intubations, or NICU admissions.¹

Similarly, a small, unblinded RCT of 40 preeclamptic patients treated in the hospital with strict bed confinement or without restrictions found no significant difference in fetal or perinatal mortality.² No power calculations were reported for detecting differences in neonatal outcome rates in either of these studies.

Studies in nonproteinuric hypertension were no different

In addition to the studies in patients with preeclampsia, 2 RCTs measured neonatal outcomes with bed rest compared with normal activity in pregnancies complicated by nonproteinuric hypertension. These studies also found that bed rest did not improve neonatal outcomes.

The first trial was a multicenter RCT involving 218 patients between 28 to 38 weeks gestation with nonproteinuric hypertension (blood pressure >140/90 mm Hg). The patients were randomized to 2 groups: bed rest in the hospital but allowed to move around the ward, and normal activity at home without restrictions. The outcomes were measured by masked assessors. There were no statistical differences in perinatal or neonatal mortality, or in the neonatal morbidities of preterm birth, newborns small for their gestational age, or NICU admissions between the 2 groups.³

A second RCT of 135 nonproteinuric but hypertensive pregnant patients with diastolic blood pressures between 90 and 109 mm Hg also demonstrated no difference between patients treated with bed rest and sedation or normal activity in fetal or neonatal outcomes.⁴

Recommendations from others

An American College of Obstetrics and Gynecology practice bulletin on diagnosis and management of preeclampsia and eclampsia does not mention bed rest.⁵ The Canadian Hypertension Society Consensus Conference in 1997 stated that a “policy of hospital admission and strict bed rest is not advised for gestational hypertension with or without proteinuria.”⁶

Evidence summary

Ten percent of preeclampsia occurs in pregnancies at less than 34 weeks of gestation. Traditionally, physicians often recommended bed rest to preterm, preeclamptic patients in the belief that it would improve neonatal outcomes.

RCTs find no difference between bed rest and ad lib movement

A single-center RCT investigated bed rest treatment for 105 patients with preeclampsia and gestational ages between 26 to 38 weeks. Patients were assigned to either strict bed rest with bathroom privileges in the hospital until delivery, or to bed rest with the ability to move freely around the hospital. Outcome assessors were not blinded to patient treatment allocation. There was no statistical difference between the 2 groups in perinatal or neonatal mortality, or in the neonatal morbidities of preterm births, endotracheal intubations, or NICU admissions.¹

Similarly, a small, unblinded RCT of 40 preeclamptic patients treated in the hospital with strict bed confinement or without restrictions found no significant difference in fetal or perinatal mortality.² No power calculations were reported for detecting differences in neonatal outcome rates in either of these studies.

Studies in nonproteinuric hypertension were no different

In addition to the studies in patients with preeclampsia, 2 RCTs measured neonatal outcomes with bed rest compared with normal activity in pregnancies complicated by nonproteinuric hypertension. These studies also found that bed rest did not improve neonatal outcomes.

The first trial was a multicenter RCT involving 218 patients between 28 to 38 weeks gestation with nonproteinuric hypertension (blood pressure >140/90 mm Hg). The patients were randomized to 2 groups: bed rest in the hospital but allowed to move around the ward, and normal activity at home without restrictions. The outcomes were measured by masked assessors. There were no statistical differences in perinatal or neonatal mortality, or in the neonatal morbidities of preterm birth, newborns small for their gestational age, or NICU admissions between the 2 groups.³

A second RCT of 135 nonproteinuric but hypertensive pregnant patients with diastolic blood pressures between 90 and 109 mm Hg also demonstrated no difference between patients treated with bed rest and sedation or normal activity in fetal or neonatal outcomes.⁴

Recommendations from others

An American College of Obstetrics and Gynecology practice bulletin on diagnosis and management of preeclampsia and eclampsia does not mention bed rest.⁵ The Canadian Hypertension Society Consensus Conference in 1997 stated that a “policy of hospital admission and strict bed rest is not advised for gestational hypertension with or without proteinuria.”⁶

