William Nichols, MLS

Evidence summary

The prevalence of hypertension is increasing. Twenty-seven percent of adult Americans are hypertensive; 31% have prehypertension (TABLE).¹ Among adults older than 50 years, the risk of developing high blood pressure approaches 90% if they live to age 80 or older.² Cardiovascular risk rises along with blood pressure readings. Blood pressure values in the range of 130/85 to 139/89 mm Hg are associated with a more than 2-fold increase in cardiovascular disease risk compared with values below 120/80 mm Hg.²

Even small reductions in blood pressure, when applied to the population as a whole, produce significant improvements in patient-oriented outcomes. A drop in systolic blood pressure of 3 mm Hg can decrease stroke mortality by 8% and coronary artery disease by 5%.²

Lifestyle interventions for treating hypertension
Lifestyle interventions for hypertensive patients include:

• Striving to maintain or achieve an ideal body weight (body mass index of 18-25).² However, even modest weight reductions in overweight and obese hypertensive patients significantly lower blood pressure and overall cardiovascular risk. A 10-kg decrease in body weight can lower systolic blood pressure by 5 to 20 mm Hg.²
• Adopting the DASH diet.¹ Consuming a diet rich in fruits, vegetables, and lowfat dairy products and limiting saturated and total fat intake can reduce systolic blood pressure by 2 to 8 mm Hg.
• Engaging in regular physical activity for at least 30 minutes most days of the week. This regimen has been shown to decrease systolic blood pressure by 4 to 9 mm Hg.²
• Limiting daily alcohol intake, if the patient drinks, to 2 servings for men and 1 for women and lower-weight individuals.² Restricting alcohol consumption may lower systolic blood pressure by 2 to 4 mm Hg.

Randomized controlled trials have consistently demonstrated that patients who combine multiple lifestyle interventions achieve the greatest benefits.^3-5 Success obviously requires patient motivation. Health care providers need to continually assess motivation and encourage adherence.

Most patients need medication, too
Lifestyle changes alone haven’t been shown to achieve the same long-term reductions in blood pressure as medication.⁵ Although some motivated patients can control their blood pressure solely by adjusting their lifestyle, few succeed in reaching and maintaining blood pressure goals. Continued attention to lifestyle should be encouraged both to control blood pressure and reduce overall cardiovascular risk, but most patients with hypertension need medication.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) doesn’t specify whether to offer a trial of therapeutic lifestyle change before starting medication.² Clinicians should negotiate interventions based on each patient’s preferences, risk factors, and the presence or absence of clinical cardiovascular disease or target organ damage. Lifestyle changes and medication both can affect quality of life. Immediate pharmacologic treatment with 2 medications has been recommended in addition to lifestyle interventions for patients with stage 2 hypertension (TABLE).²

TABLE
JNC7 classifications of blood pressure in adults

Recommendations

The European Society of Hypertension provides recommendations for the duration of lifestyle interventions before trying medication. The recommendations are based on a complex scheme of overall cardiovascular risk assessment that takes into account traditional Framingham risks and other factors (such as obesity, C-reactive protein, and micro albuminuria), as well as the stage of hypertension.⁶ The Society recommends starting drug therapy immediately in people with blood pressure >180/110 mm Hg. This blood pressure threshold drops in patients with increasing numbers of risk factors. For patients with lower, but still elevated, blood pressure, the recommendations call for “lifestyle changes for several months, then drug treatment if BP is uncontrolled.”

For patients with diabetes, the American Diabetes Association (ADA) recommends a blood pressure goal of <130/80 mm Hg and drug therapy in addition to lifestyle and behavioral therapy for patients with systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg.⁷ Like the JNC7, the ADA notes that a combination of medications is often required to achieve blood pressure targets. The ADA recommendations also state that patients with diabetes and a systolic blood pressure of 130 to 139 mm Hg or a diastolic blood pressure of 80 to 89 mm Hg should pursue lifestyle and behavioral interventions alone for a maximum of 3 months, then start drug therapy if they don’t achieve their blood pressure goals.

The American Heart Association and American College of Cardiology offer evidence-based guidelines for secondary prevention in patients with atherosclerosis.⁸ They set blood pressure goals of <140/90 mm Hg for all patients and <130/80 mm Hg for patients with diabetes or chronic kidney disease. All patients are encouraged to initiate or maintain lifestyle modifications. If a patient’s blood pressure is ≥140/90 mm Hg (>130/80 mm Hg for patients with chronic kidney disease or diabetes), medications should be titrated to goal, beginning with beta-blockers or angiotensin-converting enzyme inhibitors.

Evidence summary

The prevalence of hypertension is increasing. Twenty-seven percent of adult Americans are hypertensive; 31% have prehypertension (TABLE).¹ Among adults older than 50 years, the risk of developing high blood pressure approaches 90% if they live to age 80 or older.² Cardiovascular risk rises along with blood pressure readings. Blood pressure values in the range of 130/85 to 139/89 mm Hg are associated with a more than 2-fold increase in cardiovascular disease risk compared with values below 120/80 mm Hg.²

Even small reductions in blood pressure, when applied to the population as a whole, produce significant improvements in patient-oriented outcomes. A drop in systolic blood pressure of 3 mm Hg can decrease stroke mortality by 8% and coronary artery disease by 5%.²

Lifestyle interventions for treating hypertension
Lifestyle interventions for hypertensive patients include:

• Striving to maintain or achieve an ideal body weight (body mass index of 18-25).² However, even modest weight reductions in overweight and obese hypertensive patients significantly lower blood pressure and overall cardiovascular risk. A 10-kg decrease in body weight can lower systolic blood pressure by 5 to 20 mm Hg.²
• Adopting the DASH diet.¹ Consuming a diet rich in fruits, vegetables, and lowfat dairy products and limiting saturated and total fat intake can reduce systolic blood pressure by 2 to 8 mm Hg.
• Engaging in regular physical activity for at least 30 minutes most days of the week. This regimen has been shown to decrease systolic blood pressure by 4 to 9 mm Hg.²
• Limiting daily alcohol intake, if the patient drinks, to 2 servings for men and 1 for women and lower-weight individuals.² Restricting alcohol consumption may lower systolic blood pressure by 2 to 4 mm Hg.

Randomized controlled trials have consistently demonstrated that patients who combine multiple lifestyle interventions achieve the greatest benefits.^3-5 Success obviously requires patient motivation. Health care providers need to continually assess motivation and encourage adherence.

Most patients need medication, too
Lifestyle changes alone haven’t been shown to achieve the same long-term reductions in blood pressure as medication.⁵ Although some motivated patients can control their blood pressure solely by adjusting their lifestyle, few succeed in reaching and maintaining blood pressure goals. Continued attention to lifestyle should be encouraged both to control blood pressure and reduce overall cardiovascular risk, but most patients with hypertension need medication.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) doesn’t specify whether to offer a trial of therapeutic lifestyle change before starting medication.² Clinicians should negotiate interventions based on each patient’s preferences, risk factors, and the presence or absence of clinical cardiovascular disease or target organ damage. Lifestyle changes and medication both can affect quality of life. Immediate pharmacologic treatment with 2 medications has been recommended in addition to lifestyle interventions for patients with stage 2 hypertension (TABLE).²

TABLE
JNC7 classifications of blood pressure in adults

Recommendations

The European Society of Hypertension provides recommendations for the duration of lifestyle interventions before trying medication. The recommendations are based on a complex scheme of overall cardiovascular risk assessment that takes into account traditional Framingham risks and other factors (such as obesity, C-reactive protein, and micro albuminuria), as well as the stage of hypertension.⁶ The Society recommends starting drug therapy immediately in people with blood pressure >180/110 mm Hg. This blood pressure threshold drops in patients with increasing numbers of risk factors. For patients with lower, but still elevated, blood pressure, the recommendations call for “lifestyle changes for several months, then drug treatment if BP is uncontrolled.”

For patients with diabetes, the American Diabetes Association (ADA) recommends a blood pressure goal of <130/80 mm Hg and drug therapy in addition to lifestyle and behavioral therapy for patients with systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg.⁷ Like the JNC7, the ADA notes that a combination of medications is often required to achieve blood pressure targets. The ADA recommendations also state that patients with diabetes and a systolic blood pressure of 130 to 139 mm Hg or a diastolic blood pressure of 80 to 89 mm Hg should pursue lifestyle and behavioral interventions alone for a maximum of 3 months, then start drug therapy if they don’t achieve their blood pressure goals.

The American Heart Association and American College of Cardiology offer evidence-based guidelines for secondary prevention in patients with atherosclerosis.⁸ They set blood pressure goals of <140/90 mm Hg for all patients and <130/80 mm Hg for patients with diabetes or chronic kidney disease. All patients are encouraged to initiate or maintain lifestyle modifications. If a patient’s blood pressure is ≥140/90 mm Hg (>130/80 mm Hg for patients with chronic kidney disease or diabetes), medications should be titrated to goal, beginning with beta-blockers or angiotensin-converting enzyme inhibitors.

