Barbara Jamieson, MLS

Evidence summary

Acute chorioamnionitis (or intra-amniotic infection) poses a high risk of maternal and neonatal morbidity. Neonatal sepsis or pneumonia occurs in up to 24% of infants born to mothers with chorioamnionitis;¹ 1% to 2% of pregnancies complicated by chorioamnionitis end in neonatal death.^1,2

Acute chorioamnionitis is defined as intrapartum maternal fever and maternal tachycardia, fetal tachycardia, uterine tenderness, or purulent amniotic fluid.^1,3 Antibiotic treatment of acute chorioamnionitis is widely accepted, yet in vivo studies to determine the most effective empiric antibiotic regimens are lacking.

Intrapartum antibiotics probably reduce sepsis

Although few well-designed trials stand out, a Cochrane review⁴ summarizing 2 relevant studies is available. Gibbs et al³ performed an underpowered, randomized comparative trial of intrapartum vs postpartum treatment of chorioamnionitis, with both groups (45 patients total) receiving ampicillin 2 g IV every 6 hours plus gentamicin 1.5 mg/kg IV every 8 hours.³ Those women who underwent cesarean section also received clindamycin 900 mg IV every 8 hours starting at cord clamping. In this study, investigators reported neonatal sepsis was significantly reduced with intrapartum treatment (0 vs 21%; P=.03, number needed to treat=4.8), as were neonatal hospital stays (3.8 vs 5.7 days; P=.02), regardless of delivery method. The study had been planned for 92 patients; it was stopped early (n=48) after an interim analysis.

Because of the small sample size, other findings from the study must be viewed with caution. Intrapartum treatment with antibiotics was associated with a “significant” clinical reduction in neonatal sepsis (relative risk [RR]=0.08; 95% confidence interval [CI], 0.00–1.44) and pneumonia (RR=0.15; 95% CI, 0.01–2.92) compared with treatment given immediately postpartum; however, neither value was truly statistically significant according to the Cochrane review.⁴

The research suggests a potential benefit to adding clindamycin to ampicillin and gentamicin. In an effort to test this, 1 study randomized 133 women into 2 arms—treatment with ampicillin, gentamicin, and clindamycin compared with ampicillin and gentamicin alone—and found no additional benefit in regards to neonatal sepsis (RR=2.16; 95% CI, 0.20–23.21) or neonatal death (RR=0.72; 95% CI, 0.12–4.16).¹ There was a trend towards a decrease in the incidence of postpartum endometritis in women who received ampicillin, gentamicin, and clindamycin, but this did not reach statistical significance (RR=0.54; 95% CI, 0.19–1.49).⁴

Recommendations from others

A 2002 bulletin from American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics⁵ recommended the combination of ampicillin 2 gm IV every 4 to 6 hours or penicillin 5 million units IV every 4 to 6 hours, plus an aminoglycoside (such as gentamicin 1.5 mg/kg IV every 8 hours), since this regimen provides appropriate coverage for typical organisms associated with acute chorioamnionitis. At the time the bulletin was published, the use of single daily dosing of aminoglycoside did not have sufficient studies to back its use. In addition, ACOG recommends adding clindamycin, metronidazole, or an extended-spectrum third-generation cephalosporin to the treatment regimen if cesarean section is required, to provide coverage for anaerobic organisms. They recommend clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. The Nottingham Guideline Development Group recommends amoxicillin 2 gm IV initially then 1 gm every 8 hours, and in place of gentamicin, recommends metronidazole 500 mg IV, every 8 hours (or 1 gm PR twice a day).⁶ Both recommendations suggest clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. For patients with nonanaphylactic reactions to penicillin, they recommend cefotaxime 1 g IV every 8 hours.

Acknowledgments

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

Evidence summary

Acute chorioamnionitis (or intra-amniotic infection) poses a high risk of maternal and neonatal morbidity. Neonatal sepsis or pneumonia occurs in up to 24% of infants born to mothers with chorioamnionitis;¹ 1% to 2% of pregnancies complicated by chorioamnionitis end in neonatal death.^1,2

Acute chorioamnionitis is defined as intrapartum maternal fever and maternal tachycardia, fetal tachycardia, uterine tenderness, or purulent amniotic fluid.^1,3 Antibiotic treatment of acute chorioamnionitis is widely accepted, yet in vivo studies to determine the most effective empiric antibiotic regimens are lacking.

Intrapartum antibiotics probably reduce sepsis

Although few well-designed trials stand out, a Cochrane review⁴ summarizing 2 relevant studies is available. Gibbs et al³ performed an underpowered, randomized comparative trial of intrapartum vs postpartum treatment of chorioamnionitis, with both groups (45 patients total) receiving ampicillin 2 g IV every 6 hours plus gentamicin 1.5 mg/kg IV every 8 hours.³ Those women who underwent cesarean section also received clindamycin 900 mg IV every 8 hours starting at cord clamping. In this study, investigators reported neonatal sepsis was significantly reduced with intrapartum treatment (0 vs 21%; P=.03, number needed to treat=4.8), as were neonatal hospital stays (3.8 vs 5.7 days; P=.02), regardless of delivery method. The study had been planned for 92 patients; it was stopped early (n=48) after an interim analysis.

Because of the small sample size, other findings from the study must be viewed with caution. Intrapartum treatment with antibiotics was associated with a “significant” clinical reduction in neonatal sepsis (relative risk [RR]=0.08; 95% confidence interval [CI], 0.00–1.44) and pneumonia (RR=0.15; 95% CI, 0.01–2.92) compared with treatment given immediately postpartum; however, neither value was truly statistically significant according to the Cochrane review.⁴

The research suggests a potential benefit to adding clindamycin to ampicillin and gentamicin. In an effort to test this, 1 study randomized 133 women into 2 arms—treatment with ampicillin, gentamicin, and clindamycin compared with ampicillin and gentamicin alone—and found no additional benefit in regards to neonatal sepsis (RR=2.16; 95% CI, 0.20–23.21) or neonatal death (RR=0.72; 95% CI, 0.12–4.16).¹ There was a trend towards a decrease in the incidence of postpartum endometritis in women who received ampicillin, gentamicin, and clindamycin, but this did not reach statistical significance (RR=0.54; 95% CI, 0.19–1.49).⁴

Recommendations from others

A 2002 bulletin from American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics⁵ recommended the combination of ampicillin 2 gm IV every 4 to 6 hours or penicillin 5 million units IV every 4 to 6 hours, plus an aminoglycoside (such as gentamicin 1.5 mg/kg IV every 8 hours), since this regimen provides appropriate coverage for typical organisms associated with acute chorioamnionitis. At the time the bulletin was published, the use of single daily dosing of aminoglycoside did not have sufficient studies to back its use. In addition, ACOG recommends adding clindamycin, metronidazole, or an extended-spectrum third-generation cephalosporin to the treatment regimen if cesarean section is required, to provide coverage for anaerobic organisms. They recommend clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. The Nottingham Guideline Development Group recommends amoxicillin 2 gm IV initially then 1 gm every 8 hours, and in place of gentamicin, recommends metronidazole 500 mg IV, every 8 hours (or 1 gm PR twice a day).⁶ Both recommendations suggest clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. For patients with nonanaphylactic reactions to penicillin, they recommend cefotaxime 1 g IV every 8 hours.

Acknowledgments

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

Evidence summary

Acute chorioamnionitis (or intra-amniotic infection) poses a high risk of maternal and neonatal morbidity. Neonatal sepsis or pneumonia occurs in up to 24% of infants born to mothers with chorioamnionitis;¹ 1% to 2% of pregnancies complicated by chorioamnionitis end in neonatal death.^1,2

Acute chorioamnionitis is defined as intrapartum maternal fever and maternal tachycardia, fetal tachycardia, uterine tenderness, or purulent amniotic fluid.^1,3 Antibiotic treatment of acute chorioamnionitis is widely accepted, yet in vivo studies to determine the most effective empiric antibiotic regimens are lacking.

Intrapartum antibiotics probably reduce sepsis

Although few well-designed trials stand out, a Cochrane review⁴ summarizing 2 relevant studies is available. Gibbs et al³ performed an underpowered, randomized comparative trial of intrapartum vs postpartum treatment of chorioamnionitis, with both groups (45 patients total) receiving ampicillin 2 g IV every 6 hours plus gentamicin 1.5 mg/kg IV every 8 hours.³ Those women who underwent cesarean section also received clindamycin 900 mg IV every 8 hours starting at cord clamping. In this study, investigators reported neonatal sepsis was significantly reduced with intrapartum treatment (0 vs 21%; P=.03, number needed to treat=4.8), as were neonatal hospital stays (3.8 vs 5.7 days; P=.02), regardless of delivery method. The study had been planned for 92 patients; it was stopped early (n=48) after an interim analysis.

Because of the small sample size, other findings from the study must be viewed with caution. Intrapartum treatment with antibiotics was associated with a “significant” clinical reduction in neonatal sepsis (relative risk [RR]=0.08; 95% confidence interval [CI], 0.00–1.44) and pneumonia (RR=0.15; 95% CI, 0.01–2.92) compared with treatment given immediately postpartum; however, neither value was truly statistically significant according to the Cochrane review.⁴

The research suggests a potential benefit to adding clindamycin to ampicillin and gentamicin. In an effort to test this, 1 study randomized 133 women into 2 arms—treatment with ampicillin, gentamicin, and clindamycin compared with ampicillin and gentamicin alone—and found no additional benefit in regards to neonatal sepsis (RR=2.16; 95% CI, 0.20–23.21) or neonatal death (RR=0.72; 95% CI, 0.12–4.16).¹ There was a trend towards a decrease in the incidence of postpartum endometritis in women who received ampicillin, gentamicin, and clindamycin, but this did not reach statistical significance (RR=0.54; 95% CI, 0.19–1.49).⁴

Recommendations from others

A 2002 bulletin from American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics⁵ recommended the combination of ampicillin 2 gm IV every 4 to 6 hours or penicillin 5 million units IV every 4 to 6 hours, plus an aminoglycoside (such as gentamicin 1.5 mg/kg IV every 8 hours), since this regimen provides appropriate coverage for typical organisms associated with acute chorioamnionitis. At the time the bulletin was published, the use of single daily dosing of aminoglycoside did not have sufficient studies to back its use. In addition, ACOG recommends adding clindamycin, metronidazole, or an extended-spectrum third-generation cephalosporin to the treatment regimen if cesarean section is required, to provide coverage for anaerobic organisms. They recommend clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. The Nottingham Guideline Development Group recommends amoxicillin 2 gm IV initially then 1 gm every 8 hours, and in place of gentamicin, recommends metronidazole 500 mg IV, every 8 hours (or 1 gm PR twice a day).⁶ Both recommendations suggest clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. For patients with nonanaphylactic reactions to penicillin, they recommend cefotaxime 1 g IV every 8 hours.

Acknowledgments

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

Evidence summary

Lupus anticoagulant and anticardiolipin antibodies are known to increase risk of both arterial and venous thromboembolic events.

One study prospectively followed patients ≥15 years old recruited from 16 hospitals in Sweden, who had their first or second episode of a VTE. Patients with malignancy or a known congenital deficiency of an inhibitor of coagulation were excluded. These patients were followed for 4 years. Each received at least 6 months of warfarin therapy (INR=2.0–2.85) after initial diagnosis of a VTE.

After treatment, the 4-year recurrence rate for VTEs was 29% for patients with aPL (20/68) vs 14% for patients without (47/344) (relative risk [RR]=2.1; 95% confidence interval [CI], 1.3–3.3). The risk of death for those patients with aPL was 15% (10/68) vs 6% for those without (20/324) (RR=1.8; 95% CI, 0.9–3.6).

In the same study, those with an aPL and a second clot were randomized to a second 6 months of therapy vs indefinite therapy (INR=2.0–2.85). After 4 years, their risk of another recurrence was 20% (3/15) with 6 months of therapy vs 5% (1/19) with indefinite therapy. This underpowered study did not show a statistical difference under intention-to-treat analysis; however, the single failure in the treatment group had stopped the warfarin prior to the event.⁴

Moderate intensity therapy does the job

Two recent randomized controlled trials have shown that moderate-intensity warfarin therapy (INR=2.0–3.0) is equally efficacious to high-intensity therapy (INR=3.0–4.0).^5,6 In these small studies, those with aPL were randomized to moderate-intensity vs high-intensity therapy and followed for approximately 3 years. A meta-analysis of these studies (done in conjunction with the second study) remained insufficiently powered to show any significant differences between high- and moderate-intensity therapy, but there was a trend towards increased thrombosis and bleeding events in the high-intensity groups.⁶ Of note, the relative risk for developing a VTE was lower in these studies than in those with time-limited treatment, suggesting that indefinite treatment may be indicated.

