Clinical Inquiries

Evidence summary

Current uncertainty in diagnostic criteria makes estimates of the incidence of INPH unclear, but it is thought to cause fewer than 5% of cases of dementia.¹

Two systematic reviews have looked at the question of diagnosing INPH.^2,3 Unfortunately, there is no definitive test or physical finding for INPH. For patients over 40 years of age, INPH has an insidious onset, a progressive course, and lacks an identifiable antecedent cause. A brain imaging study reveals ventricular enlargement not attributable to other causes. Some suggest that the diagnosis be assessed as “probable,” “possible,” and “unlikely” based on the degree of fulfillment of a set of historical, imaging, clinical, and physiological criteria (TABLE).³

TABLE
Categorizing the likelihood of idiopathic normal pressure hydrocephalus³

Which patients will benefit from shunting?

Supplemental prognostic tests have been developed to help decide which patients are most likely to benefit from a ventriculoperitoneal shunt. Complicating comparisons between the various tests is the lack of a standard set of measures of function in gait, cognition, and urination; nor is there agreement on how long after shunting the clinician should make these measurements.

A systematic review⁴ of the most commonly used prognostic tests identified a response to a large-volume (40–50 mL) CSF tap test as having a positive predictive value (PPV) between 73% and 100% but a negative predictive value (NPV) of only 23% to 42%. Thus, observing an improvement of function after such a test is a good predictor of improvement after shunting, but many patients who do not respond to the test respond to shunting.

A variation of the CSF tap test is the extended lumbar drainage test, which involves placing a lumbar intrathecal catheter and allowing the drainage of 10 mL of CSF/hour for 72 hours. The PPV for this test ranges from 80% to 100%, and NPV from 66% to 100%.

A third possible test is the measurement of resistance to an infusion of saline into the lumbar subarachnoid space (CSF Ro test). This test has multiple variations of technique. Reported values for PPV are 75% to 92%, and for NPV of 27% to 92%.

Other tests, such as radionuclide cisternography or magnetic resonance imaging CSF flow void, have predictive values too low or have too few studies to be recommended.⁴

Recommendations from others

A recently published expert consensus statement proposes that the diagnosis of INPH be made using the history, clinical examination, and neuroimaging.⁴ Cases of probable INPH can proceed directly to ventriculoperitoneal shunt, or supplemental testing can be used to improve the certainty of a positive shunt response. A positive CSF tap test should lead to shunting.

Follow up negative tap tests with the extended lumbar drainage test or the CSF Ro test (or both). A positive response to any of the tests should lead to shunting; negative responses to all the tests indicates a low chance (<10%) of responding to a ventriculoperitoneal shunt.⁴

Evidence summary

Current uncertainty in diagnostic criteria makes estimates of the incidence of INPH unclear, but it is thought to cause fewer than 5% of cases of dementia.¹

Two systematic reviews have looked at the question of diagnosing INPH.^2,3 Unfortunately, there is no definitive test or physical finding for INPH. For patients over 40 years of age, INPH has an insidious onset, a progressive course, and lacks an identifiable antecedent cause. A brain imaging study reveals ventricular enlargement not attributable to other causes. Some suggest that the diagnosis be assessed as “probable,” “possible,” and “unlikely” based on the degree of fulfillment of a set of historical, imaging, clinical, and physiological criteria (TABLE).³

TABLE
Categorizing the likelihood of idiopathic normal pressure hydrocephalus³

Which patients will benefit from shunting?

Supplemental prognostic tests have been developed to help decide which patients are most likely to benefit from a ventriculoperitoneal shunt. Complicating comparisons between the various tests is the lack of a standard set of measures of function in gait, cognition, and urination; nor is there agreement on how long after shunting the clinician should make these measurements.

A systematic review⁴ of the most commonly used prognostic tests identified a response to a large-volume (40–50 mL) CSF tap test as having a positive predictive value (PPV) between 73% and 100% but a negative predictive value (NPV) of only 23% to 42%. Thus, observing an improvement of function after such a test is a good predictor of improvement after shunting, but many patients who do not respond to the test respond to shunting.

A variation of the CSF tap test is the extended lumbar drainage test, which involves placing a lumbar intrathecal catheter and allowing the drainage of 10 mL of CSF/hour for 72 hours. The PPV for this test ranges from 80% to 100%, and NPV from 66% to 100%.

A third possible test is the measurement of resistance to an infusion of saline into the lumbar subarachnoid space (CSF Ro test). This test has multiple variations of technique. Reported values for PPV are 75% to 92%, and for NPV of 27% to 92%.

Other tests, such as radionuclide cisternography or magnetic resonance imaging CSF flow void, have predictive values too low or have too few studies to be recommended.⁴

Recommendations from others

A recently published expert consensus statement proposes that the diagnosis of INPH be made using the history, clinical examination, and neuroimaging.⁴ Cases of probable INPH can proceed directly to ventriculoperitoneal shunt, or supplemental testing can be used to improve the certainty of a positive shunt response. A positive CSF tap test should lead to shunting.

Follow up negative tap tests with the extended lumbar drainage test or the CSF Ro test (or both). A positive response to any of the tests should lead to shunting; negative responses to all the tests indicates a low chance (<10%) of responding to a ventriculoperitoneal shunt.⁴

Evidence summary

Current uncertainty in diagnostic criteria makes estimates of the incidence of INPH unclear, but it is thought to cause fewer than 5% of cases of dementia.¹

Two systematic reviews have looked at the question of diagnosing INPH.^2,3 Unfortunately, there is no definitive test or physical finding for INPH. For patients over 40 years of age, INPH has an insidious onset, a progressive course, and lacks an identifiable antecedent cause. A brain imaging study reveals ventricular enlargement not attributable to other causes. Some suggest that the diagnosis be assessed as “probable,” “possible,” and “unlikely” based on the degree of fulfillment of a set of historical, imaging, clinical, and physiological criteria (TABLE).³

TABLE
Categorizing the likelihood of idiopathic normal pressure hydrocephalus³

Which patients will benefit from shunting?

Supplemental prognostic tests have been developed to help decide which patients are most likely to benefit from a ventriculoperitoneal shunt. Complicating comparisons between the various tests is the lack of a standard set of measures of function in gait, cognition, and urination; nor is there agreement on how long after shunting the clinician should make these measurements.

A systematic review⁴ of the most commonly used prognostic tests identified a response to a large-volume (40–50 mL) CSF tap test as having a positive predictive value (PPV) between 73% and 100% but a negative predictive value (NPV) of only 23% to 42%. Thus, observing an improvement of function after such a test is a good predictor of improvement after shunting, but many patients who do not respond to the test respond to shunting.

A variation of the CSF tap test is the extended lumbar drainage test, which involves placing a lumbar intrathecal catheter and allowing the drainage of 10 mL of CSF/hour for 72 hours. The PPV for this test ranges from 80% to 100%, and NPV from 66% to 100%.

A third possible test is the measurement of resistance to an infusion of saline into the lumbar subarachnoid space (CSF Ro test). This test has multiple variations of technique. Reported values for PPV are 75% to 92%, and for NPV of 27% to 92%.

Other tests, such as radionuclide cisternography or magnetic resonance imaging CSF flow void, have predictive values too low or have too few studies to be recommended.⁴

Recommendations from others

A recently published expert consensus statement proposes that the diagnosis of INPH be made using the history, clinical examination, and neuroimaging.⁴ Cases of probable INPH can proceed directly to ventriculoperitoneal shunt, or supplemental testing can be used to improve the certainty of a positive shunt response. A positive CSF tap test should lead to shunting.

Follow up negative tap tests with the extended lumbar drainage test or the CSF Ro test (or both). A positive response to any of the tests should lead to shunting; negative responses to all the tests indicates a low chance (<10%) of responding to a ventriculoperitoneal shunt.⁴

Evidence summary

Although most patients undergo surgery for hip fracture, family physicians often serve as consultants for perioperative management and rehabilitation. Several interventions have been studied that influence outcomes for hip fracture patients.

