Clinical Inquiries

Evidence summary

Prevention: No overall benefit, but some approaches may help

A Cochrane meta-analysis of pooled data from 15 RCTs (7697 women) found that psychological interventions didn’t prevent PPD based on comparison of initial depression scores with scores at the conclusion of the studies (relative risk [RR]=0.81; 95% confidence interval [CI], 0.65-1.02).¹ Although some studies suggested short-term benefit (N=4091; RR=0.65; 95% CI, 0.43-1.00), benefits diminished over time and weren’t noted when the definition of depression was limited to an Edinburgh Postpartum Depression Scale (EPDS) score below 12 (out of a maximum of 30). Some differences were found when the data were stratified.

Certain interventions were found to prevent depressive symptoms (defined differently in the various studies). They were: home visits provided by healthcare professionals (2 RCTs, N=1663; RR=0.68; 95% CI, 0.55-0.84), interventions targeting at-risk women (7 RCTs, N=1162; RR=0.67; 95% CI, 0.51-0.89), and interventions begun postnatally (10 RCTs, N=6379; RR=0.76; 95% CI, 0.58-0.98). Notably, the level of training of providers of psychological interventions included in the meta-analysis was highly variable.

A later RCT of a 6-session cognitive-behavioral, midwife-administered intervention in mothers of preterm infants showed no preventive benefit (N=176; RR=1.02; 95% CI, 0.87-1.20).²

Treatment: Counseling helps, especially in the near term

A recent systematic review of 5 RCTs (N=450) investigated the effectiveness of interpersonal psychotherapy, CBT (individual and group), nondirective counseling, and psychodynamic therapy in reducing PPD symptoms.³

Interpersonal therapy (12 weekly sessions) significantly reduced PPD symptoms as measured by the Hamilton Depression Rating Scale (HAM-D) compared with a wait-list control group (1 RCT, N=120, RR=2.11; 95% CI, 1.04-4.28).

Individual CBT and ideal standard care (weekly 20- to 60-minute supportive meetings) were equally effective in reducing depression scores immediately postintervention and 6 months thereafter as measured by the EPDS (1 RCT, N=37). Although a trend toward greater benefit for CBT was noted, the study was underpowered to identify a significant difference.

Nondirective counseling reduced the proportion of women with depression (N=55; RR=0.49; 95% CI, 0.26-0.95) and lowered EPDS scores (N=193; treatment effect=-2.1; 95% CI, -3.8 to -0.3; P=.02) compared with routine primary care. Individual CBT also reduced EPDS scores, when compared to routine primary care (N=55; treatment effect=-2.7; 95% CI, -4.5 to -0.9; P=.003).

Psychodynamic therapy reduced the proportion of women with major depression (N=55; RR=1.89; 95% CI, 1.33-2.33).

All of these interventions improved PPD immediately following treatment compared with routine primary care, but the benefits were not sustained at long-term follow-up (6 months). Study limitations included failure to control for multiple comparisons, pretreatment group differences, differential attrition among groups, and lack of sufficient power.

A later RCT (N=121) also found psychological interventions (group CBT and group and individual counseling) to be superior to routine primary care, with individual counseling yielding the greatest improvement in PPD symptoms (P<.05).⁴

Antidepressants vs CBT: Too little information

Two RCTs compared antidepressant medications to CBT.³ In the first (N=87), fluoxetine and placebo were each paired with 1 or 6 CBT sessions. After 12 weeks of treatment, fluoxetine was superior to placebo as measured by mean symptom score reduction on the HAM-D, EPDS, and clinical interview schedule; 6 CBT sessions were superior to a single session as measured by mean symptom score reduction on the Hamilton Depression Scale and clinical interview schedule.⁵ No significant interaction effect was found.

The authors reported “highly significant” improvements, but didn’t specify significance level or provide adequate information to calculate number needed to treat. Interpretation of the findings is limited by methodologic weaknesses, high withdrawal rate, and exclusion of breast-feeding women.³

A second, small RCT (N=35) compared 12 weeks of paroxetine with a combination of paroxetine and CBT.⁶ Significant improvements—defined as percentage of patients in each group demonstrating at least a 50% score reduction on the HAM-D (paroxetine, 87.5%; combination, 78.9%) and EPDS (paroxetine, 61.5%; combination, 58.3%)—occurred in both groups (P<.01), but no difference was found between the groups. The study didn’t include a placebo control group.

Recommendations

The National Collaborating Centre for Women’s and Children’s Health recommends against offering educational interventions to pregnant women because such interventions haven’t been found to reduce PPD.⁷

The Scottish Intercollegiate Guidelines Network recommends “postnatal visits, interpersonal therapy, and/or antenatal preparation” to prevent PPD. To treat PPD, they recommend psychosocial interventions, preferably those that include more than 1 family member.⁸

Evidence summary

Prevention: No overall benefit, but some approaches may help

A Cochrane meta-analysis of pooled data from 15 RCTs (7697 women) found that psychological interventions didn’t prevent PPD based on comparison of initial depression scores with scores at the conclusion of the studies (relative risk [RR]=0.81; 95% confidence interval [CI], 0.65-1.02).¹ Although some studies suggested short-term benefit (N=4091; RR=0.65; 95% CI, 0.43-1.00), benefits diminished over time and weren’t noted when the definition of depression was limited to an Edinburgh Postpartum Depression Scale (EPDS) score below 12 (out of a maximum of 30). Some differences were found when the data were stratified.

Certain interventions were found to prevent depressive symptoms (defined differently in the various studies). They were: home visits provided by healthcare professionals (2 RCTs, N=1663; RR=0.68; 95% CI, 0.55-0.84), interventions targeting at-risk women (7 RCTs, N=1162; RR=0.67; 95% CI, 0.51-0.89), and interventions begun postnatally (10 RCTs, N=6379; RR=0.76; 95% CI, 0.58-0.98). Notably, the level of training of providers of psychological interventions included in the meta-analysis was highly variable.

A later RCT of a 6-session cognitive-behavioral, midwife-administered intervention in mothers of preterm infants showed no preventive benefit (N=176; RR=1.02; 95% CI, 0.87-1.20).²

Treatment: Counseling helps, especially in the near term

A recent systematic review of 5 RCTs (N=450) investigated the effectiveness of interpersonal psychotherapy, CBT (individual and group), nondirective counseling, and psychodynamic therapy in reducing PPD symptoms.³

Interpersonal therapy (12 weekly sessions) significantly reduced PPD symptoms as measured by the Hamilton Depression Rating Scale (HAM-D) compared with a wait-list control group (1 RCT, N=120, RR=2.11; 95% CI, 1.04-4.28).

Individual CBT and ideal standard care (weekly 20- to 60-minute supportive meetings) were equally effective in reducing depression scores immediately postintervention and 6 months thereafter as measured by the EPDS (1 RCT, N=37). Although a trend toward greater benefit for CBT was noted, the study was underpowered to identify a significant difference.

Nondirective counseling reduced the proportion of women with depression (N=55; RR=0.49; 95% CI, 0.26-0.95) and lowered EPDS scores (N=193; treatment effect=-2.1; 95% CI, -3.8 to -0.3; P=.02) compared with routine primary care. Individual CBT also reduced EPDS scores, when compared to routine primary care (N=55; treatment effect=-2.7; 95% CI, -4.5 to -0.9; P=.003).

Psychodynamic therapy reduced the proportion of women with major depression (N=55; RR=1.89; 95% CI, 1.33-2.33).

All of these interventions improved PPD immediately following treatment compared with routine primary care, but the benefits were not sustained at long-term follow-up (6 months). Study limitations included failure to control for multiple comparisons, pretreatment group differences, differential attrition among groups, and lack of sufficient power.

A later RCT (N=121) also found psychological interventions (group CBT and group and individual counseling) to be superior to routine primary care, with individual counseling yielding the greatest improvement in PPD symptoms (P<.05).⁴

Antidepressants vs CBT: Too little information

Two RCTs compared antidepressant medications to CBT.³ In the first (N=87), fluoxetine and placebo were each paired with 1 or 6 CBT sessions. After 12 weeks of treatment, fluoxetine was superior to placebo as measured by mean symptom score reduction on the HAM-D, EPDS, and clinical interview schedule; 6 CBT sessions were superior to a single session as measured by mean symptom score reduction on the Hamilton Depression Scale and clinical interview schedule.⁵ No significant interaction effect was found.

The authors reported “highly significant” improvements, but didn’t specify significance level or provide adequate information to calculate number needed to treat. Interpretation of the findings is limited by methodologic weaknesses, high withdrawal rate, and exclusion of breast-feeding women.³

A second, small RCT (N=35) compared 12 weeks of paroxetine with a combination of paroxetine and CBT.⁶ Significant improvements—defined as percentage of patients in each group demonstrating at least a 50% score reduction on the HAM-D (paroxetine, 87.5%; combination, 78.9%) and EPDS (paroxetine, 61.5%; combination, 58.3%)—occurred in both groups (P<.01), but no difference was found between the groups. The study didn’t include a placebo control group.

Recommendations

The National Collaborating Centre for Women’s and Children’s Health recommends against offering educational interventions to pregnant women because such interventions haven’t been found to reduce PPD.⁷

The Scottish Intercollegiate Guidelines Network recommends “postnatal visits, interpersonal therapy, and/or antenatal preparation” to prevent PPD. To treat PPD, they recommend psychosocial interventions, preferably those that include more than 1 family member.⁸

Evidence summary

Prevention: No overall benefit, but some approaches may help

A Cochrane meta-analysis of pooled data from 15 RCTs (7697 women) found that psychological interventions didn’t prevent PPD based on comparison of initial depression scores with scores at the conclusion of the studies (relative risk [RR]=0.81; 95% confidence interval [CI], 0.65-1.02).¹ Although some studies suggested short-term benefit (N=4091; RR=0.65; 95% CI, 0.43-1.00), benefits diminished over time and weren’t noted when the definition of depression was limited to an Edinburgh Postpartum Depression Scale (EPDS) score below 12 (out of a maximum of 30). Some differences were found when the data were stratified.

Certain interventions were found to prevent depressive symptoms (defined differently in the various studies). They were: home visits provided by healthcare professionals (2 RCTs, N=1663; RR=0.68; 95% CI, 0.55-0.84), interventions targeting at-risk women (7 RCTs, N=1162; RR=0.67; 95% CI, 0.51-0.89), and interventions begun postnatally (10 RCTs, N=6379; RR=0.76; 95% CI, 0.58-0.98). Notably, the level of training of providers of psychological interventions included in the meta-analysis was highly variable.