Warfarin probably isn’t best for primary prevention

Wahl et al⁷ constructed a decision analysis of antithrombotic therapy for patients with systemic lupus erythematosus with and without aPL. They compared observation alone with aspirin and with warfarin for the primary prevention of VTE. Using a decision analysis based on the best available efficacy rates, they recommended that the benefits of prophylactic aspirin outweigh the risks. However, due to high complication rates, warfarin’s benefits are outweighed by the risks. This analysis has not been validated in an actual patient population and remains theoretical in nature, but is the best available evidence regarding primary prevention of VTE for patients with aPL.

Recommendations from others

Guidelines from the American College of Chest Physicians recommend at least 12 months of treatment with warfarin and suggest indefinite treatment for patients with a VTE and antiphospholipid antibodies. The guidelines also suggest a target INR of 3.0 (range, 2.5–3.5) for patients with recurrent VTEs or additional risk factors, and a therapeutic INR of 2.5 (range, 2.0–3.0) for patients with a VTE and lupus anticoagulant but no additional risk factors.⁸

The Thrombosis Interest Group of Canada also recommends considering indefinite treatment for those with a VTE and a positive test for any of the antiphospholipid antibodies.⁹

Evidence summary

Lupus anticoagulant and anticardiolipin antibodies are known to increase risk of both arterial and venous thromboembolic events.

One study prospectively followed patients ≥15 years old recruited from 16 hospitals in Sweden, who had their first or second episode of a VTE. Patients with malignancy or a known congenital deficiency of an inhibitor of coagulation were excluded. These patients were followed for 4 years. Each received at least 6 months of warfarin therapy (INR=2.0–2.85) after initial diagnosis of a VTE.

After treatment, the 4-year recurrence rate for VTEs was 29% for patients with aPL (20/68) vs 14% for patients without (47/344) (relative risk [RR]=2.1; 95% confidence interval [CI], 1.3–3.3). The risk of death for those patients with aPL was 15% (10/68) vs 6% for those without (20/324) (RR=1.8; 95% CI, 0.9–3.6).

In the same study, those with an aPL and a second clot were randomized to a second 6 months of therapy vs indefinite therapy (INR=2.0–2.85). After 4 years, their risk of another recurrence was 20% (3/15) with 6 months of therapy vs 5% (1/19) with indefinite therapy. This underpowered study did not show a statistical difference under intention-to-treat analysis; however, the single failure in the treatment group had stopped the warfarin prior to the event.⁴

Moderate intensity therapy does the job

Two recent randomized controlled trials have shown that moderate-intensity warfarin therapy (INR=2.0–3.0) is equally efficacious to high-intensity therapy (INR=3.0–4.0).^5,6 In these small studies, those with aPL were randomized to moderate-intensity vs high-intensity therapy and followed for approximately 3 years. A meta-analysis of these studies (done in conjunction with the second study) remained insufficiently powered to show any significant differences between high- and moderate-intensity therapy, but there was a trend towards increased thrombosis and bleeding events in the high-intensity groups.⁶ Of note, the relative risk for developing a VTE was lower in these studies than in those with time-limited treatment, suggesting that indefinite treatment may be indicated.

Warfarin probably isn’t best for primary prevention

Wahl et al⁷ constructed a decision analysis of antithrombotic therapy for patients with systemic lupus erythematosus with and without aPL. They compared observation alone with aspirin and with warfarin for the primary prevention of VTE. Using a decision analysis based on the best available efficacy rates, they recommended that the benefits of prophylactic aspirin outweigh the risks. However, due to high complication rates, warfarin’s benefits are outweighed by the risks. This analysis has not been validated in an actual patient population and remains theoretical in nature, but is the best available evidence regarding primary prevention of VTE for patients with aPL.

Recommendations from others

Guidelines from the American College of Chest Physicians recommend at least 12 months of treatment with warfarin and suggest indefinite treatment for patients with a VTE and antiphospholipid antibodies. The guidelines also suggest a target INR of 3.0 (range, 2.5–3.5) for patients with recurrent VTEs or additional risk factors, and a therapeutic INR of 2.5 (range, 2.0–3.0) for patients with a VTE and lupus anticoagulant but no additional risk factors.⁸

The Thrombosis Interest Group of Canada also recommends considering indefinite treatment for those with a VTE and a positive test for any of the antiphospholipid antibodies.⁹

Evidence summary

Lupus anticoagulant and anticardiolipin antibodies are known to increase risk of both arterial and venous thromboembolic events.

One study prospectively followed patients ≥15 years old recruited from 16 hospitals in Sweden, who had their first or second episode of a VTE. Patients with malignancy or a known congenital deficiency of an inhibitor of coagulation were excluded. These patients were followed for 4 years. Each received at least 6 months of warfarin therapy (INR=2.0–2.85) after initial diagnosis of a VTE.

After treatment, the 4-year recurrence rate for VTEs was 29% for patients with aPL (20/68) vs 14% for patients without (47/344) (relative risk [RR]=2.1; 95% confidence interval [CI], 1.3–3.3). The risk of death for those patients with aPL was 15% (10/68) vs 6% for those without (20/324) (RR=1.8; 95% CI, 0.9–3.6).

In the same study, those with an aPL and a second clot were randomized to a second 6 months of therapy vs indefinite therapy (INR=2.0–2.85). After 4 years, their risk of another recurrence was 20% (3/15) with 6 months of therapy vs 5% (1/19) with indefinite therapy. This underpowered study did not show a statistical difference under intention-to-treat analysis; however, the single failure in the treatment group had stopped the warfarin prior to the event.⁴

Moderate intensity therapy does the job

Two recent randomized controlled trials have shown that moderate-intensity warfarin therapy (INR=2.0–3.0) is equally efficacious to high-intensity therapy (INR=3.0–4.0).^5,6 In these small studies, those with aPL were randomized to moderate-intensity vs high-intensity therapy and followed for approximately 3 years. A meta-analysis of these studies (done in conjunction with the second study) remained insufficiently powered to show any significant differences between high- and moderate-intensity therapy, but there was a trend towards increased thrombosis and bleeding events in the high-intensity groups.⁶ Of note, the relative risk for developing a VTE was lower in these studies than in those with time-limited treatment, suggesting that indefinite treatment may be indicated.

Warfarin probably isn’t best for primary prevention

Wahl et al⁷ constructed a decision analysis of antithrombotic therapy for patients with systemic lupus erythematosus with and without aPL. They compared observation alone with aspirin and with warfarin for the primary prevention of VTE. Using a decision analysis based on the best available efficacy rates, they recommended that the benefits of prophylactic aspirin outweigh the risks. However, due to high complication rates, warfarin’s benefits are outweighed by the risks. This analysis has not been validated in an actual patient population and remains theoretical in nature, but is the best available evidence regarding primary prevention of VTE for patients with aPL.

Recommendations from others

Guidelines from the American College of Chest Physicians recommend at least 12 months of treatment with warfarin and suggest indefinite treatment for patients with a VTE and antiphospholipid antibodies. The guidelines also suggest a target INR of 3.0 (range, 2.5–3.5) for patients with recurrent VTEs or additional risk factors, and a therapeutic INR of 2.5 (range, 2.0–3.0) for patients with a VTE and lupus anticoagulant but no additional risk factors.⁸

The Thrombosis Interest Group of Canada also recommends considering indefinite treatment for those with a VTE and a positive test for any of the antiphospholipid antibodies.⁹

Evidence summary

Self-care can be defined as activities that a patient undertakes with the intention of improving health or preventing disease. Self-care for hypertension includes taking medicine as prescribed, monitoring blood pressure response to therapy, and adopting lifestyle recommendations—increasing exercise, decreasing salt intake, and increasing fruits and vegetable consumption.

Keeping meds simple improves adherence

Various interventions have been developed with the goal of improving medication adherence among patients with hypertension. A Cochrane review included 38 randomized controlled trials (RCTs) of 58 various types of interventions (some tested in factorial trials) designed to improve patient adherence to antihypertensive medications in ambulatory settings.¹ The quality of the studies was generally low due to inadequate allocation concealment, lack of blinding of outcome assessors, loss to follow-up, and the small number of participants in trials.

The authors grouped interventions into 4 broad categories: simplification of dosing regimens; patient education; patient motivation, support, and reminders; and complex interventions. Comparison groups received either no intervention, usual care, or—in the case of simplification of dosing regimens—a daily regimen consisting of more than 1 pill per day vs a once-daily regimen. Because of various types of interventions and different methods of assessing outcomes, pooling of results was, appropriately, not done.

Of all the interventions, simplification of dosing regimens had the most evidence of effectiveness, with 7 out of 9 studies demonstrating a statistically significant improvement in adherence in the intervention group. In the other 2 studies, improved adherence was observed in the intervention group; however, the effect was either not statistically significant or not reported.

Five of the studies used a system that electronically recorded the time and date when a medicine container was opened. All studies using this rigorous system for outcome measurement demonstrated statistically significant improvement in adherence with once-daily vs twice-daily dosage regimens. Relative improvement in adherence ranged from 8% to 20%.

Educational strategies alone were largely ineffective in improving adherence. Only 1 of 6 studies of patient education intervention demonstrated improved adherence, but the trial was small (n=110), and the effect was not seen in the other studies (total of 1103 patients).

Research on motivating patients is inconsistent

Motivation and support strategies consisted of interventions such as drug reminder charts, self-recording of blood pressure, mail reminders, and home visits.

Overall, out of 24 RCTs studying motivational, support, and reminder interventions, 10 demonstrated statistically significant but small improvements in adherence. These studies relied on measures such as pill counts and self-report to assess adherence rather than electronic monitoring. The marked inconsistency among the body of evidence makes it difficult to determine whether motivational, support, and reminder interventions alone are effective in improving adherence.

Out of 18 studies of interventions classified as complex health and organizational interventions, including many with an educational or motivational component, interventions in 8 studies led to a statistically significant improvement in adherence. Complex interventions included structured hypertension management programs such as worksite care provided by trained nurses. An example of an intervention given in combination is a program of home visits, education, and specialized dosing devices. Because these interventions varied considerably, an overall statement of effectiveness is not appropriate.

Modest success seen in improving diet

A Cochrane review of dietary advice for reducing cardiovascular disease risk among healthy adults included 29 trials.² Individuals or groups of patients received verbal or printed dietary advice over 1 or more personal contacts. They also received advice by telephone. Ten RCTs of dietary advice in 4328 participants or groups of participants assessed self-reported dietary fat intake.

Overall, intake of dietary fat (expressed as a percentage of total caloric intake) fell by 6.2% (95% confidence interval [CI], reduced 8.4% to increased 4.0%) with dietary intervention over 6 to 48 months. Due to significant heterogeneity between the studies, this overall estimate must be viewed with caution.

Eight RCT studies in 3952 participants or groups of participants assessed self-reported fruit and vegetable intake as an outcome. Overall, intake of fruits and vegetables increased by 1.2 servings per day (95% CI, 0.43–2.1) with interventions over 6 to 48 months. Again, there was significant heterogeneity between the studies. Therefore, this overall estimate must be viewed with caution.

In general, the quality of the studies included in this systematic review was low due to poor descriptions of randomization, lack of allocation concealment, and lack of blinding of outcome assessment. The use of food frequency questionnaires to measure fat and fruit/vegetable intake likely led to reporting bias in these dietary intervention studies. Also, the trials were in healthy adults and not specific to hypertensive patients.

Motiviating patents to exercise remains a challenge

We found 1 randomized trial that evaluated the effectiveness of a physician’s advice to increase physical activity among patients with hypertension in a general practice setting.³ Physical activity was measured using a validated questionnaire. Patients given the advice as part of self-care for hypertension (n=192) were no more likely to have increased their physical activity than those not given the advice (n=108) at 2- and 6-month follow-ups.

Recommendations from others

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) states that self-measurement of blood pressure may benefit patients by providing information on response to antihypertensive medication and improving adherence with therapy.⁴

The report also notes that the patient and clinician must agree on blood pressure goals, and that patient motivation to adopt lifestyle changes and take prescribed medication improves when patients have positive experiences and trust their clinicians.

Evidence summary

Self-care can be defined as activities that a patient undertakes with the intention of improving health or preventing disease. Self-care for hypertension includes taking medicine as prescribed, monitoring blood pressure response to therapy, and adopting lifestyle recommendations—increasing exercise, decreasing salt intake, and increasing fruits and vegetable consumption.