Evidence summary

No randomized controlled trials have been published regarding percutaneous vertebroplasty. A 2005 Technology Assessment by the Centers for Medicare and Medicaid Services (CMS) provides the best evidence about indications and efficacy of percutaneous vertebroplasty for vertebral fractures.¹ The CMS report is based on a search of Medline and Current Contents through April 2005 for relevant studies, along with hand searches of retrieved articles’ references and of recent pertinent journals. Study inclusion criteria included English language, vertebral fractures due to osteoporosis or malignancy, consecutive patient enrollment, outcomes reported for pain, functional status, and quality of life, and study size ≥20 patients for studies of osteoporosis or ≥10 patients for studies of malignancy. There was no description of a formal study validity assessment or attempts to control bias by use of multiple reviewers.

Fifteen studies were included, representing 1056 patients. Fourteen of the studies were observational and 1 was a nonrandomized controlled trial. The common inclusion requirement was severe pain attributable to vertebral fracture. Nine of the studies further specified failure of analgesics or conservative treatments. The studies showed statistically significant decreases in comparative visual analog pain scale scores in the short term. Four studies showed pain reduction lasting up to 1 year. These results favor the conclusion that percutaneous vertebroplasty provides short- and long-term pain reduction for patients meeting the inclusion criteria. However, the lack of randomized trials cannot control for the placebo effect, the natural history of vertebral fractures, and regression to the mean as possible reasons for the apparent efficacy of percutaneous vertebroplasty.

Two structured, but not systematic, reviews of percutaneous vertebroplasty in vertebral fractures^2,3 included 15 small observational studies, of which only 1 was included in the CMS report. These reviews examined outcomes of vertebroplasty performed from less than 1 month to a mean of 7 months after fracture, using similar inclusion criteria to those used in the CMS report. The studies’ common patient exclusion criteria were uncorrectable coagulation disorder, infection in the area, spinal cord compression, destruction of the posterior vertebral wall, and severe degrees of vertebral body collapse (defined as >67% collapse). The 2 reviews found between 67% and 100% of patients reported pain reduction after vertebroplasty in follow-up periods ranging from 24 hours to up to 10 years. Based on this limited evidence, 1 review suggested that the likelihood of alleviation of pain decreases over time and is low for fractures occurring more than 6 months in the past.³ In contradistinction, 3 subsequent observational studies, involving a total of 233 patients with 365 vertebral compression fractures failed to find an association between postprocedural pain and age of fracture (ranging from less than 2 weeks to more than 24 months from injury).^4-6

Recommendations from others

In their guideline on rehabilitation of the patient with osteoporosis, the National Osteoporosis Foundation states an experienced practitioner may perform percutaneous vertebroplasty on a patient with unremitting pain for whom conservative medical therapy has not helped.⁷ They qualify this recommendation by further stating long-term clinical studies are required before vertebroplasty becomes standard of care. The Medicare Coverage Advisory Committee, in its review of the 2005 CMS report, suggested that percutaneous vertebroplasty produces a clinically important net health benefit for patients with vertebral compression fracture compared to conservative care for both acute and chronic fractures.⁸

Evidence summary

No randomized controlled trials have been published regarding percutaneous vertebroplasty. A 2005 Technology Assessment by the Centers for Medicare and Medicaid Services (CMS) provides the best evidence about indications and efficacy of percutaneous vertebroplasty for vertebral fractures.¹ The CMS report is based on a search of Medline and Current Contents through April 2005 for relevant studies, along with hand searches of retrieved articles’ references and of recent pertinent journals. Study inclusion criteria included English language, vertebral fractures due to osteoporosis or malignancy, consecutive patient enrollment, outcomes reported for pain, functional status, and quality of life, and study size ≥20 patients for studies of osteoporosis or ≥10 patients for studies of malignancy. There was no description of a formal study validity assessment or attempts to control bias by use of multiple reviewers.