Evidence summary

The prevalence of hypertension is increasing. Twenty-seven percent of adult Americans are hypertensive; 31% have prehypertension (TABLE).¹ Among adults older than 50 years, the risk of developing high blood pressure approaches 90% if they live to age 80 or older.² Cardiovascular risk rises along with blood pressure readings. Blood pressure values in the range of 130/85 to 139/89 mm Hg are associated with a more than 2-fold increase in cardiovascular disease risk compared with values below 120/80 mm Hg.²

Even small reductions in blood pressure, when applied to the population as a whole, produce significant improvements in patient-oriented outcomes. A drop in systolic blood pressure of 3 mm Hg can decrease stroke mortality by 8% and coronary artery disease by 5%.²

Lifestyle interventions for treating hypertension
Lifestyle interventions for hypertensive patients include:

• Striving to maintain or achieve an ideal body weight (body mass index of 18-25).² However, even modest weight reductions in overweight and obese hypertensive patients significantly lower blood pressure and overall cardiovascular risk. A 10-kg decrease in body weight can lower systolic blood pressure by 5 to 20 mm Hg.²
• Adopting the DASH diet.¹ Consuming a diet rich in fruits, vegetables, and lowfat dairy products and limiting saturated and total fat intake can reduce systolic blood pressure by 2 to 8 mm Hg.
• Engaging in regular physical activity for at least 30 minutes most days of the week. This regimen has been shown to decrease systolic blood pressure by 4 to 9 mm Hg.²
• Limiting daily alcohol intake, if the patient drinks, to 2 servings for men and 1 for women and lower-weight individuals.² Restricting alcohol consumption may lower systolic blood pressure by 2 to 4 mm Hg.

Randomized controlled trials have consistently demonstrated that patients who combine multiple lifestyle interventions achieve the greatest benefits.^3-5 Success obviously requires patient motivation. Health care providers need to continually assess motivation and encourage adherence.

Most patients need medication, too
Lifestyle changes alone haven’t been shown to achieve the same long-term reductions in blood pressure as medication.⁵ Although some motivated patients can control their blood pressure solely by adjusting their lifestyle, few succeed in reaching and maintaining blood pressure goals. Continued attention to lifestyle should be encouraged both to control blood pressure and reduce overall cardiovascular risk, but most patients with hypertension need medication.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) doesn’t specify whether to offer a trial of therapeutic lifestyle change before starting medication.² Clinicians should negotiate interventions based on each patient’s preferences, risk factors, and the presence or absence of clinical cardiovascular disease or target organ damage. Lifestyle changes and medication both can affect quality of life. Immediate pharmacologic treatment with 2 medications has been recommended in addition to lifestyle interventions for patients with stage 2 hypertension (TABLE).²

TABLE
JNC7 classifications of blood pressure in adults

Recommendations

The European Society of Hypertension provides recommendations for the duration of lifestyle interventions before trying medication. The recommendations are based on a complex scheme of overall cardiovascular risk assessment that takes into account traditional Framingham risks and other factors (such as obesity, C-reactive protein, and micro albuminuria), as well as the stage of hypertension.⁶ The Society recommends starting drug therapy immediately in people with blood pressure >180/110 mm Hg. This blood pressure threshold drops in patients with increasing numbers of risk factors. For patients with lower, but still elevated, blood pressure, the recommendations call for “lifestyle changes for several months, then drug treatment if BP is uncontrolled.”

For patients with diabetes, the American Diabetes Association (ADA) recommends a blood pressure goal of <130/80 mm Hg and drug therapy in addition to lifestyle and behavioral therapy for patients with systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg.⁷ Like the JNC7, the ADA notes that a combination of medications is often required to achieve blood pressure targets. The ADA recommendations also state that patients with diabetes and a systolic blood pressure of 130 to 139 mm Hg or a diastolic blood pressure of 80 to 89 mm Hg should pursue lifestyle and behavioral interventions alone for a maximum of 3 months, then start drug therapy if they don’t achieve their blood pressure goals.

The American Heart Association and American College of Cardiology offer evidence-based guidelines for secondary prevention in patients with atherosclerosis.⁸ They set blood pressure goals of <140/90 mm Hg for all patients and <130/80 mm Hg for patients with diabetes or chronic kidney disease. All patients are encouraged to initiate or maintain lifestyle modifications. If a patient’s blood pressure is ≥140/90 mm Hg (>130/80 mm Hg for patients with chronic kidney disease or diabetes), medications should be titrated to goal, beginning with beta-blockers or angiotensin-converting enzyme inhibitors.

Evidence summary

A comprehensive review of the literature revealed no studies that compare heat and cryotherapy to treat acute soft-tissue injury. Well-designed human trials of general management of acute soft-tissue injury are rare.¹

Cryotherapy has been the recommended initial treatment for muscle strain for more than 30 years, based generally on expert opinion and physiological models, not clinical trials.² Theoretically, cryotherapy controls hemorrhage and tissue edema, whereas heat enhances the inflammatory response.²

One human RCT and animal studies find benefits from cold

A 2007 review evaluated 66 publications and found only 1 randomized controlled trial conducted on humans.³ The intervention in this trial involved applying cold gel 4 times a day for the first 14 days after the injury. The control group received a room-temperature gel application; neither group was aware of the temperature differential.

The study found significant reduction in pain at rest, pain with movement, and functional disability at intervals of 7, 14, and 28 days postinjury (P<.001) among patients receiving cold-gel applications. Patients receiving cold-gel treatment also reported increased satisfaction with treatment compared with the controls. At 28 days, cold-gel treatment patients scored 71 on a 100-point satisfaction scale compared with 44 for controls (P<.001).³ Inconclusive results or significant design flaws limited the validity of all other trials cited in this review.³

Laboratory studies on rats have also demonstrated beneficial effects of cryotherapy after simulated soft-tissue injuries.^4,5 One study cited a significant reduction in inflammatory cells, based on histologic examination, in 43 rats between 6 and 24 hours after trauma.⁴ A second study of 21 rats showed improvement in associated physiological components with cryotherapy, but no statistically significant improvement in edema.⁵

How cold is too cold?

Most authorities recommend empiric treatment with cryotherapy during the acute inflammatory phase—the first 24 to 48 hours after injury.⁶ Although not rigorously studied, some sources recommend applying cold to the involved muscle for the first 4 hours after injury at intervals of 10 to 20 minutes every 30 to 60 minutes.⁶

The literature focuses more on the optimal temperature for cryotherapy than on the duration and frequency of therapy.⁷ Temperatures below 15°to 25°C may actually result in vasodilatation rather than vasoconstriction.⁷

Evidence for heat is limited

A 2006 Cochrane review that addressed treatment of lower back muscular strain, not soft-tissue injuries in general, found moderate evidence that heat therapy reduces pain by 17% and disability in the acute setting (P=.001).⁸ The review also cited 2 head-to-head trials that compared heat and cryotherapy; however, the study designs were poor and the results were contradictory.⁸

Recommendations

Authoritative textbooks consistently recommend applying ice for initial treatment of musculoskeletal and soft-tissue strains.⁹

Acknowledgments

The opinions and assertions contained herein are the private views of the authors and not to be construed as official or as reflecting the views of the United States Air Force Medical Service or the United States Air Force at large.

Evidence summary

A comprehensive review of the literature revealed no studies that compare heat and cryotherapy to treat acute soft-tissue injury. Well-designed human trials of general management of acute soft-tissue injury are rare.¹

Cryotherapy has been the recommended initial treatment for muscle strain for more than 30 years, based generally on expert opinion and physiological models, not clinical trials.² Theoretically, cryotherapy controls hemorrhage and tissue edema, whereas heat enhances the inflammatory response.²

One human RCT and animal studies find benefits from cold

A 2007 review evaluated 66 publications and found only 1 randomized controlled trial conducted on humans.³ The intervention in this trial involved applying cold gel 4 times a day for the first 14 days after the injury. The control group received a room-temperature gel application; neither group was aware of the temperature differential.

The study found significant reduction in pain at rest, pain with movement, and functional disability at intervals of 7, 14, and 28 days postinjury (P<.001) among patients receiving cold-gel applications. Patients receiving cold-gel treatment also reported increased satisfaction with treatment compared with the controls. At 28 days, cold-gel treatment patients scored 71 on a 100-point satisfaction scale compared with 44 for controls (P<.001).³ Inconclusive results or significant design flaws limited the validity of all other trials cited in this review.³

Laboratory studies on rats have also demonstrated beneficial effects of cryotherapy after simulated soft-tissue injuries.^4,5 One study cited a significant reduction in inflammatory cells, based on histologic examination, in 43 rats between 6 and 24 hours after trauma.⁴ A second study of 21 rats showed improvement in associated physiological components with cryotherapy, but no statistically significant improvement in edema.⁵

How cold is too cold?

Most authorities recommend empiric treatment with cryotherapy during the acute inflammatory phase—the first 24 to 48 hours after injury.⁶ Although not rigorously studied, some sources recommend applying cold to the involved muscle for the first 4 hours after injury at intervals of 10 to 20 minutes every 30 to 60 minutes.⁶

The literature focuses more on the optimal temperature for cryotherapy than on the duration and frequency of therapy.⁷ Temperatures below 15°to 25°C may actually result in vasodilatation rather than vasoconstriction.⁷

Evidence for heat is limited

A 2006 Cochrane review that addressed treatment of lower back muscular strain, not soft-tissue injuries in general, found moderate evidence that heat therapy reduces pain by 17% and disability in the acute setting (P=.001).⁸ The review also cited 2 head-to-head trials that compared heat and cryotherapy; however, the study designs were poor and the results were contradictory.⁸

Recommendations

Authoritative textbooks consistently recommend applying ice for initial treatment of musculoskeletal and soft-tissue strains.⁹

Acknowledgments

The opinions and assertions contained herein are the private views of the authors and not to be construed as official or as reflecting the views of the United States Air Force Medical Service or the United States Air Force at large.