A later RCT of a 6-session cognitive-behavioral, midwife-administered intervention in mothers of preterm infants showed no preventive benefit (N=176; RR=1.02; 95% CI, 0.87-1.20).²

Treatment: Counseling helps, especially in the near term

A recent systematic review of 5 RCTs (N=450) investigated the effectiveness of interpersonal psychotherapy, CBT (individual and group), nondirective counseling, and psychodynamic therapy in reducing PPD symptoms.³

Interpersonal therapy (12 weekly sessions) significantly reduced PPD symptoms as measured by the Hamilton Depression Rating Scale (HAM-D) compared with a wait-list control group (1 RCT, N=120, RR=2.11; 95% CI, 1.04-4.28).

Individual CBT and ideal standard care (weekly 20- to 60-minute supportive meetings) were equally effective in reducing depression scores immediately postintervention and 6 months thereafter as measured by the EPDS (1 RCT, N=37). Although a trend toward greater benefit for CBT was noted, the study was underpowered to identify a significant difference.

Nondirective counseling reduced the proportion of women with depression (N=55; RR=0.49; 95% CI, 0.26-0.95) and lowered EPDS scores (N=193; treatment effect=-2.1; 95% CI, -3.8 to -0.3; P=.02) compared with routine primary care. Individual CBT also reduced EPDS scores, when compared to routine primary care (N=55; treatment effect=-2.7; 95% CI, -4.5 to -0.9; P=.003).

Psychodynamic therapy reduced the proportion of women with major depression (N=55; RR=1.89; 95% CI, 1.33-2.33).

All of these interventions improved PPD immediately following treatment compared with routine primary care, but the benefits were not sustained at long-term follow-up (6 months). Study limitations included failure to control for multiple comparisons, pretreatment group differences, differential attrition among groups, and lack of sufficient power.

A later RCT (N=121) also found psychological interventions (group CBT and group and individual counseling) to be superior to routine primary care, with individual counseling yielding the greatest improvement in PPD symptoms (P<.05).⁴

Antidepressants vs CBT: Too little information

Two RCTs compared antidepressant medications to CBT.³ In the first (N=87), fluoxetine and placebo were each paired with 1 or 6 CBT sessions. After 12 weeks of treatment, fluoxetine was superior to placebo as measured by mean symptom score reduction on the HAM-D, EPDS, and clinical interview schedule; 6 CBT sessions were superior to a single session as measured by mean symptom score reduction on the Hamilton Depression Scale and clinical interview schedule.⁵ No significant interaction effect was found.

The authors reported “highly significant” improvements, but didn’t specify significance level or provide adequate information to calculate number needed to treat. Interpretation of the findings is limited by methodologic weaknesses, high withdrawal rate, and exclusion of breast-feeding women.³

A second, small RCT (N=35) compared 12 weeks of paroxetine with a combination of paroxetine and CBT.⁶ Significant improvements—defined as percentage of patients in each group demonstrating at least a 50% score reduction on the HAM-D (paroxetine, 87.5%; combination, 78.9%) and EPDS (paroxetine, 61.5%; combination, 58.3%)—occurred in both groups (P<.01), but no difference was found between the groups. The study didn’t include a placebo control group.

Recommendations

The National Collaborating Centre for Women’s and Children’s Health recommends against offering educational interventions to pregnant women because such interventions haven’t been found to reduce PPD.⁷

The Scottish Intercollegiate Guidelines Network recommends “postnatal visits, interpersonal therapy, and/or antenatal preparation” to prevent PPD. To treat PPD, they recommend psychosocial interventions, preferably those that include more than 1 family member.⁸

Evidence summary

About 8% of the US population will develop symptoms of PTSD at some point in their lives—usually as the result of a traumatic event, such as combat, a natural disaster, accident, or physical or sexual assault.¹ Primary care settings tend to be the principal point of contact for patients with PTSD, although such patients rarely identify themselves as suffering from the disorder.^2,3

Detailed diagnostic interviews and assessments are generally impractical in primary care.⁴ Brief, easy-to-complete screening tools can help clinicians identify patients with primary symptoms of PTSD.⁴

4-item screen assesses key characteristics of PTSD

The PC-PTSD (TABLE) is a 4-item screen that assesses the underlying characteristics specific to PTSD: re-experiencing, numbing, avoidance, and hyperarousal.⁴ It’s designed to be understandable to patients with an eighth-grade reading level and has been validated in a Department of Veterans Affairs (VA) primary care population (N=188).⁴

With a cutoff score of 3, the PCPTSD has a sensitivity of 78% and specificity of 87%, compared with the gold-standard Clinician-Administered PTSD Scale (CAPS).⁴ Positive responses warrant further evaluation of trauma symptoms and completion of the CAPS by a mental health provider to determine whether the patient may have PTSD or other trauma-related problems.^5-7

TABLE
The primary care PTSD screen (PC-PTSD)⁴

Breslau’s short screen addresses 7 specific symptoms

Breslau’s 7-item screening scale (available at http://ajp.psychiatryonline.org/cgi/content/full/156/6/908#T2) is another empirically tested, brief, simple means of identifying PTSD symptoms in primary care patients.² (See also: www.pubmedcentral.nih.gov/articlerender.fcgifiartid=1484617.) Each item addresses a specific symptom.

The screen has been validated in a VA primary care clinic (N=134). With a cutoff score of 4, it has a sensitivity of 85% and specificity of 84%, yielding a positive predictive value of 71% and negative predictive value of 98%.² The likelihood of a score <3 is 0.04 and a score >5 is 13.5. Scores of 3 to 5 have an indeterminate likelihood value (1.8). Patients with a positive screen should undergo further evaluation by a mental health provider.²

Leave lengthy screens to mental health professionals

The CAPS and the civilian version of the PTSD Symptom Checklist (PCL-C), both with 17 items, are widely used as “screens” for PTSD.⁷ However, their length and the recommendation that they be administered by a mental health professional make them cumbersome and impractical for use in primary care.⁷

Recommendations

A 2007 point-of-care guide written for primary care clinicians recommends Breslau’s short screening scale and the PCPTSD screen for use in this setting.¹ Both the National Center for PTSD and Department of Defense Clinical Guidelines on PTSD recommend initial and annual screening using the PC-PTSD, PTSD Brief Screen, or Short Screening Scale for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) PTSD.⁸

Acknowledgements

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

Evidence summary

About 8% of the US population will develop symptoms of PTSD at some point in their lives—usually as the result of a traumatic event, such as combat, a natural disaster, accident, or physical or sexual assault.¹ Primary care settings tend to be the principal point of contact for patients with PTSD, although such patients rarely identify themselves as suffering from the disorder.^2,3

Detailed diagnostic interviews and assessments are generally impractical in primary care.⁴ Brief, easy-to-complete screening tools can help clinicians identify patients with primary symptoms of PTSD.⁴

4-item screen assesses key characteristics of PTSD

The PC-PTSD (TABLE) is a 4-item screen that assesses the underlying characteristics specific to PTSD: re-experiencing, numbing, avoidance, and hyperarousal.⁴ It’s designed to be understandable to patients with an eighth-grade reading level and has been validated in a Department of Veterans Affairs (VA) primary care population (N=188).⁴

With a cutoff score of 3, the PCPTSD has a sensitivity of 78% and specificity of 87%, compared with the gold-standard Clinician-Administered PTSD Scale (CAPS).⁴ Positive responses warrant further evaluation of trauma symptoms and completion of the CAPS by a mental health provider to determine whether the patient may have PTSD or other trauma-related problems.^5-7

TABLE
The primary care PTSD screen (PC-PTSD)⁴

Breslau’s short screen addresses 7 specific symptoms

Breslau’s 7-item screening scale (available at http://ajp.psychiatryonline.org/cgi/content/full/156/6/908#T2) is another empirically tested, brief, simple means of identifying PTSD symptoms in primary care patients.² (See also: www.pubmedcentral.nih.gov/articlerender.fcgifiartid=1484617.) Each item addresses a specific symptom.

The screen has been validated in a VA primary care clinic (N=134). With a cutoff score of 4, it has a sensitivity of 85% and specificity of 84%, yielding a positive predictive value of 71% and negative predictive value of 98%.² The likelihood of a score <3 is 0.04 and a score >5 is 13.5. Scores of 3 to 5 have an indeterminate likelihood value (1.8). Patients with a positive screen should undergo further evaluation by a mental health provider.²

Leave lengthy screens to mental health professionals

The CAPS and the civilian version of the PTSD Symptom Checklist (PCL-C), both with 17 items, are widely used as “screens” for PTSD.⁷ However, their length and the recommendation that they be administered by a mental health professional make them cumbersome and impractical for use in primary care.⁷

Recommendations

A 2007 point-of-care guide written for primary care clinicians recommends Breslau’s short screening scale and the PCPTSD screen for use in this setting.¹ Both the National Center for PTSD and Department of Defense Clinical Guidelines on PTSD recommend initial and annual screening using the PC-PTSD, PTSD Brief Screen, or Short Screening Scale for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) PTSD.⁸

Acknowledgements

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

Evidence summary

About 8% of the US population will develop symptoms of PTSD at some point in their lives—usually as the result of a traumatic event, such as combat, a natural disaster, accident, or physical or sexual assault.¹ Primary care settings tend to be the principal point of contact for patients with PTSD, although such patients rarely identify themselves as suffering from the disorder.^2,3

Detailed diagnostic interviews and assessments are generally impractical in primary care.⁴ Brief, easy-to-complete screening tools can help clinicians identify patients with primary symptoms of PTSD.⁴

4-item screen assesses key characteristics of PTSD

The PC-PTSD (TABLE) is a 4-item screen that assesses the underlying characteristics specific to PTSD: re-experiencing, numbing, avoidance, and hyperarousal.⁴ It’s designed to be understandable to patients with an eighth-grade reading level and has been validated in a Department of Veterans Affairs (VA) primary care population (N=188).⁴

With a cutoff score of 3, the PCPTSD has a sensitivity of 78% and specificity of 87%, compared with the gold-standard Clinician-Administered PTSD Scale (CAPS).⁴ Positive responses warrant further evaluation of trauma symptoms and completion of the CAPS by a mental health provider to determine whether the patient may have PTSD or other trauma-related problems.^5-7

TABLE
The primary care PTSD screen (PC-PTSD)⁴

Breslau’s short screen addresses 7 specific symptoms

Breslau’s 7-item screening scale (available at http://ajp.psychiatryonline.org/cgi/content/full/156/6/908#T2) is another empirically tested, brief, simple means of identifying PTSD symptoms in primary care patients.² (See also: www.pubmedcentral.nih.gov/articlerender.fcgifiartid=1484617.) Each item addresses a specific symptom.