Keeping meds simple improves adherence

Various interventions have been developed with the goal of improving medication adherence among patients with hypertension. A Cochrane review included 38 randomized controlled trials (RCTs) of 58 various types of interventions (some tested in factorial trials) designed to improve patient adherence to antihypertensive medications in ambulatory settings.¹ The quality of the studies was generally low due to inadequate allocation concealment, lack of blinding of outcome assessors, loss to follow-up, and the small number of participants in trials.

The authors grouped interventions into 4 broad categories: simplification of dosing regimens; patient education; patient motivation, support, and reminders; and complex interventions. Comparison groups received either no intervention, usual care, or—in the case of simplification of dosing regimens—a daily regimen consisting of more than 1 pill per day vs a once-daily regimen. Because of various types of interventions and different methods of assessing outcomes, pooling of results was, appropriately, not done.

Of all the interventions, simplification of dosing regimens had the most evidence of effectiveness, with 7 out of 9 studies demonstrating a statistically significant improvement in adherence in the intervention group. In the other 2 studies, improved adherence was observed in the intervention group; however, the effect was either not statistically significant or not reported.

Five of the studies used a system that electronically recorded the time and date when a medicine container was opened. All studies using this rigorous system for outcome measurement demonstrated statistically significant improvement in adherence with once-daily vs twice-daily dosage regimens. Relative improvement in adherence ranged from 8% to 20%.

Educational strategies alone were largely ineffective in improving adherence. Only 1 of 6 studies of patient education intervention demonstrated improved adherence, but the trial was small (n=110), and the effect was not seen in the other studies (total of 1103 patients).

Research on motivating patients is inconsistent

Motivation and support strategies consisted of interventions such as drug reminder charts, self-recording of blood pressure, mail reminders, and home visits.

Overall, out of 24 RCTs studying motivational, support, and reminder interventions, 10 demonstrated statistically significant but small improvements in adherence. These studies relied on measures such as pill counts and self-report to assess adherence rather than electronic monitoring. The marked inconsistency among the body of evidence makes it difficult to determine whether motivational, support, and reminder interventions alone are effective in improving adherence.

Out of 18 studies of interventions classified as complex health and organizational interventions, including many with an educational or motivational component, interventions in 8 studies led to a statistically significant improvement in adherence. Complex interventions included structured hypertension management programs such as worksite care provided by trained nurses. An example of an intervention given in combination is a program of home visits, education, and specialized dosing devices. Because these interventions varied considerably, an overall statement of effectiveness is not appropriate.

Modest success seen in improving diet

A Cochrane review of dietary advice for reducing cardiovascular disease risk among healthy adults included 29 trials.² Individuals or groups of patients received verbal or printed dietary advice over 1 or more personal contacts. They also received advice by telephone. Ten RCTs of dietary advice in 4328 participants or groups of participants assessed self-reported dietary fat intake.

Overall, intake of dietary fat (expressed as a percentage of total caloric intake) fell by 6.2% (95% confidence interval [CI], reduced 8.4% to increased 4.0%) with dietary intervention over 6 to 48 months. Due to significant heterogeneity between the studies, this overall estimate must be viewed with caution.

Eight RCT studies in 3952 participants or groups of participants assessed self-reported fruit and vegetable intake as an outcome. Overall, intake of fruits and vegetables increased by 1.2 servings per day (95% CI, 0.43–2.1) with interventions over 6 to 48 months. Again, there was significant heterogeneity between the studies. Therefore, this overall estimate must be viewed with caution.

In general, the quality of the studies included in this systematic review was low due to poor descriptions of randomization, lack of allocation concealment, and lack of blinding of outcome assessment. The use of food frequency questionnaires to measure fat and fruit/vegetable intake likely led to reporting bias in these dietary intervention studies. Also, the trials were in healthy adults and not specific to hypertensive patients.

Motiviating patents to exercise remains a challenge

We found 1 randomized trial that evaluated the effectiveness of a physician’s advice to increase physical activity among patients with hypertension in a general practice setting.³ Physical activity was measured using a validated questionnaire. Patients given the advice as part of self-care for hypertension (n=192) were no more likely to have increased their physical activity than those not given the advice (n=108) at 2- and 6-month follow-ups.

Recommendations from others

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) states that self-measurement of blood pressure may benefit patients by providing information on response to antihypertensive medication and improving adherence with therapy.⁴

The report also notes that the patient and clinician must agree on blood pressure goals, and that patient motivation to adopt lifestyle changes and take prescribed medication improves when patients have positive experiences and trust their clinicians.

Evidence summary

Self-care can be defined as activities that a patient undertakes with the intention of improving health or preventing disease. Self-care for hypertension includes taking medicine as prescribed, monitoring blood pressure response to therapy, and adopting lifestyle recommendations—increasing exercise, decreasing salt intake, and increasing fruits and vegetable consumption.

Keeping meds simple improves adherence

Various interventions have been developed with the goal of improving medication adherence among patients with hypertension. A Cochrane review included 38 randomized controlled trials (RCTs) of 58 various types of interventions (some tested in factorial trials) designed to improve patient adherence to antihypertensive medications in ambulatory settings.¹ The quality of the studies was generally low due to inadequate allocation concealment, lack of blinding of outcome assessors, loss to follow-up, and the small number of participants in trials.

The authors grouped interventions into 4 broad categories: simplification of dosing regimens; patient education; patient motivation, support, and reminders; and complex interventions. Comparison groups received either no intervention, usual care, or—in the case of simplification of dosing regimens—a daily regimen consisting of more than 1 pill per day vs a once-daily regimen. Because of various types of interventions and different methods of assessing outcomes, pooling of results was, appropriately, not done.

Of all the interventions, simplification of dosing regimens had the most evidence of effectiveness, with 7 out of 9 studies demonstrating a statistically significant improvement in adherence in the intervention group. In the other 2 studies, improved adherence was observed in the intervention group; however, the effect was either not statistically significant or not reported.

Five of the studies used a system that electronically recorded the time and date when a medicine container was opened. All studies using this rigorous system for outcome measurement demonstrated statistically significant improvement in adherence with once-daily vs twice-daily dosage regimens. Relative improvement in adherence ranged from 8% to 20%.

Educational strategies alone were largely ineffective in improving adherence. Only 1 of 6 studies of patient education intervention demonstrated improved adherence, but the trial was small (n=110), and the effect was not seen in the other studies (total of 1103 patients).

Research on motivating patients is inconsistent

Motivation and support strategies consisted of interventions such as drug reminder charts, self-recording of blood pressure, mail reminders, and home visits.

Overall, out of 24 RCTs studying motivational, support, and reminder interventions, 10 demonstrated statistically significant but small improvements in adherence. These studies relied on measures such as pill counts and self-report to assess adherence rather than electronic monitoring. The marked inconsistency among the body of evidence makes it difficult to determine whether motivational, support, and reminder interventions alone are effective in improving adherence.

Out of 18 studies of interventions classified as complex health and organizational interventions, including many with an educational or motivational component, interventions in 8 studies led to a statistically significant improvement in adherence. Complex interventions included structured hypertension management programs such as worksite care provided by trained nurses. An example of an intervention given in combination is a program of home visits, education, and specialized dosing devices. Because these interventions varied considerably, an overall statement of effectiveness is not appropriate.

Modest success seen in improving diet

A Cochrane review of dietary advice for reducing cardiovascular disease risk among healthy adults included 29 trials.² Individuals or groups of patients received verbal or printed dietary advice over 1 or more personal contacts. They also received advice by telephone. Ten RCTs of dietary advice in 4328 participants or groups of participants assessed self-reported dietary fat intake.

Overall, intake of dietary fat (expressed as a percentage of total caloric intake) fell by 6.2% (95% confidence interval [CI], reduced 8.4% to increased 4.0%) with dietary intervention over 6 to 48 months. Due to significant heterogeneity between the studies, this overall estimate must be viewed with caution.

Eight RCT studies in 3952 participants or groups of participants assessed self-reported fruit and vegetable intake as an outcome. Overall, intake of fruits and vegetables increased by 1.2 servings per day (95% CI, 0.43–2.1) with interventions over 6 to 48 months. Again, there was significant heterogeneity between the studies. Therefore, this overall estimate must be viewed with caution.

In general, the quality of the studies included in this systematic review was low due to poor descriptions of randomization, lack of allocation concealment, and lack of blinding of outcome assessment. The use of food frequency questionnaires to measure fat and fruit/vegetable intake likely led to reporting bias in these dietary intervention studies. Also, the trials were in healthy adults and not specific to hypertensive patients.

Motiviating patents to exercise remains a challenge

We found 1 randomized trial that evaluated the effectiveness of a physician’s advice to increase physical activity among patients with hypertension in a general practice setting.³ Physical activity was measured using a validated questionnaire. Patients given the advice as part of self-care for hypertension (n=192) were no more likely to have increased their physical activity than those not given the advice (n=108) at 2- and 6-month follow-ups.

Recommendations from others

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) states that self-measurement of blood pressure may benefit patients by providing information on response to antihypertensive medication and improving adherence with therapy.⁴

The report also notes that the patient and clinician must agree on blood pressure goals, and that patient motivation to adopt lifestyle changes and take prescribed medication improves when patients have positive experiences and trust their clinicians.

Evidence summary

Topical antibiotics for prophylaxis

Numerous studies support the prophylactic application of topical antibiotics to wounds that are clean. Topical bacitracin zinc (Bacitracin), a triple ointment of neomycin sulfate, bacitracin zinc, and polymyxin B sulfate (Neosporin), and silver sulfadiazine (Silvadene) were compared with petrolatum as a control in a well-conducted RCT of 426 patients with uncomplicated wounds seen at a military community hospital. Wound infection rates were 17.6% (19/108) for petrolatum, 5.5% (6/109) for Bacitracin (number needed to treat [NNT]=8), 4.5% (5/110) for Neosporin (NNT=8), and 12.1% (12/99) for Silvadene (NNT=18).¹ Most (60%) of the infections were “stitch abscesses” and were treated with local care only. There was no difference in rates of more serious infections between groups. One patient (0.9%) developed a hypersensitivity reaction to Neosporin.

A clinical trial compared the efficacy of a cetrimide, bacitracin zinc, and polymyxin B sulfate gel (a combination not available in the US) with placebo and povidone-iodine cream in preventing infections in 177 minor wounds (cuts, grazes, scrapes, and scratches) among children. The antibiotic gel was found to be superior to placebo and equivalent to povidone-iodine, in that it reduced clinical infections from 12.5% to 1.6% (absolute risk reduction [ARR]=0.109; 95% confidence interval [CI], 0.011–0.207; NNT=11).²

A double-blind study of 59 patients found Neosporin superior to placebo ointment in the prevention of streptococcal pyoderma for children with minor wounds. Infection occurred in 47% of placebo-treated children compared with 15% treated with the triple-antibiotic ointment (NNT=32; P=.01).³

A small randomized prospective trial of 99 patients, who self-reported compliance with wound care and dressing changes, compared Neosporin with mupirocin (Bactroban) in preventing infections in uncomplicated soft tissue wounds. The study found no statistical difference in infection rates, and the authors recommend the more cost-effective Neosporin, as well as a larger trial to confirm the results.⁴

Another randomized controlled trial of 933 outpatients—with a total of 1249 wounds from sterile dermatologic surgeries—compared white petrolatum with bacitracin zinc ointment prophylaxis. The study found no statistically significant differences in post-procedure infection rates, though only 13 patients developed an infection (2% in petrolatum group vs. 0.9% in bacitracin zinc group; 95% CI for the difference, –0.4 to 2.7).⁵

Topical antibiotics for treatment

Topical antimicrobials are appealing for the treatment of secondarily infected wounds for the sake of convenience and because they may reduce the risk of adverse effects.