Fifteen studies were included, representing 1056 patients. Fourteen of the studies were observational and 1 was a nonrandomized controlled trial. The common inclusion requirement was severe pain attributable to vertebral fracture. Nine of the studies further specified failure of analgesics or conservative treatments. The studies showed statistically significant decreases in comparative visual analog pain scale scores in the short term. Four studies showed pain reduction lasting up to 1 year. These results favor the conclusion that percutaneous vertebroplasty provides short- and long-term pain reduction for patients meeting the inclusion criteria. However, the lack of randomized trials cannot control for the placebo effect, the natural history of vertebral fractures, and regression to the mean as possible reasons for the apparent efficacy of percutaneous vertebroplasty.

Two structured, but not systematic, reviews of percutaneous vertebroplasty in vertebral fractures^2,3 included 15 small observational studies, of which only 1 was included in the CMS report. These reviews examined outcomes of vertebroplasty performed from less than 1 month to a mean of 7 months after fracture, using similar inclusion criteria to those used in the CMS report. The studies’ common patient exclusion criteria were uncorrectable coagulation disorder, infection in the area, spinal cord compression, destruction of the posterior vertebral wall, and severe degrees of vertebral body collapse (defined as >67% collapse). The 2 reviews found between 67% and 100% of patients reported pain reduction after vertebroplasty in follow-up periods ranging from 24 hours to up to 10 years. Based on this limited evidence, 1 review suggested that the likelihood of alleviation of pain decreases over time and is low for fractures occurring more than 6 months in the past.³ In contradistinction, 3 subsequent observational studies, involving a total of 233 patients with 365 vertebral compression fractures failed to find an association between postprocedural pain and age of fracture (ranging from less than 2 weeks to more than 24 months from injury).^4-6

Recommendations from others

In their guideline on rehabilitation of the patient with osteoporosis, the National Osteoporosis Foundation states an experienced practitioner may perform percutaneous vertebroplasty on a patient with unremitting pain for whom conservative medical therapy has not helped.⁷ They qualify this recommendation by further stating long-term clinical studies are required before vertebroplasty becomes standard of care. The Medicare Coverage Advisory Committee, in its review of the 2005 CMS report, suggested that percutaneous vertebroplasty produces a clinically important net health benefit for patients with vertebral compression fracture compared to conservative care for both acute and chronic fractures.⁸

Evidence summary

No randomized controlled trials have been published regarding percutaneous vertebroplasty. A 2005 Technology Assessment by the Centers for Medicare and Medicaid Services (CMS) provides the best evidence about indications and efficacy of percutaneous vertebroplasty for vertebral fractures.¹ The CMS report is based on a search of Medline and Current Contents through April 2005 for relevant studies, along with hand searches of retrieved articles’ references and of recent pertinent journals. Study inclusion criteria included English language, vertebral fractures due to osteoporosis or malignancy, consecutive patient enrollment, outcomes reported for pain, functional status, and quality of life, and study size ≥20 patients for studies of osteoporosis or ≥10 patients for studies of malignancy. There was no description of a formal study validity assessment or attempts to control bias by use of multiple reviewers.

Fifteen studies were included, representing 1056 patients. Fourteen of the studies were observational and 1 was a nonrandomized controlled trial. The common inclusion requirement was severe pain attributable to vertebral fracture. Nine of the studies further specified failure of analgesics or conservative treatments. The studies showed statistically significant decreases in comparative visual analog pain scale scores in the short term. Four studies showed pain reduction lasting up to 1 year. These results favor the conclusion that percutaneous vertebroplasty provides short- and long-term pain reduction for patients meeting the inclusion criteria. However, the lack of randomized trials cannot control for the placebo effect, the natural history of vertebral fractures, and regression to the mean as possible reasons for the apparent efficacy of percutaneous vertebroplasty.