Evidence summary

A comprehensive review of the literature revealed no studies that compare heat and cryotherapy to treat acute soft-tissue injury. Well-designed human trials of general management of acute soft-tissue injury are rare.¹

Cryotherapy has been the recommended initial treatment for muscle strain for more than 30 years, based generally on expert opinion and physiological models, not clinical trials.² Theoretically, cryotherapy controls hemorrhage and tissue edema, whereas heat enhances the inflammatory response.²

One human RCT and animal studies find benefits from cold

A 2007 review evaluated 66 publications and found only 1 randomized controlled trial conducted on humans.³ The intervention in this trial involved applying cold gel 4 times a day for the first 14 days after the injury. The control group received a room-temperature gel application; neither group was aware of the temperature differential.

The study found significant reduction in pain at rest, pain with movement, and functional disability at intervals of 7, 14, and 28 days postinjury (P<.001) among patients receiving cold-gel applications. Patients receiving cold-gel treatment also reported increased satisfaction with treatment compared with the controls. At 28 days, cold-gel treatment patients scored 71 on a 100-point satisfaction scale compared with 44 for controls (P<.001).³ Inconclusive results or significant design flaws limited the validity of all other trials cited in this review.³

Laboratory studies on rats have also demonstrated beneficial effects of cryotherapy after simulated soft-tissue injuries.^4,5 One study cited a significant reduction in inflammatory cells, based on histologic examination, in 43 rats between 6 and 24 hours after trauma.⁴ A second study of 21 rats showed improvement in associated physiological components with cryotherapy, but no statistically significant improvement in edema.⁵

How cold is too cold?

Most authorities recommend empiric treatment with cryotherapy during the acute inflammatory phase—the first 24 to 48 hours after injury.⁶ Although not rigorously studied, some sources recommend applying cold to the involved muscle for the first 4 hours after injury at intervals of 10 to 20 minutes every 30 to 60 minutes.⁶

The literature focuses more on the optimal temperature for cryotherapy than on the duration and frequency of therapy.⁷ Temperatures below 15°to 25°C may actually result in vasodilatation rather than vasoconstriction.⁷

Evidence for heat is limited

A 2006 Cochrane review that addressed treatment of lower back muscular strain, not soft-tissue injuries in general, found moderate evidence that heat therapy reduces pain by 17% and disability in the acute setting (P=.001).⁸ The review also cited 2 head-to-head trials that compared heat and cryotherapy; however, the study designs were poor and the results were contradictory.⁸

Recommendations

Authoritative textbooks consistently recommend applying ice for initial treatment of musculoskeletal and soft-tissue strains.⁹

Acknowledgments

The opinions and assertions contained herein are the private views of the authors and not to be construed as official or as reflecting the views of the United States Air Force Medical Service or the United States Air Force at large.

Evidence summary

Rhabdomyolysis is a well-described clinical syndrome resulting from injury to skeletal muscle and subsequent release of cellular contents into the extracellular fluid and circulation. It can lead to many complications, including renal failure, disseminated intravascular coagulation, and even death in 5% of cases.² The leading causes of rhabdomyolysis include trauma, soft tissue compression, alcohol, drugs, infections, seizures, and exercise.³

Only half of patients experience muscle pain.² Elevations occur in multiple serum markers, including CK, myoglobin, aldolase, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase, in either plasma or urine.^4,5

Variable elevations, ranging from mild to extreme, that are discovered incidentally after exercise may cause clinical uncertainty.

No clear consensus defines CK levels in rhabdomyolysis

CK is the primary serum marker for rhabdomyolysis. It’s highly sensitive, but not specific. No clear consensus exists on what threshold of CK elevation correlates with clinically relevant disease.⁶ A relationship between CK elevation and the severity of disease has been established (>6000 IU/L predicts renal failure), but patients can have significant morbidity with only moderately elevated CK levels.^7,8 Normal reference ranges for serum CK are 55 to 170 IU/L for males, and 30 to 135 IU/L for females.⁹

Recent definitions of rhabdomyolysis have been established to address muscle toxicity from lipid-lowering medications. The United States Food and Drug Administration specifies a CK level of more than 50 times the upper limit of normal (ULN)—or 10,000 IU/L—accompanied by organ damage, usually renal compromise.⁶ The National Lipid Association’s Muscle Safety Expert Panel has defined rhabdomyolysis as any evidence of muscle cell destruction regardless of the CK level and a causal relationship to a change in renal function. The panel further subdivides CK elevations into categories of mild (<10 times ULN), moderate (10-49 times ULN), and marked (≥50 times ULN).⁶

Exercise elevates CK level, but consider other factors, too

Although exercise is known to elevate CK, it produces a wide range of levels, based on a host of variables.^3,10 Increases in CK are more pronounced in males, blacks, and untrained people; age doesn’t seem to be a factor.^10,11 Higher-intensity, longer-duration, and weight-bearing exercise (eccentric muscular contractions and downhill running) cause the greatest rises in CK.¹⁰ Other influences include temperature, altitude, gravitational forces, noise, and vibration.

No studies firmly establish a normal range of CK elevation from moderate exercise; better data are available for extreme athletes, such as long-distance runners and triathletes. One study found that mean total CK elevations 24 hours after a marathon were 3322 IU/L (22.3 times baseline) for men and 946 IU/L (8.6 times baseline) for women.⁴ Another study showed that triathletes had a 12-fold mean increase in CK levels as long as 24 hours after the race.¹²

Eccentric exercises significantly raise CK

Exercise programs that include eccentric muscle contractions can result in significant serum CK elevations. One study followed 203 participants to evaluate the magnitude of CK elevation and the effect on renal function produced by exercise.³ After performing 50 maximal eccentric elbow flexor contractions, 55% of participants had CK elevations >2000 IU/L at 4 days after exercise; 25% had CK elevations >10,000 IU/L; 13% had levels >20,000 IU/L. None showed any evidence of renal compromise on clinical follow-up. Another study found significant increases in CK (approximate mean of 15,000 IU/L) after repetitive eccentric elbow flexor contractions in college-age males.¹³

Eccentric weight lifting and similar activities, like downhill running, may result in an increase in serum CK levels of 10 to 20 times normal, whereas other nonweight-bearing exercises and exercise involving no or minimal eccentric contractions, such as swimming and cycling, cause only nominal increases in serum CK.¹⁰

Recommendations

No formal guidelines from authoritative sources are available.

Acknowledgments

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

Evidence summary

Rhabdomyolysis is a well-described clinical syndrome resulting from injury to skeletal muscle and subsequent release of cellular contents into the extracellular fluid and circulation. It can lead to many complications, including renal failure, disseminated intravascular coagulation, and even death in 5% of cases.² The leading causes of rhabdomyolysis include trauma, soft tissue compression, alcohol, drugs, infections, seizures, and exercise.³

Only half of patients experience muscle pain.² Elevations occur in multiple serum markers, including CK, myoglobin, aldolase, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase, in either plasma or urine.^4,5

Variable elevations, ranging from mild to extreme, that are discovered incidentally after exercise may cause clinical uncertainty.

No clear consensus defines CK levels in rhabdomyolysis

CK is the primary serum marker for rhabdomyolysis. It’s highly sensitive, but not specific. No clear consensus exists on what threshold of CK elevation correlates with clinically relevant disease.⁶ A relationship between CK elevation and the severity of disease has been established (>6000 IU/L predicts renal failure), but patients can have significant morbidity with only moderately elevated CK levels.^7,8 Normal reference ranges for serum CK are 55 to 170 IU/L for males, and 30 to 135 IU/L for females.⁹

Recent definitions of rhabdomyolysis have been established to address muscle toxicity from lipid-lowering medications. The United States Food and Drug Administration specifies a CK level of more than 50 times the upper limit of normal (ULN)—or 10,000 IU/L—accompanied by organ damage, usually renal compromise.⁶ The National Lipid Association’s Muscle Safety Expert Panel has defined rhabdomyolysis as any evidence of muscle cell destruction regardless of the CK level and a causal relationship to a change in renal function. The panel further subdivides CK elevations into categories of mild (<10 times ULN), moderate (10-49 times ULN), and marked (≥50 times ULN).⁶

Exercise elevates CK level, but consider other factors, too

Although exercise is known to elevate CK, it produces a wide range of levels, based on a host of variables.^3,10 Increases in CK are more pronounced in males, blacks, and untrained people; age doesn’t seem to be a factor.^10,11 Higher-intensity, longer-duration, and weight-bearing exercise (eccentric muscular contractions and downhill running) cause the greatest rises in CK.¹⁰ Other influences include temperature, altitude, gravitational forces, noise, and vibration.