An open randomized trial with 48 volunteers compared the effects of Neosporin with several antiseptics (3% hydrogen peroxide, 1% povidone-iodine, 0.25% acetic acid, 0.5% sodium hydrochloride) and a wound protectant (Johnson & Johnson First Aid Cream without antimicrobial agent) on blister wounds (6 blisters per volunteer) intentionally contaminated with S aureus. Only Neosporin eliminated the infection after 2 applications (at 16 and 24 hours). Both the antibiotic ointment and the wound protectant led to faster wound healing by about 4 days compared with the antiseptics or no treatment.⁶

Another study with 2 parallel, identical RCTs of a total of 706 patients found mupirocin cream (Bactroban) to be equivalent to oral cephalexin in the treatment of secondarily infected minor wounds, such as small lacerations, abrasions, or sutured wounds. Clinical success (95.1% for mupirocin and 95.3% for cephalexin), bacteriologic success (96.9% for mupirocin and 98.9% for cephalexin), as well as the intention-to-treat success rate of 83% at follow-up were equivalent in the 2 groups.⁷

A small but well-designed study of 62 patients with major contaminated wounds failed to show any additional benefit when topical piperacillin/tazobactam (not available in US as a topical agent) was added to parenteral piperacillin/tazobactam (Zosyn) alone. Two of 31 patients on just parenteral antibiotics and 3 of 31 patients on both topical and parenteral antibiotics developed wound infections (P>.05).⁸

Finally, topical antibiotics also appear to aid in the healing of chronic wounds. However, these findings are difficult to interpret in light of small sample size and other methodological problems. A systematic review of the treatment of chronic wounds, such as diabetic foot ulcers, found 30 trials, including 25 RCTs, mostly of low quality. Little evidence supports the routine use of systemic antibiotics for patients with chronic wounds; however, some topical antiseptic and antimicrobial agents may hasten the healing of these wounds. Topical preparations that may be helpful include dimethyl sulfoxide (Rimso-50), silver sulfadiazine (Silvadene), benzoyl peroxide (Benzac, Brevoxyl, Desquam, Triaz, ZoDerm), oxyquinoline (Trimo-san Vaginal Jelly), and gentamicin (Garamycin).⁹

Honey may also make an acceptable wound dressing for chronic wounds, as it has been repeatedly shown to suppress bacterial growth. Infection with Clostridium spores does not appear to be a concern when treating chronic wounds with honey.^10,11

Recommendations from others

Guidelines for antibiotic prophylaxis of surgical wounds uniformly recommend prophylaxis for all clean-contaminated, contaminated, and dirty procedures. Prophylaxis is considered optional for most clean procedures, although it may be indicated for certain at-risk patients and for clean procedures that fulfill specific risk criteria.¹²

The Infectious Diseases Society of America recommends mupirocin as the best topical agent for the treatment and prevention of S aureus and S pyogenes infections, followed by bacitracin zinc and neomycin, although resistance is emerging.¹³ Expert and consensus opinion from the Canadian Chronic Wound Advisory Board and the International Wound Bed Preparation Advisory Board for wound care management of infected chronic wounds recommend that since bacterial infection can develop gradually, good-quality wound cultures should be used in conjunction with clinical assessment. Iodine and silver-based dressings, topical antibiotics, and systemic antibiotics can be helpful.¹⁴

Evidence summary

Topical antibiotics for prophylaxis

Numerous studies support the prophylactic application of topical antibiotics to wounds that are clean. Topical bacitracin zinc (Bacitracin), a triple ointment of neomycin sulfate, bacitracin zinc, and polymyxin B sulfate (Neosporin), and silver sulfadiazine (Silvadene) were compared with petrolatum as a control in a well-conducted RCT of 426 patients with uncomplicated wounds seen at a military community hospital. Wound infection rates were 17.6% (19/108) for petrolatum, 5.5% (6/109) for Bacitracin (number needed to treat [NNT]=8), 4.5% (5/110) for Neosporin (NNT=8), and 12.1% (12/99) for Silvadene (NNT=18).¹ Most (60%) of the infections were “stitch abscesses” and were treated with local care only. There was no difference in rates of more serious infections between groups. One patient (0.9%) developed a hypersensitivity reaction to Neosporin.

A clinical trial compared the efficacy of a cetrimide, bacitracin zinc, and polymyxin B sulfate gel (a combination not available in the US) with placebo and povidone-iodine cream in preventing infections in 177 minor wounds (cuts, grazes, scrapes, and scratches) among children. The antibiotic gel was found to be superior to placebo and equivalent to povidone-iodine, in that it reduced clinical infections from 12.5% to 1.6% (absolute risk reduction [ARR]=0.109; 95% confidence interval [CI], 0.011–0.207; NNT=11).²

A double-blind study of 59 patients found Neosporin superior to placebo ointment in the prevention of streptococcal pyoderma for children with minor wounds. Infection occurred in 47% of placebo-treated children compared with 15% treated with the triple-antibiotic ointment (NNT=32; P=.01).³

A small randomized prospective trial of 99 patients, who self-reported compliance with wound care and dressing changes, compared Neosporin with mupirocin (Bactroban) in preventing infections in uncomplicated soft tissue wounds. The study found no statistical difference in infection rates, and the authors recommend the more cost-effective Neosporin, as well as a larger trial to confirm the results.⁴

Another randomized controlled trial of 933 outpatients—with a total of 1249 wounds from sterile dermatologic surgeries—compared white petrolatum with bacitracin zinc ointment prophylaxis. The study found no statistically significant differences in post-procedure infection rates, though only 13 patients developed an infection (2% in petrolatum group vs. 0.9% in bacitracin zinc group; 95% CI for the difference, –0.4 to 2.7).⁵

Topical antibiotics for treatment

Topical antimicrobials are appealing for the treatment of secondarily infected wounds for the sake of convenience and because they may reduce the risk of adverse effects.

An open randomized trial with 48 volunteers compared the effects of Neosporin with several antiseptics (3% hydrogen peroxide, 1% povidone-iodine, 0.25% acetic acid, 0.5% sodium hydrochloride) and a wound protectant (Johnson & Johnson First Aid Cream without antimicrobial agent) on blister wounds (6 blisters per volunteer) intentionally contaminated with S aureus. Only Neosporin eliminated the infection after 2 applications (at 16 and 24 hours). Both the antibiotic ointment and the wound protectant led to faster wound healing by about 4 days compared with the antiseptics or no treatment.⁶

Another study with 2 parallel, identical RCTs of a total of 706 patients found mupirocin cream (Bactroban) to be equivalent to oral cephalexin in the treatment of secondarily infected minor wounds, such as small lacerations, abrasions, or sutured wounds. Clinical success (95.1% for mupirocin and 95.3% for cephalexin), bacteriologic success (96.9% for mupirocin and 98.9% for cephalexin), as well as the intention-to-treat success rate of 83% at follow-up were equivalent in the 2 groups.⁷

A small but well-designed study of 62 patients with major contaminated wounds failed to show any additional benefit when topical piperacillin/tazobactam (not available in US as a topical agent) was added to parenteral piperacillin/tazobactam (Zosyn) alone. Two of 31 patients on just parenteral antibiotics and 3 of 31 patients on both topical and parenteral antibiotics developed wound infections (P>.05).⁸

Finally, topical antibiotics also appear to aid in the healing of chronic wounds. However, these findings are difficult to interpret in light of small sample size and other methodological problems. A systematic review of the treatment of chronic wounds, such as diabetic foot ulcers, found 30 trials, including 25 RCTs, mostly of low quality. Little evidence supports the routine use of systemic antibiotics for patients with chronic wounds; however, some topical antiseptic and antimicrobial agents may hasten the healing of these wounds. Topical preparations that may be helpful include dimethyl sulfoxide (Rimso-50), silver sulfadiazine (Silvadene), benzoyl peroxide (Benzac, Brevoxyl, Desquam, Triaz, ZoDerm), oxyquinoline (Trimo-san Vaginal Jelly), and gentamicin (Garamycin).⁹

Honey may also make an acceptable wound dressing for chronic wounds, as it has been repeatedly shown to suppress bacterial growth. Infection with Clostridium spores does not appear to be a concern when treating chronic wounds with honey.^10,11

Recommendations from others

Guidelines for antibiotic prophylaxis of surgical wounds uniformly recommend prophylaxis for all clean-contaminated, contaminated, and dirty procedures. Prophylaxis is considered optional for most clean procedures, although it may be indicated for certain at-risk patients and for clean procedures that fulfill specific risk criteria.¹²

The Infectious Diseases Society of America recommends mupirocin as the best topical agent for the treatment and prevention of S aureus and S pyogenes infections, followed by bacitracin zinc and neomycin, although resistance is emerging.¹³ Expert and consensus opinion from the Canadian Chronic Wound Advisory Board and the International Wound Bed Preparation Advisory Board for wound care management of infected chronic wounds recommend that since bacterial infection can develop gradually, good-quality wound cultures should be used in conjunction with clinical assessment. Iodine and silver-based dressings, topical antibiotics, and systemic antibiotics can be helpful.¹⁴

Evidence summary

Topical antibiotics for prophylaxis

Numerous studies support the prophylactic application of topical antibiotics to wounds that are clean. Topical bacitracin zinc (Bacitracin), a triple ointment of neomycin sulfate, bacitracin zinc, and polymyxin B sulfate (Neosporin), and silver sulfadiazine (Silvadene) were compared with petrolatum as a control in a well-conducted RCT of 426 patients with uncomplicated wounds seen at a military community hospital. Wound infection rates were 17.6% (19/108) for petrolatum, 5.5% (6/109) for Bacitracin (number needed to treat [NNT]=8), 4.5% (5/110) for Neosporin (NNT=8), and 12.1% (12/99) for Silvadene (NNT=18).¹ Most (60%) of the infections were “stitch abscesses” and were treated with local care only. There was no difference in rates of more serious infections between groups. One patient (0.9%) developed a hypersensitivity reaction to Neosporin.

A clinical trial compared the efficacy of a cetrimide, bacitracin zinc, and polymyxin B sulfate gel (a combination not available in the US) with placebo and povidone-iodine cream in preventing infections in 177 minor wounds (cuts, grazes, scrapes, and scratches) among children. The antibiotic gel was found to be superior to placebo and equivalent to povidone-iodine, in that it reduced clinical infections from 12.5% to 1.6% (absolute risk reduction [ARR]=0.109; 95% confidence interval [CI], 0.011–0.207; NNT=11).²

A double-blind study of 59 patients found Neosporin superior to placebo ointment in the prevention of streptococcal pyoderma for children with minor wounds. Infection occurred in 47% of placebo-treated children compared with 15% treated with the triple-antibiotic ointment (NNT=32; P=.01).³

A small randomized prospective trial of 99 patients, who self-reported compliance with wound care and dressing changes, compared Neosporin with mupirocin (Bactroban) in preventing infections in uncomplicated soft tissue wounds. The study found no statistical difference in infection rates, and the authors recommend the more cost-effective Neosporin, as well as a larger trial to confirm the results.⁴

Another randomized controlled trial of 933 outpatients—with a total of 1249 wounds from sterile dermatologic surgeries—compared white petrolatum with bacitracin zinc ointment prophylaxis. The study found no statistically significant differences in post-procedure infection rates, though only 13 patients developed an infection (2% in petrolatum group vs. 0.9% in bacitracin zinc group; 95% CI for the difference, –0.4 to 2.7).⁵

Topical antibiotics for treatment

Topical antimicrobials are appealing for the treatment of secondarily infected wounds for the sake of convenience and because they may reduce the risk of adverse effects.

An open randomized trial with 48 volunteers compared the effects of Neosporin with several antiseptics (3% hydrogen peroxide, 1% povidone-iodine, 0.25% acetic acid, 0.5% sodium hydrochloride) and a wound protectant (Johnson & Johnson First Aid Cream without antimicrobial agent) on blister wounds (6 blisters per volunteer) intentionally contaminated with S aureus. Only Neosporin eliminated the infection after 2 applications (at 16 and 24 hours). Both the antibiotic ointment and the wound protectant led to faster wound healing by about 4 days compared with the antiseptics or no treatment.⁶

Another study with 2 parallel, identical RCTs of a total of 706 patients found mupirocin cream (Bactroban) to be equivalent to oral cephalexin in the treatment of secondarily infected minor wounds, such as small lacerations, abrasions, or sutured wounds. Clinical success (95.1% for mupirocin and 95.3% for cephalexin), bacteriologic success (96.9% for mupirocin and 98.9% for cephalexin), as well as the intention-to-treat success rate of 83% at follow-up were equivalent in the 2 groups.⁷

A small but well-designed study of 62 patients with major contaminated wounds failed to show any additional benefit when topical piperacillin/tazobactam (not available in US as a topical agent) was added to parenteral piperacillin/tazobactam (Zosyn) alone. Two of 31 patients on just parenteral antibiotics and 3 of 31 patients on both topical and parenteral antibiotics developed wound infections (P>.05).⁸

Finally, topical antibiotics also appear to aid in the healing of chronic wounds. However, these findings are difficult to interpret in light of small sample size and other methodological problems. A systematic review of the treatment of chronic wounds, such as diabetic foot ulcers, found 30 trials, including 25 RCTs, mostly of low quality. Little evidence supports the routine use of systemic antibiotics for patients with chronic wounds; however, some topical antiseptic and antimicrobial agents may hasten the healing of these wounds. Topical preparations that may be helpful include dimethyl sulfoxide (Rimso-50), silver sulfadiazine (Silvadene), benzoyl peroxide (Benzac, Brevoxyl, Desquam, Triaz, ZoDerm), oxyquinoline (Trimo-san Vaginal Jelly), and gentamicin (Garamycin).⁹

