Clinical Inquiries

Evidence summary

MTSS, or shin splints, is the most common cause of exertional leg pain in athletes. MTSS is an overuse injury characterized by pain along the posteromedial aspect of the distal two-thirds of the tibia.

Reduced running time, frequency, and distance may prevent injury

A systematic review of 12 trials of 8806 mostly young male military recruits, evaluated nonsurgical interventions to prevent lower limb soft tissue running injuries, including MTSS.¹ Five trials investigating stretching and 4 trials of shoe insoles showed no benefit. Three studies showed that reducing the duration of running (to between 15 and 30 minutes), frequency (to 1 or 3 days a week), or distance (to 16.5 fewer kilometers over 12 weeks) reduced the risk of all injuries. Methods and outcome measures of the studies were heterogeneous, limiting the generalizability of these results.

A prospective RCT of custom semi-rigid shoe orthoses in the boots of Danish army recruits found a significantly lower prevalence of MTSS at 3-month follow-up in the intervention group (13% compared with 24%, P=.005; NNT=5).² However, a systematic review of methods to prevent MTSS in sports found no high-quality studies in nonmilitary populations.³ No difference in the incidence of MTSS was noted with shoe inserts, different combat boots, or stretching routines.

To treat shin splints, consider orthotics, rest, and ice

Two studies retrospectively surveyed runners about their response to orthotics to treat MTSS.^4,5 In one study, 16 of 41 collegiate cross-country runners were prescribed orthotics; 14 (88%) reported relief or improvement in their symptoms and return to running within 4 weeks.⁴ The other survey, of long-distance runners, found that 70% who had used or were using orthotics for a presumed diagnosis of MTSS reported complete relief or great improvement.⁵

A study of 97 US naval midshipmen who developed MTSS during summer training programs compared randomly assigned treatments of rest and ice to rest and ice plus anti-inflammatory medication (aspirin or phenylbutazone), rest and ice plus heel-cord stretching, or use of a short walking cast for 1 week.⁶ Subjects assigned to a treatment program of rest and ice alone lost significantly fewer days from running than the other treatment groups (P<.03).

A recent RCT of soldiers with MTSS compared treatment with a leg orthosis with no orthotic use; all subjects underwent icing and activity modification.⁷ No significant differences in outcome measures (days to completion of a 0.5-mile run, global rating of change, or number of treatment sessions) were noted between the treatment groups. Small sample size, high dropout rate, and small effect size limit the power of this study.

Fasciotomy can relieve symptoms but may not improve postop activity

Three case series reported on deep posterior compartment fasciotomy to treat MTSS in athletes.^8-10 Surgery significantly reduced pain levels (P<.001) by an average of 72% on the visual analog pain scale for 46 patients who had failed conservative therapy for at least 12 months.⁸ However, only 41% returned to their pre-symptom level of sports activity. Another case series of mostly running athletes reported that 21 (78%) of 27 patients exhibited excellent or good healing after surgery.⁹ In a series of 9 patients with an average of 39 months of symptoms, 5 reported complete relief at follow-up (42±6 months), and 7 trained more than they had preoperatively.¹⁰

One case series of superficial posterior compartment fasciotomy for MTSS in 35 athletes reported that, among the 32 athletes available for follow-up, 72% (23) reported improved symptoms, but 69% (22) had a lower level of activity postoperatively.¹¹

Recommendations

The American College of Sports Medicine (ACSM) recommends at least 7 to 10 days of rest from painful activities to treat MTSS.¹² Running in a pool and cycling to maintain aerobic fitness during the rest period are considered safe activities. Stretching and strengthening exercises are not recommended while symptoms persist. Patients should return to running gradually. ACSM also suggests that orthotics are useful for preventing injury and treating some patients.

Evidence summary

MTSS, or shin splints, is the most common cause of exertional leg pain in athletes. MTSS is an overuse injury characterized by pain along the posteromedial aspect of the distal two-thirds of the tibia.

Reduced running time, frequency, and distance may prevent injury

A systematic review of 12 trials of 8806 mostly young male military recruits, evaluated nonsurgical interventions to prevent lower limb soft tissue running injuries, including MTSS.¹ Five trials investigating stretching and 4 trials of shoe insoles showed no benefit. Three studies showed that reducing the duration of running (to between 15 and 30 minutes), frequency (to 1 or 3 days a week), or distance (to 16.5 fewer kilometers over 12 weeks) reduced the risk of all injuries. Methods and outcome measures of the studies were heterogeneous, limiting the generalizability of these results.

A prospective RCT of custom semi-rigid shoe orthoses in the boots of Danish army recruits found a significantly lower prevalence of MTSS at 3-month follow-up in the intervention group (13% compared with 24%, P=.005; NNT=5).² However, a systematic review of methods to prevent MTSS in sports found no high-quality studies in nonmilitary populations.³ No difference in the incidence of MTSS was noted with shoe inserts, different combat boots, or stretching routines.

To treat shin splints, consider orthotics, rest, and ice

Two studies retrospectively surveyed runners about their response to orthotics to treat MTSS.^4,5 In one study, 16 of 41 collegiate cross-country runners were prescribed orthotics; 14 (88%) reported relief or improvement in their symptoms and return to running within 4 weeks.⁴ The other survey, of long-distance runners, found that 70% who had used or were using orthotics for a presumed diagnosis of MTSS reported complete relief or great improvement.⁵

A study of 97 US naval midshipmen who developed MTSS during summer training programs compared randomly assigned treatments of rest and ice to rest and ice plus anti-inflammatory medication (aspirin or phenylbutazone), rest and ice plus heel-cord stretching, or use of a short walking cast for 1 week.⁶ Subjects assigned to a treatment program of rest and ice alone lost significantly fewer days from running than the other treatment groups (P<.03).

A recent RCT of soldiers with MTSS compared treatment with a leg orthosis with no orthotic use; all subjects underwent icing and activity modification.⁷ No significant differences in outcome measures (days to completion of a 0.5-mile run, global rating of change, or number of treatment sessions) were noted between the treatment groups. Small sample size, high dropout rate, and small effect size limit the power of this study.

Fasciotomy can relieve symptoms but may not improve postop activity

Three case series reported on deep posterior compartment fasciotomy to treat MTSS in athletes.^8-10 Surgery significantly reduced pain levels (P<.001) by an average of 72% on the visual analog pain scale for 46 patients who had failed conservative therapy for at least 12 months.⁸ However, only 41% returned to their pre-symptom level of sports activity. Another case series of mostly running athletes reported that 21 (78%) of 27 patients exhibited excellent or good healing after surgery.⁹ In a series of 9 patients with an average of 39 months of symptoms, 5 reported complete relief at follow-up (42±6 months), and 7 trained more than they had preoperatively.¹⁰

One case series of superficial posterior compartment fasciotomy for MTSS in 35 athletes reported that, among the 32 athletes available for follow-up, 72% (23) reported improved symptoms, but 69% (22) had a lower level of activity postoperatively.¹¹

Recommendations

The American College of Sports Medicine (ACSM) recommends at least 7 to 10 days of rest from painful activities to treat MTSS.¹² Running in a pool and cycling to maintain aerobic fitness during the rest period are considered safe activities. Stretching and strengthening exercises are not recommended while symptoms persist. Patients should return to running gradually. ACSM also suggests that orthotics are useful for preventing injury and treating some patients.

Evidence summary

MTSS, or shin splints, is the most common cause of exertional leg pain in athletes. MTSS is an overuse injury characterized by pain along the posteromedial aspect of the distal two-thirds of the tibia.

Reduced running time, frequency, and distance may prevent injury

A systematic review of 12 trials of 8806 mostly young male military recruits, evaluated nonsurgical interventions to prevent lower limb soft tissue running injuries, including MTSS.¹ Five trials investigating stretching and 4 trials of shoe insoles showed no benefit. Three studies showed that reducing the duration of running (to between 15 and 30 minutes), frequency (to 1 or 3 days a week), or distance (to 16.5 fewer kilometers over 12 weeks) reduced the risk of all injuries. Methods and outcome measures of the studies were heterogeneous, limiting the generalizability of these results.

A prospective RCT of custom semi-rigid shoe orthoses in the boots of Danish army recruits found a significantly lower prevalence of MTSS at 3-month follow-up in the intervention group (13% compared with 24%, P=.005; NNT=5).² However, a systematic review of methods to prevent MTSS in sports found no high-quality studies in nonmilitary populations.³ No difference in the incidence of MTSS was noted with shoe inserts, different combat boots, or stretching routines.

To treat shin splints, consider orthotics, rest, and ice

Two studies retrospectively surveyed runners about their response to orthotics to treat MTSS.^4,5 In one study, 16 of 41 collegiate cross-country runners were prescribed orthotics; 14 (88%) reported relief or improvement in their symptoms and return to running within 4 weeks.⁴ The other survey, of long-distance runners, found that 70% who had used or were using orthotics for a presumed diagnosis of MTSS reported complete relief or great improvement.⁵

A study of 97 US naval midshipmen who developed MTSS during summer training programs compared randomly assigned treatments of rest and ice to rest and ice plus anti-inflammatory medication (aspirin or phenylbutazone), rest and ice plus heel-cord stretching, or use of a short walking cast for 1 week.⁶ Subjects assigned to a treatment program of rest and ice alone lost significantly fewer days from running than the other treatment groups (P<.03).

A recent RCT of soldiers with MTSS compared treatment with a leg orthosis with no orthotic use; all subjects underwent icing and activity modification.⁷ No significant differences in outcome measures (days to completion of a 0.5-mile run, global rating of change, or number of treatment sessions) were noted between the treatment groups. Small sample size, high dropout rate, and small effect size limit the power of this study.

Fasciotomy can relieve symptoms but may not improve postop activity

Three case series reported on deep posterior compartment fasciotomy to treat MTSS in athletes.^8-10 Surgery significantly reduced pain levels (P<.001) by an average of 72% on the visual analog pain scale for 46 patients who had failed conservative therapy for at least 12 months.⁸ However, only 41% returned to their pre-symptom level of sports activity. Another case series of mostly running athletes reported that 21 (78%) of 27 patients exhibited excellent or good healing after surgery.⁹ In a series of 9 patients with an average of 39 months of symptoms, 5 reported complete relief at follow-up (42±6 months), and 7 trained more than they had preoperatively.¹⁰

One case series of superficial posterior compartment fasciotomy for MTSS in 35 athletes reported that, among the 32 athletes available for follow-up, 72% (23) reported improved symptoms, but 69% (22) had a lower level of activity postoperatively.¹¹

Recommendations

The American College of Sports Medicine (ACSM) recommends at least 7 to 10 days of rest from painful activities to treat MTSS.¹² Running in a pool and cycling to maintain aerobic fitness during the rest period are considered safe activities. Stretching and strengthening exercises are not recommended while symptoms persist. Patients should return to running gradually. ACSM also suggests that orthotics are useful for preventing injury and treating some patients.

Evidence summary

PVD is a progressive atherosclerotic narrowing of arteries in the extremities. The prevalence increases with age—it is less than 1% in people between 40 and 49 years of age and 15% in people 70 years and older.^1,2 Risk factors are the same as for coronary artery disease.¹

Weighing your options

Methods for evaluating patients for PVD include medical history, physical examination (inspection of the extremities and palpation of peripheral pulses), and ancillary testing (ankle-brachial index, duplex ultrasound, and magnetic resonance imaging with contrast, and angiography). The toe-brachial index may be useful in the elderly and patients with advanced diabetes because noncompressible vasculature in these patients may render the ankle-brachial index unreliable.³

The Edinburgh Claudication Questionnaire

1. Do you get a pain or discomfort in your leg(s) when you walk?

□ Yes □ No □ I am unable to walk

If you answered “Yes” to question (1), please answer the following questions. Otherwise, you need not continue.

2. Does this pain ever begin when you are standing still or sitting?

□ Yes □ No

3. Do you get it if you walk uphill or hurry?

□ Yes □ No

4. Do you get it when you walk at an ordinary pace on the level?

□ Yes □ No

5. What happens to it if you stand still?

□ Usually continues more than 10 minutes.

□ Usually disappears in 10 minutes or less.

6. Where do you get this pain or discomfort?

Mark the place(s) with an “x” on the diagram below.

Definition of positive classification requires all of the following responses: “Yes” to (1), “No” to (2), “Yes” to (3), and “usually disappears in 10 minutes or less” to (5); grade 1=“No” to (4) and grade 2=“Yes” to (4). If these criteria are fulfilled, a definite claudicant is one who indicates pain in the calf, regardless of whether pain is also marked in other sites; a diagnosis of atypical claudication is made if pain is indicated in the thigh or buttock, in the absence of any calf pain. Patients should not be considered to have claudication if pain is indicated in the hamstrings, feet, shins, joints, or appears to radiate, in the absence of any pain in the calf.