No studies firmly establish a normal range of CK elevation from moderate exercise; better data are available for extreme athletes, such as long-distance runners and triathletes. One study found that mean total CK elevations 24 hours after a marathon were 3322 IU/L (22.3 times baseline) for men and 946 IU/L (8.6 times baseline) for women.⁴ Another study showed that triathletes had a 12-fold mean increase in CK levels as long as 24 hours after the race.¹²

Eccentric exercises significantly raise CK

Exercise programs that include eccentric muscle contractions can result in significant serum CK elevations. One study followed 203 participants to evaluate the magnitude of CK elevation and the effect on renal function produced by exercise.³ After performing 50 maximal eccentric elbow flexor contractions, 55% of participants had CK elevations >2000 IU/L at 4 days after exercise; 25% had CK elevations >10,000 IU/L; 13% had levels >20,000 IU/L. None showed any evidence of renal compromise on clinical follow-up. Another study found significant increases in CK (approximate mean of 15,000 IU/L) after repetitive eccentric elbow flexor contractions in college-age males.¹³

Eccentric weight lifting and similar activities, like downhill running, may result in an increase in serum CK levels of 10 to 20 times normal, whereas other nonweight-bearing exercises and exercise involving no or minimal eccentric contractions, such as swimming and cycling, cause only nominal increases in serum CK.¹⁰

Recommendations

No formal guidelines from authoritative sources are available.

Acknowledgments

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

Evidence summary

Rhabdomyolysis is a well-described clinical syndrome resulting from injury to skeletal muscle and subsequent release of cellular contents into the extracellular fluid and circulation. It can lead to many complications, including renal failure, disseminated intravascular coagulation, and even death in 5% of cases.² The leading causes of rhabdomyolysis include trauma, soft tissue compression, alcohol, drugs, infections, seizures, and exercise.³

Only half of patients experience muscle pain.² Elevations occur in multiple serum markers, including CK, myoglobin, aldolase, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase, in either plasma or urine.^4,5

Variable elevations, ranging from mild to extreme, that are discovered incidentally after exercise may cause clinical uncertainty.

No clear consensus defines CK levels in rhabdomyolysis

CK is the primary serum marker for rhabdomyolysis. It’s highly sensitive, but not specific. No clear consensus exists on what threshold of CK elevation correlates with clinically relevant disease.⁶ A relationship between CK elevation and the severity of disease has been established (>6000 IU/L predicts renal failure), but patients can have significant morbidity with only moderately elevated CK levels.^7,8 Normal reference ranges for serum CK are 55 to 170 IU/L for males, and 30 to 135 IU/L for females.⁹

Recent definitions of rhabdomyolysis have been established to address muscle toxicity from lipid-lowering medications. The United States Food and Drug Administration specifies a CK level of more than 50 times the upper limit of normal (ULN)—or 10,000 IU/L—accompanied by organ damage, usually renal compromise.⁶ The National Lipid Association’s Muscle Safety Expert Panel has defined rhabdomyolysis as any evidence of muscle cell destruction regardless of the CK level and a causal relationship to a change in renal function. The panel further subdivides CK elevations into categories of mild (<10 times ULN), moderate (10-49 times ULN), and marked (≥50 times ULN).⁶

Exercise elevates CK level, but consider other factors, too

Although exercise is known to elevate CK, it produces a wide range of levels, based on a host of variables.^3,10 Increases in CK are more pronounced in males, blacks, and untrained people; age doesn’t seem to be a factor.^10,11 Higher-intensity, longer-duration, and weight-bearing exercise (eccentric muscular contractions and downhill running) cause the greatest rises in CK.¹⁰ Other influences include temperature, altitude, gravitational forces, noise, and vibration.

No studies firmly establish a normal range of CK elevation from moderate exercise; better data are available for extreme athletes, such as long-distance runners and triathletes. One study found that mean total CK elevations 24 hours after a marathon were 3322 IU/L (22.3 times baseline) for men and 946 IU/L (8.6 times baseline) for women.⁴ Another study showed that triathletes had a 12-fold mean increase in CK levels as long as 24 hours after the race.¹²

Eccentric exercises significantly raise CK

Exercise programs that include eccentric muscle contractions can result in significant serum CK elevations. One study followed 203 participants to evaluate the magnitude of CK elevation and the effect on renal function produced by exercise.³ After performing 50 maximal eccentric elbow flexor contractions, 55% of participants had CK elevations >2000 IU/L at 4 days after exercise; 25% had CK elevations >10,000 IU/L; 13% had levels >20,000 IU/L. None showed any evidence of renal compromise on clinical follow-up. Another study found significant increases in CK (approximate mean of 15,000 IU/L) after repetitive eccentric elbow flexor contractions in college-age males.¹³

Eccentric weight lifting and similar activities, like downhill running, may result in an increase in serum CK levels of 10 to 20 times normal, whereas other nonweight-bearing exercises and exercise involving no or minimal eccentric contractions, such as swimming and cycling, cause only nominal increases in serum CK.¹⁰

Recommendations

No formal guidelines from authoritative sources are available.

Acknowledgments

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

Evidence summary

Breast augmentation is one of the most popular plastic surgeries in the United States; an estimated 291,350 such procedures were performed in 2005.¹ Breast cancer occurs in 1 of every 8 women; a projected 32,000 women who received breast implants in 2003 will develop cancer.¹ Available research has focused on retrospective and prospective designs because of the ethical limitations of experimental designs. No US studies directly compare mammography with alternate screening methods, such as sonography or magnetic resonance imaging.

With implants: Lower screening sensitivity but similar prognosis

Studies show that augmentation decreases the sensitivity of screening mammography but doesn’t affect breast cancer prognosis.² A 2004 prospective cohort study of 986,270 women found that, among asymptomatic women diagnosed with breast cancer (40 augmented, 238 nonaugmented), the sensitivity of screening mammograms was lower in women with breast implants (45%; 95% confidence interval [CI], 29.3%–61.5%) than those without (66.8%; 95% CI, 60.4%–72.8%); P=.008).² Similarly, in symptomatic women diagnosed with breast cancer (41 augmented, 145 nonaugmented), screening sensitivity was lower in the augmented women (73.2%) than the nonaugmented women (81.4%)—although the results weren’t significant (P=.25).

Despite lower screening sensitivity, breast tumors in asymptomatic women, whether augmented or not, had similar characteristics, except for larger tumor size (3 mm) at diagnosis in augmented women. Symptomatic women with breast implants had cancers that were smaller, lower-grade, and more likely to be estrogen receptor dependent and invasive (P=.052) compared with nonaugmented women. The authors concluded that augmentation doesn’t influence the prognostic characteristics of tumors, and they recommended screening mammography at appropriate intervals.

Two other prospective cohort studies produced similar findings. A 2006 study of 4082 breast cancer patients concluded that mammography yielded a false-negative rate of 41.4% in augmented patients compared with 8.8% in nonaugmented patients (P<.0001).³ However, both augmented (n=129) and nonaugmented (n=3953) women had a comparable prognosis at diagnosis. The authors of the studies suggested diagnostic mammography for augmented patients and correlation with physical exam findings.

An earlier study of 2956 cancer patients found that mammography detected an abnormal breast mass in 66.3% of augmented women compared with 94.6% of nonaugmented women (P=.001).⁴ No significant differences were noted in cancer characteristics at diagnosis or survival rates (P=.78). The authors of this study concluded that mammography should be used for augmented women until a more effective screening tool is found.

Sonography vs mammography: The jury is still out

Although studies comparing screening methods have not been performed in the United States, a small Taiwanese study directly compared ultrasound to mammography in 105 women without breast implants. This retrospective cohort study found sonography to be a more useful diagnostic tool than mammography in Taiwanese women.⁵ Sonography had the highest sensitivity (87.5%) compared to physical examination (50.0%) and mammography (25.5%).

Sonography was recommended as the imaging tool for Asian women with smaller, denser breasts. However, it is unclear whether this result applies to US women or women who have undergone breast augmentation surgery.

Training in implant imaging is needed

Mammography appears to be the most effective screening method for women with breast implants. Despite the small differences in cancer characteristics at diagnosis between augmented and nonaugmented women, overall prognosis and survival rates are no different.^1-3,6 This is true whether a screening mammogram or diagnostic mammogram is used. In any case, all available findings suggest that clinicians who perform mammography should be trained in imaging the augmented breast.^6-8

Recommendations

The National Cancer Institute indicates that the best screening method for augmented women is mammography performed at a facility with employees trained in implant imaging.⁷ The American College of Radiology’s practice guidelines affirm that mammography is the best imaging tool available.⁸ The American College of Obstetrics and Gynecology and the US Preventive Services Task Force don’t comment on screening augmented women.

Acknowledgments

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

Evidence summary

Breast augmentation is one of the most popular plastic surgeries in the United States; an estimated 291,350 such procedures were performed in 2005.¹ Breast cancer occurs in 1 of every 8 women; a projected 32,000 women who received breast implants in 2003 will develop cancer.¹ Available research has focused on retrospective and prospective designs because of the ethical limitations of experimental designs. No US studies directly compare mammography with alternate screening methods, such as sonography or magnetic resonance imaging.