The screen has been validated in a VA primary care clinic (N=134). With a cutoff score of 4, it has a sensitivity of 85% and specificity of 84%, yielding a positive predictive value of 71% and negative predictive value of 98%.² The likelihood of a score <3 is 0.04 and a score >5 is 13.5. Scores of 3 to 5 have an indeterminate likelihood value (1.8). Patients with a positive screen should undergo further evaluation by a mental health provider.²

Leave lengthy screens to mental health professionals

The CAPS and the civilian version of the PTSD Symptom Checklist (PCL-C), both with 17 items, are widely used as “screens” for PTSD.⁷ However, their length and the recommendation that they be administered by a mental health professional make them cumbersome and impractical for use in primary care.⁷

Recommendations

A 2007 point-of-care guide written for primary care clinicians recommends Breslau’s short screening scale and the PCPTSD screen for use in this setting.¹ Both the National Center for PTSD and Department of Defense Clinical Guidelines on PTSD recommend initial and annual screening using the PC-PTSD, PTSD Brief Screen, or Short Screening Scale for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) PTSD.⁸

Acknowledgements

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

Evidence summary

Initial treatments for cervical radiculopathy encompass:

• rest
• cervical immobilization
• NSAIDs
• analgesics (including muscle relaxants and antiepileptics)
• physical therapy.

Because few RCTs of these treatment options have been conducted,¹ recommendations are based primarily on cohort studies and clinical experience.

Analgesia: Try anticonvulsants last

No clinical trials have been published that look specifically at rest, immobilization, or oral analgesics for cervical radiculopathy. A Cochrane review of studies of anticonvulsants for treating acute and chronic pain found none that focused on cervical radiculopathy. The review concluded that “surprisingly few trials show analgesic effectiveness of anticonvulsants,” and “anticonvulsants should be withheld until other interventions have been tried.”²

Physical therapy seems to help

No RCTs of physical therapy for cervical radiculopathy been reported. However, a case series of patients treated specifically for cervical radiculopathy found that 10 of 11 patients who underwent physical therapy (including manual therapy, cervical traction, and strengthening exercises) were improved—defined as a self-report of being “quite a bit better”—at 6-month follow-up.³

A 1995 systematic, blinded review of RCTs of cervical traction found 3 studies. However, the inclusion criteria of these studies weren’t limited to cervical radiculopathy, limiting the applicability of the results. The 3 RCTs showed no advantages (2 studies) or modest advantages (1 study) for cervical traction over placebo or standard physical therapy without traction. Each study defined improvement differently, but most patients in all groups showed improvement.⁴

Epidural steroids appear effective

Epidural corticosteroid injections have demonstrated success in both retrospective and prospective studies. One case series of cortisone epidural injections reported 60% of patients (12 of 20) had good or excellent response at long-term follow-up (mean follow-up=21.2 months; range=2–45 months). Six of the 20 patients proceeded to surgery.⁵

Another series of 32 patients who had failed conventional treatment showed a 62% response—defined as “good or excellent” pain relief—to epidural steroid injection at 14 days. At 6 months, 53% continued to report good or excellent pain relief. No significant side effects occurred. The 44% of patients who didn’t report success also didn’t report any further deterioration.⁶

Surgery can relieve pain, but has risks

Laminectomy to reduce nerve compression may alleviate pain and improve function, but it has risks. Surgical procedures for cervical radiculomyelopathy have reported death rates of 0% to 1.8%; nonfatal complications occurred in 1% to 8% of patients.

A Cochrane review found only one RCT (N=81) that compared surgery with conservative treatment (physiotherapy and the cervical collar).⁷ Twenty patients crossed over to another treatment, including 3 surgical patients who improved before surgery and 11 who did postop physiotherapy.⁸ Patients were still analyzed by intention to treat, however.

The surgery group showed greater pain improvement at 3 months, as assessed by visual analogue scale (0 to 100), than the physiotherapy group (mean difference [MD]=–14; 95% confidence interval [CI], –27.84 to –0.16) and the cervical collar (MD=–21; 95% CI, –33.32 to –8.68). At 1 year, however, no difference was seen between surgery and physiotherapy (MD=–9; 95% CI, –23.39 to 5.39) or between surgery and the cervical collar (MD=–5; 95% CI, –18.84 to 8.84).⁷

Symptoms often resolve spontaneously

The natural course of cervical radiculopathy is uncertain, but symptoms often resolve with conservative measures or no treatment at all. A 1994 community-based epidemiological survey of 561 patients showed that 75% of patients had a spontaneous symptomatic improvement within 5 years. Earlier studies (6 studies from 1957 to 1972) concluded that untreated patients wouldn’t necessarily develop progressive disability and that patients with severe disability sometimes improve without treatment.⁷

Recommendations

Brigham and Women’s Hospital’s guideline recommends treating cervical radiculopathy with a soft collar, rest, nonsteroidal anti-inflammatory drugs, and physical therapy with cervical traction. If initial management isn’t effective after 6 weeks, the guideline advises referral to a specialist such as an orthopedic surgeon, neurologist, or rheumatologist. Surgical intervention is indicated if the patient shows signs of spinal cord compression or if pain is hindering function.⁹

An evidence-based practice guideline from The American Society of Interventional Pain Physicians states that moderate evidence supports the efficacy of interlaminar and transforaminal steroid injections.¹⁰

Evidence summary

Initial treatments for cervical radiculopathy encompass:

• rest
• cervical immobilization
• NSAIDs
• analgesics (including muscle relaxants and antiepileptics)
• physical therapy.

Because few RCTs of these treatment options have been conducted,¹ recommendations are based primarily on cohort studies and clinical experience.

Analgesia: Try anticonvulsants last

No clinical trials have been published that look specifically at rest, immobilization, or oral analgesics for cervical radiculopathy. A Cochrane review of studies of anticonvulsants for treating acute and chronic pain found none that focused on cervical radiculopathy. The review concluded that “surprisingly few trials show analgesic effectiveness of anticonvulsants,” and “anticonvulsants should be withheld until other interventions have been tried.”²

Physical therapy seems to help

No RCTs of physical therapy for cervical radiculopathy been reported. However, a case series of patients treated specifically for cervical radiculopathy found that 10 of 11 patients who underwent physical therapy (including manual therapy, cervical traction, and strengthening exercises) were improved—defined as a self-report of being “quite a bit better”—at 6-month follow-up.³

A 1995 systematic, blinded review of RCTs of cervical traction found 3 studies. However, the inclusion criteria of these studies weren’t limited to cervical radiculopathy, limiting the applicability of the results. The 3 RCTs showed no advantages (2 studies) or modest advantages (1 study) for cervical traction over placebo or standard physical therapy without traction. Each study defined improvement differently, but most patients in all groups showed improvement.⁴

Epidural steroids appear effective

Epidural corticosteroid injections have demonstrated success in both retrospective and prospective studies. One case series of cortisone epidural injections reported 60% of patients (12 of 20) had good or excellent response at long-term follow-up (mean follow-up=21.2 months; range=2–45 months). Six of the 20 patients proceeded to surgery.⁵

Another series of 32 patients who had failed conventional treatment showed a 62% response—defined as “good or excellent” pain relief—to epidural steroid injection at 14 days. At 6 months, 53% continued to report good or excellent pain relief. No significant side effects occurred. The 44% of patients who didn’t report success also didn’t report any further deterioration.⁶

Surgery can relieve pain, but has risks

Laminectomy to reduce nerve compression may alleviate pain and improve function, but it has risks. Surgical procedures for cervical radiculomyelopathy have reported death rates of 0% to 1.8%; nonfatal complications occurred in 1% to 8% of patients.

A Cochrane review found only one RCT (N=81) that compared surgery with conservative treatment (physiotherapy and the cervical collar).⁷ Twenty patients crossed over to another treatment, including 3 surgical patients who improved before surgery and 11 who did postop physiotherapy.⁸ Patients were still analyzed by intention to treat, however.

The surgery group showed greater pain improvement at 3 months, as assessed by visual analogue scale (0 to 100), than the physiotherapy group (mean difference [MD]=–14; 95% confidence interval [CI], –27.84 to –0.16) and the cervical collar (MD=–21; 95% CI, –33.32 to –8.68). At 1 year, however, no difference was seen between surgery and physiotherapy (MD=–9; 95% CI, –23.39 to 5.39) or between surgery and the cervical collar (MD=–5; 95% CI, –18.84 to 8.84).⁷

Symptoms often resolve spontaneously

The natural course of cervical radiculopathy is uncertain, but symptoms often resolve with conservative measures or no treatment at all. A 1994 community-based epidemiological survey of 561 patients showed that 75% of patients had a spontaneous symptomatic improvement within 5 years. Earlier studies (6 studies from 1957 to 1972) concluded that untreated patients wouldn’t necessarily develop progressive disability and that patients with severe disability sometimes improve without treatment.⁷

Recommendations

Brigham and Women’s Hospital’s guideline recommends treating cervical radiculopathy with a soft collar, rest, nonsteroidal anti-inflammatory drugs, and physical therapy with cervical traction. If initial management isn’t effective after 6 weeks, the guideline advises referral to a specialist such as an orthopedic surgeon, neurologist, or rheumatologist. Surgical intervention is indicated if the patient shows signs of spinal cord compression or if pain is hindering function.⁹

An evidence-based practice guideline from The American Society of Interventional Pain Physicians states that moderate evidence supports the efficacy of interlaminar and transforaminal steroid injections.¹⁰

Evidence summary

Initial treatments for cervical radiculopathy encompass:

• rest
• cervical immobilization
• NSAIDs
• analgesics (including muscle relaxants and antiepileptics)
• physical therapy.

Because few RCTs of these treatment options have been conducted,¹ recommendations are based primarily on cohort studies and clinical experience.

Analgesia: Try anticonvulsants last

No clinical trials have been published that look specifically at rest, immobilization, or oral analgesics for cervical radiculopathy. A Cochrane review of studies of anticonvulsants for treating acute and chronic pain found none that focused on cervical radiculopathy. The review concluded that “surprisingly few trials show analgesic effectiveness of anticonvulsants,” and “anticonvulsants should be withheld until other interventions have been tried.”²

Physical therapy seems to help

No RCTs of physical therapy for cervical radiculopathy been reported. However, a case series of patients treated specifically for cervical radiculopathy found that 10 of 11 patients who underwent physical therapy (including manual therapy, cervical traction, and strengthening exercises) were improved—defined as a self-report of being “quite a bit better”—at 6-month follow-up.³

A 1995 systematic, blinded review of RCTs of cervical traction found 3 studies. However, the inclusion criteria of these studies weren’t limited to cervical radiculopathy, limiting the applicability of the results. The 3 RCTs showed no advantages (2 studies) or modest advantages (1 study) for cervical traction over placebo or standard physical therapy without traction. Each study defined improvement differently, but most patients in all groups showed improvement.⁴

Epidural steroids appear effective

Epidural corticosteroid injections have demonstrated success in both retrospective and prospective studies. One case series of cortisone epidural injections reported 60% of patients (12 of 20) had good or excellent response at long-term follow-up (mean follow-up=21.2 months; range=2–45 months). Six of the 20 patients proceeded to surgery.⁵

Another series of 32 patients who had failed conventional treatment showed a 62% response—defined as “good or excellent” pain relief—to epidural steroid injection at 14 days. At 6 months, 53% continued to report good or excellent pain relief. No significant side effects occurred. The 44% of patients who didn’t report success also didn’t report any further deterioration.⁶

Surgery can relieve pain, but has risks

Laminectomy to reduce nerve compression may alleviate pain and improve function, but it has risks. Surgical procedures for cervical radiculomyelopathy have reported death rates of 0% to 1.8%; nonfatal complications occurred in 1% to 8% of patients.