Honey may also make an acceptable wound dressing for chronic wounds, as it has been repeatedly shown to suppress bacterial growth. Infection with Clostridium spores does not appear to be a concern when treating chronic wounds with honey.^10,11

Recommendations from others

Guidelines for antibiotic prophylaxis of surgical wounds uniformly recommend prophylaxis for all clean-contaminated, contaminated, and dirty procedures. Prophylaxis is considered optional for most clean procedures, although it may be indicated for certain at-risk patients and for clean procedures that fulfill specific risk criteria.¹²

The Infectious Diseases Society of America recommends mupirocin as the best topical agent for the treatment and prevention of S aureus and S pyogenes infections, followed by bacitracin zinc and neomycin, although resistance is emerging.¹³ Expert and consensus opinion from the Canadian Chronic Wound Advisory Board and the International Wound Bed Preparation Advisory Board for wound care management of infected chronic wounds recommend that since bacterial infection can develop gradually, good-quality wound cultures should be used in conjunction with clinical assessment. Iodine and silver-based dressings, topical antibiotics, and systemic antibiotics can be helpful.¹⁴

Evidence summary

In areas where tuberculosis is prevalent, the World Health Organization recommends BCG vaccination at birth, without booster doses, to prevent childhood complications of TB infection;¹ however, the vaccine’s efficacy is known to be inconsistent. Though BCG vaccine given at birth can decrease the risk of miliary TB and TB meningitis among children, estimates of its effectiveness in preventing adult pulmonary TB range widely from 0% to 80%.¹

Though prior BCG vaccination increases the risk of a reactive PPD, this effect is also known to be inconsistent. A 2002 meta-analysis showed that the person’s age at the time of their BCG vaccination and the years since vaccination influence the relative risk of a positive PPD (TABLE). The highest relative risk of a positive PPD occurred among patients who received BCG vaccination after infancy and within 15 years of the PPD testing. This same meta-analysis also examined the significance of the size of the PPD response; a subset of 4 studies showed that equal proportions of BCG vaccinated and unvaccinated patients had indurations of 14 mm or more.²

BCG vaccine may confound PPD readings, but several studies indicate that PPD can still be a useful screening tool for tuberculosis infection after vaccination. A Brazilian case-control study found that reactions by those BCG recipients later exposed to TB were significantly greater than those with no TB exposure.³ The study noted that 47.5% of exposed children (defined as those with a household contact) had PPD readings of >10 mm, compared with just 3.6% of control children. In a Quebec cohort of 1198 foreign-born children and young adults, prior BCG vaccination could account for 50% of PPDs with induration of 5 to 9 mm, but only 4% of reactions 10 mm or greater. This study also showed that patients from countries with a high or moderate incidence of TB were more likely to have reactive PPDs than those from countries of low incidence, suggesting that exposure to TB accounts for some of the positive PPDs.⁴

Where it is available, the QuantiFERON-TB Gold test may be used in place of, or in addition to, the PPD for patients who are known to have received a BCG vaccine. This blood test detects interferon-gamma in the serum of people sensitized to Mycobacterium tuberculosis. Because the test is specific to proteins found in M tuberculosis, there is no cross-reactivity with BCG. A Japanese study of 216 BCG-vaccinated individuals showed interferon-gamma assays to be 98.1% specific. The same study reported 89.0% sensitivity for the combination of 2 interferon-gamma assays among 118 TB culture-confirmed individuals.⁵ A published report estimated the cost to the health care system per patient tested by a single interferon-gamma release assay as $33.67, compared with approximately $11 for PPD testing.⁶

TABLE
PPD reactions >10 mm when BCG was given during and after infancy

Recommendations from others

While the US Preventive Services Task Force (USPSTF) does not make a specific recommendation regarding PPD readings after BCG vaccine, it does recommend screening high-risk populations. The USPSTF further notes that reactions >10 mm should not be attributed to prior BCG vaccine.⁷

The Centers for Disease Control and Prevention (CDC) and American Thoracic Society joint statement recommends against altering guidelines for testing and interpretation among BCG recipients.⁸ In 2005, the CDC recommended the QuantiFERON-TB Gold test be used under the same indications as the PPD, noting its potential benefit among those previously immunized with BCG.⁹

Evidence summary

In areas where tuberculosis is prevalent, the World Health Organization recommends BCG vaccination at birth, without booster doses, to prevent childhood complications of TB infection;¹ however, the vaccine’s efficacy is known to be inconsistent. Though BCG vaccine given at birth can decrease the risk of miliary TB and TB meningitis among children, estimates of its effectiveness in preventing adult pulmonary TB range widely from 0% to 80%.¹

Though prior BCG vaccination increases the risk of a reactive PPD, this effect is also known to be inconsistent. A 2002 meta-analysis showed that the person’s age at the time of their BCG vaccination and the years since vaccination influence the relative risk of a positive PPD (TABLE). The highest relative risk of a positive PPD occurred among patients who received BCG vaccination after infancy and within 15 years of the PPD testing. This same meta-analysis also examined the significance of the size of the PPD response; a subset of 4 studies showed that equal proportions of BCG vaccinated and unvaccinated patients had indurations of 14 mm or more.²

BCG vaccine may confound PPD readings, but several studies indicate that PPD can still be a useful screening tool for tuberculosis infection after vaccination. A Brazilian case-control study found that reactions by those BCG recipients later exposed to TB were significantly greater than those with no TB exposure.³ The study noted that 47.5% of exposed children (defined as those with a household contact) had PPD readings of >10 mm, compared with just 3.6% of control children. In a Quebec cohort of 1198 foreign-born children and young adults, prior BCG vaccination could account for 50% of PPDs with induration of 5 to 9 mm, but only 4% of reactions 10 mm or greater. This study also showed that patients from countries with a high or moderate incidence of TB were more likely to have reactive PPDs than those from countries of low incidence, suggesting that exposure to TB accounts for some of the positive PPDs.⁴

Where it is available, the QuantiFERON-TB Gold test may be used in place of, or in addition to, the PPD for patients who are known to have received a BCG vaccine. This blood test detects interferon-gamma in the serum of people sensitized to Mycobacterium tuberculosis. Because the test is specific to proteins found in M tuberculosis, there is no cross-reactivity with BCG. A Japanese study of 216 BCG-vaccinated individuals showed interferon-gamma assays to be 98.1% specific. The same study reported 89.0% sensitivity for the combination of 2 interferon-gamma assays among 118 TB culture-confirmed individuals.⁵ A published report estimated the cost to the health care system per patient tested by a single interferon-gamma release assay as $33.67, compared with approximately $11 for PPD testing.⁶

TABLE
PPD reactions >10 mm when BCG was given during and after infancy

Recommendations from others

While the US Preventive Services Task Force (USPSTF) does not make a specific recommendation regarding PPD readings after BCG vaccine, it does recommend screening high-risk populations. The USPSTF further notes that reactions >10 mm should not be attributed to prior BCG vaccine.⁷

The Centers for Disease Control and Prevention (CDC) and American Thoracic Society joint statement recommends against altering guidelines for testing and interpretation among BCG recipients.⁸ In 2005, the CDC recommended the QuantiFERON-TB Gold test be used under the same indications as the PPD, noting its potential benefit among those previously immunized with BCG.⁹

Evidence summary

In areas where tuberculosis is prevalent, the World Health Organization recommends BCG vaccination at birth, without booster doses, to prevent childhood complications of TB infection;¹ however, the vaccine’s efficacy is known to be inconsistent. Though BCG vaccine given at birth can decrease the risk of miliary TB and TB meningitis among children, estimates of its effectiveness in preventing adult pulmonary TB range widely from 0% to 80%.¹

Though prior BCG vaccination increases the risk of a reactive PPD, this effect is also known to be inconsistent. A 2002 meta-analysis showed that the person’s age at the time of their BCG vaccination and the years since vaccination influence the relative risk of a positive PPD (TABLE). The highest relative risk of a positive PPD occurred among patients who received BCG vaccination after infancy and within 15 years of the PPD testing. This same meta-analysis also examined the significance of the size of the PPD response; a subset of 4 studies showed that equal proportions of BCG vaccinated and unvaccinated patients had indurations of 14 mm or more.²

BCG vaccine may confound PPD readings, but several studies indicate that PPD can still be a useful screening tool for tuberculosis infection after vaccination. A Brazilian case-control study found that reactions by those BCG recipients later exposed to TB were significantly greater than those with no TB exposure.³ The study noted that 47.5% of exposed children (defined as those with a household contact) had PPD readings of >10 mm, compared with just 3.6% of control children. In a Quebec cohort of 1198 foreign-born children and young adults, prior BCG vaccination could account for 50% of PPDs with induration of 5 to 9 mm, but only 4% of reactions 10 mm or greater. This study also showed that patients from countries with a high or moderate incidence of TB were more likely to have reactive PPDs than those from countries of low incidence, suggesting that exposure to TB accounts for some of the positive PPDs.⁴

Where it is available, the QuantiFERON-TB Gold test may be used in place of, or in addition to, the PPD for patients who are known to have received a BCG vaccine. This blood test detects interferon-gamma in the serum of people sensitized to Mycobacterium tuberculosis. Because the test is specific to proteins found in M tuberculosis, there is no cross-reactivity with BCG. A Japanese study of 216 BCG-vaccinated individuals showed interferon-gamma assays to be 98.1% specific. The same study reported 89.0% sensitivity for the combination of 2 interferon-gamma assays among 118 TB culture-confirmed individuals.⁵ A published report estimated the cost to the health care system per patient tested by a single interferon-gamma release assay as $33.67, compared with approximately $11 for PPD testing.⁶

TABLE
PPD reactions >10 mm when BCG was given during and after infancy

Recommendations from others

While the US Preventive Services Task Force (USPSTF) does not make a specific recommendation regarding PPD readings after BCG vaccine, it does recommend screening high-risk populations. The USPSTF further notes that reactions >10 mm should not be attributed to prior BCG vaccine.⁷

The Centers for Disease Control and Prevention (CDC) and American Thoracic Society joint statement recommends against altering guidelines for testing and interpretation among BCG recipients.⁸ In 2005, the CDC recommended the QuantiFERON-TB Gold test be used under the same indications as the PPD, noting its potential benefit among those previously immunized with BCG.⁹

Evidence summary

Depletion of iron stores leads to IDA, which, among children, is associated with motor and cognitive deficits that may be irreversible. Little is known about whether iron deficiency, in the absence of anemia, results in physiologic sequelae. A Cochrane review of iron therapy for children with IDA aged >3 years found no short-term (5–11 days) improvement in Bayley scores of mental and motor development following iron therapy.¹ A 10-year longitudinal cohort study in Costa Rica found that adolescents treated for severe chronic IDA in infancy (n=48) scored 0.4 to 0.7 standard deviations lower on cognitive and motor testing relative to controls (n=114).² In an Indonesian randomized controlled trial (RCT), baseline Bayley scores were 10% to 15% lower (P<.01) for infants (12–18 months) with IDA compared with both nonanemic iron-deficient and iron-sufficient infants.³ Following treatment with ferrous sulfate (3 mg/kg/d of elemental iron) for 4 months, the IDA infants’ Bayley scores improved compared with those of nonanemic children.

Consensus recommendations suggest that iron deficiency should be the presumptive diagnosis in a child with anemia, and that a trial of ferrous sulfate at a dose of 3 mg/kg/d of elemental iron be instituted because of low cost, tolerability, and relative simplicity.^4,5 In a prospective study of 75 1-year-olds with anemia (hemoglobin <11.0 g/dL), 45% achieved an increase in hemoglobin ≥1 g/dL after 3 months of iron therapy (3 mg/kg/d).⁶ An RCT of 278 nonanemic 1-year-olds found no difference in adverse effects from this dose compared with placebo.⁷ However, an analysis of data from NHANES III showed that a Hgb <11.0 had a positive predictive value of just 29% and sensitivity of 30% for diagnosing iron-deficiency in children aged <3 years.⁸

The recommended dose of 3 mg/kg/d was derived from models of bioavailability and iron needs⁹; no studies compare alternative doses. An RCT of 557 anemic children under 24 months of age in Ghana demonstrated that ferrous sulfate (5 mg/kg/d) given once daily was equivalent to 3-times-daily dosing in terms of effectiveness (61% vs 56%) and tolerance.¹⁰ Less frequent dosing has been studied in developing countries with mixed results.