With implants: Lower screening sensitivity but similar prognosis

Studies show that augmentation decreases the sensitivity of screening mammography but doesn’t affect breast cancer prognosis.² A 2004 prospective cohort study of 986,270 women found that, among asymptomatic women diagnosed with breast cancer (40 augmented, 238 nonaugmented), the sensitivity of screening mammograms was lower in women with breast implants (45%; 95% confidence interval [CI], 29.3%–61.5%) than those without (66.8%; 95% CI, 60.4%–72.8%); P=.008).² Similarly, in symptomatic women diagnosed with breast cancer (41 augmented, 145 nonaugmented), screening sensitivity was lower in the augmented women (73.2%) than the nonaugmented women (81.4%)—although the results weren’t significant (P=.25).

Despite lower screening sensitivity, breast tumors in asymptomatic women, whether augmented or not, had similar characteristics, except for larger tumor size (3 mm) at diagnosis in augmented women. Symptomatic women with breast implants had cancers that were smaller, lower-grade, and more likely to be estrogen receptor dependent and invasive (P=.052) compared with nonaugmented women. The authors concluded that augmentation doesn’t influence the prognostic characteristics of tumors, and they recommended screening mammography at appropriate intervals.

Two other prospective cohort studies produced similar findings. A 2006 study of 4082 breast cancer patients concluded that mammography yielded a false-negative rate of 41.4% in augmented patients compared with 8.8% in nonaugmented patients (P<.0001).³ However, both augmented (n=129) and nonaugmented (n=3953) women had a comparable prognosis at diagnosis. The authors of the studies suggested diagnostic mammography for augmented patients and correlation with physical exam findings.

An earlier study of 2956 cancer patients found that mammography detected an abnormal breast mass in 66.3% of augmented women compared with 94.6% of nonaugmented women (P=.001).⁴ No significant differences were noted in cancer characteristics at diagnosis or survival rates (P=.78). The authors of this study concluded that mammography should be used for augmented women until a more effective screening tool is found.

Sonography vs mammography: The jury is still out

Although studies comparing screening methods have not been performed in the United States, a small Taiwanese study directly compared ultrasound to mammography in 105 women without breast implants. This retrospective cohort study found sonography to be a more useful diagnostic tool than mammography in Taiwanese women.⁵ Sonography had the highest sensitivity (87.5%) compared to physical examination (50.0%) and mammography (25.5%).

Sonography was recommended as the imaging tool for Asian women with smaller, denser breasts. However, it is unclear whether this result applies to US women or women who have undergone breast augmentation surgery.

Training in implant imaging is needed

Mammography appears to be the most effective screening method for women with breast implants. Despite the small differences in cancer characteristics at diagnosis between augmented and nonaugmented women, overall prognosis and survival rates are no different.^1-3,6 This is true whether a screening mammogram or diagnostic mammogram is used. In any case, all available findings suggest that clinicians who perform mammography should be trained in imaging the augmented breast.^6-8

Recommendations

The National Cancer Institute indicates that the best screening method for augmented women is mammography performed at a facility with employees trained in implant imaging.⁷ The American College of Radiology’s practice guidelines affirm that mammography is the best imaging tool available.⁸ The American College of Obstetrics and Gynecology and the US Preventive Services Task Force don’t comment on screening augmented women.

Acknowledgments

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

Evidence summary

Breast augmentation is one of the most popular plastic surgeries in the United States; an estimated 291,350 such procedures were performed in 2005.¹ Breast cancer occurs in 1 of every 8 women; a projected 32,000 women who received breast implants in 2003 will develop cancer.¹ Available research has focused on retrospective and prospective designs because of the ethical limitations of experimental designs. No US studies directly compare mammography with alternate screening methods, such as sonography or magnetic resonance imaging.

With implants: Lower screening sensitivity but similar prognosis

Studies show that augmentation decreases the sensitivity of screening mammography but doesn’t affect breast cancer prognosis.² A 2004 prospective cohort study of 986,270 women found that, among asymptomatic women diagnosed with breast cancer (40 augmented, 238 nonaugmented), the sensitivity of screening mammograms was lower in women with breast implants (45%; 95% confidence interval [CI], 29.3%–61.5%) than those without (66.8%; 95% CI, 60.4%–72.8%); P=.008).² Similarly, in symptomatic women diagnosed with breast cancer (41 augmented, 145 nonaugmented), screening sensitivity was lower in the augmented women (73.2%) than the nonaugmented women (81.4%)—although the results weren’t significant (P=.25).

Despite lower screening sensitivity, breast tumors in asymptomatic women, whether augmented or not, had similar characteristics, except for larger tumor size (3 mm) at diagnosis in augmented women. Symptomatic women with breast implants had cancers that were smaller, lower-grade, and more likely to be estrogen receptor dependent and invasive (P=.052) compared with nonaugmented women. The authors concluded that augmentation doesn’t influence the prognostic characteristics of tumors, and they recommended screening mammography at appropriate intervals.

Two other prospective cohort studies produced similar findings. A 2006 study of 4082 breast cancer patients concluded that mammography yielded a false-negative rate of 41.4% in augmented patients compared with 8.8% in nonaugmented patients (P<.0001).³ However, both augmented (n=129) and nonaugmented (n=3953) women had a comparable prognosis at diagnosis. The authors of the studies suggested diagnostic mammography for augmented patients and correlation with physical exam findings.

An earlier study of 2956 cancer patients found that mammography detected an abnormal breast mass in 66.3% of augmented women compared with 94.6% of nonaugmented women (P=.001).⁴ No significant differences were noted in cancer characteristics at diagnosis or survival rates (P=.78). The authors of this study concluded that mammography should be used for augmented women until a more effective screening tool is found.

Sonography vs mammography: The jury is still out

Although studies comparing screening methods have not been performed in the United States, a small Taiwanese study directly compared ultrasound to mammography in 105 women without breast implants. This retrospective cohort study found sonography to be a more useful diagnostic tool than mammography in Taiwanese women.⁵ Sonography had the highest sensitivity (87.5%) compared to physical examination (50.0%) and mammography (25.5%).

Sonography was recommended as the imaging tool for Asian women with smaller, denser breasts. However, it is unclear whether this result applies to US women or women who have undergone breast augmentation surgery.

Training in implant imaging is needed

Mammography appears to be the most effective screening method for women with breast implants. Despite the small differences in cancer characteristics at diagnosis between augmented and nonaugmented women, overall prognosis and survival rates are no different.^1-3,6 This is true whether a screening mammogram or diagnostic mammogram is used. In any case, all available findings suggest that clinicians who perform mammography should be trained in imaging the augmented breast.^6-8

Recommendations

The National Cancer Institute indicates that the best screening method for augmented women is mammography performed at a facility with employees trained in implant imaging.⁷ The American College of Radiology’s practice guidelines affirm that mammography is the best imaging tool available.⁸ The American College of Obstetrics and Gynecology and the US Preventive Services Task Force don’t comment on screening augmented women.

Acknowledgments

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

Evidence summary

The number of children 2 years and older who are overweight has tripled in the past 2 decades; the current prevalence of over-weight children and adolescents in the US is 15%.¹ By contrast with adults—in whom overweight and obesity are defined separately as a body mass index (BMI) above 25 kg/m² and 30 kg/m², respectively—overweight and obesity are synonymous in children and are defined as a BMI above the 95th percentile for age and sex.² Children and adolescents with a BMI between the 85th and 95th percentiles are considered at risk for overweight.²

Overweight children are vulnerable to adverse health outcomes, including insulin resistance, hyperlipidemia, hypertension, depression, sleep apnea, asthma, steatohepatitis, genu varum, and slipped capital femoral epiphysis.² The many variables that have been suggested to influence childhood obesity include birth weight, gestational age, parental obesity, socioeconomic status, single parent household, and birth order.^3-5

Birth weight and later BMI: Consistently linked

A systematic review of 19 longitudinal, observational studies comparing birth weight with later BMI indicates that the association between the 2 is positive and consistent in multiple cohorts.³ Eleven studies focused on outcomes in childhood; another 8 measured outcomes into adulthood.

Fifteen of the 19 studies (79%), ranging in size from 1028 to 92,940 subjects, found a positive association between birth weight and later BMI. However, the data were too heterogeneous to combine into a single summary measure. One representative study quantified the relative risk (RR) for severe obesity (>95th percentile BMI) at 5 years of age as 1.7 (95% confidence interval [CI], 1.2-2.9) for birth weights between the 85th and 94th percentiles and 1.8 (95% CI, 1.1-2.9) for birth weights greater than the 95th percentile.³ Studies that didn’t find such an association had smaller sample sizes (137 to 432 subjects) and, therefore, may have lacked the power to detect an association.

Gestational diabetes. A subsequent retrospective cohort survey of 14,881 children born to mothers with gestational diabetes—and controlled for age, sex, and Tanner stage—found that the odds ratio (OR) for adolescent overweight was 1.4 (95% CI, 1.2-1.6) for each 1-kg increment in birth weight.⁴ The correlation persisted (OR=1.3; 95% CI, 1.1-1.5) when other covariates were controlled (television viewing, physical activity, energy intake, breastfeeding duration, birth order, household income, mother’s smoking, dietary restraint, and mother’s current BMI).