A Cochrane review found only one RCT (N=81) that compared surgery with conservative treatment (physiotherapy and the cervical collar).⁷ Twenty patients crossed over to another treatment, including 3 surgical patients who improved before surgery and 11 who did postop physiotherapy.⁸ Patients were still analyzed by intention to treat, however.

The surgery group showed greater pain improvement at 3 months, as assessed by visual analogue scale (0 to 100), than the physiotherapy group (mean difference [MD]=–14; 95% confidence interval [CI], –27.84 to –0.16) and the cervical collar (MD=–21; 95% CI, –33.32 to –8.68). At 1 year, however, no difference was seen between surgery and physiotherapy (MD=–9; 95% CI, –23.39 to 5.39) or between surgery and the cervical collar (MD=–5; 95% CI, –18.84 to 8.84).⁷

Symptoms often resolve spontaneously

The natural course of cervical radiculopathy is uncertain, but symptoms often resolve with conservative measures or no treatment at all. A 1994 community-based epidemiological survey of 561 patients showed that 75% of patients had a spontaneous symptomatic improvement within 5 years. Earlier studies (6 studies from 1957 to 1972) concluded that untreated patients wouldn’t necessarily develop progressive disability and that patients with severe disability sometimes improve without treatment.⁷

Recommendations

Brigham and Women’s Hospital’s guideline recommends treating cervical radiculopathy with a soft collar, rest, nonsteroidal anti-inflammatory drugs, and physical therapy with cervical traction. If initial management isn’t effective after 6 weeks, the guideline advises referral to a specialist such as an orthopedic surgeon, neurologist, or rheumatologist. Surgical intervention is indicated if the patient shows signs of spinal cord compression or if pain is hindering function.⁹

An evidence-based practice guideline from The American Society of Interventional Pain Physicians states that moderate evidence supports the efficacy of interlaminar and transforaminal steroid injections.¹⁰

Evidence summary

GBS infection is a leading cause of neonatal bacteremia, pneumonia, and meningitis.¹ Approximately 10% to 30% of pregnant women are colonized with GBS in the vagina or rectum.^2,3 Giving intrapartum antibiotics to women at high risk for GBS colonization (TABLE 1) has significantly reduced the incidence of neonatal sepsis, from approximately 2 cases to 0.5 cases per 1000 live births.^1,3

TABLE 1
Risk factors for GBS

Universal screening is the way to go

A multistate retrospective cohort study (N=5144) concluded that universal screening by culture for GBS at 35 to 37 weeks’ gestation is more effective than treating patients based on risk-factor criteria (relative risk [RR]=0.46; 95% confidence interval [CI], 0.36-0.60).⁴ The Centers for Disease Control and Prevention’s (CDC) 2002 revised guidelines recommend universal screening by culture at 35 to 37 weeks, with 2 exceptions: women who had GBS bacteriuria during the current pregnancy and women who have given birth to an infant with invasive GBS disease.⁵ The GBS status of 5% to 10% of term patients remains unknown at onset of labor because of inadequate prenatal care or out-of-date GBS culture results (>5 weeks).^6,7

PCR is the most accurate rapid test for GBS

A 2006 systematic review of 29 prospective studies found the PCR test to be the most accurate rapid assessment for GBS status at onset of labor.⁸ The test was 96% sensitive (95% CI, 0.88-0.99) and 98% specific (95% CI, 0.96-0.99) compared with optical immunoassay, DNA hybridization, enzyme immunoassay, latex agglutination, and Islam starch medium tests (TABLE 2).⁸ Culture, usually on selective media, was the gold standard.

The rapid PCR test takes about 40 minutes, making it useful to determine the need for antibiotic prophylaxis in laboring, full-term, GBS-status-unknown women. If a rapid PCR test isn’t available, a woman with unknown GBS status and 1 or more of the CDC risk factor criteria should receive intrapartum antibiotics.⁵

TABLE 2
How accurate are intrapartum tests for GBS?

Chlorhexidine has no effect

Vaginal disinfection with chlorhexidine during delivery has been used to prevent GBS transmission, but no highly controlled trials have demonstrated a benefit or consequence of this approach. A systematic review of 5 randomized and quasi-randomized, variable-quality trials comparing vaginal disinfection with chlorhexidine with placebo found no statistically significant reduction in early-onset neonatal GBS sepsis (RR=2.32; 95% CI, 0.34-15.63), pneumonia (RR=0.35; 95% CI, 0.01-8.60), or meningitis (RR=0.35; 95% CI, 0.01-8.60).⁹

Recommendations

The American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the CDC recommend screening all pregnant women at 35 to 37 weeks’ gestation and administering prophylaxis to all GBS carriers.^5,10 They also advocate intrapartum antibiotic prophylaxis for pregnant women whose GBS status is unknown and who have a risk factor for GBS listed in TABLE 1.^5,10 Rapid tests to detect GBS when status is unknown should replace the risk-based approach only if the test has a sensitivity of at least 85%.⁵

Acknowledgements

The opinions and assertions contained herein are the private views of the authors and should not 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

GBS infection is a leading cause of neonatal bacteremia, pneumonia, and meningitis.¹ Approximately 10% to 30% of pregnant women are colonized with GBS in the vagina or rectum.^2,3 Giving intrapartum antibiotics to women at high risk for GBS colonization (TABLE 1) has significantly reduced the incidence of neonatal sepsis, from approximately 2 cases to 0.5 cases per 1000 live births.^1,3

TABLE 1
Risk factors for GBS

Universal screening is the way to go

A multistate retrospective cohort study (N=5144) concluded that universal screening by culture for GBS at 35 to 37 weeks’ gestation is more effective than treating patients based on risk-factor criteria (relative risk [RR]=0.46; 95% confidence interval [CI], 0.36-0.60).⁴ The Centers for Disease Control and Prevention’s (CDC) 2002 revised guidelines recommend universal screening by culture at 35 to 37 weeks, with 2 exceptions: women who had GBS bacteriuria during the current pregnancy and women who have given birth to an infant with invasive GBS disease.⁵ The GBS status of 5% to 10% of term patients remains unknown at onset of labor because of inadequate prenatal care or out-of-date GBS culture results (>5 weeks).^6,7

PCR is the most accurate rapid test for GBS

A 2006 systematic review of 29 prospective studies found the PCR test to be the most accurate rapid assessment for GBS status at onset of labor.⁸ The test was 96% sensitive (95% CI, 0.88-0.99) and 98% specific (95% CI, 0.96-0.99) compared with optical immunoassay, DNA hybridization, enzyme immunoassay, latex agglutination, and Islam starch medium tests (TABLE 2).⁸ Culture, usually on selective media, was the gold standard.

The rapid PCR test takes about 40 minutes, making it useful to determine the need for antibiotic prophylaxis in laboring, full-term, GBS-status-unknown women. If a rapid PCR test isn’t available, a woman with unknown GBS status and 1 or more of the CDC risk factor criteria should receive intrapartum antibiotics.⁵

TABLE 2
How accurate are intrapartum tests for GBS?

Chlorhexidine has no effect

Vaginal disinfection with chlorhexidine during delivery has been used to prevent GBS transmission, but no highly controlled trials have demonstrated a benefit or consequence of this approach. A systematic review of 5 randomized and quasi-randomized, variable-quality trials comparing vaginal disinfection with chlorhexidine with placebo found no statistically significant reduction in early-onset neonatal GBS sepsis (RR=2.32; 95% CI, 0.34-15.63), pneumonia (RR=0.35; 95% CI, 0.01-8.60), or meningitis (RR=0.35; 95% CI, 0.01-8.60).⁹

Recommendations

The American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the CDC recommend screening all pregnant women at 35 to 37 weeks’ gestation and administering prophylaxis to all GBS carriers.^5,10 They also advocate intrapartum antibiotic prophylaxis for pregnant women whose GBS status is unknown and who have a risk factor for GBS listed in TABLE 1.^5,10 Rapid tests to detect GBS when status is unknown should replace the risk-based approach only if the test has a sensitivity of at least 85%.⁵

Acknowledgements

The opinions and assertions contained herein are the private views of the authors and should not 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

GBS infection is a leading cause of neonatal bacteremia, pneumonia, and meningitis.¹ Approximately 10% to 30% of pregnant women are colonized with GBS in the vagina or rectum.^2,3 Giving intrapartum antibiotics to women at high risk for GBS colonization (TABLE 1) has significantly reduced the incidence of neonatal sepsis, from approximately 2 cases to 0.5 cases per 1000 live births.^1,3

TABLE 1
Risk factors for GBS

Universal screening is the way to go

A multistate retrospective cohort study (N=5144) concluded that universal screening by culture for GBS at 35 to 37 weeks’ gestation is more effective than treating patients based on risk-factor criteria (relative risk [RR]=0.46; 95% confidence interval [CI], 0.36-0.60).⁴ The Centers for Disease Control and Prevention’s (CDC) 2002 revised guidelines recommend universal screening by culture at 35 to 37 weeks, with 2 exceptions: women who had GBS bacteriuria during the current pregnancy and women who have given birth to an infant with invasive GBS disease.⁵ The GBS status of 5% to 10% of term patients remains unknown at onset of labor because of inadequate prenatal care or out-of-date GBS culture results (>5 weeks).^6,7

PCR is the most accurate rapid test for GBS

A 2006 systematic review of 29 prospective studies found the PCR test to be the most accurate rapid assessment for GBS status at onset of labor.⁸ The test was 96% sensitive (95% CI, 0.88-0.99) and 98% specific (95% CI, 0.96-0.99) compared with optical immunoassay, DNA hybridization, enzyme immunoassay, latex agglutination, and Islam starch medium tests (TABLE 2).⁸ Culture, usually on selective media, was the gold standard.

The rapid PCR test takes about 40 minutes, making it useful to determine the need for antibiotic prophylaxis in laboring, full-term, GBS-status-unknown women. If a rapid PCR test isn’t available, a woman with unknown GBS status and 1 or more of the CDC risk factor criteria should receive intrapartum antibiotics.⁵

TABLE 2
How accurate are intrapartum tests for GBS?