Source: Leng GC, Fowkes FG.⁴ Adapted with permission.

The TABLE lists the sensitivities, specificities, positive predictive values, and likelihood ratios for commonly used tests.^3-8 The calculations assume peripheral vascular disease to have a prevalence of 14% among people older than 60 years, based on pooled results from several epidemiologic studies.¹

A questionnaire-based history of claudication (the Edinburgh Claudication Questionnaire) has been shown to have a high positive predictive value and likelihood ratio for PVD; physical examination techniques appear to be less predictive.^4-7 However, the gold standard in the questionnaire study was “clinician determination,” which carries a risk of subjectivity and lack of testing independence that may make the test appear more accurate than it is in typical application.

A stepwise approach

After balancing the accuracy, cost, and risk of available tests, an appropriate stepwise approach to evaluation for PVD is:

First, do a complete history and targeted physical examination (palpation of pulses).

Next, obtain an ankle-brachial index to confirm the diagnosis.

Then, proceed directly to either duplex ultrasonography or magnetic resonance angiography when revascularization is clearly needed.⁹

TABLE
Commonly used tests for peripheral vascular disease

The major advantages of the ankle-brachial index include low cost and non-invasiveness (low potential for harm). However, it doesn’t detect proximal aneurysms or PVD distal to the ankle, and it may be difficult to perform on patients with noncompressible distal vasculature. Adequately evaluating such patients may require invasive testing.

Recommendations

The US Preventive Services Task Force recommends against (D recommendation) any screening tests for PVD in patients without symptoms.¹⁰ The American College of Cardiology gives a class I recommendation (tests for which there is evidence or general agreement that a procedure is useful, beneficial, or effective) to the ankle-brachial index as the baseline diagnostic tool for establishing peripheral vascular disease, except in elderly patients or those with advanced diabetes, for whom the test is unreliable.¹¹

Evidence summary

PVD is a progressive atherosclerotic narrowing of arteries in the extremities. The prevalence increases with age—it is less than 1% in people between 40 and 49 years of age and 15% in people 70 years and older.^1,2 Risk factors are the same as for coronary artery disease.¹

Weighing your options

Methods for evaluating patients for PVD include medical history, physical examination (inspection of the extremities and palpation of peripheral pulses), and ancillary testing (ankle-brachial index, duplex ultrasound, and magnetic resonance imaging with contrast, and angiography). The toe-brachial index may be useful in the elderly and patients with advanced diabetes because noncompressible vasculature in these patients may render the ankle-brachial index unreliable.³

The Edinburgh Claudication Questionnaire

1. Do you get a pain or discomfort in your leg(s) when you walk?

□ Yes □ No □ I am unable to walk

If you answered “Yes” to question (1), please answer the following questions. Otherwise, you need not continue.

2. Does this pain ever begin when you are standing still or sitting?

□ Yes □ No

3. Do you get it if you walk uphill or hurry?

□ Yes □ No

4. Do you get it when you walk at an ordinary pace on the level?

□ Yes □ No

5. What happens to it if you stand still?

□ Usually continues more than 10 minutes.

□ Usually disappears in 10 minutes or less.

6. Where do you get this pain or discomfort?

Mark the place(s) with an “x” on the diagram below.

Definition of positive classification requires all of the following responses: “Yes” to (1), “No” to (2), “Yes” to (3), and “usually disappears in 10 minutes or less” to (5); grade 1=“No” to (4) and grade 2=“Yes” to (4). If these criteria are fulfilled, a definite claudicant is one who indicates pain in the calf, regardless of whether pain is also marked in other sites; a diagnosis of atypical claudication is made if pain is indicated in the thigh or buttock, in the absence of any calf pain. Patients should not be considered to have claudication if pain is indicated in the hamstrings, feet, shins, joints, or appears to radiate, in the absence of any pain in the calf.

Source: Leng GC, Fowkes FG.⁴ Adapted with permission.

The TABLE lists the sensitivities, specificities, positive predictive values, and likelihood ratios for commonly used tests.^3-8 The calculations assume peripheral vascular disease to have a prevalence of 14% among people older than 60 years, based on pooled results from several epidemiologic studies.¹

A questionnaire-based history of claudication (the Edinburgh Claudication Questionnaire) has been shown to have a high positive predictive value and likelihood ratio for PVD; physical examination techniques appear to be less predictive.^4-7 However, the gold standard in the questionnaire study was “clinician determination,” which carries a risk of subjectivity and lack of testing independence that may make the test appear more accurate than it is in typical application.

A stepwise approach

After balancing the accuracy, cost, and risk of available tests, an appropriate stepwise approach to evaluation for PVD is:

First, do a complete history and targeted physical examination (palpation of pulses).

Next, obtain an ankle-brachial index to confirm the diagnosis.

Then, proceed directly to either duplex ultrasonography or magnetic resonance angiography when revascularization is clearly needed.⁹

TABLE
Commonly used tests for peripheral vascular disease

The major advantages of the ankle-brachial index include low cost and non-invasiveness (low potential for harm). However, it doesn’t detect proximal aneurysms or PVD distal to the ankle, and it may be difficult to perform on patients with noncompressible distal vasculature. Adequately evaluating such patients may require invasive testing.

Recommendations

The US Preventive Services Task Force recommends against (D recommendation) any screening tests for PVD in patients without symptoms.¹⁰ The American College of Cardiology gives a class I recommendation (tests for which there is evidence or general agreement that a procedure is useful, beneficial, or effective) to the ankle-brachial index as the baseline diagnostic tool for establishing peripheral vascular disease, except in elderly patients or those with advanced diabetes, for whom the test is unreliable.¹¹

Evidence summary

PVD is a progressive atherosclerotic narrowing of arteries in the extremities. The prevalence increases with age—it is less than 1% in people between 40 and 49 years of age and 15% in people 70 years and older.^1,2 Risk factors are the same as for coronary artery disease.¹

Weighing your options

Methods for evaluating patients for PVD include medical history, physical examination (inspection of the extremities and palpation of peripheral pulses), and ancillary testing (ankle-brachial index, duplex ultrasound, and magnetic resonance imaging with contrast, and angiography). The toe-brachial index may be useful in the elderly and patients with advanced diabetes because noncompressible vasculature in these patients may render the ankle-brachial index unreliable.³

The Edinburgh Claudication Questionnaire

1. Do you get a pain or discomfort in your leg(s) when you walk?

□ Yes □ No □ I am unable to walk

If you answered “Yes” to question (1), please answer the following questions. Otherwise, you need not continue.

2. Does this pain ever begin when you are standing still or sitting?

□ Yes □ No

3. Do you get it if you walk uphill or hurry?

□ Yes □ No

4. Do you get it when you walk at an ordinary pace on the level?

□ Yes □ No

5. What happens to it if you stand still?

□ Usually continues more than 10 minutes.

□ Usually disappears in 10 minutes or less.

6. Where do you get this pain or discomfort?

Mark the place(s) with an “x” on the diagram below.

Definition of positive classification requires all of the following responses: “Yes” to (1), “No” to (2), “Yes” to (3), and “usually disappears in 10 minutes or less” to (5); grade 1=“No” to (4) and grade 2=“Yes” to (4). If these criteria are fulfilled, a definite claudicant is one who indicates pain in the calf, regardless of whether pain is also marked in other sites; a diagnosis of atypical claudication is made if pain is indicated in the thigh or buttock, in the absence of any calf pain. Patients should not be considered to have claudication if pain is indicated in the hamstrings, feet, shins, joints, or appears to radiate, in the absence of any pain in the calf.

Source: Leng GC, Fowkes FG.⁴ Adapted with permission.

The TABLE lists the sensitivities, specificities, positive predictive values, and likelihood ratios for commonly used tests.^3-8 The calculations assume peripheral vascular disease to have a prevalence of 14% among people older than 60 years, based on pooled results from several epidemiologic studies.¹

A questionnaire-based history of claudication (the Edinburgh Claudication Questionnaire) has been shown to have a high positive predictive value and likelihood ratio for PVD; physical examination techniques appear to be less predictive.^4-7 However, the gold standard in the questionnaire study was “clinician determination,” which carries a risk of subjectivity and lack of testing independence that may make the test appear more accurate than it is in typical application.

A stepwise approach

After balancing the accuracy, cost, and risk of available tests, an appropriate stepwise approach to evaluation for PVD is:

First, do a complete history and targeted physical examination (palpation of pulses).

Next, obtain an ankle-brachial index to confirm the diagnosis.

Then, proceed directly to either duplex ultrasonography or magnetic resonance angiography when revascularization is clearly needed.⁹

TABLE
Commonly used tests for peripheral vascular disease

The major advantages of the ankle-brachial index include low cost and non-invasiveness (low potential for harm). However, it doesn’t detect proximal aneurysms or PVD distal to the ankle, and it may be difficult to perform on patients with noncompressible distal vasculature. Adequately evaluating such patients may require invasive testing.

Recommendations

The US Preventive Services Task Force recommends against (D recommendation) any screening tests for PVD in patients without symptoms.¹⁰ The American College of Cardiology gives a class I recommendation (tests for which there is evidence or general agreement that a procedure is useful, beneficial, or effective) to the ankle-brachial index as the baseline diagnostic tool for establishing peripheral vascular disease, except in elderly patients or those with advanced diabetes, for whom the test is unreliable.¹¹

Evidence summary

Effects of self-examination on patients with melanoma

Two studies of a group of Connecticut residents examined the relationship between skin self-examination (SSE) and melanoma. The first, a case-control study compared SSE among 650 Caucasian patients newly diagnosed with melanoma and 549 age- and sex-matched controls.¹ Fifteen percent of all patients practiced SSE. Investigators monitored a statewide registry system for 5.4 years to identify 110 participants with melanoma who had major adverse outcomes (distant metastases or death).

Patients with a history of melanoma who practiced SSE had lower mortality (odds ratio [OR]=0.42; 95% confidence interval [CI], 0.21-0.85) than those who didn’t. One potential weakness of the study was possible lead-time bias, which could overestimate the risk reduction from SSE. Another was the 5.4-year follow-up, because malignant melanoma can recur as long as 10 years later.

In the second study, involving a cohort of 255 patients from the first study who discovered their own melanomas, researchers questioned patients about their knowledge of melanoma signs and symptoms, awareness of the appearance of their own skin, and whether they delayed seeking medical attention for >3 months after detecting the initial lesion.²

More knowledgeable patients were less likely to have a thick (≥0.75 mm) tumor and a delayed diagnosis (OR=0.34; 95% CI, 0.13-0.88). Similarly, patients with greater awareness of their skin were less likely to have a thick tumor and a delayed diagnosis (OR=0.50; 95% CI, 0.28-0.89 and OR=0.30; 95% CI, 0.12-0.71, respectively). Investigators found no significant difference in mortality based on knowledge or skin awareness.

Which patients are more likely to detect melanoma?

A retrospective series of 816 consecutive cases of newly diagnosed melanoma investigated the frequency of self-detection in a Mediterranean population at intermediate risk.³ Subjects were statistically more likely to find melanoma themselves if they had a lesion on the lower limbs, were of younger age (49.8 vs 52.9 years of age), had fewer atypical nevi, had >8 years education, were knowledgeable about the characteristic features of melanoma, and performed regular SSE (P<.01 for all comparisons).

Recommendations

The US Preventive Services Task Force finds insufficient evidence to recommend for or against routine counseling by primary care clinicians to prevent skin cancer.⁴

The Cancer Care Ontario Program in Evidence-based Care, on the other hand, advises health care providers to perform annual total-body skin examinations of high-risk patients and teach the patients to examine themselves.⁵

The American Cancer Society (ACS) and the American Academy of Dermatology (AAD) both provide information about recognizing melanoma on their Web sites and recommend that people at high risk perform monthly self-examinations. They further advise such people to periodically see a health care professional qualified to diagnose skin cancer (ACS), or a dermatologist (AAD), for a complete skin examination.^6,7

Evidence summary

Effects of self-examination on patients with melanoma

Two studies of a group of Connecticut residents examined the relationship between skin self-examination (SSE) and melanoma. The first, a case-control study compared SSE among 650 Caucasian patients newly diagnosed with melanoma and 549 age- and sex-matched controls.¹ Fifteen percent of all patients practiced SSE. Investigators monitored a statewide registry system for 5.4 years to identify 110 participants with melanoma who had major adverse outcomes (distant metastases or death).

Patients with a history of melanoma who practiced SSE had lower mortality (odds ratio [OR]=0.42; 95% confidence interval [CI], 0.21-0.85) than those who didn’t. One potential weakness of the study was possible lead-time bias, which could overestimate the risk reduction from SSE. Another was the 5.4-year follow-up, because malignant melanoma can recur as long as 10 years later.