Surgical interventions: Timing is critical

Most ambulatory, medically stable patients elect to have surgical repair of their fractures. A meta-analysis found few randomized trials comparing operative with nonoperative therapy; it concluded that surgical treatment seems to be associated with a reduced length of hospital stay and improved rehabilitation.¹

The timing of surgery appears to be an important variable, particularly whether patients should undergo surgery within 24 hours of the fracture. Some studies found decreased mortality with earlier surgical intervention,² while others have not.³ A 2006 observational study⁴ found that delay in operating was associated with an increased risk of death in the hospital, even after adjusting for comorbidities. For all deaths in the hospital, the odds ratio [OR] for delaying more than 1 day, relative to 1 day or less, was 1.27 (95% confidence interval [CI], 1.23–1.32). Despite the inconsistency regarding mortality rates, complication rates (such as decubitus ulcers) do increase with a delay in surgery.³

Unfractionated vs LMW heparin

After a hip fracture, patients are at very high risk for VTE. For untreated patients, the rate of deep vein thromboses (DVT) may be as high as 50%, with an associated fatal pulmonary embolism rate as high as 7.5%.⁵

The effectiveness of unfractionated and low-molecular-weight heparin was evaluated in a 2002 Cochrane systematic review.⁶ While evidence was insufficient to recommend 1 agent over another, both were found to significantly decrease the incidence of lower-extremity DVT over placebo (for unfractionated heparin, relative risk [RR]=0.59 [95% CI, 0.49–0.72]; for low-molecular-weight heparin, RR=0.60 [95% CI, 0.50–0.71]). Number needed to treat [NNT] with either agent was 7.

Reduce infections with antibiotic prophylaxis

Antibiotic prophylaxis has been supported by a Cochrane review, which concluded that single-dose antibiotic prophylaxis before surgery significantly reduced the risk of deep wound infections (RR=0.40; 95% CI, 0.24–0.67; NNT=55), as well as superficial wound, urinary, and respiratory tract infections.⁷

Patients should receive antibiotics less than 2 hours before surgery to reduce the risk of infection.⁸ Classen et al found that patients treated less than 2 hours before surgery had a 0.6% rate of infection (10/1208), compared with a 3.85% rate for those treated 2 to 24 hours ahead (14/369) (NNT=31).⁸ It is unclear whether multiple-dose therapy provides additional benefit when administered over the first 24 to 36 hours after surgery⁹ (OR=0.60; 95% CI, 0.18–2.02). First- or second-generation cephalosporins were used in most studies.

Delirium: A common but avoidable complication

Delirium is a common complication seen after hip fracture, affecting approximately 10% to 16% of patients.^10,11 Delirium may increase the duration of hospitalization, and may be associated with an increased mortality at 1 year.¹² Delirium can be avoided by looking at each patient’s risk factors.¹³ Studies suggest avoiding use of meperidine, benzodiazepines, and medications with anticholinergic side effects.^11,13 Sleep deprivation, delayed mobility, and inadequate pain control are also associated with the development of delirium.¹³

One study showed that prophylaxis with haloperidol for hip fracture patients did not decrease the incidence of postoperative delirium but did reduce its duration and severity.¹⁴ Haloperidol prophylaxis was also associated with shorter hospital stays. Treatment with haloperidol or risperidone for the agitation of postoperative delirium has been recommended when behavioral interventions fail.¹³

Pain control improves recovery

Providing adequate analgesia is of the utmost importance. In a 2003 prospective cohort study, patients without sufficient analgesia had an increased risk of poor functional recovery and longer hospitalization.¹⁵ In another cohort study, those patients whose pain was inadequately controlled also had an increased risk for delirium (RR=9.0; 95% CI, 1.8–45.2).¹¹ Meperidine use increased the risk for delirium compared with other opioid analgesics (RR=2.4; 95% CI, 1.3–4.5).¹¹

Recommendations of others

The American College of Physicians provides a comprehensive evidence-based guideline for the management of hip fracture patients in their PIER series (Physicians’ Information and Education Resource) (TABLE).¹⁶

The American College of Chest Physicians has published evidence-based guidelines for the prevention of VTE.⁵ For patients undergoing hip fracture surgery, they recommend routine use of fondaparinux, low-molecular-weight heparin at high-risk dosing, adjusted-dose warfarin (at a target international normalized ratio [INR] of 2.5, range 2.0–3.0), or unfractionated heparin. They recommend against routine use of aspirin alone. If surgery must be delayed, physicians should initiate prophylaxis with unfractionated or low-molecular-weight heparin at the time of hospital admission. Anticoagulation should routinely continue for 10 days after surgery or until the patient is ambulatory. If anticoagulation is contraindicated, mechanical prophylaxis of VTE with foot and calf pumping devices is recommended.^5,6

TABLE
6 steps for managing hip fracture from the American College of Physicians

Evidence summary

Although most patients undergo surgery for hip fracture, family physicians often serve as consultants for perioperative management and rehabilitation. Several interventions have been studied that influence outcomes for hip fracture patients.

Surgical interventions: Timing is critical

Most ambulatory, medically stable patients elect to have surgical repair of their fractures. A meta-analysis found few randomized trials comparing operative with nonoperative therapy; it concluded that surgical treatment seems to be associated with a reduced length of hospital stay and improved rehabilitation.¹

The timing of surgery appears to be an important variable, particularly whether patients should undergo surgery within 24 hours of the fracture. Some studies found decreased mortality with earlier surgical intervention,² while others have not.³ A 2006 observational study⁴ found that delay in operating was associated with an increased risk of death in the hospital, even after adjusting for comorbidities. For all deaths in the hospital, the odds ratio [OR] for delaying more than 1 day, relative to 1 day or less, was 1.27 (95% confidence interval [CI], 1.23–1.32). Despite the inconsistency regarding mortality rates, complication rates (such as decubitus ulcers) do increase with a delay in surgery.³

Unfractionated vs LMW heparin

After a hip fracture, patients are at very high risk for VTE. For untreated patients, the rate of deep vein thromboses (DVT) may be as high as 50%, with an associated fatal pulmonary embolism rate as high as 7.5%.⁵

The effectiveness of unfractionated and low-molecular-weight heparin was evaluated in a 2002 Cochrane systematic review.⁶ While evidence was insufficient to recommend 1 agent over another, both were found to significantly decrease the incidence of lower-extremity DVT over placebo (for unfractionated heparin, relative risk [RR]=0.59 [95% CI, 0.49–0.72]; for low-molecular-weight heparin, RR=0.60 [95% CI, 0.50–0.71]). Number needed to treat [NNT] with either agent was 7.

Reduce infections with antibiotic prophylaxis

Antibiotic prophylaxis has been supported by a Cochrane review, which concluded that single-dose antibiotic prophylaxis before surgery significantly reduced the risk of deep wound infections (RR=0.40; 95% CI, 0.24–0.67; NNT=55), as well as superficial wound, urinary, and respiratory tract infections.⁷

Patients should receive antibiotics less than 2 hours before surgery to reduce the risk of infection.⁸ Classen et al found that patients treated less than 2 hours before surgery had a 0.6% rate of infection (10/1208), compared with a 3.85% rate for those treated 2 to 24 hours ahead (14/369) (NNT=31).⁸ It is unclear whether multiple-dose therapy provides additional benefit when administered over the first 24 to 36 hours after surgery⁹ (OR=0.60; 95% CI, 0.18–2.02). First- or second-generation cephalosporins were used in most studies.