Two structured, but not systematic, reviews of percutaneous vertebroplasty in vertebral fractures^2,3 included 15 small observational studies, of which only 1 was included in the CMS report. These reviews examined outcomes of vertebroplasty performed from less than 1 month to a mean of 7 months after fracture, using similar inclusion criteria to those used in the CMS report. The studies’ common patient exclusion criteria were uncorrectable coagulation disorder, infection in the area, spinal cord compression, destruction of the posterior vertebral wall, and severe degrees of vertebral body collapse (defined as >67% collapse). The 2 reviews found between 67% and 100% of patients reported pain reduction after vertebroplasty in follow-up periods ranging from 24 hours to up to 10 years. Based on this limited evidence, 1 review suggested that the likelihood of alleviation of pain decreases over time and is low for fractures occurring more than 6 months in the past.³ In contradistinction, 3 subsequent observational studies, involving a total of 233 patients with 365 vertebral compression fractures failed to find an association between postprocedural pain and age of fracture (ranging from less than 2 weeks to more than 24 months from injury).^4-6

Recommendations from others

In their guideline on rehabilitation of the patient with osteoporosis, the National Osteoporosis Foundation states an experienced practitioner may perform percutaneous vertebroplasty on a patient with unremitting pain for whom conservative medical therapy has not helped.⁷ They qualify this recommendation by further stating long-term clinical studies are required before vertebroplasty becomes standard of care. The Medicare Coverage Advisory Committee, in its review of the 2005 CMS report, suggested that percutaneous vertebroplasty produces a clinically important net health benefit for patients with vertebral compression fracture compared to conservative care for both acute and chronic fractures.⁸

Evidence summary

The 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) defines malingering as “the intentional production of false or grossly exaggerated physical or psychological symptoms motivated by external incentives such as avoiding military duty, avoiding work, obtaining financial compensation, evading criminal prosecution, or obtaining drugs.”¹ Malingering is not considered a mental disorder because symptoms are intentionally produced for external incentives.

No physical exam maneuver can determine a patient's external incentives. Traditionally, a physician uses certain exam techniques to determine if symptoms are of functional, or nonorganic, origin. Both terms denote the absence of a structural or physiological source for the phenomena, and include malingering and mental disorders such as factitious disorder, conversion disorder, and somatoform disorders. Our literature search only found studies concerning the detection of nonorganic causes of back pain, paralysis, and sensory loss.

Several exam tests are commonly thought to detect nonorganic causes of low back pain. Gordon Waddell described 8 signs in 5 categories (TABLE 2) used to “identify [back pain] patients who require more detailed psychological assessment.”² A systematic review critiqued 60 studies of Waddell’s signs published between 1980 and 2000.³ The authors performed a thorough database search, including hand searches of key pain journals, meeting abstracts, and textbooks. The majority of the reviewed studies were small and of lower quality. The review found little evidence on test-retest or interrater reliability. There was consistent evidence that Waddell’s signs are associated with poorer treatment outcomes and generally consistent evidence that they are not associated with secondary gain and cannot discriminate organic from nonorganic problems.

A small, diagnostic case-control study of Mankopf’s test, which is based on the theory that pain increases heart rate, investigated 20 chronic low back pain patients considered nonorganic vs 20 pain-free controls using mechanical pain stimulus applied to subjects’ fingers.⁴ There was no significant difference in heart rate response between groups, and no significant effect of pain on heart rate in either group. The authors did not define their criteria for determining patients’ back pain as non-organic, nor did they include patients with low back pain caused by an identifiable pathology. There was no mention of blinding. This literature search found no published studies of McBride’s test, where the patient’s refusal to stand on the unaffected leg and flex the affected leg to the chest determines a feigned radiculopathy.