Chlorhexidine has no effect

Vaginal disinfection with chlorhexidine during delivery has been used to prevent GBS transmission, but no highly controlled trials have demonstrated a benefit or consequence of this approach. A systematic review of 5 randomized and quasi-randomized, variable-quality trials comparing vaginal disinfection with chlorhexidine with placebo found no statistically significant reduction in early-onset neonatal GBS sepsis (RR=2.32; 95% CI, 0.34-15.63), pneumonia (RR=0.35; 95% CI, 0.01-8.60), or meningitis (RR=0.35; 95% CI, 0.01-8.60).⁹

Recommendations

The American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the CDC recommend screening all pregnant women at 35 to 37 weeks’ gestation and administering prophylaxis to all GBS carriers.^5,10 They also advocate intrapartum antibiotic prophylaxis for pregnant women whose GBS status is unknown and who have a risk factor for GBS listed in TABLE 1.^5,10 Rapid tests to detect GBS when status is unknown should replace the risk-based approach only if the test has a sensitivity of at least 85%.⁵

Acknowledgements

The opinions and assertions contained herein are the private views of the authors and should not 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

There is very little patient-oriented research to help answer this question. Virtually all of the literature is based on bench research and expert opinion.

Wait at least 6 weeks to follow up after starting therapy

Serial serum TSH measurements are adequate to follow adults with newly diagnosed, uncomplicated primary hypothyroidism. However, serum thyroid hormone levels normalize before serum TSH. Serum thyroid hormone concentrations increase first, then the TSH secretion falls because of the negative feedback action of levothyroxine on the pituitary and hypothalamus. Levothyroxine has a 1-week plasma half-life; a steady state is achieved about 6 weeks (6 half-lives) after the start of treatment or a change in dose. The TSH level should, therefore, be evaluated no earlier than 6 weeks after initiating therapy or adjusting levothyroxine dosage.^1,2 The full effects of thyroid hormone replacement on the TSH level may not become apparent until 8 weeks of therapy.³

Check TSH 4 to 6 months after initial follow-up

If the initial dose doesn’t require adjustment, reevaluate the patient and measure serum TSH again in 4 to 6 months because levothyroxine clearance can increase after the euthyroid state is established.⁴ If a dosage change is needed, make adjustments every 6 weeks, based on serum TSH values, until TSH values return to the reference range. Successful treatment reverses all the signs and symptoms of hypothyroidism, although some neuropsychologic and biochemical abnormalities, such as depressed mood and lipid abnormalities, may persist for several months.³

Monitor stable patients annually, especially the elderly

Examine the patient and measure serum TSH annually after identifying the proper maintenance dose, more often if an abnormal result or a change in the patient’s status occurs.² Certain situations such as pregnancy, initiation of new medications, or liver or kidney disease may require more frequent monitoring.

Generally, once a stable maintenance dosage of levothyroxine is achieved, the dosage will remain adequate until the patient has a significant weight change or reaches his or her seventh or eighth decade.¹ Although monitoring less often than once a year can be justified in younger adult patients whose weight is stable, patients older than 65 years must be monitored annually to avoid overreplacement. With age, thyroid binding may decrease, and the serum albumin level may decline. This can result in a 20% reduction in the dose of levothyroxine required.^5,6

Recommendations

The American Association of Clinical Endocrinologists (AACE) recommends reassessment and repeat lab work at least 6 weeks after any change in levothyroxine brand or dose. The AACE practice guidelines suggest follow-up with appropriate interim history, physical exam, and pertinent lab studies at 6 months, and then annually after the TSH level has normalized.⁷

Evidence summary

There is very little patient-oriented research to help answer this question. Virtually all of the literature is based on bench research and expert opinion.

Wait at least 6 weeks to follow up after starting therapy

Serial serum TSH measurements are adequate to follow adults with newly diagnosed, uncomplicated primary hypothyroidism. However, serum thyroid hormone levels normalize before serum TSH. Serum thyroid hormone concentrations increase first, then the TSH secretion falls because of the negative feedback action of levothyroxine on the pituitary and hypothalamus. Levothyroxine has a 1-week plasma half-life; a steady state is achieved about 6 weeks (6 half-lives) after the start of treatment or a change in dose. The TSH level should, therefore, be evaluated no earlier than 6 weeks after initiating therapy or adjusting levothyroxine dosage.^1,2 The full effects of thyroid hormone replacement on the TSH level may not become apparent until 8 weeks of therapy.³

Check TSH 4 to 6 months after initial follow-up

If the initial dose doesn’t require adjustment, reevaluate the patient and measure serum TSH again in 4 to 6 months because levothyroxine clearance can increase after the euthyroid state is established.⁴ If a dosage change is needed, make adjustments every 6 weeks, based on serum TSH values, until TSH values return to the reference range. Successful treatment reverses all the signs and symptoms of hypothyroidism, although some neuropsychologic and biochemical abnormalities, such as depressed mood and lipid abnormalities, may persist for several months.³

Monitor stable patients annually, especially the elderly

Examine the patient and measure serum TSH annually after identifying the proper maintenance dose, more often if an abnormal result or a change in the patient’s status occurs.² Certain situations such as pregnancy, initiation of new medications, or liver or kidney disease may require more frequent monitoring.

Generally, once a stable maintenance dosage of levothyroxine is achieved, the dosage will remain adequate until the patient has a significant weight change or reaches his or her seventh or eighth decade.¹ Although monitoring less often than once a year can be justified in younger adult patients whose weight is stable, patients older than 65 years must be monitored annually to avoid overreplacement. With age, thyroid binding may decrease, and the serum albumin level may decline. This can result in a 20% reduction in the dose of levothyroxine required.^5,6

Recommendations

The American Association of Clinical Endocrinologists (AACE) recommends reassessment and repeat lab work at least 6 weeks after any change in levothyroxine brand or dose. The AACE practice guidelines suggest follow-up with appropriate interim history, physical exam, and pertinent lab studies at 6 months, and then annually after the TSH level has normalized.⁷

Evidence summary

There is very little patient-oriented research to help answer this question. Virtually all of the literature is based on bench research and expert opinion.

Wait at least 6 weeks to follow up after starting therapy

Serial serum TSH measurements are adequate to follow adults with newly diagnosed, uncomplicated primary hypothyroidism. However, serum thyroid hormone levels normalize before serum TSH. Serum thyroid hormone concentrations increase first, then the TSH secretion falls because of the negative feedback action of levothyroxine on the pituitary and hypothalamus. Levothyroxine has a 1-week plasma half-life; a steady state is achieved about 6 weeks (6 half-lives) after the start of treatment or a change in dose. The TSH level should, therefore, be evaluated no earlier than 6 weeks after initiating therapy or adjusting levothyroxine dosage.^1,2 The full effects of thyroid hormone replacement on the TSH level may not become apparent until 8 weeks of therapy.³

Check TSH 4 to 6 months after initial follow-up

If the initial dose doesn’t require adjustment, reevaluate the patient and measure serum TSH again in 4 to 6 months because levothyroxine clearance can increase after the euthyroid state is established.⁴ If a dosage change is needed, make adjustments every 6 weeks, based on serum TSH values, until TSH values return to the reference range. Successful treatment reverses all the signs and symptoms of hypothyroidism, although some neuropsychologic and biochemical abnormalities, such as depressed mood and lipid abnormalities, may persist for several months.³

Monitor stable patients annually, especially the elderly

Examine the patient and measure serum TSH annually after identifying the proper maintenance dose, more often if an abnormal result or a change in the patient’s status occurs.² Certain situations such as pregnancy, initiation of new medications, or liver or kidney disease may require more frequent monitoring.

Generally, once a stable maintenance dosage of levothyroxine is achieved, the dosage will remain adequate until the patient has a significant weight change or reaches his or her seventh or eighth decade.¹ Although monitoring less often than once a year can be justified in younger adult patients whose weight is stable, patients older than 65 years must be monitored annually to avoid overreplacement. With age, thyroid binding may decrease, and the serum albumin level may decline. This can result in a 20% reduction in the dose of levothyroxine required.^5,6

Recommendations

The American Association of Clinical Endocrinologists (AACE) recommends reassessment and repeat lab work at least 6 weeks after any change in levothyroxine brand or dose. The AACE practice guidelines suggest follow-up with appropriate interim history, physical exam, and pertinent lab studies at 6 months, and then annually after the TSH level has normalized.⁷

Evidence summary

Patients with severe acute alcoholic hepatitis have elevated levels of serum tumor necrosis factor (TNF), suggesting that TNF release may play a role in liver inflammation.¹ Because pentoxifylline inhibits TNF synthesis, it has been evaluated as a potential therapy for alcoholic hepatitis.

Decreases in mortality and hepatorenal syndrome

In a hospital-based clinical trial, 101 patients admitted with severe alcoholic hepatitis (mean age 42 years, 74% men) were randomized to oral pentoxifylline 400 mg twice a day or placebo (vitamin B₁₂ tablets) for 4 weeks.¹ The main outcome measures were short-term survival and progression to hepatorenal syndrome. Severe alcoholic hepatitis was defined as a Maddrey discriminant factor (DF) >32, jaundice, and at least one of the following: tender hepatomegaly, fever, leukocytosis, hepatic encephalopathy, or hepatic systolic bruit. The DF is calculated as follows: 4.6 × [prothrombin time in seconds – control time] + bilirubin (mg/dL). Medical management was “individualized according to each patient’s condition.”

Pentoxifylline therapy was associated with decreased mortality during the index hospitalization (relative risk [RR]=0.59; 95% confidence interval [CI], 0.35-0.97; number needed to treat [NNT]=5). Hepatorenal syndrome also decreased (RR=0.29; 95% CI, 0.13-0.65; NNT=4). Patients in the pentoxifylline group tended to have more headaches and gastrointestinal side effects, but no other serious health hazards were observed.

In a recently published abstract, 50 patients with severe alcoholic hepatitis (defined as DF >32) were enrolled in a randomized, double-blind, placebo-controlled trial of oral pentoxifylline, 400 mg twice a day or placebo for 4 weeks.² Short-term survival and changes in laboratory values (TNF, creatinine, and DF) were the primary outcome measures.

Survival was 76% in the pentoxifylline group compared with 60% in the placebo group (P not given). In the sub-group of patients who died, however, hepatorenal syndrome was the cause of death in 83% of the pentoxifylline group and 60% of the placebo group (P not given).

In a 1991 pilot study, also published only in abstract form, 22 patients admitted to the hospital with severe alcoholic hepatitis were randomized to receive oral pentoxifylline (1200 mg daily) or placebo for 10 days. Serum creatinine dropped 0.3 mg/dL in the treatment group and rose 2.1 mg/dL in the control group (P<.05). At 30 days, 3 patients in the control group had died compared with 1 in the treatment group (P=not significant).³

It’s not effective for patients who don’t respond to steroids

A cohort study evaluated the effect of switching to pentoxifylline in hospitalized patients with severe alcoholic hepatitis who didn’t respond to initial therapy with steroids. Researchers identified 121 patients who were treated initially with 40 mg oral prednisolone daily. The 36 patients who failed to show a drop in bilirubin levels within 7 days were switched to oral pentoxifylline, 400 mg twice a day.