In the second study, involving a cohort of 255 patients from the first study who discovered their own melanomas, researchers questioned patients about their knowledge of melanoma signs and symptoms, awareness of the appearance of their own skin, and whether they delayed seeking medical attention for >3 months after detecting the initial lesion.²

More knowledgeable patients were less likely to have a thick (≥0.75 mm) tumor and a delayed diagnosis (OR=0.34; 95% CI, 0.13-0.88). Similarly, patients with greater awareness of their skin were less likely to have a thick tumor and a delayed diagnosis (OR=0.50; 95% CI, 0.28-0.89 and OR=0.30; 95% CI, 0.12-0.71, respectively). Investigators found no significant difference in mortality based on knowledge or skin awareness.

Which patients are more likely to detect melanoma?

A retrospective series of 816 consecutive cases of newly diagnosed melanoma investigated the frequency of self-detection in a Mediterranean population at intermediate risk.³ Subjects were statistically more likely to find melanoma themselves if they had a lesion on the lower limbs, were of younger age (49.8 vs 52.9 years of age), had fewer atypical nevi, had >8 years education, were knowledgeable about the characteristic features of melanoma, and performed regular SSE (P<.01 for all comparisons).

Recommendations

The US Preventive Services Task Force finds insufficient evidence to recommend for or against routine counseling by primary care clinicians to prevent skin cancer.⁴

The Cancer Care Ontario Program in Evidence-based Care, on the other hand, advises health care providers to perform annual total-body skin examinations of high-risk patients and teach the patients to examine themselves.⁵

The American Cancer Society (ACS) and the American Academy of Dermatology (AAD) both provide information about recognizing melanoma on their Web sites and recommend that people at high risk perform monthly self-examinations. They further advise such people to periodically see a health care professional qualified to diagnose skin cancer (ACS), or a dermatologist (AAD), for a complete skin examination.^6,7

Evidence summary

Effects of self-examination on patients with melanoma

Two studies of a group of Connecticut residents examined the relationship between skin self-examination (SSE) and melanoma. The first, a case-control study compared SSE among 650 Caucasian patients newly diagnosed with melanoma and 549 age- and sex-matched controls.¹ Fifteen percent of all patients practiced SSE. Investigators monitored a statewide registry system for 5.4 years to identify 110 participants with melanoma who had major adverse outcomes (distant metastases or death).

Patients with a history of melanoma who practiced SSE had lower mortality (odds ratio [OR]=0.42; 95% confidence interval [CI], 0.21-0.85) than those who didn’t. One potential weakness of the study was possible lead-time bias, which could overestimate the risk reduction from SSE. Another was the 5.4-year follow-up, because malignant melanoma can recur as long as 10 years later.

In the second study, involving a cohort of 255 patients from the first study who discovered their own melanomas, researchers questioned patients about their knowledge of melanoma signs and symptoms, awareness of the appearance of their own skin, and whether they delayed seeking medical attention for >3 months after detecting the initial lesion.²

More knowledgeable patients were less likely to have a thick (≥0.75 mm) tumor and a delayed diagnosis (OR=0.34; 95% CI, 0.13-0.88). Similarly, patients with greater awareness of their skin were less likely to have a thick tumor and a delayed diagnosis (OR=0.50; 95% CI, 0.28-0.89 and OR=0.30; 95% CI, 0.12-0.71, respectively). Investigators found no significant difference in mortality based on knowledge or skin awareness.

Which patients are more likely to detect melanoma?

A retrospective series of 816 consecutive cases of newly diagnosed melanoma investigated the frequency of self-detection in a Mediterranean population at intermediate risk.³ Subjects were statistically more likely to find melanoma themselves if they had a lesion on the lower limbs, were of younger age (49.8 vs 52.9 years of age), had fewer atypical nevi, had >8 years education, were knowledgeable about the characteristic features of melanoma, and performed regular SSE (P<.01 for all comparisons).

Recommendations

The US Preventive Services Task Force finds insufficient evidence to recommend for or against routine counseling by primary care clinicians to prevent skin cancer.⁴

The Cancer Care Ontario Program in Evidence-based Care, on the other hand, advises health care providers to perform annual total-body skin examinations of high-risk patients and teach the patients to examine themselves.⁵

The American Cancer Society (ACS) and the American Academy of Dermatology (AAD) both provide information about recognizing melanoma on their Web sites and recommend that people at high risk perform monthly self-examinations. They further advise such people to periodically see a health care professional qualified to diagnose skin cancer (ACS), or a dermatologist (AAD), for a complete skin examination.^6,7

Evidence Summary

Several cross-sectional studies indicate that patients with subjective memory loss are more likely to be older, female, less physically active, in poorer health, less educated, and more depressed or anxious than unaffected patients.^1-4 These studies concentrate mostly on elderly people living in the community.

A study of 1883 patients with normal baseline short-cognitive test results found that those with subjective memory complaints had a higher incidence of dementia.⁵ At 5-year follow-up, 15% of patients with baseline subjective memory complaints had developed dementia compared to only 6% of those without such complaints (odds ratio=2.7; 95% confidence interval [CI], 1.45-4.98).

A prospective cohort study that followed 158 patients with no evidence of dementia showed a significant correlation between informant-reported memory problems and development of dementia at 5 years.⁶ Forty-five percent of patients with informant-reported memory problems developed dementia after 5 years compared with 25% of patients who had only self-reported memory problems (P =.02). This result suggests that subjective memory problems reported by observers (family or caregivers) may be more predictive of dementia than self-reported memory complaints.

Donepezil, ginkgo biloba may not help these patients

Most trials of interventions to preserve memory have not enrolled patients with subjective memory complaints. However, data from trials that enrolled either asymptomatic elderly patients or patients with mild cognitive impairment don’t support the use of donepezil, ginkgo biloba, NSAIDs, COX-2 inhibitors, vitamin E, vitamin B₆, vitamin B₁₂, statins, hormone replacement therapy, or omega-3 fatty acids to delay progression to dementia.^7-16

Could mental exercise help?

One systematic review of 22 longitudinal cohort studies, which included more than 29,000 patients, evaluated complex patterns of mental activity in early, mid-, and late-life in relation to the incidence of dementia. Dementia was diagnosed at a significantly lower rate in patients with a higher level of cognitive exercise, such as memory-based leisure activities and social interactions, than those with less rigorous daily cognitive challenges (relative risk=0.54; 95% CI, 0.49-0.59).¹⁷

This raises the possibility that mental exercise has neuroprotective effects. No randomized trials exist to support this hypothesis, however.

Recommendations

There is no consensus regarding the nomenclature applied to reported memory loss and mild cognitive impairment. The Clinical Manual of Geriatric Psychiatry provides definitions that can be used in the clinical setting (TABLE).¹⁸

The US Preventive Services Task Force concludes that evidence is insufficient to recommend for or against routine screening for dementia in older adults (I recommendation).¹⁹ However, the Task Force notes that clinicians should assess cognitive function whenever they suspect impairment or deterioration based on direct observation, patient report, or concerns raised by family members, friends, or care-takers.

The American Geriatrics Society²⁰ and American Academy of Neurology (AAN)²¹ acknowledge the subtle difference between age-associated memory impairment and mild cognitive impairment, and the difficulty of differentiating normal changes of aging from abnormal changes. The AAN’s guidelines for early detection of dementia emphasize the importance of diagnosing mild cognitive impairment or dementia early. However, the guidelines specifically exclude patients with subjective memory loss unaccompanied by objective cognitive deficits and offer no further discussion about these patients.

TABLE
Features of age-associated memory impairment vs mild cognitive impairment

Evidence Summary

Several cross-sectional studies indicate that patients with subjective memory loss are more likely to be older, female, less physically active, in poorer health, less educated, and more depressed or anxious than unaffected patients.^1-4 These studies concentrate mostly on elderly people living in the community.

A study of 1883 patients with normal baseline short-cognitive test results found that those with subjective memory complaints had a higher incidence of dementia.⁵ At 5-year follow-up, 15% of patients with baseline subjective memory complaints had developed dementia compared to only 6% of those without such complaints (odds ratio=2.7; 95% confidence interval [CI], 1.45-4.98).

A prospective cohort study that followed 158 patients with no evidence of dementia showed a significant correlation between informant-reported memory problems and development of dementia at 5 years.⁶ Forty-five percent of patients with informant-reported memory problems developed dementia after 5 years compared with 25% of patients who had only self-reported memory problems (P =.02). This result suggests that subjective memory problems reported by observers (family or caregivers) may be more predictive of dementia than self-reported memory complaints.

Donepezil, ginkgo biloba may not help these patients

Most trials of interventions to preserve memory have not enrolled patients with subjective memory complaints. However, data from trials that enrolled either asymptomatic elderly patients or patients with mild cognitive impairment don’t support the use of donepezil, ginkgo biloba, NSAIDs, COX-2 inhibitors, vitamin E, vitamin B₆, vitamin B₁₂, statins, hormone replacement therapy, or omega-3 fatty acids to delay progression to dementia.^7-16

Could mental exercise help?

One systematic review of 22 longitudinal cohort studies, which included more than 29,000 patients, evaluated complex patterns of mental activity in early, mid-, and late-life in relation to the incidence of dementia. Dementia was diagnosed at a significantly lower rate in patients with a higher level of cognitive exercise, such as memory-based leisure activities and social interactions, than those with less rigorous daily cognitive challenges (relative risk=0.54; 95% CI, 0.49-0.59).¹⁷

This raises the possibility that mental exercise has neuroprotective effects. No randomized trials exist to support this hypothesis, however.

Recommendations

There is no consensus regarding the nomenclature applied to reported memory loss and mild cognitive impairment. The Clinical Manual of Geriatric Psychiatry provides definitions that can be used in the clinical setting (TABLE).¹⁸

The US Preventive Services Task Force concludes that evidence is insufficient to recommend for or against routine screening for dementia in older adults (I recommendation).¹⁹ However, the Task Force notes that clinicians should assess cognitive function whenever they suspect impairment or deterioration based on direct observation, patient report, or concerns raised by family members, friends, or care-takers.

The American Geriatrics Society²⁰ and American Academy of Neurology (AAN)²¹ acknowledge the subtle difference between age-associated memory impairment and mild cognitive impairment, and the difficulty of differentiating normal changes of aging from abnormal changes. The AAN’s guidelines for early detection of dementia emphasize the importance of diagnosing mild cognitive impairment or dementia early. However, the guidelines specifically exclude patients with subjective memory loss unaccompanied by objective cognitive deficits and offer no further discussion about these patients.

TABLE
Features of age-associated memory impairment vs mild cognitive impairment

Evidence Summary

Several cross-sectional studies indicate that patients with subjective memory loss are more likely to be older, female, less physically active, in poorer health, less educated, and more depressed or anxious than unaffected patients.^1-4 These studies concentrate mostly on elderly people living in the community.

A study of 1883 patients with normal baseline short-cognitive test results found that those with subjective memory complaints had a higher incidence of dementia.⁵ At 5-year follow-up, 15% of patients with baseline subjective memory complaints had developed dementia compared to only 6% of those without such complaints (odds ratio=2.7; 95% confidence interval [CI], 1.45-4.98).

A prospective cohort study that followed 158 patients with no evidence of dementia showed a significant correlation between informant-reported memory problems and development of dementia at 5 years.⁶ Forty-five percent of patients with informant-reported memory problems developed dementia after 5 years compared with 25% of patients who had only self-reported memory problems (P =.02). This result suggests that subjective memory problems reported by observers (family or caregivers) may be more predictive of dementia than self-reported memory complaints.

Donepezil, ginkgo biloba may not help these patients

Most trials of interventions to preserve memory have not enrolled patients with subjective memory complaints. However, data from trials that enrolled either asymptomatic elderly patients or patients with mild cognitive impairment don’t support the use of donepezil, ginkgo biloba, NSAIDs, COX-2 inhibitors, vitamin E, vitamin B₆, vitamin B₁₂, statins, hormone replacement therapy, or omega-3 fatty acids to delay progression to dementia.^7-16

Could mental exercise help?

One systematic review of 22 longitudinal cohort studies, which included more than 29,000 patients, evaluated complex patterns of mental activity in early, mid-, and late-life in relation to the incidence of dementia. Dementia was diagnosed at a significantly lower rate in patients with a higher level of cognitive exercise, such as memory-based leisure activities and social interactions, than those with less rigorous daily cognitive challenges (relative risk=0.54; 95% CI, 0.49-0.59).¹⁷

This raises the possibility that mental exercise has neuroprotective effects. No randomized trials exist to support this hypothesis, however.