Delirium: A common but avoidable complication

Delirium is a common complication seen after hip fracture, affecting approximately 10% to 16% of patients.^10,11 Delirium may increase the duration of hospitalization, and may be associated with an increased mortality at 1 year.¹² Delirium can be avoided by looking at each patient’s risk factors.¹³ Studies suggest avoiding use of meperidine, benzodiazepines, and medications with anticholinergic side effects.^11,13 Sleep deprivation, delayed mobility, and inadequate pain control are also associated with the development of delirium.¹³

One study showed that prophylaxis with haloperidol for hip fracture patients did not decrease the incidence of postoperative delirium but did reduce its duration and severity.¹⁴ Haloperidol prophylaxis was also associated with shorter hospital stays. Treatment with haloperidol or risperidone for the agitation of postoperative delirium has been recommended when behavioral interventions fail.¹³

Pain control improves recovery

Providing adequate analgesia is of the utmost importance. In a 2003 prospective cohort study, patients without sufficient analgesia had an increased risk of poor functional recovery and longer hospitalization.¹⁵ In another cohort study, those patients whose pain was inadequately controlled also had an increased risk for delirium (RR=9.0; 95% CI, 1.8–45.2).¹¹ Meperidine use increased the risk for delirium compared with other opioid analgesics (RR=2.4; 95% CI, 1.3–4.5).¹¹

Recommendations of others

The American College of Physicians provides a comprehensive evidence-based guideline for the management of hip fracture patients in their PIER series (Physicians’ Information and Education Resource) (TABLE).¹⁶

The American College of Chest Physicians has published evidence-based guidelines for the prevention of VTE.⁵ For patients undergoing hip fracture surgery, they recommend routine use of fondaparinux, low-molecular-weight heparin at high-risk dosing, adjusted-dose warfarin (at a target international normalized ratio [INR] of 2.5, range 2.0–3.0), or unfractionated heparin. They recommend against routine use of aspirin alone. If surgery must be delayed, physicians should initiate prophylaxis with unfractionated or low-molecular-weight heparin at the time of hospital admission. Anticoagulation should routinely continue for 10 days after surgery or until the patient is ambulatory. If anticoagulation is contraindicated, mechanical prophylaxis of VTE with foot and calf pumping devices is recommended.^5,6

TABLE
6 steps for managing hip fracture from the American College of Physicians

Evidence summary

Although most patients undergo surgery for hip fracture, family physicians often serve as consultants for perioperative management and rehabilitation. Several interventions have been studied that influence outcomes for hip fracture patients.

Surgical interventions: Timing is critical

Most ambulatory, medically stable patients elect to have surgical repair of their fractures. A meta-analysis found few randomized trials comparing operative with nonoperative therapy; it concluded that surgical treatment seems to be associated with a reduced length of hospital stay and improved rehabilitation.¹

The timing of surgery appears to be an important variable, particularly whether patients should undergo surgery within 24 hours of the fracture. Some studies found decreased mortality with earlier surgical intervention,² while others have not.³ A 2006 observational study⁴ found that delay in operating was associated with an increased risk of death in the hospital, even after adjusting for comorbidities. For all deaths in the hospital, the odds ratio [OR] for delaying more than 1 day, relative to 1 day or less, was 1.27 (95% confidence interval [CI], 1.23–1.32). Despite the inconsistency regarding mortality rates, complication rates (such as decubitus ulcers) do increase with a delay in surgery.³

Unfractionated vs LMW heparin

After a hip fracture, patients are at very high risk for VTE. For untreated patients, the rate of deep vein thromboses (DVT) may be as high as 50%, with an associated fatal pulmonary embolism rate as high as 7.5%.⁵

The effectiveness of unfractionated and low-molecular-weight heparin was evaluated in a 2002 Cochrane systematic review.⁶ While evidence was insufficient to recommend 1 agent over another, both were found to significantly decrease the incidence of lower-extremity DVT over placebo (for unfractionated heparin, relative risk [RR]=0.59 [95% CI, 0.49–0.72]; for low-molecular-weight heparin, RR=0.60 [95% CI, 0.50–0.71]). Number needed to treat [NNT] with either agent was 7.

Reduce infections with antibiotic prophylaxis

Antibiotic prophylaxis has been supported by a Cochrane review, which concluded that single-dose antibiotic prophylaxis before surgery significantly reduced the risk of deep wound infections (RR=0.40; 95% CI, 0.24–0.67; NNT=55), as well as superficial wound, urinary, and respiratory tract infections.⁷

Patients should receive antibiotics less than 2 hours before surgery to reduce the risk of infection.⁸ Classen et al found that patients treated less than 2 hours before surgery had a 0.6% rate of infection (10/1208), compared with a 3.85% rate for those treated 2 to 24 hours ahead (14/369) (NNT=31).⁸ It is unclear whether multiple-dose therapy provides additional benefit when administered over the first 24 to 36 hours after surgery⁹ (OR=0.60; 95% CI, 0.18–2.02). First- or second-generation cephalosporins were used in most studies.

Delirium: A common but avoidable complication

Delirium is a common complication seen after hip fracture, affecting approximately 10% to 16% of patients.^10,11 Delirium may increase the duration of hospitalization, and may be associated with an increased mortality at 1 year.¹² Delirium can be avoided by looking at each patient’s risk factors.¹³ Studies suggest avoiding use of meperidine, benzodiazepines, and medications with anticholinergic side effects.^11,13 Sleep deprivation, delayed mobility, and inadequate pain control are also associated with the development of delirium.¹³

One study showed that prophylaxis with haloperidol for hip fracture patients did not decrease the incidence of postoperative delirium but did reduce its duration and severity.¹⁴ Haloperidol prophylaxis was also associated with shorter hospital stays. Treatment with haloperidol or risperidone for the agitation of postoperative delirium has been recommended when behavioral interventions fail.¹³

Pain control improves recovery

Providing adequate analgesia is of the utmost importance. In a 2003 prospective cohort study, patients without sufficient analgesia had an increased risk of poor functional recovery and longer hospitalization.¹⁵ In another cohort study, those patients whose pain was inadequately controlled also had an increased risk for delirium (RR=9.0; 95% CI, 1.8–45.2).¹¹ Meperidine use increased the risk for delirium compared with other opioid analgesics (RR=2.4; 95% CI, 1.3–4.5).¹¹

Recommendations of others

The American College of Physicians provides a comprehensive evidence-based guideline for the management of hip fracture patients in their PIER series (Physicians’ Information and Education Resource) (TABLE).¹⁶

The American College of Chest Physicians has published evidence-based guidelines for the prevention of VTE.⁵ For patients undergoing hip fracture surgery, they recommend routine use of fondaparinux, low-molecular-weight heparin at high-risk dosing, adjusted-dose warfarin (at a target international normalized ratio [INR] of 2.5, range 2.0–3.0), or unfractionated heparin. They recommend against routine use of aspirin alone. If surgery must be delayed, physicians should initiate prophylaxis with unfractionated or low-molecular-weight heparin at the time of hospital admission. Anticoagulation should routinely continue for 10 days after surgery or until the patient is ambulatory. If anticoagulation is contraindicated, mechanical prophylaxis of VTE with foot and calf pumping devices is recommended.^5,6

TABLE
6 steps for managing hip fracture from the American College of Physicians

Evidence summary

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

RCTs find no difference between bed rest and ad lib movement

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

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

Studies in nonproteinuric hypertension were no different

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

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

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

Recommendations from others

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

Evidence summary

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

RCTs find no difference between bed rest and ad lib movement

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

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

Studies in nonproteinuric hypertension were no different

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

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

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

Recommendations from others

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

Evidence summary

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

RCTs find no difference between bed rest and ad lib movement

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

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

Studies in nonproteinuric hypertension were no different

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

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

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

Recommendations from others

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

Evidence summary

The use of DMARDs has become standard of care for rheumatoid arthritis, for both therapy and prevention of progression of this debilitating disease. However, the use of DMARDs in nonrheumatoid rheumatologic disease is still under investigation, and at this point, the use of DMARDs as first-line therapy is not recommended; however, second-line therapy with DMARDs is common.