A few tests attempt to detect nonorganic causes of paralysis. In Hoover’s test, a patient is asked to alternately press down with the paralyzed leg and raise the unaffected leg to resistance, while the hand of the examiner cups the heel of the affected leg.⁵ A small, diagnostic case-control study using a computer-assisted strain gauge to measure movement effort during Hoover’s test involved 7 women with true paresis, 9 with nonorganic paresis, and 10 controls.⁶ The investigators diagnosed nonorganic paresis by history, neurological exam, and lack of positive neuroradiologic findings. The authors calculated a maximal involuntary to voluntary ratio for each patient’s extremities. The calculation discriminated between all 9 nonorganic patients and both the normal controls and patients with true paresis. The authors did not mention blinding in the study. No attempt was made to compare the strain gauge measurements with a clinician-performed Hoover’s test.

The Abductor sign, based on a similar theory that thigh abductors work in concert, was developed and studied by one individual.⁷ In this diagnostic case-control study, the single author tested 33 patients from his practice, 17 with organic paresis, and 16 with nonorganic paresis. The author differentiated organic from nonorganic paresis by history, physical exam, and various imaging studies with no independent assessment. He reported his test as 100% accurate. We did not find any published studies of the Arm Drop test, where feigned paralysis of an upper extremity is tested by holding the arm over the face of the supine patient and letting go.

The Midline Split test attempts to detect nonorganic causes of sensory loss. The fact that cutaneous nerves cross the midline is the basis for the idea that a sharp midline split denotes nonorganic sensory loss. In 1 diagnostic cohort study of 100 people presenting to a neurology department with complaints of decreased sensation on one side of the face, 80 patients were determined to have organic deficits such as multiple sclerosis or stroke. The author did not describe how these diseases were diagnosed. Of those with organic deficits, 7.5% showed midline splitting of sensory loss, falsely suggesting a nonorganic process. Only 20% of the patients with nonorganic sensory loss showed the expected midline split.⁸ The author apparently performed the sensory exam without blinding or independent confirmation.

TABLE 1
Summary of tests for the detection of malingering

TABLE 2
Waddell’s signs

Recommendations from others

The DSM-IV recommends suspicion of malingering for patients who present with 2 or more of the following: medicolegal issues, disagreement between objective and subjective stress or disability, noncompliance with evaluation or treatment, or antisocial personality disorder.¹

The American Medical Association published the Guides to the Evaluation of Permanent Impairment, which states, “Confirmation of malingering is extremely difficult and generally depends on intentional or inadvertent surveillance.”⁹

Evidence summary

The 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) defines malingering as “the intentional production of false or grossly exaggerated physical or psychological symptoms motivated by external incentives such as avoiding military duty, avoiding work, obtaining financial compensation, evading criminal prosecution, or obtaining drugs.”¹ Malingering is not considered a mental disorder because symptoms are intentionally produced for external incentives.

No physical exam maneuver can determine a patient's external incentives. Traditionally, a physician uses certain exam techniques to determine if symptoms are of functional, or nonorganic, origin. Both terms denote the absence of a structural or physiological source for the phenomena, and include malingering and mental disorders such as factitious disorder, conversion disorder, and somatoform disorders. Our literature search only found studies concerning the detection of nonorganic causes of back pain, paralysis, and sensory loss.

Several exam tests are commonly thought to detect nonorganic causes of low back pain. Gordon Waddell described 8 signs in 5 categories (TABLE 2) used to “identify [back pain] patients who require more detailed psychological assessment.”² A systematic review critiqued 60 studies of Waddell’s signs published between 1980 and 2000.³ The authors performed a thorough database search, including hand searches of key pain journals, meeting abstracts, and textbooks. The majority of the reviewed studies were small and of lower quality. The review found little evidence on test-retest or interrater reliability. There was consistent evidence that Waddell’s signs are associated with poorer treatment outcomes and generally consistent evidence that they are not associated with secondary gain and cannot discriminate organic from nonorganic problems.