In the pentoxifylline group, 69% of patients died within 2 months, 27.6% of whom had some form of renal insufficiency. This outcome wasn’t statistically different from that of 58 matched historical controls with severe alcoholic hepatitis who were maintained on oral prednisolone despite failure to respond within the first week of therapy (65% mortality, 20% with renal insufficiency).⁴

Recommendations

The American College of Gastroenterology doesn’t recommend giving pentoxifylline to patients with severe alcoholic hepatitis, citing lack of evidence for improvement of patient-oriented outcomes.⁵ However, a group of French hepatologists consider pentoxifylline a reasonable alternative to corticosteroids for severe acute alcoholic hepatitis based on the studies cited here.⁶

Evidence summary

Patients with severe acute alcoholic hepatitis have elevated levels of serum tumor necrosis factor (TNF), suggesting that TNF release may play a role in liver inflammation.¹ Because pentoxifylline inhibits TNF synthesis, it has been evaluated as a potential therapy for alcoholic hepatitis.

Decreases in mortality and hepatorenal syndrome

In a hospital-based clinical trial, 101 patients admitted with severe alcoholic hepatitis (mean age 42 years, 74% men) were randomized to oral pentoxifylline 400 mg twice a day or placebo (vitamin B₁₂ tablets) for 4 weeks.¹ The main outcome measures were short-term survival and progression to hepatorenal syndrome. Severe alcoholic hepatitis was defined as a Maddrey discriminant factor (DF) >32, jaundice, and at least one of the following: tender hepatomegaly, fever, leukocytosis, hepatic encephalopathy, or hepatic systolic bruit. The DF is calculated as follows: 4.6 × [prothrombin time in seconds – control time] + bilirubin (mg/dL). Medical management was “individualized according to each patient’s condition.”

Pentoxifylline therapy was associated with decreased mortality during the index hospitalization (relative risk [RR]=0.59; 95% confidence interval [CI], 0.35-0.97; number needed to treat [NNT]=5). Hepatorenal syndrome also decreased (RR=0.29; 95% CI, 0.13-0.65; NNT=4). Patients in the pentoxifylline group tended to have more headaches and gastrointestinal side effects, but no other serious health hazards were observed.

In a recently published abstract, 50 patients with severe alcoholic hepatitis (defined as DF >32) were enrolled in a randomized, double-blind, placebo-controlled trial of oral pentoxifylline, 400 mg twice a day or placebo for 4 weeks.² Short-term survival and changes in laboratory values (TNF, creatinine, and DF) were the primary outcome measures.

Survival was 76% in the pentoxifylline group compared with 60% in the placebo group (P not given). In the sub-group of patients who died, however, hepatorenal syndrome was the cause of death in 83% of the pentoxifylline group and 60% of the placebo group (P not given).

In a 1991 pilot study, also published only in abstract form, 22 patients admitted to the hospital with severe alcoholic hepatitis were randomized to receive oral pentoxifylline (1200 mg daily) or placebo for 10 days. Serum creatinine dropped 0.3 mg/dL in the treatment group and rose 2.1 mg/dL in the control group (P<.05). At 30 days, 3 patients in the control group had died compared with 1 in the treatment group (P=not significant).³

It’s not effective for patients who don’t respond to steroids

A cohort study evaluated the effect of switching to pentoxifylline in hospitalized patients with severe alcoholic hepatitis who didn’t respond to initial therapy with steroids. Researchers identified 121 patients who were treated initially with 40 mg oral prednisolone daily. The 36 patients who failed to show a drop in bilirubin levels within 7 days were switched to oral pentoxifylline, 400 mg twice a day.

In the pentoxifylline group, 69% of patients died within 2 months, 27.6% of whom had some form of renal insufficiency. This outcome wasn’t statistically different from that of 58 matched historical controls with severe alcoholic hepatitis who were maintained on oral prednisolone despite failure to respond within the first week of therapy (65% mortality, 20% with renal insufficiency).⁴

Recommendations

The American College of Gastroenterology doesn’t recommend giving pentoxifylline to patients with severe alcoholic hepatitis, citing lack of evidence for improvement of patient-oriented outcomes.⁵ However, a group of French hepatologists consider pentoxifylline a reasonable alternative to corticosteroids for severe acute alcoholic hepatitis based on the studies cited here.⁶

Evidence summary

Patients with severe acute alcoholic hepatitis have elevated levels of serum tumor necrosis factor (TNF), suggesting that TNF release may play a role in liver inflammation.¹ Because pentoxifylline inhibits TNF synthesis, it has been evaluated as a potential therapy for alcoholic hepatitis.

Decreases in mortality and hepatorenal syndrome

In a hospital-based clinical trial, 101 patients admitted with severe alcoholic hepatitis (mean age 42 years, 74% men) were randomized to oral pentoxifylline 400 mg twice a day or placebo (vitamin B₁₂ tablets) for 4 weeks.¹ The main outcome measures were short-term survival and progression to hepatorenal syndrome. Severe alcoholic hepatitis was defined as a Maddrey discriminant factor (DF) >32, jaundice, and at least one of the following: tender hepatomegaly, fever, leukocytosis, hepatic encephalopathy, or hepatic systolic bruit. The DF is calculated as follows: 4.6 × [prothrombin time in seconds – control time] + bilirubin (mg/dL). Medical management was “individualized according to each patient’s condition.”

Pentoxifylline therapy was associated with decreased mortality during the index hospitalization (relative risk [RR]=0.59; 95% confidence interval [CI], 0.35-0.97; number needed to treat [NNT]=5). Hepatorenal syndrome also decreased (RR=0.29; 95% CI, 0.13-0.65; NNT=4). Patients in the pentoxifylline group tended to have more headaches and gastrointestinal side effects, but no other serious health hazards were observed.

In a recently published abstract, 50 patients with severe alcoholic hepatitis (defined as DF >32) were enrolled in a randomized, double-blind, placebo-controlled trial of oral pentoxifylline, 400 mg twice a day or placebo for 4 weeks.² Short-term survival and changes in laboratory values (TNF, creatinine, and DF) were the primary outcome measures.

Survival was 76% in the pentoxifylline group compared with 60% in the placebo group (P not given). In the sub-group of patients who died, however, hepatorenal syndrome was the cause of death in 83% of the pentoxifylline group and 60% of the placebo group (P not given).

In a 1991 pilot study, also published only in abstract form, 22 patients admitted to the hospital with severe alcoholic hepatitis were randomized to receive oral pentoxifylline (1200 mg daily) or placebo for 10 days. Serum creatinine dropped 0.3 mg/dL in the treatment group and rose 2.1 mg/dL in the control group (P<.05). At 30 days, 3 patients in the control group had died compared with 1 in the treatment group (P=not significant).³

It’s not effective for patients who don’t respond to steroids

A cohort study evaluated the effect of switching to pentoxifylline in hospitalized patients with severe alcoholic hepatitis who didn’t respond to initial therapy with steroids. Researchers identified 121 patients who were treated initially with 40 mg oral prednisolone daily. The 36 patients who failed to show a drop in bilirubin levels within 7 days were switched to oral pentoxifylline, 400 mg twice a day.

In the pentoxifylline group, 69% of patients died within 2 months, 27.6% of whom had some form of renal insufficiency. This outcome wasn’t statistically different from that of 58 matched historical controls with severe alcoholic hepatitis who were maintained on oral prednisolone despite failure to respond within the first week of therapy (65% mortality, 20% with renal insufficiency).⁴

Recommendations

The American College of Gastroenterology doesn’t recommend giving pentoxifylline to patients with severe alcoholic hepatitis, citing lack of evidence for improvement of patient-oriented outcomes.⁵ However, a group of French hepatologists consider pentoxifylline a reasonable alternative to corticosteroids for severe acute alcoholic hepatitis based on the studies cited here.⁶

Evidence summary

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

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

One human RCT and animal studies find benefits from cold

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

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

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

How cold is too cold?

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

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

Evidence for heat is limited

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

Recommendations

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

Acknowledgments

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

Evidence summary

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

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

One human RCT and animal studies find benefits from cold

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

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

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

How cold is too cold?

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

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

Evidence for heat is limited

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

Recommendations

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

Acknowledgments

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

Evidence summary

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

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

One human RCT and animal studies find benefits from cold

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

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

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

How cold is too cold?

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

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

Evidence for heat is limited

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

Recommendations

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

Acknowledgments

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

Evidence summary

The prophylactic use of oxytocic drugs reduces the risk of postpartum hemorrhage (PPH) by about 40% and has been widely adopted as a routine policy in the active management of the third stage of labor.¹ A number of studies have evaluated the timing of oxytocin after delivery (TABLE).

TABLE
What studies say about the timing of oxytocin and PPH risk

Which timing is best? It depends on the study

A well-constructed double-blinded RCT found no significant difference in the incidence of PPH when oxytocin was given after delivery of the anterior shoulder or the placenta.² The study included 1486 patients; 745 received 20 units of oxytocin on delivery of the anterior shoulder, and 741 received an identical dose of oxytocin on delivery of the placenta. The incidence of PPH was 5.4% for the anterior shoulder group and 5.8% for the placenta group (P=.72). Likewise, no significant difference between the groups was noted in the proportion of women with estimated blood loss (EBL) ≥500 mL (7.5% vs 9.7%; P=.15).

A much smaller double-blinded RCT found that PPH occurred significantly less often when oxytocin was delayed until after delivery of the placenta.³ The study comprised 51 patients; 27 received 10 units of oxytocin on delivery of the anterior shoulder and 24 received an identical dose after delivery of the placenta. The incidence of PPH ≥500 mL was 0% when oxytocin was given after delivery of the placenta vs 14.8% when it was given on delivery of the anterior shoulder (P=.049). However, the study was limited by its size and potential inaccuracies in estimating blood loss.

A prospective cohort study noted a significant reduction in the risk of PPH when oxytocin was given after delivery of the anterior shoulder, compared with the placenta.⁴ In this study, 82 patients received 5 units of oxytocin on delivery of the anterior shoulder, and 52 received an identical dose after delivery of the placenta. The incidence of PPH ≥500 mL was 7.3% in the anterior shoulder group and 19.2% in the placenta group. However, the study was not blinded and was limited by its small sample size.

Two earlier studies, an RCT and a prospective cohort study, concluded that oxytocin is more effective in reducing PPH when given before placental delivery (after delivery of the anterior shoulder and head, respectively).^5,6 Neither of these studies was blinded nor controlled for nonpharmacologic interventions, however.

Recommendations

The American College of Obstetricians and Gynecologists (ACOG) states that ongoing blood loss accompanied by decreased uterine tone requires uterotonic agents as first-line treatment for PPH.⁷ ACOG doesn’t make specific recommendations regarding the timing of oxytocin administration.

The American Academy of Family Physicians (AAFP) recommends oxytocin as the uterotonic agent of choice for preventing PPH.⁸ The AAFP further advocates active management of the third stage of labor to decrease PPH by administering oxytocin as soon as possible after delivery of the anterior shoulder and before delivery of the placenta.