For psoriatic arthritis, DMARDs are beneficial as a second-line therapy

A Cochrane systematic review identified 13 randomized controlled trials enrolling a combined 1022 patients with psoriatic arthritis randomly assigned to receive a DMARD—methotrexate, sulfasalazine (Azulfidine), azathioprine (Imuran/ Azasan), or etretinate (Tegison; no longer available in the US)—compared with placebo.² All agents were better than placebo; however, only 2 agents (parenteral high-dose methotrexate and sulfasalazine) had clinically important benefits for more than half the patients. The studies were too small to establish toxicity or to evaluate the other agents.

NSAIDs are still the preferred first-line therapy, concluded a recent publication on the treatment of psoriatic arthritis, which looked at 54 different studies; however, second-line therapy could include methotrexate, sulfasalazine, etanercept (Enbrel), infliximab (Remicade), cyclosporine, or combination therapy.³ Sulfasalazine appeared to be clinically beneficial for peripheral psoriatic arthritis.

Etanercept vs placebo. An initial study (60 patients) of etanercept vs placebo among patients who were permitted to stay on methotrexate or prednisone showed a response rate of 87% vs 23% (P<.0001; number needed to treat [NNT]=1.56).⁴

Infliximab vs placebo. A study of infliximab vs placebo involving 104 patients had similar results, with good response in 65% vs 10% (NNT=1.81) at 16 weeks; infliximab also inhibited radiographic progression by 22%.⁵

Cyclosporine. Although it is effective, reserve cyclosporine for patients who do not improve on other regimens, because of its nephrotoxicity.³

DMARDs show some benefit in treating ankylosing spondylitis

Two recent Cochrane systematic reviews on ankylosing spondylitis examined the use of sulfasalazine and methotrexate as second-line agents.^6,7 Eleven trials were included in the sulfasalazine analysis, with a total of 895 patients. Sulfasalazine demonstrated some benefit in reducing erythrocyte sedimentation rates (ESRs) and morning stiffness, but there was no evidence that the drug reduced pain or improved physical function, spinal mobility, or rate of enthesitis. Sulfasalazine was well tolerated and may be useful in early mild disease for patients with peripheral arthritis and high ESRs. On the other hand, evidence was insufficient to determine whether methotrexate benefited patients with ankylosing spondylitis.

In other trials, infliximab and etanercept showed good potential for benefit in treating ankylosing spondylitis.

One study of infliximab vs placebo showed 61.2% vs 19.2% patients with good clinical benefit at 24 weeks and only mild or moderate adverse events (P<.001; NNT=2.38).⁸

Similarly, a smaller study (84 patients) showed that 60% of patients on etanercept vs 20% on placebo had good clinical benefit at only 12 weeks (P<.001, NNT=2.5).⁹

For other rheumatic diseases, studies are mixed

Due to cyclosporine’s toxicity, less toxic DMARDs are being evaluated to replace it for treatment of other rheumatic diseases. A recent randomized controlled trial of 100 patients with antineutrophil cytoplasmic antibody–associated systemic vasculitis showed methotrexate may be able to replace cyclosporine for both induction of remission (methotrexate=89.8% vs cyclosporine=93.5%; P=.041) and maintenance of remission (69.5% vs 46.5% at 18 months; P=.023).¹⁰

Initial trials on other rheumatic diseases have been small and have had varied results. There are mixed studies on the effectiveness of adding methotrexate to corticosteroids for giant cell arteritis.^11,12

There has been no evidence of efficacy for the new TNF antagonists in either a small study on Sjögren’s syndrome (n=14)¹³ or a larger study on Wegener’s granulomatosis (n=180).¹⁴

The studies for use of DMARDs in lupus or scleroderma are of limited quality.

Recommendations from others

The Italian Society for Rheumatology consensus guidelines recommends TNF antagonists be considered in active psoriatic arthritis resistant to (a) NSAIDs, (b) at least 2 local steroid injections, and (c) at least 2 conventional DMARDs for patients with peripheral arthritis or enthesitis. They also recommend TNF antagonists be considered for psoriatic spondylitis resistant to NSAIDs.¹⁵

The Assessment in Ankylosing Spondylitis (ASAS) International Working Group and the European League Against Rheumatism (EULAR) recommendations for the treatment of ankylosing spondylitis, based on a systematic review of the literature and expert opinion, indicate that:

• There is good evidence for using NSAIDs and COX-2 inhibitors for symptomatic treatment.
• Conventional DMARDs are not well supported.
• TNF antagonists show a large benefit in both pain and function.

The ASAS/EULAR recommendation indicate that there is no evidence that any of these treatments actually modify the disease progression.¹⁶

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

The use of DMARDs has become standard of care for rheumatoid arthritis, for both therapy and prevention of progression of this debilitating disease. However, the use of DMARDs in nonrheumatoid rheumatologic disease is still under investigation, and at this point, the use of DMARDs as first-line therapy is not recommended; however, second-line therapy with DMARDs is common.

For psoriatic arthritis, DMARDs are beneficial as a second-line therapy

A Cochrane systematic review identified 13 randomized controlled trials enrolling a combined 1022 patients with psoriatic arthritis randomly assigned to receive a DMARD—methotrexate, sulfasalazine (Azulfidine), azathioprine (Imuran/ Azasan), or etretinate (Tegison; no longer available in the US)—compared with placebo.² All agents were better than placebo; however, only 2 agents (parenteral high-dose methotrexate and sulfasalazine) had clinically important benefits for more than half the patients. The studies were too small to establish toxicity or to evaluate the other agents.

NSAIDs are still the preferred first-line therapy, concluded a recent publication on the treatment of psoriatic arthritis, which looked at 54 different studies; however, second-line therapy could include methotrexate, sulfasalazine, etanercept (Enbrel), infliximab (Remicade), cyclosporine, or combination therapy.³ Sulfasalazine appeared to be clinically beneficial for peripheral psoriatic arthritis.

Etanercept vs placebo. An initial study (60 patients) of etanercept vs placebo among patients who were permitted to stay on methotrexate or prednisone showed a response rate of 87% vs 23% (P<.0001; number needed to treat [NNT]=1.56).⁴

Infliximab vs placebo. A study of infliximab vs placebo involving 104 patients had similar results, with good response in 65% vs 10% (NNT=1.81) at 16 weeks; infliximab also inhibited radiographic progression by 22%.⁵

Cyclosporine. Although it is effective, reserve cyclosporine for patients who do not improve on other regimens, because of its nephrotoxicity.³

DMARDs show some benefit in treating ankylosing spondylitis

Two recent Cochrane systematic reviews on ankylosing spondylitis examined the use of sulfasalazine and methotrexate as second-line agents.^6,7 Eleven trials were included in the sulfasalazine analysis, with a total of 895 patients. Sulfasalazine demonstrated some benefit in reducing erythrocyte sedimentation rates (ESRs) and morning stiffness, but there was no evidence that the drug reduced pain or improved physical function, spinal mobility, or rate of enthesitis. Sulfasalazine was well tolerated and may be useful in early mild disease for patients with peripheral arthritis and high ESRs. On the other hand, evidence was insufficient to determine whether methotrexate benefited patients with ankylosing spondylitis.

In other trials, infliximab and etanercept showed good potential for benefit in treating ankylosing spondylitis.

One study of infliximab vs placebo showed 61.2% vs 19.2% patients with good clinical benefit at 24 weeks and only mild or moderate adverse events (P<.001; NNT=2.38).⁸

Similarly, a smaller study (84 patients) showed that 60% of patients on etanercept vs 20% on placebo had good clinical benefit at only 12 weeks (P<.001, NNT=2.5).⁹

For other rheumatic diseases, studies are mixed

Due to cyclosporine’s toxicity, less toxic DMARDs are being evaluated to replace it for treatment of other rheumatic diseases. A recent randomized controlled trial of 100 patients with antineutrophil cytoplasmic antibody–associated systemic vasculitis showed methotrexate may be able to replace cyclosporine for both induction of remission (methotrexate=89.8% vs cyclosporine=93.5%; P=.041) and maintenance of remission (69.5% vs 46.5% at 18 months; P=.023).¹⁰

Initial trials on other rheumatic diseases have been small and have had varied results. There are mixed studies on the effectiveness of adding methotrexate to corticosteroids for giant cell arteritis.^11,12

There has been no evidence of efficacy for the new TNF antagonists in either a small study on Sjögren’s syndrome (n=14)¹³ or a larger study on Wegener’s granulomatosis (n=180).¹⁴

The studies for use of DMARDs in lupus or scleroderma are of limited quality.