A small, diagnostic case-control study of Mankopf’s test, which is based on the theory that pain increases heart rate, investigated 20 chronic low back pain patients considered nonorganic vs 20 pain-free controls using mechanical pain stimulus applied to subjects’ fingers.⁴ There was no significant difference in heart rate response between groups, and no significant effect of pain on heart rate in either group. The authors did not define their criteria for determining patients’ back pain as non-organic, nor did they include patients with low back pain caused by an identifiable pathology. There was no mention of blinding. This literature search found no published studies of McBride’s test, where the patient’s refusal to stand on the unaffected leg and flex the affected leg to the chest determines a feigned radiculopathy.

A few tests attempt to detect nonorganic causes of paralysis. In Hoover’s test, a patient is asked to alternately press down with the paralyzed leg and raise the unaffected leg to resistance, while the hand of the examiner cups the heel of the affected leg.⁵ A small, diagnostic case-control study using a computer-assisted strain gauge to measure movement effort during Hoover’s test involved 7 women with true paresis, 9 with nonorganic paresis, and 10 controls.⁶ The investigators diagnosed nonorganic paresis by history, neurological exam, and lack of positive neuroradiologic findings. The authors calculated a maximal involuntary to voluntary ratio for each patient’s extremities. The calculation discriminated between all 9 nonorganic patients and both the normal controls and patients with true paresis. The authors did not mention blinding in the study. No attempt was made to compare the strain gauge measurements with a clinician-performed Hoover’s test.

The Abductor sign, based on a similar theory that thigh abductors work in concert, was developed and studied by one individual.⁷ In this diagnostic case-control study, the single author tested 33 patients from his practice, 17 with organic paresis, and 16 with nonorganic paresis. The author differentiated organic from nonorganic paresis by history, physical exam, and various imaging studies with no independent assessment. He reported his test as 100% accurate. We did not find any published studies of the Arm Drop test, where feigned paralysis of an upper extremity is tested by holding the arm over the face of the supine patient and letting go.

The Midline Split test attempts to detect nonorganic causes of sensory loss. The fact that cutaneous nerves cross the midline is the basis for the idea that a sharp midline split denotes nonorganic sensory loss. In 1 diagnostic cohort study of 100 people presenting to a neurology department with complaints of decreased sensation on one side of the face, 80 patients were determined to have organic deficits such as multiple sclerosis or stroke. The author did not describe how these diseases were diagnosed. Of those with organic deficits, 7.5% showed midline splitting of sensory loss, falsely suggesting a nonorganic process. Only 20% of the patients with nonorganic sensory loss showed the expected midline split.⁸ The author apparently performed the sensory exam without blinding or independent confirmation.

TABLE 1
Summary of tests for the detection of malingering

TABLE 2
Waddell’s signs

Recommendations from others

The DSM-IV recommends suspicion of malingering for patients who present with 2 or more of the following: medicolegal issues, disagreement between objective and subjective stress or disability, noncompliance with evaluation or treatment, or antisocial personality disorder.¹

The American Medical Association published the Guides to the Evaluation of Permanent Impairment, which states, “Confirmation of malingering is extremely difficult and generally depends on intentional or inadvertent surveillance.”⁹

Evidence summary

The 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) defines malingering as “the intentional production of false or grossly exaggerated physical or psychological symptoms motivated by external incentives such as avoiding military duty, avoiding work, obtaining financial compensation, evading criminal prosecution, or obtaining drugs.”¹ Malingering is not considered a mental disorder because symptoms are intentionally produced for external incentives.

No physical exam maneuver can determine a patient's external incentives. Traditionally, a physician uses certain exam techniques to determine if symptoms are of functional, or nonorganic, origin. Both terms denote the absence of a structural or physiological source for the phenomena, and include malingering and mental disorders such as factitious disorder, conversion disorder, and somatoform disorders. Our literature search only found studies concerning the detection of nonorganic causes of back pain, paralysis, and sensory loss.