Large for gestational age. A US national cohort study of 3192 children adjusted for gestational age, found that large-for-gestational-age (LGA) infants with birth weights above the 90th percentile remained longer and heavier through 83 months of life.⁵ The triceps and subscapular skinfold measurements at 3 years of age for children born LGA were virtually identical to those of children born appropriate for gestational age, but by 6 years of age, skinfold measurements had diverged considerably, to more than 0.60 standard deviations. The researchers concluded that intrauterine growth is associated with obesity in early childhood.

Finally, a large Chinese population-based, case-control study (N=1322), found birth weight above 4.0 kg to be a risk factor for obesity in preschool-age children (OR=3.77; 95% CI, 2.06-6.29).⁶ The absolute rate of overweight increased from 8% to 26% among LGA infants.

In adolescence, parental weight may be a factor

A prospective cohort study of 1993 white LGA infants found a greater propensity to become obese in adolescence, but only if their mothers or fathers were also obese (RR=5.7).⁷ Children with lean parents did not have an increased risk of being over-weight in adolescence.

Recommendations

Although major organizations don’t focus on infant birth weight as a predictor of overweight, they do address childhood obesity. The American Academy of Pediatrics states that genetic, environmental, or combinations of risk factors predisposing children to obesity can and should be identified.² The US Preventive Services Task Force concludes that the evidence is insufficient to recommend for or against routine screening for overweight in children and adolescents as a means of preventing adverse health outcomes (Grade I recommendation).¹

Acknowledgements

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

Evidence summary

The number of children 2 years and older who are overweight has tripled in the past 2 decades; the current prevalence of over-weight children and adolescents in the US is 15%.¹ By contrast with adults—in whom overweight and obesity are defined separately as a body mass index (BMI) above 25 kg/m² and 30 kg/m², respectively—overweight and obesity are synonymous in children and are defined as a BMI above the 95th percentile for age and sex.² Children and adolescents with a BMI between the 85th and 95th percentiles are considered at risk for overweight.²

Overweight children are vulnerable to adverse health outcomes, including insulin resistance, hyperlipidemia, hypertension, depression, sleep apnea, asthma, steatohepatitis, genu varum, and slipped capital femoral epiphysis.² The many variables that have been suggested to influence childhood obesity include birth weight, gestational age, parental obesity, socioeconomic status, single parent household, and birth order.^3-5

Birth weight and later BMI: Consistently linked

A systematic review of 19 longitudinal, observational studies comparing birth weight with later BMI indicates that the association between the 2 is positive and consistent in multiple cohorts.³ Eleven studies focused on outcomes in childhood; another 8 measured outcomes into adulthood.

Fifteen of the 19 studies (79%), ranging in size from 1028 to 92,940 subjects, found a positive association between birth weight and later BMI. However, the data were too heterogeneous to combine into a single summary measure. One representative study quantified the relative risk (RR) for severe obesity (>95th percentile BMI) at 5 years of age as 1.7 (95% confidence interval [CI], 1.2-2.9) for birth weights between the 85th and 94th percentiles and 1.8 (95% CI, 1.1-2.9) for birth weights greater than the 95th percentile.³ Studies that didn’t find such an association had smaller sample sizes (137 to 432 subjects) and, therefore, may have lacked the power to detect an association.

Gestational diabetes. A subsequent retrospective cohort survey of 14,881 children born to mothers with gestational diabetes—and controlled for age, sex, and Tanner stage—found that the odds ratio (OR) for adolescent overweight was 1.4 (95% CI, 1.2-1.6) for each 1-kg increment in birth weight.⁴ The correlation persisted (OR=1.3; 95% CI, 1.1-1.5) when other covariates were controlled (television viewing, physical activity, energy intake, breastfeeding duration, birth order, household income, mother’s smoking, dietary restraint, and mother’s current BMI).

Large for gestational age. A US national cohort study of 3192 children adjusted for gestational age, found that large-for-gestational-age (LGA) infants with birth weights above the 90th percentile remained longer and heavier through 83 months of life.⁵ The triceps and subscapular skinfold measurements at 3 years of age for children born LGA were virtually identical to those of children born appropriate for gestational age, but by 6 years of age, skinfold measurements had diverged considerably, to more than 0.60 standard deviations. The researchers concluded that intrauterine growth is associated with obesity in early childhood.

Finally, a large Chinese population-based, case-control study (N=1322), found birth weight above 4.0 kg to be a risk factor for obesity in preschool-age children (OR=3.77; 95% CI, 2.06-6.29).⁶ The absolute rate of overweight increased from 8% to 26% among LGA infants.

In adolescence, parental weight may be a factor

A prospective cohort study of 1993 white LGA infants found a greater propensity to become obese in adolescence, but only if their mothers or fathers were also obese (RR=5.7).⁷ Children with lean parents did not have an increased risk of being over-weight in adolescence.

Recommendations

Although major organizations don’t focus on infant birth weight as a predictor of overweight, they do address childhood obesity. The American Academy of Pediatrics states that genetic, environmental, or combinations of risk factors predisposing children to obesity can and should be identified.² The US Preventive Services Task Force concludes that the evidence is insufficient to recommend for or against routine screening for overweight in children and adolescents as a means of preventing adverse health outcomes (Grade I recommendation).¹

Acknowledgements

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

Evidence summary

The number of children 2 years and older who are overweight has tripled in the past 2 decades; the current prevalence of over-weight children and adolescents in the US is 15%.¹ By contrast with adults—in whom overweight and obesity are defined separately as a body mass index (BMI) above 25 kg/m² and 30 kg/m², respectively—overweight and obesity are synonymous in children and are defined as a BMI above the 95th percentile for age and sex.² Children and adolescents with a BMI between the 85th and 95th percentiles are considered at risk for overweight.²

Overweight children are vulnerable to adverse health outcomes, including insulin resistance, hyperlipidemia, hypertension, depression, sleep apnea, asthma, steatohepatitis, genu varum, and slipped capital femoral epiphysis.² The many variables that have been suggested to influence childhood obesity include birth weight, gestational age, parental obesity, socioeconomic status, single parent household, and birth order.^3-5

Birth weight and later BMI: Consistently linked

A systematic review of 19 longitudinal, observational studies comparing birth weight with later BMI indicates that the association between the 2 is positive and consistent in multiple cohorts.³ Eleven studies focused on outcomes in childhood; another 8 measured outcomes into adulthood.

Fifteen of the 19 studies (79%), ranging in size from 1028 to 92,940 subjects, found a positive association between birth weight and later BMI. However, the data were too heterogeneous to combine into a single summary measure. One representative study quantified the relative risk (RR) for severe obesity (>95th percentile BMI) at 5 years of age as 1.7 (95% confidence interval [CI], 1.2-2.9) for birth weights between the 85th and 94th percentiles and 1.8 (95% CI, 1.1-2.9) for birth weights greater than the 95th percentile.³ Studies that didn’t find such an association had smaller sample sizes (137 to 432 subjects) and, therefore, may have lacked the power to detect an association.

Gestational diabetes. A subsequent retrospective cohort survey of 14,881 children born to mothers with gestational diabetes—and controlled for age, sex, and Tanner stage—found that the odds ratio (OR) for adolescent overweight was 1.4 (95% CI, 1.2-1.6) for each 1-kg increment in birth weight.⁴ The correlation persisted (OR=1.3; 95% CI, 1.1-1.5) when other covariates were controlled (television viewing, physical activity, energy intake, breastfeeding duration, birth order, household income, mother’s smoking, dietary restraint, and mother’s current BMI).

Large for gestational age. A US national cohort study of 3192 children adjusted for gestational age, found that large-for-gestational-age (LGA) infants with birth weights above the 90th percentile remained longer and heavier through 83 months of life.⁵ The triceps and subscapular skinfold measurements at 3 years of age for children born LGA were virtually identical to those of children born appropriate for gestational age, but by 6 years of age, skinfold measurements had diverged considerably, to more than 0.60 standard deviations. The researchers concluded that intrauterine growth is associated with obesity in early childhood.

Finally, a large Chinese population-based, case-control study (N=1322), found birth weight above 4.0 kg to be a risk factor for obesity in preschool-age children (OR=3.77; 95% CI, 2.06-6.29).⁶ The absolute rate of overweight increased from 8% to 26% among LGA infants.

In adolescence, parental weight may be a factor

A prospective cohort study of 1993 white LGA infants found a greater propensity to become obese in adolescence, but only if their mothers or fathers were also obese (RR=5.7).⁷ Children with lean parents did not have an increased risk of being over-weight in adolescence.

Recommendations

Although major organizations don’t focus on infant birth weight as a predictor of overweight, they do address childhood obesity. The American Academy of Pediatrics states that genetic, environmental, or combinations of risk factors predisposing children to obesity can and should be identified.² The US Preventive Services Task Force concludes that the evidence is insufficient to recommend for or against routine screening for overweight in children and adolescents as a means of preventing adverse health outcomes (Grade I recommendation).¹

Acknowledgements

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

Evidence summary

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

Travelers to malaria-endemic areas should avoid mosquito bites by using netting and repellents, and use chemoprophylaxis to prevent infection.

Although no drug regimen guarantees protection against malaria, physicians should prescribe 1 of several options based on the location of travel, the susceptibility of indigenous P falciparum, and the side-effect profile.¹

Timing and dosage of prophylactic drugs

Prophylactic medications must be started at different times before travel, but for some medications the optimal time to initiate treatment is unclear. Evidence-based recommendations^2,3 with consideration for side-effect profiles are given in the TABLE.