Recommendations

There is no consensus regarding the nomenclature applied to reported memory loss and mild cognitive impairment. The Clinical Manual of Geriatric Psychiatry provides definitions that can be used in the clinical setting (TABLE).¹⁸

The US Preventive Services Task Force concludes that evidence is insufficient to recommend for or against routine screening for dementia in older adults (I recommendation).¹⁹ However, the Task Force notes that clinicians should assess cognitive function whenever they suspect impairment or deterioration based on direct observation, patient report, or concerns raised by family members, friends, or care-takers.

The American Geriatrics Society²⁰ and American Academy of Neurology (AAN)²¹ acknowledge the subtle difference between age-associated memory impairment and mild cognitive impairment, and the difficulty of differentiating normal changes of aging from abnormal changes. The AAN’s guidelines for early detection of dementia emphasize the importance of diagnosing mild cognitive impairment or dementia early. However, the guidelines specifically exclude patients with subjective memory loss unaccompanied by objective cognitive deficits and offer no further discussion about these patients.

TABLE
Features of age-associated memory impairment vs mild cognitive impairment

Evidence summary

In 2003, the United Kingdom’s Expert Working Group of the Committee on Safety of Medicines (CSM) and the FDA conducted a review and meta-analysis, respectively, of the newer antidepressants used in children and adolescents.^1,2 Based on these studies, the FDA mandated that all antidepressant labels carry a black box warning about the increased risk of suicidal thinking and behavior (suicidality) among adolescents taking the medications.

No suicides, but a two-fold increase in suicidality

A recent study that incorporated the FDA meta-analysis analyzed data from 4582 patients. Although no completed suicides were reported in any trial, the drug-treated groups had a two-fold in-crease in suicidality compared with placebo groups (4% vs 2%; number needed to harm [NNH]=50).³ A recent Cochrane review confirmed the increase in absolute risk (1.8; 95% confidence interval [CI], 1.19-2.72).⁴

Two subsequent analyses estimated the difference in risk to be 1.6-fold with a 95% CI of 1.0-2.7 (3% vs 2%; NNH=112).^5,6 The lower estimated risk results largely from a statistical reframing rather than any major difference in data analyzed. The analyses used a random-effects model instead of a fixed-effects model to calculate suicidality, assuming heterogeneity in the drugs used, trial de-signs, and outcome measures.^3,6 All of the analyzed trials excluded patients at high risk for suicide, defined uniquely in the exclusion criteria for each trial.

The TABLE summarizes the increased risk of suicidality for each drug. Notably, venlafaxine had the greatest—and only statistically significant—increased risk, mostly because of suicidal ideation (7 of 9 events in 182 treated patients vs none in 179 placebo patients).⁶ (For a de-tailed look at the risk of suicidal ideation, suicidal behavior, or suicide attempt, see TABLE W1, available online at www. jfponline.com.)

Data on tricyclics in adolescents are scarce

Evidence concerning the safety of tri-cyclic antidepressants in adolescents is limited because adverse effects have not been systematically reported. A 2002 Cochrane meta-analysis found a statistically significant increase in rates of vertigo, orthostatic hypotension, tremor, and dry mouth among children and adolescents taking tricyclic antidepressants compared with placebo. The drugs are modestly effective in treating depression in adolescents; concerns about side effects and safety, however, have limited their use.⁷

Recommendations

The FDA encourages patients taking antidepressants and their families to be alert for signs of impulsive behavior or suicidal tendencies and to have a safety plan. The FDA, American Academy of Child and Adolescent Psychiatry, and the Society for Adolescent Medicine endorse close follow-up with periodic objective assessment.^8-10

The Society for Adolescent Medicine explicitly directs clinicians to consider the FDA black box warning in the con-text of the need to treat major depressive disorder in adolescents and endorses pharmacotherapy for appropriately selected patients.¹⁰ Similarly, the American College of Neuropsychopharmacology argues that the risk-to-benefit ratio favors drug treatment for moderate to severe adolescent depression.¹¹

TABLE
Risk of suicidality among young people taking antidepressants—Pooled results of 2 meta-analyses^1,4

Evidence summary

In 2003, the United Kingdom’s Expert Working Group of the Committee on Safety of Medicines (CSM) and the FDA conducted a review and meta-analysis, respectively, of the newer antidepressants used in children and adolescents.^1,2 Based on these studies, the FDA mandated that all antidepressant labels carry a black box warning about the increased risk of suicidal thinking and behavior (suicidality) among adolescents taking the medications.

No suicides, but a two-fold increase in suicidality

A recent study that incorporated the FDA meta-analysis analyzed data from 4582 patients. Although no completed suicides were reported in any trial, the drug-treated groups had a two-fold in-crease in suicidality compared with placebo groups (4% vs 2%; number needed to harm [NNH]=50).³ A recent Cochrane review confirmed the increase in absolute risk (1.8; 95% confidence interval [CI], 1.19-2.72).⁴

Two subsequent analyses estimated the difference in risk to be 1.6-fold with a 95% CI of 1.0-2.7 (3% vs 2%; NNH=112).^5,6 The lower estimated risk results largely from a statistical reframing rather than any major difference in data analyzed. The analyses used a random-effects model instead of a fixed-effects model to calculate suicidality, assuming heterogeneity in the drugs used, trial de-signs, and outcome measures.^3,6 All of the analyzed trials excluded patients at high risk for suicide, defined uniquely in the exclusion criteria for each trial.

The TABLE summarizes the increased risk of suicidality for each drug. Notably, venlafaxine had the greatest—and only statistically significant—increased risk, mostly because of suicidal ideation (7 of 9 events in 182 treated patients vs none in 179 placebo patients).⁶ (For a de-tailed look at the risk of suicidal ideation, suicidal behavior, or suicide attempt, see TABLE W1, available online at www. jfponline.com.)

Data on tricyclics in adolescents are scarce

Evidence concerning the safety of tri-cyclic antidepressants in adolescents is limited because adverse effects have not been systematically reported. A 2002 Cochrane meta-analysis found a statistically significant increase in rates of vertigo, orthostatic hypotension, tremor, and dry mouth among children and adolescents taking tricyclic antidepressants compared with placebo. The drugs are modestly effective in treating depression in adolescents; concerns about side effects and safety, however, have limited their use.⁷

Recommendations

The FDA encourages patients taking antidepressants and their families to be alert for signs of impulsive behavior or suicidal tendencies and to have a safety plan. The FDA, American Academy of Child and Adolescent Psychiatry, and the Society for Adolescent Medicine endorse close follow-up with periodic objective assessment.^8-10

The Society for Adolescent Medicine explicitly directs clinicians to consider the FDA black box warning in the con-text of the need to treat major depressive disorder in adolescents and endorses pharmacotherapy for appropriately selected patients.¹⁰ Similarly, the American College of Neuropsychopharmacology argues that the risk-to-benefit ratio favors drug treatment for moderate to severe adolescent depression.¹¹

TABLE
Risk of suicidality among young people taking antidepressants—Pooled results of 2 meta-analyses^1,4

Evidence summary

In 2003, the United Kingdom’s Expert Working Group of the Committee on Safety of Medicines (CSM) and the FDA conducted a review and meta-analysis, respectively, of the newer antidepressants used in children and adolescents.^1,2 Based on these studies, the FDA mandated that all antidepressant labels carry a black box warning about the increased risk of suicidal thinking and behavior (suicidality) among adolescents taking the medications.

No suicides, but a two-fold increase in suicidality

A recent study that incorporated the FDA meta-analysis analyzed data from 4582 patients. Although no completed suicides were reported in any trial, the drug-treated groups had a two-fold in-crease in suicidality compared with placebo groups (4% vs 2%; number needed to harm [NNH]=50).³ A recent Cochrane review confirmed the increase in absolute risk (1.8; 95% confidence interval [CI], 1.19-2.72).⁴

Two subsequent analyses estimated the difference in risk to be 1.6-fold with a 95% CI of 1.0-2.7 (3% vs 2%; NNH=112).^5,6 The lower estimated risk results largely from a statistical reframing rather than any major difference in data analyzed. The analyses used a random-effects model instead of a fixed-effects model to calculate suicidality, assuming heterogeneity in the drugs used, trial de-signs, and outcome measures.^3,6 All of the analyzed trials excluded patients at high risk for suicide, defined uniquely in the exclusion criteria for each trial.

The TABLE summarizes the increased risk of suicidality for each drug. Notably, venlafaxine had the greatest—and only statistically significant—increased risk, mostly because of suicidal ideation (7 of 9 events in 182 treated patients vs none in 179 placebo patients).⁶ (For a de-tailed look at the risk of suicidal ideation, suicidal behavior, or suicide attempt, see TABLE W1, available online at www. jfponline.com.)

Data on tricyclics in adolescents are scarce

Evidence concerning the safety of tri-cyclic antidepressants in adolescents is limited because adverse effects have not been systematically reported. A 2002 Cochrane meta-analysis found a statistically significant increase in rates of vertigo, orthostatic hypotension, tremor, and dry mouth among children and adolescents taking tricyclic antidepressants compared with placebo. The drugs are modestly effective in treating depression in adolescents; concerns about side effects and safety, however, have limited their use.⁷

Recommendations

The FDA encourages patients taking antidepressants and their families to be alert for signs of impulsive behavior or suicidal tendencies and to have a safety plan. The FDA, American Academy of Child and Adolescent Psychiatry, and the Society for Adolescent Medicine endorse close follow-up with periodic objective assessment.^8-10

The Society for Adolescent Medicine explicitly directs clinicians to consider the FDA black box warning in the con-text of the need to treat major depressive disorder in adolescents and endorses pharmacotherapy for appropriately selected patients.¹⁰ Similarly, the American College of Neuropsychopharmacology argues that the risk-to-benefit ratio favors drug treatment for moderate to severe adolescent depression.¹¹

TABLE
Risk of suicidality among young people taking antidepressants—Pooled results of 2 meta-analyses^1,4

Evidence summary

A consistent definition of frequent PVCs doesn’t exist in the literature. Some studies have found a significant risk of death or acute myocardial infarction associated with >30 PVCs per hour.^1,2 The 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guideline defines frequent PVCs as >10 per hour.³

Despite the association between frequent PVCs and increased risk of death and cardiac events, our review didn’t find studies that indicate the utility of evaluation strategies for higher-risk patients.

Frequent PVCs predict increased mortality

The Framingham study looked at the prognostic implications of frequent PVCs (>30 per hour) in a cohort of symptomatic patients examined over a 6-year period.¹ Men, but not women, had a significant increase in all-cause mortality (relative risk [RR]=2.36; 95% confidence interval [CI], 1.65-3.2) and myocardial infarction or sudden death (RR=2.12; 95% CI, 1.33-3.38). The Copenhagen Holter study of a cohort of healthy patients demonstrated an increased risk of myocardial infarction or cardiovascular death in patients with >30 PVCs per hour (hazard ratio [HR]=2.85, 95% CI, 1.16-7.0).²

Frequent PVCs occurring during recovery from stress testing are also associated with increased mortality. A large prospective cohort study followed more than 29,000 patients with varying degrees of risk for 5 years. After adjusting for confounding variables, frequent PVCs (≥7 per minute or more complex ventricular ectopy) during recovery predicted an increased risk of death (HR=1.5; 95% CI, 1.1-1.9). Frequent PVCs arising during exercise stress testing were not associated with increased risk.⁴

Suppressing PVCs is a bad idea

Studies have evaluated whether suppressing PVCs with antiarrhythmic agents improves prognosis. Both Cardiac Arrhythmia Suppression Trials (CAST I: encainide and flecainide; CAST II: moricizine) showed that suppressing frequent PVCs significantly increased mortality in the treatment groups.^5,6

Recommendations

In 2006, the American College of Cardiology, American Heart Association, and European Society of Cardiology published their Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death.³

The TABLE summarizes characteristics of patients with PVCs who were at higher risk of underlying cardiac disease and death. All patients with PVCs should have a history and physical examination, electrocardiogram, and electrolyte studies. Higher-risk patients should be considered for further evaluation, including stress testing, echocardiography, and ambulatory electrocardiogram (SOR: C, opinion).

TABLE
Characteristics of patients with PVCs who are at higher risk of cardiac disease/death

Evidence summary

A consistent definition of frequent PVCs doesn’t exist in the literature. Some studies have found a significant risk of death or acute myocardial infarction associated with >30 PVCs per hour.^1,2 The 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guideline defines frequent PVCs as >10 per hour.³

Despite the association between frequent PVCs and increased risk of death and cardiac events, our review didn’t find studies that indicate the utility of evaluation strategies for higher-risk patients.