Recommendations from others

The Italian Society for Rheumatology consensus guidelines recommends TNF antagonists be considered in active psoriatic arthritis resistant to (a) NSAIDs, (b) at least 2 local steroid injections, and (c) at least 2 conventional DMARDs for patients with peripheral arthritis or enthesitis. They also recommend TNF antagonists be considered for psoriatic spondylitis resistant to NSAIDs.¹⁵

The Assessment in Ankylosing Spondylitis (ASAS) International Working Group and the European League Against Rheumatism (EULAR) recommendations for the treatment of ankylosing spondylitis, based on a systematic review of the literature and expert opinion, indicate that:

• There is good evidence for using NSAIDs and COX-2 inhibitors for symptomatic treatment.
• Conventional DMARDs are not well supported.
• TNF antagonists show a large benefit in both pain and function.

The ASAS/EULAR recommendation indicate that there is no evidence that any of these treatments actually modify the disease progression.¹⁶

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

The use of DMARDs has become standard of care for rheumatoid arthritis, for both therapy and prevention of progression of this debilitating disease. However, the use of DMARDs in nonrheumatoid rheumatologic disease is still under investigation, and at this point, the use of DMARDs as first-line therapy is not recommended; however, second-line therapy with DMARDs is common.

For psoriatic arthritis, DMARDs are beneficial as a second-line therapy

A Cochrane systematic review identified 13 randomized controlled trials enrolling a combined 1022 patients with psoriatic arthritis randomly assigned to receive a DMARD—methotrexate, sulfasalazine (Azulfidine), azathioprine (Imuran/ Azasan), or etretinate (Tegison; no longer available in the US)—compared with placebo.² All agents were better than placebo; however, only 2 agents (parenteral high-dose methotrexate and sulfasalazine) had clinically important benefits for more than half the patients. The studies were too small to establish toxicity or to evaluate the other agents.

NSAIDs are still the preferred first-line therapy, concluded a recent publication on the treatment of psoriatic arthritis, which looked at 54 different studies; however, second-line therapy could include methotrexate, sulfasalazine, etanercept (Enbrel), infliximab (Remicade), cyclosporine, or combination therapy.³ Sulfasalazine appeared to be clinically beneficial for peripheral psoriatic arthritis.

Etanercept vs placebo. An initial study (60 patients) of etanercept vs placebo among patients who were permitted to stay on methotrexate or prednisone showed a response rate of 87% vs 23% (P<.0001; number needed to treat [NNT]=1.56).⁴

Infliximab vs placebo. A study of infliximab vs placebo involving 104 patients had similar results, with good response in 65% vs 10% (NNT=1.81) at 16 weeks; infliximab also inhibited radiographic progression by 22%.⁵

Cyclosporine. Although it is effective, reserve cyclosporine for patients who do not improve on other regimens, because of its nephrotoxicity.³

DMARDs show some benefit in treating ankylosing spondylitis

Two recent Cochrane systematic reviews on ankylosing spondylitis examined the use of sulfasalazine and methotrexate as second-line agents.^6,7 Eleven trials were included in the sulfasalazine analysis, with a total of 895 patients. Sulfasalazine demonstrated some benefit in reducing erythrocyte sedimentation rates (ESRs) and morning stiffness, but there was no evidence that the drug reduced pain or improved physical function, spinal mobility, or rate of enthesitis. Sulfasalazine was well tolerated and may be useful in early mild disease for patients with peripheral arthritis and high ESRs. On the other hand, evidence was insufficient to determine whether methotrexate benefited patients with ankylosing spondylitis.

In other trials, infliximab and etanercept showed good potential for benefit in treating ankylosing spondylitis.

One study of infliximab vs placebo showed 61.2% vs 19.2% patients with good clinical benefit at 24 weeks and only mild or moderate adverse events (P<.001; NNT=2.38).⁸

Similarly, a smaller study (84 patients) showed that 60% of patients on etanercept vs 20% on placebo had good clinical benefit at only 12 weeks (P<.001, NNT=2.5).⁹

For other rheumatic diseases, studies are mixed

Due to cyclosporine’s toxicity, less toxic DMARDs are being evaluated to replace it for treatment of other rheumatic diseases. A recent randomized controlled trial of 100 patients with antineutrophil cytoplasmic antibody–associated systemic vasculitis showed methotrexate may be able to replace cyclosporine for both induction of remission (methotrexate=89.8% vs cyclosporine=93.5%; P=.041) and maintenance of remission (69.5% vs 46.5% at 18 months; P=.023).¹⁰

Initial trials on other rheumatic diseases have been small and have had varied results. There are mixed studies on the effectiveness of adding methotrexate to corticosteroids for giant cell arteritis.^11,12

There has been no evidence of efficacy for the new TNF antagonists in either a small study on Sjögren’s syndrome (n=14)¹³ or a larger study on Wegener’s granulomatosis (n=180).¹⁴

The studies for use of DMARDs in lupus or scleroderma are of limited quality.

Recommendations from others

The Italian Society for Rheumatology consensus guidelines recommends TNF antagonists be considered in active psoriatic arthritis resistant to (a) NSAIDs, (b) at least 2 local steroid injections, and (c) at least 2 conventional DMARDs for patients with peripheral arthritis or enthesitis. They also recommend TNF antagonists be considered for psoriatic spondylitis resistant to NSAIDs.¹⁵

The Assessment in Ankylosing Spondylitis (ASAS) International Working Group and the European League Against Rheumatism (EULAR) recommendations for the treatment of ankylosing spondylitis, based on a systematic review of the literature and expert opinion, indicate that:

• There is good evidence for using NSAIDs and COX-2 inhibitors for symptomatic treatment.
• Conventional DMARDs are not well supported.
• TNF antagonists show a large benefit in both pain and function.

The ASAS/EULAR recommendation indicate that there is no evidence that any of these treatments actually modify the disease progression.¹⁶

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

A wide variety of conditions can cause scrotal masses (see TABLE 1 for a list of causes of acute scrotal swelling and TABLE 2 for causes of nonacute swelling).^1,2 Many just require that you reassure the patient; however, some conditions do need diagnostic testing to determine appropriate treatment.

TABLE 1
Causes of acute scrotal swelling^1,2

TABLE 2
Causes of nonacute scrotal swelling¹

Ultrasound is the best initial test

Testicular torsion and acute epididymoorchitis are the most common causes of an acute scrotum.³ Patients with an acute scrotum require an urgent ultrasound to exclude pathology that requires immediate surgery (TABLES 1 AND 2).¹ Although clinical exam identifies almost all cases of torsion, a few cases are missed.⁴ In a study of 209 emergency scrotal explorations, clinical exam by general practitioners and surgeons correctly diagnosed only 92.5% and 94% of testicular torsion cases, respectively, compared with the surgical diagnosis.⁴

In another study, which used surgery as the diagnostic gold standard, color Doppler ultrasound had a sensitivity of 93.5% for the diagnosis of testicular torsion;⁵ this has led some to say the combination of both clinical exam and ultrasound should be used to determine the need for surgery.¹ However, this combination has not been thoroughly evaluated by researchers, and the best evidence shows that physician exam is essentially the same as color Doppler ultrasound for diagnosing testicular torsion. If torsion cannot be reliably excluded, emergent surgical exploration is mandatory.⁴