Because anemia may lead to developmental impairment, primary prevention is critical. In a cohort study, infants given iron-fortified formula (n=98) were less likely to become iron-deficient by their 12-month visit than infants fed whole cow milk (n=69) (11.2% vs 24.6%, number needed to treat [NNT]=8).¹¹ In a RCT of innercity children who had been switched to cows’ milk by 6 months, half (n=50) were randomized to receive iron-fortified formula for another year, resulting in a decreased risk of anemia at 24 months (0% vs 26%, NNT=4), and smaller declines in developmental functioning compared with those on cows’ milk.¹²

Recommendations from others

The CDC and the Institute of Medicine recommend parental dietary counseling, treatment with oral ferrous sulfate at 3 mg/kg/d for 3 months to restore iron stores, and monitoring of hemoglobin or hematocrit to assess response.^4,5 To prevent IDA, the American Academy of Pediatrics (AAP) recommends that all infants who are not breastfed or are partially breastfed should receive an iron-fortified formula (containing between 4.0–12 mg/L of iron) from birth to 12 months. The AAP also recommends that parents should refrain from feeding cow’s milk to infants until after age 12 months and introduce iron-enriched foods between ages 4 and 6 months.¹³

Evidence summary

Depletion of iron stores leads to IDA, which, among children, is associated with motor and cognitive deficits that may be irreversible. Little is known about whether iron deficiency, in the absence of anemia, results in physiologic sequelae. A Cochrane review of iron therapy for children with IDA aged >3 years found no short-term (5–11 days) improvement in Bayley scores of mental and motor development following iron therapy.¹ A 10-year longitudinal cohort study in Costa Rica found that adolescents treated for severe chronic IDA in infancy (n=48) scored 0.4 to 0.7 standard deviations lower on cognitive and motor testing relative to controls (n=114).² In an Indonesian randomized controlled trial (RCT), baseline Bayley scores were 10% to 15% lower (P<.01) for infants (12–18 months) with IDA compared with both nonanemic iron-deficient and iron-sufficient infants.³ Following treatment with ferrous sulfate (3 mg/kg/d of elemental iron) for 4 months, the IDA infants’ Bayley scores improved compared with those of nonanemic children.

Consensus recommendations suggest that iron deficiency should be the presumptive diagnosis in a child with anemia, and that a trial of ferrous sulfate at a dose of 3 mg/kg/d of elemental iron be instituted because of low cost, tolerability, and relative simplicity.^4,5 In a prospective study of 75 1-year-olds with anemia (hemoglobin <11.0 g/dL), 45% achieved an increase in hemoglobin ≥1 g/dL after 3 months of iron therapy (3 mg/kg/d).⁶ An RCT of 278 nonanemic 1-year-olds found no difference in adverse effects from this dose compared with placebo.⁷ However, an analysis of data from NHANES III showed that a Hgb <11.0 had a positive predictive value of just 29% and sensitivity of 30% for diagnosing iron-deficiency in children aged <3 years.⁸

The recommended dose of 3 mg/kg/d was derived from models of bioavailability and iron needs⁹; no studies compare alternative doses. An RCT of 557 anemic children under 24 months of age in Ghana demonstrated that ferrous sulfate (5 mg/kg/d) given once daily was equivalent to 3-times-daily dosing in terms of effectiveness (61% vs 56%) and tolerance.¹⁰ Less frequent dosing has been studied in developing countries with mixed results.

Because anemia may lead to developmental impairment, primary prevention is critical. In a cohort study, infants given iron-fortified formula (n=98) were less likely to become iron-deficient by their 12-month visit than infants fed whole cow milk (n=69) (11.2% vs 24.6%, number needed to treat [NNT]=8).¹¹ In a RCT of innercity children who had been switched to cows’ milk by 6 months, half (n=50) were randomized to receive iron-fortified formula for another year, resulting in a decreased risk of anemia at 24 months (0% vs 26%, NNT=4), and smaller declines in developmental functioning compared with those on cows’ milk.¹²

Recommendations from others

The CDC and the Institute of Medicine recommend parental dietary counseling, treatment with oral ferrous sulfate at 3 mg/kg/d for 3 months to restore iron stores, and monitoring of hemoglobin or hematocrit to assess response.^4,5 To prevent IDA, the American Academy of Pediatrics (AAP) recommends that all infants who are not breastfed or are partially breastfed should receive an iron-fortified formula (containing between 4.0–12 mg/L of iron) from birth to 12 months. The AAP also recommends that parents should refrain from feeding cow’s milk to infants until after age 12 months and introduce iron-enriched foods between ages 4 and 6 months.¹³

Evidence summary

Depletion of iron stores leads to IDA, which, among children, is associated with motor and cognitive deficits that may be irreversible. Little is known about whether iron deficiency, in the absence of anemia, results in physiologic sequelae. A Cochrane review of iron therapy for children with IDA aged >3 years found no short-term (5–11 days) improvement in Bayley scores of mental and motor development following iron therapy.¹ A 10-year longitudinal cohort study in Costa Rica found that adolescents treated for severe chronic IDA in infancy (n=48) scored 0.4 to 0.7 standard deviations lower on cognitive and motor testing relative to controls (n=114).² In an Indonesian randomized controlled trial (RCT), baseline Bayley scores were 10% to 15% lower (P<.01) for infants (12–18 months) with IDA compared with both nonanemic iron-deficient and iron-sufficient infants.³ Following treatment with ferrous sulfate (3 mg/kg/d of elemental iron) for 4 months, the IDA infants’ Bayley scores improved compared with those of nonanemic children.

Consensus recommendations suggest that iron deficiency should be the presumptive diagnosis in a child with anemia, and that a trial of ferrous sulfate at a dose of 3 mg/kg/d of elemental iron be instituted because of low cost, tolerability, and relative simplicity.^4,5 In a prospective study of 75 1-year-olds with anemia (hemoglobin <11.0 g/dL), 45% achieved an increase in hemoglobin ≥1 g/dL after 3 months of iron therapy (3 mg/kg/d).⁶ An RCT of 278 nonanemic 1-year-olds found no difference in adverse effects from this dose compared with placebo.⁷ However, an analysis of data from NHANES III showed that a Hgb <11.0 had a positive predictive value of just 29% and sensitivity of 30% for diagnosing iron-deficiency in children aged <3 years.⁸

The recommended dose of 3 mg/kg/d was derived from models of bioavailability and iron needs⁹; no studies compare alternative doses. An RCT of 557 anemic children under 24 months of age in Ghana demonstrated that ferrous sulfate (5 mg/kg/d) given once daily was equivalent to 3-times-daily dosing in terms of effectiveness (61% vs 56%) and tolerance.¹⁰ Less frequent dosing has been studied in developing countries with mixed results.

Because anemia may lead to developmental impairment, primary prevention is critical. In a cohort study, infants given iron-fortified formula (n=98) were less likely to become iron-deficient by their 12-month visit than infants fed whole cow milk (n=69) (11.2% vs 24.6%, number needed to treat [NNT]=8).¹¹ In a RCT of innercity children who had been switched to cows’ milk by 6 months, half (n=50) were randomized to receive iron-fortified formula for another year, resulting in a decreased risk of anemia at 24 months (0% vs 26%, NNT=4), and smaller declines in developmental functioning compared with those on cows’ milk.¹²

Recommendations from others

The CDC and the Institute of Medicine recommend parental dietary counseling, treatment with oral ferrous sulfate at 3 mg/kg/d for 3 months to restore iron stores, and monitoring of hemoglobin or hematocrit to assess response.^4,5 To prevent IDA, the American Academy of Pediatrics (AAP) recommends that all infants who are not breastfed or are partially breastfed should receive an iron-fortified formula (containing between 4.0–12 mg/L of iron) from birth to 12 months. The AAP also recommends that parents should refrain from feeding cow’s milk to infants until after age 12 months and introduce iron-enriched foods between ages 4 and 6 months.¹³

Evidence summary

Rotator cuff tears can cause shoulder pain, decreased strength, and decreased range of motion. Clinical findings associated with a rotator cuff injury can vary. Full-thickness and partial-thickness tears may present differently, and it is important to test clinically for both of these conditions.

A meta-analysis of 10 cohort studies found the overall sensitivity and specificity of a clinical exam to rule out a full-thickness rotator cuff tear to be 0.9 (95% confidence interval [CI], 0.87–0.93) and 0.54 (95% CI, 0.47–0.61).¹ However, no single physical exam finding provided comparable accuracy. Another prospective study of 400 patients comparing 23 different clinical exams found that 3 simple clinical tests—supraspinatus weakness, weakness in external rotation, and the presence of impingement—were highly predictive of rotator cuff tear. When all 3 tests were positive, or when 2 tests were positive for a patient aged >60 years, there was a 98% chance of the patient having a rotator cuff tear.²

Ultrasound can be used to evaluate both suspected full- and partial-thickness rotator cuff tears. In a systematic review of 38 cohort studies, the overall sensitivity and specificity of ultrasound for full-thickness rotator cuff tears was 0.87 (95% CI, 0.84–0.89) and 0.96 (95% CI, 0.94–0.97).¹ For partial-thickness tears, ultrasound sensitivity was 0.67 (95% CI, 0.61–0.73).¹ The incidence of rotator cuff tears increases with age and with athletic activity.⁵

Positive and negative predictive values of a test depend on the prevalence of the condition in the study population. In the case of rotator cuff tears, such differences in prevalence of rotator cuff tears in the 38 cohort studies left it unclear whether a negative ultrasound could reliably rule out a tear.

A meta-analysis of 29 cohort studies of MRI for the diagnosis of full-thickness tears found a pooled sensitivity of 0.89 (95% CI, 0.86–0.92) and a pooled specificity of 0.93 (95% CI, 0.91–0.95), respectively.¹ For partial-thickness tears, the pooled MRI sensitivity was lower at 0.44 (95% CI, 0.36–0.51), but with a high specificity of 0.90 (95% CI, 0.87–0.92).¹ This implies that MRI is the most valuable test to rule out a partial-thickness tear. However, we found no studies that directly compared the test characteristics of ultrasound and MRI.

Conventional arthrography can be used as an invasive alternative to MRI imaging for full-thickness tears, particularly when an implanted device precludes the use of MRI. One prospective trial (in which patients were randomized to the order in which MRI or arthrography were performed) of 38 patients showed arthrography to have a sensitivity of 0.50 and a specificity of 0.96 when used to diagnose full-thickness tears.^3,6

Magnetic resonance arthrography (MRA), based on 6 cohort studies, may be accurate in the diagnosis of a full-thickness tear, with a sensitivity of 0.95 (95% CI, 0.82–0.98) and specificity of 0.93 (95% CI, 0.84–0.97).¹ In these studies, diagnosis of partial-thickness tears with MRA was inconsistent.¹ The invasiveness of MRA limits its utility as compared with MRI and ultrasound. The TABLE summarizes these findings.

TABLE
Summary of test characteristics of diagnostic studies for rotator cuff injuries

Recommendations from others

The American Academy of Orthopaedic Surgeons has a clinical guideline on shoulder pain,⁴ and the Brigham and Women’s Hospital has a guide to the prevention, diagnosis and treatment of upper extremity musculoskeletal disorders.⁵ These guidelines emphasize the importance and utility of physical examination of the shoulder. A patient with a full-thickness tear will likely demonstrate compromised strength in shoulder active mid-arc abduction and resisted external rotation with elbow flexed at patient’s side. However, a partial tear might not compromise strength. Atrophy of the infraspinatus or supra-spinatus muscles is sometimes seen with a full-thickness tear that is several weeks old.⁵

Following a clinical assessment, the guidelines give no preference to any of the diagnostic tests mentioned above, with the exception of arthrography in the presence of implantable devices. Plain X-rays are typically unrevealing, but could be used to rule out other reasons for pain, such as calcific tendonitis.

Evidence summary

Rotator cuff tears can cause shoulder pain, decreased strength, and decreased range of motion. Clinical findings associated with a rotator cuff injury can vary. Full-thickness and partial-thickness tears may present differently, and it is important to test clinically for both of these conditions.

A meta-analysis of 10 cohort studies found the overall sensitivity and specificity of a clinical exam to rule out a full-thickness rotator cuff tear to be 0.9 (95% confidence interval [CI], 0.87–0.93) and 0.54 (95% CI, 0.47–0.61).¹ However, no single physical exam finding provided comparable accuracy. Another prospective study of 400 patients comparing 23 different clinical exams found that 3 simple clinical tests—supraspinatus weakness, weakness in external rotation, and the presence of impingement—were highly predictive of rotator cuff tear. When all 3 tests were positive, or when 2 tests were positive for a patient aged >60 years, there was a 98% chance of the patient having a rotator cuff tear.²

Ultrasound can be used to evaluate both suspected full- and partial-thickness rotator cuff tears. In a systematic review of 38 cohort studies, the overall sensitivity and specificity of ultrasound for full-thickness rotator cuff tears was 0.87 (95% CI, 0.84–0.89) and 0.96 (95% CI, 0.94–0.97).¹ For partial-thickness tears, ultrasound sensitivity was 0.67 (95% CI, 0.61–0.73).¹ The incidence of rotator cuff tears increases with age and with athletic activity.⁵

Positive and negative predictive values of a test depend on the prevalence of the condition in the study population. In the case of rotator cuff tears, such differences in prevalence of rotator cuff tears in the 38 cohort studies left it unclear whether a negative ultrasound could reliably rule out a tear.