Frequent PVCs predict increased mortality

The Framingham study looked at the prognostic implications of frequent PVCs (>30 per hour) in a cohort of symptomatic patients examined over a 6-year period.¹ Men, but not women, had a significant increase in all-cause mortality (relative risk [RR]=2.36; 95% confidence interval [CI], 1.65-3.2) and myocardial infarction or sudden death (RR=2.12; 95% CI, 1.33-3.38). The Copenhagen Holter study of a cohort of healthy patients demonstrated an increased risk of myocardial infarction or cardiovascular death in patients with >30 PVCs per hour (hazard ratio [HR]=2.85, 95% CI, 1.16-7.0).²

Frequent PVCs occurring during recovery from stress testing are also associated with increased mortality. A large prospective cohort study followed more than 29,000 patients with varying degrees of risk for 5 years. After adjusting for confounding variables, frequent PVCs (≥7 per minute or more complex ventricular ectopy) during recovery predicted an increased risk of death (HR=1.5; 95% CI, 1.1-1.9). Frequent PVCs arising during exercise stress testing were not associated with increased risk.⁴

Suppressing PVCs is a bad idea

Studies have evaluated whether suppressing PVCs with antiarrhythmic agents improves prognosis. Both Cardiac Arrhythmia Suppression Trials (CAST I: encainide and flecainide; CAST II: moricizine) showed that suppressing frequent PVCs significantly increased mortality in the treatment groups.^5,6

Recommendations

In 2006, the American College of Cardiology, American Heart Association, and European Society of Cardiology published their Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death.³

The TABLE summarizes characteristics of patients with PVCs who were at higher risk of underlying cardiac disease and death. All patients with PVCs should have a history and physical examination, electrocardiogram, and electrolyte studies. Higher-risk patients should be considered for further evaluation, including stress testing, echocardiography, and ambulatory electrocardiogram (SOR: C, opinion).

TABLE
Characteristics of patients with PVCs who are at higher risk of cardiac disease/death

Evidence summary

A consistent definition of frequent PVCs doesn’t exist in the literature. Some studies have found a significant risk of death or acute myocardial infarction associated with >30 PVCs per hour.^1,2 The 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guideline defines frequent PVCs as >10 per hour.³

Despite the association between frequent PVCs and increased risk of death and cardiac events, our review didn’t find studies that indicate the utility of evaluation strategies for higher-risk patients.

Frequent PVCs predict increased mortality

The Framingham study looked at the prognostic implications of frequent PVCs (>30 per hour) in a cohort of symptomatic patients examined over a 6-year period.¹ Men, but not women, had a significant increase in all-cause mortality (relative risk [RR]=2.36; 95% confidence interval [CI], 1.65-3.2) and myocardial infarction or sudden death (RR=2.12; 95% CI, 1.33-3.38). The Copenhagen Holter study of a cohort of healthy patients demonstrated an increased risk of myocardial infarction or cardiovascular death in patients with >30 PVCs per hour (hazard ratio [HR]=2.85, 95% CI, 1.16-7.0).²

Frequent PVCs occurring during recovery from stress testing are also associated with increased mortality. A large prospective cohort study followed more than 29,000 patients with varying degrees of risk for 5 years. After adjusting for confounding variables, frequent PVCs (≥7 per minute or more complex ventricular ectopy) during recovery predicted an increased risk of death (HR=1.5; 95% CI, 1.1-1.9). Frequent PVCs arising during exercise stress testing were not associated with increased risk.⁴

Suppressing PVCs is a bad idea

Studies have evaluated whether suppressing PVCs with antiarrhythmic agents improves prognosis. Both Cardiac Arrhythmia Suppression Trials (CAST I: encainide and flecainide; CAST II: moricizine) showed that suppressing frequent PVCs significantly increased mortality in the treatment groups.^5,6

Recommendations

In 2006, the American College of Cardiology, American Heart Association, and European Society of Cardiology published their Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death.³

The TABLE summarizes characteristics of patients with PVCs who were at higher risk of underlying cardiac disease and death. All patients with PVCs should have a history and physical examination, electrocardiogram, and electrolyte studies. Higher-risk patients should be considered for further evaluation, including stress testing, echocardiography, and ambulatory electrocardiogram (SOR: C, opinion).

TABLE
Characteristics of patients with PVCs who are at higher risk of cardiac disease/death

Evidence summary

Make sure it’s true hypercalcemia

Measuring calcium levels in asymptomatic patients often leads to false-positive elevations caused by random error or changes in the level of physiologically active calcium because of alterations in blood pH or serum albumin. Serum calcium levels between 10.0 and 12.0 mg/dL indicate mild hypercalcemia; levels >14.0 mg/dL are severe. Because changes in pH and serum albumin levels alter levels of physiologically active calcium, authoritative sources recommend measuring or calculating physiologically active calcium if blood pH or albumin is abnormal.^1,2 To determine the level, use the equation [4.0 – (plasma albumin)] × 0.8 + (serum calcium) or measure serum ionized calcium.² Normal levels of serum ionized calcium for adults older than 19 years are 1.13 to 1.32 mmol/L, although the exact range can vary from laboratory to laboratory. Elevated physiologically active calcium indicates true hypercalcemia.

Assess for the most common causes, PHPT and malignancy

Evaluation of the patient with true hypercalcemia should include a detailed history, physical examination, and assessment of risk factors for all causes of hypercalcemia.^1,2 PHPT and malignancy are the two most common causes of asymptomatic true hypercalcemia (TABLE).²

Laboratory evaluation targeting these causes, beginning with an intact PTH level, is a logical first step.^1,2 Persistent hypercalcemia in the presence of elevated or inappropriately normal PTH concentrations confirms the diagnosis of PHPT.³ When serum calcium rises, PTH is normally suppressed. Normal intact PTH and low 24-hour urinary calcium excretion distinguishes patients with PHPT from those with less common familial hypocalciuric hypercalcemia.^1,2

Most patients with PHPT are asymptomatic, although some eventually develop bone loss, nephrolithiasis, and renal colic.^4,5 A 10-year prospective cohort study of patients with PHPT found that 21% of asymptomatic patients developed decreased bone density at one or more sites.⁶ None acquired kidney stones, but hypercalcemia and hypercalciuria did worsen in 10 of 52 patients. A guideline and a review on PHPT recommend measuring creatinine clearance and obtaining a bone densitometry study of the distal third of the radius, hip, and lumbar spine to assess for end-organ changes related to the condition; declining renal function and osteoporosis may be indications for surgery.^3,5

Malignancy is the most common cause of low intact PTH and true hypercalcemia, especially when the calcium level is >14 mg/dL.¹ A PTHrP >1.0 pmol/L is highly specific for malignancy because this level does not occur in healthy people.¹ In a prospective case series of patients with hypercalcemia and malignancy, 54% had elevated PTHrP levels.⁷ The authors found that an elevated PTHrP in patients younger than 65 years of age doubles the risk of death from malignancy compared to patients the same age with normal PTHrP (hazard ratio=1.9; 95% CI, 1.1-3.4).

TABLE
Causes of hypercalcemia

Identify less common causes

Serum calcitriol in association with a low intact PTH level and elevated calcium lower than 14 mg/dL helps differentiate the less common causes of hypercalcemia. Calcitriol is high in granulomatous diseases such as sarcoidosis, tuberculosis, and histoplasmosis, and normal in hyperthyroidism and Addison’s disease.¹

Immobilization as a cause of hypercalcemia can be distinguished from PHPT by history and normal PTH levels and from malignancy by a normal alkaline phosphatase level.¹

Recommendations

In addition to the recommendations discussed previously, Williams Textbook of Endocrinology advises repeating the initial calcium level twice and measuring serum BUN, creatinine, electrolytes, albumin, globulin, and phosphate.⁸ The authors recommend a generalized work-up for malignancy, including mammography, chest radiography with or without CT, abdominal CT, serum and urine immunoelectrophoresis, and temporary discontinuation of lithium for patients taking the drug. They also recommend using PTHrP only when PTH is suppressed but an underlying malignancy can’t be found.

Evidence summary

Make sure it’s true hypercalcemia

Measuring calcium levels in asymptomatic patients often leads to false-positive elevations caused by random error or changes in the level of physiologically active calcium because of alterations in blood pH or serum albumin. Serum calcium levels between 10.0 and 12.0 mg/dL indicate mild hypercalcemia; levels >14.0 mg/dL are severe. Because changes in pH and serum albumin levels alter levels of physiologically active calcium, authoritative sources recommend measuring or calculating physiologically active calcium if blood pH or albumin is abnormal.^1,2 To determine the level, use the equation [4.0 – (plasma albumin)] × 0.8 + (serum calcium) or measure serum ionized calcium.² Normal levels of serum ionized calcium for adults older than 19 years are 1.13 to 1.32 mmol/L, although the exact range can vary from laboratory to laboratory. Elevated physiologically active calcium indicates true hypercalcemia.

Assess for the most common causes, PHPT and malignancy

Evaluation of the patient with true hypercalcemia should include a detailed history, physical examination, and assessment of risk factors for all causes of hypercalcemia.^1,2 PHPT and malignancy are the two most common causes of asymptomatic true hypercalcemia (TABLE).²

Laboratory evaluation targeting these causes, beginning with an intact PTH level, is a logical first step.^1,2 Persistent hypercalcemia in the presence of elevated or inappropriately normal PTH concentrations confirms the diagnosis of PHPT.³ When serum calcium rises, PTH is normally suppressed. Normal intact PTH and low 24-hour urinary calcium excretion distinguishes patients with PHPT from those with less common familial hypocalciuric hypercalcemia.^1,2

Most patients with PHPT are asymptomatic, although some eventually develop bone loss, nephrolithiasis, and renal colic.^4,5 A 10-year prospective cohort study of patients with PHPT found that 21% of asymptomatic patients developed decreased bone density at one or more sites.⁶ None acquired kidney stones, but hypercalcemia and hypercalciuria did worsen in 10 of 52 patients. A guideline and a review on PHPT recommend measuring creatinine clearance and obtaining a bone densitometry study of the distal third of the radius, hip, and lumbar spine to assess for end-organ changes related to the condition; declining renal function and osteoporosis may be indications for surgery.^3,5

Malignancy is the most common cause of low intact PTH and true hypercalcemia, especially when the calcium level is >14 mg/dL.¹ A PTHrP >1.0 pmol/L is highly specific for malignancy because this level does not occur in healthy people.¹ In a prospective case series of patients with hypercalcemia and malignancy, 54% had elevated PTHrP levels.⁷ The authors found that an elevated PTHrP in patients younger than 65 years of age doubles the risk of death from malignancy compared to patients the same age with normal PTHrP (hazard ratio=1.9; 95% CI, 1.1-3.4).

TABLE
Causes of hypercalcemia

Identify less common causes

Serum calcitriol in association with a low intact PTH level and elevated calcium lower than 14 mg/dL helps differentiate the less common causes of hypercalcemia. Calcitriol is high in granulomatous diseases such as sarcoidosis, tuberculosis, and histoplasmosis, and normal in hyperthyroidism and Addison’s disease.¹

Immobilization as a cause of hypercalcemia can be distinguished from PHPT by history and normal PTH levels and from malignancy by a normal alkaline phosphatase level.¹

Recommendations

In addition to the recommendations discussed previously, Williams Textbook of Endocrinology advises repeating the initial calcium level twice and measuring serum BUN, creatinine, electrolytes, albumin, globulin, and phosphate.⁸ The authors recommend a generalized work-up for malignancy, including mammography, chest radiography with or without CT, abdominal CT, serum and urine immunoelectrophoresis, and temporary discontinuation of lithium for patients taking the drug. They also recommend using PTHrP only when PTH is suppressed but an underlying malignancy can’t be found.

Evidence summary

Make sure it’s true hypercalcemia

Measuring calcium levels in asymptomatic patients often leads to false-positive elevations caused by random error or changes in the level of physiologically active calcium because of alterations in blood pH or serum albumin. Serum calcium levels between 10.0 and 12.0 mg/dL indicate mild hypercalcemia; levels >14.0 mg/dL are severe. Because changes in pH and serum albumin levels alter levels of physiologically active calcium, authoritative sources recommend measuring or calculating physiologically active calcium if blood pH or albumin is abnormal.^1,2 To determine the level, use the equation [4.0 – (plasma albumin)] × 0.8 + (serum calcium) or measure serum ionized calcium.² Normal levels of serum ionized calcium for adults older than 19 years are 1.13 to 1.32 mmol/L, although the exact range can vary from laboratory to laboratory. Elevated physiologically active calcium indicates true hypercalcemia.