For patients who have a nonacute scrotal mass, ultrasound is often indicated to distinguish intratesticular from extratesticular masses.¹ Although testicular neoplasm is relatively rare, it is a concern for patients with non-painful masses. Fortunately, false-negative scrotal ultrasounds are rare. In a small study comparing clinical exam with ultrasound for diagnosis of testicular tumor, the negative predictive value of ultrasound was 100%.⁶

Although ultrasound has high sensitivity for detection of testicular neoplasm, it cannot differentiate benign from malignant tumors.² Additionally, ultrasound sometimes fails to differentiate a neoplastic process from a complication of an infection such as an abscess. In those instances, a repeat ultrasound is suggested after antibiotic administration to ensure resolution of the mass.²

When ultrasound is inconclusive, MRI may be helpful

When clinical and ultrasound findings are inconclusive, MRI may help deter-mine a diagnosis. For example, MRI can help distinguish inflammation or abscess from neoplasm, thus preventing a patient from undergoing unnecessary surgical intervention.^2,7 If testicular neoplasm cannot be excluded based on clinical and radiographic findings, surgery is indicated.¹

Recommendations from others

Few current evidence-based recommendations exist on the approach to patients with scrotal masses. The National Collaborating Centre for Primary Care (UK) suggests an urgent ultrasound when a scrotal mass does not transilluminate or when the examiner cannot distinguish the body of the testis.⁸

Evidence summary

A wide variety of conditions can cause scrotal masses (see TABLE 1 for a list of causes of acute scrotal swelling and TABLE 2 for causes of nonacute swelling).^1,2 Many just require that you reassure the patient; however, some conditions do need diagnostic testing to determine appropriate treatment.

TABLE 1
Causes of acute scrotal swelling^1,2

TABLE 2
Causes of nonacute scrotal swelling¹

Ultrasound is the best initial test

Testicular torsion and acute epididymoorchitis are the most common causes of an acute scrotum.³ Patients with an acute scrotum require an urgent ultrasound to exclude pathology that requires immediate surgery (TABLES 1 AND 2).¹ Although clinical exam identifies almost all cases of torsion, a few cases are missed.⁴ In a study of 209 emergency scrotal explorations, clinical exam by general practitioners and surgeons correctly diagnosed only 92.5% and 94% of testicular torsion cases, respectively, compared with the surgical diagnosis.⁴

In another study, which used surgery as the diagnostic gold standard, color Doppler ultrasound had a sensitivity of 93.5% for the diagnosis of testicular torsion;⁵ this has led some to say the combination of both clinical exam and ultrasound should be used to determine the need for surgery.¹ However, this combination has not been thoroughly evaluated by researchers, and the best evidence shows that physician exam is essentially the same as color Doppler ultrasound for diagnosing testicular torsion. If torsion cannot be reliably excluded, emergent surgical exploration is mandatory.⁴

For patients who have a nonacute scrotal mass, ultrasound is often indicated to distinguish intratesticular from extratesticular masses.¹ Although testicular neoplasm is relatively rare, it is a concern for patients with non-painful masses. Fortunately, false-negative scrotal ultrasounds are rare. In a small study comparing clinical exam with ultrasound for diagnosis of testicular tumor, the negative predictive value of ultrasound was 100%.⁶

Although ultrasound has high sensitivity for detection of testicular neoplasm, it cannot differentiate benign from malignant tumors.² Additionally, ultrasound sometimes fails to differentiate a neoplastic process from a complication of an infection such as an abscess. In those instances, a repeat ultrasound is suggested after antibiotic administration to ensure resolution of the mass.²

When ultrasound is inconclusive, MRI may be helpful

When clinical and ultrasound findings are inconclusive, MRI may help deter-mine a diagnosis. For example, MRI can help distinguish inflammation or abscess from neoplasm, thus preventing a patient from undergoing unnecessary surgical intervention.^2,7 If testicular neoplasm cannot be excluded based on clinical and radiographic findings, surgery is indicated.¹

Recommendations from others

Few current evidence-based recommendations exist on the approach to patients with scrotal masses. The National Collaborating Centre for Primary Care (UK) suggests an urgent ultrasound when a scrotal mass does not transilluminate or when the examiner cannot distinguish the body of the testis.⁸

Evidence summary

A wide variety of conditions can cause scrotal masses (see TABLE 1 for a list of causes of acute scrotal swelling and TABLE 2 for causes of nonacute swelling).^1,2 Many just require that you reassure the patient; however, some conditions do need diagnostic testing to determine appropriate treatment.

TABLE 1
Causes of acute scrotal swelling^1,2

TABLE 2
Causes of nonacute scrotal swelling¹

Ultrasound is the best initial test

Testicular torsion and acute epididymoorchitis are the most common causes of an acute scrotum.³ Patients with an acute scrotum require an urgent ultrasound to exclude pathology that requires immediate surgery (TABLES 1 AND 2).¹ Although clinical exam identifies almost all cases of torsion, a few cases are missed.⁴ In a study of 209 emergency scrotal explorations, clinical exam by general practitioners and surgeons correctly diagnosed only 92.5% and 94% of testicular torsion cases, respectively, compared with the surgical diagnosis.⁴

In another study, which used surgery as the diagnostic gold standard, color Doppler ultrasound had a sensitivity of 93.5% for the diagnosis of testicular torsion;⁵ this has led some to say the combination of both clinical exam and ultrasound should be used to determine the need for surgery.¹ However, this combination has not been thoroughly evaluated by researchers, and the best evidence shows that physician exam is essentially the same as color Doppler ultrasound for diagnosing testicular torsion. If torsion cannot be reliably excluded, emergent surgical exploration is mandatory.⁴

For patients who have a nonacute scrotal mass, ultrasound is often indicated to distinguish intratesticular from extratesticular masses.¹ Although testicular neoplasm is relatively rare, it is a concern for patients with non-painful masses. Fortunately, false-negative scrotal ultrasounds are rare. In a small study comparing clinical exam with ultrasound for diagnosis of testicular tumor, the negative predictive value of ultrasound was 100%.⁶

Although ultrasound has high sensitivity for detection of testicular neoplasm, it cannot differentiate benign from malignant tumors.² Additionally, ultrasound sometimes fails to differentiate a neoplastic process from a complication of an infection such as an abscess. In those instances, a repeat ultrasound is suggested after antibiotic administration to ensure resolution of the mass.²

When ultrasound is inconclusive, MRI may be helpful

When clinical and ultrasound findings are inconclusive, MRI may help deter-mine a diagnosis. For example, MRI can help distinguish inflammation or abscess from neoplasm, thus preventing a patient from undergoing unnecessary surgical intervention.^2,7 If testicular neoplasm cannot be excluded based on clinical and radiographic findings, surgery is indicated.¹

Recommendations from others

Few current evidence-based recommendations exist on the approach to patients with scrotal masses. The National Collaborating Centre for Primary Care (UK) suggests an urgent ultrasound when a scrotal mass does not transilluminate or when the examiner cannot distinguish the body of the testis.⁸

Evidence summary

Exercise vs diet: Some conflicting results

Studies comparing the effectiveness of exercise and diet in weight reduction have yielded conflicting results. Earlier studies, including a meta-analysis and randomized (noncontrolled) study, favored interventions that included caloric restriction (diet alone or diet plus exercise).^1,2

However, subjects on caloric restriction regained a significant amount of weight over time (0.9 kg±7.7 at 2-year follow-up). Subjects who did aerobic exercise but did not diet lost less weight initially (0.7 kg±2.8) but maintained their weight loss better than those who dieted or dieted with exercise.

These earlier studies failed to control for the confounding variable of energy balance—that is, ensuring the amount of calories reduced was comparable with the amount of calories burned through exercise between groups. A more recent randomized controlled trial suggests that aerobic exercise and caloric restriction are equally beneficial in reducing weight for obese men when controlling for negative energy balance.³ However, those who exercised experienced greater fat reduction and maintenance of skeletal muscle mass than those who only restricted calories. Similar findings regarding fat reduction have been reported elsewhere.⁴

Combining diet and exercise appears to be superior to diet alone, based on the results of a recent meta-analysis of randomized controlled trials.⁵ However, this meta-analysis did not specify type of exercise, so it is unclear whether outcomes varied by activity.