In contrast to the pretreatment times for all other malarial prophylaxes, the generally accepted pretreatment time for mefloquine is 1 to 2 weeks before entering a risk area. However, this may still be inadequate due to the drug’s long half-life, which results in a long delay in reaching therapeutic blood levels.⁴ The evidence indicates that mefloquine should be started at least 2, and as many as 7, weeks before travel.

The standard recommended dose of 250 mg/week of mefloquine “produces maximum steady-state plasma concentrations of 1000 to 2000 mcg/L, which are reached only after 7 to 10 weeks.”⁴ One study of 293 children under the age of 5 years in Malawi found that plasma concentrations of mefloquine were below prophylactic level (500 mcg/mL) against P falciparum until the fourth to seventh week of once-weekly dosing (P<.0003).⁵

One way of reaching prophylactic levels earlier would be to give mefloquine 250 mg daily for 3 days followed by 250 mg weekly.⁴ A safety study of 157 healthy US Marine volunteers showed that preloading achieves prophylactic blood levels of mefloquine by the third day while weekly mefloquine is subprophylactic until the fifth week.⁴

While a study of the long-term use of mefloquine in 421 healthy Peace Corps volunteers has shown it to be safe,⁶ clinical trials and case reports indicate that a loading dose of mefloquine is associated with adverse drug events, which include neuropsychiatric and gastrointestinal symptoms.^4,7

TABLE
Evidence-based recommendations for prevention of malaria^2-3,8

Recommendations from others

The World Health Organization (WHO) states that “weekly mefloquine should be started at least 1 week, but preferably 2–3 weeks before departure, to achieve higher pre-travel blood levels and to allow side effects to be detected before travel so that possible alternatives can be considered.”⁸

Centers for Disease Control and Prevention recommendations integrate recommendations from WHO and Cochrane.

Acknowledgments

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

Evidence summary

Travelers to malaria-endemic areas should avoid mosquito bites by using netting and repellents, and use chemoprophylaxis to prevent infection.

Although no drug regimen guarantees protection against malaria, physicians should prescribe 1 of several options based on the location of travel, the susceptibility of indigenous P falciparum, and the side-effect profile.¹

Timing and dosage of prophylactic drugs

Prophylactic medications must be started at different times before travel, but for some medications the optimal time to initiate treatment is unclear. Evidence-based recommendations^2,3 with consideration for side-effect profiles are given in the TABLE.

In contrast to the pretreatment times for all other malarial prophylaxes, the generally accepted pretreatment time for mefloquine is 1 to 2 weeks before entering a risk area. However, this may still be inadequate due to the drug’s long half-life, which results in a long delay in reaching therapeutic blood levels.⁴ The evidence indicates that mefloquine should be started at least 2, and as many as 7, weeks before travel.

The standard recommended dose of 250 mg/week of mefloquine “produces maximum steady-state plasma concentrations of 1000 to 2000 mcg/L, which are reached only after 7 to 10 weeks.”⁴ One study of 293 children under the age of 5 years in Malawi found that plasma concentrations of mefloquine were below prophylactic level (500 mcg/mL) against P falciparum until the fourth to seventh week of once-weekly dosing (P<.0003).⁵

One way of reaching prophylactic levels earlier would be to give mefloquine 250 mg daily for 3 days followed by 250 mg weekly.⁴ A safety study of 157 healthy US Marine volunteers showed that preloading achieves prophylactic blood levels of mefloquine by the third day while weekly mefloquine is subprophylactic until the fifth week.⁴

While a study of the long-term use of mefloquine in 421 healthy Peace Corps volunteers has shown it to be safe,⁶ clinical trials and case reports indicate that a loading dose of mefloquine is associated with adverse drug events, which include neuropsychiatric and gastrointestinal symptoms.^4,7

TABLE
Evidence-based recommendations for prevention of malaria^2-3,8

Recommendations from others

The World Health Organization (WHO) states that “weekly mefloquine should be started at least 1 week, but preferably 2–3 weeks before departure, to achieve higher pre-travel blood levels and to allow side effects to be detected before travel so that possible alternatives can be considered.”⁸

Centers for Disease Control and Prevention recommendations integrate recommendations from WHO and Cochrane.

Acknowledgments

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

Evidence summary

Travelers to malaria-endemic areas should avoid mosquito bites by using netting and repellents, and use chemoprophylaxis to prevent infection.

Although no drug regimen guarantees protection against malaria, physicians should prescribe 1 of several options based on the location of travel, the susceptibility of indigenous P falciparum, and the side-effect profile.¹

Timing and dosage of prophylactic drugs

Prophylactic medications must be started at different times before travel, but for some medications the optimal time to initiate treatment is unclear. Evidence-based recommendations^2,3 with consideration for side-effect profiles are given in the TABLE.

In contrast to the pretreatment times for all other malarial prophylaxes, the generally accepted pretreatment time for mefloquine is 1 to 2 weeks before entering a risk area. However, this may still be inadequate due to the drug’s long half-life, which results in a long delay in reaching therapeutic blood levels.⁴ The evidence indicates that mefloquine should be started at least 2, and as many as 7, weeks before travel.

The standard recommended dose of 250 mg/week of mefloquine “produces maximum steady-state plasma concentrations of 1000 to 2000 mcg/L, which are reached only after 7 to 10 weeks.”⁴ One study of 293 children under the age of 5 years in Malawi found that plasma concentrations of mefloquine were below prophylactic level (500 mcg/mL) against P falciparum until the fourth to seventh week of once-weekly dosing (P<.0003).⁵

One way of reaching prophylactic levels earlier would be to give mefloquine 250 mg daily for 3 days followed by 250 mg weekly.⁴ A safety study of 157 healthy US Marine volunteers showed that preloading achieves prophylactic blood levels of mefloquine by the third day while weekly mefloquine is subprophylactic until the fifth week.⁴

While a study of the long-term use of mefloquine in 421 healthy Peace Corps volunteers has shown it to be safe,⁶ clinical trials and case reports indicate that a loading dose of mefloquine is associated with adverse drug events, which include neuropsychiatric and gastrointestinal symptoms.^4,7

TABLE
Evidence-based recommendations for prevention of malaria^2-3,8

Recommendations from others

The World Health Organization (WHO) states that “weekly mefloquine should be started at least 1 week, but preferably 2–3 weeks before departure, to achieve higher pre-travel blood levels and to allow side effects to be detected before travel so that possible alternatives can be considered.”⁸

Centers for Disease Control and Prevention recommendations integrate recommendations from WHO and Cochrane.

Acknowledgments

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

Evidence summary

Approximately 10% to 15% of adults complain of chronic insomnia, best defined as difficulty initiating or maintaining sleep 3 or more nights per week for 6 months or longer, with secondary impairments in daytime functioning, including fatigue and disturbed mood.^1-3

Behavioral and psychological treatments have emerged as increasingly popular adjunctive interventions to pharmacotherapy and as independent interventions for chronic insomnia. No evidence exists that behavioral treatments have adverse effects.¹

Sleep hygiene, relaxation training, and cognitive therapy improve sleep

CBT interventions are based on the notion that distorted thoughts about sleep and learned behavior patterns hyperarouse the central nervous system and deregulate sleep cycles, resulting in chronic insomnia.⁴ CBT interventions combine empirically tested behavioral, cognitive, and educational procedures to alter faulty beliefs and attitudes, modify sleep habits, and regulate sleep-wake schedules.³

These interventions include stimulus control, sleep hygiene, sleep restriction, relaxation training, and cognitive therapy.⁵ These methods can be used separately; however, they are increasingly being used together to treat the complexities of individual patients.⁵

Five recent high-quality randomized control trials (RCTs) confirmed findings from earlier RCTs that CBT methods improve sleep.⁵ Compared with those given a placebo or placed on a waiting list, CBT-treated patients in these RCTs reported clinically significant improvements in sleep onset latency, sleep efficiency, time awake after sleep onset, and total sleep time. In one RCT, 64% of CBT patients had improvements in sleep efficiency and time awake after sleep onset, compared with 8% who improved with a placebo intervention (number needed to treat [NNT]=1.8).⁵ Further, sleep onset latency for primary care patients with chronic insomnia was decreased from 61 to 28 minutes, compared with 74 to 70 minutes for a waiting-list group.⁵ The maintenance of sleep gains from CBT beyond 1 year is unknown since no published RCT clinical trials to date have lasted longer than 12 months.¹

An important related meta-analysis of 21 studies validated behavior therapy, and revealed CBT reduced sleep onset latency by an additional 8.8 minutes over medication (95% confidence interval, 0.17–1.04 minutes).⁶ Although not superior on other outcomes, behavior therapy produced similar short-term results to pharmacotherapy across all other sleep measures, without attendant medication side effects.