A meta-analysis of 29 cohort studies of MRI for the diagnosis of full-thickness tears found a pooled sensitivity of 0.89 (95% CI, 0.86–0.92) and a pooled specificity of 0.93 (95% CI, 0.91–0.95), respectively.¹ For partial-thickness tears, the pooled MRI sensitivity was lower at 0.44 (95% CI, 0.36–0.51), but with a high specificity of 0.90 (95% CI, 0.87–0.92).¹ This implies that MRI is the most valuable test to rule out a partial-thickness tear. However, we found no studies that directly compared the test characteristics of ultrasound and MRI.

Conventional arthrography can be used as an invasive alternative to MRI imaging for full-thickness tears, particularly when an implanted device precludes the use of MRI. One prospective trial (in which patients were randomized to the order in which MRI or arthrography were performed) of 38 patients showed arthrography to have a sensitivity of 0.50 and a specificity of 0.96 when used to diagnose full-thickness tears.^3,6

Magnetic resonance arthrography (MRA), based on 6 cohort studies, may be accurate in the diagnosis of a full-thickness tear, with a sensitivity of 0.95 (95% CI, 0.82–0.98) and specificity of 0.93 (95% CI, 0.84–0.97).¹ In these studies, diagnosis of partial-thickness tears with MRA was inconsistent.¹ The invasiveness of MRA limits its utility as compared with MRI and ultrasound. The TABLE summarizes these findings.

TABLE
Summary of test characteristics of diagnostic studies for rotator cuff injuries

Recommendations from others

The American Academy of Orthopaedic Surgeons has a clinical guideline on shoulder pain,⁴ and the Brigham and Women’s Hospital has a guide to the prevention, diagnosis and treatment of upper extremity musculoskeletal disorders.⁵ These guidelines emphasize the importance and utility of physical examination of the shoulder. A patient with a full-thickness tear will likely demonstrate compromised strength in shoulder active mid-arc abduction and resisted external rotation with elbow flexed at patient’s side. However, a partial tear might not compromise strength. Atrophy of the infraspinatus or supra-spinatus muscles is sometimes seen with a full-thickness tear that is several weeks old.⁵

Following a clinical assessment, the guidelines give no preference to any of the diagnostic tests mentioned above, with the exception of arthrography in the presence of implantable devices. Plain X-rays are typically unrevealing, but could be used to rule out other reasons for pain, such as calcific tendonitis.

Evidence summary

Rotator cuff tears can cause shoulder pain, decreased strength, and decreased range of motion. Clinical findings associated with a rotator cuff injury can vary. Full-thickness and partial-thickness tears may present differently, and it is important to test clinically for both of these conditions.

A meta-analysis of 10 cohort studies found the overall sensitivity and specificity of a clinical exam to rule out a full-thickness rotator cuff tear to be 0.9 (95% confidence interval [CI], 0.87–0.93) and 0.54 (95% CI, 0.47–0.61).¹ However, no single physical exam finding provided comparable accuracy. Another prospective study of 400 patients comparing 23 different clinical exams found that 3 simple clinical tests—supraspinatus weakness, weakness in external rotation, and the presence of impingement—were highly predictive of rotator cuff tear. When all 3 tests were positive, or when 2 tests were positive for a patient aged >60 years, there was a 98% chance of the patient having a rotator cuff tear.²

Ultrasound can be used to evaluate both suspected full- and partial-thickness rotator cuff tears. In a systematic review of 38 cohort studies, the overall sensitivity and specificity of ultrasound for full-thickness rotator cuff tears was 0.87 (95% CI, 0.84–0.89) and 0.96 (95% CI, 0.94–0.97).¹ For partial-thickness tears, ultrasound sensitivity was 0.67 (95% CI, 0.61–0.73).¹ The incidence of rotator cuff tears increases with age and with athletic activity.⁵

Positive and negative predictive values of a test depend on the prevalence of the condition in the study population. In the case of rotator cuff tears, such differences in prevalence of rotator cuff tears in the 38 cohort studies left it unclear whether a negative ultrasound could reliably rule out a tear.

A meta-analysis of 29 cohort studies of MRI for the diagnosis of full-thickness tears found a pooled sensitivity of 0.89 (95% CI, 0.86–0.92) and a pooled specificity of 0.93 (95% CI, 0.91–0.95), respectively.¹ For partial-thickness tears, the pooled MRI sensitivity was lower at 0.44 (95% CI, 0.36–0.51), but with a high specificity of 0.90 (95% CI, 0.87–0.92).¹ This implies that MRI is the most valuable test to rule out a partial-thickness tear. However, we found no studies that directly compared the test characteristics of ultrasound and MRI.

Conventional arthrography can be used as an invasive alternative to MRI imaging for full-thickness tears, particularly when an implanted device precludes the use of MRI. One prospective trial (in which patients were randomized to the order in which MRI or arthrography were performed) of 38 patients showed arthrography to have a sensitivity of 0.50 and a specificity of 0.96 when used to diagnose full-thickness tears.^3,6

Magnetic resonance arthrography (MRA), based on 6 cohort studies, may be accurate in the diagnosis of a full-thickness tear, with a sensitivity of 0.95 (95% CI, 0.82–0.98) and specificity of 0.93 (95% CI, 0.84–0.97).¹ In these studies, diagnosis of partial-thickness tears with MRA was inconsistent.¹ The invasiveness of MRA limits its utility as compared with MRI and ultrasound. The TABLE summarizes these findings.

TABLE
Summary of test characteristics of diagnostic studies for rotator cuff injuries

Recommendations from others

The American Academy of Orthopaedic Surgeons has a clinical guideline on shoulder pain,⁴ and the Brigham and Women’s Hospital has a guide to the prevention, diagnosis and treatment of upper extremity musculoskeletal disorders.⁵ These guidelines emphasize the importance and utility of physical examination of the shoulder. A patient with a full-thickness tear will likely demonstrate compromised strength in shoulder active mid-arc abduction and resisted external rotation with elbow flexed at patient’s side. However, a partial tear might not compromise strength. Atrophy of the infraspinatus or supra-spinatus muscles is sometimes seen with a full-thickness tear that is several weeks old.⁵

Following a clinical assessment, the guidelines give no preference to any of the diagnostic tests mentioned above, with the exception of arthrography in the presence of implantable devices. Plain X-rays are typically unrevealing, but could be used to rule out other reasons for pain, such as calcific tendonitis.

Evidence summary

Electrocardiograms have been a mainstay in the evaluation for MI for many years. A systematic review of the workup of acute chest pain found that the ECG was the most useful bedside test for MI.¹ In this review, ST segment elevation and Q waves were found to be equally reliable predictors of MI (positive likelihood ratio [LR+]=22). A normal ECG was also found to be the most important bedside finding for ruling out the diagnosis of MI (LR–=0.2).

New ST segment elevation is the most important ECG feature in increasing the probability of diagnosing an MI, with LRs ranging from 5.7 to 53.9.² Another systematic review revealed similar findings where ST segment elevation (most commonly defined as at least 1 mm in 2 or more contiguous limb leads or at least 2 mm in 2 contiguous precordial leads) had a LR+=13.1 (95% confidence interval [CI], 8.28–20.6).³ This review also found that a “completely normal” ECG is reasonably useful in ruling out MI with a LR–=0.14 (95% CI, 0.11–0.20).³

In 2001, a working group of the National Heart Attack Alert Program (NHAAP) performed a systematic review to define the accuracy of “out of hospital” ECG in the diagnosis of acute cardiac ischemia (ACI) and MI. Based on the 8 studies for which data were available, the random effects pooled sensitivity for acute MI was 68% (95% CI, 59%–76%), the specificity was 97% (95% CI, 89%–92%), and the diagnostic odds ratio (DOR) was 104 (95% CI, 48–224).⁴ (The DOR is the change in post-test odds from a negative test to a positive test. It is used as a summary measure in meta-analyses of diagnostic studies. A DOR of 1 represents a useless test, with higher values representing more useful tests.)

There were sparse data available in our search results that specifically addressed the effect of serial ECGs on accuracy of diagnosis of MI. Another systematic review performed by a NHAAP working group evaluating different technologies in the emergency department diagnosis of ACI found only 1 study on the accuracy of serial ECGs in acute MI (sensitivity 39%, specificity 88%).⁵

As part of the Myocardial Infarction Triage and Intervention Project, the investigators found that when compared with a single ECG, serial exams increased the diagnostic sensitivity for acute coronary syndrome from ~34% to 46% with a reduction in specificity from 96% to 93% and positive predictive value from 88% to 84%.⁶ This particular study was unusual in that it used the hospital discharge diagnosis to define the outcome. In most other studies, cardiac enzymes were used as the gold standard for defining outcome.

Recommendations from others

In 2000, the European Society of Cardiology and the American College of Cardiology (ACC) issued a joint consensus statement redefining MI in which ECG findings such as ST segment elevation or new Q waves were insufficient for the diagnosis of MI without concomitant detection of elevated blood levels of cardiac biomarkers such as troponins.⁷

The ACC also published guidelines for management of ST elevation MIs in 2004 that recommended obtaining a 12-lead ECG on all patients presenting with symptoms suggestive of MI. If the initial ECG was not diagnostic, the guideline suggested obtaining either serial ECGs at 5- to 10-minute intervals or continuous 12-lead ST segment monitoring in order to detect the development of ST elevation.⁸

Evidence summary

Electrocardiograms have been a mainstay in the evaluation for MI for many years. A systematic review of the workup of acute chest pain found that the ECG was the most useful bedside test for MI.¹ In this review, ST segment elevation and Q waves were found to be equally reliable predictors of MI (positive likelihood ratio [LR+]=22). A normal ECG was also found to be the most important bedside finding for ruling out the diagnosis of MI (LR–=0.2).

New ST segment elevation is the most important ECG feature in increasing the probability of diagnosing an MI, with LRs ranging from 5.7 to 53.9.² Another systematic review revealed similar findings where ST segment elevation (most commonly defined as at least 1 mm in 2 or more contiguous limb leads or at least 2 mm in 2 contiguous precordial leads) had a LR+=13.1 (95% confidence interval [CI], 8.28–20.6).³ This review also found that a “completely normal” ECG is reasonably useful in ruling out MI with a LR–=0.14 (95% CI, 0.11–0.20).³

In 2001, a working group of the National Heart Attack Alert Program (NHAAP) performed a systematic review to define the accuracy of “out of hospital” ECG in the diagnosis of acute cardiac ischemia (ACI) and MI. Based on the 8 studies for which data were available, the random effects pooled sensitivity for acute MI was 68% (95% CI, 59%–76%), the specificity was 97% (95% CI, 89%–92%), and the diagnostic odds ratio (DOR) was 104 (95% CI, 48–224).⁴ (The DOR is the change in post-test odds from a negative test to a positive test. It is used as a summary measure in meta-analyses of diagnostic studies. A DOR of 1 represents a useless test, with higher values representing more useful tests.)

There were sparse data available in our search results that specifically addressed the effect of serial ECGs on accuracy of diagnosis of MI. Another systematic review performed by a NHAAP working group evaluating different technologies in the emergency department diagnosis of ACI found only 1 study on the accuracy of serial ECGs in acute MI (sensitivity 39%, specificity 88%).⁵

As part of the Myocardial Infarction Triage and Intervention Project, the investigators found that when compared with a single ECG, serial exams increased the diagnostic sensitivity for acute coronary syndrome from ~34% to 46% with a reduction in specificity from 96% to 93% and positive predictive value from 88% to 84%.⁶ This particular study was unusual in that it used the hospital discharge diagnosis to define the outcome. In most other studies, cardiac enzymes were used as the gold standard for defining outcome.