Exercise: Is there a dose-response relationship?

Several studies have looked at the relationship between duration and intensity for exercise and weight loss. A dose-response relationship has been observed between the amount of time spent in aerobic exercise per week and the amount of weight lost for overweight women.^6,7

There appears to be no significant difference in weight loss based on duration of a single aerobic exercise episode; rather, weight loss is similar whether completed in short or long bouts.^7,8 One study found that at 12 months, individuals exercising more than 200 minutes per week lost 7.8 kg more (P<.01) than those exercising less than 150 minutes per week.⁷ Another study noted that at 18 months, subjects exercising more than 200 minutes per week lost 9.6 kg more than subjects exercising less than 150 minutes per week (P<.05).⁶

Studies with energy expenditure, rather than time spent exercising, as the independent variable had similar results. At 18 months, individuals with higher energy expenditure (2500 kcal/week) lost 6.7 kg±8.1 compared with a mean loss of 4.1±8.3 in subjects with lower energy expenditure (maximum of 1000 kcal/week).⁹

Recommendations from others

The National Institutes of Health’s National Heart, Lung and Blood Institute,¹⁰ the US Department of Health and Human Services,¹¹ the Centers for Disease Control and Prevention’s Healthy People 2010¹² recommend between 30 to 90 minutes of daily moderate physical activity, and that this activity be done at least 5 days a week—or even 7 days per week—depending on whether a person’s goal is weight maintenance or weight loss.

Another option, offered by the CDC, is that people do 20 minutes of vigorous activity 3 days or more per week. All of the groups recommend staying within caloric intake requirements (TABLE).

TABLE
How much exercise is best? Government agencies weigh in

Evidence summary

Exercise vs diet: Some conflicting results

Studies comparing the effectiveness of exercise and diet in weight reduction have yielded conflicting results. Earlier studies, including a meta-analysis and randomized (noncontrolled) study, favored interventions that included caloric restriction (diet alone or diet plus exercise).^1,2

However, subjects on caloric restriction regained a significant amount of weight over time (0.9 kg±7.7 at 2-year follow-up). Subjects who did aerobic exercise but did not diet lost less weight initially (0.7 kg±2.8) but maintained their weight loss better than those who dieted or dieted with exercise.

These earlier studies failed to control for the confounding variable of energy balance—that is, ensuring the amount of calories reduced was comparable with the amount of calories burned through exercise between groups. A more recent randomized controlled trial suggests that aerobic exercise and caloric restriction are equally beneficial in reducing weight for obese men when controlling for negative energy balance.³ However, those who exercised experienced greater fat reduction and maintenance of skeletal muscle mass than those who only restricted calories. Similar findings regarding fat reduction have been reported elsewhere.⁴

Combining diet and exercise appears to be superior to diet alone, based on the results of a recent meta-analysis of randomized controlled trials.⁵ However, this meta-analysis did not specify type of exercise, so it is unclear whether outcomes varied by activity.

Exercise: Is there a dose-response relationship?

Several studies have looked at the relationship between duration and intensity for exercise and weight loss. A dose-response relationship has been observed between the amount of time spent in aerobic exercise per week and the amount of weight lost for overweight women.^6,7

There appears to be no significant difference in weight loss based on duration of a single aerobic exercise episode; rather, weight loss is similar whether completed in short or long bouts.^7,8 One study found that at 12 months, individuals exercising more than 200 minutes per week lost 7.8 kg more (P<.01) than those exercising less than 150 minutes per week.⁷ Another study noted that at 18 months, subjects exercising more than 200 minutes per week lost 9.6 kg more than subjects exercising less than 150 minutes per week (P<.05).⁶

Studies with energy expenditure, rather than time spent exercising, as the independent variable had similar results. At 18 months, individuals with higher energy expenditure (2500 kcal/week) lost 6.7 kg±8.1 compared with a mean loss of 4.1±8.3 in subjects with lower energy expenditure (maximum of 1000 kcal/week).⁹

Recommendations from others

The National Institutes of Health’s National Heart, Lung and Blood Institute,¹⁰ the US Department of Health and Human Services,¹¹ the Centers for Disease Control and Prevention’s Healthy People 2010¹² recommend between 30 to 90 minutes of daily moderate physical activity, and that this activity be done at least 5 days a week—or even 7 days per week—depending on whether a person’s goal is weight maintenance or weight loss.

Another option, offered by the CDC, is that people do 20 minutes of vigorous activity 3 days or more per week. All of the groups recommend staying within caloric intake requirements (TABLE).

TABLE
How much exercise is best? Government agencies weigh in

Evidence summary

Exercise vs diet: Some conflicting results

Studies comparing the effectiveness of exercise and diet in weight reduction have yielded conflicting results. Earlier studies, including a meta-analysis and randomized (noncontrolled) study, favored interventions that included caloric restriction (diet alone or diet plus exercise).^1,2

However, subjects on caloric restriction regained a significant amount of weight over time (0.9 kg±7.7 at 2-year follow-up). Subjects who did aerobic exercise but did not diet lost less weight initially (0.7 kg±2.8) but maintained their weight loss better than those who dieted or dieted with exercise.

These earlier studies failed to control for the confounding variable of energy balance—that is, ensuring the amount of calories reduced was comparable with the amount of calories burned through exercise between groups. A more recent randomized controlled trial suggests that aerobic exercise and caloric restriction are equally beneficial in reducing weight for obese men when controlling for negative energy balance.³ However, those who exercised experienced greater fat reduction and maintenance of skeletal muscle mass than those who only restricted calories. Similar findings regarding fat reduction have been reported elsewhere.⁴

Combining diet and exercise appears to be superior to diet alone, based on the results of a recent meta-analysis of randomized controlled trials.⁵ However, this meta-analysis did not specify type of exercise, so it is unclear whether outcomes varied by activity.

Exercise: Is there a dose-response relationship?

Several studies have looked at the relationship between duration and intensity for exercise and weight loss. A dose-response relationship has been observed between the amount of time spent in aerobic exercise per week and the amount of weight lost for overweight women.^6,7

There appears to be no significant difference in weight loss based on duration of a single aerobic exercise episode; rather, weight loss is similar whether completed in short or long bouts.^7,8 One study found that at 12 months, individuals exercising more than 200 minutes per week lost 7.8 kg more (P<.01) than those exercising less than 150 minutes per week.⁷ Another study noted that at 18 months, subjects exercising more than 200 minutes per week lost 9.6 kg more than subjects exercising less than 150 minutes per week (P<.05).⁶

Studies with energy expenditure, rather than time spent exercising, as the independent variable had similar results. At 18 months, individuals with higher energy expenditure (2500 kcal/week) lost 6.7 kg±8.1 compared with a mean loss of 4.1±8.3 in subjects with lower energy expenditure (maximum of 1000 kcal/week).⁹

Recommendations from others

The National Institutes of Health’s National Heart, Lung and Blood Institute,¹⁰ the US Department of Health and Human Services,¹¹ the Centers for Disease Control and Prevention’s Healthy People 2010¹² recommend between 30 to 90 minutes of daily moderate physical activity, and that this activity be done at least 5 days a week—or even 7 days per week—depending on whether a person’s goal is weight maintenance or weight loss.

Another option, offered by the CDC, is that people do 20 minutes of vigorous activity 3 days or more per week. All of the groups recommend staying within caloric intake requirements (TABLE).