Assess for the most common causes, PHPT and malignancy

Evaluation of the patient with true hypercalcemia should include a detailed history, physical examination, and assessment of risk factors for all causes of hypercalcemia.^1,2 PHPT and malignancy are the two most common causes of asymptomatic true hypercalcemia (TABLE).²

Laboratory evaluation targeting these causes, beginning with an intact PTH level, is a logical first step.^1,2 Persistent hypercalcemia in the presence of elevated or inappropriately normal PTH concentrations confirms the diagnosis of PHPT.³ When serum calcium rises, PTH is normally suppressed. Normal intact PTH and low 24-hour urinary calcium excretion distinguishes patients with PHPT from those with less common familial hypocalciuric hypercalcemia.^1,2

Most patients with PHPT are asymptomatic, although some eventually develop bone loss, nephrolithiasis, and renal colic.^4,5 A 10-year prospective cohort study of patients with PHPT found that 21% of asymptomatic patients developed decreased bone density at one or more sites.⁶ None acquired kidney stones, but hypercalcemia and hypercalciuria did worsen in 10 of 52 patients. A guideline and a review on PHPT recommend measuring creatinine clearance and obtaining a bone densitometry study of the distal third of the radius, hip, and lumbar spine to assess for end-organ changes related to the condition; declining renal function and osteoporosis may be indications for surgery.^3,5

Malignancy is the most common cause of low intact PTH and true hypercalcemia, especially when the calcium level is >14 mg/dL.¹ A PTHrP >1.0 pmol/L is highly specific for malignancy because this level does not occur in healthy people.¹ In a prospective case series of patients with hypercalcemia and malignancy, 54% had elevated PTHrP levels.⁷ The authors found that an elevated PTHrP in patients younger than 65 years of age doubles the risk of death from malignancy compared to patients the same age with normal PTHrP (hazard ratio=1.9; 95% CI, 1.1-3.4).

TABLE
Causes of hypercalcemia

Identify less common causes

Serum calcitriol in association with a low intact PTH level and elevated calcium lower than 14 mg/dL helps differentiate the less common causes of hypercalcemia. Calcitriol is high in granulomatous diseases such as sarcoidosis, tuberculosis, and histoplasmosis, and normal in hyperthyroidism and Addison’s disease.¹

Immobilization as a cause of hypercalcemia can be distinguished from PHPT by history and normal PTH levels and from malignancy by a normal alkaline phosphatase level.¹

Recommendations

In addition to the recommendations discussed previously, Williams Textbook of Endocrinology advises repeating the initial calcium level twice and measuring serum BUN, creatinine, electrolytes, albumin, globulin, and phosphate.⁸ The authors recommend a generalized work-up for malignancy, including mammography, chest radiography with or without CT, abdominal CT, serum and urine immunoelectrophoresis, and temporary discontinuation of lithium for patients taking the drug. They also recommend using PTHrP only when PTH is suppressed but an underlying malignancy can’t be found.

Evidence summary

While patients may refer to this condition as “Achilles tendonitis,” the phrase is actually a misnomer. That’s because in tendonitis, the inflammation is limited to the surrounding structures, but doesn’t involve the tendon itself.

Acute symptoms respond to NSAIDs

A Cochrane review of treatments for acute Achilles tendonopathy included 9 randomized trials with a total of 697 patients. Two RCTs showed evidence that NSAIDs alleviate acute symptoms. In 1 trial of 212 patients who received an oral NSAID or placebo for 14 days, significantly fewer patients in the placebo group achieved a good or excellent symptom relief (relative risk [RR]=0.42; 95% confidence interval [CI], 0.21-0.86). A second RCT of 243 patients compared treatment with a topical NSAID to placebo for 21 days; significantly fewer participants who took placebo returned to their pre-injury level of activity (RR=0.78; 95% CI, 0.63-0.95). Low-dose heparin injection, heel pads, topical laser therapy, and peritendinous steroid injection produced no significant decrease in pain compared with placebo.¹

Continue to exercise?

Eccentric calf-muscle training helps chronic tendonopathy

ECMT is an effective intervention for chronic noninsertional Achilles tendonopathy. An observational study of ECMT in 78 patients (101 tendons total) with chronic noninsertional Achilles tendonopathy found that 89% were back to their preinjury activity level after a 12-week regimen of ECMT, as indicated by significantly lower scores on a 100-point visual analog scale (67 at baseline vs 10.2 at 12 weeks; P<0.001).²

An RCT compared ECMT or repetitive shock wave therapy to a “wait-and-see” control group (25 patients in each group). After 4 months, both the ECMT and shock wave therapy groups reported a significant decrease in pain compared with controls (P< 0.001; mean difference in 10-point pain score, 2.4; 95% CI, 1.3-3.5). Sixty percent of participants in the ECMT group reported complete recovery or significant improvement (P<0.001; number needed to treat [NNT]=3; mean difference in 6-point Likert scale=–1.6; 95% CI, –2.4 to 0.8).³

During an ECMT program, patients may be able to continue activity without exacerbating Achilles tendonopathy. An RCT of 38 patients compared rest with eccentric training and continued activity and eccentric training for 12 weeks to 6 months using a pain-monitored model. Both groups showed similar improvement in pain and function when measured with the Swedish version of the Achilles assessment questionnaire (VISA-A-S 100-point scale: 0=worst function, 100=completely recovered). The baseline mean VISA-A-S scores were 57 for both groups; the mean scores after 12 months were 85 for the exercise group and 91 for the rest group.⁴

Another option: The AirHeel brace

An AirHeel brace may be a viable alternative to ECMT, especially if the patient can’t tolerate eccentric muscle training because of pain. The brace was designed for Achilles tendonopathy and posterior heel pain. It applies intermittent compression to minimize swelling and promote circulation.

An RCT evaluated 100 patients with chronic noninsertional Achilles tendonopathy who were treated with ECMT, an AirHeel Brace, or a combination of the 2 for 12 weeks. At 1-year follow-up, all 3 groups showed a significant reduction in pain measured by a 10-point visual analog scale (ECMT 30%, brace 27%, combination 53%; P<0.0001). All the groups also showed significantly improved function as measured by an American Orthopaedic Foot and Ankle Society Score (10%, 10%, and 30%, respectively; P<0.001). No significant differences in outcomes were found across the treatment groups, and 90% of participants reached their preinjury activity level after 1 year.⁴

Shock wave therapy and topical glyceryl trinitrate

The role of repetitive shock wave therapy and topical glyceryl trinitrate in the treatment of chronic noninsertional Achilles tendonopathy is less clear. In a double-blinded RCT of 49 patients, shock wave therapy did not produce better outcomes than placebo.⁵

However, a prospective cohort study of 68 patients found that patients who received shock wave therapy had significantly lower mean visual analog scale scores for pain compared with controls after 1 month (P<0.001), 3 months (P<0.001), and 12 months (P<0.001) of treatment.⁶ In a double-blinded RCT of 65 patients, more patients treated with topical glyceryl trinitrate therapy were asymptomatic during activities of daily living at 6 months compared with placebo (P<0.001).⁷

Both shock wave therapy and topical glyceryl trinitrate may have a significant role to play in treating chronic noninsertional Achilles tendonopathy, but more studies are needed to support their use.

Surgery appears to work better for athletes

Surgery is an option for patients with chronic noninsertional Achilles tendonopathy who have failed conservative measures and a 3- to 6-month rehabilitation program. In a systematic review of 26 studies of patients managed surgically, the mean success rate (full return to preinjury activity level) was 77%. However, a negative correlation was observed between the reported success rate and the overall methods score, a rating of the quality of studies (r=0.53; P<0.01). Only 5 of the studies reviewed were prospective cohort studies; the remaining 21 were retrospective cohort studies and case studies.⁸

Athletes responded significantly better to surgery than nonathletic patients, returning to full activity in 4.5 months compared with 7.1 months for nonathletes (P<0.03). Fewer athletes had surgical complications (9% compared with 19% of nonathletes).⁹ More studies are needed to clarify the role of surgery in managing Achilles tendonopathy.

Recommendations

The American College of Foot and Ankle Surgeons recommends initial management by reducing pressure around the affected area combined with heel lifts, orthotics, NSAID therapy, and physical therapy. Immobilization may be used on a case-by-case basis. Local steroid injections aren’t recommended. Patients with resistant tendonopathy should be referred to a foot and ankle surgeon.¹⁰

Evidence summary

While patients may refer to this condition as “Achilles tendonitis,” the phrase is actually a misnomer. That’s because in tendonitis, the inflammation is limited to the surrounding structures, but doesn’t involve the tendon itself.

Acute symptoms respond to NSAIDs

A Cochrane review of treatments for acute Achilles tendonopathy included 9 randomized trials with a total of 697 patients. Two RCTs showed evidence that NSAIDs alleviate acute symptoms. In 1 trial of 212 patients who received an oral NSAID or placebo for 14 days, significantly fewer patients in the placebo group achieved a good or excellent symptom relief (relative risk [RR]=0.42; 95% confidence interval [CI], 0.21-0.86). A second RCT of 243 patients compared treatment with a topical NSAID to placebo for 21 days; significantly fewer participants who took placebo returned to their pre-injury level of activity (RR=0.78; 95% CI, 0.63-0.95). Low-dose heparin injection, heel pads, topical laser therapy, and peritendinous steroid injection produced no significant decrease in pain compared with placebo.¹

Continue to exercise?

Eccentric calf-muscle training helps chronic tendonopathy

ECMT is an effective intervention for chronic noninsertional Achilles tendonopathy. An observational study of ECMT in 78 patients (101 tendons total) with chronic noninsertional Achilles tendonopathy found that 89% were back to their preinjury activity level after a 12-week regimen of ECMT, as indicated by significantly lower scores on a 100-point visual analog scale (67 at baseline vs 10.2 at 12 weeks; P<0.001).²

An RCT compared ECMT or repetitive shock wave therapy to a “wait-and-see” control group (25 patients in each group). After 4 months, both the ECMT and shock wave therapy groups reported a significant decrease in pain compared with controls (P< 0.001; mean difference in 10-point pain score, 2.4; 95% CI, 1.3-3.5). Sixty percent of participants in the ECMT group reported complete recovery or significant improvement (P<0.001; number needed to treat [NNT]=3; mean difference in 6-point Likert scale=–1.6; 95% CI, –2.4 to 0.8).³

During an ECMT program, patients may be able to continue activity without exacerbating Achilles tendonopathy. An RCT of 38 patients compared rest with eccentric training and continued activity and eccentric training for 12 weeks to 6 months using a pain-monitored model. Both groups showed similar improvement in pain and function when measured with the Swedish version of the Achilles assessment questionnaire (VISA-A-S 100-point scale: 0=worst function, 100=completely recovered). The baseline mean VISA-A-S scores were 57 for both groups; the mean scores after 12 months were 85 for the exercise group and 91 for the rest group.⁴

Another option: The AirHeel brace

An AirHeel brace may be a viable alternative to ECMT, especially if the patient can’t tolerate eccentric muscle training because of pain. The brace was designed for Achilles tendonopathy and posterior heel pain. It applies intermittent compression to minimize swelling and promote circulation.

An RCT evaluated 100 patients with chronic noninsertional Achilles tendonopathy who were treated with ECMT, an AirHeel Brace, or a combination of the 2 for 12 weeks. At 1-year follow-up, all 3 groups showed a significant reduction in pain measured by a 10-point visual analog scale (ECMT 30%, brace 27%, combination 53%; P<0.0001). All the groups also showed significantly improved function as measured by an American Orthopaedic Foot and Ankle Society Score (10%, 10%, and 30%, respectively; P<0.001). No significant differences in outcomes were found across the treatment groups, and 90% of participants reached their preinjury activity level after 1 year.⁴

Shock wave therapy and topical glyceryl trinitrate

The role of repetitive shock wave therapy and topical glyceryl trinitrate in the treatment of chronic noninsertional Achilles tendonopathy is less clear. In a double-blinded RCT of 49 patients, shock wave therapy did not produce better outcomes than placebo.⁵

However, a prospective cohort study of 68 patients found that patients who received shock wave therapy had significantly lower mean visual analog scale scores for pain compared with controls after 1 month (P<0.001), 3 months (P<0.001), and 12 months (P<0.001) of treatment.⁶ In a double-blinded RCT of 65 patients, more patients treated with topical glyceryl trinitrate therapy were asymptomatic during activities of daily living at 6 months compared with placebo (P<0.001).⁷

Both shock wave therapy and topical glyceryl trinitrate may have a significant role to play in treating chronic noninsertional Achilles tendonopathy, but more studies are needed to support their use.

Surgery appears to work better for athletes

Surgery is an option for patients with chronic noninsertional Achilles tendonopathy who have failed conservative measures and a 3- to 6-month rehabilitation program. In a systematic review of 26 studies of patients managed surgically, the mean success rate (full return to preinjury activity level) was 77%. However, a negative correlation was observed between the reported success rate and the overall methods score, a rating of the quality of studies (r=0.53; P<0.01). Only 5 of the studies reviewed were prospective cohort studies; the remaining 21 were retrospective cohort studies and case studies.⁸

Athletes responded significantly better to surgery than nonathletic patients, returning to full activity in 4.5 months compared with 7.1 months for nonathletes (P<0.03). Fewer athletes had surgical complications (9% compared with 19% of nonathletes).⁹ More studies are needed to clarify the role of surgery in managing Achilles tendonopathy.