The World Health Organization (WHO) also recommends oxytocin as the uterotonic of choice.⁹ WHO advocates administration within 1 minute of delivery of the baby.

Evidence summary

The prophylactic use of oxytocic drugs reduces the risk of postpartum hemorrhage (PPH) by about 40% and has been widely adopted as a routine policy in the active management of the third stage of labor.¹ A number of studies have evaluated the timing of oxytocin after delivery (TABLE).

TABLE
What studies say about the timing of oxytocin and PPH risk

Which timing is best? It depends on the study

A well-constructed double-blinded RCT found no significant difference in the incidence of PPH when oxytocin was given after delivery of the anterior shoulder or the placenta.² The study included 1486 patients; 745 received 20 units of oxytocin on delivery of the anterior shoulder, and 741 received an identical dose of oxytocin on delivery of the placenta. The incidence of PPH was 5.4% for the anterior shoulder group and 5.8% for the placenta group (P=.72). Likewise, no significant difference between the groups was noted in the proportion of women with estimated blood loss (EBL) ≥500 mL (7.5% vs 9.7%; P=.15).

A much smaller double-blinded RCT found that PPH occurred significantly less often when oxytocin was delayed until after delivery of the placenta.³ The study comprised 51 patients; 27 received 10 units of oxytocin on delivery of the anterior shoulder and 24 received an identical dose after delivery of the placenta. The incidence of PPH ≥500 mL was 0% when oxytocin was given after delivery of the placenta vs 14.8% when it was given on delivery of the anterior shoulder (P=.049). However, the study was limited by its size and potential inaccuracies in estimating blood loss.

A prospective cohort study noted a significant reduction in the risk of PPH when oxytocin was given after delivery of the anterior shoulder, compared with the placenta.⁴ In this study, 82 patients received 5 units of oxytocin on delivery of the anterior shoulder, and 52 received an identical dose after delivery of the placenta. The incidence of PPH ≥500 mL was 7.3% in the anterior shoulder group and 19.2% in the placenta group. However, the study was not blinded and was limited by its small sample size.

Two earlier studies, an RCT and a prospective cohort study, concluded that oxytocin is more effective in reducing PPH when given before placental delivery (after delivery of the anterior shoulder and head, respectively).^5,6 Neither of these studies was blinded nor controlled for nonpharmacologic interventions, however.

Recommendations

The American College of Obstetricians and Gynecologists (ACOG) states that ongoing blood loss accompanied by decreased uterine tone requires uterotonic agents as first-line treatment for PPH.⁷ ACOG doesn’t make specific recommendations regarding the timing of oxytocin administration.

The American Academy of Family Physicians (AAFP) recommends oxytocin as the uterotonic agent of choice for preventing PPH.⁸ The AAFP further advocates active management of the third stage of labor to decrease PPH by administering oxytocin as soon as possible after delivery of the anterior shoulder and before delivery of the placenta.

The World Health Organization (WHO) also recommends oxytocin as the uterotonic of choice.⁹ WHO advocates administration within 1 minute of delivery of the baby.

Evidence summary

The prophylactic use of oxytocic drugs reduces the risk of postpartum hemorrhage (PPH) by about 40% and has been widely adopted as a routine policy in the active management of the third stage of labor.¹ A number of studies have evaluated the timing of oxytocin after delivery (TABLE).

TABLE
What studies say about the timing of oxytocin and PPH risk

Which timing is best? It depends on the study

A well-constructed double-blinded RCT found no significant difference in the incidence of PPH when oxytocin was given after delivery of the anterior shoulder or the placenta.² The study included 1486 patients; 745 received 20 units of oxytocin on delivery of the anterior shoulder, and 741 received an identical dose of oxytocin on delivery of the placenta. The incidence of PPH was 5.4% for the anterior shoulder group and 5.8% for the placenta group (P=.72). Likewise, no significant difference between the groups was noted in the proportion of women with estimated blood loss (EBL) ≥500 mL (7.5% vs 9.7%; P=.15).

A much smaller double-blinded RCT found that PPH occurred significantly less often when oxytocin was delayed until after delivery of the placenta.³ The study comprised 51 patients; 27 received 10 units of oxytocin on delivery of the anterior shoulder and 24 received an identical dose after delivery of the placenta. The incidence of PPH ≥500 mL was 0% when oxytocin was given after delivery of the placenta vs 14.8% when it was given on delivery of the anterior shoulder (P=.049). However, the study was limited by its size and potential inaccuracies in estimating blood loss.

A prospective cohort study noted a significant reduction in the risk of PPH when oxytocin was given after delivery of the anterior shoulder, compared with the placenta.⁴ In this study, 82 patients received 5 units of oxytocin on delivery of the anterior shoulder, and 52 received an identical dose after delivery of the placenta. The incidence of PPH ≥500 mL was 7.3% in the anterior shoulder group and 19.2% in the placenta group. However, the study was not blinded and was limited by its small sample size.

Two earlier studies, an RCT and a prospective cohort study, concluded that oxytocin is more effective in reducing PPH when given before placental delivery (after delivery of the anterior shoulder and head, respectively).^5,6 Neither of these studies was blinded nor controlled for nonpharmacologic interventions, however.

Recommendations

The American College of Obstetricians and Gynecologists (ACOG) states that ongoing blood loss accompanied by decreased uterine tone requires uterotonic agents as first-line treatment for PPH.⁷ ACOG doesn’t make specific recommendations regarding the timing of oxytocin administration.

The American Academy of Family Physicians (AAFP) recommends oxytocin as the uterotonic agent of choice for preventing PPH.⁸ The AAFP further advocates active management of the third stage of labor to decrease PPH by administering oxytocin as soon as possible after delivery of the anterior shoulder and before delivery of the placenta.

The World Health Organization (WHO) also recommends oxytocin as the uterotonic of choice.⁹ WHO advocates administration within 1 minute of delivery of the baby.

Evidence summary

Our search retrieved no randomized controlled clinical trials evaluating the screening tests required to work-up a male with low testosterone. We therefore examined 2 consensus guidelines, 9 review articles, and disease-oriented evidence. The recommendations discussed here are based primarily on consensus guidelines and disease-oriented evidence.

Hypogonadism increases with age

Hypogonadism is a common endocrinologic disorder in men. Advancing age, increased life expectancy, and a rising prevalence of obesity and type 2 diabetes may increase the occurrence of hypogonadism.³ Many cases result from partial androgen deficiency in the aging male, because testosterone levels decline an estimated 1% to 2% per year in adult men.^1,3 A focused, cost-effective work-up will become ever more critical because an estimated 19% of men will be 65 years or older by 2050.⁴

TABLE
Causes of hypogonadism

Serum testosterone: The first-choice test

Serum testosterone measurements are considered the initial test of choice be-cause they’re reliable, inexpensive, and widely available. Testosterone levels vary from hour to hour and diurnally, so a repeat morning measurement is recommended to confirm subnormal levels.^3,5

In some cases—including patients with obesity, type 2 diabetes, or hypothyroidism—the total testosterone level can be misleading; tests for free testosterone and sex hormone-binding globulin levels should be ordered. These tests can also help evaluate men with low-normal total testosterone levels (200-400 ng/dL).^6,7

Is the patient pre- or postpubertal?

Assessment of low testosterone should distinguish between pre- and postpubertal males. In prepubertal males, chromosomal analysis is indicated because hypothalamic-pituitary-gonadal axis defects are common—especially Klinefelter syndrome (1 in 500 males).^6,8

Men with very low testosterone levels (<150 ng/dL) or signs and symptoms suggesting pituitary pathology warrant pituitary imaging and measurement of thyroxine, cortisol, and prolactin levels.⁶ Both pre- and postpubertal males with low testosterone should have FSH, LH, and prolactin levels tested to differentiate primary from secondary hypogonadism.^6,9

Be alert for hemochromatosis and low bone density

Order biopsy or ultrasound examination of testicular masses and iron studies if hemochromatosis is suspected. Hemochromatosis is the most common single gene disorder of Caucasian Americans (1 in 250-300 are homozygous; 1 in 10 are heterozygous) and is associated with hypogonadotrophic hypogonadism.^5,10 In a series of 3 studies, 30% (26 of 89) of men with hemochromatosis had hypogonadism.¹¹ The prevalence of hemochromatosis in males with hypogonadism hasn’t been reported.

Because chronic hypogonadism leads to low bone density and increased risk of fracture, baseline bone densitometry may be prudent.¹² A chart review study of nursing home residents found that 66% of men with hip fractures and 20% of men with vertebral fractures had low testosterone.¹³ Notably, 50% of men in their 80s have testosterone levels in the hypogonadal range (<300 ng/dL), compared with 12% of men <50 years.^1,14

Recommendations

Scant guidance is available concerning what screening tests to order for a male with low testosterone. The United States Preventive Services Task Force and Canadian Task Force on Preventive Health Care make no recommendations; the Cochrane collaboration has no reviews on the topic. The American Association of Clinical Endocrinologists’ (AACE) guidelines are based on expert opinion.³

The AACE consensus guideline used peer review for validation and didn’t specify the method used to assess the quality and strength of the evidence used to write the statement. The AACE guideline recommends a history and physical exam, obtaining repeat morning testosterone levels, prolactin, FSH, LH, bone densitometry, and a semen analysis if fertility is an issue.

In acquired hypogonadism, pituitary imaging is recommended along with thyroid, adrenal, and growth hormone axis testing. Prepubertal males should undergo chromosome analysis, and men with a suspected mass should have a testicular ultrasound examination.

Evidence summary

Our search retrieved no randomized controlled clinical trials evaluating the screening tests required to work-up a male with low testosterone. We therefore examined 2 consensus guidelines, 9 review articles, and disease-oriented evidence. The recommendations discussed here are based primarily on consensus guidelines and disease-oriented evidence.

Hypogonadism increases with age

Hypogonadism is a common endocrinologic disorder in men. Advancing age, increased life expectancy, and a rising prevalence of obesity and type 2 diabetes may increase the occurrence of hypogonadism.³ Many cases result from partial androgen deficiency in the aging male, because testosterone levels decline an estimated 1% to 2% per year in adult men.^1,3 A focused, cost-effective work-up will become ever more critical because an estimated 19% of men will be 65 years or older by 2050.⁴

TABLE
Causes of hypogonadism

Serum testosterone: The first-choice test

Serum testosterone measurements are considered the initial test of choice be-cause they’re reliable, inexpensive, and widely available. Testosterone levels vary from hour to hour and diurnally, so a repeat morning measurement is recommended to confirm subnormal levels.^3,5

In some cases—including patients with obesity, type 2 diabetes, or hypothyroidism—the total testosterone level can be misleading; tests for free testosterone and sex hormone-binding globulin levels should be ordered. These tests can also help evaluate men with low-normal total testosterone levels (200-400 ng/dL).^6,7

Is the patient pre- or postpubertal?