TABLE
How much exercise is best? Government agencies weigh in

Evidence summary

Retrospective analysis of 2 large cohort studies of adults with bipolar disorder indicated that at least 50% of these patients had an onset of illness before age 19, establishing support for the presence of bipolar disorder among children and adolescents.¹ The criteria in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) cannot be easily applied to most children and adolescents with bipolar disorder because most do not meet the criteria for Bipolar I or II, but fall into the less well-defined category Bipolar NOS (not otherwise specified).^2,3

Compared with adults, children and adolescents are more difficult to diagnose because they are less likely to have discrete episodes of mania, and instead present with severe irritability, rapid cycling, or mixed mania.^2,4 In laddition, symptoms progress and evolve as children and adolescents grow.¹ Comorbid disorders such as ADHD, oppositional defiant disorder, conduct disorder, and learning disorders are common in this population, further complicating diagnosis.²

Screening instruments are imperfect

Different versions of the KSADS have been used in most research studies on this disorder.² Despite this, concerns about the validity of the instrument still exist because of lack of sufficient testing, vagueness of the diagnostic criteria, and the subjective nature of the test.^5,6 Because specialized training is required to administer the test and testing can last a full day, its use in most office settings is impractical. It is also not meant as a stand-alone test, but to be used in conjunction with a clinical evaluation by a trained mental health professional.⁷

In a general clinical setting, family history and selected screening instruments may help to increase or decrease clinical suspicion for the disorder and guide referral for more specialized evaluation by a child mental health provider. In addition, a meta-analysis found that children or adolescents who have a biologic parent with bipolar disorder have 2 to 10 times the odds of being diagnosed with bipolar disorder.⁷

Three screening tests (CBCL, P-GBI, and P-YMRS) available for the office setting use parent-reported scores, and perform best when compared with KSADS as the standard.³ These instruments were associated with likelihood ratios that significantly improved the odds of diagnosis and could allow clinicians to stratify patients as high or low risk (TABLE).³

TABLE
Likelihood ratios for 3 screening tools you can use in the office

Recommendations from others

Two consensus conferences, a Canadian guideline, and a National Institute of Mental Health round-table all concluded that there is currently no ideal test for the diagnosis of child and adolescent bipolar disorder, but that such an instrument needed to be developed.^2,5,6,8 One consensus conference further concluded that the diagnosis is best made by childhood mental health specialists based on multiple informants, such as the child and parents, with symptoms present in at least 2 settings or by direct observation.⁶

A Canadian consensus conference proposed screening patients with depressive symptoms for a history of hypomanic or manic symptoms, and consider an underlying mood disorder in those with vague or nonspecific somatic symptoms or reverse vegetative symptoms (eg, hypersomnia and hyperphagia). Their recommendations also emphasized screening for family history of bipolar disorder when there were clinical concerns.⁸

Evidence summary

Retrospective analysis of 2 large cohort studies of adults with bipolar disorder indicated that at least 50% of these patients had an onset of illness before age 19, establishing support for the presence of bipolar disorder among children and adolescents.¹ The criteria in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) cannot be easily applied to most children and adolescents with bipolar disorder because most do not meet the criteria for Bipolar I or II, but fall into the less well-defined category Bipolar NOS (not otherwise specified).^2,3

Compared with adults, children and adolescents are more difficult to diagnose because they are less likely to have discrete episodes of mania, and instead present with severe irritability, rapid cycling, or mixed mania.^2,4 In laddition, symptoms progress and evolve as children and adolescents grow.¹ Comorbid disorders such as ADHD, oppositional defiant disorder, conduct disorder, and learning disorders are common in this population, further complicating diagnosis.²

Screening instruments are imperfect

Different versions of the KSADS have been used in most research studies on this disorder.² Despite this, concerns about the validity of the instrument still exist because of lack of sufficient testing, vagueness of the diagnostic criteria, and the subjective nature of the test.^5,6 Because specialized training is required to administer the test and testing can last a full day, its use in most office settings is impractical. It is also not meant as a stand-alone test, but to be used in conjunction with a clinical evaluation by a trained mental health professional.⁷

In a general clinical setting, family history and selected screening instruments may help to increase or decrease clinical suspicion for the disorder and guide referral for more specialized evaluation by a child mental health provider. In addition, a meta-analysis found that children or adolescents who have a biologic parent with bipolar disorder have 2 to 10 times the odds of being diagnosed with bipolar disorder.⁷

Three screening tests (CBCL, P-GBI, and P-YMRS) available for the office setting use parent-reported scores, and perform best when compared with KSADS as the standard.³ These instruments were associated with likelihood ratios that significantly improved the odds of diagnosis and could allow clinicians to stratify patients as high or low risk (TABLE).³

TABLE
Likelihood ratios for 3 screening tools you can use in the office

Recommendations from others

Two consensus conferences, a Canadian guideline, and a National Institute of Mental Health round-table all concluded that there is currently no ideal test for the diagnosis of child and adolescent bipolar disorder, but that such an instrument needed to be developed.^2,5,6,8 One consensus conference further concluded that the diagnosis is best made by childhood mental health specialists based on multiple informants, such as the child and parents, with symptoms present in at least 2 settings or by direct observation.⁶

A Canadian consensus conference proposed screening patients with depressive symptoms for a history of hypomanic or manic symptoms, and consider an underlying mood disorder in those with vague or nonspecific somatic symptoms or reverse vegetative symptoms (eg, hypersomnia and hyperphagia). Their recommendations also emphasized screening for family history of bipolar disorder when there were clinical concerns.⁸

Evidence summary

Retrospective analysis of 2 large cohort studies of adults with bipolar disorder indicated that at least 50% of these patients had an onset of illness before age 19, establishing support for the presence of bipolar disorder among children and adolescents.¹ The criteria in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) cannot be easily applied to most children and adolescents with bipolar disorder because most do not meet the criteria for Bipolar I or II, but fall into the less well-defined category Bipolar NOS (not otherwise specified).^2,3

Compared with adults, children and adolescents are more difficult to diagnose because they are less likely to have discrete episodes of mania, and instead present with severe irritability, rapid cycling, or mixed mania.^2,4 In laddition, symptoms progress and evolve as children and adolescents grow.¹ Comorbid disorders such as ADHD, oppositional defiant disorder, conduct disorder, and learning disorders are common in this population, further complicating diagnosis.²

Screening instruments are imperfect

Different versions of the KSADS have been used in most research studies on this disorder.² Despite this, concerns about the validity of the instrument still exist because of lack of sufficient testing, vagueness of the diagnostic criteria, and the subjective nature of the test.^5,6 Because specialized training is required to administer the test and testing can last a full day, its use in most office settings is impractical. It is also not meant as a stand-alone test, but to be used in conjunction with a clinical evaluation by a trained mental health professional.⁷

In a general clinical setting, family history and selected screening instruments may help to increase or decrease clinical suspicion for the disorder and guide referral for more specialized evaluation by a child mental health provider. In addition, a meta-analysis found that children or adolescents who have a biologic parent with bipolar disorder have 2 to 10 times the odds of being diagnosed with bipolar disorder.⁷

Three screening tests (CBCL, P-GBI, and P-YMRS) available for the office setting use parent-reported scores, and perform best when compared with KSADS as the standard.³ These instruments were associated with likelihood ratios that significantly improved the odds of diagnosis and could allow clinicians to stratify patients as high or low risk (TABLE).³

TABLE
Likelihood ratios for 3 screening tools you can use in the office

Recommendations from others

Two consensus conferences, a Canadian guideline, and a National Institute of Mental Health round-table all concluded that there is currently no ideal test for the diagnosis of child and adolescent bipolar disorder, but that such an instrument needed to be developed.^2,5,6,8 One consensus conference further concluded that the diagnosis is best made by childhood mental health specialists based on multiple informants, such as the child and parents, with symptoms present in at least 2 settings or by direct observation.⁶

A Canadian consensus conference proposed screening patients with depressive symptoms for a history of hypomanic or manic symptoms, and consider an underlying mood disorder in those with vague or nonspecific somatic symptoms or reverse vegetative symptoms (eg, hypersomnia and hyperphagia). Their recommendations also emphasized screening for family history of bipolar disorder when there were clinical concerns.⁸

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.