Recommendations from others

In 2000, the European Society of Cardiology and the American College of Cardiology (ACC) issued a joint consensus statement redefining MI in which ECG findings such as ST segment elevation or new Q waves were insufficient for the diagnosis of MI without concomitant detection of elevated blood levels of cardiac biomarkers such as troponins.⁷

The ACC also published guidelines for management of ST elevation MIs in 2004 that recommended obtaining a 12-lead ECG on all patients presenting with symptoms suggestive of MI. If the initial ECG was not diagnostic, the guideline suggested obtaining either serial ECGs at 5- to 10-minute intervals or continuous 12-lead ST segment monitoring in order to detect the development of ST elevation.⁸

Evidence summary

Electrocardiograms have been a mainstay in the evaluation for MI for many years. A systematic review of the workup of acute chest pain found that the ECG was the most useful bedside test for MI.¹ In this review, ST segment elevation and Q waves were found to be equally reliable predictors of MI (positive likelihood ratio [LR+]=22). A normal ECG was also found to be the most important bedside finding for ruling out the diagnosis of MI (LR–=0.2).

New ST segment elevation is the most important ECG feature in increasing the probability of diagnosing an MI, with LRs ranging from 5.7 to 53.9.² Another systematic review revealed similar findings where ST segment elevation (most commonly defined as at least 1 mm in 2 or more contiguous limb leads or at least 2 mm in 2 contiguous precordial leads) had a LR+=13.1 (95% confidence interval [CI], 8.28–20.6).³ This review also found that a “completely normal” ECG is reasonably useful in ruling out MI with a LR–=0.14 (95% CI, 0.11–0.20).³

In 2001, a working group of the National Heart Attack Alert Program (NHAAP) performed a systematic review to define the accuracy of “out of hospital” ECG in the diagnosis of acute cardiac ischemia (ACI) and MI. Based on the 8 studies for which data were available, the random effects pooled sensitivity for acute MI was 68% (95% CI, 59%–76%), the specificity was 97% (95% CI, 89%–92%), and the diagnostic odds ratio (DOR) was 104 (95% CI, 48–224).⁴ (The DOR is the change in post-test odds from a negative test to a positive test. It is used as a summary measure in meta-analyses of diagnostic studies. A DOR of 1 represents a useless test, with higher values representing more useful tests.)

There were sparse data available in our search results that specifically addressed the effect of serial ECGs on accuracy of diagnosis of MI. Another systematic review performed by a NHAAP working group evaluating different technologies in the emergency department diagnosis of ACI found only 1 study on the accuracy of serial ECGs in acute MI (sensitivity 39%, specificity 88%).⁵

As part of the Myocardial Infarction Triage and Intervention Project, the investigators found that when compared with a single ECG, serial exams increased the diagnostic sensitivity for acute coronary syndrome from ~34% to 46% with a reduction in specificity from 96% to 93% and positive predictive value from 88% to 84%.⁶ This particular study was unusual in that it used the hospital discharge diagnosis to define the outcome. In most other studies, cardiac enzymes were used as the gold standard for defining outcome.

Recommendations from others

In 2000, the European Society of Cardiology and the American College of Cardiology (ACC) issued a joint consensus statement redefining MI in which ECG findings such as ST segment elevation or new Q waves were insufficient for the diagnosis of MI without concomitant detection of elevated blood levels of cardiac biomarkers such as troponins.⁷

The ACC also published guidelines for management of ST elevation MIs in 2004 that recommended obtaining a 12-lead ECG on all patients presenting with symptoms suggestive of MI. If the initial ECG was not diagnostic, the guideline suggested obtaining either serial ECGs at 5- to 10-minute intervals or continuous 12-lead ST segment monitoring in order to detect the development of ST elevation.⁸

Evidence summary

Solar ultraviolet (UV) rays are grouped into 2 wavelengths: UVB (290–320 nm) causes acute inflammation, pain and erythema of sunburn; UVA (320–400 nm) is implicated in long-term damage to the skin, including photoaging and skin cancer, following carcinogenic induction by UVB.¹ Sun protection factor (SPF) refers to the dose of UVB required to produce erythema in protected skin vs unprotected skin.¹ UVA protection is offered in broad-spectrum sunscreens, but is not reflected by the SPF.

SPF-15 is considered by experts to be adequate to prevent sunburn, assuming use of a 2 mg/cm² layer of sunscreen (typically, 30 cc for an average adult). However, observations suggest people apply less than half that.² Most experts recommend reapplication every 2 to 3 hours, though the quantity of sunscreen applied may be more important. A paired, split-body study of children receiving supervised single vs multiple applications of SPF-25 sunscreen to randomly assigned lateral halves of their bodies found protection to be equal for 6 hours of direct sunlight exposure. When the study was repeated with 8 hours of exposure, half the children developed mild erythema on the side with 1 application.³

Because of the causal link between exposure to solar UV radiation and skin cancers, experts believe that sunscreens protect the wearer against the development of skin cancer. Case-control studies demonstrate that sunburn in childhood raises the risk of melanotic and nonmelanotic skin cancers, particularly among those with fair skin.⁴ However, studies of sunscreen’s ability to prevent skin cancer are limited due to variability in use, sun exposure, and susceptibility factors. A randomized controlled trial in adults supports that daily sunscreen use reduces the risk of squamous cell carcinoma but not basal cell carcinoma (number needed to treat=884 for 4.5 years).⁵

Sunscreen permits longer sun exposure and may increase the development of nevi, known to be associated with malignant melanoma risk.^6,7 A retrospective study of 6- to 7-year-old children found that sunscreen use correlated with an increasing number of nevi, though wearing clothing to cover skin while in the sun was protective.⁶ However, a randomized controlled trial (RCT) demonstrated that regular use of broad-spectrum sunscreen in young school-aged children resulted in fewer melanotic nevi compared with controls.⁷ A meta-analysis of 18 observational studies did not show an association between sunscreen use and melanoma incidence.⁸

Sunscreens can cause skin irritation or allergic reaction to either the active ingredient or vehicle.^9,10 A RCT of 603 adults found no allergic reactions to active sunscreen ingredients, though 19% of subjects had an irritant reaction or allergy to the base compounds.⁹ Because infants’ skin may have different absorptive characteristics from that of older children, the US Food and Drug Administration recommends avoiding sunscreen before 6 months of age. As research is lacking for this age group, and the risk of harm due to sunburn is real, it would be reasonably prudent to use sunscreen when physical protection from the sun is impossible, and to avoid ingredients that caused a previous reaction.

Recommendations from others

The Centers for Disease Control and Prevention¹⁰ and the American Academy of Pediatrics¹¹ recommend protection from sun exposure for all children and adolescents, including regular and adequate use of broad-spectrum sunscreen for children over 6 months, protective clothing, and sunglasses. The US Preventive Services Task Force¹² reports that evidence is insufficient to recommend for or against counseling by primary care clinicians to prevent skin cancer.

Evidence summary

Solar ultraviolet (UV) rays are grouped into 2 wavelengths: UVB (290–320 nm) causes acute inflammation, pain and erythema of sunburn; UVA (320–400 nm) is implicated in long-term damage to the skin, including photoaging and skin cancer, following carcinogenic induction by UVB.¹ Sun protection factor (SPF) refers to the dose of UVB required to produce erythema in protected skin vs unprotected skin.¹ UVA protection is offered in broad-spectrum sunscreens, but is not reflected by the SPF.

SPF-15 is considered by experts to be adequate to prevent sunburn, assuming use of a 2 mg/cm² layer of sunscreen (typically, 30 cc for an average adult). However, observations suggest people apply less than half that.² Most experts recommend reapplication every 2 to 3 hours, though the quantity of sunscreen applied may be more important. A paired, split-body study of children receiving supervised single vs multiple applications of SPF-25 sunscreen to randomly assigned lateral halves of their bodies found protection to be equal for 6 hours of direct sunlight exposure. When the study was repeated with 8 hours of exposure, half the children developed mild erythema on the side with 1 application.³

Because of the causal link between exposure to solar UV radiation and skin cancers, experts believe that sunscreens protect the wearer against the development of skin cancer. Case-control studies demonstrate that sunburn in childhood raises the risk of melanotic and nonmelanotic skin cancers, particularly among those with fair skin.⁴ However, studies of sunscreen’s ability to prevent skin cancer are limited due to variability in use, sun exposure, and susceptibility factors. A randomized controlled trial in adults supports that daily sunscreen use reduces the risk of squamous cell carcinoma but not basal cell carcinoma (number needed to treat=884 for 4.5 years).⁵

Sunscreen permits longer sun exposure and may increase the development of nevi, known to be associated with malignant melanoma risk.^6,7 A retrospective study of 6- to 7-year-old children found that sunscreen use correlated with an increasing number of nevi, though wearing clothing to cover skin while in the sun was protective.⁶ However, a randomized controlled trial (RCT) demonstrated that regular use of broad-spectrum sunscreen in young school-aged children resulted in fewer melanotic nevi compared with controls.⁷ A meta-analysis of 18 observational studies did not show an association between sunscreen use and melanoma incidence.⁸

Sunscreens can cause skin irritation or allergic reaction to either the active ingredient or vehicle.^9,10 A RCT of 603 adults found no allergic reactions to active sunscreen ingredients, though 19% of subjects had an irritant reaction or allergy to the base compounds.⁹ Because infants’ skin may have different absorptive characteristics from that of older children, the US Food and Drug Administration recommends avoiding sunscreen before 6 months of age. As research is lacking for this age group, and the risk of harm due to sunburn is real, it would be reasonably prudent to use sunscreen when physical protection from the sun is impossible, and to avoid ingredients that caused a previous reaction.

Recommendations from others

The Centers for Disease Control and Prevention¹⁰ and the American Academy of Pediatrics¹¹ recommend protection from sun exposure for all children and adolescents, including regular and adequate use of broad-spectrum sunscreen for children over 6 months, protective clothing, and sunglasses. The US Preventive Services Task Force¹² reports that evidence is insufficient to recommend for or against counseling by primary care clinicians to prevent skin cancer.

Evidence summary

Solar ultraviolet (UV) rays are grouped into 2 wavelengths: UVB (290–320 nm) causes acute inflammation, pain and erythema of sunburn; UVA (320–400 nm) is implicated in long-term damage to the skin, including photoaging and skin cancer, following carcinogenic induction by UVB.¹ Sun protection factor (SPF) refers to the dose of UVB required to produce erythema in protected skin vs unprotected skin.¹ UVA protection is offered in broad-spectrum sunscreens, but is not reflected by the SPF.

SPF-15 is considered by experts to be adequate to prevent sunburn, assuming use of a 2 mg/cm² layer of sunscreen (typically, 30 cc for an average adult). However, observations suggest people apply less than half that.² Most experts recommend reapplication every 2 to 3 hours, though the quantity of sunscreen applied may be more important. A paired, split-body study of children receiving supervised single vs multiple applications of SPF-25 sunscreen to randomly assigned lateral halves of their bodies found protection to be equal for 6 hours of direct sunlight exposure. When the study was repeated with 8 hours of exposure, half the children developed mild erythema on the side with 1 application.³

Because of the causal link between exposure to solar UV radiation and skin cancers, experts believe that sunscreens protect the wearer against the development of skin cancer. Case-control studies demonstrate that sunburn in childhood raises the risk of melanotic and nonmelanotic skin cancers, particularly among those with fair skin.⁴ However, studies of sunscreen’s ability to prevent skin cancer are limited due to variability in use, sun exposure, and susceptibility factors. A randomized controlled trial in adults supports that daily sunscreen use reduces the risk of squamous cell carcinoma but not basal cell carcinoma (number needed to treat=884 for 4.5 years).⁵

Sunscreen permits longer sun exposure and may increase the development of nevi, known to be associated with malignant melanoma risk.^6,7 A retrospective study of 6- to 7-year-old children found that sunscreen use correlated with an increasing number of nevi, though wearing clothing to cover skin while in the sun was protective.⁶ However, a randomized controlled trial (RCT) demonstrated that regular use of broad-spectrum sunscreen in young school-aged children resulted in fewer melanotic nevi compared with controls.⁷ A meta-analysis of 18 observational studies did not show an association between sunscreen use and melanoma incidence.⁸

Sunscreens can cause skin irritation or allergic reaction to either the active ingredient or vehicle.^9,10 A RCT of 603 adults found no allergic reactions to active sunscreen ingredients, though 19% of subjects had an irritant reaction or allergy to the base compounds.⁹ Because infants’ skin may have different absorptive characteristics from that of older children, the US Food and Drug Administration recommends avoiding sunscreen before 6 months of age. As research is lacking for this age group, and the risk of harm due to sunburn is real, it would be reasonably prudent to use sunscreen when physical protection from the sun is impossible, and to avoid ingredients that caused a previous reaction.

Recommendations from others

The Centers for Disease Control and Prevention¹⁰ and the American Academy of Pediatrics¹¹ recommend protection from sun exposure for all children and adolescents, including regular and adequate use of broad-spectrum sunscreen for children over 6 months, protective clothing, and sunglasses. The US Preventive Services Task Force¹² reports that evidence is insufficient to recommend for or against counseling by primary care clinicians to prevent skin cancer.