Recommendations

The American College of Foot and Ankle Surgeons recommends initial management by reducing pressure around the affected area combined with heel lifts, orthotics, NSAID therapy, and physical therapy. Immobilization may be used on a case-by-case basis. Local steroid injections aren’t recommended. Patients with resistant tendonopathy should be referred to a foot and ankle surgeon.¹⁰

Evidence summary

While patients may refer to this condition as “Achilles tendonitis,” the phrase is actually a misnomer. That’s because in tendonitis, the inflammation is limited to the surrounding structures, but doesn’t involve the tendon itself.

Acute symptoms respond to NSAIDs

A Cochrane review of treatments for acute Achilles tendonopathy included 9 randomized trials with a total of 697 patients. Two RCTs showed evidence that NSAIDs alleviate acute symptoms. In 1 trial of 212 patients who received an oral NSAID or placebo for 14 days, significantly fewer patients in the placebo group achieved a good or excellent symptom relief (relative risk [RR]=0.42; 95% confidence interval [CI], 0.21-0.86). A second RCT of 243 patients compared treatment with a topical NSAID to placebo for 21 days; significantly fewer participants who took placebo returned to their pre-injury level of activity (RR=0.78; 95% CI, 0.63-0.95). Low-dose heparin injection, heel pads, topical laser therapy, and peritendinous steroid injection produced no significant decrease in pain compared with placebo.¹

Continue to exercise?

Eccentric calf-muscle training helps chronic tendonopathy

ECMT is an effective intervention for chronic noninsertional Achilles tendonopathy. An observational study of ECMT in 78 patients (101 tendons total) with chronic noninsertional Achilles tendonopathy found that 89% were back to their preinjury activity level after a 12-week regimen of ECMT, as indicated by significantly lower scores on a 100-point visual analog scale (67 at baseline vs 10.2 at 12 weeks; P<0.001).²

An RCT compared ECMT or repetitive shock wave therapy to a “wait-and-see” control group (25 patients in each group). After 4 months, both the ECMT and shock wave therapy groups reported a significant decrease in pain compared with controls (P< 0.001; mean difference in 10-point pain score, 2.4; 95% CI, 1.3-3.5). Sixty percent of participants in the ECMT group reported complete recovery or significant improvement (P<0.001; number needed to treat [NNT]=3; mean difference in 6-point Likert scale=–1.6; 95% CI, –2.4 to 0.8).³

During an ECMT program, patients may be able to continue activity without exacerbating Achilles tendonopathy. An RCT of 38 patients compared rest with eccentric training and continued activity and eccentric training for 12 weeks to 6 months using a pain-monitored model. Both groups showed similar improvement in pain and function when measured with the Swedish version of the Achilles assessment questionnaire (VISA-A-S 100-point scale: 0=worst function, 100=completely recovered). The baseline mean VISA-A-S scores were 57 for both groups; the mean scores after 12 months were 85 for the exercise group and 91 for the rest group.⁴

Another option: The AirHeel brace

An AirHeel brace may be a viable alternative to ECMT, especially if the patient can’t tolerate eccentric muscle training because of pain. The brace was designed for Achilles tendonopathy and posterior heel pain. It applies intermittent compression to minimize swelling and promote circulation.

An RCT evaluated 100 patients with chronic noninsertional Achilles tendonopathy who were treated with ECMT, an AirHeel Brace, or a combination of the 2 for 12 weeks. At 1-year follow-up, all 3 groups showed a significant reduction in pain measured by a 10-point visual analog scale (ECMT 30%, brace 27%, combination 53%; P<0.0001). All the groups also showed significantly improved function as measured by an American Orthopaedic Foot and Ankle Society Score (10%, 10%, and 30%, respectively; P<0.001). No significant differences in outcomes were found across the treatment groups, and 90% of participants reached their preinjury activity level after 1 year.⁴

Shock wave therapy and topical glyceryl trinitrate

The role of repetitive shock wave therapy and topical glyceryl trinitrate in the treatment of chronic noninsertional Achilles tendonopathy is less clear. In a double-blinded RCT of 49 patients, shock wave therapy did not produce better outcomes than placebo.⁵

However, a prospective cohort study of 68 patients found that patients who received shock wave therapy had significantly lower mean visual analog scale scores for pain compared with controls after 1 month (P<0.001), 3 months (P<0.001), and 12 months (P<0.001) of treatment.⁶ In a double-blinded RCT of 65 patients, more patients treated with topical glyceryl trinitrate therapy were asymptomatic during activities of daily living at 6 months compared with placebo (P<0.001).⁷

Both shock wave therapy and topical glyceryl trinitrate may have a significant role to play in treating chronic noninsertional Achilles tendonopathy, but more studies are needed to support their use.

Surgery appears to work better for athletes

Surgery is an option for patients with chronic noninsertional Achilles tendonopathy who have failed conservative measures and a 3- to 6-month rehabilitation program. In a systematic review of 26 studies of patients managed surgically, the mean success rate (full return to preinjury activity level) was 77%. However, a negative correlation was observed between the reported success rate and the overall methods score, a rating of the quality of studies (r=0.53; P<0.01). Only 5 of the studies reviewed were prospective cohort studies; the remaining 21 were retrospective cohort studies and case studies.⁸

Athletes responded significantly better to surgery than nonathletic patients, returning to full activity in 4.5 months compared with 7.1 months for nonathletes (P<0.03). Fewer athletes had surgical complications (9% compared with 19% of nonathletes).⁹ More studies are needed to clarify the role of surgery in managing Achilles tendonopathy.

Recommendations

The American College of Foot and Ankle Surgeons recommends initial management by reducing pressure around the affected area combined with heel lifts, orthotics, NSAID therapy, and physical therapy. Immobilization may be used on a case-by-case basis. Local steroid injections aren’t recommended. Patients with resistant tendonopathy should be referred to a foot and ankle surgeon.¹⁰

Evidence summary

Giardia lamblia is a protozoan parasite found worldwide. Infection typically results from ingesting cysts in contaminated food or water. Patients with giardiasis may be asymptomatic or have mild to severe gastrointestinal symptoms, including explosive diarrhea, abdominal pain, steatorrhea, flatulence, bloating, nausea, and vomiting. Treatment varies widely based on geographic location, physician preference, and availability and cost of medication (TABLE).¹

TABLE 1
Drugs commonly used to treat giardiasis

Tinidazole is the treatment of choice

A 2006 Cochrane Review compared 34 trials of many drug therapies for giardiasis.² The review, which is being updated to include additional publications, evaluated both head-to-head and placebo-controlled studies, looking at dosage as well as length of drug therapy.

The review found that a single dose of tinidazole had a higher clinical cure rate than other therapies such as metronidazole (odds ratio [OR]=5.33; 95% confidence interval [CI], 2.66-10.67)² along with a comparable side-effect profile. These findings favor tinidazole as the treatment of choice for symptomatic giardiasis.

How effective are other drugs?

The 2006 Cochrane Review found no difference in clinical cure rate between short-term treatment (3 days) with metronidazole and longer therapy with metronidazole or other drugs. Subsequently, a single dose of metronidazole was found to be as effective as treatment for 5 days or longer (OR=0.33, 95% CI 0.08-1.34).

Since publication of the Cochrane review, several studies have further evaluated mebendazole.

• An RCT in Cuban children 5 to 15 years of age found no difference in clinical cure rate between a 5-day course of mebendazole and more traditional therapy with quinacrine.³
• Another RCT comparing 5 days of mebendazole with 7 days of metronidazole in 7- to 12-year-old Iranian children showed no statistical difference in microbiologic cure between the 2 regimens.⁴
• Single-dose tinidazole was superior to 3 doses of mebendazole in a single day in an RCT of 122 Cuban children that measured microbiologic cure (NNT=5.5 patients with tinidazole vs mebendazole).⁵

Two RCTs found nitazoxanide to be effective (number needed to treat [NNT]=1.82) compared to placebo in adolescents and adults.⁶ A 3-day course of nitazoxanide was as effective as 5 days of metronidazole (80% vs 85%, P=0.61) in resolving clinical giardiasis.⁷

An RCT of albendazole, 400 mg for 5 days, in 28 adults found it to be as effective as 500 mg metronidazole given 3 times a day for 5 days (80% vs 83%) but less likely than metronidazole (2% vs 18%) to cause anorexia (number needed to harm [NNH]=6.25).

Recommendations

The Centers for Disease Control and Prevention recommends tinidazole, metronidazole, quinacrine, albendazole, or nitazoxanide to treat giardiasis; however, it doesn’t indicate a preference for 1 medicine over another.¹ The Infectious Diseases Society of America has no guideline. The Sanford Guide to Antimicrobial Therapy recommends either a single 2-g dose of tinidazole or 500 mg of nitazoxanide PO bid for 3 days as primary treatment.⁸

Acknowledgments

The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Air Force Medical Service, nor the US Air Force.

Evidence summary

Giardia lamblia is a protozoan parasite found worldwide. Infection typically results from ingesting cysts in contaminated food or water. Patients with giardiasis may be asymptomatic or have mild to severe gastrointestinal symptoms, including explosive diarrhea, abdominal pain, steatorrhea, flatulence, bloating, nausea, and vomiting. Treatment varies widely based on geographic location, physician preference, and availability and cost of medication (TABLE).¹

TABLE 1
Drugs commonly used to treat giardiasis

Tinidazole is the treatment of choice

A 2006 Cochrane Review compared 34 trials of many drug therapies for giardiasis.² The review, which is being updated to include additional publications, evaluated both head-to-head and placebo-controlled studies, looking at dosage as well as length of drug therapy.

The review found that a single dose of tinidazole had a higher clinical cure rate than other therapies such as metronidazole (odds ratio [OR]=5.33; 95% confidence interval [CI], 2.66-10.67)² along with a comparable side-effect profile. These findings favor tinidazole as the treatment of choice for symptomatic giardiasis.

How effective are other drugs?

The 2006 Cochrane Review found no difference in clinical cure rate between short-term treatment (3 days) with metronidazole and longer therapy with metronidazole or other drugs. Subsequently, a single dose of metronidazole was found to be as effective as treatment for 5 days or longer (OR=0.33, 95% CI 0.08-1.34).

Since publication of the Cochrane review, several studies have further evaluated mebendazole.

• An RCT in Cuban children 5 to 15 years of age found no difference in clinical cure rate between a 5-day course of mebendazole and more traditional therapy with quinacrine.³
• Another RCT comparing 5 days of mebendazole with 7 days of metronidazole in 7- to 12-year-old Iranian children showed no statistical difference in microbiologic cure between the 2 regimens.⁴
• Single-dose tinidazole was superior to 3 doses of mebendazole in a single day in an RCT of 122 Cuban children that measured microbiologic cure (NNT=5.5 patients with tinidazole vs mebendazole).⁵

Two RCTs found nitazoxanide to be effective (number needed to treat [NNT]=1.82) compared to placebo in adolescents and adults.⁶ A 3-day course of nitazoxanide was as effective as 5 days of metronidazole (80% vs 85%, P=0.61) in resolving clinical giardiasis.⁷

An RCT of albendazole, 400 mg for 5 days, in 28 adults found it to be as effective as 500 mg metronidazole given 3 times a day for 5 days (80% vs 83%) but less likely than metronidazole (2% vs 18%) to cause anorexia (number needed to harm [NNH]=6.25).

Recommendations

The Centers for Disease Control and Prevention recommends tinidazole, metronidazole, quinacrine, albendazole, or nitazoxanide to treat giardiasis; however, it doesn’t indicate a preference for 1 medicine over another.¹ The Infectious Diseases Society of America has no guideline. The Sanford Guide to Antimicrobial Therapy recommends either a single 2-g dose of tinidazole or 500 mg of nitazoxanide PO bid for 3 days as primary treatment.⁸

Acknowledgments

The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Air Force Medical Service, nor the US Air Force.

Evidence summary

Giardia lamblia is a protozoan parasite found worldwide. Infection typically results from ingesting cysts in contaminated food or water. Patients with giardiasis may be asymptomatic or have mild to severe gastrointestinal symptoms, including explosive diarrhea, abdominal pain, steatorrhea, flatulence, bloating, nausea, and vomiting. Treatment varies widely based on geographic location, physician preference, and availability and cost of medication (TABLE).¹

TABLE 1
Drugs commonly used to treat giardiasis

Tinidazole is the treatment of choice

A 2006 Cochrane Review compared 34 trials of many drug therapies for giardiasis.² The review, which is being updated to include additional publications, evaluated both head-to-head and placebo-controlled studies, looking at dosage as well as length of drug therapy.