Several exam tests are commonly thought to detect nonorganic causes of low back pain. Gordon Waddell described 8 signs in 5 categories (TABLE 2) used to “identify [back pain] patients who require more detailed psychological assessment.”² A systematic review critiqued 60 studies of Waddell’s signs published between 1980 and 2000.³ The authors performed a thorough database search, including hand searches of key pain journals, meeting abstracts, and textbooks. The majority of the reviewed studies were small and of lower quality. The review found little evidence on test-retest or interrater reliability. There was consistent evidence that Waddell’s signs are associated with poorer treatment outcomes and generally consistent evidence that they are not associated with secondary gain and cannot discriminate organic from nonorganic problems.

A small, diagnostic case-control study of Mankopf’s test, which is based on the theory that pain increases heart rate, investigated 20 chronic low back pain patients considered nonorganic vs 20 pain-free controls using mechanical pain stimulus applied to subjects’ fingers.⁴ There was no significant difference in heart rate response between groups, and no significant effect of pain on heart rate in either group. The authors did not define their criteria for determining patients’ back pain as non-organic, nor did they include patients with low back pain caused by an identifiable pathology. There was no mention of blinding. This literature search found no published studies of McBride’s test, where the patient’s refusal to stand on the unaffected leg and flex the affected leg to the chest determines a feigned radiculopathy.

A few tests attempt to detect nonorganic causes of paralysis. In Hoover’s test, a patient is asked to alternately press down with the paralyzed leg and raise the unaffected leg to resistance, while the hand of the examiner cups the heel of the affected leg.⁵ A small, diagnostic case-control study using a computer-assisted strain gauge to measure movement effort during Hoover’s test involved 7 women with true paresis, 9 with nonorganic paresis, and 10 controls.⁶ The investigators diagnosed nonorganic paresis by history, neurological exam, and lack of positive neuroradiologic findings. The authors calculated a maximal involuntary to voluntary ratio for each patient’s extremities. The calculation discriminated between all 9 nonorganic patients and both the normal controls and patients with true paresis. The authors did not mention blinding in the study. No attempt was made to compare the strain gauge measurements with a clinician-performed Hoover’s test.

The Abductor sign, based on a similar theory that thigh abductors work in concert, was developed and studied by one individual.⁷ In this diagnostic case-control study, the single author tested 33 patients from his practice, 17 with organic paresis, and 16 with nonorganic paresis. The author differentiated organic from nonorganic paresis by history, physical exam, and various imaging studies with no independent assessment. He reported his test as 100% accurate. We did not find any published studies of the Arm Drop test, where feigned paralysis of an upper extremity is tested by holding the arm over the face of the supine patient and letting go.

The Midline Split test attempts to detect nonorganic causes of sensory loss. The fact that cutaneous nerves cross the midline is the basis for the idea that a sharp midline split denotes nonorganic sensory loss. In 1 diagnostic cohort study of 100 people presenting to a neurology department with complaints of decreased sensation on one side of the face, 80 patients were determined to have organic deficits such as multiple sclerosis or stroke. The author did not describe how these diseases were diagnosed. Of those with organic deficits, 7.5% showed midline splitting of sensory loss, falsely suggesting a nonorganic process. Only 20% of the patients with nonorganic sensory loss showed the expected midline split.⁸ The author apparently performed the sensory exam without blinding or independent confirmation.

TABLE 1
Summary of tests for the detection of malingering

TABLE 2
Waddell’s signs

Recommendations from others

The DSM-IV recommends suspicion of malingering for patients who present with 2 or more of the following: medicolegal issues, disagreement between objective and subjective stress or disability, noncompliance with evaluation or treatment, or antisocial personality disorder.¹

The American Medical Association published the Guides to the Evaluation of Permanent Impairment, which states, “Confirmation of malingering is extremely difficult and generally depends on intentional or inadvertent surveillance.”⁹