Stimulus control is the most effective CBT intervention

A recent systematic review with meta-analysis of 37 clinical investigations determined that stimulus control was the most effective CBT intervention.³ Stimulus control consists of 5 basic instructions (TABLE) designed to help the patient reassociate sleep stimuli (ie, bed/bedroom) with falling asleep and establishing consistent sleep-wake schedules. These 5 instructions are frequently used in combination with CBT sleep hygiene techniques (TABLE) and can be easily integrated into the office setting.^3,4

Among the CBT techniques, stimulus control and sleep hygiene are the least time-consuming and may be more easily applied in the primary care setting; however, minimal research has been done into the specific incorporation of CBT into primary care settings.

Researchers conducting a single-blind randomized group study in a Veterans Affairs primary care clinic concluded that an abbreviated CBT approach with two 25-minute sessions effectively improved participant sleep onset latency, and time awake after sleep onset.⁷ Researchers reviewed participants’ sleep logs and a behavioral health provider offered patients a condensed education on sleep hygiene, stimulus control, and sleep restrictions strategies. The study was limited because of small sample size (<25). Generalizability to practice is restricted because sessions were conducted by a behavioral health provider, not a family physician.

TABLE
Patient needs a good night’s sleep? Offer this advice

Recommendations from others

The Agency for Healthcare Research and Quality recommends CBT as an effective treatment in the management of chronic .⁸ It also recommends that further large-scale RCTs be conducted to establish CBT’s effectiveness across subsets of the population of individuals with chronic (ie, gender, age, shift workers, and those with psychiatric illnesses).

The American Psychological Association (APA) recommends CBT as the “treatment of choice” for chronic , with 70% to 80% of patients showing a treatment response.⁹

Acknowledgments

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

Evidence summary

Approximately 10% to 15% of adults complain of chronic insomnia, best defined as difficulty initiating or maintaining sleep 3 or more nights per week for 6 months or longer, with secondary impairments in daytime functioning, including fatigue and disturbed mood.^1-3

Behavioral and psychological treatments have emerged as increasingly popular adjunctive interventions to pharmacotherapy and as independent interventions for chronic insomnia. No evidence exists that behavioral treatments have adverse effects.¹

Sleep hygiene, relaxation training, and cognitive therapy improve sleep

CBT interventions are based on the notion that distorted thoughts about sleep and learned behavior patterns hyperarouse the central nervous system and deregulate sleep cycles, resulting in chronic insomnia.⁴ CBT interventions combine empirically tested behavioral, cognitive, and educational procedures to alter faulty beliefs and attitudes, modify sleep habits, and regulate sleep-wake schedules.³

These interventions include stimulus control, sleep hygiene, sleep restriction, relaxation training, and cognitive therapy.⁵ These methods can be used separately; however, they are increasingly being used together to treat the complexities of individual patients.⁵

Five recent high-quality randomized control trials (RCTs) confirmed findings from earlier RCTs that CBT methods improve sleep.⁵ Compared with those given a placebo or placed on a waiting list, CBT-treated patients in these RCTs reported clinically significant improvements in sleep onset latency, sleep efficiency, time awake after sleep onset, and total sleep time. In one RCT, 64% of CBT patients had improvements in sleep efficiency and time awake after sleep onset, compared with 8% who improved with a placebo intervention (number needed to treat [NNT]=1.8).⁵ Further, sleep onset latency for primary care patients with chronic insomnia was decreased from 61 to 28 minutes, compared with 74 to 70 minutes for a waiting-list group.⁵ The maintenance of sleep gains from CBT beyond 1 year is unknown since no published RCT clinical trials to date have lasted longer than 12 months.¹

An important related meta-analysis of 21 studies validated behavior therapy, and revealed CBT reduced sleep onset latency by an additional 8.8 minutes over medication (95% confidence interval, 0.17–1.04 minutes).⁶ Although not superior on other outcomes, behavior therapy produced similar short-term results to pharmacotherapy across all other sleep measures, without attendant medication side effects.

Stimulus control is the most effective CBT intervention

A recent systematic review with meta-analysis of 37 clinical investigations determined that stimulus control was the most effective CBT intervention.³ Stimulus control consists of 5 basic instructions (TABLE) designed to help the patient reassociate sleep stimuli (ie, bed/bedroom) with falling asleep and establishing consistent sleep-wake schedules. These 5 instructions are frequently used in combination with CBT sleep hygiene techniques (TABLE) and can be easily integrated into the office setting.^3,4

Among the CBT techniques, stimulus control and sleep hygiene are the least time-consuming and may be more easily applied in the primary care setting; however, minimal research has been done into the specific incorporation of CBT into primary care settings.

Researchers conducting a single-blind randomized group study in a Veterans Affairs primary care clinic concluded that an abbreviated CBT approach with two 25-minute sessions effectively improved participant sleep onset latency, and time awake after sleep onset.⁷ Researchers reviewed participants’ sleep logs and a behavioral health provider offered patients a condensed education on sleep hygiene, stimulus control, and sleep restrictions strategies. The study was limited because of small sample size (<25). Generalizability to practice is restricted because sessions were conducted by a behavioral health provider, not a family physician.

TABLE
Patient needs a good night’s sleep? Offer this advice

Recommendations from others

The Agency for Healthcare Research and Quality recommends CBT as an effective treatment in the management of chronic .⁸ It also recommends that further large-scale RCTs be conducted to establish CBT’s effectiveness across subsets of the population of individuals with chronic (ie, gender, age, shift workers, and those with psychiatric illnesses).

The American Psychological Association (APA) recommends CBT as the “treatment of choice” for chronic , with 70% to 80% of patients showing a treatment response.⁹

Acknowledgments

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

Evidence summary

Approximately 10% to 15% of adults complain of chronic insomnia, best defined as difficulty initiating or maintaining sleep 3 or more nights per week for 6 months or longer, with secondary impairments in daytime functioning, including fatigue and disturbed mood.^1-3

Behavioral and psychological treatments have emerged as increasingly popular adjunctive interventions to pharmacotherapy and as independent interventions for chronic insomnia. No evidence exists that behavioral treatments have adverse effects.¹

Sleep hygiene, relaxation training, and cognitive therapy improve sleep

CBT interventions are based on the notion that distorted thoughts about sleep and learned behavior patterns hyperarouse the central nervous system and deregulate sleep cycles, resulting in chronic insomnia.⁴ CBT interventions combine empirically tested behavioral, cognitive, and educational procedures to alter faulty beliefs and attitudes, modify sleep habits, and regulate sleep-wake schedules.³

These interventions include stimulus control, sleep hygiene, sleep restriction, relaxation training, and cognitive therapy.⁵ These methods can be used separately; however, they are increasingly being used together to treat the complexities of individual patients.⁵

Five recent high-quality randomized control trials (RCTs) confirmed findings from earlier RCTs that CBT methods improve sleep.⁵ Compared with those given a placebo or placed on a waiting list, CBT-treated patients in these RCTs reported clinically significant improvements in sleep onset latency, sleep efficiency, time awake after sleep onset, and total sleep time. In one RCT, 64% of CBT patients had improvements in sleep efficiency and time awake after sleep onset, compared with 8% who improved with a placebo intervention (number needed to treat [NNT]=1.8).⁵ Further, sleep onset latency for primary care patients with chronic insomnia was decreased from 61 to 28 minutes, compared with 74 to 70 minutes for a waiting-list group.⁵ The maintenance of sleep gains from CBT beyond 1 year is unknown since no published RCT clinical trials to date have lasted longer than 12 months.¹

An important related meta-analysis of 21 studies validated behavior therapy, and revealed CBT reduced sleep onset latency by an additional 8.8 minutes over medication (95% confidence interval, 0.17–1.04 minutes).⁶ Although not superior on other outcomes, behavior therapy produced similar short-term results to pharmacotherapy across all other sleep measures, without attendant medication side effects.

Stimulus control is the most effective CBT intervention

A recent systematic review with meta-analysis of 37 clinical investigations determined that stimulus control was the most effective CBT intervention.³ Stimulus control consists of 5 basic instructions (TABLE) designed to help the patient reassociate sleep stimuli (ie, bed/bedroom) with falling asleep and establishing consistent sleep-wake schedules. These 5 instructions are frequently used in combination with CBT sleep hygiene techniques (TABLE) and can be easily integrated into the office setting.^3,4

Among the CBT techniques, stimulus control and sleep hygiene are the least time-consuming and may be more easily applied in the primary care setting; however, minimal research has been done into the specific incorporation of CBT into primary care settings.

Researchers conducting a single-blind randomized group study in a Veterans Affairs primary care clinic concluded that an abbreviated CBT approach with two 25-minute sessions effectively improved participant sleep onset latency, and time awake after sleep onset.⁷ Researchers reviewed participants’ sleep logs and a behavioral health provider offered patients a condensed education on sleep hygiene, stimulus control, and sleep restrictions strategies. The study was limited because of small sample size (<25). Generalizability to practice is restricted because sessions were conducted by a behavioral health provider, not a family physician.

TABLE
Patient needs a good night’s sleep? Offer this advice

Recommendations from others

The Agency for Healthcare Research and Quality recommends CBT as an effective treatment in the management of chronic .⁸ It also recommends that further large-scale RCTs be conducted to establish CBT’s effectiveness across subsets of the population of individuals with chronic (ie, gender, age, shift workers, and those with psychiatric illnesses).

The American Psychological Association (APA) recommends CBT as the “treatment of choice” for chronic , with 70% to 80% of patients showing a treatment response.⁹

Acknowledgments

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