The review found that a single dose of tinidazole had a higher clinical cure rate than other therapies such as metronidazole (odds ratio [OR]=5.33; 95% confidence interval [CI], 2.66-10.67)² along with a comparable side-effect profile. These findings favor tinidazole as the treatment of choice for symptomatic giardiasis.

How effective are other drugs?

The 2006 Cochrane Review found no difference in clinical cure rate between short-term treatment (3 days) with metronidazole and longer therapy with metronidazole or other drugs. Subsequently, a single dose of metronidazole was found to be as effective as treatment for 5 days or longer (OR=0.33, 95% CI 0.08-1.34).

Since publication of the Cochrane review, several studies have further evaluated mebendazole.

• An RCT in Cuban children 5 to 15 years of age found no difference in clinical cure rate between a 5-day course of mebendazole and more traditional therapy with quinacrine.³
• Another RCT comparing 5 days of mebendazole with 7 days of metronidazole in 7- to 12-year-old Iranian children showed no statistical difference in microbiologic cure between the 2 regimens.⁴
• Single-dose tinidazole was superior to 3 doses of mebendazole in a single day in an RCT of 122 Cuban children that measured microbiologic cure (NNT=5.5 patients with tinidazole vs mebendazole).⁵

Two RCTs found nitazoxanide to be effective (number needed to treat [NNT]=1.82) compared to placebo in adolescents and adults.⁶ A 3-day course of nitazoxanide was as effective as 5 days of metronidazole (80% vs 85%, P=0.61) in resolving clinical giardiasis.⁷

An RCT of albendazole, 400 mg for 5 days, in 28 adults found it to be as effective as 500 mg metronidazole given 3 times a day for 5 days (80% vs 83%) but less likely than metronidazole (2% vs 18%) to cause anorexia (number needed to harm [NNH]=6.25).

Recommendations

The Centers for Disease Control and Prevention recommends tinidazole, metronidazole, quinacrine, albendazole, or nitazoxanide to treat giardiasis; however, it doesn’t indicate a preference for 1 medicine over another.¹ The Infectious Diseases Society of America has no guideline. The Sanford Guide to Antimicrobial Therapy recommends either a single 2-g dose of tinidazole or 500 mg of nitazoxanide PO bid for 3 days as primary treatment.⁸

Acknowledgments

The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Air Force Medical Service, nor the US Air Force.

Evidence summary

FTT is a generic term used to describe a child whose current weight (or trajectory of weight gain) does not equal that of other children of similar age, gender, and ethnicity. No single accepted anthropometric measure can be used to diagnose the condition.¹

FTT has been variously defined in children who:

• drop more than 2 standard percentile lines on standardized growth charts,²
• are below the third percentile for weight,
• have weight-for-length <80% of ideal weight,³
• have height-for-weight less than the third percentile,⁴
• have weight-for-height less than the 10th percentile, or have weight-for-age less than 2 standard deviations below the mean for age.

Recent updates of standardized growth charts for children are available from the Centers for Disease Control and Prevention at www.cdc.gov/nchs/about/major/nhanes/growthcharts/clinical_charts.htm.

A complex diagnosis

FTT occurs when nutritive intake is insufficient to meet demands for growth (TABLE). It is usually manifested by failure to gain weight. In more severe cases, height and head circumference are affected. FTT is also associated with lower developmental testing scores,⁵ persistent poor growth, increased susceptibility to infections, and an increased prevalence of behavioral disorders and neurologic disability.⁴ As many as 10% of children seen in primary-care settings show signs of FTT.²

Children with FTT are most often identified when parents raise concerns about the child’s feeding or growth patterns or when a physician notes a decrease in the child’s growth on physical examination. The terms “organic” and “inorganic” or “nonorganic” FTT, often used to guide diagnostic thinking, are outdated because most cases of FTT are influenced by many variables.⁶ FTT represents the final common pathway of disruptions in the complex system of biological, psychosocial, and environmental factors contributing to a child’s growth and development.

TABLE
Failure to thrive: Causes and physical findings

FTT has 3 basic causes

1. Inadequate caloric intake. More than 80% of children with poor growth do not have an underlying medical disorder.⁷ The initial workup, therefore, should include a thorough dietary and psychosocial history. Find out exactly what the child eats, how often he eats, and what behaviors he exhibits at mealtimes.

A detailed prenatal history (including birth weight and pregnancy complications) and medical history for both the child and parents can identify underlying metabolic, endocrine, or familial disorders. It is always important to look for signs of child abuse, because children with FTT are more likely to be victims of abuse than normal-weight peers.³ That said, other factors are responsible for poor nutritional intake in as many as 80% of cases.⁸

2. Inadequate caloric absorption (mal-absorption). This usually results from persistent emesis or malabsorption. Emesis can be caused by reflux, obstruction, medication, food sensitivities, or underlying metabolic disease. Malabsorption most often arises from chronic diarrhea, celiac disease, protein-losing enteropathy, food sensitivities, or excessive juice intake.

3. Excessive caloric expenditure. Such expenditure is associated with underlying medical conditions such as congenital heart disease, chronic hypoxia (pulmonary disease), hyperthyroidism, metabolic disease (diabetes, renal tubular acidosis), chronic immunodeficiency, recurrent infection, or malignancy.

FTT accounts for between 1% and 5% of all pediatric hospitalizations.⁹ Children who continue to exhibit poor growth despite adequate outpatient evaluation should be admitted to the hospital. Admission is also indicated if abuse is suspected.

Recommendations

The American Academy of Pediatrics recommends that physicians consider child neglect as a cause of FTT, particularly in cases that do not resolve with appropriate medical intervention.³

The American Gastroenterological Association¹⁰ and World Gastroenterology Organization¹¹ recommend that physicians consider celiac sprue in children presenting with FTT. Interestingly, the Cochrane Database of Systematic Reviews suggests that there is little systematic evidence to support routine growth monitoring in children.¹²

Evidence summary

FTT is a generic term used to describe a child whose current weight (or trajectory of weight gain) does not equal that of other children of similar age, gender, and ethnicity. No single accepted anthropometric measure can be used to diagnose the condition.¹

FTT has been variously defined in children who:

• drop more than 2 standard percentile lines on standardized growth charts,²
• are below the third percentile for weight,
• have weight-for-length <80% of ideal weight,³
• have height-for-weight less than the third percentile,⁴
• have weight-for-height less than the 10th percentile, or have weight-for-age less than 2 standard deviations below the mean for age.

Recent updates of standardized growth charts for children are available from the Centers for Disease Control and Prevention at www.cdc.gov/nchs/about/major/nhanes/growthcharts/clinical_charts.htm.

A complex diagnosis

FTT occurs when nutritive intake is insufficient to meet demands for growth (TABLE). It is usually manifested by failure to gain weight. In more severe cases, height and head circumference are affected. FTT is also associated with lower developmental testing scores,⁵ persistent poor growth, increased susceptibility to infections, and an increased prevalence of behavioral disorders and neurologic disability.⁴ As many as 10% of children seen in primary-care settings show signs of FTT.²

Children with FTT are most often identified when parents raise concerns about the child’s feeding or growth patterns or when a physician notes a decrease in the child’s growth on physical examination. The terms “organic” and “inorganic” or “nonorganic” FTT, often used to guide diagnostic thinking, are outdated because most cases of FTT are influenced by many variables.⁶ FTT represents the final common pathway of disruptions in the complex system of biological, psychosocial, and environmental factors contributing to a child’s growth and development.

TABLE
Failure to thrive: Causes and physical findings

FTT has 3 basic causes

1. Inadequate caloric intake. More than 80% of children with poor growth do not have an underlying medical disorder.⁷ The initial workup, therefore, should include a thorough dietary and psychosocial history. Find out exactly what the child eats, how often he eats, and what behaviors he exhibits at mealtimes.

A detailed prenatal history (including birth weight and pregnancy complications) and medical history for both the child and parents can identify underlying metabolic, endocrine, or familial disorders. It is always important to look for signs of child abuse, because children with FTT are more likely to be victims of abuse than normal-weight peers.³ That said, other factors are responsible for poor nutritional intake in as many as 80% of cases.⁸

2. Inadequate caloric absorption (mal-absorption). This usually results from persistent emesis or malabsorption. Emesis can be caused by reflux, obstruction, medication, food sensitivities, or underlying metabolic disease. Malabsorption most often arises from chronic diarrhea, celiac disease, protein-losing enteropathy, food sensitivities, or excessive juice intake.

3. Excessive caloric expenditure. Such expenditure is associated with underlying medical conditions such as congenital heart disease, chronic hypoxia (pulmonary disease), hyperthyroidism, metabolic disease (diabetes, renal tubular acidosis), chronic immunodeficiency, recurrent infection, or malignancy.

FTT accounts for between 1% and 5% of all pediatric hospitalizations.⁹ Children who continue to exhibit poor growth despite adequate outpatient evaluation should be admitted to the hospital. Admission is also indicated if abuse is suspected.

Recommendations

The American Academy of Pediatrics recommends that physicians consider child neglect as a cause of FTT, particularly in cases that do not resolve with appropriate medical intervention.³

The American Gastroenterological Association¹⁰ and World Gastroenterology Organization¹¹ recommend that physicians consider celiac sprue in children presenting with FTT. Interestingly, the Cochrane Database of Systematic Reviews suggests that there is little systematic evidence to support routine growth monitoring in children.¹²

Evidence summary

FTT is a generic term used to describe a child whose current weight (or trajectory of weight gain) does not equal that of other children of similar age, gender, and ethnicity. No single accepted anthropometric measure can be used to diagnose the condition.¹

FTT has been variously defined in children who:

• drop more than 2 standard percentile lines on standardized growth charts,²
• are below the third percentile for weight,
• have weight-for-length <80% of ideal weight,³
• have height-for-weight less than the third percentile,⁴
• have weight-for-height less than the 10th percentile, or have weight-for-age less than 2 standard deviations below the mean for age.

Recent updates of standardized growth charts for children are available from the Centers for Disease Control and Prevention at www.cdc.gov/nchs/about/major/nhanes/growthcharts/clinical_charts.htm.

A complex diagnosis

FTT occurs when nutritive intake is insufficient to meet demands for growth (TABLE). It is usually manifested by failure to gain weight. In more severe cases, height and head circumference are affected. FTT is also associated with lower developmental testing scores,⁵ persistent poor growth, increased susceptibility to infections, and an increased prevalence of behavioral disorders and neurologic disability.⁴ As many as 10% of children seen in primary-care settings show signs of FTT.²

Children with FTT are most often identified when parents raise concerns about the child’s feeding or growth patterns or when a physician notes a decrease in the child’s growth on physical examination. The terms “organic” and “inorganic” or “nonorganic” FTT, often used to guide diagnostic thinking, are outdated because most cases of FTT are influenced by many variables.⁶ FTT represents the final common pathway of disruptions in the complex system of biological, psychosocial, and environmental factors contributing to a child’s growth and development.

TABLE
Failure to thrive: Causes and physical findings

FTT has 3 basic causes

1. Inadequate caloric intake. More than 80% of children with poor growth do not have an underlying medical disorder.⁷ The initial workup, therefore, should include a thorough dietary and psychosocial history. Find out exactly what the child eats, how often he eats, and what behaviors he exhibits at mealtimes.

A detailed prenatal history (including birth weight and pregnancy complications) and medical history for both the child and parents can identify underlying metabolic, endocrine, or familial disorders. It is always important to look for signs of child abuse, because children with FTT are more likely to be victims of abuse than normal-weight peers.³ That said, other factors are responsible for poor nutritional intake in as many as 80% of cases.⁸

2. Inadequate caloric absorption (mal-absorption). This usually results from persistent emesis or malabsorption. Emesis can be caused by reflux, obstruction, medication, food sensitivities, or underlying metabolic disease. Malabsorption most often arises from chronic diarrhea, celiac disease, protein-losing enteropathy, food sensitivities, or excessive juice intake.

3. Excessive caloric expenditure. Such expenditure is associated with underlying medical conditions such as congenital heart disease, chronic hypoxia (pulmonary disease), hyperthyroidism, metabolic disease (diabetes, renal tubular acidosis), chronic immunodeficiency, recurrent infection, or malignancy.

FTT accounts for between 1% and 5% of all pediatric hospitalizations.⁹ Children who continue to exhibit poor growth despite adequate outpatient evaluation should be admitted to the hospital. Admission is also indicated if abuse is suspected.

Recommendations

The American Academy of Pediatrics recommends that physicians consider child neglect as a cause of FTT, particularly in cases that do not resolve with appropriate medical intervention.³

The American Gastroenterological Association¹⁰ and World Gastroenterology Organization¹¹ recommend that physicians consider celiac sprue in children presenting with FTT. Interestingly, the Cochrane Database of Systematic Reviews suggests that there is little systematic evidence to support routine growth monitoring in children.¹²