Assessment of low testosterone should distinguish between pre- and postpubertal males. In prepubertal males, chromosomal analysis is indicated because hypothalamic-pituitary-gonadal axis defects are common—especially Klinefelter syndrome (1 in 500 males).^6,8

Men with very low testosterone levels (<150 ng/dL) or signs and symptoms suggesting pituitary pathology warrant pituitary imaging and measurement of thyroxine, cortisol, and prolactin levels.⁶ Both pre- and postpubertal males with low testosterone should have FSH, LH, and prolactin levels tested to differentiate primary from secondary hypogonadism.^6,9

Be alert for hemochromatosis and low bone density

Order biopsy or ultrasound examination of testicular masses and iron studies if hemochromatosis is suspected. Hemochromatosis is the most common single gene disorder of Caucasian Americans (1 in 250-300 are homozygous; 1 in 10 are heterozygous) and is associated with hypogonadotrophic hypogonadism.^5,10 In a series of 3 studies, 30% (26 of 89) of men with hemochromatosis had hypogonadism.¹¹ The prevalence of hemochromatosis in males with hypogonadism hasn’t been reported.

Because chronic hypogonadism leads to low bone density and increased risk of fracture, baseline bone densitometry may be prudent.¹² A chart review study of nursing home residents found that 66% of men with hip fractures and 20% of men with vertebral fractures had low testosterone.¹³ Notably, 50% of men in their 80s have testosterone levels in the hypogonadal range (<300 ng/dL), compared with 12% of men <50 years.^1,14

Recommendations

Scant guidance is available concerning what screening tests to order for a male with low testosterone. The United States Preventive Services Task Force and Canadian Task Force on Preventive Health Care make no recommendations; the Cochrane collaboration has no reviews on the topic. The American Association of Clinical Endocrinologists’ (AACE) guidelines are based on expert opinion.³

The AACE consensus guideline used peer review for validation and didn’t specify the method used to assess the quality and strength of the evidence used to write the statement. The AACE guideline recommends a history and physical exam, obtaining repeat morning testosterone levels, prolactin, FSH, LH, bone densitometry, and a semen analysis if fertility is an issue.

In acquired hypogonadism, pituitary imaging is recommended along with thyroid, adrenal, and growth hormone axis testing. Prepubertal males should undergo chromosome analysis, and men with a suspected mass should have a testicular ultrasound examination.

Evidence summary

Our search retrieved no randomized controlled clinical trials evaluating the screening tests required to work-up a male with low testosterone. We therefore examined 2 consensus guidelines, 9 review articles, and disease-oriented evidence. The recommendations discussed here are based primarily on consensus guidelines and disease-oriented evidence.

Hypogonadism increases with age

Hypogonadism is a common endocrinologic disorder in men. Advancing age, increased life expectancy, and a rising prevalence of obesity and type 2 diabetes may increase the occurrence of hypogonadism.³ Many cases result from partial androgen deficiency in the aging male, because testosterone levels decline an estimated 1% to 2% per year in adult men.^1,3 A focused, cost-effective work-up will become ever more critical because an estimated 19% of men will be 65 years or older by 2050.⁴

TABLE
Causes of hypogonadism

Serum testosterone: The first-choice test

Serum testosterone measurements are considered the initial test of choice be-cause they’re reliable, inexpensive, and widely available. Testosterone levels vary from hour to hour and diurnally, so a repeat morning measurement is recommended to confirm subnormal levels.^3,5

In some cases—including patients with obesity, type 2 diabetes, or hypothyroidism—the total testosterone level can be misleading; tests for free testosterone and sex hormone-binding globulin levels should be ordered. These tests can also help evaluate men with low-normal total testosterone levels (200-400 ng/dL).^6,7

Is the patient pre- or postpubertal?

Assessment of low testosterone should distinguish between pre- and postpubertal males. In prepubertal males, chromosomal analysis is indicated because hypothalamic-pituitary-gonadal axis defects are common—especially Klinefelter syndrome (1 in 500 males).^6,8

Men with very low testosterone levels (<150 ng/dL) or signs and symptoms suggesting pituitary pathology warrant pituitary imaging and measurement of thyroxine, cortisol, and prolactin levels.⁶ Both pre- and postpubertal males with low testosterone should have FSH, LH, and prolactin levels tested to differentiate primary from secondary hypogonadism.^6,9

Be alert for hemochromatosis and low bone density

Order biopsy or ultrasound examination of testicular masses and iron studies if hemochromatosis is suspected. Hemochromatosis is the most common single gene disorder of Caucasian Americans (1 in 250-300 are homozygous; 1 in 10 are heterozygous) and is associated with hypogonadotrophic hypogonadism.^5,10 In a series of 3 studies, 30% (26 of 89) of men with hemochromatosis had hypogonadism.¹¹ The prevalence of hemochromatosis in males with hypogonadism hasn’t been reported.

Because chronic hypogonadism leads to low bone density and increased risk of fracture, baseline bone densitometry may be prudent.¹² A chart review study of nursing home residents found that 66% of men with hip fractures and 20% of men with vertebral fractures had low testosterone.¹³ Notably, 50% of men in their 80s have testosterone levels in the hypogonadal range (<300 ng/dL), compared with 12% of men <50 years.^1,14

Recommendations

Scant guidance is available concerning what screening tests to order for a male with low testosterone. The United States Preventive Services Task Force and Canadian Task Force on Preventive Health Care make no recommendations; the Cochrane collaboration has no reviews on the topic. The American Association of Clinical Endocrinologists’ (AACE) guidelines are based on expert opinion.³

The AACE consensus guideline used peer review for validation and didn’t specify the method used to assess the quality and strength of the evidence used to write the statement. The AACE guideline recommends a history and physical exam, obtaining repeat morning testosterone levels, prolactin, FSH, LH, bone densitometry, and a semen analysis if fertility is an issue.

In acquired hypogonadism, pituitary imaging is recommended along with thyroid, adrenal, and growth hormone axis testing. Prepubertal males should undergo chromosome analysis, and men with a suspected mass should have a testicular ultrasound examination.

Evidence summary

A Cochrane review of 6 relatively small (N=24-94) RCTs found insufficient evidence to support using steroids to manage infectious mononucleosis.^1-7 We found no other studies.

Steroids don’t significantly reduce throat pain, weight loss

In an RCT of 40 patients, 1 dose of dexamethasone reduced throat pain at 12 hours in 60% of the treatment group, compared with placebo.² However, no significant differences were noted at 1 and 7 days.

A trial of combined therapy with acyclovir and prednisolone in 94 patients found no differences in resolution of sore throat, weight loss, and absence from school or work in the treatment group.³ Likewise, a study of a 6-day prednisone taper found no difference in resolution of symptoms in the prednisone group (N=47).⁴

Conflicting findings on steroids and fever—and adverse effects

One small, double-blind study of prednisone (N=26 hospitalized college students) showed a significant difference in duration of fever and antibody titers compared with aspirin.⁵ Two other studies of the duration of fever didn’t find convincing evidence of benefit, however.^2,7 One of these studies did find that patients’ infirmary stays were shortened an average of 3 days, although the data to support this finding were not reported.⁷

Two studies also reported that 3 patients experienced adverse events, including dehydration and severe pharyngitis,² acute onset of diabetes mellitus,⁵ and peritonsillar cellulitis.⁵ Other potential adverse reactions include transient hyperglycemia, sodium retention, nausea, vomiting, and insomnia.⁸

Recommendations

We found no recommendations concerning the use of steroids to treat infectious mononucleosis. A review article from American Family Physician recommends avoiding corticosteroids to treat the condition unless the patient is experiencing severe complications.⁹

Evidence summary

A Cochrane review of 6 relatively small (N=24-94) RCTs found insufficient evidence to support using steroids to manage infectious mononucleosis.^1-7 We found no other studies.

Steroids don’t significantly reduce throat pain, weight loss

In an RCT of 40 patients, 1 dose of dexamethasone reduced throat pain at 12 hours in 60% of the treatment group, compared with placebo.² However, no significant differences were noted at 1 and 7 days.

A trial of combined therapy with acyclovir and prednisolone in 94 patients found no differences in resolution of sore throat, weight loss, and absence from school or work in the treatment group.³ Likewise, a study of a 6-day prednisone taper found no difference in resolution of symptoms in the prednisone group (N=47).⁴

Conflicting findings on steroids and fever—and adverse effects

One small, double-blind study of prednisone (N=26 hospitalized college students) showed a significant difference in duration of fever and antibody titers compared with aspirin.⁵ Two other studies of the duration of fever didn’t find convincing evidence of benefit, however.^2,7 One of these studies did find that patients’ infirmary stays were shortened an average of 3 days, although the data to support this finding were not reported.⁷

Two studies also reported that 3 patients experienced adverse events, including dehydration and severe pharyngitis,² acute onset of diabetes mellitus,⁵ and peritonsillar cellulitis.⁵ Other potential adverse reactions include transient hyperglycemia, sodium retention, nausea, vomiting, and insomnia.⁸

Recommendations

We found no recommendations concerning the use of steroids to treat infectious mononucleosis. A review article from American Family Physician recommends avoiding corticosteroids to treat the condition unless the patient is experiencing severe complications.⁹

Evidence summary

A Cochrane review of 6 relatively small (N=24-94) RCTs found insufficient evidence to support using steroids to manage infectious mononucleosis.^1-7 We found no other studies.

Steroids don’t significantly reduce throat pain, weight loss

In an RCT of 40 patients, 1 dose of dexamethasone reduced throat pain at 12 hours in 60% of the treatment group, compared with placebo.² However, no significant differences were noted at 1 and 7 days.

A trial of combined therapy with acyclovir and prednisolone in 94 patients found no differences in resolution of sore throat, weight loss, and absence from school or work in the treatment group.³ Likewise, a study of a 6-day prednisone taper found no difference in resolution of symptoms in the prednisone group (N=47).⁴

Conflicting findings on steroids and fever—and adverse effects

One small, double-blind study of prednisone (N=26 hospitalized college students) showed a significant difference in duration of fever and antibody titers compared with aspirin.⁵ Two other studies of the duration of fever didn’t find convincing evidence of benefit, however.^2,7 One of these studies did find that patients’ infirmary stays were shortened an average of 3 days, although the data to support this finding were not reported.⁷

Two studies also reported that 3 patients experienced adverse events, including dehydration and severe pharyngitis,² acute onset of diabetes mellitus,⁵ and peritonsillar cellulitis.⁵ Other potential adverse reactions include transient hyperglycemia, sodium retention, nausea, vomiting, and insomnia.⁸

Recommendations

We found no recommendations concerning the use of steroids to treat infectious mononucleosis. A review article from American Family Physician recommends avoiding corticosteroids to treat the condition unless the patient is experiencing severe complications.⁹